Earn 2 CE Credits: Get to Know HZO, p. 78 • Comanagement Series: Neuro, p. 70

14th Annual Pharmaceuticals Report

• Systemic meds • Antibiotics • Mydriatics and miotics • Glaucoma care

May 15, 2021 • reviewofoptometry.com Leadership in clinical care

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© 2021 AbbVie. All rights reserved. All trademarks are the property of their respective owners. REF141368 10/20 Earn 2 CE Credits: Get to Know HZO, p. 78 • Comanagement Series: Neuro, p. 70

14th Annual Pharmaceuticals Report

• Systemic meds • Antibiotics • Mydriatics and miotics • Glaucoma care

May 15, 2021 • reviewofoptometry.com Leadership in clinical care

stay alert for systemic med surprises Many ocular adverse effects may be hiding inside your patient’s pill bottle. Here’s a new way to think about them. Page 34

ALSO INSIDE

Using Antibiotics in Anterior Segment Care Page 50

Managing Miotics and Mydriatics Page 56

Make Glaucoma Therapy More Patient-Friendly Page 62 INDICATION Upneeq® (oxymetazoline hydrochloride ophthalmic solution), 0.1% is indicated for the treatment of acquired blepharoptosis in adults. IMPORTANT SAFETY INFORMATION WARNINGS AND PRECAUTIONS • Alpha-adrenergic agonists as a class may impact blood pressure. Advise Upneeq patients with cardiovascular disease, orthostatic hypotension, and/or uncontrolled hypertension or hypotension to seek medical care if their condition worsens. • Use Upneeq with caution in patients with cerebral or coronary insuffi ciency or Sjögren’s syndrome. Advise patients to seek medical care if signs and symptoms of potentiation of vascular insuffi ciency develop. • Upneeq may increase the risk of angle closure glaucoma in patients with untreated narrow-angle glaucoma. Advise patients to seek immediate medical care if signs and symptoms of acute narrow- angle glaucoma develop. • Patients should not touch the tip of the single patient-use container to their eye or to any surface, in order to avoid eye injury or contamination of the solution.

Distributed by: RVL Pharmaceuticals, Inc. Bridgewater, NJ 08807

PMS 541 C PMS