Glaucoma Grand Rounds: When a Surgery—and Surgeon—Fails, P. 86

UNDERSTANDING TODAY’S PROGRESSIVES Help patients choose and use these lenses with fewer hassles and greater success.

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June 15, 2021 • reviewofoptometry.com Leadership in clinical care Stake your claim in care OPEN YOUR EYES TOWith more patients in need than ophthalmologists can handle, optometry needs to gain ground for the good of all.

DISCOVER EXCLUSIVE ACCESS TO ALL THINGS REFRESH®. 12th Annual Retina Report

Retina Care: The Next Wave, P. 42 REFRESH® PATIENT PRODUCT REFRESH® DIRECT SAMPLESGet SeriousCOUPONS About Central SerousEDUCATION Chorioretinopathy,ECOMMERCEP. 52 CALLStroke NOW! of the Eye: 833-REF-SMPL Are You Prepared?, P. 60 Be a7:30 Retina a.m.–7 Referral p.m. CT, Rock M–F Star, P. 68 © 2021 AbbVie. All rights reserved. All trademarks are the property of their respective owners. REF144069 02/21 EARN 2 CE CREDITS: What to Do When it’s Not AMD, P. 72

Glaucoma Grand Rounds: When a Surgery—and Surgeon—Fails, P. 86

UNDERSTANDING TODAY’S PROGRESSIVES Help patients choose and use these lenses with fewer hassles and greater success.

Page 34

June 15, 2021 • reviewofoptometry.com Leadership in clinical care Stake your claim in retina care With more patients in need than ophthalmologists can handle, optometry needs to gain ground for the good of all.

12th Annual Retina Report

Retina Care: The Next Wave, P. 42

Get Serious About Central Serous Chorioretinopathy, P. 52

Stroke of the Eye: Are You Prepared?, P. 60

Be a Retina Referral Rock Star, P. 68

EARN 2 CE CREDITS: What to Do When it’s Not AMD, P. 72 THE HORSEPOWER YOU NEED TO LOWER IOP

Powerful IOP reduction with excellent tolerability1,2

VYZULTA delivered up to 9.1 mmHg mean IOP reduction from baseline in pivotal trials. 1,2*

TAKE A TEST RIDE AT VYZULTAHCP.COM

* Pivotal study designs: Two Phase 3, randomized, multicenter, parallel-group studies, APOLLO and LUNAR, evaluating noninferiority of once-daily VYZULTA vs twice-daily timolol maleate 0.5% in patients with open-angle glaucoma or . Primary endpoint was IOP measured at 9 assessment time points in study eye. APOLLO (VYZULTA, n=284; timolol, n=133) and LUNAR (VYZULTA, n=278; timolol, n=136).2,3

INDICATION VYZULTA® (latanoprostene bunod ophthalmic solution), 0.024% is indicated for the reduction of (IOP) in patients with open-angle glaucoma or ocular hypertension.

IMPORTANT SAFETY INFORMATION • Increased pigmentation of the and periorbital tissue () can occur. Iris pigmentation is likely to be permanent • Gradual changes to , including increased length, increased thickness, and number of eyelashes, may occur. These changes are usually reversible upon treatment discontinuation • Use with caution in patients with a history of intraocular infl ammation (iritis/). VYZULTA should generally not be used in patients with active intraocular infl ammation • , including cystoid macular edema, has been reported during treatment with prostaglandin analogs. Use with caution in aphakic patients, in pseudophakic patients with a torn posterior capsule, or in patients with known risk factors for macular edema • There have been reports of bacterial associated with the use of multiple-dose containers of topical ophthalmic products that were inadvertently contaminated by patients • Contact lenses should be removed prior to the administration of VYZULTA and may be reinserted 15 minutes after administration • Most common ocular adverse reactions with incidence ≥2% are conjunctival hyperemia (6%), eye irritation (4%), eye pain (3%), and instillation site pain (2%)

For more information, please see Brief Summary of full Prescribing Information on adjacent page.

References: 1. VYZULTA Prescribing Information. Bausch & Lomb Incorporated. 2. Weinreb RN, Scassellati Sforzolini B, Vittitow J, Liebmann J. Latanoprostene bunod 0.024% versus timolol maleate 0.5% in subjects with open-angle glaucoma or ocular hypertension: the APOLLO study. . 2016;123(5):965-973. 3. Medeiros FA, Martin KR, Peace J, Scassellati Sforzolini B, Vittitow JL, Weinreb RN. Comparison of latanoprostene bunod 0.024% and timolol maleate 0.5% in open-angle glaucoma or ocular hypertension: the LUNAR study. Am J Ophthalmol. 2016;168:250-259.

VYZULTA and the V design are trademarks of Bausch & Lomb Incorporated or its a liates. Any other product/brand names and/or logos are trademarks of the respective owners. ©2021 Bausch & Lomb Incorporated or its a liates. All rights reserved. VYZ.0258.USA.20 BRIEF SUMMARY OF PRESCRIBING INFORMATION and malrotation, abdominal distension and edema. Latanoprostene bunod was not teratogenic in the rat when administered IV at 150 mcg/kg/day (87 times the clinical dose) [see Data]. This Brief Summary does not include all the information needed to use VYZULTA safely and effectively. See full Prescribing Information for VYZULTA. The background risk of major birth defects and miscarriage for the indicated population is unknown. However, the background risk in the U.S. general population of major birth defects ® VYZULTA (latanoprostene bunod ophthalmic solution), 0.024%, for topical is 2 to 4%, and of miscarriage is 15 to 20%, of clinically recognized pregnancies. ophthalmic use. Data Initial U.S. Approval: 2017 Animal Data 1 INDICATIONS AND USAGE ® Embryofetal studies were conducted in pregnant rabbits administered latanoprostene bunod daily VYZULTA (latanoprostene bunod ophthalmic solution) 0.024% is indicated for the reduction by intravenous injection on gestation days 7 through 19, to target the period of organogenesis. The of intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension. doses administered ranged from 0.24 to 80 mcg/kg/day. Abortion occurred at doses ≥ 0.24 mcg/kg/day 4 CONTRAINDICATIONS latanoprostene bunod (0.28 times the clinical dose, on a body surface area basis, assuming None 100% absorption). Embryofetal lethality (resorption) was increased in latanoprostene bunod treatment groups, as evidenced by increases in early resorptions at doses ≥ 0.24 mcg/kg/day 5 WARNINGS AND PRECAUTIONS and late resorptions at doses ≥ 6 mcg/kg/day (approximately 7 times the clinical dose). 5.1 Pigmentation No fetuses survived in any rabbit pregnancy at doses of 20 mcg/kg/day (23 times the clinical dose) VYZULTA® (latanoprostene bunod ophthalmic solution), 0.024% may cause changes to or greater. Latanoprostene bunod produced structural abnormalities at doses ≥ 0.24 mcg/kg/day pigmented tissues. The most frequently reported changes with prostaglandin analogs (0.28 times the clinical dose). Malformations included anomalies of sternum, coarctation have been increased pigmentation of the iris and periorbital tissue (eyelid). of the aorta with pulmonary trunk dilation, retroesophageal subclavian artery with absent brachiocephalic artery, domed head, forepaw hyperextension and hindlimb malrotation, Pigmentation is expected to increase as long as latanoprostene bunod ophthalmic solution abdominal distention/edema, and missing/fused caudal vertebrae. is administered. The pigmentation change is due to increased melanin content in the melanocytes rather than to an increase in the number of melanocytes. After discontinuation An embryofetal study was conducted in pregnant rats administered latanoprostene bunod daily of VYZULTA, pigmentation of the iris is likely to be permanent, while pigmentation of the by intravenous injection on gestation days 7 through 17, to target the period of organogenesis. periorbital tissue and changes are likely to be reversible in most patients. Patients The doses administered ranged from 150 to 1500 mcg/kg/day. Maternal toxicity was produced who receive prostaglandin analogs, including VYZULTA, should be informed of the possibility at 1500 mcg/kg/day (870 times the clinical dose, on a body surface area basis, assuming 100% of increased pigmentation, including permanent changes. The long-term effects of increased absorption), as evidenced by reduced maternal weight gain. Embryofetal lethality (resorption pigmentation are not known. and fetal death) and structural anomalies were produced at doses ≥ 300 mcg/kg/day (174 times the clinical dose). Malformations included anomalies of the sternum, domed head, forepaw Iris change may not be noticeable for several months to years. Typically, the pigmentation hyperextension and hindlimb malrotation, vertebral anomalies and delayed ossication of distal around the spreads concentrically towards the periphery of the iris and the entire iris or parts of limb bones. A no observed adverse effect level (NOAEL) was established at 150 mcg/kg/day the iris become more brownish. Neither nevi nor freckles of the iris appear to be affected by treatment. (87 times the clinical dose) in this study. While treatment with VYZULTA® (latanoprostene bunod ophthalmic solution), 0.024% can be continued in patients who develop noticeably increased iris pigmentation, these patients should be examined 8.2 Lactation regularly [see Patient Counseling Information (17) in full Prescribing Information]. Risk Summary 5.2 Eyelash Changes There are no data on the presence of VYZULTA in human milk, the effects on the breastfed VYZULTA may gradually change eyelashes and vellus hair in the treated eye. These changes infant, or the effects on milk production. The developmental and health benets of breastfeeding include increased length, thickness, and the number of lashes or hairs. Eyelash changes are should be considered, along with the mother’s clinical need for VYZULTA, and any potential usually reversible upon discontinuation of treatment. adverse effects on the breastfed infant from VYZULTA. 5.3 Intraocular In ammation 8.4 Pediatric Use VYZULTA should be used with caution in patients with a history of intraocular in ammation Use in pediatric patients aged 16 years and younger is not recommended because of potential (iritis/uveitis) and should generally not be used in patients with active intraocular in ammation safety concerns related to increased pigmentation following long-term chronic use. as it may exacerbate this condition. 8.5 Geriatric Use 5.4 Macular Edema No overall clinical differences in safety or effectiveness have been observed between elderly Macular edema, including cystoid macular edema, has been reported during treatment and other adult patients. with prostaglandin analogs. VYZULTA should be used with caution in aphakic patients, in 13 NONCLINICAL TOXICOLOGY pseudophakic patients with a torn posterior lens capsule, or in patients with known risk 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility factors for macular edema. Latanoprostene bunod was not mutagenic in bacteria and did not induce micronuclei formation 5.5 Bacterial Keratitis in the in vivo rat bone marrow micronucleus assay. Chromosomal aberrations were observed There have been reports of bacterial keratitis associated with the use of multiple-dose in vitro with human lymphocytes in the absence of metabolic activation. containers of topical ophthalmic products. These containers had been inadvertently Latanoprostene bunod has not been tested for carcinogenic activity in long-term animal studies. contaminated by patients who, in most cases, had a concurrent corneal disease or a Latanoprost acid is a main metabolite of latanoprostene bunod. Exposure of rats and mice to disruption of the ocular epithelial surface. latanoprost acid, resulting from oral dosing with latanoprost in lifetime rodent bioassays, was 5.6 Use with not carcinogenic. Contact lenses should be removed prior to the administration of VYZULTA because this product Fertility studies have not been conducted with latanoprostene bunod. The potential to impact contains benzalkonium chloride. Lenses may be reinserted 15 minutes after administration. fertility can be partially characterized by exposure to latanoprost acid, a common metabolite of 6 ADVERSE REACTIONS both latanoprostene bunod and latanoprost. Latanoprost acid has not been found to have any effect on male or female fertility in animal studies. The following adverse reactions are described in the Warnings and Precautions section: pigmentation (5.1), eyelash changes (5.2), intraocular in ammation (5.3), macular edema (5.4), 13.2 Animal Toxicology and/or Pharmacology bacterial keratitis (5.5), use with contact lens (5.6). A 9-month toxicology study administered topical ocular doses of latanoprostene bunod to one 6.1 Clinical Trials Experience eye of cynomolgus monkeys: control (vehicle only), one drop of 0.024% bid, one drop of 0.04% bid and two drops of 0.04% per dose, bid. The systemic exposures are equivalent to 4.2-fold, Because clinical trials are conducted under widely varying conditions, adverse reaction 7.9-fold, and 13.5-fold the clinical dose, respectively, on a body surface area basis (assuming rates observed in the clinical trials of a drug cannot be directly compared to rates in the 100% absorption). Microscopic evaluation of the lungs after 9 months observed pleural/subpleural clinical trials of another drug and may not re ect the rates observed in practice. chronic brosis/in ammation in the 0.04% dose male groups, with increasing incidence and VYZULTA was evaluated in 811 patients in 2 controlled clinical trials of up to 12 months severity compared to controls. Lung toxicity was not observed at the 0.024% dose. duration. The most common ocular adverse reactions observed in patients treated with U.S. Patent Numbers: 7,273,946; 7,629,345; 7,910,767; 8,058,467. latanoprostene bunod were: conjunctival hyperemia (6%), eye irritation (4%), eye pain (3%), and instillation site pain (2%). Approximately 0.6% of patients discontinued therapy due to VYZULTA is a trademark of Bausch & Lomb Incorporated or its afliates. ocular adverse reactions including ocular hyperemia, conjunctival irritation, eye irritation, © 2020 Bausch & Lomb Incorporated or its afliates. eye pain, conjunctival edema, vision blurred, punctate keratitis and foreign body sensation. Distributed by: 8 USE IN SPECIFIC POPULATIONS Bausch + Lomb, a division of 8.1 Pregnancy Bausch Health US, LLC Risk Summary Bridgewater, NJ 08807 USA There are no available human data for the use of VYZULTA during pregnancy to inform any drug Based on 9612403 (Folded), 9612303 (Flat) 5/2019 associated risks. VYZ.0109.USA.20 Issued: 5/2020 Latanoprostene bunod has caused miscarriages, abortion, and fetal harm in rabbits. Latanoprostene bunod was shown to be abortifacient and teratogenic when administered intravenously (IV) to pregnant rabbits at exposures ≥ 0.28 times the clinical dose. Doses ≥ 20 μg/kg/day (23 times the clinical dose) produced 100% embryofetal lethality. Structural abnormalities observed in rabbit fetuses included anomalies of the great vessels and aortic arch vessels, domed head, sternebral and vertebral skeletal anomalies, limb hyperextension Get the latest at news review www.reviewofoptometry.com/news Clinical, legislative and practice development updates for ODs. Stories post every weekday

Covid vaccine and corneal graft rejection, p. 6 >> Pre-op gland expression and surgery, p. 6 >> at arvo, p. 9 >> 10-2 vf test and central progression, p. 10 >> ors case report contest winners, p. 12

ODs Fire Back at MIPS Report’s So-So Marks Advocates call out the 2017 data from the first year of the CMS program as skewed.

recent analysis suggesting the MIPS program, making available gists, 15,193 optometrists and 293,210 ophthalmologists who a “pick your pace” participation that other physicians. Aparticipated in the Merit-based allowed three reporting options for “MIPS is still relatively new and not Incentive Payment System (MIPS) in clinicians, including test, partial and well understood by most doctors of 2017 earned higher scores than other full-year reporting.2 The first option al- optometry,” says Chris Wroten, OD. physicians—including optometrists—is lowed providers to report “some data” “As is true for all health care provid- drawing fire among the profession and to avoid a negative adjustment and gain ers, assessing quality of care based on its advocates. familiarity with the program, while the whether a box in an EHR was checked The paper stated that ophthalmolo- latter options stepped up data require- or not doesn’t ensure the accuracy of gists had significantly higher MIPS ments, incentives and penalties.2 the care reported, nor does it ensure scores in all categories compared with the quality of care provided.” ODs and other physicians.1 Specifically, Ophthalmology has a built-in the paper reports that mean final MIPS “Ophthalmology is grasping advantage in its exclusive IRIS registry, scores for ophthalmologists in 2017 at any conclusion they which streamlines reporting for MIPS were 10 to 20 points higher than op- and enhances scoring, Dr. Wroten can to prove their worth, tometry and other physician specialties adds. Additionally, several eye care in both group and individual reporting. and the article contradicts quality measures developed through The authors also noted that ophthal- the viewpoint of their the IRIS registry and then approved by mologists are more likely to perform at own most experienced CMS exclude optometry’s participation a higher level in MIPS. and compel ODs to use other topped- ophthalmologists.” Citing the AOA’s 2018 American out quality measures with maximum Eye-Q Survey, optometrist Jeffrey —Jeffrey Michaels, OD scores that are capped at 70% or less Michaels suggests that ophthalmol- than the maximum available for other ogy knows optometry is the preferred Additionally, the overall performance measures. source for eye care in America and that threshold for MIPS was established at “Further, CMS has acknowledged optometrists are trusted more than any a relatively low level of three points from the start of MIPS that it favors other source for ocular health exams. out of a possible 100, and ODs earned providers in large practices that have “Ophthalmology is grasping at any far above that with an average of 55 more resources to assist with compli- conclusion they can to prove their points.2 The AOA affirms nearly every ance and reporting requirements. A worth, and the article contradicts the OD who participated in MIPS during much higher percentage of MIPS-eli- viewpoint of their own most experi- 2017 earned a passing score.2 gible ophthalmologists practice within enced ophthalmologists,” he says. “As Although performance for MIPS hospital systems, multispecialty groups optometrists continue to expand scope began broadly in 2017, CMS gradually and large eye care clinics compared of practice across the country, the op- rolled out the program with that year with doctors of optometry, further position begins to show desperation.” acting as a transitional period, but also explaining any potential discrepancy in Advocates say the data, which came narrowed criteria for eligible providers MIPS scores,” Dr. Wroten says. out in 2017 when the Centers for based on strong feedback.2 1. Sheth N, French DD, Tanna A P. Merit-based incentive Medicare & Medicaid Services rolled The group reporting database payment system scores in ophthalmology and optometry. out the program, should be taken with included 6,776 ophthalmologists, Ophthalmology. 2021;128(5):793-5. 2. AOA faults ophthalmology journal analysis of optometrist, a grain of salt. 12,206 optometrists and 231,285 other ophthalmologist MIPS scores. American Optometric Associa- That year, CMS granted widespread physicians. The individual clinician tion. www.aoa.org/news/practice-management/perfect-your- practice/aoa-faults-ophthalmology-journal-mips-study?sso=y. flexibilities to help ease providers into database included 8,595 ophthalmolo- May 13, 2021. Accessed May 17, 2021.

4 REVIEW OF OPTOMETRY | JUNE 15, 2021 TIME IS RUNNING OUT! UPGRADE CURRENT AIR OPTIX® WEARERS WITH NO REFIT REQUIRED!1,2

THE TRIPLE UPGRADE

Longer-lasting lens surface moisture3-5*

MORE LUBRICATION

Increased surface wett ing and lubricating eff ects5-7**

IMPROVED MARKINGS

Bett er scribe mark visibility and reduced markings

Bring more lens surface moisture3-5* and outstanding comfort8,9† to their AIR OPTIX® performance now!

*vs. AIR OPTIX® contact lenses. **AIR OPTIX® plus HydraGlyde® sphere lenses compared to AIR OPTIX® AQUA and O2 OPTIX® sphere lenses. †Based on clinical studies with AIR OPTIX® AQUA, AIR OPTIX® AQUA Multifocal and AIR OPTIX® for contact lenses. Important information for AIR OPTIX® plus HydraGlyde® (lotrafi lcon B) contact lenses: For daily wear or extended wear up to 6 nights for near/far-sightedness. Risk of serious eye problems (i.e., ) is greater for extended wear. In rare cases, loss of vision may result. Side eff ects like discomfort, mild burning or stinging may occur. Important information for AIR OPTIX® plus HydraGlyde® Multifocal (lotrafi lcon B) contact lenses: For daily wear or extended wear up to 6 nights for near/far-sightedness and/or . Risk of serious eye problems (i.e., corneal ulcer) is greater for extended wear. In rare cases, loss of vision may result. Side eff ects like discomfort, mild burning or stinging may occur. Important information for AIR OPTIX® plus HydraGlyde® for Astigmatism (lotrafi lcon B) contact lenses: For daily wear or extended wear up to 6 nights for near/far sightedness and astigmatism. Risk of serious eye problems (i.e., corneal ulcer) is greater for extended wear. In rare cases, loss of vision may result. Side eff ects like discomfort, mild burning or stinging may occur. References: 1. Alcon data on file, 2017. 2. Alcon data on file, 2018. 3. Marx S, Sickenberger W. Wettability of different silicone hydrogel lens materials and blister solutions measured using non-invasive keratographic drying up time (NIK-DUT). Optom Vis Sci. 2016;93:E-abstract 165113. 4. Tucker R, Lemp J, Guillon M. In vitro and on eye wettability of lotrafilcon B lenses packaged with a substantive wetting agent. Invest Ophthalmol Vis Sci. 2017;58: ARVO E-Abstract 3070. 5. Lemp J, Muya L, Driver-Scott A, Alvord L. A comparison of two methods for assessing wetting substantivity. Poster presented at: 2016 Global Specialty Lens Symposium (GSLS); January 21-24, 2016; Las Vegas, NV. 6. Alcon data on file, 2017. 7. Lemp J, Zhao X, Perry S. Retention of packing solution comfort agents. Poster presented at: 2017 American Academy of Optometry Annual Meeting; October 11-14, 2017; Chicago, IL. 8. Eiden SB, Davis R, Bergenske P. Prospective study of lotrafilcon B lenses comparing 2 versus 4 weeks of wear for objective and subjective measures of health, comfort, and vision. Eye Contact Lens. 2013;39(4):290-294. 9. Lemp J, Kern J. A comparison of real time and recall comfort assessments. Optom Vis Sci. 2016;93:E-abstract 165256.

See product instructions for complete wear, care and safety information. ©2021 Alcon Inc. 4/21 US-AHA-2100003 NEWS REVIEW | Get the latest at www.reviewofoptometry.com/news

COVID Vaccines and Corneal Graft Rejection recent paper reveals that OD Photo: Mitch Ibach, OD, Scott Hauswirth, presented with symptoms of rejection clinicians and patients should two months after receiving her first Abe aware of the potential of COVID vaccine dose and three corneal graft rejection associated with weeks after the second dose. Bilateral, COVID-19 vaccine administration simultaneous acute endothelial graft and consider vaccination in advance rejection was diagnosed, and she was of planned non-urgent keratoplasties. put on hourly steroid drops. Seven The researchers believe that their days later, signs of inflammation study is the first report of temporal were reduced and both grafts were association between corneal transplant Failed graft patients were successfully functioning well, at which time the rejection following immunization treated with topical corticosteroids. frequency of topical dexamethasone against COVID-19 and the first report was reduced.1 of DMEK rejection following any she received the first dose of Pfizer’s In an email to Reuters Health, immunization. They hypothesize that COVID vaccine. She presented a the authors speculated that, “The the allogeneic response may have been week later with acute-onset blurred patient’s antibody response triggered initiated by the host antibody response vision, redness and in her by vaccination caused immunological following vaccination. right eye. Clinical examination found injury to the internal (endothelial) In one case, DMEK was performed indications typical of acute endothelial surface of the transplanted donor around the time of vaccination, but graft rejection. The frequency of .”2 it had taken place years earlier in the topical steroid (dexamethasone 0.1%) Nevertheless, their report states, other. In both cases, one unilateral was increased from four times daily “Patients with corneal transplants and and the other bilateral, the transplant to every hour. their clinicians should not be deterred rejection was treated successfully with began to resolve after three days, from COVID-19 vaccination.” topical corticosteroids. and by four weeks after the rejection In the first case, a 66-year-old onset, was good and there 1. Phylactou M, Li JPO, Larkin DFP. Characteristics of endothelial corneal transplant rejection following im- woman underwent an uneventful was no active inflammation. munisation with SARS-CoV-2 messenger RNA vaccine. DMEK in her right eye. Her history In the second case, an 83-year-old Br J Ophthalmol. April 28, 2021. [Epub ahead of print]. was notable for HIV infection that woman had undergone DMEK in 2. Baltic S. SARS-CoV-2 mRNA vaccine might trig- was well controlled (undetectable her right eye six years earlier and in ger corneal-transplant rejection. Medscape. www. medscape.com/viewarticle/950985. May 13, 2021. viral load). Two weeks after DMEK, her left eye three years earlier. She Accessed May 26, 2021. Gland Expression Improves Cataract Surgery Results pon investigating the effects postoperatively. They also took tear The improvement of each parameter of administering meibomian film break-up time (TBUT), Oxford in the treatment group showed a linear Ugland warming and expres- corneal staining score and tear film lipid correlation with baseline MGD grade. sion prior to cataract surgery, research- layer thickness (LLT) measurements at Patients without baseline MGD also ers recently found that preoperative each visit, in addition to Ocular Surface showed improvement in DED induced treatment may be a safe and effective Disease Index (OSDI) and Dry Eye by surgery from preoperative gland intervention for relieving MGD and Questionnaire (DEQ) scores. expression. DED induced by surgery. The investigators reported a sig- “[This treatment] might be This prospective, randomized con- nificant decrease in meibomian gland recommended not only for the trolled study assessed 124 eyes sched- expressibility, meibum quality, L LT, patients with preoperative MGD, uled for cataract surgery. Participants corneal staining and dry eye symptoms but also for those without baseline were randomly allocated to control and in controls following cataract surgery. MGD to prevent the development treatment groups, with the treatment Conversely, the treatment group of MGD and dry eye induced by cohort receiving therapy three weeks showed significantly improved meibo- ocular surgeries,” the study authors prior to surgery. The team evaluated mian gland patency, meibum quality, concluded in their paper. meibomian gland atrophy, gland ex- TBUT and corneal staining. This Park J, Yoo YS, Shin K, et al. Effects of Lipiflow treatment prior pressibility and gland secretion quality group also reported better subjective to cataract surgery: a prospective, randomized, controlled at baseline and one and three months outcomes on both OSDI and DEQ. study. Am J Ophthalmol. May 13, 2021. [Epub ahead of print].

6 REVIEW OF OPTOMETRY | JUNE 15, 2021 IN THE BATTLEGROUND OF DRY EYE...

• EYSUVIS is THE FIRST AND ON LY FDA APPROVED SHORT TERM (up to two weeks) RX TREATMENT for the signs and symptoms of Dry • EYSUVIS RAPIDLY REDUCED* Dry Eye signs and symptoms in the largest clinical development program in Dry Eye (N=2871)1 • EYSUVIS TARGETS OCULAR SURFACE INFLAMMATION, an underlying pathology of Dry Eye • EYSUVIS is formulated with AMPPLIFY® Drug Delivery Technology, designed to ENHANCE OCULAR SURFACE TISSUE DISTRIBUTION AND PENETRATION 2,3 • EYSUVIS had a LOW INCIDENCE OF INTRAOCULAR PRESSURE ELEVATION (similar to vehicle) and was well-tolerated in clinical trials4 —Please see Warning on Intraocular Pressure Increase below

*The safety and efficacy of EYSUVIS was assessed in 4 multicentered, randomized, double-masked, placebo-controlled trials in 2871 patients with documented Dry Eye. Patients received either EYSUVIS or vehicle 4 times a day for at least 2 weeks. Patients taking EYSUVIS showed significant reduction in the symptoms of Dry Eye (ocular discomfort) as early as Day 4 after starting treatment (versus vehicle). Symptoms continued to improve up to the end of the treatment period (Day 15). Patients taking EYSUVIS also showed significant reduction in signs of Dry Eye (conjunctival hyperemia) at Day 15 versus vehicle.

INDICATION EYSUVIS is a corticosteroid indicated for the short-term (up to two weeks) treatment of the signs and symptoms of dry eye disease. IMPORTANT SAFETY INFORMATION Contraindication: Bacterial Infections: Use of corticosteroids may suppress the host response EYSUVIS, as with other ophthalmic corticosteroids, is contraindicated in most and thus increase the hazard of secondary ocular infections. In acute purulent viral diseases of the cornea and including epithelial herpes simplex conditions, corticosteroids may mask infection or enhance existing infection. keratitis (dendritic keratitis), vaccinia, and varicella, and also in mycobacterial Viral Infections: Use of a corticosteroid medication in the treatment of patients infection of the eye and fungal diseases of ocular structures. with a history of herpes simplex requires great caution. Use of ocular Warnings and Precautions: corticosteroids may prolong the course and may exacerbate the severity Delayed Healing and Corneal Perforation: Topical corticosteroids have been of many viral infections of the eye (including herpes simplex). known to delay healing and cause corneal and scleral thinning. Use of topical Fungal Infections: Fungal infections of the cornea are particularly prone to corticosteroids in the presence of thin corneal or scleral tissue may lead to develop coincidentally with long-term local corticosteroid application. Fungus perforation. The initial prescription and each renewal of the medication order invasion must be considered in any persistent corneal ulceration where a should be made by a physician only after examination of the patient with the corticosteroid has been used or is in use. aid of magnification, such as slit lamp biomicroscopy, and, where appropriate, fluorescein staining. Adverse Reactions: Intraocular Pressure (IOP) Increase: Prolonged use of corticosteroids may result The most common adverse drug reaction following the use of EYSUVIS for in glaucoma with damage to the , as well as defects in visual acuity two weeks was instillation site pain, which was reported in 5% of patients. and fields of vision. Corticosteroids should be used with caution in the presence Please see Brief Summary of Prescribing Information for EYSUVIS on the next page. of glaucoma. Renewal of the medication order should be made by a physician References: 1. Holland E, Nichols K, Foulks G, et al. Safety and efficacy of KPI-121 only after examination of the patient and evaluation of the IOP ophthalmic suspension 0.25% for dry eye disease in four randomized controlled trials. : Use of corticosteroids may result in posterior subcapsular Presented at: AAO 2020: November 13-15, 2020; virtual meeting. 2. Schopf L, cataract formation. Enlow E, Popov A, et al. Ocular pharmacokinetics of a novel loteprednol etabonate 0.4% ophthalmic formulation. Ophthalmol Ther. 2014;3(1-2):63-72. 3. Popov A. Mucus-penetrating particles and the role of ocular mucus as a barrier to micro- and nanosuspensions. J Ocul Pharmacol Ther. 2020;36(6): 366-375. 4. Korenfeld M, Nichols KK, Goldberg D, et al. Safety of KPI-121 ophthalmic suspension 0.25% in patients with dry eye disease: a pooled analysis of 4 multicenter, randomized, vehicle- US-EYS-2100022 www.EYSUVIS.com controlled studies. Cornea. 2020. In press. EYSUVIS (loteprednol etabonate ophthalmic suspension) 0.25%, The background risk in the U.S. general population of major birth defects is for topical ophthalmic use 2 to 4%, and of miscarriage is 15 to 20%, of clinically recognized pregnancies. Data—Animal Data: Embryofetal studies were conducted in pregnant rabbits BRIEF SUMMARY OF FULL PRESCRIBING INFORMATION administered loteprednol etabonate by oral gavage on gestation days 6 to 18, to target the period of organogenesis. Loteprednol etabonate produced fetal INDICATIONS AND USAGE malformations at 0.1 mg/kg (1.4 times the recommended human ophthalmic EYSUVIS is a corticosteroid indicated for the short-term (up to two weeks) dose (RHOD) based on body surface area, assuming 100% absorption). treatment of the signs and symptoms of dry eye disease. Spina bifida (including meningocele) was observed at 0.1 mg/kg, and CONTRAINDICATIONS exencephaly and craniofacial malformations were observed at 0.4 mg/kg EYSUVIS, as with other ophthalmic corticosteroids, is contraindicated in (5.6 times the RHOD). At 3 mg/kg (41 times the RHOD), loteprednol most viral diseases of the cornea and conjunctiva including epithelial herpes etabonate was associated with increased incidences of abnormal left simplex keratitis (dendritic keratitis), vaccinia, and varicella, and also in common carotid artery, limb flexures, umbilical hernia, scoliosis, and mycobacterial infection of the eye and fungal diseases of ocular structures. delayed ossification. Abortion and embryofetal lethality (resorption) occurred at 6 mg/kg (83 times the RHOD). A NOAEL for developmental WARNINGS AND PRECAUTIONS toxicity was not established in this study. The NOAEL for maternal toxicity Delayed Healing and Corneal Perforation—Topical corticosteroids have in rabbits was 3 mg/kg/day. been known to delay healing and cause corneal and scleral thinning. Use of Embryofetal studies were conducted in pregnant rats administered topical corticosteroids in the presence of thin corneal or scleral tissue may loteprednol etabonate by oral gavage on gestation days 6 to 15, to target lead to perforation. The initial prescription and each renewal of the medication the period of organogenesis. Loteprednol etabonate produced fetal order should be made by a physician only after examination of the patient malformations, including absent innominate artery at 5 mg/kg (34 times the with the aid of magnification, such as slit lamp biomicroscopy, and, where RHOD); and cleft palate, agnathia, cardiovascular defects, umbilical hernia, appropriate, fluorescein staining. decreased fetal body weight and decreased skeletal ossification at 50 mg/kg Intraocular Pressure (IOP) Increase—Prolonged use of corticosteroids may (347 times the RHOD). Embryofetal lethality (resorption) was observed at result in glaucoma with damage to the optic nerve, as well as defects in visual 100 mg/kg (695 times the RHOD). The NOAEL for developmental toxicity acuity and fields of vision. Corticosteroids should be used with caution in the in rats was 0.5 mg/kg (3.4 times the RHOD). Loteprednol etabonate was presence of glaucoma. Renewal of the medication order should be made by a maternally toxic (reduced body weight gain) at 50 mg/kg/day. The NOAEL physician only after examination of the patient and evaluation of the IOP. for maternal toxicity was 5 mg/kg. Cataracts—Use of corticosteroids may result in posterior subcapsular A peri-/postnatal study was conducted in rats administered loteprednol cataract formation. etabonate by oral gavage from gestation day 15 (start of fetal period) to postnatal day 21 (the end of lactation period). At 0.5 mg/kg (3.4 times Bacterial Infections—Use of corticosteroids may suppress the host response the clinical dose), reduced survival was observed in live-born offspring. and thus increase the hazard of secondary ocular infections. In acute purulent Doses 5 mg/kg (34 times the RHOD) caused umbilical hernia/incomplete conditions of the eye, corticosteroids may mask infection or enhance existing ≥ gastrointestinal tract. Doses 50 mg/kg (347 times the RHOD) produced infection. ≥ maternal toxicity (reduced body weight gain, death), decreased number Viral Infections—Use of corticosteroid medication in the treatment of of live-born offspring, decreased birth weight, and delays in postnatal patients with a history of herpes simplex requires great caution. Use of ocular development. A developmental NOAEL was not established in this study. corticosteroids may prolong the course and may exacerbate the severity of The NOAEL for maternal toxicity was 5 mg/kg. many viral infections of the eye (including herpes simplex). Lactation—There are no data on the presence of loteprednol etabonate Fungal Infections—Fungal infections of the cornea are particularly prone to in human milk, the effects on the breastfed infant, or the effects on milk develop coincidentally with long-term local corticosteroid application. Fungus production. The developmental and health benefits of breastfeeding should invasion must be considered in any persistent corneal ulceration where a be considered, along with the mother’s clinical need for EYSUVIS and any corticosteroid has been used or is in use. Fungal cultures should be taken potential adverse effects on the breastfed infant from EYSUVIS. when appropriate. Pediatric Use—Safety and effectiveness in pediatric patients have not been Risk of Contamination—Do not to allow the dropper tip to touch any surface, established. as this may contaminate the suspension. Geriatric Use—No overall differences in safety and effectiveness have been Contact Lens Wear—The preservative in EYSUVIS may be absorbed by observed between elderly and younger adult patients. soft contact lenses. Contact lenses should be removed prior to instillation of EYSUVIS and may be reinserted 15 minutes following administration. NONCLINICAL TOXICOLOGY Carcinogenesis, Mutagenesis, Impairment of Fertility—Long-term animal ADVERSE REACTIONS studies have not been conducted to evaluate the carcinogenic potential of Adverse reactions associated with ophthalmic corticosteroids include loteprednol etabonate. Loteprednol etabonate was not genotoxic in vitro elevated intraocular pressure, which may be associated with infrequent optic in the Ames test, the mouse lymphoma thymidine kinase (tk) assay, in a nerve damage, visual acuity and field defects, posterior subcapsular cataract chromosome aberration test in human lymphocytes, or in vivo in the single formation, delayed wound healing and secondary ocular infection from dose mouse micronucleus assay. Treatment of male and female rats with pathogens including herpes simplex, and perforation of the where 25 mg/kg/day of loteprednol etabonate (174 times the RHOD based on body there is thinning of the cornea or . surface area, assuming 100% absorption) prior to and during mating caused Clinical Trials Experience—Because clinical trials are conducted under pre-implantation loss and decreased the number of live fetuses/live births. widely varying conditions, adverse reaction rates observed in the clinical trials The NOAEL for fertility in rats was 5 mg/kg/day (34 times the RHOD). of a drug cannot be directly compared to rates in the clinical trials of another For a copy of the Full Prescribing Information, please visit drug and may not reflect the rates observed in practice. www.EYSUVIS.com. The most common adverse reaction observed in clinical trials with EYSUVIS was instillation site pain, which was reported in 5% of patients. Manufactured for: Kala Pharmaceuticals, Inc. USE IN SPECIFIC POPULATIONS Watertown, MA 02472 Pregnancy—Risk Summary: There are no adequate and well controlled studies with loteprednol etabonate in pregnant women. Loteprednol Part # 2026R02 etabonate produced teratogenicity at clinically relevant doses in the rabbit Marks designated by TM or ® are owned by Kala Pharmaceuticals, Inc. and rat when administered orally during pregnancy. Loteprednol etabonate Patented. www.kalarx.com/patents produced malformations when administered orally to pregnant rabbits at © 2020 Kala Pharmaceuticals, Inc. All rights reserved. doses 1.4 times the recommended human ophthalmic dose (RHOD) and October 2020 to pregnant rats at doses 34 times the RHOD. In pregnant rats receiving Kala® oral doses of loteprednol etabonate during the period equivalent to the last trimester of pregnancy through lactation in humans, survival of offspring was US-EYS-2000115 reduced at doses 3.4 times the RHOD. Maternal toxicity was observed in rats at doses 347 times the RHOD, and a maternal no observed adverse effect level (NOAEL) was established at 34 times the RHOD. NEWS REVIEW | Get the latest at www.reviewofoptometry.com/news

Recent Myopia Demographics Examined t the 2021 ARVO virtual Photo: and 2020, which included a total of

meeting, presenters discussed Breanne McGhee, OD 194,904 tests from 389,808 eyes. Non- Anew research on myopia cycloplegic and spherical prevalence. One found that girls equivalent refraction were recorded were more prone to the condition in for each child and the prevalence of a study of kids vs. adults. In the latter myopia for each age group in each year group, men had a higher prevalence.1 was calculated. The mean spherical In another, researchers found that equivalent and prevalence of myopia home confinement during the were compared between 2020 (after COVID-19 epidemic increased the home confinement) and the previous burden in kids between the ages of five years for each age group. six and eight, who are more sensitive Gender may be correlated with trends in A substantial myopic shift (around to environmental changes than older myopia development. -0.3D) was found in the 2020 school- patients.2 based screenings when compared with In children, the rate of myopia previous years for school-aged children Gender Shift steadily increased from 2.5% to 11.5% at ages six (-0.32D), seven (-0.28D) Rising rates of myopia worldwide are and then nearly doubled to 22.5% at and eight (-0.29D). The prevalence prompting researchers and clinicians to ages six, nine and 13, respectively. of myopia in the 2020 tests was much find ways to understand its course and The prevalence was higher in adults at higher than the highest rates from 2015 halt its progression. This study sug- roughly 31%. to 2019 for children at ages six (21.5% gests gender may play a role in (or at Female gender was linked to child- vs. 5.7%), seven (26.2% vs. 16.2%) and least be correlated with) development hood myopia, but this finding was the eight (37.2% vs. 27.7%). of this condition, which was found to opposite in adults. Whether a child The differences in spherical equiva- be more common in younger girls of developed myopia or not appeared to lent and prevalence of myopia between the present generation of children, be influenced by several factors includ- 2020 and previous years were minimal yet, in adults, had a greater prevalence ing outdoor exposure, height growth, in children ages nine to 13. among males.1 sports participation, reading time and “Home confinement due to The research team from the Nether- the number of books read per month. COVID-19 was associated with a lands and Poland explored gender dif- Controlling for these factors collec- significant myopic shift for children,” ferences in myopia development based tively lessened the gender effect by the authors concluded in their on two prospective, population-based roughly 35%. In adults, education was presentation. “Younger children (ages cohorts from different generations. the most important mediator and less- six to eight) are more sensitive to The first investigation, Generation R, ened gender’s influence by about 90%. environmental changes to develop enrolled roughly 7,000 participants and These findings provide compelling myopia than older children, given tracked them from birth until young evidence that lifestyle factors and edu- that the younger children are in a adulthood. The second, the Rotterdam cation are strong drivers of myopia and critical period for the development of Study I-III, included about 9,000 par- that girls in particular should be guided myopia.”2 ticipants who were older than 45. to adhere to behaviors that lessen their “This very interesting study look- Cycloplegic refraction was measured myopia risk, the researchers said.1 ing at home confinement due to in the children at ages six, nine and COVID-19 confirms many of our 13, while automated refraction was Younger Shift During COVID-19 clinical impressions related to myopic evaluated in the adults and axial Lockdowns that were enacted during progression in this vulnerable age length and height were calculated in the COVID pandemic have meant group,” Joseph Shovlin, OD, noted. both groups. Myopia was defined as a less time spent outdoors for millions of “Home confinement likely is associ- spherical equivalent less than -0.5D in children, which raised concerns about ated with more close work, fewer out- at least one eye. whether home confinement worsened door activities and ultimately seems to Children responded to question- myopia burden. A school-based cross- lead to more myopic progression.” naires about their lifestyle, including sectional study in China investigated 1. Enthoven C, Haarman AEG, Swierkowska J, et al. Gender near work and outdoor exposure, and the refractive change and prevalence of predisposition to myopia shifts to girls in the young genera- adults were additionally queried about myopia for school-aged kids.2 tion. ARVO 2021 Annual Meeting. 2. Qian X, Li Y, Musch DC, et al. The critical period of myopia, their education levels. Change in A total of 123,535 children ages six insight from the myopic shift in school age children after height was also taken into account. to 13 were screened between 2015 COVID-19 home confinement. ARVO 2021 Annual Meeting.

JUNE 15, 2021 | REVIEW OF OPTOMETRY 9 NEWS REVIEW | Get the latest at www.reviewofoptometry.com/news

Black Patients May Have Stiffer

rimary open-angle glaucoma Photo: tonometry, IOP, Pascal dynamic

(POAG) is more prevalent and Rim Makhlouf, OD contour tonometry, or central corneal Pmore severe in popula- thickness. Mean scleral stiffness was as tions compared with subjects. follows: The reason for this is unknown, but re- • 14.37mm Hg/mm in the sub- searchers believe differences in ocular Saharan African cohort biomechanics may play a role. Joshua • 13.86mm Hg/mm in the Canavan, an OD candidate at Ohio European cohort State University, presented his group’s • 14.72mm Hg/mm in the mixed- findings on this topic in a poster ses- race cohort sion recently at the ARVO 2021 virtual The researchers noted that when Stiffer scleras might contribute to POAG’s meeting. The researchers investigated pathophysiology. adjusted for central corneal thickness corneal and scleral stiffness responses and higher IOP in the mixed-race in healthy eyes of sub-Saharan African, In the question-and-answer virtual cohort, mean scleral stiffness was European and mixed-race individuals chat, Mr. Canavan explained that significantly higher among sub-Saharan to gather baseline data and found scler- scleral stiffness was derived from the African individuals than the other two al stiffness may contribute to POAG. Corvis ST (Oculus) and calculated cohorts. Subjects included in the study had as the “difference between corneal They concluded that individuals of no history of ocular disease. They were deflection amplitude at maximum sub-Saharan African descent may have categorized by self-reported ancestry: capacity and at first applanation.” greater scleral stiffness independent of sub-Saharan African (n=40 eyes, mean He noted, “It also considers the load other ocular biomechanical parameters. age 37, 65% female), European (n=84 imposed on the cornea by the device. They believe this may contribute eyes, mean age 35, 60% female) and The sclera limits the maximum to the pathophysiology of POAG. mixed-race (n=36 eyes, mean age deformation of the cornea in response “The ramifications of this finding 32, 61% female). The researchers to the air puff, so SP-HC is a biomarker warrant further investigation,” said Mr. measured corneal hysteresis, central for scleral stiffness.” Canavan. corneal thickness and biomechanically His team found no significant corrected intraocular pressure (IOP) difference between the three ancestry Canavan J, Koons A, Mahmoud A, et al. Corneal and scleral biomechanical differences among individuals of Sub- to derive in vivo parameters of corneal cohorts in corneal hysteresis, corneal Saharan African, European and mixed-race descent. ARVO and scleral (SP-HC) stiffness. stiffness, Goldmann applanation 2021 Meeting. 10-2 Test a Better Predictor of Central Progression esearchers recently compared 24-2 pattern, can miss small changes and a decrease of 22.9% to 26.5% when the variability and ability to due to the degree of spacing of tested compared with the central 24-2.1 Rdetect visual field (VF) progres- points.”2 The researchers believe these sion of the 24-2, central 24-2 and 10-2 The study included a total of 52,806 findings contribute to current evidence tests in eyes with abnormal VFs. The 24-2 and 11,966 10-2 VF tests from of the potential value of 10-2 testing team determined that the time to 7,307 eyes from the Glaucoma Re- in glaucoma patient management and detect central VF progression was re- search Network database. Only eyes in clinical trial design. Using 10-2 tests duced with 10-2 mean deviation (MD) with five or more visits and two or more could result in a moderate increase due to the test’s lower variability.1 years of follow-up were included.1 in the ability to detect progression “Identifying glaucoma progression Upon evaluating all three patterns, centrally, without compromising the perimetrically can be challenging due MD variability was highest within the clinician’s assessment of non-central to variability in testing and patient -5dB to -20dB range and consistently regions.1 responses,” noted Joseph Sowka, an lower with the 10-2 compared with the 1. Susanna FN, Melchior B, Paula JS, et al. Variability and attending optometric physician at 24-2 and central 24-2. Overall, time to power to detect progression of different pat- Center for Sight in Sarasota, FL, in his detect confirmed significant progression terns. Ophthalmology. April 20, 2021. [Epub ahead of print]. commentary on the study for Practice at 80% power was the lowest with the 2. Freeman KF, Sowka J. Progression detection with different visual field patterns. Practice Update. www.prac- Update. “Additionally, the most used 10-2 test, with a decrease of 14.6% to ticeupdate.com/c/117552/2/5. May 10, 2021. Accessed perimetric program in glaucoma, the 18.5% when compared with the 24-2 May 19, 2021.

10 REVIEW OF OPTOMETRY | JUNE 15, 2021 Helping Heroes See Clear And Stay Safe

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ORS Resident Case Report Contest Winners n April 2016, optometry lost a The report detailed the manage- The full text and images of both case reports are giant when the author of the available online at www.reviewofoptometry.com. ment of a Native American woman Iseminal work Primary Care of the diagnosed with a choroidal melanoma Posterior Segment, Larry Alexander, information to the community,”says and discussed the findings and clinical OD, died. In addition to being an Julie Rodman, OD, professor and utility of supplementary multimodal optometric physician, author and chief of the Fort Lauderdale (Bro- imaging. According to Dr. Bade, early educator at the University of Alabama ward) Eye Care Institute at Nova and accurate detection of choroidal Birmingham School of Optometry, Southeastern University in Florida, melanoma has greatly improved Dr. Alexander was a past president and ORS treasurer.“This year, our with the use of contemporary multi- of the Optometric Retina Society winning manuscripts focused on modal imaging technology including (ORS). That group chose to honor his timely topics and provided insight enhanced-depth imaging OCT, fundus legacy by accepting case reports from into the diagnosis and management of autofluorescence and widefield fundus optometric residents across the coun- entities that are often challenging to photography. try relating to vitreoretinal disease. diagnose,” she notes. Contemporary management of The two cases shown here, selected choroidal melanoma most often in- by the ORS Awards Committee, were Case 1: Choroidal Melanoma cludes plaque radiotherapy, and newer, co-winners of the fifth annual Larry This case study, presented by Amy innovative methods are promising. Alexander Resident Case Report Bade, OD, a low vision and ocular Although the condition is uncommon, Contest. The contest is sponsored by disease resident at the Northeastern Dr. Bade believes it is highly critical Zeiss, Heidelberg and Optos. State University College of Optometry, that eye care providers be familiar with “When reviewing submissions, we reviewed characteristic risk factors for and able to recognize high-risk features look for manuscripts that are well choroidal melanoma and the use of suggestive of small choroidal melano- written, include high-quality im- multimodal imaging to assist in the mas by using multimodal imaging. ages and provide new and innovative detection of these key features.

Photos: Case 2: CHRRPE in a Pediatric Patient Amy Bade, OD Isis Topete, OD, a pediatric optometry resident at the Duke University Eye Center, presented a case of bilateral, combined hamartoma of the retina and retinal pigment epithelium (CHRRPE) leading to a suspected diagnosis of neu- rofibromatosis type 2 (NF2). CHRRPE are rare intraocular tumors charac- terized by the malformation of the neurosensory retina, retinal pigment Case 1. Comparing images from 2020 (left) and 2018 (right) of the pigmented choroidal epithelium and adjacent vitreous. NF2 tumor of the right eye demonstrates obvious expansion of the choroidal melanoma. is a multiple neoplasia syndrome that

Photos: Isis Topete predisposes patients to the develop- ment of tumors in the nervous system, eyes and skin. In her case report, Dr. Topete , OD discussed the clinical characteristics of CHRRPE, as well as other potential ocular manifestations of neurofibroma- tosis type 2 and the importance of early diagnosis. She noted that it is important for eye care practitioners to recognize that children with NF2 more common- ly present with ocular, dermatological Case 2. Fundus images of the right and left eyes reveal that CHRRPE lesions often appear and/or neurological signs and require elevated and pigmented (usually , white or brown, but may be , or ). careful ophthalmic examination..

12 REVIEW OF OPTOMETRY | JUNE 15, 2021 ADVERTORIAL Helping Parents Find Confidence in Myopia Management Using Clinical Data Clinical studies and data prove contact lenses are safe for children to use, but many parents are hesitant to say “yes” to a contact lens program at the start due to concerns about ocular side eŸ ects such as redness or infections, and the maturity of the child to handle the lenses appropriately. Here’s how Dr. Roxanne Achong-Coan from Coan Eye Care & Optical Boutique uses clinical data in her myopia management conversations with parents. Roxanne Achong-Coan, OD, FAAO, FIAOMC, FSLS, Coan Eye Care & Optical Boutique, Ocoee, Florida

When discussing contact lens • Ocular health. I share a new study myopia is, why and when it progresses options for myopia management that followed children wearing and how it can aŸ ect their child’s eye with parents, what is your primary MiSight® 1 day* daily disposable health long-term. Once a parent learns recommendation? lenses over six years and found their that myopia progresses quickly at a I always lead with CooperVision’s ocular health was similar to when young age, and we use data to show they started wearing lenses, proving what could happen to their vision and Brilliant Futures™ Myopia Management there is a minimal impact on the ocular health long-term, then parents Program with MiSight® 1 day because ocular surface and that lenses are truly understand the importance of it is the only FDA-approved* so“ very safe.4 managing myopia early rather than contact lens to slow the progression waiting until their child is older. of myopia in children, aged 8 – 12 • Applying and removing contact years at the initiation of treatment. lenses. I talk about the CLIP study What tips do you have for ECPs The supporting clinical data is also that concludes it only takes younger who are just starting to have incredibly strong. The fi rst three years children about 15 minutes longer to conversations with parents about of data conclusions showed the lens learn how to apply and remove their 5 myopia management and want to slowed myopia progression by 59% in lenses. cite clinical data? and 52% in axial length • Switching from glasses to contact 1† Know the studies you want to share on average. Over a 6-year period, lenses. I share the ACHIEVE study thoroughly. In conversation, you should one-in-four children wearing MiSight® that found children and teens had 2†‡ simply summarize studies and mention 1 day did not change in prescription . signifi cantly improved satisfaction a few of the best results because Early identifi cation of myopia risk and with their vision correction, and hearing all the data could overwhelm early intervention is key. I am confi dent contact lenses also improved how a parent. Most parents won’t press in communicating these clinically they felt about themselves, their further into the data, but if a parent proven outcomes to parents. For appearance, self-esteem and ability does, you’ll want to know your 6 parents, they are confi dent because it’s to perform activities. numbers and details of the study. Your the only option that is FDA approved. confi dence translates into a parents’ Does sharing clinical data help confi dence. Parents look for your Which studies do you fi nd are most parents in deciding to pursue clinical expertise to prescribe the best informational for parents to help myopia management for their child? option for their child. It’s also a best them overcome their hesitations Sharing data is a great way to show practice to provide trifold brochures or regarding their child wearing parents that these medical devices a summary sheet that parents can take contact lenses? have been studied intently over time home to review with their spouse. Choosing studies to share depends on and having so many studies with the specifi c parent concern: positive outcomes proves that contact lenses are safe for their young child, • Ocular side eŸ ects. I share a study so that is helpful in the decision- that concludes the incident of making process. However, discussing corneal infi ltrative events in children clinical data is only one part of the 8 – 12 years old is no higher than conversation. Parents ultimately it is in adults, and in some cases is decide to pursue myopia management markedly lower.3 because we educate them on what

References: * Indications for use: MiSight® 1 day (omafi lcon A) so“ (hydrophilic) contact 1 Chamberlain P, et al. A 3-year randomized clinical trial of MiSight® lenses for myopia control. Optom Vis Sci. 2019; 96(8):556-567. Compared lenses for daily wear are indicated for the correction of myopic ametropia and to a single vision 1 day lens over a 3 year period. for slowing the progression of myopia in children with non-diseased eyes, 2 Chamberlain P, Arumugam B, Jones D et al. Myopia Progression in Children wearing Dual-Focus Contact Lenses: 6-year fi ndings. Optom Vis who at the initiation of treatment are 8-12 years of age and have a refraction Sci. 2020;97(E-abstract): 200038. of -0.75 to -4.00 diopters (spherical equivalent) with ≤ 0.75 diopters of 3 Bullimore, M. The Safety of So“ Contact Lenses in Children. Optom Vis Sci. 2017 Jun; 94(6):638-646. astigmatism. The lens is to be discarded a“ er each removal. 4 Woods, J., et al. Ocular Health of Children Wearing Daily Disposable Contact Lenses Over a 6-Year Period. Contact Lens Anterior Eye. 2021. 5 Walline JJ, Jones LA, Rah MJ, et al. Contact lenses in pediatrics (CLIP) study: chair time and ocular health. Optom Vis Sci. 2007;84: 896-902. † Compared to a single vision 1 day lens over a 3 year period. 6 Walline JJ, et al. The Adolescent and Child Health Initiative to Encourage Vision Empowerment (ACHIEVE) study design and baseline data. ‡ No clinically meaningful change in refractive error -0.25D or less from baseline. Optom Vis Sci. 2006 Jan;83(1):37-45. ©2021 CooperVision, Inc. 11137RO 05/21 KIDS SHOULD GROW STRONGER Their myopia shouldn’t.

ICAL LIN LY C

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Introducing the Brilliant Futures™ Myopia Management Program with MiSight® 1 day contact lenses. MiSight® 1 day is the fi rst and only FDA-approved* so contact lens to slow the progression of myopia in children aged 8-12 at the initiation of treatment.1† 59 % 52 % Slows Myopia Progression Axial Length Child Friendly1 on average1† Elongation Reduction 1 day lens on average1†

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*Indications for use: MiSight® 1 day (omafi lcon A) so (hydrophilic) contact lenses for daily wear are indicated for the correction of myopic ametropia and for slowing the progression of myopia in children with non-diseased eyes, who at the initiation of treatment are 8-12 years of age and have a refraction of -0.75 to -4.00 diopters(spherical equivalent) with ≤ 0.75 diopters of astigmatism. The lens is to be discarded a er each removal. †Compared to a single vision 1 day lens over a 3 year period. 1Chamberlain P, et al. A 3-year randomized clinical trial of MiSight® lenses for myopia control.Optom Vis Sci. 2019; 96(8):556-567. ©2021 CooperVision, Inc. 10307RCCL 02/21 CATCH UP ON THE LATEST NEWS Stories post online every weekday features Weekly recap emailed every Sunday REVIEW OF OPTOMETRY • Vol. 158, No. 6 • JUNE 15, 2021 34 12th ANNUAL Understanding Today’s RETINA Progressives REPORT Help patients choose and use these lenses with fewer hassles and greater success. By Barry Santini, ABOM, Van Y. Rue and Brent McCardle, LDO

42 60 Retina Care: Stroke of the Eye: The Next Wave Are You Prepared? Fifteen years into the anti-VEGF era, When retinal arterial occlusion strikes, protocols are evolving to improve you and the patient have only a few outcomes, reduce treatment burden hours to act if you want the best odds or both. Here’s what’s new and what’s of preserving vision. coming soon. By Marc Myers, OD, By Anna Bedwell, OD, and Andrew Gurwood, OD and Larissa Krenk, OD 52 68 Get Serious About Be a Retina Referral Central Serous Rock Star We Welcome Chorioretinopathy ODs can—and should—take the lead Your Comments Mineralocorticoid receptor antagonists on screening and monitoring routine Feedback from the may present an effective option for cases, only sending to specialists the community provides important insights early intervention. patients that truly need advanced care. about clinical practice. If you would like to share your thoughts on the topics By Mohammad Rafieetary, OD, By Catlin Nalley, discussed in this issue—or the wider fi eld Jessica Haynes, OD, and Roya Attar, OD Contributing Writer of optometry at large—please write to: [email protected] 72 EARN 2 CE CREDITS What to Do When it’s Not AMD Recently added! Learn how to identify and diagnose the multitude of Enjoy our content on other macular dystrophies and degenerations. Instagram at @revoptom By Jessica Haynes, OD

JUNE 15, 2021 | REVIEW OF OPTOMETRY 15 departments REVIEW OF OPTOMETRY • JUNE 15, 2021 5 28 90 NEWS REVIEW FOCUS ON REFRACTION OCULAR SURFACE REVIEW Space: The Final Frontier Five Easy Pieces Work cheiroscopic tracing into your workup. Simple steps to increase diagnostic accuracy. 20 Marc B. Taub, OD, MS, and Paul Harris, OD Paul M. Karpecki, OD OUTLOOK Profit and Loss Who wins and who loses as more optometrists 91 choose employment over entrepreneurship? ADVERTISERS INDEX Jack Persico, Editor-in-Chief 32 92 22 CODING CONNECTION RETINA QUIZ THROUGH MY EYES Bring the Retina into View Dredging Up the Past Rescuing the Retina The often forgotten is now in focus. Scarring and a telltale history point to the diagnosis. John Rumpakis, OD, MBA Innovations are expanding optometry’s role in care Mark Dunbar, OD, and Stéphane Fitoussi, OD as specialists find themselves overburdened and demand piles up. Paul M. Karpecki, OD 84 CORNEA AND CONTACT LENS Q+A Through Thick and Thin 24 Drug helps endothelial function but also yields edema. CHAIRSIDE Joseph P. Shovlin, OD 94 The New New SURGICAL MINUTE More and more people are getting vaccinated—you know what that means. 86 IOP Control: Montgomery Vickers, OD GLAUCOMA GRAND ROUNDS Time to Play Offense? Don’t Feed the Hand Early surgery minimizes the treatment burden. Derek Cunningham, OD, Walter Whitley, OD, that Bites You and Mackenzie Macintyre, OD 26 Manage patients to the best of your ability before a CLINICAL QUANDARIES referral that may do more harm than good. Burn, Baby, Burn James L. Fanelli, OD 95 It is essential to determine the nature of a chemical injury when faced with this ocular emergency. PRODUCT REVIEW Paul C. Ajamian, OD 88 THERAPEUTIC REVIEW 96 Not a BRITE Idea CLASSIFIED ADVERTISING Beware this severe complication from a rare cosmetic procedure. Joseph W. Sowka, OD 106 VISIT US ON SOCIAL MEDIA DIAGNOSTIC QUIZ Facebook: www.facebook.com/revoptom The Plot Thickens When a patient’s clinical outlook changes radically, Twitter: twitter.com/revoptom so too should your approach to differential diagnosis. Instagram: www.instagram.com/revoptom Andrew S. Gurwood, OD

16 REVIEW OF OPTOMETRY | JUNE 15, 2021 The most studied eye vitamin brand.†

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PreserVision is a trademark of Bausch & Lomb Incorporated or its affi liates. AREDS and AREDS2 are registered trademarks of the United States Department of Health and Human Services (HHS). © 2021 Bausch & Lomb Incorporated or its affi liates. PN09897 PVN.0040.USA.21 Business Offices 19 Campus Boulevard, Suite 101 Leadership in clinical care Newtown Square, PA 19073 Subscription inquiries (877) 529-1746 (USA only) CLINICAL EDITORS outside USA, call (847) 763-9630 PUBLISHER MICHAEL HOSTER CHIEF CLINICAL EDITOR ~ PAUL M. KARPECKI, OD (610) 492-1028 ASSOCIATE CLINICAL EDITORS ~ JOSEPH P. SHOVLIN, OD, CHRISTINE SINDT, OD [email protected]

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18 REVIEW OF OPTOMETRY | JUNE 15, 2021 Give Patients an EYE-OPENING Lift With a Daily Drop of Upneeq® (oxymetazoline hydrochloride ophthalmic solution), 0.1% 1 The only FDA-approved prescription eyedrop proven to lift upper in adults with acquired blepharoptosis (low-lying lids)1 Learn more at Upneeq.com.

INDICATION ADVERSE REACTIONS Upneeq® (oxymetazoline hydrochloride ophthalmic Adverse reactions that occurred in 1-5% of subjects solution), 0.1% is indicated for the treatment of treated with Upneeq were punctate keratitis, acquired blepharoptosis in adults. conjunctival hyperemia, dry eye, blurred vision, instillation site pain, eye irritation, and headache. IMPORTANT SAFETY INFORMATION DRUG INTERACTIONS WARNINGS AND PRECAUTIONS • Alpha-adrenergic agonists, as a class, may impact • Alpha-adrenergic agonists as a class may impact blood pressure. Caution in using drugs such as blood pressure. Advise Upneeq patients with beta blockers, anti-hypertensives, and/or cardiac cardiovascular disease, orthostatic hypotension, glycosides is advised. Caution should also be and/or uncontrolled hypertension or hypotension exercised in patients receiving alpha adrenergic to seek medical care if their condition worsens. receptor antagonists such as in the treatment • Use Upneeq with caution in patients with cerebral of cardiovascular disease, or benign prostatic or coronary insuffi ciency or Sjögren’s syndrome. hypertrophy. Advise patients to seek medical care if signs • Caution is advised in patients taking monoamine and symptoms of potentiation of vascular oxidase inhibitors which can affect the metabolism insuffi ciency develop. and uptake of circulating amines. • Upneeq may increase the risk of angle closure glaucoma in patients with untreated narrow-angle To report SUSPECTED ADVERSE REACTIONS glaucoma. Advise patients to seek immediate or product complaints, contact medical care if signs and symptoms of acute RVL Pharmaceuticals at 1-877-482-3788. narrow-angle glaucoma develop. You may also report SUSPECTED ADVERSE • Patients should not touch the tip of the single REACTIONS to the FDA at 1-800-FDA-1088 patient-use container to their eye or to any surface, or www.fda.gov/medwatch. in order to avoid eye injury or contamination of Please see next page for Brief Summary of full the solution. Prescribing Information.

Reference: 1. Upneeq® (oxymetazoline hydrochloride ophthalmic solution), 0.1%. [Prescribing Information].

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FONTSUpneeq is a registered trademark of RVL Pharmaceuticals, Inc. RVL: Verdigris MVB Pro Text PHARMACEUTICALS,©2021 INC.: RVL Forma DJR Pharmaceuticals, Text Inc. PM-US-UPN-0197 01/21 UPNEEQ® (oxymetazoline hydrochloride ophthalmic 8 USE IN SPECIFIC POPULATIONS * solution), 0.1%, for topical ophthalmic use 8.1 Pregnancy * Each mL of UPNEEQ contains 1 mg of oxymetazoline hydrochloride, equivalent to 0.09 mg (0.09%) of oxymetazoline free base. Risk Summary There are no available data on UPNEEQ use in pregnant women BRIEF SUMMARY: The following is a brief summary only; to inform a drug-associated risk for major birth defects and see full Prescribing Information at https://www.upneeq.com/ miscarriage. In animal reproduction studies, there were no Upneeq-PI.pdf for complete information. adverse developmental effects observed after oral administration of oxymetazoline hydrochloride in pregnant rats and rabbits 1 INDICATIONS AND USAGE at systemic exposures up to 7 and 278 times the maximum UPNEEQ is indicated for the treatment of acquired blepharoptosis recommended human ophthalmic dose (MRHOD), respectively, in adults. based on dose comparison. [see Data]. The estimated background risks of major birth defects and miscarriage for the indicated 2 DOSAGE AND ADMINISTRATION population are unknown. All pregnancies have a background risk Contact lenses should be removed prior to instillation of UPNEEQ of , loss, or other adverse outcomes. In the U.S. general and may be reinserted 15 minutes following its administration. population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15- If more than one topical ophthalmic drug is being used, the drugs 20%, respectively. should be administered at least 15 minutes between applications. Data 4 CONTRAINDICATIONS Animal Data None. Effects on embryo-fetal development were evaluated in rats and rabbits following oral administration of oxymetazoline hydrochloride 5 WARNINGS AND PRECAUTIONS during the period of organogenesis. Oxymetazoline hydrochloride 5.1 Potential Impacts on Cardiovascular Disease did not cause adverse effects to the fetus at oral doses up to 0.2 Alpha-adrenergic agonists may impact blood pressure. UPNEEQ mg/kg/day in pregnant rats during the period of organogenesis (28 should be used with caution in patients with severe or unstable times the MRHOD, on a dose comparison basis). Oxymetazoline cardiovascular disease, orthostatic hypotension, and uncontrolled hydrochloride did not cause adverse effects to the fetus at oral hypertension or hypotension. Advise patients with cardiovascular doses up to 1 mg/kg/day in pregnant rabbits during the period of disease, orthostatic hypotension, and/or uncontrolled hypertension/ organogenesis (278 times the MRHOD, on a dose comparison basis). hypotension to seek immediate medical care if their condition Maternal toxicity, including decreased maternal body weight, was worsens. produced at the high dose of 1 mg/kg/day in pregnant rabbits and was associated with findings of delayed skeletal ossification. 5.2 Potentiation of Vascular Insufficiency In a rat prenatal and postnatal development study, oxymetazoline UPNEEQ should be used with caution in patients with cerebral or hydrochloride was orally administered to pregnant rats once daily coronary insufficiency, or Sjögren’s syndrome. Advise patients to from gestation day 6 through lactation day 20. Maternal toxicity was seek immediate medical care if signs and symptoms of potentiation produced at the high dose of 0.2 mg/kg/day (28 times the MRHOD, of vascular insufficiency develop. on a dose comparison basis) in pregnant rats and was associated 5.3 Risk of Angle Closure Glaucoma with an increase in pup mortality and reduced pup body weights. UPNEEQ may increase the risk of angle closure glaucoma in patients Delayed sexual maturation was noted at 0.1 mg/kg/day (14 times the with untreated narrow-angle glaucoma. Advise patients to seek MRHOD, on a dose comparison basis). Oxymetazoline hydrochloride immediate medical care if signs and symptoms of acute angle did not have any adverse effects on fetal development at a dose of closure glaucoma develop. 0.05 mg/kg/day (7 times the MRHOD, on a dose comparison basis). 5.4 Risk of Contamination 8.2 Lactation Patients should not touch the tip of the single patient-use container Risk Summary to their eye or to any surface, in order to avoid eye injury or No clinical data are available to assess the effects of oxymetazoline contamination of the solution. on the quantity or rate of breast milk production, or to establish the level of oxymetazoline present in human breast milk post- 6 ADVERSE REACTIONS dose. Oxymetazoline was detected in the milk of lactating rats. The 6.1 Clinical Trials Experience developmental and health benefits of breastfeeding should be Because clinical trials are conducted under widely varying considered along with the mother’s clinical need for UPNEEQ and conditions, adverse reaction rates observed in the clinical trials of any potential adverse effects on the breastfed child from UPNEEQ. a drug cannot be directly compared to rates in the clinical trials of 8.4 Pediatric Use another drug and may not reflect the rates observed in practice. Safety and effectiveness of UPNEEQ have not been established in A total of 360 subjects with acquired blepharoptosis were treated pediatric patients under 13 years of age. with UPNEEQ once daily in each eye for at least 6 weeks in three 8.5 Geriatric Use controlled Phase 3 clinical trials, including 203 subjects treated with UPNEEQ for 6 weeks and 157 subjects treated with UPNEEQ for 12 Three hundred and fifteen subjects aged 65 years and older received weeks. Adverse reactions that occurred in 1-5% of subjects treated treatment with UPNEEQ (n = 216) or vehicle (n = 99) in clinical trials. with UPNEEQ were punctate keratitis, conjunctival hyperemia, dry No overall differences in safety or effectiveness were observed eye, blurred vision, instillation site pain, eye irritation, and headache. between subjects 65 years of age and older and younger subjects.

7 DRUG INTERACTIONS 10 OVERDOSAGE 7.1 Anti-hypertensives/Cardiac Glycosides Accidental oral ingestion of topical intended solutions (including ophthalmic solutions and nasal sprays) containing imidazoline Alpha-adrenergic agonists, as a class, may impact blood pressure. derivatives (e.g., oxymetazoline) in children has resulted in serious Caution in using drugs such as beta-blockers, anti-hypertensives, adverse events requiring hospitalization, including nausea, and/or cardiac glycosides is advised. vomiting, lethargy, tachycardia, decreased respiration, bradycardia, Caution should also be exercised in patients receiving alpha hypotension, hypertension, sedation, somnolence, , stupor, adrenergic receptor antagonists such as in the treatment of hypothermia, drooling, and coma. Keep UPNEEQ out of reach cardiovascular disease, or benign prostatic hypertrophy. of children. 7.2 Monoamine Oxidase Inhibitors PATIENT COUNSELING INFORMATION Caution is advised in patients taking MAO inhibitors which can Advise the patient to read the FDA-approved patient labeling affect the metabolism and uptake of circulating amines. (Instructions for Use).

Manufactured for: RVL Pharmaceuticals, Inc. Bridgewater, New Jersey 08807 ©2021 RVL Pharmaceuticals, Inc. UPNEEQ is a registered trademark of RVL Pharmaceuticals, Inc. PM-US-UPN-0203 01/21 By Jack Persico Editor-in-Chief OUTLOOK

Founded 1891 Founding Editor, Frederick Boger

EDITOR-IN-CHIEF JACK PERSICO (610) 492-1006 • [email protected] Profit and Loss SENIOR EDITOR JULIE SHANNON (610) 492-1005 • [email protected] Who wins and who loses as optometrists choose employment

ASSOCIATE EDITOR over entrepreneurship? CATHERINE MANTHORP (610) 492-1043 • [email protected] ptometry is one of the few The AOA’s workforce study found ASSOCIATE EDITOR MARK DE LEON remaining professions with a that employed and self-employed (610) 492-1021 • [email protected] still-vibrant culture of single- optometrists worked about the same

ASSOCIATE EDITOR doctor private practices, giving its number of hours and were equally LEANNE SPIEGLE O practitioners a chance to live out the productive and satisfied in their roles. (610) 492-1026 • [email protected] classic “hang a shingle” mode of mak- Interestingly, the employed ODs saw SPECIAL PROJECTS MANAGER ing a living. Or at least it used to be a more patients per week than those JILL GALLAGHER (610) 492-1037 • [email protected] thriving part of optometry. More ODs who were self-employed (58 vs. 54)

SENIOR ART DIRECTOR are turning away from private practice “This is despite the number of hours JARED ARAUJO ownership and opting instead to choose worked per week being similar,” the (610) 492-1032 • [email protected] a paycheck over a P&L statement. study points out, likely given the added DIRECTOR OF CE ADMINISTRATION A recent study dissecting the profes- hassles of practice administration that REGINA COMBS (212) 274-7160 • [email protected] sion’s workforce has much to say about fall to a self-employed doctor. the state of optometry now and in the One setback for employed ODs is Clinical Editors near future. Age, gender and ethnicity income, as those who earned the most Chief Clinical Editor • Paul M. Karpecki, OD characteristics, patient volume, hours tended to be self-employed. Another Associate Clinical Editors Joseph P. Shovlin, OD, Christine W. Sindt, OD worked, income levels and a host of seems to be fewer self-employment op-

Clinical & Education Conference Advisor other factors all get rigorous attention. portunities for women, as only 43% of Paul M. Karpecki, OD There’s much about the study, under- female ODs in the study practiced that Case Reports Coordinator • Andrew S. Gurwood, OD taken by the AOA, worth digging into; way, compared with 66% of their male Clinical Coding Editor • John Rumpakis, OD, MBA you can read our full summary of it counterparts. The report didn’t address online in our news feed now and next underlying reasons for the distinction, Columnists month in the print edition. but one popular explanation is that the Chairside – Montgomery Vickers, OD Clinical Quandaries – Paul C. Ajamian, OD One of the most interesting statistics added burden of childcare that women Coding Connection – John Rumpakis, OD was the report’s finding that the ranks disproportionately shoulder makes self- Cornea and Contact Lens Q+A – Joseph P. Shovlin, OD of employed optometrists jumped 15% employment a harder proposition for Diagnostic Quiz – Andrew S. Gurwood, OD (from 29% to 44%) in five years, from them. (Does that ring true? Please write The Essentials – Bisant A. Labib, OD Focus on Refraction – Marc Taub, OD, Paul Harris, OD 2012 to 2017. This period, mind you, to us at [email protected] Glaucoma Grand Rounds – James L. Fanelli, OD is just before a wave of private equity with your thoughts!) Ocular Surface Review – Paul M. Karpecki, OD acquisitions gobbled up optometry Who’s doing the employing? That’s Retina Quiz – Mark T. Dunbar, OD practices. Surely, the number of em- not delineated either, but anecdot- Surgical Minute – Derek Cunningham, OD, Walter Whitley, OD Therapeutic Review – Joseph W. Sowka, OD ployed ODs today is even higher. ally I encounter more and more ODs Through My Eyes – Paul M. Karpecki, OD Is this a good or a bad thing? I doubt who hail from within ophthalmology’s Urgent Care – Richard B. Mangan, OD there’s a simple answer, as there are private practices and teaching institu- so many different stakeholders in the tions among the doctors who write for Editorial Offices delivery of optometric care: ODs of Review. This is obviously not a repre- 19 Campus Blvd., Suite 101• Newtown Square, PA 19073 course, their patients and employees, sentative sample, but perhaps it is a medical equipment and pharma com- bellwether. New grads enter the field panies, health insurers and lots more. with abundant clinical skill in medi-

Jobson Medical Information/WebMD Some bemoan the decline of solo cal eye care and eagerness to use it. If 395 Hudson Street, 3rd Floor, New York, NY 10014 practice, out of a romantic attachment ophthalmologists are seeing the value

Subscription inquiries: (877) 529-1746 to the idea. But with a few exceptions, of adding an OD or two to their offices, Continuing Education inquiries: (800) 825-4696 it’s hard to see overwhelming losses it validates the strength of optometry’s

Printed in USA from the trend toward employment. institutions—and its very calling. g

JUNE 15, 2021 | REVIEW OF OPTOMETRY 21 By Paul M. Karpecki, OD Chief Clinical Editor Through my eyes

or earlier stages of AMD may be best served with a carotenoid supplement Rescuing the Retina such as MacuHealth or Ocuvite. Mac- uHealth’s new micromicellar formula- Innovations are expanding optometry’s role in care as tion showed greater bioavailability with specialists find themselves overburdened and demand piles up. a six times higher serum response and 1.5x retinal response over a six-month his month I talked all about the treat and extend approach with dosing supplementation period.2 retina with one of the best, John extending to three months in over The introduction of a head-mounted Kitchens, MD, a previous chief 70% of patients. dark adaptometer (AdaptDx Pro, Tsurgical fellow at Bascom Palmer The port delivery system (PDS, MacuLogix) is helping us improve our who practices at Retina Associates of Genentech) should also be approved ability to accurately diagnose and man- Kentucky. Here are some highlights of in 2022. This is tremendously excit- age AMD patients. This functional test our talk. ing as it is the first sustained-release can be administered anywhere there is drug delivery system for anti-VEGF. a comfortable chair and with minimal Central Serous technician time because the system’s Probably the biggest current break- voice guidance system is consistently through is in imaging, specifically The retina is one of the great administering adaptive feedback and enhanced-depth visualization using opportunities for our profession, instructions to the patient. This device spectral domain or swept-source OCT. with exciting developments allows us to make dark adaptation test- These technologies have helped us ing our standard of care for every at-risk improving our ability to help understand the critical role of the patient age 50 and older. , which is important because patients with sight-threatening Monitoring carotenoid levels in the the pathogenesis of central serous pathologies. serum, which have been shown to retinopathy (CSR) is often related correlate with macular pigment, can be to a thickened choroid (i.e., pachy- Patients in the trial benefited from easily performed with a biophotonic choroid). While there have been six-month dosing and sustainability of hand scanner in less than 30 seconds. reports of systemic therapies for CSR treatment effect. Although the Phase Now more than ever, patients under- such as mineralocorticoid receptor III trials involved six-month refills, stand the importance of overall health; antagonists, aldosterone antagonists the Phase II LADDER study (more carotenoid levels have been shown and even melatonin, the mainstay open-ended, with as-needed refills) to not only affect AMD but improve of treatment is observation for early showed the average refill time to be health and cognitive ability in Alzheim- occurrences and laser or PDT therapy over a year (median 15 months). er’s patients.1 Lastly, at-home monitor- for chronic cases or cases where rapid ing (Notal Vision) can help optometry visual improvement is necessary (e.g., Exciting Developments identify wet AMD earlier and improve pilots). There will be sustained efforts to patients’ prognosis. identify patients with diabetic eye The retina is one of the great op- In the Pipeline disease earlier, as current therapies portunities for our profession, with The retinal disease drug pipeline is show improvements in retinopathy exciting developments improving our also exciting. First, we should have and a decrease in vision-threatening ability to help patients with sight- faricimab (Genentech) approved in complications such as PDR and DME. threatening pathologies. ■ early 2022. This is a bispecific anti- The NEI’s 10-year follow-on study of 1. Yuan C, Chen H, Wang Y, et al. Dietary carotenoids related body, meaning it binds two different AREDS2 reaffirms that we can signifi- to risk of incident Alzheimer dementia (AD) and brain AD targets: VEGF and ANG-2. The latter cantly slow progression of intermediate neuropathology: a community-based cohort of older adults. The is felt to play a role in inflammation to advanced dry AMD with AREDS2 American Journal of Clinical Nutrition. 2021 Jan 113(1):200-08. and vascular destabilization. Phase formulations like Pre-serVision and 2. Green-Gomez M, Prado-Cabrero A, Moran R, et al. The impact of formulation on lutein, ze-axanthin, and meso-zeaxanthin III studies for wet AMD and DME many others. Patients with a family bioavailability: A Randomised Double-Blind Placebo-Controlled showed this drug could be used in a history of AMD, low carotenoid levels Study. Antioxidants (Basel). 2020 Aug 18;9(8):767.

Dr. Karpecki is medical director for Keplr Vision and the Dry Eye Institutes of Kentucky and Indiana. He is the Chief Clinical Editor for Review of Optometry and About Dr. Karpecki chair of the New Technologies & Treatments conferences. A fixture in optometric clinical education, he consults for a wide array of ophthalmic clients, including ones discussed in this article. Dr. Karpecki’s full disclosure list can be found in the online version of this article at www.reviewofoptometry.com.

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2021. MacuLogix, Inc. All rights reserved. MM-487 By Montgomery Vickers, OD ChairSide

formerly very happy glasses wearers who are now so sick of mask-induced The New New foggy glasses that they want contact More and more people are getting vaccinated—you know what lenses for the first time. Too bad they are all 53 years old, their prescription that means. is plano -3.25x137 with a +2.50 add and they just took a new job working o, the country is slowly but First, the fallout from COVID on computers all day. Darn that Gill surely evolving from the hide- did not improve anyone’s eyesight. Bates! It would be much easier if in-your-attic, the-sky-is-falling, Years ago, in a smoky room in they all just stuck with the retinal Swhy-should-I-pay-for-a-year’s- Philadelphia, a few of us barely- detachments. supply-of-contact-lenses-when-we- passing optometry students came up And my staffers? God bless ’em. are-all-going-to-die mentality. with something people would have They are all pregnant. Well, not Bill. Have you had your vaccine? I have. to use every day that would screw Not yet. Has this changed my day-to-day up their eyes. This is how the idea Now that I am vaccinated, I do existence? Yes; I no longer have an of the sandpaper contact lens came sense that my patients, overall, excuse not to dog- and babysit every to be. Since we were only dreaming, are less scared to come in and are weekend. (Hey, prior to the vaccine, someone suggested we call a college quicker to pull their masks off their I sat around doing nothing out of love dropout and get him to use all his noses when the phoropter fogs up. I for my family. I am just naturally a newly-acquired free time to create guess they think that my vaccination giving person.) this monster. To protect the innocent, protects them. I’m sorry, did I miss In the office, we still wear masks. I’ll just call him “Gill Bates.” something? Our patients still wear masks. Guess Unfortunately, Gill moved on to his On my end, I decided, now that we’ll have to start brushing our teeth other project, which eventually still the pandemic has been going on for again soon, but that can wait a little screwed up everyone’s eyes, before more than a year, maybe, as a first- longer. this one could take off. All’s well that line healthcare provider, I should My wife and I have gained the ends well, I guess. learn what the symptoms of courage to get back to the gym. I I also recall when COVID-19 are. Here’s what for one was surprised that I had not pharmaceutical companies I found: headaches, body declined in my ability to bench press made the important decision aches…uh, check! Did I lose 12 pounds and then spend the next to quit trying to cure my sense of hour shooting the breeze with the heart disease to make smell? Well, it lifeguards while my wife actually room for the more was certainly exercised. important research damaged during One thing that didn’t change was on eye drops to my all-male eating out. I did get more particular treat itchy eyes. Big college experience about ordering foods I can detect feather in their caps. (self defense). sneeze remnants on, though. Also, Now their sights are set And my sense before COVID, I would eat anything. on eliminating presbyopia. of taste? Have Now, I eat everything but sea urchin. Cancer can wait. Priorities. you seen how I dress? Case Getting picky. I knew there was some closed. It turns out I have In large part, optometry was not correlation between stress had COVID since 1992. permanently destroyed—just a little and various ocular conditions, You cannot defeat an bruised. We’re recovering and now but I am truly shocked at optometrist on a mission. Even able to ponder the many things that the increased numbers a worldwide pandemic cannot can help us in the next pandemic, of posterior vitreous keep us down for very long. Get which will probably come out of detachments, retinal vaccinated. Unmask. See you at the Congress from what I can tell. detachments, chalazia and disco. g

About Dr. Vickers received his optometry degree from the Pennsylvania College of Optometry in 1979 and was clinical director at Vision Associates in St. Albans, WV, for Dr. Vickers 36 years. He is now in private practice in Dallas, where he continues to practice full-scope optometry. He has no financial interests to disclose.

24 REVIEW OF OPTOMETRY | JUNE 15, 2021

Edited by Paul C. Ajamian, OD CLINICAL QUANDARIES

contact lens solutions. Some common alkaline substances that can cause seri- Burn, Baby, Burn ous ocular injuries are oven cleaner, It is essential to determine the nature of a chemical injury drain cleaner, chlorine bleach, found in plaster, cement and mortar, when faced with this ocular emergency. and ammonia products usually found in cleaning products and fertilizer. Get A patient presented with a history Alkaline chemicals can penetrate the a detailed history and ask the patient Q of accidentally getting eucalyptus eye more easily due to their lipophilic to bring in the product they got into oil in both eyes, with subsequent corneal nature, therefore can also damage the their eye(s). abrasions. What is a good protocol for trabecular meshwork, and Treatment will depend on clinical handling chemical burns? possibly the lens.1 signs, and ranges from frequent Chemical burns to the eye are lubrication and topical steroids to A an emergency all optometrists Investigate the Agent amniotic membranes. Autologous should feel comfortable treating and This particular patient was rubbing serum tears may be necessary if there managing, says Trennda Rittenbach, eucalyptus oil onto his forehead for has been a loss of limbal stem cells. If OD, staff doctor at the Palo Alto Medi- religious reasons, and it ended up in the IOP is elevated, be sure to manage cal Foundation. It is critical to train both eyes. This resulted in severe pain that as well. your front office and phone staff to get from bilateral epithelial defects cen- The patient did well with erythro- these patients in immediately when trally extending to the periphery OU. mycin ointment every four hours and they call. The first and most important “After doing some quick research, I Refresh Celluvisc (carboxymethylcel- step is copious irrigation of the eye was able to find that an alcohol-based lulose sodium 1% gel, Allergan) six to with any brand of sterile irrigating so- agent is sometimes used in non-pure eight times per day, according to Dr. lution, something you should stock in forms of essential oils,” Dr. Rittenbach Rittenbach. The next day, slit lamp every exam lane. “Evert the upper and notes. exam showed immense improvement lower lids to irrigate all parts of the eye Acidic chemicals that commonly with only a small central area of epi- and adnexa, as chemical could remain cause ocular injuries are battery acid, thelial loss. By day six, the epithelium trapped in the lower cul-de-sac or acetic acid such as nail polish remover was completely healed. under the upper lid,” she advises. Use or vinegar, toilet bowl cleaners and It is vital to assess the presence and litmus paper five to 10 minutes after ir- some swimming pool agents. A very degree of limbal ischemia as well as rigation in order to determine the pH. common injury optometrists see any opacification of the cornea. An It is imperative to continue irrigation is from hydrogen peroxide–based injected conjunctiva puts one a little

until the pH is neutralized. Photo: Brian Den Beste, OD more at ease. Blanching can indicate Dr. Rittenbach cautions that a ischemia, usually associated with an al- careful corneal exam, along with kali burn, that can lead to limbal stem the conjunctiva and anterior cell loss and tissue necrosis. These chamber, is critical in order to patients may have a poor outcome not miss any collateral damage. with corneal scarring, loss of vision “I commonly see oil splash and life-long dry eye and may possibly burns from cooking that result need surgical intervention such as a in first- and sometimes second- corneal transplant. degree burns to the eyelids, A white, blanched eye or a cornea so also carefully examine the that is not healing quickly warrants adnexa,” she advises. Pay a referral to an anterior segment or attention to intraocular pressure cornea specialist. g (IOP) readings, as alkaline 1. Baradaran-Rafii A, Eslani M, Haq Z, et al. Current and chemical burns may cause upcoming therapies for ocular surface chemical injuries. Ocul immediate or delayed rises. Chemical burns can create painful epithelial defects. Surf. 2017;15(1):48-64.

About Dr. Ajamian is the center director of Omni Eye Services of Atlanta. He currently serves as general chairman of the education committee for SECO International. Dr. Ajamian He has no financial interests to disclose.

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ence picture and the other is below). There is a misconception that Space: the Final Frontier is nearly always present when different refractive powers Where appropriate, work cheiroscopic tracing into your workup exist between the right and left eyes. to get a better handle of the case in your chair. However, this is not always the case. We have seen cases with large differ- ences in refraction between the right he June 2017 installment of When performing the test, first the and left eyes with no size perception this column, “Putting Pen to printed target is placed before one differences and cases where it is Paper,” included a cheiroscopic eye in the stereoscope. Then, the present. Ttracing to show size perception patient is given a pencil and asked differences in how a patient with to trace the figure. When the figure aniseikonia saw the world. Cheiro- is in front of the left eye, the right There is a misconception that scopic tracings are not a routine part hand performs the tracing, and vice aniseikonia is nearly always of optometric practice, but they come versa. This gives us two ways to see present when different refractive in handy as a problem-solver in some the variations between the spatial of the more difficult cases. In this percepts as formed through each powers exist between the right month’s column, we will reacquaint eye. This helps with size differences and left eyes. However, this is you with the procedure and, more im- (aniseikonia), cyclodeviations (where not always the case. portantly, help you understand which one eye relative to the other sees an types of cases it is best suited for. altered scene) and vertical deviations (where one tracing is above the refer- We have also seen our fair share The Process of cases with nearly equal refrac- A typical example of a stereoscope tive powers on each side, in which a can be seen in Figure 1. The op- clinically significant size perception tics can vary, but most have +5.00 difference existed. Without testing sphere lenses, which set the work- for it, we would be searching in the ing distance at 20.00cm, simulating dark for something that is rather easy distance demand for . to identify and if present, is rather Additionally, they have base-out easy to prescribe for. As the late Rob- prism in front of each eye, allowing ert A. Kraskin, OD, used to say, “It’s the two pictures to be separated in not what a lens does to a person, but space, even though they appear to what a person does with a lens” that be overlapping to the viewer with really matters. little vergence demand. In one form or another, each also has a septum, More Than Meets the Eye which prevents the right eye from Figure 3b shows a size perception seeing the left target and the left eye difference between a pair of eyes from seeing the right target. of about 10%. When the reference We now have the two channels figure is in front of the right eye, the isolated, but the sense is that they left hand traces a larger figure than is are unified. Figure 2 shows a patient referenced. While tracing, the point completing a tracing. The standard of the pencil looks like it follows the paper used is 11.50in wide by 4.25in outline of the reference figure, and tall with the reference figure printed Fig. 1. The Wolff Standup Cheiroscope when done, the two figures look as in the center (Figure 3a). (Bernell). if they are one solid figure—both

Dr. Taub is a professor, chief of the Vision Therapy and Rehabilitation service and co-supervisor of the Vision Therapy and Pediatrics residency at Southern College of About Drs. Taub and Harris Optometry (SCO) in Memphis. He specializes in vision therapy, pediatrics and brain injury. Dr. Harris is also a professor at SCO. Previously, he was in private practice in Baltimore for 30 years. His interests are in behavioral vision care, vision therapy, pediatrics, brain injury and electrodiagnostics. They have no financial interests to disclose.

28 REVIEW OF OPTOMETRY | JUNE 15, 2021 • 89% First fit success rate* • Simplified lens design, and ease of ordering • Highly adjustable parameters • Multiple diameter and optic zone options • Dynamic Edge Profile™ delivers remarkable comfort • Worry-free refits with REMLens® for other leading designs • Design consultation from NCLE certified experts • Online lens design calculator • Practice management tools • 24-hour turnaround time • Competitive pricing • Hassle-free, no return warranty FOCUS ON REFRACTION | Space the Final Frontier appearing to be the same size. The Cover testing A spatial transformation is the result in primary gaze at of optics plus perception and is not distance revealed secondary to only the optics. a 10 prism-diopter When the reference figure is in with a 2 front of the left eye, the right hand prism-diopter ver- traces a smaller figure by the same tical deviation. At amount on the right side of the paper, near, the amount of which, again, appears to be the same exo increased, but B size as the target. It is important to the patient did not have both representations to compare show a tropia until the size differences between the two we did some eye figures. The more similar the size movements. transformations are, the higher the When looking in likelihood those measures are clini- any direction 20° cally significant. to 25° away from Figure 3c shows a similar set of straight ahead, he tracings where no size difference is saw double vision C present but the perception of what with a horizontal is vertical and horizontal is clearly and vertical com- off with respect to how the world ponent. However, is viewed through each eye. In this he also mentioned instance, we can see 10° of outward that every time his cyclorotation. We always label the di- vision doubled, rection of the rotation relative to the one image was top and whether it is shifted inwards twisted, or, as he Fig. 3. On top (A) is the blank form used to perform the tracings. toward the nose or outwards toward said, “vertical The middle image (B) shows a roughly 10% size difference. Note the ear. wasn’t vertical in that each side must show a similar amount of size difference, one of the images.” but in the opposite direction. On the bottom (C) is a clinically The Case We performed significant cyclorotation. An older male patient was referred a double Maddox due to sudden-onset . In a rod test and measured 10° of cyclode- out diplopia interfering or any break person aged 65+, this is always a viation in primary gaze. This same in fusion occurring. A repeat of the flag. His history included acute sinus cyclo was seen on a cheiroscopic trac- cheiroscopic tracing showed equal- infections, which required medical ing, similar to Figure 3c. sized images and no evidence of the treatment but no surgery. Because the patient was not seeing prior cyclorotation. double in primary gaze and showed Imaging was not ordered because normal global stereo acuity and no it seemed like he was already well other signs of eye, vision or systemic along on the road to recovery by the health issues, we decided to take no time we saw him. further action and simply see him four to six weeks later. We expected Takeaways him to continue recovering and There are times when our stan- explained our hypothesis that the dard chair and analytic tests don’t episode of double vision was second- give us the whole picture. Adding ary to his sinus issues, which may some insights from our optometric have interfered with innervation to heritage, which in this case included the extraocular motor system. cheiroscopic tracing and the double At the follow-up visit, the cyclo Maddox rod for confirmation, helped was fully resolved, though the patient us understand how best to approach still showed a mild exophoria at both the care of our patient. Having these Fig. 2. A modified Brewster Stereoscope distance and near. The slight vertical adjunct tests available when needed (Keystone). This version is affixed to the deviation had also resolved. He was can save chair time as well as reduce wall and can be adjusted to meet the needs able to move his eyes out to 50° in all patient anxiety, which might be trig- of most people. directions at distance and near with- gered by additional testing. g

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Extended Ophthalmoscopy Bring the Retina into View (92201, -02) Described as a “unilateral or bilateral” The often forgotten is now in focus. procedure, this is coded and paid the same whether it is performed on one eye or both. Redefined in January 2020, he retina has traditionally been OCT (92133 for Optic Nerve, these codes now reflect examination of the domain of ophthalmology and -34 for Retina) specific areas of the retina with specific not a typical area for optometrists. Described as a “unilateral or bilateral” examination techniques. Watch out TOver the past decade, that has procedure, OCT is coded and paid the for a Correct Coding Initiative (CCI) changed with the advent of technolo- same whether it is performed on one edit preventing you from performing gies that have since improved in clinical eye or both. 92133 and 92134 cannot either code on the same day as fundus application. In January 2021, the under any circumstances be performed photography. redefinition of the CPT language asso- on the same date of service according ciated with E&M services dictated the to the CCI edit rules. OCT and OCT Visual Fields (92081, -82, -83) practitioner only perform “a medically angiography are coded in the same Described as a “unilateral or bilat- appropriate history and examination.” manner and follow the same guidelines. eral” procedure, visual fields are There is now no requirement to dilate coded and paid the same whether to meet the definition of a 992XX code, performed on one eye or both. Make and because of that, it may change how Medical necessity is required sure that the level of visual fields per- you decide to employ various technolo- when performing the test based formed matches the level of medical gies into your clinical regimen. Let’s necessity established in the medical on clinical findings. explore some of these technologies and record. In general, visual fields can be their code requirements. performed on the same day of service In order to use OCT to follow a as most other ophthalmic tests but Fundus Photography (92250) Plaquenil (hydroxychloroquine, Sanofi) have a CCI edit rule preventing them If medical necessity for bilateral use is patient, you must be using spectral do- from being performed on the same not established in the record, it should main–level equipment or better. Watch day as 99211. be performed unilaterally and coded out for performing 92133 or 92134 on (92250-52-RT/LT). Photo documen- the same day of service as any of these Electroretinogram (92273, -74) tation requires that the need for the other common ophthalmic codes: 76513 In January 2019, 92275 was supplanted image be determined on the day of 99211, 92227, 92228, 92229, 92250. by these two CPT codes specify- service and after you examined the ing specific examination techniques. patient. It generally is not ordered in Dark Adaptation (92284) These tests are true bilateral tests. advance of the examination. Like the Using this technology for early detec- can be performed five following technologies, it requires tion of has be- on the same day of service as most an interpretation and report that dem- come more user-friendly. Like fundus other ophthalmic tests but has a CCI onstrates how it added to the care and photography, it is also a true bilateral edit rule that prevents it from being management of the patient rather than test requiring that it be performed performed on the same day as 99211. just act as a confirmatory test. bilaterally. Like all special testing, The retina is fertile territory for Fundus autofluorescence is also medical necessity is required when optometric specialization. Using coded as 92250 and follows the same performing the test based upon clinical technology to boost your clinical rules for use and medical necessity. findings. acumen and knowing the coding Watch out for performing 92250 on In general, 92284 can be performed rules surrounding this technology will the same day of service as any of these on the same day of service as most benefit your patients and boost your other common ophthalmic codes: other ophthalmic tests but has a CCI practice. ■ 92201, 92202, 99211, 92227, 92228, edit rule that prevents it from being Send your coding questions to 92229, 92133, 92134, 92235, 92240. performed on the same day as 99211. [email protected].

Dr. Rumpakis is president and CEO of Practice Resource Management, a firm that provides consulting, appraisal and management services for healthcare About Dr. Rumpakis professionals and industry partners. As a full-time consultant, he provides services to a wide array of ophthalmic clients. Dr. Rumpakis’s full disclosure list can be found in the online version of this article at www.reviewofoptometry.com.

32 REVIEW OF OPTOMETRY | JUNE 15, 2021 All-day comfort for today’s busy eyeseyes 05/21 ©2021 Carl Zeiss Vision Inc. Rev.

ZEISS SmartLife Lenses Today’s mobile technology and on-the-move lifestyles are stressing our eyes. Frequent gaze changes to and from smart devices can lead to eyestrain. ZEISS SmartLife lenses are specially designed to support quick and easy peripheral vision for all-day comfort. Learn more at www.zeiss.com/pro/SmartLife Feature PROGRESSIVE LENSES PEER REVIEWED

Understanding Today’s Progressives

Help patients choose and use these lenses with fewer hassles and greater success.

By Barry Santini, ABOM,1 Van Y. Rue2 and Brent McCardle, LDO3 dissatisfaction. Although creating 1 seaford, ny, 2 renton, wa, 3 Raleigh, NC the best progressive begins with an accurate refraction, it sometimes ye care professionals (ECPs) or adaptable—does hinder choosing goes awry when the well-intentioned probably spend more time trying the best lens for any individual PAL prescriber’s discretion influences the to make their progressive wearers wearer. The eye/brain’s ability to final Rx in a way that works against Esatisfied than any other cat- adapt and function well in a matrix of progressive success. Below is a short egory of eyeglass wearer. But despite less-than-optimal conditions, such as list of suggestions that can improve advances in lens design and manufac- eyewear routinely made off-spec or progressive satisfaction: ture over the last 25 years, ECPs still with poor lens materials and center- 1. Don’t massage the astigmatism. yearn to discover the perfect progres- ing, can hide what matters most for Full correction of astigmatism deliv- sive—the one design that balances any individual patient. This squishi- ers the best bang for the buck when acuity, comfort and utility just right. ness also helps in defining the larger chasing optimal acuity. But prescrib- And while balancing these elements area of wearer satisfaction colloquially ing the full astigmatism can come is essential, frame fit, cosmetics and called “20/happy,” which can guide in with a price: an alteration of habitual perceived value also remain important determining the most efficient use of perspective that negatively impacts ingredients in a successful experience. professional time and materials. comfort for some wearers. For this To help both sides of the dispensing But even 20/happy can be elusive, reason, prescribers often reduce or desk arrive at the best solution, let’s and therefore ECPs should always eliminate minor amounts of astigma- start with a review of the fundamen- remain open to novel information as tism up to 0.50D. tals for dispensing progressive addi- they juggle prescription, progressive Additionally, orthogonalizing the tion lenses (PALs). While challenging, design and placement to deliver a axis—adjusting it closer to the prime these conditions can be comanaged superlative progressive experience. meridians of 90º or 180º—is often successfully, and optometrists are in used to further reduce perspective the perfect position to take a leader- Prescription side effects. But all progressive lenses ship role in the care of this sizable Perhaps nothing impacts a prescrib- possess some residual astigmatism patient population. er’s approach more than time spent distributed across the lens surface.1 performing eyeglass rechecks. By the This residual astigmatism can interact The Juggling Act time a wearer lands in the doctor’s with any leftover refractive astig- One of human vision’s biggest advan- chair for a recheck, usually the Rx is matic error in a progressive lens and tages—that it’s inherently “squishy,” the top suspect behind their eyewear decrease acuity and utility.

About Mr. Santini is a New York state licensed and ABOM-certified master optician and contact lens fitter at Long Island Opticians. Mr. Rue is an optical the authors consultant and educator and progressive lens expert in the Seattle area. Mr. McCardle is a technical education specialist in North Carolina for Carl Zeiss Vision NA. Mr. Santini and Mr. Rue have no financial interests to disclose.

34 REVIEW OF OPTOMETRY | JUNE 15, 2021 Recommendation: Prescribe the full in the 1970s and 1980s, front-surface Today, outcome-based visual satis- cylinder found and avoid orthogonal- designs tried to reduce this in two faction has become the target goal of izing the axis. Although satisfaction ways: one approach—exemplified by PAL design. To this end, optimizing here is not guaranteed, the prospects the multi-add design of Varilux Infin- dynamic prism and dynamic magni- for progressive success almost always ity—favored adjusting corridor length fication—the differing prismatic and improve when the eye’s astigmatism to optimize the astigmatism gradient magnifying effects encountered be- is properly and optimally corrected. for increasing add powers, thereby tween the eyes as they gaze across the If the wearer experiences perceptual optimizing corridor width and reduc- lens—becomes particularly important discomfort tracked to their astigma- ing swim-related effects.2 in any anisometropic and/or oblique tism correction, try switching to a The other, exemplified by American cylinder axis prescription. softer-design progressive. Optical’s Omni, dispensed with retain- Optimization of these prescriptions 2. Consider maximum plus and ing areas of stable power almost alto- can be achieved by using steeper or acuity. Approach this timeless gether, and spread surface astigmatism dissimilar base curves and differential recommendation with caution. With throughout the entire lens through a lens thickness to help improve fusion the standard exam distance set at bipolar design.3 Nether design ulti- and reduce swim. But the resulting 20 feet, which equals a vergence mately garnered sustained success for cosmetics of these lenses are often less of +0.16D, the final subjective lens two reasons: Infinity required uncom- well-received by both practitioner and choices could easily flip into an fortable eye rotation in higher add patient. However, wearers of lenses undesirable over-plus situation for powers, while unhappy Omni wearers optimized in this way realize improved driving distance. Further, anything found the bipolar design possessed binocular function, with many report- that compromises axial acuity will insufficient areas of clear, stabilized ing they are enjoying progressive further degrade peripheral acuity by prescription power. comfort for the very first time. Shaw compounding the inherent peripheral But Omni did become the choice progressives are an example of this blur of progressive lenses. of wearers sensitive to swim effects— specialty approach, using an advanced, Recommendation: Trial frame the Rx and provided insight on how residual global iseikonic analysis to achieve outdoors to discover the optimal flip astigmatism and magnification effects binocular optimization.5 point for achieving best acuity while might be better managed. Eventually, Today, the latest design process driving. There are exceptions—see progressive design evolved from just analyzes a wearer’s head and neck “Troubleshooting Mature Presbyopes” on optimizing optics to full consideration posture over time, combined with p. 39. of binocular needs. Zeiss’s horizontal comprehensive tracking data that 3. Be aware of pupil sampling. Pupil symmetry—which debuted in the reveals how we actually aim our eyes size controls more than luminous flux Gradal HS lens—was among the first and tilt our heads in everyday tasks. and near vision depth of field: the progressive lenses to address the This data is then used to optimize eye’s pupil size determines the effec- importance of binocularity.4 Gradal HS corridor length, width and specific tive cross section of the eye’s refrac- has since been discontinued. distribution of residual astigmatism

tive optical train—cornea, crystalline Adapted from: Zeiss lens and retina—that is contributing 045º 030º Global to the final refractive result. Sphere, Best 060º Maximum cylinder power and axis can vary in Vision value between a daytime pupil of 015º

2.5mm diameter and a nighttime pu- 075º 20 pil of 5.5mm or greater diameter. Recommendation: Again, trial frame 10 180º the Rx outside the exam room, º060

particularly at night if possible. The best correction for night use might be 10 different enough to recommend two

different prescriptions (Figure 1). 105º 20 Local

165º Maximum

Design Worst Early progressives, such as the original Vision 120º 150º Varilux (now Essilor) of 1959, came 135º with substantial unwanted astigma- tism in the transition zones near the Fig. 1. Pupil size determines the effective cross section of the eye’s refractive optical progressive umbilic. As PALs evolved train—cornea, crystalline lens and retina—that is contributing to the final refractive result.

JUNE 15, 2021 | REVIEW OF OPTOMETRY 35 Feature PROGRESSIVE LENSES

MATCHING PROGRESSIVE DESIGN TO THE WEARER At the same time, Johnson & Johnson’s Definity (now an Essilor Your assortment of 10 to 20 odd-sized and multi-colored contact lens) greatly improved on the original Owen Aves 1907 design, lens trial sets says a lot more about your curated wisdom than you with its bi-surface design allowing advanced surface astigmatism may realize. You carefully choose a contact lens because each management to push distortion away from areas nearest the fulfills a unique Rx or lifestyle need among your patient base. pupil out to the upper and lower corners. The first advantage Every modality, base curve and diameter earns its place in your was increased intermediate width near the center—just below the lens toolbox because it enables you to better serve patients or pupil—not at the top or bottom lens edge. As a general purpose solve a problem. Progressive lenses are no different. lens design, Definity became a computer user’s dream. The second Older, cast-front progressives have an inescapable physics advantage was that the feeling of swim and sway, especially problem because about half of the surface area was rendered while walking, was greatly reduced, in part because distortion was useless by an inability to optimally manage the greater surface pushed more outside the foveal cone. But a disadvantage was that usable distance width was sometimes perceived to be narrower astigmatism of these designs. The areas near the intermediate 1 corridor and peripheral distance zones have been politely termed than other traditional lenses. “soft-focus areas.” To maintain a stable umbilic, traditional Matching a lens’s inherent strengths to a patient’s unique needs, progressives defaulted to using a profile shaped like an hourglass. lifestyle and Rx can tremendously improve patient satisfaction But this profile is problematic, as surface astigmatism of these and reduce non-adapts. Most free-form lenses today are distance, older designs narrows the visual areas adjacent to the pupil while intermediate or reading prioritized, and knowing which designs placing the widest and clearest areas at the very top and bottom best match a wearer’s needs is critical to improving satisfaction of the lens.1 and creating viral patient referrals. It’s widely agreed that free-form progressive technology has delivered wider usable zones and reduced but never fully eliminated unwanted surface astigmatism. Not well discussed is that free-form technology gives designers enormous control over where that remaining distortion is placed, and as a consequence, what zones will benefit the most. Today, free-form lens designers can literally move distortion anywhere on the lens, thereby optimizing the zones they choose. As a result, free-form progressives—just like contact lenses—have become a vastly more specialized family of lenses and far more fit-specific in their application.1 During the early 2000s, progressive lens technology exploded. The “T-shape” design—only possible in free-form—appeared first in the Rodenstock Multigressiv (Free Form Technologies), followed by the Shamir Autograph. A T-shape could offer almost edge-to-edge distance clarity at the pupil height compared to the average 5mm to 12mm of usable distance width offered by traditional molded progressive designs of the time. Astute ECPs immediately found that patient complaints about driving at night utterly plummeted. As a trade-off, T-shape designs often suffer in intermediate width. And, in many cases, the reading zones of “Hard” and “soft” are the two main categories of progressive T-shape designs were found to be narrower than popular traditional lens design. Both refer to the amount of blur located at the lenses of the time, such as Varlilux Comfort. Even free-form peripheral blending zones. Soft lenses spread the blending technology has limitations. zones out into the distance and reading portions of the lens. in creating the best balance between There are further personalization ing perpendicular to the floor (Figure acuity, comfort and utility. A sampling frontiers to consider, such as the dif- 2). This is also the proper head align- of today’s premium progressives that ferences in axial length and center of ment for measuring the pantoscopic employ this comprehensive approach rotation found between hyperopes tilt of the frame chosen. is found here: and myopes. Finally, there’s the dark Here are three interrelated factors • Hoya ID Mystyle 2 and ID arts of trying to match the best lens to always keep in mind when placing Lifestyle 3 for any individual wearer (see “Match- a progressive: • Independent Owners Network ing Progressive Design to the Wearer”). 1. Posture. A patient’s habitual head (ION) Love Our Lens posture often must be taken into • IOT Camber Steady and Placement account when specifying a fitting Camber Mobile PAL designers expect their lenses will height. Habitual head posture reflects • Shamir Autograph Intelligence be fit according to a stated protocol, the routine manner in which an • Varilux X and Comfort Max where the fitting cross of the lens is individual carries their head, i.e., facial • Zeiss Individual Smart Life placed over the center of the pupil plane tilted forward or back—with and DriveSafe with the facial plane vertical—mean- tilt-back posing more significance

36 REVIEW OF OPTOMETRY | JUNE 15, 2021 Change the outlook for dry eye disease

Only CEQUA™ features NCELL™, an innovative technology that helps improve the ocular penetration of cyclosporine1-3

• NCELL helps improve the delivery of cyclosporine to where it is needed2,3 • Signi cant improvement in tear production at 3 months1 • Signi cant improvement in corneal staining as early as 1 month2,4 • In a comfort assessment at 3 minutes post instillation, 90% (Day 0) and 85% (Day 84) of patients had no or mild ocular discomfort4 Visit GetCequa.com to learn more.

INDICATIONS AND USAGE CEQUA™ (cyclosporine ophthalmic solution) 0.09% is a calcineurin inhibitor immunosuppressant indicated to increase tear production in patients with sicca (dry eye). IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS Potential for Eye Injury and Contamination: To avoid the potential for eye injury and contamination, advise patients not to touch the vial tip to the eye or other surfaces. Use with Contact Lenses: CEQUA should not be administered while wearing contact lenses. If contact lenses are worn, they should be removed prior to administration of the solution. Lenses may be reinserted 15 minutes following administration of CEQUA ophthalmic solution. ADVERSE REACTIONS The most common adverse reactions reported in greater than 5% of patients were pain on instillation of drops (22%) and conjunctival hyperemia (6%). Other adverse reactions reported in 1% to 5% of patients were , eye irritation, headache, and urinary tract infection. Please see brief summary of Full Prescribing Information on the adjacent page.

References: 1. CEQUA [package insert]. Cranbury, NJ: Sun Pharmaceutical Industries, Inc.; 2018. 2. Data on le. Cranbury, NJ: Sun Pharmaceutical Industries, Inc. 3. US Patent 9,937,225 B2. 4. Tauber J, Schechter BA, Bacharach J, et al. A Phase II/III, randomized, double-masked, vehicle-controlled, dose-ranging study of the safety and ef cacy of OTX-101 in the treatment of dry eye disease. Clin Ophthalmol. 2018;12:1921-1929.

© 2019 Sun Ophthalmics, a division of Sun Pharmaceutical Industries, Inc. All rights reserved. CEQUA and NCELL are trademarks of Sun Pharma Global FZE. PM-US-CQA-0327 10/2019 Brief Summary of Prescribing Information for An oral dose of 45 mg/kg/day cyclosporine (approximately CEQUA™ (cyclosporine ophthalmic solution) 0.09%, 4800 times higher than MRHOD) administered to rats from for topical ophthalmic use Day 15 of pregnancy until Day 21 postpartum produced CEQUA™ (cyclosporine ophthalmic solution) 0.09% maternal toxicity and an increase in postnatal mortality in See package insert for Full Prescribing Information. offspring. No adverse effects in dams or offspring were observed at oral doses up to 15 mg/kg/day (approximately INDICATIONS AND USAGE 1600 times greater than the MRHOD). CEQUA ophthalmic solution is a calcineurin inhibitor Lactation immunosuppressant indicated to increase tear production Risk Summary in patients with keratoconjunctivitis sicca (dry eye). Cyclosporine blood concentrations are low following topical CONTRAINDICATIONS ocular administration of CEQUA. There is no information None. regarding the presence of cyclosporine in human milk following topical administration or on the effects of CEQUA on breastfed WARNINGS AND PRECAUTIONS infants and milk production. Administration of oral cyclosporine Potential for Eye Injury and Contamination to rats during lactation did not produce adverse effects in To avoid the potential for eye injury and contamination, advise offspring at clinically relevant doses. The developmental and patients not to touch the vial tip to the eye or other surfaces. health benets of breastfeeding should be considered along Use with Contact Lenses with the mother’s clinical need for CEQUA and any potential CEQUA should not be administered while wearing contact adverse effects on the breastfed child from cyclosporine. lenses. If contact lenses are worn, they should be removed Pediatric Use prior to administration of the solution. Lenses may be The safety and efcacy of CEQUA ophthalmic solution have reinserted 15 minutes following administration of CEQUA not been established in pediatric patients below the age of 18. ophthalmic solution. Geriatric Use ADVERSE REACTIONS No overall differences in safety or effectiveness have been Clinical Trials Experience observed between elderly and younger adult patients. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical PATIENT COUNSELING INFORMATION trials of a drug cannot be directly compared to rates in the Handling the Vial clinical trials of another drug and may not re ect the rates Advise patients to not allow the tip of the vial to touch the eye observed in practice. or any surface, as this may contaminate the solution. Advise patients also not to touch the vial tip to their eye to avoid the In clinical trials, 769 patients received at least 1 dose of potential for injury to the eye. cyclosporine ophthalmic solution. The majority of the treated patients were female (83%). Use with Contact Lenses CEQUA should not be administered while wearing contact The most common adverse reactions reported in greater than lenses. Patients with decreased tear production typically should 5% of patients were pain on instillation of drops (22%) and not wear contact lenses. Advise patients that if contact lenses conjunctival hyperemia (6%). Other adverse reactions reported are worn, they should be removed prior to the administration in 1% to 5% of patients were blepharitis, eye irritation, of the solution. Lenses may be reinserted 15 minutes following headache, and urinary tract infection. administration of CEQUA ophthalmic solution. USE IN SPECIFIC POPULATIONS Administration Pregnancy Advise patients that the solution from one individual single-use Risk Summary vial is to be used immediately after opening for administration There are no adequate and well-controlled studies of CEQUA to one or both eyes, and the remaining contents should be administration in pregnant women to inform a drug-associated discarded immediately after administration. risk. Oral administration of cyclosporine to pregnant rats or rabbits did not produce teratogenicity at clinically relevant doses. Rx Only Distributed by: Sun Pharmaceutical Industries, Inc. Data Cranbury, NJ 08512 Animal Data Oral administration of cyclosporine oral solution (USP) to pregnant rats or rabbits was teratogenic at maternally toxic doses of 30 mg/kg/day in rats and 100 mg/kg/day in rabbits, as indicated by increased pre- and postnatal mortality, reduced fetal weight, and skeletal retardations. These doses (normalized to body weight) were approximately 3200 and 21,000 times higher than the maximum recommended human ophthalmic dose (MRHOD) of 1.5 mcg/kg/day, respectively. No adverse embryofetal effects were observed in rats or rabbits receiving cyclosporine during organogenesis at oral doses up to © 2018 Sun Ophthalmics, a division of Sun Pharmaceutical Industries, Inc. 17 mg/kg/day or 30 mg/kg/day, respectively (approximately All rights reserved. CEQUA is a trademark of Sun Pharma Global FZE. 1800 and 6400 times higher than the MRHOD, respectively). PLR-00020 2018 Feature PROGRESSIVE LENSES

in progressive fitting. The normal have required revising normal eye eyelash clearance and sinus or skin approach has been to adjust the depression angles from 26º to 28º sensitivity may require modifying the fitting height to compensate for these to a less demanding 22º to 25º.1 But fitting cross placement from its posi- postural deviations. as the effective corridor value is tion in front of the pupil. Alternately, the corridor length may often defined differently between be adjusted as well—longer corridors manufacturers, comparing corridors Troubleshooting Dissatisfaction for the head-back tilt or shorter for between different PALs remains a Despite the best laid plans of pre- head-forward postures. An example challenge. For example, manufacturers scriber, fitter and lens designer, wear- of a combined approach might lower may use either a varying metric of ers will inevitably return dissatisfied placement of the fitting cross by 1mm 85%, 95% or 100% of add power to with their progressive lenses. When to 1.5mm and compensate the reading define their corridor length.6 rechecking the Rx, here are two ex- area by specifying a 1mm to 2mm 3. Frame fit. To further complicate ceptional situations to keep in mind: shorter corridor. achieving the best placement for a 1. Mature presbyopes. Defined as 2. Corridor length. Today, issues progressive, factors such as patient near additions of +2.00D and above, arising from cell phone usage preference for a loose frame fit, lenticular changes often precipitate

Adapted from OptiCampus changes seen in total astigmatism and Major Reference Points of a Progressive Lens sphere power. With all progressive lenses possessing some residual Distance astigmatism, not fully correcting Reference the eye’s astigmatism can result Fitting Point in patients having to hold their Point head “just so” to see clearly in the distance—which is colloquially called Alignment “hot-spotting.” Reference As stated previously, this effect + Marking arises from uncorrected refractive ADD LOGO cylinder alternately interacting with the varying surface astigmatism of the progressive surface. Do not shy from Prism Near prescribing the full change found in Reference Reference the cylinder and axis. Point Point Further, reducing habituated plus power in the distance Rx can backfire Fig. 2. The fitting cross is an important marker that designates the point of the lens that in mature presbyopes—with new should be placed along the center of the patient’s pupil. distance or driving improvements offset by unexpected loss of face-level computer utility. 2. Eye and the binocular pupillary distance (PD). Essilor introduced the importance of using monocular PDs when fitting progressive lenses to help better align the narrow intermediate and near areas of early progressives. But maintaining an accurate binocular PD is of greater importance. Patients will naturally align their dominant eye to that lens’s progressive umbilic—thereby placing the total error in binocular PD, if any, into the companion eye.7 This means that the current ANSI fabrication tolerance of 1mm per eye Fig. 3. Expand your knowledge and skill with progressive lenses to create a personalized could actually result in a 2mm error in experience that keeps patients coming back. corridor placement for the companion

JUNE 15, 2021 | REVIEW OF OPTOMETRY 39 Feature PROGRESSIVE LENSES

NEAR VISION NEEDS CHANGE THE GAME Squishy Satisfaction In today’s world, people are performing more varied and different types of near activities, The one aspect of vision care that many of which are centered on multitasking while using a phone or tablet. Whether it’s online vendors cannot address easily walking down the street, cooking a meal, or having a conversation while waiting for an is the ability to follow-up on the com- important text, the arrival of the smartphone, smartwatch and a cornucopia of associated plaints of an unsatisfied progressive apps has changed the visual experience dramatically. And people are using their phone for wearer. So, never shy from welcoming more than just calling and texting. They use them to secure home loans, pay bills, watch anyone who requires after-sale atten- movies and even to monitor their workouts. All of this added near activity comes with a tion—whether they’ve purchased the cost to our eyes and our visual comfort. Zeiss has assembled a portfolio of progressive lens products call SmartLife for this glasses from you or not. very reason, with a goal of creating general-use progressive lenses that will—in one From the ECP’s end, the time lens—attempt to better address all these new visual challenges.1 But remember that even spent learning to troubleshoot any today’s most robust, premium designs cannot fully solve all the unique challenges of every spectacle wearer’s problems informs situation in one lens design. and readies oneself better for the next Throughout our day we do many tasks that require differing visual needs, which in turn patient who may have similar prob- requires a lens specifically made for that task. For example, 67% of middle-aged drivers lems (Figure 3). complain of traveling at night, which requires a design that is very wide in the distance and intermediate to allow drivers the freedom to move their eyes. Zeiss’s DriveSafe attempts to My mantra has always been: “What address these needs.2 do you learn from a patient who never Drivers prefer to move their eyes rather than move their head—Zeiss DriveSafe starts the returns?” So, while getting wearers progressive corridor 2mm to 3mm lower than general purpose designs. The result is more to 20/happy is a convenient goal, true freedom of eye movement in the distance and intermediate areas. progressive experts never refrain from Zeiss DriveSafe is optimized for a mesoscopic pupil, which results in wider areas of exploring where the limits of progres- lateral vision from smoother surface contour and reduced astigmatism power. sive satisfaction lie for an individual Newer LED headlights are a source of debilitating glare and emit an elevated amount of spectrum compared with halogen headlights. DriveSafe has an advanced blue light wearer. Patient satisfaction will always filter tailored to reduce glare specific to LED headlights. be a moving target and new lens While DriveSafe is an excellent lens choice for everyone who drives at night, its lowered designs will always be introduced, so progressive corridor may be less ideal for office tasks like face-level computing. There remain a lifelong learner in order to are many types of task-specific lenses that you can recommend alongside an optimized, stay at the top of your game. general purpose progressive, such as a computer lens. So, the best approach to choosing Keep in mind that trying to choose one, best general-use progressive might just be to prescribe two or more pairs. an overall “one best lens” solution

1. Zeiss. Smartlife fact sheet. www.zeiss.com/content/dam/vision-care/download/pdf/factsheets/fact-sheet-zeiss-smartlife.pdf. for many patients may not really be a 2019. Accessed May 14, 2021. solution at all, and this is where pre- 2. Zeiss. Zeiss Drivesafe white paper. glarminy.files.wordpress.com/2019/07/d1b1a-9aff8-zeiss-drivesafe-white-paper.pdf. 2019. scribing two or more pairs is really the Accessed May 14, 2021. best recipe for optimal visual comfort

Image: Zeiss and utility. ■

1. Alonso J, Gómez-Pedrero Jm, Quiroga J. Modern Oph- thalmic Optics. Madrid, Spain: Cambridge University Press. 2019: 301-22. 2. Koeppen W. Progressive memories. www.wernerkoeppen. com. 2010. Accessed May 14, 2021. 3. Whitney, R. American Optical history. www.dickwhitney. net/AOHistoryLensDesigners.html. 2011. Accessed May 14, 2021. 4. Zeiss. How a patent filed by ZEISS set new standards for progressive lenses 30 years ago. www.zeiss.com/ vision-care/us/better-vision/understanding-vision/how-a- patent-filed-by-zeiss-set-new-standards-for-progressive- lenses-30-years-ago.html. October 16, 2017. Accessed May 14, 2021. 5. Shaw Lens. What makes the Shaw lens different? shawlens.com/the_shaw_lens/the_science. Accessed May Personal technology, intended for frequent use throughout the day, has radically 14, 2021. changed the habitual visual needs of patients—and, with that, their expectations. 6. Santini B. Deep secrets. 20/20. www.2020mag.com/ article/deep-secrets. 2014. Accessed May 14, 2021. 7. Clark TH. Improve PAL success with improved PAL fitting. eye—something most wearers will sive corridor overlap involves a chart 20/20. www.2020mag.com/article/improve-pal-success- with-improved-pal-fitting-4-1. 2018. Accessed May 14, 2021. find disturbing to their reading and light source, wherein the patient 8. Clark TH. Apparatus for and methods of determining if comfort and utility. views the chart and wears the light progressive add lenses (PALs) are properly positioned in a subject’s eyeglasses. US Patent no. 9,104,046 B1. August A proven technique to effectively source during a progressive lens verifi- 15, 2015. patents.google.com/patent/US9104046. Ac- evaluate optimal binocular progres- cation process.8 cessed May 14, 2021.

40 REVIEW OF OPTOMETRY | JUNE 15, 2021 Shamir Autograph Intelligence™ Designed to match your Visual Age™

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“As a pre-presbyope who just entered my 40s, I have found the Shamir Autograph Intelligence™ progressive lens very easy to adapt to and makes my computer and near work more comfortable. I previously wore the Shamir Relax and had no trouble adjusting to this new lens.” ~ Rob Szeliga, OD

“I found the lenses very easy to adapt to. I am typically a “progressive lens whiner” that adapts VERY slowly to new lenses (and I complain a lot!!). However, that was not the case with these new lenses.” ~ Mario Gutierrez, O.D., F.A.A.O.

shamirlens.com • 877.514.8330

Follow us • /ShamirInsight • @ Shamir_ Insight © Copyright 2021 Shamir Insight, Inc. All Rights Reserved. 12th Annual Retina Report PEER REVIEWED RETINA RESEARCH

retina care: the neXT wave

Fifteen years into the anti-VEGF era, protocols are evolving to improve outcomes, reduce treatment burden or both. Here’s what’s new and what’s coming soon.

Most of the focus is on diabetic eye By anna bedwell, od, disease and macular degeneration, but The DRCR Retina Network, formed in 2002, and larissa krenk, od is a collaborative group dedicated to clinical indianapolis, in there are also exciting prospects for inherited retinal dystrophies. Here are research applicable to improving patient s always, an extensive number several trials, active or recently com- care. The network originally focused on dia- of promising clinical trials are pleted, with the potential to infl uence betic retinopathy research, but since 2018 underway in the retina world. our clinical practice. has expanded their research to all retinal Much of the current focus is on disorders. DRCR protocols, past and present, A can be accessed at public.jaeb.org/drcrnet therapeutic development and drug Nonproliferative Diabetic delivery systems, with the ultimate Retinopathy goal of reducing the treatment burden There may well be no topic in retina have referred those patients to retina for those receiving anti-VEGF. Many more deserving of attention from specialists. Protocol W is looking at of the therapeutics in the pipeline— researchers than diabetic eye disease, those patients with severe nonprolif- mainly injectables—will have mini- especially in its earliest stages, given erative (NPDR) mal direct infl uence on an optome- the pervasiveness of diabetes and its to see if earlier intervention leads to a trist’s role, as those patients still need unfortunately inevitable increase in better outcome; specifi cally, whether a referral, but they could substantially prevalence in the coming years. it prevents progression to PDR and/or change the patient’s experience at the center-involved DME (CI-DME).1,2 retina specialty clinic that we prepare • DRCR Protocol W The study boasts 328 participants them for at the outset of care. So, it’s Status: in progress with half randomized to sham injec- incumbent on us to be as up to date as Anticipated completion: May 2022 tion and the other half to afl ibercept possible even on interventions we do • PANORAMA injection.1,2 In the trial, afl ibercept is not personally administer. Status: complete dosed at months one, two and four, More directly affecting our own The goal with diabetic retinopathy and then every four months thereafter. protocols, there are also a number of (DR) certainly is to preserve vision. At the two-year mark, dosing will be current and completed clinical trials of But when is intervention necessary? decided as needed by the examining particular interest to ODs that would Historically, only eyes with prolif- investigator.1,2 allow us to keep patients in the chair erative diabetic retinopathy (PDR) Protocol W is not the fi rst pro- longer, have an active role in treat- or diabetic macular edema (DME) spective study to look into treating ment or change our referral patterns. have been treated, and optometrists NPDR. The PANORAMA study

Dr. Bedwell is a clinical associate professor at Indiana University School of Optometry. She serves as editor of the Optometric Retina Society’s e-newsletter. About Dr. Krenk completed a primary care residency at the Indianapolis Eye Care Center. She is now a visiting lecturer for Indiana University School of Optometry and the authors continues to teach optometry students and see patients at the Indianapolis Eye Care Center. They have no fi nancial interests to disclose.

42 REVIEW OF OPTOMETRY | JUNE 15, 2021 demonstrated an impressive two-step Table 1. Diabetic Retinopathy Severity Scale reduction in Diabetic Retinopathy Disease Severity Scale (DRSS) for Level Severity Characteristics 58% of aflibercept-treated participants 10 No DR — at six months.3,4 Unlike Protocol W, PANORAMA included eyes with both 20 Very mild NPDR MAs only moderately severe NPDR (DRSS 35 Mild NPDR MAs + HEs, CWS, +/- mild RHs level 47) and severe NPDR (DRSS level 53). PANORAMA included two 43 Moderate NPDR 43A: moderate RHs in four quadrants or severe in one different treatment groups: Q8-week 43B: mild IRMA in one to three quadrants aflibercept dosing and Q16-week.3,4 With the two-year results of 47 Moderately severe NPDR 47A: 43A + 43B PANORAMA, announced in spring 47B: mild IRMA in four quadrants 2020, additional questions arose regarding treatment frequency. 47C: severe RH in two to three quadrants For study year two, the Q16-week 47D: venous beading in one quadrant treatment group maintained a two or 53 Severe NPDR 53A: ≥ 2 level 47 characteristics more step improvement.5 However, the Q8-week group, when switched 53B: severe RH in four quadrants at week 52 to PRN dosing, showed a 53C: moderate-severe IRMA in 1+ quadrant decline from 80% to 50% with two or more step improvement.5 Very severe NPDR 53D: ≥ two level 53A-D characteristics The PANORAMA results unques- 61 Mild PDR NVE < 0.5 DA in 1+ quadrants tionably support earlier treatment in NPDR, but there are still lingering 65 Moderate PDR 65A: NVE ≥ 0.5 DA in 1+ quadrants questions, such as how frequently to 65B: NVD < ¼ to ⅓ DAs treat and when anti-VEGF injections Larger NVD, or NVE ≥ 0.5 DA with VH or PRH, or VH can be stopped or tapered. 71, 75 High-risk PDR or PRH obscuring ≥ 1 DA Clinical take home: Change in man- View partially obscured by VH or PRH from NV, or agement of moderately severe and severe 81, 85 Advanced PDR NPDR is on the horizon. Consider referral macula involving for patients that fall into either category. Level 43 and higher all require MAs. Abbreviations—CWS: cotton wool spot, DA: disc area, HE: hard exudate, IRMA: intraretinal microvascular • DRCR Protocol AF abnormality, MA: microaneurysm, NPDR: non-proliferative diabetic retinopathy, NVD: neovascularization Status: enrolling at the disc, NVE: neovascularization elsewhere, PDR: proliferative diabetic retinopathy, PRH: preretinal Anticipated completion: January 2027 hemorrhage, RH: retinal hemorrhage, VH: vitreous hemorrhage The DRCR recently announced the Source: Adapted from the American Society of Retina Specialists Clinical Practice Guidelines start of a Phase III clinical trial called Protocol AF that will study the effect plus simvastatin compared to the Clinical take home: Fenofibrate is an of fenofibrate on NPDR.6,7 Fenofi- placebo plus simvastatin group.10 oral treatment under investigation for brate is a peroxisome proliferator- Neither the FIELD or ACCORD mild to moderately severe NPDR. activated receptor alpha agonist used studies were primarily focused on the to treat hypercholesterolemia by outcome of DR progression, which Diabetic Macular Edema lowering triglycerides and low density makes Protocol AF unique. Even Recalcitrance to treatment makes lipoprotein and increasing high den- though this study is still in the enroll- DME particularly nettlesome, but sity lipoprotein.8 ment phase, it is worthy of being on new treatment protocols offer hope for Fenofibrate’s positive effect on DR optometrist’s radar as this is a potential substantial improvement. was first recognized by the FIELD means for our involvement—whether study, which showed the number of in comanagement or direct treatment • DRCR Protocol V patients on fenofibrate that went on to roles—in an intervention for NPDR. Status: complete need laser treatment for DR or DME Protocol AF seeks to enroll 910 partic- In the current era, with OCT at our was significantly lower compared to ipants with NPDR (without CI-DME) fingertips, DME is assessed as either controls.9 Additionally, the ACCORD to follow over four years.6,7 Participants center involved or non-CI, depending study found a lower rate of NPDR will be randomized to once daily feno- on the presence of thickening within progression in those taking fenofibrate fibrate 160mg or placebo.6,7 the central subfield zone at the fovea.

JUNE 15, 2021 | REVIEW OF OPTOMETRY 43 12th Annual Retina Report RETINA RESEARCH

Fundus images and OCT of a patient with moderate NPDR OU and CI-DME OD. The patient’s best corrected acuities were 20/25 OD and 20/20 OS. The comanaging retina specialist elected to monitor the CI-DME OD based on the fi ndings of DRCR Protocol V.

This is a change from the historical • YOSEMITE, RHINE Dry Macular Degeneration means of looking for characteristics Status: in progress One of the toughest nuts to crack in of clinically signifi cant macular Anticipated completion: summer/fall 2021 retina, dry AMD may be on the verge edema (CSME). But what about A new therapeutic that allows for of breakthroughs that could fi nally patients who have mild CI-DME and fewer injections would be quite offer more direct interventions. a preserved visual acuity? Protocol exciting news for our patients, V proved instrumental in providing particularly those in rural areas • SAGA guidance, as it assessed CI-DME who may not be able to easily get Status: in progress eyes with 20/25 vision or better.11 to a retina specialist. Anti-VEGF Anticipated completion: March 2022 A total of 702 participants were therapy has done wonders for DME Even though many therapeutics have randomized to observation, treatment and wet AMD, but it comes at a been explored, none to date have with afl ibercept or treatment with price: frequent offi ce visits impose been successful in slowing the pro- laser photocoagulation.11,12 After a time burden on patients and their gression of (GA), two years, the study found no caregivers, and its cost weighs heavily much to the frustration of patients and signifi cant difference in visual acuity on the healthcare system. optometrists alike. between each treatment groups Faricimab (Roche) could be Currently, there a few oral treat- and observation.11,12 The patients a game-changer. It’s not just ments in trial that, if successful, could in the observation group that went another anti-VEGF treatment but bring optometrists into the treatment on to decline in visual acuity were rather a bispecifi c antibody that protocol. SAGA is a Phase II/III ultimately treated with afl ibercept.12 targets two pathways: VEGF-A multicenter placebo-controlled clinical Even though this trial has been and angiopoietin-2.13 The Phase trial investigating the role of ALK-001 completed and published, it is still III clinical trial data, released in (Alkeus) in patients with GA.16 not widely known among ODs, who February, was positive, showing half This drug is a modifi ed form of vi- have to pull the trigger on referral. of faricimab-treated individuals were tamin A taken daily as an oral capsule. It is further challenging for patients able to be dosed every four months.13 Over time, aggregates of vitamin A alike who have good visual acuities The YOSEMITE and RHINE create dimers that accumulate in the with minimal visual complaint trials are investigating faricimab RPE and underlying Bruch’s mem- and are not ready to be locked in the treatment of CI-DME, brane.16 The dimers are thought to into a sometimes-endless cycle of with each trial including over 900 be toxic to the retina, which has been injections. participants.14,15 There are sister trials proposed as a mechanism for the Clinical take home: Patients with underway for wet AMD (TENAYA AMD development.17 Synthetic ALK- CI-DME and a visual acuity of 20/25 and LUCERNE) that anticipate 001 contains vitamin A with deuteri- or better can be safely observed. This completion in 2022. um, which slows formation of vitamin warrants a discussion with your local Clinical take home: Faricimab is A dimers without compromising the retina specialists to see if these patients an investigational drug targeting two normal function of the visual cycle.17 necessitate a referral or can continue pathways with the potential to be dosed less The primary outcome of the study observation by you. frequently than traditional anti-VEGF. is to assess the growth rate of GA

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treated subjects showed improvement of fi ve or more letters vs. 13.6% in sham-treated subjects directly after treatments at one month.19 This was followed by a decline over the next six months and repeated treatments over time will be needed to maintain effi cacy.19 Additionally, improvements in drusen volume and thickness were observed, although the authors admit- ted that more long-term evidence is needed to correlate these anatomical changes with disease regression or progression.19 If this therapy is approved in the United States, optometrists could be at the forefront of providing regular PBM treatments in addition to the close monitoring already provided to patients with dry AMD. Clinical take home: Photobiomodula- tion is a low-level light therapy that may improve visual function in patients with dry AMD. Treatments will likely be needed Color fundus images (top) and fundus autofl uorescence (bottom) of a patient with at regular intervals to maintain effi cacy. geographic atrophy (GA) from macular degeneration OU. The SAGA study is exploring modifi ed vitamin A treatment for GA patients such as seen here. Wet Macular Degeneration The most successful area of retina lesions over a two-year period in Photobiomodulation (PBM)—a care—anti-VEGF therapy for wet those taking ALK-001 compared to growing trend in medicine—is low- AMD—is swiftly evolving beyond placebo.16 If ALK-001 proves to be level light therapy that uses specifi c traditional monthly or bimonthly effective in slowing the progression of wavelengths in the visible light to injections to more patient-friendly atrophy, it could provide a new treat- near-infrared ranges, to target certain approaches. ment option to help reduce vision loss tissues and stimulate cellular func- in those with geographic atrophy from tion.19 The idea behind PBM focuses • ARCHWAY AMD. on changes at the mitochondrial level, Status: in progress Additionally, Stargardt’s disease is leading to the upregulation of ATP Anticipated completion: late June 2021 caused by a mutation in the ABC4 production, which is a major form of The introduction of intravitreal anti- gene, which affects the processing of energy necessary for normal cellular VEGF agents signifi cantly changed vitamin A.18 This also leads to the ac- functions.19 Other changes produced the treatment of wet AMD, allowing cumulation of toxic vitamin A dimers at the cellular level may also work to patients to retain and even improve that may contribute to vision loss.18 A reduce oxidative stress.19 visual function. However, repeated similar clinical trial is being conducted LIGHTSITE III is a two-year injections, often every four to six for patients with Stargardt’s and is also study consisting of 96 subjects with weeks, place a considerable burden expected to be completed in early dry AMD that will receive repeated on patients and make it diffi cult for 2022.18 sham or PBM treatments at several optometrists to continue follow-up Clinical take home: Oral supplementa- time-points using the Valeda Light care after referral to ophthalmology. tion with ALK-001 is in trial for slowing Delivery System (LumiThera).20 ARCHWAY is an exciting the progression of geographic atrophy in Findings from LIGHTSITE I development in that it studies a new patients with AMD and Stargardt’s. demonstrated clinically signifi cant way to deliver anti-VEGF therapy improvements in best-corrected visual through a port delivery system • LIGHTSITE III acuity and contrast sensitivity after a (PDS, Genentech).21 The PDS is Status: enrolling series of nine treatments over three a permanent, refi llable intraocular Anticipated completion: June 2022 weeks.19 Approximately 50% of PBM- implant that provides continuous

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normal retinal structure or function in non-human primates.26 OPTIC is a Phase I clinical trial studying the safety and tolerability of high and low doses of ADVM-022 in subjects with active choroidal neovascularization secondary to AMD.25 New interim data as of November 2020 showed that ADVM-022 is well tolerated with a favorable safety profi le at both high and low doses.27 Secondary outcomes found that mean BCVA is maintained and mean central subfi eld thickness is maintained or improved at both doses.27 In addition, most patients remain free of supplemental anti-VEGF injections with one patient in the higher dose ARCHWAY marks a change in anti-VEGF treatment as it focuses on how the therapeutic is cohort showing sustained effi cacy out 27 delivered, as opposed to the drug itself. to 92 weeks from initial injection. In the lower-dose cohorts, two-thirds of delivery of a customized formulation the PAGODA and PAVILION trials, patients did not need supplemental of ranibizumab.22 The device is respectively. They are still actively anti-VEGF injections with follow-up surgically implanted and then can be enrolling and are estimated to be ranging from 34 to 68 weeks after refi lled in a normal clinical setting.22 completed in September 2024.23,24 injection.27 ARCHWAY is a Phase III trial that Clinical take home: Continuous The results of the OPTIC trial compares PDS refi lled every six anti-VEGF therapy through use of an thus far are extremely promising and months to monthly ranibizumab intraocular implant may reduce the could potentially represent a one- intravitreal injections.21 frequency of anti-VEGF intravitreal time treatment for wet AMD. This PDS was shown to be non- injections in patients with wet AMD and could allow optometrists to continue inferior and equivalent to monthly DME. to be a more active part of a patient’s ranibizumab injections, both in terms management and follow-up care, as of BCVA and controlling retinal • OPTIC frequent anti-VEGF injections would thickness.22 Additionally, 98.4% of Status: in progress be obviated. Two Phase III trials are patients were able to maintain the Anticipated completion: June 2022 planned to begin at the end of 2021.28 six-month refi ll schedule, which could In one of the most promising trials Additionally, the INFINITY trial, a signifi cantly reduce the number of to date, OPTIC has the potential Phase II study looking at the effect of anti-VEGF treatments to as few as to greatly reduce the frequency of ADVM-022 on subjects with DME, is two per year.22 An extension of the intravitreal anti-VEGF injections, set to fi nish in January 2022.29 ARCHWAY study, called PORTAL, using as a treatment Clinical take home: ADVM-022 is a is underway to examine long-term approach.25 The candidate, ADVM- gene therapy vector given as a one-time effects of PDS. 022 (Adverum), is a gene therapy intravitreal injection and carries a genetic At this time, it is diffi cult to say how vector that can be delivered in- coding sequence for endogenous intraocular this effort might affect optometrists, offi ce by intravitreal injection.25 It production of afl ibercept. as refi lls of the PDS are still necessary contains an adeno-associated virus to maintain therapeutic levels of anti- capsid carrying a coding sequence for Inherited Retinal Disease VEGF. However, this study marks afl ibercept, which the eye can use to Gene therapy continues to be inves- an exciting change in anti-VEGF endogenously produce continuous tigated for inherited retinal diseases treatment, as it focuses on how the levels of anti-VEGF molecules.26 (IRDs), even though new applications therapeutic is delivered, as opposed to The safety and effi cacy of into wet AMD and DME—described the agent itself. prolonged intraocular expression above—have been initiated. At this Additionally, there are two trials of afl ibercept was evaluated in time, Luxturna (Spark therapeutics) underway to study the safety and preclinical trials and therapeutic continues to be the only FDA-ap- effi cacy of PDS in subjects with DME levels were confi rmed out to at least proved gene therapy for an IRD. It is and those with DR without CI-DME, 30 months with no adverse effects on specifi c to a biallelic RPE65 mutation

48 REVIEW OF OPTOMETRY | JUNE 15, 2021 A NEW WAY TO EXPERIENCE REVIEW OF OPTOMETRY Follow us on Instagram at @revoptom for striking clinical images, daily news headlines, issue previews and great content from the magazine—all formatted for mobile 12th Annual Retina Report RETINA RESEARCH

Table 2. Clinical Trials Underway for inherited retinal diseases Drug Manufacturer Disease Studied Stage AAV-RPGR MeiraGTx X-linked RP Phase I/II; 46 participants AAV-CNGB3 or AAV- CNGA3 MeiraGTx Achromatopsia Phase I/II; 72 participants AAV2-REP1 (BIIB111) Biogen Phase III; 160 participants rAAV2tYF-GRK1-RPGR (AGTC- Applied Genetic Technologies X-linked RP Moving into Phase II/III (SKYLINE, 501) VISTA) AGTC-402 or AGTC-402 Applied Genetic Technologies Achromatopsia Phase I/II; 24 participants CNGA3 Corporation mutation, and 28 with CNGB3 HORA-PDE6B Horama Autosomal recessive RP (PDE6B Phase I/II; 15 participants mutation)

Source: Manufacturers’ press releases and clinicaltrials.gov. that is present in a small subset of 1. ClinicalTrials.gov. Anti-VEGF treatment for prevention 16. ClinicalTrials.gov. Phase III study of ALK-001 in geographic of PDR/DME (Protocol W). clinicaltrials.gov/ct2/show/ atrophy (SAGA). clinicaltrials.gov/ct2/show/nct03845582. those with either Leber’s congenital nct02634333. Accessed March 23, 2021. Accessed March 22, 2021. 30 amaurosis or pigmentosa. 2. DR Clinical Research Network. Intravitreous anti-VEGF treat- 17. SAGA. www.sagastudy.com/physicians. Accessed March Other clinical trials show promise, ment for prevention of vision threatening diabetic retinopathy 29, 2021. in eyes at high risk. public.jaeb.org/drcrnet/stdy/340. Accessed 18. ClinicalTrials.gov. Phase II tolerability and effects of ALK- particularly in choroidermia. Table 2 March 2, 2021. 001 on (TEASE). clinicaltrials.gov/ct2/show/ details the gene therapy trials that are 3. ClinicalTrials.gov. Study of the effi cacy and safety of nct02402660. Accessed March 22, 2021. intravitreal (IVT) afl ibercept for the improvement of moderately 19. Markowitz SN, Devenyi RG, Munk MR, et al. A double- underway for IRDs. The majority of severe to severe nonproliferative diabetic retinopathy (NPDR) masked, randomized, sham-controlled, single-center study (PANORAMA). clinicaltrials.gov/ct2/show/nct02718326. Ac- gene therapy trials use an adenovirus with photobiomodulation for the treatment of dry age-related cessed March 23, 2021. vector and subretinal delivery. macular degeneration. Retina. 2020;40(8):1471-1482. 4. Eyelea (afl ibercept). Highlights of prescribing infor- 20. ClinicalTrials.gov. Study of photobiomodulation to treat dry Nevertheless, trials with intravit- mation. www.accessdata.fda.gov/drugsatfda_docs/ age-related macular degeneration (LIGHTSITE III). clinicaltrials. label/2019/125387s061lbl.pdf. real delivery and optogenetic gene gov/ct2/show/nct04065490. Accessed March 24, 2021. 5. Puliafi to CA, Wykoff CC. New frontiers in retina: highlights therapy have also made their way to 21. ClinicalTrials.gov. A Phase III study to evaluate the port of the 2020 angiogenesis, exudation and degeneration sympo- delivery system with ranibizumab compared with monthly human clinical trials. However, such a sium. Int J Retina Vitreous. 2020;6:18. ranibizumab injections in participants with wet age-related small portion of the population is af- 6. DR Clinical Research Network. Randomized trial evaluating macular degeneration (ARCHWAY). clinicaltrials.gov/ct2/show/ fl icted with an IRD, which adds to the fenofi brate for prevention of diabetic retinopathy worsening. nct03677934. Accessed March 29, 2021. public.jaeb.org/drcrnet/stdy/568. Accessed March 30, 2021. 22. Genentech. (2020, July 22). [Press release]. gene.com/ challenge of designing clinical trials 7. ClinicalTrials.gov Fenofi brate for Prevention of DR Worsening media/press-releases/14865/2020-07-22/phase-iii-data-show- with suffi cient participants. (Protocol AF). clinicaltrials.gov/ct2/show/nct04661358. Ac- port-delivery-system. Accessed March 29, 2021. cessed March 30, 2021. No cost, in-offi ce genetic testing 23. ClinicalTrials.gov. This study will evaluate the effi cacy, 8. Fenoglide (Fenofi brate) Highlights of prescribing safety, and pharmacokinetics of the port delivery system with programs for inherited retinal dis- information. www.accessdata.fda.gov/drugsatfda_docs/ ranibizumab in participants with diabetic macular edema com- eases can diagnose these conditions label/2012/022118s005lbl.pdf. Accessed March 23, 2021. pared with intravitreal ranibizumab (PAGODA). clinicaltrials. gov/ct2/show/NCT04108156. Accessed March 29, 2021. promptly and isolate the causative 9. Keech AC, Mitchell P, Summanen PA, et al. Effect of fenofi brate on the need for laser treatment for diabetic reti- 24. ClinicalTrials.gov. A multicenter, randomized study in gene mutation, which helps to iden- nopathy (FIELD study): a randomised controlled trial. Lancet. participants with diabetic retinopathy without center-involved tify patients eligible for trials. 2007;370:1687–97. diabetic macular edema to evaluate the effi cacy, safety, and pharmacokinetics of ranibizumab delivered via the port delivery 10. Chew EY, Davis MD, Danis R P, et al. The effects of medical system relative to the comparator arm (PAVILION). clinicaltri- management on the progression of diabetic retinopathy in als.gov/ct2/show/NCT04503551. Accessed March 29, 2021. Takeaways persons with type 2 diabetes: the action to control cardiovas- cular risk in diabetes (ACCORD) eye study. Ophthalmology. 25. ClinicalTrials.gov. ADVM-022 Intravitreal gene therapy for At times, the clinical trial landscape in 2014;121:2443-51. wet AMD (OPTIC). clinicaltrials.gov/ct2/show/nct03748784. Accessed March 29, 2021. the retina world may seem to be dom- 11. ClinicalTrials.gov. Treatment for CI-DME in eyes with inated by injectable therapeutics—it very good VA study (Protocol V). clinicaltrials.gov/ct2/show/ 26. Kiss S, Oresic Bender K, Grishanin RN, et al. Long-term nct01909791. Accessed March 25, 2021. safety evaluation of continuous intraocular delivery of Afl iber- certainly has been since the early cept by the intravitreal gene therapy candidate ADVM-022 in 12. Baker CW, Glassman AR, Beaulieu WT, et al. DRCR Retina nonhuman primates. Trans Vis Sci Tech. 2021;10(1):34. 2000s—but there are still many retina Network. Effect of initial management with afl ibercept vs laser clinical trials applicable and relevant photocoagulation vs observation on vision loss among patients 27. Regillo CD. Phase 1 study of intravitreal gene therapy with with diabetic macular edema involving the center of the macula ADVM-022 for neovascular age-related macular degenera- to optometry. These research projects and good visual acuity: a randomized clinical trial. JAMA. tion (OPTIC Trial Cohorts 1–4). Data presented virtually at 321(19):1880-94. Angiogenesis 2021 Program. adverum.com/wp-content/up- guide our referral patterns, facilitate loads/2020/12/november-2020-advm-022-optic-phase-1-data- 13. Roche. (2021, February 12). [Press release]. www.roche. update.pdf. Accessed March 29, 2021. our patient education and identify com/media/releases/med-cor-2021-02-12.htm. 28. Adverum Pipeline. adverum.com/pipeline/#wet-amd. Ac- prospective treatment, including 14. ClinicalTrials.gov. A study to evaluate the effi cacy and cessed March 29, 2021. some potentially prescribed by ODs. safety of faricimab (RO6867461) in participants with diabetic macular edema (YOSEMITE). clinicaltrials.gov/ct2/show/ 29. ADVM-022 Intravitreal gene therapy for DME (INFINITY). Several of these trials are infl uencing nct03622580. Accessed March 25, 2021. clinicaltrials.gov/ct2/show/nct04418427. Accessed March 29, 2021. patient care at the moment, while 15. ClinicalTrials.gov. A study to evaluate the effi cacy others should be kept on our radar in and safety of faricimab (RO6867461) in participants with 30. Luxturna (voretigene neparvovec-rzyl) Highlights of diabetic macular edema (RHINE). clinicaltrials.gov/ct2/show/ prescribing information. sparktx.com/luxturna_us_prescrib- the years to come.  nct03622593. Accessed March 25, 2021. ing_information.pdf. Accessed April 1, 2021.

50 REVIEW OF OPTOMETRY | JUNE 15, 2021 Menicon Celebrates Milestone 70th Anniversary

ay 17, 2021 – Billerica, MA – Menicon Co., generation of contact lenses, lens care products and re- Ltd. (Headquarters: 21-19, Aoi 3-chome, lated services with leading-edge technology, including Naka-ku, Nagoya City; President & CEO: the unique and revolutionary package concept Smart Hidenari Tanaka) is proud to be celebrating Touch™, a design which makes it possible to apply con- Mits 70th anniversary as a leading manufacturer of in- tact lenses without touching the inner surface. novative contact lenses and related products. Menicon greatly appreciates its customers, business partners, New vision of Miru for the world and stakeholders around the world who have helped and a better society make the 70th anniversary possible. In 2021, Menicon renewed its vision of Miru. “Miru” means to see, but it is also about having fun and enjoy- Menicon’s 70-year history of ment through the five senses as well as being empa- challenge, safety and innovation thetic. With this new vision of Miru, Menicon will make Since Kyoichi Tanaka’s creation of Japan’s first practical everyday life richer and filled with laughter through all corneal contact lens from scratch in 1951, to becoming the senses, not only the sense of sight. a global enterprise represented in over 80 Menicon is devoted to sustainable development countries, Menicon has been dedicated to for a better society by delivering safe and secure vi- eye safety, and strived to create comfort- sion products, as well as developing environmentally able and convenient products to provide friendly products and implementing sustainable mea- people around the world the joy of sight. sures in its factories. Faced with the increasing preva- As a comprehensive vision care en- lence of myopia, the Menicon Bloom™ Myopia Control terprise, Menicon is the first manufactur- Management System has been developed to provide er to offer a full range of products and eye care professionals worldwide with a comprehen- services including everything from rigid sive response. In addition, Menicon launched Japan’s gas-permeable (RGP) lenses, disposable first intraocular lens for animals and continues to de- contact lenses, and velop products to advance animal medical care. “We are so proud to be celebrating lens care solutions, Menicon looks forward to continuing to refine its to a myopia control products and services. In the coming decades, Menicon this milestone 70th anniversary. management system will continue to contribute to society and take on new Menicon manufactures specially in order to satisfy the challenges to achieve its mission of providing the joy of controlled medical devices, so our needs of all custom- sight and better vision for the world. top priority has always been the ers worldwide. Over With your support, Menicon has led the industry safety of our customers’ eyes,” the course of its long for 70 years, taking pride in its steadfast principles — Dr. Hidenari Tanaka, history, Menicon has and shining history. Further information and a special President & CEO of Menicon. resolutely grappled video of Menicon’s 70-year history can be found at with and overcome Menicon’s official website: https://www.menicon.com/ numerous and di- verse challenges. About Menicon Co. Ltd. “We are so proud to be celebrating this milestone Menicon Co., Ltd., founded by Mr. Kyoichi Tanaka in 70th anniversary. Menicon manufactures specially con- 1951, is Japan’s first and largest contact lens manufac- trolled medical devices, so our top priority has always turer, and is represented in over 80 countries. Menicon been the safety of our customers’ eyes,” said Dr. Hide- is a manufacturer dedicated to all areas of soft and nari Tanaka, President & CEO of Menicon. “Challenge, gas-permeable contact lens-related businesses includ- safety, end-user first philosophy and high-quality prod- ing manufacturing, sales, export and import of contact ucts remain the cornerstone of Menicon’s continued lenses and other medical goods; manufacturing and growth and success. These principles are why we are sales of medical instruments; sales of medical supplies; able to celebrate such a significant anniversary.” and research and development of intraocular lenses. Menicon is committed to providing the highest qual- For more information, please visit: https://www. ity products and spares no effort to create the next menicon.com/

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Get Serious About Central Serous Chorioretinopathy

Mineralocorticoid receptor antagonists may present an effective option for early intervention.

By Mohammad Rafieetary, OD1 Jessica Haynes, OD1 Roya Attar, OD2 1memphis, TN, 2Jackson, MS

entral serous chorioretinopathy (CSCR) is a common retinal disorder that results in vision loss and alteration of visual func- C1 tion. It is considered a pachychoroid disease, a category of diseases that in- cludes polypoidal choroidal vasculopa- Fig. 1. In patients with acute CSCR, serous retinal detachment can be seen (yellow thy, pachychoroid neovasculopathy arrows). PED is not clinically detected in patient A but can be seen in patient B (blue). and pachychoroid pigment epitheli- opathy.2 Despite CSCR’s prevalence as produced hopeful results. With these corticosteroids and adrenergic receptor the fourth most common non-surgical medications in mind as an early inter- inhibitors. Other identifi ed potential retinopathy behind macular degenera- vention option, this article proposes risk factors include systemic hyperten- tion, diabetic retinopathy and branch a potential treatment scheme for sion, Helicobacter pylori gastrointestinal retinal vein occlusion, there is still no patients diagnosed with CSCR. disease, testosterone supplementation standard treatment regimen for the and sleep apnea.5-7 condition.1 Background Clinical fi ndings depend on the A variety of therapies and poten- CSCR is typically found in men and duration of CSCR, with fi ndings tial lifestyle modifi cations have been women of all ethnic backgrounds after associated with the condition detect- explored with different outcomes, the third decade of life. The common able during retinal examination. In including focal photocoagulation, acute presentation occurs most often acute cases, patients will present with photodynamic therapy (PDT) with in middle-aged Caucasian males.3,4 varying degrees of visual disturbance. verteporfi n, intravitreal anti-vascular The incidence rate is approximately Usually, a round serous retinal detach- endothelial growth factor (anti-VEGF) 10 men and two women per 100,000 ment (SRD) that varies in size is noted agents and several classes of oral and people.3,4 within the posterior pole. A pigment topical medications. More recently, The most common risk factors for epithelial detachment (PED) may investigation into mineralocorticoid the condition include “type A” person- or may not be detectable clinically receptor antagonist (MRA) drugs has ality, pregnancy and systemic use of (Figure 1).

About Dr. Rafi eetary is a consultative optometrist at the Charles Retina Institute in Germantown, TN. Dr. Haynes is also a consultative optometrist at the Charles the authors Retina Institute and a consulting faculty member at the Southern College of Optometry in Memphis, TN. Dr. Attar is an assistant professor in the Department of Ophthalmology at the University of Mississippi Medical Center. None of the authors have any fi nancial interests to disclose.

52 REVIEW OF OPTOMETRY | JUNE 15, 2021 Ancillary tests, such as spectral- domain OCT, fluorescein angiography (FA), indocyanine green (ICGA) angi- ography, OCT angiography and fundus autofluorescence (FAF), are helpful to detect the various associated features of CSCR.8-10 These imaging modalities are not only useful in proper diagnosis of the condition, but also in determi- nation of staging (acute or chronic) (Figures 2 and 3). On OCT, a common feature of CSCR is a greater-than-average cho- roidal thickness (Figure 4).11 One study reported that patients with CSCR had a mean subfoveal choroidal thick- ness of 475±138µm compared with 372±120µm in healthy patients.11 Although most acute cases sponta- neously resolve with minimal to no Fig. 2. This patient has acute CSCR. OCT imaging demonstrates neurosensory serous retinal long-term vision loss, persistent or detachments, with (A) showing a flat PED while (B) shows a bulging PED (red arrows). chronic CSCR can result in perma- Fluorescein angiography (C) shows the classic “smokestack” pattern of leakage and (D) nent alteration of the retinal pigment the more common “inkblot” pattern. Indocyanine green angiography shows the mid (E) epithelium (RPE) and retinal photore- and late (F) phases. Active leakage can be seen in the late phase (yellow arrow). Fundus ceptors (RPs). This can consequently autofluorescence (G) shows hypo-autofluorescence in acute or early cases (blue circle). cause permanent vision loss. There- fore, in chronic cases lasting longer than four months, therapy should be targeted to lessen the risk of perma- nent functional visual loss.12-14 The exact pathophysiology of CSCR is not well known, thus a standard of care has not yet been established.6 Investigational treatments have been based on the potential pathophysi- ological and etiologic factors.

Treatment Strategies Optometry, in collaboration with retina surgeons, has taken several different routes in treating CSCR and establish- ing a consistent treatment protocol. Thermal photocoagulation with argon Fig. 3. This patient is suffering from chronic CSCR. In (A), RPE changes can be seen in laser. This modality—the oldest form the macula. Fluorescein angiography (A1) shows staining of the altered RPE, and fundus of treatment—is based on mechani- autofluorescense (A2) shows hyper-autofluorescence indicative of RPE damage. OCT cally treating the PED or RPE defect, (B) shows accumulation of RP outer segment shedding (“shaggy” photoreceptors), a which is the assumed defective, phenomenon associated with choroidal melanomas (blue arrow). Autofluorescence (C and “leaky” area causing SRD. This area D) in other cases shows a variable mix of autofluorescence associated with chronicity and can be detected by FA and ICGA.15,16 recurrence. OCT (C1 and D1) shows adverse alteration of the outer retina (blue arrows). Damage to this area can terminate the active leakage and result in faster that are too close to the fovea. Risks PDT with verteporfin. This treat- resolution of the SRD; however, due include formation of , forma- ment addresses the notion that CSCR to collateral damage caused by the tion of laser scars and potentially is a condition of leaky, abnormal cho- thermal laser, this therapy cannot be development of choroidal neovascular roidal vessels, specifically within the applied to diffuse areas or regions membranes.15 choriocapillaris. Application of PDT

JUNE 15, 2021 | REVIEW OF OPTOMETRY 53 12th Annual Retina Report MANAGING CSCR

trial investigated topical dorzolamide in patients with chronic CSCR and found a greater improvement in central macular thickness at three months compared with controls.32 Systemic meds. Another known driving factor behind this condition is increased levels of corticosteroids, as a high incidence of CSCR is associated with systemic steroid use, pregnancy and potentially episodes of high stress Fig. 4. A thicker-than-average choroid is characteristic of CSCR. in susceptible individuals. A number of off-label systemic medications have been explored with this mechanism in mind, showing a range of therapeutic effi cacy. These therapeutic agents in- clude MRAs, rifampin and CAIs such as acetazolamide.33-37 At present, the most promising drug category for the treatment of CSCR is MRAs. MRAs. A number of reports have shown the benefi t of two steroidal compound mineralocorticoid receptor antagonists in the treatment of acute and chronic CSCR: spironolactone and eplerenone.38-47 Spironolactone is a non-selective Fig. 5. Acute case of CSCR (top). Resolution at one year without treatment (bottom). aldosterone (a mineralocorticoid hormone) antagonist and potassium- laser is thought to lead to a cascade of However, skepticism of the treatment sparing diuretic indicated for the events causing reduced choriocapillaris exists, as CSCR does not seem to be management of primary hyperaldo- congestion and vascular remolding, VEGF-driven and increased levels steronism and edematous-related resulting in decreased choroidal per- of VEGF are not found in those with conditions, congestive heart failure meability.17 PDT laser can be applied the condition. A recent meta-analysis (CHF), cirrhosis of the liver and ne- to broader and more central areas than could not verify a positive effect of phrotic syndrome. It is also indicated focal argon laser, and is often guided by intravitreal bevacizumab in patients for treatment of essential hypertension, FA or ICGA to target leaky areas. The with CSCR.25 It is of importance to hypokalemia and severe heart failure. initial short-term case series followed note that patients with CSCR are at This agent is contraindicated in pa- standard PDT protocol.18 Since then, increased risk of developing choroidal tients with anuria, acute renal insuffi - investigation into modifi ed strategies, neovascularization, of which anti- ciency, signifi cant impairment of renal such as half-dose PDT and half- VEGF is the treatment of choice.1 excretory function or hyperkalemia. It fl uence PDT, have shown good results Topical meds. Various topical agents interacts with angiotensin-converting with a better risk profi le. Unfortunate- have been investigated, including enzyme inhibitors, alcohol, barbitu- ly, a consensus still hasn’t been reached non-steroidal anti-infl ammatory drugs rates, narcotics, pressor amines and on PDT protocol in CSCR patients.19 (NSAIDs) and carbonic anhydrase in- skeletal muscle relaxants. Clinically, PDT laser availability and hibitors (CAIs). Multiple small-cohort While spironolactone has a good cost coverage are practical barriers to retrospective trials and case studies re- affi nity for the mineralocorticoid recep- the treatment. port increased rates of subretinal fl uid tor, being non-specifi c it also binds to Intravitreal injection of anti-VEGF. (SRF) reabsorption in acute CSCR progesterone receptors, causing dose- This route has also been explored as a with use of topical NSAIDs.26-30 dependent hormonal side effects.4 possible therapeutic option for CSCR, Critics of this treatment modality Adverse reactions may include as a chemical method of altering cho- suggest a possible placebo effect, espe- gastric bleeding, nausea/vomiting, diar- riocapillaris hyper-permeability. Mul- cially in those with a type A personal- rhea, gynecomastia, erectile dysfunc- tiple small case series show potential ity, and dispute a proven infl ammatory tion, irregular menses, agranulocytosis, benefi t with anti-VEGF treatment.20-24 etiology of CSCR.31 A prospective hypersensitivity, hyperkalemia, mental

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References: 1. Rao P et al. Ophthalmology. 2018;125(4):522-528. 2. Domalpally A, Clemons TE, Bressler SB, et al. Mon-Fri, 8 AM to 6 PM EST Ophthalmol Retina. 2019;3(4):326-335. See website for FDA Indication for Use. SM-068.02 www.foreseehome.com/hcp 12th Annual Retina Report MANAGING CSCR

always be at the forefront of the physi- cian’s treatment approach. A tentative treatment protocol, incorporating MRA as an early treatment option, involves the following: • Obtain case history. • Alter any modifi able risk factors. • Determine if condition is chronic or acute. • If acute, monitor. If the case doesn’t resolve in four months, proceed to chronic staging. • If chronic, initiate treatment with MRA if not contraindicated and obtain baseline serum potassium levels. Monitor for one month. • If improvement is observed, con- tinue therapy until SRD resolves before discontinuing and monitor- ing. • If improvement is not observed, Fig. 6. CFT was 342μm at initial presentation (top), 298μm after one month of treatment consider switching to an alternate with eplerenone (middle) and 190μm after two months (bottom). MRA and obtain FA or ICGA to guide laser treatment. dysfunction, headache, drowsiness and to 50mg daily for eplerenone until • In the case of localized, non-central renal dysfunction. resolution of SRF.38-47 At this dose, leakage, apply a focal laser. Eplerenone, created to lessen the spironolactone can reduce hormonal side effects of spironolac- both SRF and subfoveal tone, is a selective aldosterone antago- choroidal thickness com- nist indicated for improving survival pared with placebo in pa- of stable patients with left ventricu- tients with persistent SRF lar systolic dysfunction, CHF after due to CSCR.38-40 Eplere- myocardial infarctions or hypertension none has also resulted in as a mono or combination therapy. signifi cant structural and While the side effects of eplerenone functional improvement are favorable compared to those of in patients suffering from spironolactone, it is a much less potent chronic CSCR.41-47 MRA. Spironolactone has a 40-fold Proposed strategy. Due higher binding affi nity to the mineralo- to the variability of treat- corticoid receptor in comparison with ment response, there is eplerenone.4 currently no standard of For a complete list of contraindica- care in managing CSCR tions, precautions and adverse reac- patients. As evidenced by tions associated with both MRAs, refer combined treatment strat- to the prescribing information that egies and ongoing inves- accompanies each. In addition to ob- tigation, no single therapy taining a complete history of illnesses, works suffi ciently in all medications and allergies, prescribers patients. As such, treat- should consult the patient’s primary ing patients with CSCR care physician and obtain baseline is a highly individualized serum potassium levels before admin- process with many differ- istering these medications. ent considerations and op- The usual off-label administered tions to take into account. dose for treatment of CSCR with Weighing the risk vs. the Fig. 7. Fundus autofl uorescence (top) and OCT (bottom) spironolactone is 50mg daily and 25mg benefi t of therapy must are both suggestive of chronic disease.

56 REVIEW OF OPTOMETRY | JUNE 15, 2021 JUNE 15, 2021 | REVIEW OF OPTOMETRY 56 ADVERTORIAL

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Pinhole Optics from the center outward in a smooth, continuous and and EDOF uninterrupted fashion —reaching 3 diopters or more. Because there’s so much plus power near the treatment NaturalVue® (etafi lcon A) zone, the eff ect of the lens may be greater vs. traditional Multifocal 1 Day Contact designs in terms of its ability to move defocused light Lenses uniquely employs the rays inside the retina. Other published studies suggest principle of pinhole optics, that more plus power in the near periphery (closer to the creating an Extended Depth 2 fovea) may create a stronger eff ect. of Focus (EDOF). Douglas P. Benoit, OD, FAAO Executive Director, Additionally, the BLINK study supports the benefi t Professional Services for VTI To harness the power of higher ADD power in a lens. That study concluded of pinhole optics in its that treatment with the higher ADD power multifocal design, the Neurofocus Optics® Technology of contact lenses tested was more eff ective with NaturalVue Multifocal relies on the rapid, continuous 3 progressing myopes. and uninterrupted progression in relative plus power outward from the center of the lens. Multiple Types of Patients Benefi t from NaturalVue® Multifocal. With this design, NaturalVue Multifocal can deliver spectacle-level visual acuity across all distances.1 The versatility of this lens comes, in part, from a very unique extended depth of focus (EDOF) design. The A “Powerful” Eff ect: 3 or More Diopters high amount of relative plus can be tolerated well of Plus Power with all types of patients because the EDOF design creates pinhole optics that are unique to each person’s In the NaturalVue Multifocal, with no conventional own optical system. This enables clear vision at near, “transition zones,” the plus power increases rapidly intermediate and importantly, distance.

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References: 1. VTI data on fi le 2015. N=59. Data assessed after one week of wear. 2. Smith EL III. Optical treatment strategies to slow myopia progression: Eff ects on the visual extent of the optical treatment zone. Exp Eye Res. 2013 Sep;114:77-88 3. Walline JJ, Walker MK, Mutti DO, et al. Eff ect of High Add Power, Medium Add Power, or Single-Vision Contact Lenses on Myopia Progression in Children: The BLINK Randomized Clinical Trial. JAMA. 2020;324(6):571–580. doi:10.1001/jama.2020.10834 © 2021 Visioneering Technologies, Inc. MKT-GBL-NVM-AP7 12th Annual Retina Report MANAGING CSCR

25mg daily was initiated following a re- view of risks, benefi ts and alternatives. The patient’s CFT at one month was 298µm, and at two months follow- up, it was 190µm with complete resolu- tion of SRF (Figure 6). Upon resolution of SRF, treatment with eplerenone was discontinued. Her fi nal visual acuity was 20/30. Unknown. A 46-year-old African American female presented with a his- tory of CSCR. She reported symptoms that had been present for four months. Her medical history was positive for Fig. 8. Localized area of leakage on fl uorescein angiography in (A) and ICGA in (B). high blood pressure, asthma, anemia and kidney disease with a prior kidney • In the case of diffuse, central leak- (fl uticasone, GlaxoSmithKline) daily. transplant. Her medications included age, apply PDT. At presentation, her CFT was 342µm. amlodipine 5mg BID, calcium carbon- • If improvement is observed, monitor With a case history positive for ate 500mg BID, clonidine 0.1mg TID, and coordinate additional therapy as steroid use with Flonase, it was recom- aspirin 81mg daily, docusate 100mg needed. mended that the patient discontinue BID, dapsone 100mg daily, fl uconazole • If improvement is not observed, the medication immediately. The 100mg daily, hydralazine 25mg TID, consider treatment with anti-VEGF. condition was deemed to be chronic furosemide 40mg daily, two tablets of based on the patient’s history and magnesium oxide 400mg QID, meto- Case Examples OCT fi ndings. Due to the chronicity of prolol tartrate 25mg BID, mycopheno- The following cases illustrate the the CSCR, treatment with eplerenone late sodium 180mg TID, pantoprazole proposed treatment strategy for various clinical scenarios: Acute. A 46-year-old white male pre- sented with an acute-onset dark spot in his vision OS for 10 days. The patient reported no recent increase in stress and no use of any steroid medications. OCT imaging was consistent with an acute case of CSCR, with an enter- ing central foveal thickness (CFT) of 420µm. His baseline visual acuity was 20/25. Due to the acute nature of the condition, the patient was monitored without treatment. The one-month follow-up showed signifi cant improve- ment of CFT. The patient was lost to follow-up at this point but presented one year later with complete resolu- tion of SRF and visual acuity of 20/20 (Figure 5). Chronic. A 53-year-old white female presented with a history of chronic CSCR for two years. Her baseline visual acuity was 20/50. Her previous treatment included intravitreal bevacizumab injections and oral acetazolamide without Fig. 9. Chronic CSCR with shaggy photoreceptors at time of laser therapy (top), one month improvement. She was using Flonase (top middle), two months (bottom middle) and six months (bottom) after focal laser.

58 REVIEW OF OPTOMETRY | JUNE 15, 2021 3. Kitzmann AS, Pulido JS, Diehl NN, et al. The incidence 26. Alkin Z, Osmanbasoglu OA, Ozkaya A, et al. Topical 40mg daily, prednisone 5mg daily, of central serous chorioretinopathy in Olmsted County, nepafenac in treatment of acute central serous chorio- montelukast 10mg daily and tacrolimus Minnesota, 1980-2002. Ophthalmology. 2008;115(1):169- retinopathy. Med Hypothesis Discov Innov Ophthalmol. 2013;2(4):96-101. 1mg six times daily. 73. 4. Spaide RF, Campeas L, Haas A, et al. Central serous 27. Wuarin R, Kakkassery V, Consigli A, et al. Combined OCT and FAF imaging were both chorioretinopathy in younger and older adults. Ophthal- topical anti-inflammatory and oral acetazolamide in the mology. 1996;103(12):2070-9. treatment of central serious chorioretinopathy. Optom Vis suggestive of chronic CSCR (Figure Sci. 2019;96(7):500-6. 5. Daruich A, Matet A, Dirani A, et al. Central serous cho- 7). While the patient’s medical history rioretinopathy: recent findings and new physiopathology 28. Bahadorani S, Maclean K, Wannamaker K, et al. was positive for steroid use, her options hypothesis. Prog Retin Eye Res. 2015;48:82-118. Treatment of central serous chorioretinopathy with topical NSAIDs. Clin Ophthalmol. 2019;13:1543-8. for discontinuation were limited by 6. Abouammoh MA. Advances in the treatment of central serous chorioretinopathy. Saudi J Ophthalmol. 29. Chong CF, Yang D, Pham TQ, et al. A novel treatment her prior kidney transplant. Since her 2015;29(4):278-86. of central serous chorioretinopathy with topical anti- inflammatory therapy. BMJ Case Rep. 2012;2012. condition was chronic, therapy was 7. Nudleman E, Witmer MT, Kiss S, et al. Central serous chorioretinopathy in patients receiving exogenous testos- 30. An SH, Kwon YH. Effect of a topical nonsteroidal initiated with oral spironolactone 50mg terone therapy. Retina. 2014;34(10):2128-32. anti-inflammatory agent (0.1 % pranoprofen) on acute daily. Due to her extensive medical central serous chorioretinopathy. Graefes Arch Clin Exp 8. Montero JA, Ruiz-Moreno JM. Optical coherence Ophthalmol. 2016;254(8):1489-96. history, the patient’s nephrologist was tomography characterisation of idiopathic central serous chorioretinopathy. Br J of Ophthalmol. 2005;89(5):562-4. 31. Kaya A, Aksoy Y, Sevinç MK, et al. Comment on: “Effect consulted prior to initiation of treat- of a topical nonsteroidal anti-inflammatory agent (0.1 % 9. How ACSW, Koh AHC. Angiographic characteristic of pranoprofen) on acute central serous chorioretinopathy.” ment. There was no improvement acute central serous chorioretinopathy in an Asian popula- Graefes Arch Clin Exp Ophthalmol. 2016;254(7):1429. tion. Ann Acad Med Singap. 2006;35(2):77-9. with spironolactone therapy; therefore, 32. Liew G, Ho IV, Ong S, et al. Efficacy of topical carbonic treatment was changed to eplerenone 10. Menchini U, Virgili G, Lanzetta P, et al. Indocyanine anhydrase inhibitors in reducing duration of chronic green angiography in central serous chorioretinopathy. Int central serous chorioretinopathy. Transl Vis Sci Technol. 25mg daily, also without success. Ophthalmol. 1997;21(2):57-69. 2020;9(13):6. FA and ICGA were performed. 11. Kuroda S, Ikuno Y, Yasuno Y, et al. Choroidal 33. Jaisser F, Farman N. Emerging roles of the mineralo- thickness in central serous chorioretinopathy. Retina. corticoid receptor in pathology: toward new paradigms in Both revealed a focal, non-central area 2013;33(2):302-8. clinical pharmacology. Pharmacol Rev. 2016;68(1):49-75. of late leakage (Figure 8). Focal laser 12. Ross A, Ross AH, Mohamed Q. Review and update of 34. Shulman S, Goldberg D, Schwartz R, et al. Oral was applied to this area. There was central serous chorioretinopathy. Curr Opin Ophthalmol. rifampin treatment for longstanding chronic central serous 2011;22(3):166-73. chorioretinopathy. Graefes Arch Clin Exp Ophthalmol. significant improvement of serous fluid 13. Klein ML, Van Buskirk EM, Friedman E, et al. Experi- 2016;254(1):15-22. one month after and complete resolu- ence with nontreatment of central serous choroidopathy. 35. Sabouri MR. Evaluation of therapeutic effect of Arch Ophthalmol. 1974;91(4):247-50. tion two months after, with continued rifampin for acute central serous chorioretinopathy. Bina J 14. Aggio FB, Roisman L, Melo GB, et al. Clinical factors Ophthalmol. 2013;19(1):46-51. improvement in outer retinal anatomy related to visual outcome in central serous chorioretinopa- 36. Witjaksana R, Sumual V. Treatment of central serous six months post-treatment (Figure 9). thy. Retina. 2010;30(7):1128-34. chorioretinopathy with carbonic anhydrase inhibitor. 15. Robertson DM, Ilstrup D. Direct, indirect, and sham la- Ophthalmologica Indonesiana. 2016;42(2):119-22. ser photocoagulation in the management of central serous 37. Pikkel J, Beiran I, Ophir A, et al. Acetazolamide Takeaways chorioretinopathy. Am J Ophthalmol. 1983;95(4):457-66. for central serous retinopathy. Ophthalmology. While the management of patients 16. Leaver P, Williams C. Argon laser photocoagulation in 2002;109(9):1723-5. the treatment of central serous retinopathy. Br J Ophthal- 38. Bousquet E, Beydoun T, Rothschild PR, et al. Spirono- with CSCR remains up to each clini- mol. 1979;63(10):674-7. lactone for nonresolving central serous chorioretinopa- cian’s discretion, the proposed treat- 17. Chan WM, Lam DSC, Lai TYY, et al. Choroidal vascular thy: a randomized controlled crossover study. Retina. 2015;35(12):2505-15. ment protocol takes into account the remodeling in central serous chorioretinopathy after indocyanine green guided photodynamic therapy with 39. Herold TR, Prause K, Wolf A, et al. Spironolactone risk vs. benefit of treatment as well as verteporfin: a novel treatment at the primary disease level. in the treatment of central serous chorioretinopathy— Br J Ophthalmol. 2003;87(12):1453-8. the currently understood effectiveness a case series. Graefes Arch Clin Exp Ophthalmol. 18. Yannuzzi LA, Slakter JS, Gross NE, et al. Indocyanine 2014;252(12):1985-91. of proposed therapies. green angiography-guided photodynamic therapy for treat- 40. Ryan EH, Pulido CM. Central serous chorioretinopathy While no therapy is without risk, ment of chronic central serous chorioretinopathy: a pilot treatment with spironolactone: a challenge-rechallenge study. Retina. 2003;23(3):288-98. case. Retin Cases Brief Rep. 2015;9(3):235-8. the possibility of improved outcomes 19. Iacono P, Parodi MB, Falcomatà B, et al. Central serous 41. Sun X, Shuai Y, Fang W, et al. Spironolactone versus in CSCR patients with readily avail- chorioretinopathy treatments: a mini review. Ophthalmic observation in the treatment of acute central serous cho- Res. 2015;55(2):76-83. able oral medications makes treatment rioretinopathy. Br J Ophthalmol. 2018;102(8):1060-5. 20. Schaal KB, Hoeh AE, Scheuerle A, et al. Intravitreal 42. Cakir B, Fischer F, Ehlken C, et al. Clinical experi- with MRA a good first-line option bevacizumab for treatment of chronic central serous ence with eplerenone to treat chronic central serous in cases of chronic disease persisting chorioretinopathy. Eur J Ophthalmol. 2009;19(4):613-7. chorioretinopathy. Graefes Arch Clin Exp Ophthalmol. 21. Mehany SA, Shawkat AM, Sayed MF, et al. Role of 2016;254(11):2151-7. longer than four months. Those who Avastin in management of central serous chorioretinopa- 43. Breukink MB, den Hollander AI, Keunen JEE, et al. The do not respond well to MRAs should thy. Saudi J Ophthalmol. 2010; 24(3):69-75. use of eplerenone in therapy-resistant chronic serous be considered for additional therapies 22. Tekin K, Sekeroglu MA, Cankaya AB, et al. Intravitreal chorioretinopathy. Acta Ophthalmol. 2014;92(6):e488-90. bevacizumab and ranibizumab in the treatment of acute 44. Singh RP, Sears JE, Bedi R, et al. Oral eplerenone for such as angiographically guided PDT central serous chorioretinopathy: a single center retro- the management of chronic central serous chorioretinopa- or focal laser, and possibly intravitreal spective study. Semin Ophthalmol. 2018;33(2):265-70. thy. Int J Ophthalmol. 2015;8(2):310-4. 23. Park SU, Lee SJ, Kim M. Intravitreal anti-vascular 45. Cioboata M, Alexandrescu C, Hopinca CA, et al. A new anti-VEGF. Observation of acute cases endothelial growth factor versus observation in acute treatment approach—eplerenone—in central serous chorio- initially is recommended. ■ central serous chorioretinopathy: one year results. Korean retinopathy—case report. J Med Life. 2016;9(1):92-4. J Ophthalmol. 2014;28(4):306-13. 46. Rahimy E, Pitcher JD, Hsu J, et al. A randomized 1. Wang M, Munch IC, Hasler PW, et al. Central serous 24. Kim M, Lee SC, Lee SJ. Intravitreal ranibizumab for double-blind placebo-control pilot study of eplerenone for chorioretinopathy. Acta Ophthalmol. 2008;86(2):126-45. acute central serous chorioretinopathy. Ophthalmologica. the treatment of central serous chorioretinopathy. Retina. 2013;229(3):152-7. 2018;38(5):962-9. 2. Demirel S, Değirmenci MFK, Batıoğlu F, et al. Evalua- tion of the choroidal features in pachychoroid spectrum 25. Chung YR, Seo EJ, Lew HM, et al. Lack of positive 47. Schwartz R, Habot-Wilner Z, Martinez MR, et al. diseases by optical coherence tomography and optical effect of intravitreal bevacizumab in central serous Eplerenone for chronic central serous chorioretinopathy—a coherence tomography angiography. Eur J Ophthalmol. chorioretinopathy: meta-analysis and review. Eye (Lond). randomized controlled prospective study. Acta Ophthal- 2021;31(1):184-93. 2013;27(12):1339-46. mol. 2017;95(7):e610-8.

JUNE 15, 2021 | REVIEW OF OPTOMETRY 59 12th Annual Retina Report PEER REVIEWED RETINAL ISCHEMIA

Stroke of the Eye: Are You Prepared?

When retinal arterial occlusion strikes, you and the patient have only a few hours to act if you want the best odds of preserving vision.

By marc myers, od1 and andrew gurwood, od2 1 Coatesville, PA 2 Philadelphia, PA here are quite a few eye condi- tions that cause discomfort and pain, but some require immedi- Tate attention and prompt action not just from eyecare providers, but medical professionals at emergency rooms. Retinal arterial occlusion (RAO) is one of those conditions and should be considered a true ocular emergency. This is because the retinal ischemia Fig. 1. The photo on the left shows a Hollenhorst cholesterol plaque within the superior- that is produced creates immediate temporal vascular arcade. At follow-up three months later, the plaque is not present. and permanent cell damage—even when timely interventions are proper- retinal arterial blood supply.1-3 Em- Transient Monocular Vision Loss ly dispensed. The condition compro- bolic events are just one mechanism; Episodes of visual compromise that mises tissues so quickly there is little vascular compression (mass effect are reversible and last less than 24 likelihood of even modest functional and acute IOP rise), arteritic and hours are termed transient vision improvements. Today, treatment ex- vasospastic pathologies also have the loss (TVL); these can be binocular or tends beyond heroic ocular measures, ability to interrupt arterial circulation, monocular.4,5 Transient monocular vi- recognizing that emergent medical resulting in ischemia and permanent sion loss (TMVL) may be permanent interventions are required to curtail tissue damage. or reversible and has an incidence of associated systemic comorbidities. These events can be transient or approximately 14 per 100,000 people Acute retinal arterial ischemia permanent and may involve the oph- per year.2 Patients generally report can be caused by any process that thalmic artery, central retinal artery or that episodes of TMVL last 20 to 30 interrupts the blood fl ow within the a branch retinal artery.1-3 minutes and describe it as a curtain of

Dr. Myers is senior staff optometrist at Coatesville Veterans Affairs Medical Center in Coatesville, PA. He is also a guest lecturer and adjunct clinical faculty at About the Pennsylvania College of Optometry. Dr. Gurwood is a professor of clinical sciences at The Eye Institute of the Pennsylvania College of Optometry at Salus the authors University. He is a co-chief of Primary Care Suite 3. He is also attending medical staff in the department of ophthalmology at Albert Einstein Medical Center in Philadelphia. They have no fi nancial interests to disclose.

60 REVIEW OF OPTOMETRY | JUNE 15, 2021 4,5 darkness occluding the affected eye. Table 1. Emboli and their common origins Specifically, TMVL is caused by oc- clusive arterial pathology anterior to Type of Embolus Origin of Embolus the chiasm, at the level of the optic nerve or retina.4,5 Cholesterol Extracranial carotid artery The underlying cause of an episode Calcium Valve of heart is uncovered thorough history—which serves to verify timing, pattern, pro- Platelet fibrin aggregates Aortic arch, artery system voking factors and associated symp- Fat Fat droplet from a fractured long bone toms—laboratory testing and imag- ing.1-3 The most common sources of Septic (bacteria containing tissue) Infected tissue (e.g., endocarditis) emboli consist of cholesterol, platelet- Air Air enters circulation via needle fibrin material and calcium emanat- ing from the heart, aorta or internal Amniotic fluid Enters mother’s circulation via placenta during birth carotid artery.1-3 Foreign body Injection of material into blood circulation, ingestion In instances of binocular TVL, le- of foreign substances (e.g., cocaine, talc) sions are localized to the optic chiasm or retro-chiasmal visual pathway and Paradoxical (originates from a vein) Patent foramen ovale may be the result of disease processes that involve the vasculature of both the conjunctiva, rubeosis irides, mid- CRAO.3,6-10 Emboli also travel from optic nerves.4,5 peripheral retinal hemorrhages and distant sources such as the heart and non-tortuous retinal veins.4,5 TMVL the aortic arch, and may consist of Sources of RAO events associated with OIS typically cholesterol, calcium or platelet fibrin Non-embolic events producing have a gradual onset that lasts from aggregates.3,6-10 TMVL are accompanied by unique seconds to minutes.4,5 There are less common sources of patterns of signs and symptoms, Systemic hypotension and reduced emboli that may result in the occlu- including retinal migraines, which cardiac output may result in hypoper- sion of the retinal arterial system commonly last up to 20 minutes and fusion of the eye. In such cases, the (Table 1). For instance, a fat embolus may recur several times a day. These TVL event is binocular and accompa- can occur when a fractured long attacks include reversible visual phe- nied by lightheadedness and confu- bone releases droplets of fat into the nomena such as sion.4,5 Other, less common diagnoses bloodstream. These commonly travel and are frequently accompanied by include the hypercoagulable states to the lungs or the brain, resulting in headaches.4,5 Retinal vasospasm can and orbitopathies.4,5 pulmonary emboli or stroke.6-10 Septic produce a constellation of symptoms In contrast to TMVL, long-term emboli consist of bacteria or bacteria- similar to those of ocular migraines or permanent vision loss associated containing tissues entering the without the associated headache. with acute retinal arterial ischemia bloodstream from a site of infection, A relative afferent pupillary defect is the result of longer lasting partial such as an infected heart valve (infec- (RAPD) may be present during the or complete occlusion of the retinal tious endocarditis).6-10 Air emboli are episode, but can be resolved as perfu- arterial system.3,6-10 Ophthalmic artery formed when small amounts of air sion is restored so long as retinal tis- occlusion, central retinal artery oc- enter the blood circulation during a sues are not permanently damaged.4,5 clusion (CRAO) and branch retinal medical procedure such as surgery or Giant cell arteritis (GCA) has clini- artery occlusion (BRAO) often lead catheterization, or during injectable cal features that include headache, to permanent visual dysfunction substance abuse.6-10 jaw claudication, scalp tenderness, depending on the region of the retina Amniotic fluid embolus—while fever, polymyalgia rheumatica and involved, and may produce reduced rare—is the result of amniotic fluid TMVL.4,5 Episodes of vision loss visual acuity and noticeable visual entering a mother’s circulation via the are of short duration—under five field deficits. placenta during childbirth.6-10 Also minutes—may be exacerbated by The most common cause of rare is the formation of a foreign body postural changes, can recur over a acute retinal arterial ischemia is embolus. These emboli form as the short period of time and have associ- embolism (non-arteritic) originat- result of a medical procedure (iat- ated photopsia.4,5 ing from atheromatous stenosis of rogenic) or recreational drug abuse, (OIS), the ipsilateral internal carotid artery such as cocaine use or additives like which results from carotid artery dis- (ICA).3,6-10 Extracranial ICA stenosis talc. Iatrogenic causes may also be the ease, presents with ophthalmic signs of greater than 70% has been seen in result of an injection during a dental that include vascular congestion of up to 40% of patients diagnosed with procedure or from a facial cosmetic

JUNE 15, 2021 | REVIEW OF OPTOMETRY 61 12th Annual Retina Report RETINAL ISCHEMIA

either the emergency department or eye doctor. Men reportedly have a higher inci- dence than women, and the average age of presentation is approximately 65.3,10-13 The patient’s medical history will frequently include cardiovascular disease, diabetes, hypercholester- olemia and/or a history of cigarette smoking.14,15 These systemic dis- eases are also confounding factors in the presence of an acute ischemic stroke.9,16,17

Signs and Symptoms A clinical examination will confi rm a precipitous reduction in visual acuity (20/400 or worse), visual fi eld loss and an afferent pupillary defect. impairment directly correlates with the decline of visual acuity and involvement of the macular region. General medical procedures that may be performed in-offi ce include mea- surements of blood pressure, pulse, pulse oximetry and assessment for carotid bruit. A fi brinogen platelet embolus is seen at the location of the large blue arrow. A small Posterior segment fi ndings are is seen at the small blue arrow. highly variable, depending on the du- ration of the event and the time from procedure where a drug or fi ller mate- Rapid changes in intraocular pres- onset of symptoms to examination. rial is injected into a vessel.11 An sure have the potential to result in The alteration of retinal blood vessels embolus that originates in a vein and occlusion of the retinal arterial system may include “cattle trucking” (seg- eventually causes the occlusion of by way of compression. Acutely mentation of the blood column within an artery is a “paradoxical” embolus. elevated intraocular pressure in cases the vessel) and retinal arterial attenu- These emboli require a pathway from of glaucoma, ocular compression as a ation.1-3,6 Other fi ndings that may be the right side of the heart to the left, result of pressure on the eye due to observed include pallid edema of the as in the case of a patent foramen positioning for an extended period of , the presence of an em- ovale.3,6-10 time in supine position (as in the case bolus, pale and swollen retinal tissue Giant cell arteritis is the most com- of spinal surgery), , and a cherry red-spot involving the mon arteritic cause of retinal arterial retrobulbar injection and peribulbar macula.1-3,6 occlusion and should be included in anesthesia have all been associated every vascular workup, even when with retinal arterial occlusion.1-10 Pathophysiology suspicion is minimal.3,6-10 The doctor The posterior segment examination must be aware of the clinical features Epidemiology may reveal the presence of an em- of GCA, as mentioned above, when In the United States, CRAO has bolus within an artery of the retina. In investigating the etiology of sudden an incidence of 1.9 per 100,000 many cases, the embolus is not able to vision loss and its association with people.1-12 This incidence increases be visualized. The presentation of an an arterial occlusive event.3,6-10 Other to 10.1 per 100,000 for those age 80 embolus is helpful because it provides non-embolic causes of retinal arterial years and older.12 Retinal and oph- information regarding its consistency occlusion may include hematologic thalmic artery occlusive events are and origin. abnormalities resulting from sickle marked by acute, painless monocular A plaque that is highly refl ective cell hemoglobinopathies, leukemia visual acuity and/or visual fi eld loss, and white in color most likely consists and systemic non-Hodgkin’s lym- and it is only when these symptoms of cholesterol originating from the phoma.3, 6-10 persist that patients make their way to ipsilateral carotid artery (Hollenhorst

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been challenged based upon a review Table 2. Laboratory studies and medical indications of the original research designs.10 It has been proposed that clamping the Laboratory Test Indication for Test central retinal artery, as was done in the original work, would not have Complete blood count (CBC) Overall health, anemia, infection, leukemia resulted in complete obstruction of Basic metabolic panel Measures glucose, electrolyte, kidney function blood to the retina. Further, it would not have eliminated the collateral cir- Prothrombin time/Partial Bleeding disorder, excessive clotting disorder culation to the retina. In this instance, thromboplastin time the created arterial occlusion would be incomplete. While collateral cir- International normalized ration (INR) Time to prevent formation of blood clot culation would not permit complete perfusion of the retina, it certainly Lipid panel Measure of total cholesterol levels might have lengthened the time necessary to achieve inner retinal Hemoglobin A1c (HA1c) Average level of blood sugars over 60-90 days ischemia.10,18 This has led to thinking that retinal survival time is actually Erythrocyte sedimentation rate (ESR) Degree of inflammation present in the body much less. C-reactive protein Measure a liver protein that responds to Tissue of the brain and the retina inflammation are thought to be the most energy consuming structures of the body. Comparative studies of brain and plaque). Plaques often originate from Interestingly, calcifi c emboli are retina reveal that retinal oxygen the bifurcation or within the internal rough in texture and tend to get consumption per gram is greater carotid artery.3,6-9 Emboli consisting of impacted within the vessel walls. than that of the brain, making the calcifi c debris or platelet fi brin aggre- Cholesterol and platelet-fi brin emboli retina at least as vulnerable to oxygen gates present as elongated dull grey have a less rough texture and tend to deprivation.19-23 Hence, opponents opacities. Calcium emboli commonly migrate easily.3,10 Therefore, in a case of the original models postulate that originate from a heart valve. Platelet of monocular acute painless vision during complete central retinal artery fi brin aggregates are frequently a loss, a conclusion that “this is not a occlusion, irreversible retinal ganglion byproduct of artery damage caused retinal artery occlusion” may not be cell death begins after just 12 to 15 by atherosclerosis and can involve the made just because no retinal embolus minutes.19-23 aortic arch or the carotid or internal was observed.3,10 Not all CRAOs or BRAOs are carotid artery.3,6-9 permanent and/or complete, as the Emboli have the greatest likeli- Retinal Survival Time involved vessels may only be partially hood of occluding the central retinal Occlusion of any retinal artery ulti- occluded or the obstruction transient. artery where its lumen is narrowest, at mately results in the infarction of the These factors, along with the pres- the point where it pierces the dura of retinal ganglion cells found within their ence of a cilioretinal artery (a retinal the optic nerve, and is less likely just vascular range.18 Research suggests that vessel deriving its blood supply from posterior to the lamina cribrosa.3,10 the ganglion cell layer of the retina can the uninvolved choroidal circulation, As both of these anatomical sites are survive interrupted blood fl ow if circu- present in 15% to 30% of eyes) allow behind the globe, the vast majority lation is restored in up to 97 minutes of for a prognosis that predicts spared of emboli that cause CRAO are not the occlusion.18 Beyond the 97-minute sectors and potential for recovery.3,6,24 able to be visualized during dilated mark and up to 240 minutes, more ex- The variability in both visual acuity funduscopy.3,10 tensive and irreversible damage occurs. and spared fi eld will correlate with The phenomenon known as “mi- Occlusion beyond the 240 minutes re- the extent of the distribution of the gration of retinal emboli” can occur sults in catastrophic, irreversible retinal anatomical variation of the cilioretinal in both CRAO and BRAO, and may damage.18 artery.3,6 account for why emboli are not found Hayrah’s classic research of CRAO at the time of the acute examination. included experimental occlusion of Ocular Management In this case, by the time the patient the central retinal artery of rhesus The critical period in any case of presents to the clinic, the embolus monkeys. These experiments pro- retinal artery occlusion is from the has migrated from its original position vided us with the 97 to 240 minute onset of symptoms to when the within a retinal artery and may no boundaries that are recited today.18 patient presents for ophthalmic care. longer be visible.3,10 Recently, retinal survival times have The goal of acute ocular treatment

64 REVIEW OF OPTOMETRY | JUNE 15, 2021 is to reverse retinal ischemia by re- storing perfusion before permanent cell death occurs.1-3 Unfortunately, acute treatment remains controver- sial, as there is no proven standard of care. The intervention of IOP lowering (topical timolol, iopidine, oral acet- azolamide and IV mannitol, anterior chamber paracentesis) is directed toward decreasing the resistance to perfusion into the eye. By making it easier for blood to enter the eye, perhaps an increased flow might destabilize and move the embolus This shows the early presentation of a CRAO of the left eye with pale edema of the retina, downstream or provide adequate a cherry red spot at the time of presentation of a central retinal artery occlusion. Artery nutrition to avert cell death. attenuation is also noted. Inhaling carbon dioxide or taking other oral or IV vasodilating agents recognized an ischemic stroke as an occur. To reduce this risk, confound- are efforts directed toward dilation “episode of neurological dysfunc- ing factors such as active bleeding, of the blood vessels of the retina. As tion caused by focal cerebral, spinal recent stroke or hemorrhage or use retinal arterioles become pharma- or retinal infraction.”9 The common of anticoagulation therapy should be cologically enlarged, the involved pathophysiology shared by stroke identified.9,28 arteriole might loosen its grip on patients and retinal artery occlusion IAT involves the introduction of an embolus, permitting it to be patients has prompted experts to the thrombolytic agent (tPA) directly jettisoned downstream, restoring categorize RAO as a “stroke of the into the ophthalmic circulation via perfusion. eye.” This philosophy mandates con- microcatheterization.29 The advan- Direct pressure to the globe comitant and rapid triage of CRAO tage is that therapy is delivered to the (“mashing” the eye or digital ocular patients with an aggressive systemic thrombus, limiting systemic circula- massage) in combination with the workup, with the goal of reducing tion and reducing the risk of intracra- first two interventions is intended cardiac and associated central nervous nial and systemic hemorrhage.29 In- to create a back pressure for the system (CNS) comorbidities.9,25,26 herent risks include possible arterial blood that is trying to enter the eye, Specifically, intravenous tissue dissection, catheter-induced spasm such that when the direct pressure plasminogen activator (tPA) and and dislodgement with distal embo- is released, an increase of blood intra-arterial thrombolysis (IAT) are lization of an atheromatous plaque flow might impact the embolus with commonly used in the management withing the ophthalmic circulation.29 such force that it dislodges the em- of occlusive ischemic cerebral infarcts Prompt triage and referral to an bolus, restoring retinal perfusion.3-6,8 and are being more closely investigat- emergency department, with the Another treatment being explored ed as a more standardized treatment goal of admission to a stroke floor is hyperbaric oxygen. Here, by of CRAO.9,26,27 for a comprehensive medical assess- supersaturating the red blood cells Intravenous fibrinolysis most com- ment by experts who understand and “collateral retinal systems” monly uses the infusion of alteplase this syndrome, is now the standard of (the choroidal circulation), unused (which acts as a tPA) and is proven care.1,2,9,27 Laboratory studies should oxygen might diffuse forward into to be most efficacious when admin- include a complete blood count, basic the starving retina to emergently istered within 4.5 hours of the onset metabolic panel, prothrombin time/ nourish it and postpone cell death.25 of symptoms.26,27 A meta-analysis of partial thromboplastin time, interna- Unfortunately, there is little if any observational studies found that pa- tional normalized ratio, lipid panel, evidence-based data that supports tients with acute CRAO treated with hemoglobin A1c, erythrocyte sedi- any of the above therapies as a way this modality had a 50% rate of clini- mentation rate and C-reactive protein to reverse the often catastrophic cal recovery (visual acuity of 20/100 (Table 2). These studies assess the outcome.3,6,8,9 when initial acuity was 20/200) when overall wellness of the patients and treated within 4.5 hours of onset of target the most common vascular risk Systemic Management symptoms.28 Unfortunately, treatment factors (HTN, DM, hyperlipidemia) A March 2021 statement from the must be used selectively, as symp- that may lead to other vascular occlu- American Heart Association formally tomatic intracranial hemorrhage can sive events or myocardial infarction.1-3

JUNE 15, 2021 | REVIEW OF OPTOMETRY 65 12th Annual Retina Report RETINAL ISCHEMIA

15. Long C P, Chan AX, Bakhoum CY, et al. Prevalence of Diagnostic imaging should be CRAO patients who do not make subclinical retinal ischemia in patients with cardiovascu- ordered in all cases of retinal vascular lifestyle changes has been estimated lar disease – a hypothesis driven study. EClinicalMedi- occlusion to search for the potential to be reduced by 10 years vs. healthy cine. 2021. origin of an embolus. If vascular nar- controls.6-9 16. Fallico M, Lotery AJ, Longo A, et al. Risk of acute stroke in patients with retinal artery occlusion: a system- rowing or blockage exists, it must be atic review and meta-analysis. Eye 2020; 34(4):683-89. identifi ed to eliminate the potential Summary 17. Park SJ, Choi NK, Yang BR, et al. Risk and risk periods for subsequent occlusive events in Historically, even the most heroic for stroke and acute myocardial infarction in patients with 7-9,14 central retinal artery occlusion. Ophthalmol 2015; 122(11): the brain or heart. Imaging studies ophthalmic treatments rarely result 2236-43. include computed tomography (CT), in the restoration of functional vi- 18. Hayreh SS, Zimmerman MB. Fundus changes in cen- magnetic resonance imaging (MRI), sion. Acknowledging the association tral retinal artery occlusion. Retina 2007;27(3):276-89. CT angiogram, MR angiogram, between cardiac and central nervous 19. Astrup J, Siesjo BK, Symon L. Thresholds in carotid doppler, transthoracic echocar- cerebral ischemia – the ischemic penumbra. Stroke. system conditions makes retinal 1981;12(6):723-5. diogram and transesophageal echocar- ischemic events a true medical emer- 20. Raichle ME. The pathophysiology of brain ischemia. diogram. Ambulatory cardiac rhythm gency and the need to refer cases of Ann Neurol 1983;13(1):2-10. monitoring is frequently performed to retinal ischemia to the emergency 21. Lee VM, Grab MC, Zipfel GJ, et al. Brain tissue diagnose atrial fi brillation.7-9,14 department must not be understated. response to ischemia. J Clin Invest 2000;106(6):723-31. Treatment goals on the stroke fl oor Eyecare providers should have a plan 22. Wangsa-Wirawan ND, Linsenmeier RA. Retinal oxygen: fundamental and clinical aspects. Arch Ophthalmol. include tight management of vascu- that incorporates the primary care pro- 2003;121(4):547-57. lar risk factors that have a common vider, the emergency department and 23. Yu DY, Cringle SJ. Oxygen distribution and consump- impact on CRAO, stroke and carotid a stroke center into the global care of tion within the retina in vascularized and avascular artery disease.7,14 Control of hyperten- and in animal models of retinal disease. Prog Retin Eye the patient with CRAO. ■ Res. 2001;20(2):175-208. sion (the leading risk factor for retinal 24. Hayreh SS. Prevalent misconceptions about acute 1. Biousse V, Nahb F, Newman NJ. Management of acute ischemia), hyperlipidemia (the second retinal vascular occlusive disorders. Prog Retin Eye Res retinal ischemia. Ophthalmol. 2018;125(10):1597-1607. most common risk factor associated), 2005;24(4):493-519. 2. Dattilo M, Newman NJ, Biousse V. Acute retinal arterial diabetes and obstructive sleep apnea ischemia. Ann Eye Sci. 2018;3(6):1-19. 25. Masters TC, Westgard BC, Hendriksen SM, et al. Case series of hyperbaric oxygen therapy for central are of most importance. Lifestyle 3. Hayreh SS. Central retinal artery occlusion. Indian J retinal artery occlusion. Retinal cases and brief reports. changes and education include smok- Ophthalmol. 2018;66(12):1684-94. 2019;00(00):1-6. ing cessation, exercise and dietary 4. Feroze KB, O’Rourke MC. Transient vision loss. 26. Feltgen N, Neubauer, Jurklies B, et al. Multicenter StatPearls, NCBI bookshelf. www.ncbi.nim.gov/books/ study of the European Assessment Group for Lysis in restrictions to reduce obesity and NBK430845. the Eye (EAGLE) for the treatment of central retina l BMI.7-9,14 5. Fitzpatrick T, Gocan S, Wang CQ, et al. How do neurolo- artery occlusion: design issues and implications. Eagle gist diagnose transient ischemic attack: A systematic Study report no. 1. Graefe’s Arch Clin Exp Ophthalmol. review. Int J Stroke. 2019;14(2):115-24. Prognosis 2006;244(8):950-56. 6. Chen CS, Varma D, Lee A. Arterial occlusions to the eye: 27. Mac Grory B, Nackenoff A, Spitzer MS, et al. Intrave- Prompt recognition of the signs and from retinal emboli to ocular ischemic syndrome. Asia nous fi brinolysis for central retinal artery occlusion: A symptoms associated with acute Pac J Ophthalmol. 2020;9(4):349-57. cohort study and updated patient-level meta-analysis. retinal ischemia secondary to retinal 7. Schorr EM, Rossi KC, Stein LK, et al. Characteristics Stroke. 2020;51(7):2018-25. and outcomes of retinal artery occlusions: Nationally 28. Schrag M, Youn T, Schindler J, et al. Intravenous artery occlusion play a critical role representative data. Stroke. 2020;51(3):800-07. fi brinolytic therapy in central retinal artery occlu- in the preservation of visual func- 8. Lee KE, Tschoe C, Coffman SA, et al. Management of sion: a patient-level meta-analysis. JAMA Neurol. acute central retinal artery occlusion, a “Retinal Stroke”: 2015;72(10):1148-54. tion and prevention of stroke and An institutional series and literature review. J Stroke 29. Hakim N, Hakim J. Intra-arterial thrombolysis cardiovascular events. It is has been Cerebrovasc Dis 2021;30(2):1-9. for central retinal artery occlusion. Clin Ophthalmol. reported that 25% of patients present- 9. Mac Grory B, Schrag M, Biousse V, et al. Management 2019;13:2489-2509. of central retinal artery occlusion: A scientifi c statement ing with CRAO have had a “silent” from the American Heart Association. Stroke. 2021 March 30. Hankey GI, Slattery JM, Warlow C P. Prognosis and stroke that is visible upon MRI, with 8. Epub ahead of print. prognostic factors of retinal infarction: a prospective cohort study. BMJ. 1991;302(6775):499-504. no patient awareness or symptoms.1,2 10. Tobalem S, Schutz JS, Chronopoulos A. Central retinal artery occlusion – rethinking retinal survival time. 31. Chang YS, Jan RL, Weng SF, et al. Retinal artery The risk of an ischemic neurologic BMC Ophthalmol 2018;18(1):1-6. occlusion and the 3-year risk of stroke in Taiwan: a nationwide population-based study. Am J Ophthalmol. event occurring within months follow- 11. Lee JS, Kim JY, Jung C, et al. Iatrogenic ophthalmic 2012;154(4):645-52. ing a CRAO is 2.7 times higher when artery occlusion and retinal artery occlusion. Prog Retin compared to control subjects.9 Eye Res. 2020 March 10, 2020. Epub ahead of print. 32. Avery MB, Magal I, Kherani A, et al. Risk of stroke 12. Leavitt JA, Larson TA, Hodge DO, et al. The incidence in patients with ocular arterial occlusive disorders: Studies have documented a range of central retinal artery occlusion in Olmstead County, a retrospective Canadian study. J Am Heart Assoc. of 7.4% to 24.2% of patients having a Minnesota. Am J Ophthalmol. 2011;152(5):820-3. 2019;8(3):e010509. stroke in the fi rst four years following 13. Lawlor M, Perry R, Hunt BJ, et al. Strokes and 33. Lee J, Kim SW, Lee SC, et al. Co-occurrence of acute 30-33 vision: The management of ischemic arterial disease retinal artery occlusion and acute ischemic stroke: a CRAO. The incidence of acuter effecting the retina and the optic lobe. Surv Ophthalmol diffusion-weighted magnetic resonance imaging study. coronary syndrome in patients with 2015;60(4):296-309 Am J Ophthalmol. 2014:157(6):1231-8. CRAO 70 years of age and higher 14. Callizo J, Feltgen N, Pantenburg S, et al. Cardiovascu- 34. Chang YS, Chu CC, Weng SF, et al. The risk of lar risk factors in central retinal artery occlusion: Results acute coronary syndrome after retinal artery occlu- was 2.48 times higher versus aged of a prospective and standardized medical examination. sion: a population-based cohort study. Br J Ophthalmol matched controls.34 The lifetime of Ophthalmol 2015;122(9):1881-88. 2015;99(2):227-31.

66 REVIEW OF OPTOMETRY | JUNE 15, 2021 LIVE COPE*

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Be a retina referral rock star

ODs can—and should—take the lead on screening and monitoring routine cases, only sending to specialists the patients that truly need advanced care.

By catlin nalley ment needs a little bit of tough love, or physician strive for than better care and contributing writer perhaps they are scared and need more outcomes for their patients?” of a nurturing environment,” notes ostering viable comanagement Jessica Haynes, OD, of the Charles Building Connections relationships requires time and Retina Institute in Memphis. “Then Successful comanagement requires effort from all parties. There must on the other side, the patient walking strong relationships and open lines of Fbe a desire to collaborate as well into a specialist’s offi ce has never seen communication. This begins by build- as mutual trust and respect. As the this doctor before. They may not know ing connections with ophthalmologists primary providers of eye care, ODs are what to expect, and when certain treat- and other specialists in your area. perfectly positioned to take a leader- ments are recommended, they may be “First, we have to realize that these ship role when working with oph- distrustful of that advice,” she notes. relationships and trust have to work thalmologic subspecialists and other both ways. So, at times the ophthal- medical specialists. mologists are the ones reaching out to Effective comanagement is benefi - develop referral relationships,” says cial for a number of reasons. It gives pa- Series Mohammad Rafi eetary, OD, also of the tients easier access to care than waiting COMANAGEMENT Charles Retina Institute in Memphis. CONNECTIONS for an opening with an ophthalmologist “Often, ODs learn who to refer to by and lessens travel and cost burdens, Part 4 of 6 word of mouth from other area col- to name a few. From the standpoint of leagues, either through personal con- the surgical provider, sharing post-op The procedures of a retina practice— nections or local society meetings.” responsibilities allows them to allocate anti-VEGF injections, panretinal If ophthalmologists host seminars or more time to surgical care. For ODs, it photocoagulation and the array of social events, Dr. Rafi eetary encour- is a way to enhance your practice and complex surgeries—all require strong ages ODs to attend. This is an opportu- professional development. buy-in from the patient for things to nity to get to know doctors and staff on ODs often have strong relationships go smoothly. Having an existing con- both a personal and professional level. with their patients developed over nection with a trusted doctor can help Being proactive is key. Dr. years or even decades of care. They not immensely. Rafi eetary also recommends optom- only understand their visual demands Optometrists must use the relation- etrists take the initiative and invite and needs, but also their personalities ships they build with patients to walk specialists to events. “This is not and what approach will work best. The with them through any journey of only benefi cial to establish personal specialist, on the other hand, does not referral and treatment, Dr. Haynes relationships but create referrals for have this baseline knowledge. emphasizes. “By building good coman- services an ophthalmologist does not “They don’t know whether the agement strategies, patients will have offer in their practice,” he notes. “It patient who is noncompliant with treat- better outcomes. And what more can a always works better if both sides of the

68 REVIEW OF OPTOMETRY | JUNE 15, 2021 referral relationship know each other Optimizing Retina Care Photo: Jessica Haynes, OD on a personal level.” Unlike cataract and refractive surgery, Spending time shadowing local there is no standard or protocol for providers is another way to build con- retina comanagement; however, it is nections as well as learn more about still an important aspect of successful their practice and how they interact patient care. with patients. “This type of approach is Effective comanagement begins very likely to open up the lines of com- with the basics, notes Dr. Haynes. This munication,” notes Dr. Haynes. “You includes dilating and properly examin- may even get the doctor’s personal cell ing patients as well as a comprehensive phone number, so the next time you understanding of diagnostic imaging in have a patient who needs to be seen retina care, such as OCT, and staying emergently, you don’t have to rely on current on the latest treatment options. their receptionist getting your patient The conversations you have with in. You can go directly to the source.” your patients before they even see a Inviting specialists into the optomet- retina specialist are a crucial compo- ric community can lay the foundation nent of care and comanagement. ODs Monitoring dry AMD patients for risk for comanagement. For instance, many must feel confident in their ability factors for conversion to the wet form state and local optometry chapters to educate patients and help them (such as the large, soft drusen shown here) ask ophthalmologists to speak at their through this process. And, depending is an ideal role for optometric skills in the meetings. “A good turnout and discus- on the patient, it may take multiple continuum of retina care. sion shows ophthalmologists our bond discussions to help them truly under- as a community and builds respect,” stand their condition and the need for with that patient. The appointment says Dr. Haynes. “So, if you aren’t a referral as well as the role of their can always be adjusted if the specialist active in your state and local chapters, optometrist. asks you to see them sooner, suggests that’s another good place to start.” As with other forms of comanage- Dr. Rafieetary. It’s also important to note that true ment, the optometrist should take the Taking the lead also means clearly comanagement depends on a level of lead to ensure they maintain their posi- defining your role with the retina spe- respect that goes beyond education and tion as the patient’s primary eye care cialist. For instance, a common reason mutual referrals. “If a retina specialist is provider. “If you believe in the impor- for retina comanagement is neovascular truly respectful of the optometric level tance of continuity of care, stay in con- AMD. Today’s standard of care is intra- of care, they will support optometry trol of your patient’s care,” emphasizes vitreal anti-VEGF injections. not just in patient care but also in the Dr. Rafieetary. “Schedule a follow-up “This is a recipe for the patient political arena,” explains James Fanelli, appointment for your patient regardless being lost to an ophthalmology retina OD, of Wilmington, NC. “A retinolo- of why you are referring them.” practice,” notes Dr. Fanelli. “However, gist who opposes scope expansion by Even if the condition does not re- ODs can take this as an opportunity to optometry but is happy to receive your quire a set follow-up, scheduling anoth- maintain control and even determine referrals is not really a respectful refer- er appointment perhaps three months the injection schedule.” ral partner.” out helps you maintain your connection While you don’t know if the patient will need six monthly injections for six months or monthly injections for REFER, BUT DON’T RELINQUISH, YOUR PATIENTS the rest of their life, you can schedule • Don’t tell patients that you are referring them because you don’t have the right the patients for a series of injections, equipment, know-how or legal privileges. It undermines your position as a provider. explains Dr. Fanelli. “The OD then is seeing the patient between injections, • Never tell the patient you will see them “when the specialist is done with you.” Some of these patients will require ongoing care from a specialist. Such phrasing also takes you evaluating the effect of the injections out of the chain of decision-making. Instead, communicate that you will continue to see using their OCT, and forwarding that them whenever appropriate, even if it’s just for routine eye exams and vision correction info to the retina specialist prior to the plus a “check in” on their progress with the specialist’s regimen during such a visit. next visit. By doing this, the OD stays • Set a follow-up appointment for patients to return to your office regardless of referral. actively involved with the management This follow-up can always be changed if needed; however, you have a better safety net and acre of the AMD patient.” to make sure the patient is receiving appropriate treatment and more importantly is not Optometrists must stay current on lost to follow-up. the latest advancements in anti-VEGF • Make sure to follow through on the referral and all recommended follow-up with the therapies as well as how to manage retina specialist. and follow patients long-term. This

JUNE 15, 2021 | REVIEW OF OPTOMETRY 69 12th Annual Retina Report COMANAGEMENT

includes recognizing potential adverse me again.’ And that, I think, is the per- criteria and have the knowledge to events and any other safety concerns. fect, two-way referral relationship.” monitor and refer these patients ap- ODs need to be aware of what the propriately. injected eye should look like 24 hours Challenges and Gaps For DME, it is recommended after the injection, as well as what signs Recognizing when and when not to re- that ODs send the patient to a retina and symptoms can develop shortly fer to a retina specialist is an important, specialist; however, Dr. Chous notes, thereafter that indicate, for example, yet challenging, aspect of optometric there is a role for the optometrist, early . practice. especially among patients who require Externally, injection sites should One example is diabetic retinopathy. observation and not immediate treat- look relatively benign, save for the oc- In these cases, the OD should fi rst ment, such as non–center involved casional subconjunctival hemorrhage, determine the severity. And then, no DME or center involved DME with notes Dr. Fanelli. Immediately post matter the stage, the optometrist must normal visual acuity. To make this injection, visual acuity will be reduced, identify if diabetic macular edema determination and diagnose accurate- but that should return to pre-injection (DME) is present, notes Paul Chous, ly, Dr. Chous says an OD must have levels within 24 to 48 hours. Decreased OD, an expert in diabetes and diabetic access to an OCT. vision and increased discomfort are disease from Tacoma, WA. “Retina “I would encourage every optom- fl ags for complications. specialists don’t need to see patients etrist seeing patients with diabetes to Creating a dynamic where the with mild, nonproliferative diabetic have an OCT, but if they don’t, work- optometrist takes the lead goes back to retinopathy without any diabetic ing with a nearby optometric colleague fi nding the right ophthalmologist and macular edema,” he explains, noting who does can be very helpful and fostering a relationship of mutual trust that in those cases ODs should moni- spare patients an unnecessary visit to a and respect. “Not only must the OD tor patients for progression and counsel retina specialist’s offi ce,” he explains, have confi dence in their own skills, but on the importance of individually noting this is also an opportunity to the retina specialist must also believe optimized metabolic control, which is get another opinion on whether or not in your abilities,” Dr. Fanelli says. far more important in early rather than that patient should be referred to a “If they do, they will be comfortable later-stage diabetic retinal disease. specialist. following your lead and this also helps As the disease progresses and moves One condition that is often referred them eliminate unnecessary visits to beyond moderate severity in nonprolif- unnecessarily to ophthalmology is reti- their practice. erative cases, the likelihood of pa- nal artery occlusions. These patients, “There are retina specialists out tients developing a vision-threatening in particular those with branch retinal there who will work with you at a level complication like proliferative diabetic artery occlusions, do not need retinal where you are the one making the de- retinopathy or center-involved DME surgery, Dr. Fanelli says, noting that terminations,” he emphasizes. “They increases dramatically, according to they will need an internal medicine or will see your patient and say, ‘Dr. OD Dr. Chous. Therefore, it is critical that vascular work-up. will let you know if you need to see ODs are well-versed in the staging In these cases, the OD can and should begin the initial workup by

Photo: Carolyn Majcher, OD, Susan Ly Johnson, OD assessing the stroke risk of the patient (medical history, medications, carotid auscultation) and make the determi- nation of whether the patient needs immediate referral to a stroke center or the emergency department for carotid and cerebral imaging, explains Dr. Fanelli. If the artery occlusion appears more to be related to fi brin deposits, then cardiology involvement is necessary. This is also true for retinal vein occlusion without macular edema. Patients with retinal vein occlusions New technology is elevating the importance of early diagnosis and, with it, the profi le need evaluation of those etiolo- of optometrists equipped to do so. These O CT- A images show foveal enlargement and gies that precipitate occlusion, such perifoveal capillary remodeling in a diabetic eye without funduscopically visible diabetic as poorly controlled hypertension, retinopathy. Red arrows point to subtle areas of capillary nonperfusion while yellow circles atherosclerosis and diabetes, or in highlight microaneurysms. patients without retinal vascular evi-

70 REVIEW OF OPTOMETRY | JUNE 15, 2021 As diagnostic technology becomes REFERRAL LETTER DOs AND DON’TS increasingly more able to detect early A key component of any comanagement relationship is the referral letter. This an important retinal disease or at least risk factors line of communication with the specialist and helps lay the foundation for clinical for development, the momentum in management. retina care is inevitably shifting toward “Start with the basics. Why am I referring this patient? What am I worried about right optometry, where routine screening and now?” suggests Dr. Chous. “Try to list the specific pathology and provide as much detail as possible. ODs should also share the fundamental findings, including best-corrected vision monitoring visits are commonplace for and IOP as well as any other factors that might be responsible for a decline in vision, like many ocular conditions. Dark adapta- media opacity or history of .” tion testing, for instance, is capable of While you want to be as specific as possible, don’t provide a diagnosis if you are picking up the earliest signs of AMD, unsure. “Call it as you see it,” notes Dr. Rafieetary. “Do not make up a diagnosis. ‘Retinal which manifest at a point in the disease detachment’ is a frequently mispresented diagnosis, to justify or expedite a referral. Better to describe your findings generally than give a wrong, specific diagnosis.” course when the optometrist can The referral letter is an opportunity to clearly outline your expectations. Do you simply discuss lifestyle modifications, recom- want the retina specialist to evaluate your patient and send them back if treatment is mend AREDS vitamins and initiate a not indicated? Or is this something you want the specialist to monitor long-term? Let the monitoring regimen to give patients a specialist know if and when you have scheduled a follow-up with your patient. better shot at minimizing the disease’s “Be specific in what you are referring a patient for and provide any necessary background information that may be needed in the form of recent patient records or a short summary,” effects. Dr. Haynes advises. With ongoing education—whether Use this letter as a tool to reiterate the comanagement relationship, suggests Dr. Chous. through continuing education, confer- “Emphasize to the specialist that you want to comanage this patient and look forward to ences or mentorship—ODs can hone working together.” their skills and be more equipped to It’s also a good idea to note if specific patients are more likely to be lost-to-follow-up (LTFU) based on known risk factors like poverty, presence of other vascular comorbidities, recognize what requires a referral and and educational and cognitive status, so that both doctors can work to mitigate this, Dr. what can be handled in their own prac- Chous notes. “Studies suggest that more than 25% of patients referred to retina specialists tice. Additionally, optometrists will be are LTFU, resulting in worse outcomes, so it’s a big deal.” able to better educate patients on their condition and what to expect from a dence of the above, perhaps evaluation Here again the strength of your referral visit, suggests Dr. Haynes. of coagulability, notes Dr. Fanelli. relationship with longstanding patients “We can make a difference in the “If we’re going to market ourselves may make you uniquely well-posi- visual outcomes of these patients,” as frontline eye care providers, we tioned to discuss such things. An oph- she adds. “A patient who comes into a can’t just cherry-pick the easy cases thalmologist with no prior relationship retina clinic with a better baseline un- and manage those,” Dr. Fanelli urges. and level of trust with a new patient derstanding of their condition from the “We must create a culture of, ‘It’s OK may have a harder time of it. get-go is much more likely to be com- to treat corneal ulcers on the visual pliant and have a good final outcome.” axis, it’s OK to manage vein occlusion Learning and Development Optometrists can and should take the and so on, because I know what I’m Effective comanagement depends lead in comanagement, using their role doing and I’m comfortable with that.’” not only on the relationship between as primary eye care providers to drive Optometrists must also step up and providers, but also an optometrist’s disease management while also build- be more forthcoming about discussing understanding of retinal disease, vary- ing strong relationships with specialists prevention. “We are the primary eye ing clinical presentations, diagnostic that allow them to practice to the full care providers and it behooves all of imaging findings and available treat- extent of their scope and abilities. ■ us in optometry to talk to our patients ment options. about preventing retinal disease,” says “Just because optometrists are not Dr. Chous. “We have the chance to performing retinal surgeries, laser KEY TAKEAWAYS educate our patients on the benefits of procedures or intravitreal injections • Build strong connections with healthy lifestyle choices and encourage for these conditions doesn’t give us specialists. them to make a change.” an out to not understand the diseases • Be confident in the skills of the “From a comanaging perspective, and treatment options available to our specialists you are referring to. I inform the retina specialist that I patients,” Dr. Haynes notes. “A greater • Take the lead when determining a have advised the patient on lifestyle understanding of retinal disease is management plan. management of the retinal disease, going to allow us to make better refer- • Constantly hone your skills and including better diet, exercise, smok- rals.” Dr. Fanelli concurs. “Not only knowledge. ing cessation, compliance with sleep will it facilitate appropriate referrals, it • Communicate with patients therapy and other prudent lifestyle can eliminate the need for unnecessary throughout the referral process. changes,” he explains. referrals,” he says.

JUNE 15, 2021 | REVIEW OF OPTOMETRY 71 12th Annual Retina Report PEER REVIEWED MACULAR DYSTROPHY

Optometric Study Center

Earn 2 CE Credits (COPE APPROVED) What to Do When It’s Not AMD

Learn how to identify and diagnose the multitude of other macular dystrophies and degenerations.

What Stresses the Macula? By JESSICA HAYNES, OD As it turns out, the lifelong respon- What is a Dystrophy? memphis sibility of converting light energy This umbrella term loosely describes various progressive degenerative disor- into electrical potential to initiate ders. The term dystrophy also implies ptometrists have become the process of sight is a very stressful a monogenic or Mendelian inheritance, well versed in the presenta- job. The photoreceptors, RPE and meaning the condition results from tions of age-related macular choroid must constantly work in sync a specific variant of a single gene. Numerous degenerative conditions, such Odegeneration (AMD), given its to maintain the visual cycle, regener- as AMD, are not considered dystrophies prevalence. Once that’s been fi rmly ate photoreceptor outer segments and as they do not exhibit Mendelian inheri- entrenched in your clinical skillset, remove and phagocytize metabolic tance. to take it to the next level you’ll want waste products. Environmental factors to make sure that you’re inclusive of such as UV light exposure and tobacco important, as these vary among differ- the non-AMD macular problems that smoke put strain on this delicate bal- ent conditions. present in your practice. By doing so, ance, as do systemic conditions such as you’ll be able to isolate and differen- vascular disease. In addition, numer- Stargardt’s Disease tially diagnose these conditions to bet- ous faulty pathways can disrupt this The most commonly encountered ter counsel and manage your patients. system through various mechanisms.2,3 inherited macular dystrophy, Star- The list of AMD masqueraders is Phenotypical outcomes of various gardt’s, affects one in 8,000 to 10,000 lengthy and variable, including condi- stressors can present similarly. Differ- individuals.4 Stargardt’s disease is most tions that are degenerative, infectious, ent pathways of damage may lead to commonly inherited in an autosomal infl ammatory, toxic, vascular, trau- clinically similar presentations that are recessive fashion primarily by disease- matic, neoplastic and paraneoplastic. diffi cult to distinguish from each other. causing variants of the ABCA4 gene. Any condition that affects the retinal Diagnostic imaging such as optical This condition typically presents pigment epithelium (RPE) and outer coherence tomography (OCT), fundus between the ages of 10 and 20, with a retina may lead to drusenoid or lipo- autofl uorescence (FAF), fl uorescein resultant visual acuity around 20/200.5,6 fuscin deposition and/or pigmentary angiography (FA) and OCT angiog- Presentation later in life usually results alteration that can mimic AMD.1 In raphy (OCT-A) alongside evaluation in better visual acuity outcomes. this article, we will focus only on the of retinal function with tools such as Patients often present with classic non-AMD dystrophies and degen- electrodiagnostics may help to narrow pisiform-shaped, yellow lesions or erations that affect the macula—a down a diagnosis. Additional fac- fl eck-like lesions as well as macular list that is already quite diverse and tors such as age of onset, presenting atrophy with a “beaten ” ap- extensive. symptoms and family history are also pearance (Figure 1).6 Presentation of

About the Dr. Haynes is a consultative optometrist at the Charles Retina Institute in Germantown, TN, and a consulting faculty member at the Southern College of Optometry in author Memphis, TN. She has no fi nancial interests to disclose.

72 REVIEW OF OPTOMETRY | JUNE 15, 2021 Fig. 1. A 60-year-old white female with longstanding vision loss since her late teens and 20/150 best-corrected vision OD and OS. She presented with: (A) macular atrophy and surrounding yellow fl eck lesions, (B) a bull’s eye-type pattern, (C) infrared refl ectance OU on FAF and (D) outer retinal atrophy on OCT OU. One of her three siblings (a brother) had the same ocular condition. The others had normal vision, and there were no other affected family members, including her parents. The patient’s history was consistent with an autosomal recessively inherited condition, and she was clinically diagnosed with Stargardt’s disease. Genetic testing was offered, but she declined. pisiform lesions without evidence of ing of the external limiting membrane. The classic sign of Stargardt’s is macular atrophy was initially termed FAF may uncover early alterations and a silent or dark choroid on FA with fundus fl avimaculatus, but is now lipofuscin accumulation.8 some citing its presence in up to 80% recognized as a phenotypic variant of In later stages, OCT imaging may of patients.11 This sign is not present Stargardt’s disease.7 demonstrate drusen-like subretinal, in all cases, however, and its absence Diagnostic imaging is very useful in hyper-refl ective deposits and varying cannot rule out Stargardt’s. While the identifying and differentiating patients amounts of photoreceptor atrophy and condition is classifi ed as an autosomal with Stargardt’s. Presentation is often RPE disruption. FAF often reveals a recessive condition, reports of altered subtle at fi rst with visual symptoms reticular pattern of hyper-autofl uores- visual function and retinal appearance being more severe than clinical signs.8 cent lipofuscin deposition. Areas of have been described in carriers as well Care must be taken to identify these RPE atrophy will present as hypo- (Figure 2).12,13 Genetic testing should patients as to not misdiagnose them or autofl uorescent regions. In addition, a be considered to aid in diagnosis. perform unnecessary testing or proce- bull’s eye pattern of altered autofl uo- Electrodiagnostic testing is variable dures. OCT may show early thicken- rescence may be seen on FA F. 9,10 in patients with this condition. Pattern

Release Date: June 15, 2021 been planned and implemented by the Postgraduate Institute for Medicine and Expiration Date: June 15, 2024 Review Education Group. Postgraduate Institute for Medicine is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Estimated Time to Complete Activity: 2 hours Accreditation Council for Pharmacy Education (ACPE) and the American Nurses Jointly provided by Postgraduate Institute for Medicine Credentialing Center (ANCC) to provide continuing education for the healthcare (PIM) and Review Education Group team. Postgraduate Institute for Medicine is accredited by COPE to provide Educational Objectives: After completing this activity, the participant should be continuing education to optometrists. better able to: Reviewed by: Salus University, Elkins Park, PA • Understand the pathophysiology of macular disorders and dystrophies. Faculty/Editorial Board: Jessica Haynes, OD • Differentiate between common macular disorders and dystrophies. Credit Statement: This course is COPE approved for 2 hours of CE credit. Activ- • Use the clinical exam techniques and tools to diagnose their patients. ity #121904 and course ID 72957-PS. Check with your local state licensing board • Understand how different macular conditions progress as well as their role to see if this counts toward your CE requirement for relicensure. in monitoring and managing care. Disclosure Statements: Author: Dr. Haynes has no fi nancial interests to disclose. Target Audience: This activity is intended for optometrists engaged in eye care Managers and Editorial Staff: The PIM planners and managers have nothing to of macular disorders and dystrophies. disclose. The Review Education Group planners, managers and editorial staff Accreditation Statement: In support of improving patient care, this activity has have nothing to disclose.

JUNE 15, 2021 | REVIEW OF OPTOMETRY 73 12th Annual Retina Report MACULAR DYSTROPHY

ERG and focal or multifocal ERG Clinical appear- are typically signifi cantly diminished ance, age of onset Phenotype vs. Genotype or abolished, suggestive of macular and visual outcome The attempt to discuss this group of conditions with disease. Some patients have a normal are variable. Visual strict, discrete categorization is very difficult due to their full-fi eld ERG, while others have acuity reduction typi- convoluted and often not entirely understood inheritance 14 patterns alongside the phenotype/genotype conundrum. more widespread disease. cally presents in the Genotype describes what genes are responsible for There is currently no cure or treat- fi rst decade of life.14 a particular condition, while phenotype outlines how a ment for Stargardt’s. Patients should Patients may pres- condition presents clinically. What does it actually look like? be monitored for the rare occurrence ent with pigmentary Even among family members who share the same genotype, the phenotypical presentation of the same condition may be of choroidal neovascularization (CNV). abnormalities, a bull’s inconsistent due to variable gene expression. In addition, low vision training should eye macular appear- Conditions were originally grouped primarily based on be offered to those with reduced visual ance, macular atrophy phenotypical appearance. With more information about these conditions and the genes that cause them, the classification acuity. Confi rming a genetic variant or normal signs and and nomenclature used has evolved. However, this has left 14-17 may be useful in light of clinical trials symptoms. Those us with a bit of a mess to sift through when trying to give a and future treatment options. with cone rod dystro- name to a particular presentation. phy may later develop As genetic testing becomes more readily available and more is known about the genetic variants that cause certain Cone and Cone Rod Dystrophies peripheral bone spic- conditions, we are able to arrive at more definitive clinical This heterogenous group of disorders ules.14 Varying levels diagnoses. Access to genetic testing has significantly involves progressive, widespread at- of disc pallor are also increased in recent years, becoming more standard of care rophy of cone photoreceptors leading reported.15 in the management of inherited conditions. We must use the tools at our disposal along with patient demographics to symptoms of visual acuity loss, de- OCT is very and our current knowledge and access to genetic testing to creased color vision and photophobia. useful in identify- differentiate these conditions as best we can. In the same spectrum of disease are ing photoreceptor cone rod dystrophies that also involve atrophy, which may present as loss Genetic testing should be considered rod photoreceptors. of the photoreceptor integrity line to if available to aid in the diagnosis. Patients with clinically diagnosed more advanced loss of outer retinal There is currently no cure or treat- cone dystrophies may eventually tissue including the outer nuclear layer ment for cone or cone rod dystrophies. develop rod involvement with age and RPE.14 FAF is useful in identify- Patients should be monitored for the leading to symptoms of and ing alterations to the RPE that may rare occurrence of CNV. In addition, visual fi eld loss. These conditions are not be readily visible clinically (Figure low vision training should be consid- genetically diverse and share affected 3).14 The earliest fi nding on ERG is ered for those with impaired ability to genes with other retinal and macular delayed 30Hz fl icker implicit time perform activities associated with daily dystrophies such as retinitis pigmen- followed by reduced 30Hz amplitude living. Identifying underlying ge- tosa, considered a rod cone dystrophy, and reduced a-wave and b-wave am- netic variants may be benefi cial when and Stargardt’s. Inheritance may be plitude with full-fi eld photopic ERG. considering clinical trials and future either autosomal dominant, recessive Those with cone rod dystrophies will treatment options. or x-linked.14-16 later develop scotopic dysfunction.14 Pattern Dystrophies This is an umbrella term that includes adult-onset vitelliform dystrophy (AOVD), butterfl y-shaped pattern dystrophy (BSD), reticular dystrophy, multifocal pattern dystrophy simulat- ing Stargardt’s and fundus pulverul- entus. These conditions were initially categorized and classifi ed based on clinical appearance. Pattern dystro- phies in general were once thought to be inherited autosomal dominantly through disease-causing variants of the Fig. 2. A 39-year-old Black female with 20/20 BCVA OD and OS presented with yellow, PRPH2 gene; however, a wide variety pisciform-shaped subretinal lesions. Images: (A) infrared photography reveals a reticular of affected genes and inheritance pat- pattern of hyper-refl ectance, (B) OCT shows areas of subretinal drusen-like deposits and terns are now being recognized. RPE disruption and (C) FAF shows hyper-autofl uorescence of the pisciform lesions. Genetic In general, while pattern dystro- testing revealed she is an ABCA4 pathogenic variant carrier for Stargardt’s. phies are progressive conditions,

74 REVIEW OF OPTOMETRY | JUNE 15, 2021 Fig. 3. A 22-year-old white male presented with a homozygous pathogenic variant identifi ed in TTLL5, consistent with cone rod dystrophy. OCT images show diffuse disruption of the photoreceptor integrity line. The macula has mild pigmentary alterations while the peripheral retina has a bone spicule-type appearance. FAF shows hypo-autofl uorescence in the peripheral retina with hyper-autofl uorescence centrally indicating both central (cone) and peripheral (rod) dysfunction. patients tend to maintain good visual This leads to the consideration that in with the presence of “fl uid.”22-24 On acuity. However, vision loss can occur some individuals AOVD may be more FA F, these lesions are typically hyper- from formation of macular atrophy, for of a degenerative condition than a true autofl uorescent since they are accu- which there is no treatment, or devel- dystrophy. Diagnosis is typically made mulations of lipofuscin (Figure 4).22,23 opment of CNV, for which treatment in the sixth to eighth decade of life Electrodiagnostic testing is typically with anti-VEGF is benefi cial.18 Due to and is based on the clinical fi nding of normal in these patients.20 the development of visual symptoms bilateral, central vitelliform lesions.20 BSD. The diagnosis of BSD is later in life, these patients are more Variable amounts of additional RPE primarily clinical with a bilateral easily misdiagnosed with AMD. disruption and drusen deposition butterfl y-shaped pattern of lipofuscin AOVD. This commonly encoun- including reticular pseudodrusen have deposition and RPE disruption. OCT tered pattern dystrophy was fi rst also been described.21 imaging reveals variable amounts described as an autosomal dominant OCT is a useful diagnostic tool in of subretinal deposition and RPE condition with bilateral, symmetric, this case. Vitelliform lesions present disruption. FAF often highlights the circular subretinal lipofuscin deposits as hyper-refl ective deposits between butterfl y-shaped pattern of disease. called vitelliform lesions (Figure 4).19 the RPE and the photoreceptors. Patients are typically diagnosed in Since then, numerous publications Hypo-refl ective regions of the lesion the second to third decade of life and have described the clinical, OCT, may also be present, causing confusion usually have normal electrodiagnostic FAF and electrodiagnostic fi ndings of the disease as well as its inheritance patterns. Confusion does exist in the literature due to the wide variety of names given to this condition as well as a lack of exact criteria needed to make the diagnosis.20 Another chal- lenge is that vitelliform lesions can occur in a wide variety of outer retinal disease including AMD. While the PRPH2 gene is causative in some patients with AOVD, a variety of other genes including BEST1 have been implicated in the condition as Fig. 4. A 69-year-old white female with AOVD has bilateral, circular, yellow, central well. Most patients present without a vitelliform lesions (left). These lesions are hyper-autofl uorescent on FAF (middle) and family history, and in many, a responsi- present on OCT as refl ective subretinal deposits between the RPE and the photoreceptors ble gene variant cannot be identifi ed.20 (right). The patient presented with good visual acuity of 20/30 OD and OS.

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leading to calcifi cation of elastic fi bers Table 1. Clinical Staging Criteria of Best Disease in the eye, skin and vasculature. In I Normal fundus, abnormal EOG the retina, this can lead to calcifi ca- tion of Bruch’s membrane causing II Egg yolk lesion pigmentary abnormalities such as III Pseudohypopyon (yellow vitelliform material settles inferiorly) peau d’orange and angioid streaks. Peau d’orange presents as a peb- IV Vitelleruptive (scrambled egg appearane) bly orange appearance of the retina V Central RPE atrophy typically in the temporal macula and VI CNV mid-peripheral retina. Angioid streaks present as linear, radial pigmentary studies. The condition is still thought pattern. Patients will typically present alterations extending from the optic to be autosomal dominantly inherited with fi ndings later in life (fi fth decade) nerve.33 In addition, PXE has been as- due to variants in the PRPH2 gene.25,26 and have on average a more stable sociated with pattern dystrophy-type Reticular dystrophy. This condition disease course and better visual acuity appearances.32,34 PXE is a progressive is typically diagnosed clinically by the later in life than those with Stargardt’s. condition in which vision loss can oc- presence of bilateral, subretinal yellow In addition, they do not present with cur through tissue atrophy or develop- deposition and pigmentary alterations fi ndings of a dark choroid on FA which ment of CNV.35 Patients should be in a reticular pattern. OCT and FAF is reported in the majority of Star- monitored carefully for development are also helpful in visualizing and gardt’s patients.28,29 of CNV as it is common. distinguishing alterations to the outer Fundus pulverulentus. The least OCT can be used to image RPE retina and RPE in this disease as other commonly encountered pattern and Bruch’s membrane alterations, pattern dystrophies.27 dystrophy, fundus pulverulentus, is and is also useful in identifying Multifocal pattern dystrophy simulat- characterized by bilateral course pig- presence of CNV.33 Angioid streaks ing Stargardt’s. Considered to be inher- ment deposition in the macula. FA is may be more apparent with FAF ited autosomal dominantly by patho- helpful to show a typical pattern of imaging than with fundus evalua- genic PRPH2 variants, this condition hypo-fl uorescent spots corresponding tion, and more diffuse alteration and appears clinically and diagnostically to the areas of pigment deposition. atrophy of the RPE may be visible similar to Stargardt’s disease (Figure OCT and FAF fi ndings have been with FAF than on clinical examina- 5). It may be differentiated through rarely described.30-32 tion.33,36 OCT-A and FA are useful for family history consistent with autoso- further evaluation and identifi cation mal dominant inheritance; however, Pseudoxanthoma Elasticum of CNV.37 incomplete penetrance and variable PXE is caused by autosomal recessive Angioid streaks present during the expression may mask the inheritance inheritance of mutations on ABCC6, lifetime of almost all patients with PXE, but they are not exclusive to PXE.38 They are also seen in pa- tients with Ehlers-Danlos syndrome, Paget’s disease and sickle cell disease, and they may be idiopathic.

Bestrophinopathies This is a term used to describe a phenotypically heterogenous group of disorders caused by variants of the BEST1 gene. Most gene mutations lead to the phenotype consistent with Best disease, which we will focus on in this article. Fig. 5. A 54-year-old white male presented with BCVA 20/70 OD and 20/50 OS. He Best disease. An autosomal dominant complained of gradually worsening vision over the last two to three years. He had no dystrophy, this condition can present family history of blindness. Fundus exam revealed bilateral yellow, fl eck-type lesions scatted in the posterior pole and macular atrophy. FAF showed diffuse alteration of as early as the fi rst decade of life. A the autofl uorescent signal. OCT showed hyper-refl ective outer retinal deposits OU, generally accepted staging criteria photoreceptor atrophy OS and more extensive macular atrophy OD. The appearance is for Best disease is shown in Table 1. similar to Stargardt’s disease, but genetic testing identifi ed a heterozygous pathogenic Lesions in Best disease are typically variant in PRPH2 more consistent with multifocal pattern dystrophy mimicking Stargardt’s. bilateral and fairly symmetric. While

76 REVIEW OF OPTOMETRY | JUNE 15, 2021 (OCT, FA F, intravenous FA, etc.) Table 2. Grading Criteria for North Carolina Macular Dystrophy revealed that many in this young pa- Grade Fundus Findings tient demographic have a phenotype of drusen called cuticular drusen. The 1 Central yellow drusen deposits term cuticular drusen was fi rst used 2 Confluent drusen, possible pigmentary changes by Donald Gass in 1977 to describe drusen that appeared as numerous 3 Well-defined chorioretinal atrophy small hyper-fl uorescent lesions on VA, lesions tend to be solitary, reports of tinese (ML) are names both used appearing like a “starry sky.” This multiple lesions per eye do exist. This to describe a phenotype of radially phenotype is currently being con- has been termed “multifocal Best oriented macular drusen seen in rela- sidered as a specifi c clinical subtype disease.”39 Patients often present with tively young individuals who may be of AMD.46 Cuticular drusen seem to good visual acuity despite the striking in their 20s. These individuals often have a strong genetic component. fundus appearance. As the condition have peripapillary drusen as well. Multiple genes are currently associ- progresses, patients can develop loss The phenotype was fi rst described ated with the condition.18 of central acuity, metamorphopsias by Walter Doyne in 1899 in Oxford, OCT imaging can be used to visu- and central . Symptoms typi- England, who coined the name alize the drusen deposition and is also cally begin in the vitteleruptive stage DHRD.41 In 1932, a similar condition useful for the detection of CNV. Cu- with more severe loss occurring with was described in several individuals ticular drusen often have a saw tooth- progressive RPE atrophy or develop- in the Leventine Valley of Switzer- type appearance on OCT (Figure 6). ment of CNV. Sudden vision loss can land, then called ML.42 It is now FAF fi ndings are variable, but FAF is occur with development of CNV.15 generally accepted that these two useful to get a sense of the distribu- OCT is useful to image vitelliform names represent the same condition, tion and amount of RPE disruption lesions, which appear similarly to caused by autosomal inheritance of and to identify regions of RPE atro- those in AOVD. On FA F, the lesions a defect in the EFEMP1 gene that phy.46 OCT-A and FA may be useful are typically hyper-autofl uorescent codes for a protein called fi bulin 3, an for identifying CNV. Electrophysiol- due to the presence of lipofuscin. extracellular matrix protein.43 Other ogy testing in those confi rmed with RPE atrophy may appear as hypo- names used to describe the pheno- EFEMP1 macular disease has been autofl uorescent. OCT-A and FA are type are dominant drusen and familial reported as normal.47 useful in identifying the development drusen. However, evidence suggests Despite the signifi cant amount of of CNV.40 ERG is normal, but EOG is that many patients with a phenotype drusen seen on clinical examination, abnormal.15 of dominant drusen do not have the patients tend to present with good EFEMP1 gene mutation consistent visual acuity. These conditions are Macular Drusen with DHRD and ML.44,45 progressive, however, with the pos- Doyne honeycomb retinal dystro- More recently, evaluation of drusen sibility of visual decline from macular phy (DHRD) and Mallatia Leven- subtypes with multimodal imaging atrophy or development of CNV.46

Fig. 6. A 42-year-old Black male presented with a phenotypic appearance of autosomal dominant drusen. He had no family history and presented asymptomatically with 20/20 vision OD and OS. Images: (A) widefi eld photo, (B) FAF, (C) infrared refl ectance and (D) OCT.

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to more advanced stages of CACD. Table 3. Clinical Staging of Central Areolar Choroidal Dystrophy Alterations may be subtle at fi rst, Grade Fundus Findings but more advanced stages will show signifi cant RPE and photoreceptor I Slight parafoveal RPE changes atrophy on OCT and FA F. 54,55 II Pigment mottling encircling the fovea III Choriocapillaris atrophy without central involvement Myopic Macular Degeneration MMD describes the atrophic changes IV Central choriocapillaris and RPE atrophy that occur in highly myopic eyes, at- tributed to axial elongation. There is North Carolina Macular Dystrophy trally. This progresses to atrophy of the increased risk of MMD with higher re- This autosomal dominant condition choriocapillaris, RPE and photorecep- fractive error, longer axial length, pres- has highly variable expressivity. A tors with vision loss beginning in the ence of posterior staphyloma involving grading system has been created for fourth and fi fth decades of life.52 The the macula and older age (Figure 7). the condition, but rather than acting condition presents as well defi ned, Findings in MMD include lacquer as a staging criteria of disease pro- circular areas of macular atrophy. cracks (LCs), pigmentary alterations, gression, this is more of a staging of CACD progression has been staged in macular atrophy and development of the phenotypic presentation as the Table 3.15 CNV.56 condition is usually non-progressive Color vision is often abnormal, LCs are breaks in the RPE, Bruch’s (Table 2). The condition tends to be and later stages lead to visual acuity membrane and choriocapillaris bilateral and symmetric. Vision loss is loss and central scotomas. Full-fi eld complex. These are typically seen in grade-dependent, but patients often ERG tends to be normal, aside from younger patients because as patients have surprisingly good visual acuity reduction in some advanced cases.15 age, LCs often coalesce to form larger on fundus presentation. The median Multifocal ERG has recently been areas of macular atrophy.57 Patients acuity is reported to be 20/50. Patients reported to show dysfunction in with LCs can develop spontaneous, of all grades must be monitored for broader regions than appear clinically not CNV-related, subretinal hemor- development of CNV.15,48 diseased.53 Pattern VEP and pattern rhage due to choriocapillaris ruptures. Grade 3 lesions may appear exca- ERG are reported to be the earli- This is a sign of likely LC expansion.58 vated, and the terms staphyloma and est electrophysiological indicators of In addition, MMD patients are at high coloboma have been used to describe disease in patients with normal fundus risk for CNV development, and any them. Researchers describe this exca- appearance.53 presence of subretinal hemorrhage vation as a deep chorioretinal excava- OCT and FAF are very useful in must be thoroughly investigated to tion and have suggested the name detecting RPE disruptions from early rule out the presence of CNV on “macular caldera” to describe these lesions.48 Dispute over the appropriate nomenclature for this excavation still exists.49-51 OCT and FAF can demonstrate the level of RPE and photorecep- tor disruption. In addition, the deep chorioretinal excavation can be well visualized with OCT imaging. OCT-A and FA may be useful for identifying CNV. EOG and ERG are typically normal.15,48

Central Areolar Choroidal Dystrophy Fig. 7. Patients with MT2 may present with the following fi ndings: (A) pigmentary CACD is a rare autosomal dominant plaques (red arrow), (B) juxtafoveal whitening concentrated temporally, crystalline deposits and right angle vessels (black arrow), (C) variable retinal and photoreceptor condition. A variant in PRPH2 is one atrophy and classic appearance of internal limiting membrane drape on OCT, (D) altered known cause of CACD, but this is not autofl uorescent patterns typically showing fi rst as hyper-autofl uorescence temporally the only gene identifi ed in the condi- (blue arrow), (E) juxtafoveal telangiectatic vessels concentrated temporally on intravenous tion. Patients present in the second FA that leak in late stages and (F) telangiectatic vessels concentrated temporally in both decade of life with subtle bilateral, the superfi cial (G) and deep (H) vascular plexus on OCT-A. These images are all examples symmetrical pigment mottling cen- of different patients.

78 REVIEW OF OPTOMETRY | JUNE 15, 2021 Fig. 8. Various presentations of myopic degeneration. The top images show myopic CNV (red arrows) on fundus photo, OCT and in the avascular complex of the OCT-A. Bottom left shows a patient with posterior staphyloma and myopic macular atrophy. The bottom right shows progressive lacquer crack formation. In 2016, the patient had subretinal hemorrhage not associated with CNV.

OCT, OCT-A and FA as needed.59 frequently reported initial symptom.63 juxtafoveal telangiectatic vessels most Macular atrophy can also develop Patients with MT2 may present with concentrated temporally. These vessels without the presence of LCs. Regions subtle retinal fi ndings, making misdi- leak in the later stages, but the condi- of atrophy expand at variable rates agnosis easy (Figure 8). Initially, there tion is not considered to be an exuda- with an increased risk of vision loss is a mild, juxtafoveal retinal whitening tive disease in the absence of CNV. with age.56 While there is no treatment most concentrated temporally. Later This irregular vasculature can also be for macular atrophy, early detection of fi ndings such as refl ective deposits, detected on OCT-A, showing evidence CNV and treatment with anti-VEGF pigmentary plaques and right-angle of telangiectatic vascular alterations can lead to better visual outcomes.60 vessels may also be visible.61 The most concentrated temporally in both condition is bilateral, affecting the tem- the superfi cial and deep capillary Macular Telangiectasia Type 2 poral juxtafoveal region to the greatest plexus. OCT, FA and OCT-A are also Patients with MT2 have abnormal extent, but fi ndings can be asymmetric. helpful in identifying the presence of parafoveal retinal capillaries most The cause of vision loss in these CNV.61 concentrated temporally. While these patients stems from retinal and photo- There is no treatment to slow the capillary abnormalities have given rise receptor atrophy that typically affects progression of MT2. Treatment of to the condition’s name, at its core the temporal juxtafoveal region. This CNV with anti-VEGF has shown to be MT2 is best described as a neurovas- can create scotomas in the presence of favorable.64 cular macular degenerative condition. good central visual acuity, hence the The pathophysiology is unclear, but diffi culty with reading. Progression of Conclusions it has been said that the cause may be the disease can lead to macular atrophy When the macula encounters stress, from dysfunction in Muller cells that and decreased visual acuity. In addition, either from extraneous sources or are vital for the maintenance of retinal patients may develop CNV.61 underlying defects in the system, the health.61 While a genetic component OCT shows variable levels of retinal phenotypic results may not be unique is suspected, MT2 is not considered a and photoreceptor atrophy. The pres- to a particular condition. Findings macular dystrophy.61 ence of internal limiting membrane such as drusen, lipofuscin deposition, Patients with MT2 tend to present drape on OCT is classic for MT2. FAF pigmentary alterations, macular atrophy with good visual acuity. The MacTel shows hyper-autofl uorescence tempo- and CNV are seen in a wide variety of study group showed that 42% of all pa- rally early in the disease with increased conditions. tients had best corrected vision of 20/25 disruptions in the autofl uorescent signal Careful clinical examination along or better.62 Symptoms tend to occur as the disease progresses. Pigmentary with imaging strategies such as OCT, in the sixth or seventh decade of life plaques appear as hypo-autofl uores- FA F, OCT-A and FA help to guide us with impaired reading being the most cent. Early-phase FA shows irregular to a particular condition. Additional

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16. Hamel CP. Cone rod dystrophies. Orphanet J Rare Dis. 40. Ferrara DC, Costa RA, Tsang S, et al. Multimodal fundus information such as electrodiagnostic 2007;2(1):7. imaging in Best vitelliform macular dystrophy. Graefes Arch Clin Exp Ophthalmol. 2010;248(10):1377-86. studies, age of onset and family history 17. Kominami A, Ueno S, Kominami T, et al. Case of cone also help to narrow the possibilities. dystrophy with normal fundus appearance associated with bi- 41. Doyne RW. Peculiar condition of choroiditis occurring in allelic POC1B variants. Ophthalmic Genet. 2018;39(2):255-62. several members of the same family. Trans Ophthalmol Soc UK. 1899;19:71. While we are extremely limited 18. Duvvari MR, van de Ven JPH, Geerlings MJ, et al. Whole in our treatment options for macular exome sequencing in patients with the cuticular drusen 42. Klainguti R. Die tapetoretinal degeneration im kanton tes- dystrophies and degenerations, arriving subtype of age-related macular degeneration. PLoS One. sin. Klin Monatsbl Augenheilkd. 1932;89:253-4. 2016;11(3):e0152047. 43. Stone EM, Lotery AJ, Munier FL, et al. A single EFEMP1 at an accurate diagnosis allows us to 19. Gass JD. A clinicopathologic study of a peculiar foveo- mutation associated with both Malattia Leventinese educate patients and their family mem- macular dystrophy. Trans Am Ophthalmol Soc. 1974;72:139- and Doyne honeycomb retinal dystrophy. Nat Genet. 56. 1999;22(2):199-202. bers about their visual prognoses. It can 20. Chowers I, Tiosano L, Audo I, et al. Adult-onset foveo- 44. Tarttelin EE, Gregory-Evans CY, Bird AC, et al. Molecular also help guide decisions on the value macular vitelliform dystrophy: a fresh perspective. Prog Retin genetic heterogeneity in autosomal dominant drusen. J Med Genet. 2001;38(6):381-4. of genetic testing. Eye Res. 2015;47:64-85. 21. Wilde C, Lakshmanan A, Patel M, et al. Prevalence of 45. Sauer CG, White K, Kellner U, et al. EFEMP1 is not associ- All patients with macular degenera- reticular pseudodrusen in newly presenting adult onset foveo- ated with sporadic early onset drusen. Ophthalmic Genet. tions or dystrophies are at increased macular vitelliform dystrophy. Eye (Lond). 2016;30(6):817-24. 2001;22(1):27-34. 22. Grob S, Yonekawa Y, Eliott D. Multimodal imaging of 46. Balaratnasingam C, Cherepanoff S, Dolz-Marco R, risk of developing CNV and should adult-onset foveomacular vitelliform dystrophy. Saudi J et al. Cuticular drusen: clinical phenotypes and natural be monitored for this occurrence. In Ophthalmol. 2014;28(2):104-10. history defi ned using multimodal imaging. Ophthalmology. 2018;125(1):100-18. general, treatment with intravitreal 23. Bastos RR, Ferreira CS, Brandão E, et al. Multimodal image analysis in acquired vitelliform lesions and adult- 47. Haimovici R, Wroblewski J, Piguet B, et al. Symptomatic anti-VEGF is favorable in those who onset foveomacular vitelliform dystrophy. 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Retina. 2018;38(7):e55-8. imaging. Invest Ophthalmol Vis Sci. 2011;52(12):8908-18. mology. 2019;126(12):1712-21. 32. Ebran JM, Martin L, Leftheriotis, et al. Subretinal fi brosis 56. Ruiz-Medrano J, Montero JA, Flores-Moreno I, et al. 7. Haji Abdollahi S, Hirose T. Stargardt-fundus fl avimaculatus: is associated with fundus pulverulentus in pseudoxan- Myopic : current status and proposal for a new recent advancements and treatment. Semin Ophthalmol. thoma elasticum. Graefes Arch Clin Exp Ophthalmol. classifi cation and grading system (ATN). Prog Retin Eye Res. 2013;28(5-6):372-6. 2018;256(4):699-707. 2019;69:80-115. 8. Bax NM, Lambertus S, Cremers FPM, et al. The absence of 33. Gliem M, De Zaeytijd J, Finger RP, et al. An update on the 57. Ohno-Matsui K, Tokoro T. The progression of lacquer fundus abnormalities in Stargardt disease. Graefes Arch Clin ocular phenotype in patients with pseudoxanthoma elasti- cracks in pathologic myopia. Retina. 1996;16(1):29-37. Exp Ophthalmol. 2019;257(6):1147-57. cum. Front Genet. 2013;4:14. 58. Ohno-Matsui K, Ito M, Tokoro T. Subretinal bleeding with- 9. Arrigo A, Grazioli A, Romano F, et al. Multimodal evaluation 34. Agarwal A, Patel P, Adkins T, et al. Spectrum of pattern out choroidal neovascularization in pathologic myopia. A sign of central and peripheral alterations in Stargardt disease: a dystrophy in pseudoxanthoma elasticum. Arch Ophthalmol. of new lacquer crack formation. Retina. 1996;16(3):196-202. pilot study. Br J Ophthalmol. 2020;104(9):1234-8. 2005;123(7):923-8. 59. Mi L, Zuo C, Zhang X, et al. Fluorescein leakage within 10. Chen Y, Roorda A, Duncan JL. Advances in imaging of 35. Finger RP, Issa CP, Ladewig M, et al. Intravitreal bevaci- recent subretinal hemorrhage in pathologic myopia: sugges- Stargardt disease. Adv Exp Med Biol. 2010;664:333-40. zumab for choroidal neovascularisation associated with pseu- tive of CNV? J Ophthalmol. 2018;2018:4707832. 11. Fishman GA, Farber M, Patel BS, et al. Visual acuity loss in doxanthoma elasticum. Br J Ophthalmol. 2008;92(4):483-7. 60. Cheung CMG, Arnold JJ, Holz FG, et al. Myopic choroidal patents with Stargardt’s macular dystrophy. Ophthalmology. 36. Shiraki K, Kohno T, Moriwaki M, et al. Fundus autofl uo- neovascularization. Ophthalmology. 2017;124(11):1690-1711. 1987;94(7):809-14. rescence in patients with pseudoxanthoma elasticum. Int 61. Issa PC, Gillies MC, Chew EY, et al. Macular telangiectasia 12. Kjellström U. Reduced macular function in ABCA4 carri- Ophthalmol. 2001;24(5):243-8. type 2. Prog Retin Eye Res. 2013;34:49-77. ers. Mol Vis. 2015;21:767-82. 37. Birtel J, Lindner M, Mishra DK, et al. Retinal imaging 62. Clemons TE, Gillies MC, Chew EY, et al. Baseline charac- 13. Duncker T, Stein GE, Lee W, et al. Quantitative fundus auto- including optical coherence tomography angiography for teristics of participants in the natural history study of macular fl uorescence and optical coherence tomography in ABCA4 detecting active choroidal neovascularization in pseudoxan- telangiectasia (MacTel) MacTel Project Report No. 2. Ophthal- carriers. Invest Ophthalmol Vis Sci. 2015;56(12):7274-85. thoma elasticum. Clin Exp Ophthalmol. 2019;47(2):240-9. mic Epidemiology. 2010:17(1):66-73. 14. Hoyt C, Taylor D. Pediatric Ophthalmology and Strabis- 38. Orssaud C, Roche O, Dufi er JL, et al. in 63. Heeren TFC, Holz FG, Issa PC. First symptoms and mus. 4th ed., Saunders/Elsevier, 2012. pseudoxanthoma elasticum: a survey of 40 patients. Ophthal- their age of onset in macular telangiectasia type 2. Retina. mic Genet. 2015;36(4):327-32. 15. Gill JS, Georgiou M, Kalitzeos A, et al. Progressive cone 2014;34(5):916-9. and cone-rod dystrophies: clinical features, molecular 39. Boon CJF, Klevering BJ, Leroy BP, et al. The spectrum of 64. Khodabande A, Roohipoor R, Zamani J, et al. Management genetics and prospects for therapy. Br J Ophthalmol. ocular phenotypes caused by mutations in the BEST1 gene. of idiopathic macular telangiectasia type 2. Ophthalmol Ther. 2019;103(5):711-20. Prog Retin Eye Res. 2009;28(3):187-205. 2019;8(2):155-75.

80 REVIEW OF OPTOMETRY | JUNE 15, 2021 OPTOMETRIC STUDY CENTER QUIZ

o obtain continuing education credit through the Optometric Study Center, com plete the test form on the following page and return it with the $35 fee to: Jobson Healthcare Information, LLC, Attn.: CE Processing, 395 Hudson Street, 3rd Floor New York, New York 10014. To be eligible, Tplease return the card within three years of publication. You can also access the test form and submit your answers and payment via credit card online at revieweducationgroup.com. You must achieve a score of 70 or higher to receive credit. Allow four weeks for processing. For each Optomet- ric Study Center course you pass, you earn 2 hours of credit. Please check with your state licensing board to see if this approval counts toward your CE requirement for relicensure.

1. What is reported as the most common 9. Which of the following is not typically 16. Which is not a risk factor for MMD? inherited macular dystrophy? seen in patients with PXE? a. Higher myopic refractive error. a. Best disease. a. Angioid streaks. b. Longer axial length. b. Stargardt’s disease. b. Peau d’orange. c. Presence of posterior staphyloma in the c. Reticular dystrophy. c. Pattern dystrophy-type appearance. macula. d. MT2. d. Macular caldera. d. Younger patient age.

2. What is the typical age of onset in 10. What gene is most often responsible 17. What is the most frequently reported Stargardt’s disease? for conditions considered to be visual symptom of MT2? a. Before 10 years old. bestrophinopathies? a. Photophobia. b. 10 to 20 years old. a. ABCA4. b. Nyctalopia. c. 20 to 40 years old. b. ABCC6. c. Impaired vision while reading. d. 40 to 50 years old. c. BEST1. d. Loss of peripheral vision. d. EFEMP1. 3. What is the earliest reported ERG 18. What is a classic OCT finding of MT? abnormality in cone dystrophies? 11. When does Best disease typically a. Internal limiting membrane drape. a. Reduced full-field scotopic ERG. present? b. Subretinal drusenoid deposits. b. Reduced full-field photopic ERG. a. Childhood. c. Thickening of the external limiting c. Delayed 30Hz flicker implicit time. b. Early adulthood. membrane. d. Reduced 30Hz amplitude. c. Mid-life. d. Vitelliform lesions. d. In the elderly. 4. Which of the following is not considered 19. Which of the following conditions would a pattern dystrophy? 12. DHRD and ML are caused by autosomal be most suitable to recommend genetic a. Best disease. dominant inheritance of which gene? testing for? b. AOVD. a. ABCA4. a. MT2. c. BSD. b. ABCC6. b. Stargardt’s disease. d. Fundus pulverulentus. c. BEST1. c. AOVD. d. EFEMP1. d. MMD. 5. What is the typical age of diagnosis of AOVD? 13. Patients with autosomal dominant 20. What is generally true regarding the a. 20 to 40 years old. drusen have increased risk of vision loss management of non-AMD macular b. 40 to 50 years old. from which of the following? dystrophies and degenerations? c. 50 to 70 years old. a. Optic nerve atrophy. a. Patients should be supplemented with d. 70 to 80 years old. b. Macular atrophy or CNV. AREDS 2 vitamins. c. Cataracts. b. Treatment options are limited, but 6. How do vitelliform lesions present on d. Retinal detachment. anti-VEGF should be recommended for FAF? CNV development, and those with vision a. Hyper-autofluorescent. 14. How would you describe the grading impairements should be referred to a low b. Hypo-autofluorescent. system of North Carolina macular vision specialist. c. Hyper-reflective. dystrophy? c. Multiple FDA-approved gene therapies d. Hypo-reflective. a. Staging system for the progression of the are now on the market for macular disease. dystrophies and degenerations. 7. Which of the following is not typical of b. Staging system of the phenotypic d. There is no way to improve the outcomes multifocal pattern dystrophy simulating presentation as it tends to be non- for patients with macular dystrophies and Stargardt’s disease? progressive. degenerations, so monitoring and referring a. Early vision loss around 20 years old. c. Staging system based on ERG findings. to specialist providers is not necessary. b. Autosomal dominant inheritance. d. Staging system based on the age of onset c. A more stable disease course with better of the disease. visual acuity than Stargardt’s disease. d. Absence of silent choroid on FA. 15. Which of the following accurately describes electrodiagnostic findings in 8. What is the inheritance pattern of PXE? CACD? a. Autosomal dominant. a. Full-field ERG is always reduced. b. Autosomal recessive. b. Multifocal ERG shows reduction only in c. X-linked. areas of visible disease. d. The inheritance pattern is unknown. c. Pattern VEP and pattern ERG are reported to be the earliest electrophysiological indicators of disease. d. The EOG is abnormal.

JUNE 15, 2021 | REVIEW OF OPTOMETRY 81 12th Annual Retina Report MACULAR DYSTROPHY

Examination Answer Sheet Mail to: Jobson Healthcare Information, LLC, Attn.: CE Processing, 395 Hudson Street, 3rd Floor New York, New York 10014 What To Do When It’s Not AMD Payment: Remit $35 with this exam. Make check payable to Jobson Healthcare Valid for credit through June 15, 2024 Information, LLC. Online: This exam can be taken online at revieweducationgroup.com. Upon passing Credit: This course is COPE approved for 2 hours of CE credit. Course ID is 72957-PS. the exam, you can view your results immediately and download a real-time CE certificate. You can also view your test history at any time from the website. Processing: There is a four-week processing time for this exam. Directions: Select one answer for each question in the exam and completely darken Jointly provided by Postgraduate Institute for Medicine and Review Education Group. the appropriate circle. A minimum score of 70% is required to earn credit. Salus University has sponsored the review and approval of this activity.

Answers to CE exam: Post-activity evaluation questions: 1. A B C D Rate how well the activity supported your achievement of these learning objectives. 1=Poor, 2=Fair, 3=Neutral, 4=Good, 5=Excellent 2. A B C D 21. Understand the pathophysiology of macular disorders and dystrophies. 1 2 3 4 5 3. A B C D 4. A B C D 22. Differentiate between common macular disorders and dystrophies. 1 2 3 4 5 A B C D 5. 23. Use the clinical exam techniques and tools to diagnose their patients. 1 2 3 4 5 6. A B C D 24. Understand how different macular conditions progress as well as their role in monitoring and managing care. 1 2 3 4 5 7. A C D 8. A B C D 25. Based upon your participation in this activity, do you intend to change your practice behavior? (Choose only one of the following options.) 9. A B C D A I do plan to implement changes in my practice based on the information presented. A B C D 10. B My current practice has been reinforced by the information presented. 11. A B C D C I need more information before I will change my practice. 12. A B C D 13. A B C D 26. Thinking about how your participation in this activity will influence your patient care, how many of your patients are likely to benefit? 14. A B C D (please use a number): 15. A B C D 27. If you plan to change your practice behavior, what type of changes do you plan to implement? (Check all that apply.) 16. A B C D 28. How confident are you that you will be able to make your intended changes? 17. A B C D 18. A B C D A Apply latest guidelines D Change in current practice for referral G More active monitoring and counseling 19. A B C D B Change in diagnostic methods E Change in vision correction offerings H Other, please specify: ______C Choice of management approach F Change in differential diagnosis 20. A B C D ______

A Very confident B Somewhat confident C Unsure D Not confident 29. Which of the following do you anticipate will be the primary barrier to implementing these changes? 30. Additional comments on this course: ______A Formulary restrictions D Insurance/financial issues G Patient adherence/compliance B Time constraints E Lack of interprofessional team support H Other, please specify: C System constraints F Treatment related adverse events ______

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82 REVIEW OF OPTOMETRY | JUNE 15, 2021 LIVE COPE*

WINTER Optometric Glaucoma Symposium DECEMBER 1011, 2021

INTERACTIVE VIRTUAL CONFERENCE PROGRAM CO†CHAIRS The Winter Optometric Glaucoma Symposium, Murray Fingeret, OD, FAAO brought to you by Review Education Group and Chief of the Optometry Section MedscapeLIVE!, comes to you virtually in 2021! Brooklyn/St. Albans Campus This Optometric Glacuoma Symposium is a Department of Veterans Administration long-running and trusted program for optometrists New York Harbor Health Care System managing patients with glaucoma. Clinical Professor SUNY, College of Optometry REGISTRATION Super early rate: $149 Robert N. Weinreb, MD Rate increases December 3, 2021: $199 Chair and Distinguished Professor of Ophthalmology Director, Shiley Eye Institute Director, Hamilton Glaucoma Center Morris Gleich, M.D. Chair in Glaucoma Board Certifi cation in Ophthalmology

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but it doesn’t seem to occur in those treated with netarsudil who have a Through Thick and Thin healthy endothelium.5 Therefore, both Drug improves endothelial function but also yields corneal edema. substantial CEC disease and netarsudil are necessary ingredients for the devel- opment of honeycomb edema. If either The effect of Rhopressa (netar- of these conditions change—the edema Q sudil, Aerie) on endothelial function clears or the medication is discontin- is exciting, yet some patients have shown ued—the honeycomb appearance will significant epithelial edema. What is the dissipate.2,5,6 exact mechanism of this drop? A “The use of Rhopressa in the Takeaways management of pathology of Honeycomb edema in a patient treated with The anterior localization of the prob- corneal endothelial cells (CECs) is Rhopressa who underwent a failed DSAEK. lem, influence of ROCK inhibitors on a therapy in its infancy, but also one cellular permeability of epithelial cells of the most exciting and active areas population, Dr. Bronner believes that and requirement of pre-existing edema of publication in cornea literature,” honeycomb epithelial edema counter- for the development of honeycomb according to Aaron Bronner, OD, of intuitively does not cause an increase edema make it very likely that this Pacific Cataract and Laser Institute in in corneal edema or have a negative adverse effect reflects a change in the Kennewick, WA. Most of this research influence on CECs. Instead, he thinks fluid balance in how epithelial cells re- has been retrospective and case-based, it’s probably associated with a change spond to edema, rather than an impact but as of March, the first randomized in the distribution of edema within cor- on endothelial cells or a worsening of clinical trial studied the use of Rho- neas altered by ROCK inhibition. He edema, Dr. Bronner notes. pressa in Fuchs’ dystrophy patients and notes that these eyes have not shown a Of course, this is all speculative. reported an improvement in corneal consistent worsening of edema as mea- Time and research will shed light on thickness and visual acuity over three sured by pachymetry.2 In fact, the eyes the full picture, but for now, Dr. Bron- months.1 he has seen with honeycomb edema ner says he feels comfortable placing A medical approach to endothelial have surprisingly exhibited thinning. his patients with corneal edema on decompensation would be a revolution- So, what is going on? Rhopressa as an off-label way to at- ary treatment, says Dr. Bronner, but When establishing a cause of hon- tempt to improve corneal edema. In notes the importance of having realistic eycomb edema, pinpoint where the the event that honeycomb edema de- expectations and recognizing potential problem is localized, who will develop velops, he gives the medication up to a complications, the most common of it and the conditions that will help month longer. If it continues to persist, which is honeycomb epithelial edema. it clear. Although ROCK inhibitors simply discontinuing the medication are gaining attention for their role in should result in its resolution with less The Nitty-Gritty endothelial healing, the endothelium of a risk for long-lasting harm. g

Honeycomb epithelial edema is isn’t the only cellular layer within the 1. Price MO and Price FW. Randomized, double-masked, pilot concerning both in that it is extremely cornea that they impact. They also play study of netarsudil 0.02% ophthalmic solution for treatment of corneal edema in Fuchs dystrophy. Am J Ophthalmol. common in patients with corneal endo- a role in epithelial healing, cellular and 2021;227:100-5. thelial disease treated with netarsudil intracellular junctions and maintenance 2. LoBue SA, Moustafa GA, Vu A, et al. Transient reticular cystic corneal epithelial edema with topical netarsudil: a case series and that its presence seemingly flies in of membrane permeability of epithelial and review. Cornea. December 22, 2020. [Epub ahead of print]. the face of the proposed benefit of the cells.3,4 3. Moshifar M, Parker L, Birdsong OC, et al. Use of rho kinase inhibitors in ophthalmology: a review of the literature. Med therapy, says Dr. Bronner, as these two The at-risk patient profile is very Hypothesis Discov Innov Ophthalmol. 2018;7(3):101-11. outcomes are distinctly at odds. specific. According to one review, 4. Yin J, Yu FSX. Rho kinases regulate corneal epithelial wound healing. Am J Physiol Cell Physiol. 2008;295(2):C378-87. The field is still in the early stages honeycomb epithelial edema is nearly 5. Wisely CE, Liu KC, Gupta D, et al. Reticular bullous epithelial of research into this question, but universal in patients treated with netar- edema in treated with netarsudil: a case series. Am J Ophthalmol. 2020;217:20-6. based on available data and augmented sudil who also have corneal edema or at 6. Davies E. Case series: novel utilization of rho-kinase inhibitor by his own use of netarsudil in this least a significant risk factor for edema, for the treatment of corneal edema. Cornea. 2021;40(1):116-20.

Dr. Shovlin, a senior optometrist at Northeastern Eye Institute in Scranton, PA, is a fellow and past president of the American Academy of Optometry and a About Dr. Shovlin clinical editor of Review of Optometry and Review of Cornea & Contact Lenses. He consults for Kala, Aerie, AbbVie, Novartis, Hubble and Bausch + Lomb and is on the medical advisory panel for Lentechs.

84 REVIEW OF OPTOMETRY | JUNE 15, 2021 LIVE COPE*

New Technologies & Treatments in Eye Care JUNE 1112, 2021

OVERVIEW New Technologies & Treatments in Eye Care, brought to you by Review Education Group and MedscapeLIVE, comes to you virtually in 2021! NT&T’s long-running and trusted program for optometrists serves to keep you up-to-date with the latest diagnosis, treatment and management in the areas of dry eye, glaucoma, and retinal disease.

CHAIR PLANNING PANEL Paul M. Karpecki, OD, FAAO Aaron Bronner, OD, FAAO Director of Cornea Danica Marrelli, OD, FAAO Kentucky Eye Institute Walter Whitley, OD, FAAO

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*Approval pending Review Education Group partners with Salus University for those ODs who are licensed in states that require university credit. Partially supported by unrestricted educational grants from Aerie, Alcon, Kala Pharmaceuticals, Oyster Point, and Sun Pharmaceuticals. by JAMES L. FANELLI, oD Glaucoma Grand Rounds

prednisone. She reported an allergy to indomethacin. Don’t Feed the Hand Slit lamp examination of her anterior segments was remarkable for bilateral LASIK flaps, with a clear interface that Bites You and no striae or epithelial ingrowth Manage your glaucoma patients to the best of your ability bilaterally. She had undergone LASIK approximately 15 years earlier. before initiating a referral that may ultimately do more harm Pachymetry readings were 522µm OD than good. and 557µm OS. Applanation tensions at 11:06am were 12mm Hg OD and 10mm Hg OS. There were scattered econd-guessing another doctor’s guttatae, and the patient was pseudo- clinical care should not be taken phakic bilaterally. She’d had cataract lightly, but if you do, be judi- surgery about seven years earlier. Scious in your approach. Here are In the right eye, there was a tube in several takeaways from when I found the anterior chamber extending to the myself in this position. visual axis on one end, and to about 2mm behind the limbus and beneath Case the conjunctiva at the other. There I was examining a 55-year-old Cau- was no valve present, nor was the tube casian female a couple of weeks ago. cut from a valve that had failed. Close During the evaluation, she mentioned examination of the conjunctiva distal her mother and how hard of a time she to the tube demonstrated no ex- was having with her glaucoma. Alarm planted valve or disrupted conjunctiva. bells went off in my head while she There was no bleb. was giving me her version of events. This MIGS device is designed to facilitate The patient was dilated in the We should always take a secondhand drainage of aqueous from the anterior usual fashion. Through dilated , impression of events with a grain of chamber into the subconjunctival space. her intraocular lenses were clear and salt, but there were several items men- centered in their capsular bags. The tioned that were, unfortunately, all too Post-op, the patient was told the posterior capsules were clear and intact familiar. One thing led to another and procedure had failed, there was some OU. Bilateral posterior vitreous de- I agreed to see the patient’s mother for bleeding and there was nothing more tachments were present. Posterior pole a second opinion. that could be done. After her third imaging demonstrated bilateral tilted She was an 81-year-old woman who follow-up, she sought my care. discs with peripapillary atrophy and presented anxiously about her “failed At her first visit with me at the end myopic stretching. The left disc was glaucoma surgery” in her left eye. She of April, entering visual acuities were tilted much more than the right, and had been treated for approximately 10 20/25 OD and 20/200 OS. Best-correct- consequently, both cup-to-disc appear- years for bilateral glaucoma, which she ed acuities were 20/25+ OD and 20/80 ances were vertically elongated due to reported was now well controlled with OS. Pupils were round, equal and the oblique nasal insertion of the optic daily Rhopressa (netarsudil, Aerie). without an afferent pupillary defect, nerves OS>OD. After moving to the area, she noted and were full in all There was concurrent glaucomatous a decline in vision in the left eye and positions of gaze. Current medications damage present OU. But my initial sought the care of a local OD who im- included Xelpros (latanoprost, Sun impression was that, although damage mediately referred her to a glaucoma Pharma) QHS OU, Cosopt (dorzol- from glaucoma was evident, neither surgeon. The surgeon changed her amide/timolol, Akorn) TID OU and nerve was at the threshold of complete glaucoma medications and scheduled prednisolone acetate QD OS, along neuroretinal rim loss. Prior to her her for surgery the following week. with oral diazepam, trazodone and LASIK surgery, the patient said she

About Dr. Fanelli is in private practice in North Carolina and is the founder and director of the Cape Fear Eye Institute in Wilmington, NC. He is chairman of the EyeSki Optometric Conference and Dr. Fanelli the CE in Italy/Europe Conference. He is an adjunct faculty member of PCO, Western U and UAB School of Optometry. He is on advisory boards for Heidelberg Engineering and Glaukos.

86 REVIEW OF OPTOMETRY | JUNE 15, 2021 eral retinal evaluations were The device implanted was a Xen remarkable for 360° cystoid and Gel Stent (Allergan), which is a flex- scattered areas of pavingstone ible stent inserted perpendicular to degeneration. I obtained optic and through the angle and extends nerve images and anterior seg- into the subconjunctival space. It ment OCTs of the tube/shunt. works to reduce intraocular pressure by facilitating aqueous movement Discussion out of the anterior chamber and into Examining this patient raised a the subconjunctival space, similar to few questions and brought home a trabeculectomy. The problem is, several points. First, the patient the stent was not properly placed in sought care due to decreased this patient, who may not have even vision OS. Was her vision needed it in the first place. decreased because of progres- sive field loss secondary to the Takeaways The patient’s left eye demonstrated an oblique glaucoma? Or, was it decreased It’s important to avoid throwing an- insertion of the optic nerve, along with macular due to progression of the macular other provider under the bus; instead, changes and thinning of the neuroretinal rim. changes in the left eye? The only give them the benefit of the doubt. way to determine the answer However, when a provider actively was a -9.00 OU myope. This would prior to glaucoma surgery would have works against optometry in scope certainly account for her myopic optic been through completing a visual field expansion issues, citing our inability to nerve characteristics. study and assessing previous records, properly manage glaucoma, and leaves The right macula was characterized neither of which was done. a trail of excessive and unnecessary by fine retinal pigment epithelial mot- Second, we must be careful about surgeries in multiple patients over tling; that of the left was characterized abruptly changing the meds of a new years, you begin to realize that involv- by more advanced retinal pigment epi- patient who had been managed by ing this provider in your patients’ care thelial disruption as well as scattered another provider for years before- is not in their best interest. drusen. Given the symmetric pre- hand. Obtaining prior records helps We as ODs can and should facilitate LASIK refractive error and the lack tremendously in determining what, if better glaucoma care by becoming of myopic stretching in the right eye, anything, needs to be done differently. more active in patient management, as it is possible that some of the macular Our patient may not have required a opposed to immediately referring to a changes in her left eye were related medication change. At the very least, glaucoma surgeon. Lean on the ODs to myopic stretching. When asked if the efficacy of the change should have in your area who manage glaucoma for she was told about the changes in her been evaluated prior to surgery. It is help, if needed, as most glaucoma pa- maculae, OS>OD, she looked sur- certainly possible that her glaucoma tients do not require surgery. Becom- prised and said no. was completely stable and her vision ing more involved in patient care can The retinal vascular examination changes were related to her macular reduce unnecessary referrals that may was essentially unremarkable, except issues instead. But in any event, the ultimately end up doing more harm for expected mild arteriolar changes glaucoma surgeon didn’t think twice than good, as well as improve overall associated with her age. Her periph- about proceeding with surgery. outcomes. g

The stent was improperly placed. Here, it runs through the cornea, anterior to the anterior chamber angle.

JUNE 15, 2021 | REVIEW OF OPTOMETRY 87 By Joseph W. Sowka, OD Therapeutic Review

ripheral ulcerative keratitis is possible.9 Glaucoma can occur from inflammation Not a BRITE Idea or angle closure secondary to choroidal effusion.10 Beware this severe complication from a rare cosmetic procedure. Necrotizing is a particularly severe form where the sclera thins to 59-year-old man presented ur- the point that the underlying dark gently with a red, painful, photo- of the choroid is visible.11 The most phobic left eye of approximately destructive form of necrotizing scleritis A10 days duration. His uncorrected is scleromalacia perforans, presenting visual acuity was 20/40 OD and finger insidiously without substantial pain or counting OS with no pinhole improve- visible inflammatory signs with uveal ment. His left eye manifested profound herniation through a perforated scleral deep injection throughout his bulbar wall.12 conjunctiva. Additionally, there was a Scleritis can be associated with both mixed papillary and follicular response infectious and non-infectious causes. of the palpebral conjunctiva. There was While the etiology remains idiopathic a grade 3 cell and flare reaction of the for many cases of scleritis, most are left eye with stromal corneal edema Anterior scleritis in a patient post-surgery. associated with a causative systemic and endothelial keratic precipitates. disease. The most common related His crystalline lens manifested an adjacent head and facial regions. Pho- disorders are rheumatoid arthritis, age-appropriate nuclear sclerosis in the tophobia and lacrimation are common. polyarteritis nodosa, systemic lupus right eye but a dense nuclear cataract in Depending on the involvement of the erythematosus, inflammatory bowel the left. His intraocular pressures (IOP) cornea and severity of inflammation, disease, sarcoidosis, granulomatosis were 18mm Hg OD and 34mm Hg vision can be reduced. While scleritis with polyangiitis, tuberculosis, herpes OS. There was also temporal conjunc- may be local and idiopathic, most cases zoster and syphilis.13 Assume that there tival and scleral thinning OS and a are secondary to systemic disease as is an underlying systemic disease until calcific scleral plaque. His right eye was arthritis, medication side effects or as a proven otherwise. Patients should normal. Cataract and posterior complication of ocular surgery.5-7 undergo a comprehensive medical prevented any views of the left fundus. Although the pathogenesis of scleritis evaluation. A rheumatologist is the best Based upon signs and symptoms, he is not entirely understood, evidence comanagement source. was diagnosed with anterior scleritis points to a deposition of immune OS. He was prescribed topical diflu- complexes within the sclera, leading Treatment prednate 0.05% QID, atropine 1% to a vasculitis with associated inflam- Topical therapy alone is typically insuf- BID, Combigan (brimonidine/timolol, matory cell infiltration and edema.8 ficient to manage most cases of scleritis Allergan) BID and oral ibuprofen There typically will be dilation of the and should be considered adjunctive 800mg QID PO. His medical history scleral vessels as well as the overlying to ameliorate initial acute symptoms. was significant only for diabetes, with vasculature of the episclera and bulbar Initial topical therapy involves potent no suggestion of autoimmune or rheu- conjunctiva.1-4 The affected eye may with atropine 1% BID and matologic diseases. He was referred assume a deep red, almost hemorrhagic topical steroids such as prednisolone for medical evaluation with a rheuma- appearance.4-6 The presentation may be acetate 1% Q2h to QID or diflupred- tologist to find a potential underlying sectorial but is usually diffuse, differen- nate TID-QID. cause. tiating it from the more common and Systemic treatment begins with benign . Scleritis is bilateral oral nonsteroidal anti-inflammatory Painful Reaction in many cases but is often asymmet- drugs (NSAIDs) for mild to moder- Scleritis is an inflammation of the ric. Corneal involvement in the form ate, non-necrotizing anterior scleritis.1 sclera.1-4 Patients often report ocular of infiltrative stromal keratitis, non- Therapy may include ibuprofen 600mg pain that may radiate to involve the inflammatory corneal thinning or pe- to 800mg QID or naproxyn sodium

About Dr. Sowka is an attending optometric physician at Center for Sight in Sarasota, FL, where he focuses on glaucoma management and neuro-ophthalmic disease. He is a Dr. Sowka consultant and advisory board member for Carl Zeiss Meditec and Bausch Health.

88 REVIEW OF OPTOMETRY | JUNE 15, 2021 250mg to 500mg TID. If insufficient, traction ultimately were able to restore oral prednisone 60mg to 80mg PO QD ocular health and visual function after can be given for two to three days and several months. He was informed that then slowly tapered to 10mg to 20mg a similar situation could still develop in daily. Immunosuppressive agents such his fellow eye as the I-BRITE proce- as cyclophosphamide, cyclosporine or dure was done bilaterally. methotrexate are sometimes neces- Be aware of cosmetic surgical con- sary in the most severe or recalcitrant junctival whitening procedures that can cases.14,15 have an unacceptably high attendant Based upon lack of insurance, the complication rate and risk of serious patient was resistant to rheumatologic vision-threatening outcomes, even consultation or any systemic medi- years after the procedure. ■ cal testing. During the course of his Scleral thinning in a patient with scleritis. 1. Rachitskaya A, Mandelcorn ED, Albini TA. An update on therapy and follow-up, he casually the cause and treatment of scleritis. Curr Opin Ophthalmol. mentioned that he had undergone underlying systemic autoimmunity or 2010;21(6):463-7. 2. Moreland LW, Curtis JR. Systemic nonarticular manifestations a cosmetic conjunctival whitening infectious etiology found. The authors of rheumatoid arthritis: focus on inflammatory mechanisms. procedure called “I-BRITE” approxi- noted that, because of the large area of Semin Arthritis Rheum. 2009;39(2):132-43. mately five years prior in another state. the ocular surface that is treated in eye 3. Galor A, Thorne JE. Scleritis and peripheral ulcerative keratitis. Rheum Dis Clin North Am. 2007;33(4):835-54. Initially, this elicited no recollection, whitening with MMC, the necrotizing 4. Kirkwood BJ, Kirkwood RA. Episcleritis and scleritis. Insight. but later investigation of this procedure scleritis that can ensue may be more 2010;35(4):5-8. proved very informative and ultimately extensive and severe than the surgically 5. Ahn SJ, Oh JY, Kim MK, et al. Clinical features, predisposing factors, and treatment outcomes of scleritis in the Korean popula- the likely cause. induced necrotizing scleritis following tion. Korean J Ophthalmol. 2010;24(6):331-5. 18 other periocular surgeries. 6. Zlatanović G, Veselinović D, Cekić S, et al. Ocular manifestation Dangers of Whitening One study reported on a patient who of rheumatoid arthritis-different forms and frequency. Bosn J Basic Med Sci. 2010;10(4):323-7. Eye whitening procedures were developed bilateral necrotizing scleritis 7. Smith JR, Mackensen F, Rosenbaum JT. Therapy insight: introduced around 2008 and have been within the nasal region of both eyes. scleritis and its relationship to systemic autoimmune disease.Nat offered as a treatment of chronic con- The patient also developed calcified Clin Pract Rheumatol. 2007;3(4):219-26. 8. Fong L P, Sainz de la Maza M, Rice BA, et al. Immunopathology junctival hyperemia. Patients variably plaques within the areas of scleroma- of scleritis. Ophthalmology 1991; 98(4):472-9 undergo conjunctivectomy with topical lacia, along with an epithelial corneal 9. Sainz de la Maza M, Foster CS, Jabbur NS, Baltatzis S. Ocular characteristics and disease associations in scleritis-associated mitomycin C (MMC) 0.02% applica- defect four years after undergoing peripheral keratopathy. Arch Ophthalmol 2002; 120(1):15-9. tion to achieve a whitened appearance I-BRITE. It found a delayed develop- 10. Ikeda N, Ikeda T, Nomura C, Mimura O. Ciliochoroidal effusion from bleaching of the avascular sclera. ment of complications.19 syndrome associated with posterior scleritis. Jpn J Ophthalmol. 2007;51(1):49-52. In some procedures, MMC is com- In an attempt to raise awareness of 11. Moreno Honrado M, del Campo Z, Buil JA. A case of necrotiz- bined with antiangiogenic bevacizumab the complications for surgical conjunc- ing scleritis resulting from Pseudomonas aeruginosa. Cornea. during the procedure. tival eye whitening procedures, one 2009;28(9):1065-6. 12. Wu CC, Yu HC, Yen JH, et al. Rare extra-articular manifestation The literature has noted compli- study reviewed the medical records of rheumatoid arthritis: scleromalacia perforans. Kaohsiung J cations of cosmetic eye whitening, of patients who received cosmetic Med Sci. 2005;21(5):233-5. including chronic conjunctival epithe- conjunctivectomy plus postsurgical 13. Pavesio CE, Meier FM. Systemic disorders associated with episcleritis and scleritis. Curr Opin Ophthalmol 2001; 12(6):471-8. lial defects, scleral thinning, avascular topical MMC treatment to eliminate 14. Kaplan-Messas A, Barkana Y, Avni I, Neumann R. Methotrexate zones in the sclera, conjunctival injection in a single facil- as a first-line corticosteroid-sparing therapy in a cohort of uveitis and diplopia requiring ity. They found that of the 48 patients and scleritis. Ocul Immunol Inflamm 2003;11(2):131-9. 16 15. Hillenkamp J, Kersten A, Althaus C, Sundmacher R. Cyclo- surgery. One review of 1,713 pa- undergoing the procedure, 44 had sporin A therapy in severe anterior scleritis. 5 severe courses tients undergoing cosmetic whitening complications related to the procedure. without verification of associated systemic disease treated with cyclosporin A. Ophthalmologe 2000; 97(12):863-9. procedures noted an overall complica- These complications included fibro- 17. Tran AQ, Hoeppner C, Venkateswaran N, et al. Complications tion rate of 83%, of which 55.6% cases vascular conjunctival adhesion at the of cosmetic eye whitening Cutis. 2017 Sep;100(3):E24-E26. were considered severe. These severe muscle insertion site, chronic dysfunc- 16. Lee S, Go J, Rhiu S, Stulting RD, et al. Cosmetic regional conjunctivectomy with postoperative mitomycin C applica- complications included fibrovascular tional tear syndrome, abnormal vessel tion with or without bevacizumab injection. Am J Ophthalmol. conjunctival tissue proliferation, scleral growth, lymphangiectasis, adhesions of 2013;156(3):616-22. 18. Ji YW, Park SY, Jung JW, et al. Necrotizing scleritis after thinning with calcified plaques, IOP Tenon’s capsule and the conjunctiva at cosmetic conjunctivectomy with mitomycin C. Am J Ophthalmol. elevation, diplopia and recurrence of the extraocular muscle insertion site, 2018;194:72-81. hyperemic conjunctiva.17 extraocular muscle fiber exposure and 19. Moshirfar M, McCaughey MV, Fenzl CR, et al. Delayed mani- 20 festation of bilateral scleral thinning after I-BRITE procedure and Another study found that the average diplopia. review of literature for cosmetic eye-whitening procedures. Clin time from the procedure to diagnosis For this patient, topical and oral anti- Ophthalmol. 2015;9:445-51. 20. Rhiu S, Shim J, Kim EK, Chung SK, Lee JS, Lee JB, Seo KY. was 51 months, and all patients had inflammatory therapy, physical removal Complications of cosmetic wide conjunctivectomy combined with unilateral findings. There was no of the calcific plaque and cataract ex- postsurgical mitomycin C application. Cornea. 2012;31(3):245-52.

JUNE 15, 2021 | REVIEW OF OPTOMETRY 89 By Paul M. Karpecki, OD Chief Clinical Editor OCULAR SURFACE REVIEW

2. Assess Risk Factors Next, look at the risk factors. The list Five Easy Pieces includes use of various medications like oral antihistamines and topi- Follow these steps to increase your dry eye diagnostic accuracy. cal glaucoma medications, as well as history of contact lens wear, previous t seems impossible that an algorithm 1. Ask Triaging Questions ocular surgery and autoimmune condi- for dry eye disease (DED) diagnosis The first action in identifying DED is tions such as thyroid disease, diabetes, can have almost 600 scientific refer- to ask a series of triaging questions. My arthritis, smoking and others. Iences and yet still be so simple every favorite ones came from the Optomet- clinician can implement it, but that’s ric Dry Eye Summit, which took place 3. Inquire about Symptoms what the TFOS DEWS II Diagnostic in Denver in 2014, although the TFOS Essential to a dry eye diagnosis is how Methodology Subcommittee came DEWS II report, released in 2017, has the patient feels. Any of the following up with—and it works! Having been far more examples. Somewhat para- could indicate DED: dryness, grit- fortunate to serve on this committee, I phrased, these questions are: tiness, burning or stinging, tearing, can tell you firsthand it’s a practical ap- • How do your eyes feel? (i.e., are foreign body sensation, itching, contact proach that streamlines your efforts and they dry, gritty, light sensitive, burning lens intolerance, fluctuating or blurred increases diagnostic accuracy. or stinging?) vision, hyperemia, photophobia and The first thing you have to recognize • How do your eyes look? (i.e., are pain/discomfort.2 is that DED requires both a sign and they red or look irritated?) Although eye dryness is likely the a symptom to make the diagnosis. For • Do you experience fluctuating best single indicator—after all, it’s right example, an extreme sign like punctate vision? there in the name of the condition—a epithelial keratitis without symptoms • Do you use, or have the urge to few others that stand out are fluctu- isn’t dry eye—it’s likely neurotrophic use, artificial tears or rewetting drops? ating vision, tearing () and keratitis. Let’s look at the five key steps • How much time do you spend on hyperemia. In fact, if you are refract- in this diagnostic methodology. digital devices? ing a patient and the image clears and then blurs with each blink, consider DED. Tearing is difficult for patients to assess, as they can’t understand how “dry” eye could cause excess tears. What typically occurs is meibomian gland dysfunction (MGD) and the body’s response to it is reflex tearing, so an explanation of mechanisms to the patient is warranted. The last indicator is hyperemia, which is often noted by patients and indicates inflammation, also strongly associated with DED. An easier way to assess symptoms is having the patient take a validated questionnaire before examination. The TFOS DEWS II Diagnostic Meth- odology Committee recommends the DEQ-5, and other options include the SPEED or OSDI questionnaires. The benefit of this step is that it provides a score that can be monitored for The TFOS DEWS II dry eye diagnostic algorithm at a glance. changes over time.

Dr. Karpecki is medical director for Keplr Vision and the Dry Eye Institutes of Kentucky and Indiana. He is the Chief Clinical Editor for Review of Optometry and About Dr. Karpecki chair of the New Technologies & Treatments conferences. A fixture in optometric clinical education, he consults for a wide array of ophthalmic clients, including ones discussed in this article. Dr. Karpecki’s full disclosure list can be found in the online version of this article at www.reviewofoptometry.com.

90 REVIEW OF OPTOMETRY | JUNE 15, 2021 ADVERTISER INDEX

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JUNE 15, 2021 | REVIEW OF OPTOMETRY 91 edited by Mark Dunbar, OD reTINA QUIZ

Take the Retina Quiz 1. Which element of the patient’s history Dredging Up the Past could have caused this retinal finding? Evident scarring and a telltale history point to the diagnosis. a. Type 2 diabetes. b. Stroke of the left hemisphere. c. Car accident injury to the right side By Mark t. dunbar, od, and Stéphane fitoussi, OD Upon exam, best-corrected visual of his body. miami acuity was 20/200 OD and 20/20 OS. d. Onset of floaters two years prior. Confrontation visual fields were full- 59-year-old African-American to-careful finger counting OU. Pupils 2. What does the orange lesion adjacent to male presented with blurry were equal, round and reactive, but the fibortic area represent? vision and a central spot in there was an afferent pupillary defect a. A retinal detachment. Ahis right eye for the past four in the right eye. The anterior segment b. A subretinal hemorrhage. years. He reported seeing floaters that exam was unremarkable except for c. A drusenoid PED. began two years prior; his past ocular mild cataracts OU, and there were no d. A PED secondary to choroidal history was also significant for a motor cells or flare in either eye. neovascularization (CNV). vehicle accident that occurred four On dilated fundus exam of the right years earlier. In the accident, he was eye, a posterior vitreous detachment 3. What is the correct diagnosis for this hit on the right side of his body and was present. There was a large fibrotic fundus presentation? reported having sudden vision loss in scar with areas of pigment surround- a. Chorioretinal scar from toxoplas- the right eye. ing in the macula (Figure 1). Upon mosis. His medical history was signifi- careful examination, a suspicious or- b. CHRPE. cant for a stroke involving the left ange area was noted temporal to that c. Choroidal rupture with secondary hemisphere, also four years prior, as lesion (see yellow arrow in Figure 1). An CNV. well as Type 2 diabetes, which was OCT was performed and is available d. Proliferative diabetic retinopathy. diagnosed nine years ago and is being for review (see red arrow in Figure 2). treated with metformin and insulin The retinal exam of the left eye was 4. Which of the following is not a injections. completely normal. treatment option for this condition? a. Observation. b. Injection of anti-VEGF agent. c. Azithromycin PO. d. Combination of A and B.

5. Which imaging technique would be helpful in order to get a definitive diag- nosis? a. B-scan ultrasound. b. Fluorescein angiography/ OCT angiography. c. Electroretinogram. d. All of the above. For answers, see page 98.

Discussion There is an obvious chorioretinal scar involving the macula of right eye in our patient. In the absence of history, Fig. 1. Fundus photo of the right eye. What might that central fibrotic lesion represent? there are a lot of possible etiologies,

About Dr. Dunbar is the director of optometric services and optometry residency supervisor at the Bascom Palmer Eye Institute at the University of Miami. He is a founding Dr. Dunbar member of the Optometric Glaucoma Society and the Optometric Retina Society. Dr. Dunbar is a consultant for Carl Zeiss Meditec, Allergan, Regeneron and Genentech.

92 REVIEW OF OPTOMETRY | JUNE 15, 2021 including an old toxoplas- to treat acute episodes. mosis scar which might be Patients are often pro- the immediate conclusion vided with an Amsler given the location and grid as a way to self- characteristic appearance. monitor for any changes However, the history of- in vision, as they carry fers a critical clue to the the risk of developing actual etiology. Our patient CNV in the future. In describes having an motor cases where it develops, vehicle accident four years intraocular injections of prior that resulted in a anti-VEGF can improve sudden loss of his central visual outcomes. vision. So, how does the clinical presentation fit Concluding Thoughts into our patient having a No doubt the vision loss traumatic event? that our patient suf- Ocular trauma can fered is from his motor present in myriad ways vehicle accident. The depending on the type large chorioretinal scar and location of the injury. involving the macula is Blunt force trauma can Fig. 2. OCT of the right eye. What could the area of RPE elevation due to a large choroidal cause a contrecoup injury possibly correspond to? rupture. Unfortunately, in which direct displace- the rupture involves his ment and deformation of the globe elasticum, Ehlers-Danlos syndrome, macula, which explains the sudden can occur. In commotio retina, the Paget’s disease, sickle cell anemia loss of vision. hydraulic forces on the eye as a result or virtually any condition involving Regrettably, that’s not the end of it. of the injury can cause disruption and angioid streaks may predispose a The OCT and clinical finding tempo- swelling of the photoreceptors, which patient to choroidal ruptures during ral to the macula are quite revealing. can even lead to death of these cells.1 an impact of even minimal intensity, The orange area that was noted with The shock waves from the trauma as these represent breaks in Bruch’s the arrow is elevated and confirmed coursing through the eye can result in membrane as well. on the OCT scan where we can see hemorrhagic or non-hemorrhagic pos- In the acute phase, these breaks an RPE detachment. There is also terior vitreous detachments, retinal are commonly associated with sub- intra- and subretinal fluid adjacent to breaks and even retinal detachment, retinal and sub-RPE hemorrhages the RPE detachment, all consistent as well as traumatic and may also be associated with other with an active CNV. and choroidal rupture, to name a few. traumatic findings. In the chronic Our patient was referred to a retina A choroidal rupture happens when phase, CNV may develop and can be specialist for possible treatment; ul- there is disruption of the choriocap- found at the edges of the rupture.2 timately, the MD decided to monitor illaris, Bruch’s membrane and the CNV may occur months to years after him without treatment because of his retinal pigment epithelium (RPE) the traumatic event and can result in poor visual prognosis. ■ from the direct result of the trauma or fibrotic scarring.3 1. Wood CM, Richardson, J. Indirect choroidal ruptures: ae- indirectly from the shock waves that The prognosis for choroidal rupture tiological factors, patterns of ocular damage, and final visual are transferred through the vitreous is highly dependent on location and outcome. Br J Ophthalmol. 1990;74(4): 208-11. and/or eye walls of the globe as a whether it involves the foveal area, 2. Bailey Freund K, Sarraf D, Mieler WF, et al. Choroidal rupture. result of the trauma. When this oc- and also if subretinal or sub-RPE the retinal atlas, 2nd Edition. 2017; 1011. 3. Fineman MS, Ho AC. Choroidal rupture. Color Atlas & Syn- curs, stretching and folding of these hemorrhages are present. Patients opsis of Clinical Ophthalmology, 2nd Edition. 2012; 316. structures leads to a break in Bruch’s with choroidal rupture should be fol- membrane and the RPE. lowed carefully for potential second- ABOUT THE AUTHOR Choroidal ruptures are typically ary CNV post-trauma, which may located in the posterior pole and most further decrease visual acuity.3 Dr. Fitoussi is an optometrist at 2 the Bascom Palmer Eye Institute at often concentric to the optic disc. The treatment of choroidal rupture the University of Miami. He earned Sports injuries and car accidents in- often involves observation and close his bachelor’s of science degree in volving the deployment of airbags are follow-up to monitor for spontaneous optometry at Bar-ilan University in Tel Aviv in 2014 and his doctorate common causes, although systemic improvement of vision, as there is no of optometry at Nova Southeastern University in conditions such as pseudoxanthoma medical or surgical therapy indicated 2020.

JUNE 15, 2021 | REVIEW OF OPTOMETRY 93 Edited by Derek N. Cunningham, OD, and Walter O. Whitley, OD, MBA Surgical Minute

Candidates for Interventional IOP Control: Glaucoma Procedures Cataract Patients: • POAG patient on two drops with blurry vision Time to Play Offense? • IOP has increased the past three months due to noncompliance with regimen Interventional glaucoma allows optometrists to minimize the • Candidate for cataract surgery treatment burden for our patients. Pseudophakic Patients: • Pseudophakic POAG patient on two drops By mackenzie macintyre, od and a more aggressive posture toward • Underwent SLT two years ago sparks, NV achieving IOP targets and disease • Visual fields reflect evidence of progression control, relying on the numerous less • Needs an additional drop e are all too familiar with the invasive surgical options. We have constraints of the classic glau- become accustomed to thinking that pseudophakic patients as an alternative coma treatment progression of minimally invasive glaucoma surger- to filtering surgery. wdrops-laser-surgery. Whether ies (MIGS) should occur at the time of • Trabectome (Microsurgical Technol- it is the cost of medications, compliance cataract surgery; however, some experts ogy). This device creates a partial tra- with administration of drugs or the need are of the opinion that at least a few of beculotomy, cauterizing and aspirating to tailor treatment to the stage of glau- these procedures could be considered the nasal trabecular meshwork tissue coma, we routinely take a customized as standalone treatment options as well roughly 90 to 180 degrees. approach to this condition already. But in appropriately selected patients. • Kahook Dual Blade (New World there is an emerging, potentially disrup- Photo: New World Medical Medical). Similar to the Trabectome tive treatment philosophy to consider: procedure, this method also removes interventional glaucoma. It expands our tissue from the trabecular meshwork; arsenal of treatment options to further however, it uses a dual-blade scalpel reduce the burden on our patients, al- rather than cautery. lowing us to take earlier, more aggres- • Ab interno canaloplasty (iTrack, sive steps to treat glaucoma before it Ellex). Viscodilation of Schlemm’s canal becomes uncontrollable. is the method here, with the added In 2019, the interventional glaucoma advantage of breaking adhesions in the philosophy received a major boost when trabecular meshwork and irrigation of the LiGHT trial outlined the benefits The Kahook Dual Blade excises a strip of the collector channels. of selective laser trabeculoplasty (SLT) trabecular meshwork to aid aqueous outflow. We know that better IOP control in over topical meds as an initial treatment earlier stages of glaucoma decreases the for glaucoma. This shift allows us to A few approaches are especially well- risk of vision loss. Therefore, it is our re- identify suboptimally controlled pa- suited to consideration when adopting sponsibility to reach out to our ophthal- tients who are being treated with topical an interventional glaucoma mindset: mological colleagues and recommend glaucoma medications and recommend • Durysta. In 2020, Allergan received less invasive, cost-saving and likely reducing those agents in favor of early FDA approval for this agent—a bio- more efficient and effective treatment S LT, yielding improved ocular comfort degradable, intracameral bimatoprost options for our patients. ■ and quality of vision, while also main- implant that can be administered either taining good glaucoma control. at the slit lamp or in the operating room ABOUT THE AUTHOR

The interventional glaucoma philoso- during the time of cataract surgery. Dr. Macintyre is an optometrist at phy encourages a proactive approach • Omni. This MIGS technique, from Eye Care Associates of Nevada. Sight Sciences, combines a canalo- He specializes in cataract surgery For a video of the procedure, read this article comanagement and perioperative plasty with a trabeculotomy and can be care of cataract patients. He has no online at www.reviewofoptometry.com. performed with cataract surgery or in financial interests to disclose.

About Drs. Dr. Cunningham is the director of optometry at Dell Laser Consultants in Austin, TX. He has no financial interests to disclose. Dr. Whitley is the Cunningham and Whitley director of professional relations and residency program supervisor at Virginia Eye Consultants in Norfolk, VA. He is a consultant for Alcon.

94 REVIEW OF OPTOMETRY | JUNE 15, 2021 ONLINE FIRST: GET THE LATEST PRODUCT NEWS AT product review www.reviewofoptometry.com New items on the market to improve clinical care and strengthen your practice.

 diagnostics literature explains. Its 20-megapixel sensor reduces motion Genetic Test Assesses Risk of artifacts and captures images large enough to allow for Now that collagen crosslinking has proved its mettle in closer examination of fine details, according to Coburn. slowing keratoconus progression, doctors need to identify The company says the range of imaging modes makes candidates right away so that the option can be considered the device versatile enough to document glaucoma (in- early. Those looking for help may wish to offer kerato- cluding fine detail of the RNFL using the cobalt filter), conus suspects a genetic test macular edema, epiretinal membranes, diabetic retinopa- that will assess their risk. Ava- thy, pigmentary abnormalities and much more. Gen, by Avellino, examines 75 The DICOM-compatible HFC-1 also features a built- keratoconus-related genes, more in PC with web browsing capabilities and an LCD touch than 2,000 gene variants and data screen to enable image analysis and sharing from the same on ethnic predispositions to the disease to come up with a device, the company points out. keratoconus genetic risk score, a company press release ex- plains. These results will allow you to offer more custom-  ized care to your patients based on their individual odds of contact lenses developing keratoconus, the company suggests. New Ortho-K Option from J&J on the Way The test can also measure susceptibility to a variety of The recent announcement that Johnson & Johnson corneal dystrophies (e.g., epithelial basement membrane, Vision’s first product for myopia management is an ortho-K granular, lattice, Reis-Bucklers, Schnyder, Theill-Behnke), lens brings renewed attention—and the only on-label allowing for more conclusive diagnoses and more effec- indication—to this longstanding modality. The company tive treatment plans, Avellino says. The test results may says its Acuvue Abiliti Overnight contact lenses have been also influence your decisions about a patient’s viability for shown to reduce axial elongation refractive surgery given that some options are contrain- in myopic children by 0.28mm on dicated in patients with certain corneal dystrophies, the average over a two-year period. company notes. The lens will be available in An in-office cheek swab yields a sample that the practice spherical and toric options. Practitioners will use custom sends to Avellino’s lab for analysis; the company says re- software that draws on corneal topography, refractive error sults should arrive in a few days. To ensure that the doctor and other data to create a lens fit that temporarily reshapes and patient both understand the results, the company also the cornea during overnight wear, a press release explains. provides genetic counseling, the press release explains. Details of the lens design are not yet available, but studies cited in the press release reference clinical trials Big Screen Camera Handles Small Pupil Patients conducted using the Menicon Z Night ortho-K lens. The A new retinal camera introduced by Coburn Technologies company previously announced a collaboration with Meni- may be just what your practice needs to take your imaging con and says this new lens is part of that effort. capabilities to the next level. The HFC-1 non-mydriatic J&J also promised “additional products and services to fundus camera uses automated pupil detection and eye address the progression of myopia” down the road. tracking to simplify image capture while producing sharp Acuvue Abiliti Overnight will be available by the end of and reliable retinal photos, the company says. Fixation the year, according to the company. targets can also be set manually for greater flexibility in recording the desired images. More Options for Astigmats The camera is able to quickly If you like fitting the Biofinity XR toric from CooperVision shift between its five imaging but sometimes find a lens power isn’t available, take heart: modes—color, blue, red, red-free the company says it has nearly doubled the prescription and cobalt—while adapting to options. The lens can now be ordered in sphere powers varying pupil sizes, saving you from -20.00D to +20.00D, a press release explains. the time of making manual ad- Cylinder powers vary based on sphere, but options begin justments during an exam. The at -0.75D and go up to -5.75D for some lenses. Axis device works even with pupils options are available in 5° increments, the press release as small as 3.3mm, company notes. g

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REVIEW OF OPTOMETRY JUNE 15, 2021 By Andrew S. Gurwood, OD diagnostic quiz

Back for More The patient was diagnosed with acute The Plot Thickens contact dermatitis and allergic blepha- When a patient’s clinical outlook changes radically, so too roconjunctivitis OD. He was educated to remove possible triggers, use sup- should your approach to differential diagnosis. portive measures (e.g., artificial tears, cold compresses) and was prescribed 69-year-old Black male present- Diagnostic Data a topical mast cell stabilizing/antihis- ed for a routine eye exam with Ocular examination revealed best- tamine agent. He was scheduled to a nebulous complaint of ocular corrected visual acuities to be 20/20 return for follow-up in five to 14 days. Adiscomfort and itching, OD>OS OU through -1.00/+2.50 DS spec- The patient did not return for his of one month’s duration. He reported tacles. External evaluation uncovered scheduled follow-up but did come in no visual loss, pain or diplopia. normal motilities and visual fields, within one month with a recurrent His pertinent medical history normal color and stereo with no acute episode. His chief complaint at included reports of hypertension and evidence of afferent pupillary defect. the return visit was worsening eyelid gout. Current medications included Refraction was negligibly different edema OD and onset of horizontal clopidogrel (Plavix, Bristol-Myers between eyes. diplopia accompanied by constant Squibb), hydrochlorothiazide and The pertinent anterior segment mild pain behind the right eye. aspirin. The patient denied allergies finding OD is demonstrated in the Forced duction testing was positive of any kind. photograph. OD, suggesting a restrictive etiol- Goldmann applanation ogy. Exophthalmometry (base 103) tonometry was 15mm Hg. measured 25mm OD and 21mm OS. Dilated fundus examination There was a 3mm ptosis OD pro- revealed normal and quiet duced by the weight of the edema- posterior segments with no tous lid tissue. There was no afferent peripheral pathology OU. defect. Slit lamp exam confirmed upper lid edema and revealed possible Additional Testing lacrimal gland enlargement OD. Mild Other efforts might include bulbar conjunctival injection OD was palpation of the region to also observed. Posterior segment find- ensure the absence of cel- ings remained unchanged. lulitis. Also, topical sodium fluorescein could be used to Your Diagnosis assess the corneal surface for What would be your diagnosis in this What seemed like a routine case of contact dermatitis damage and to evaluate the case? To find out, read the online ver- actually turned out to be far less commonplace. status of the lacrimal lake. sion at www.reviewofoptometry.com. g

About Dr. Gurwood is a professor of clinical sciences at The Eye Institute of the Pennsylvania College of Optometry at Salus University. He is a co-chief of Primary Care Dr. Gurwood Suite 3. He is attending medical staff in the department of ophthalmology at Albert Einstein Medical Center, Philadelphia. He has no financial interests to disclose.

Retina Quiz Answers (from page 92)—Q1: c, Q2: d, Q3: c, Q4: c, Q5: b

Next Month in the Mag • Comanagement Series: Keep Glaucoma Care Close to Home In July, we present our annual glaucoma report. Articles will include: Also included in July: • How to Make Sense of OCT Scans for Glaucoma • The Results-oriented Neuro Work-up • Beware These Diagnostic Pitfalls in Glaucoma • Cataract Q&A: Expert Answers to Common Dilemmas • Optic Nerve Head Dynamics in Glaucoma and Beyond • The Optometric Workforce: Changes and Challenges

98 REVIEW OF OPTOMETRY | JUNE 15, 2021 BAUSCH + LOMB ULTRA ® MULTIFOCAL FOR ASTIGMATISM FIT FOR SUCCESS

The results are in. Eye Care Professionals gave Bausch + Lomb ULTRA® Multifocal for Astigmatism high marks across the board thanks to its easy fi tting process.

COMING SOON -2.25D and -2.75D Cylinders, available as standard offerings

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agreed that it is easy 80% agreed that it took agreed that this lens allows to get a successful fi t no more than 5 minutes them to fi t patients who during the fi rst visit longer to fi t this lens have previously dropped with this lens.* compared to toric lenses.† out of contact lenses.‡

SCAN CODE FOR SUCCESS STORIES

*Results of an online survey with Eye Care Professionals who completed an evaluation program for Bausch + Lomb ULTRA® Multifocal for Astigmatism contact lenses (n=219). Survey results include Eye Care Professionals who reported that successful fi tting was extremely easy, easy, or somewhat easy (on a 6-point scale) during the fi rst visit, with a margin of error ±4.1%.

†Results of an online survey with Eye Care Professionals who completed an evaluation program for Bausch + Lomb ULTRA® Multifocal for Astigmatism contact lenses (n=219). Survey results include Eye Care Professionals who reported that it took less chair time, no extra chair time, 1-2 minutes of additional chair time, or 3-5 minutes of additional chair time to fi t Bausch + Lomb ULTRA® Multifocal for Astigmatism with a margin of error ±5.3%.

‡Results of an online survey with Eye Care Professionals who completed an evaluation program for Bausch + Lomb ULTRA® Multifocal for Astigmatism contact lenses (n=219). Survey results include Eye Care Professionals who strongly agreed, agreed, or slightly agreed (on a 6-point agreement scale) with the surveyed statement, with a margin of error ±2.8%.

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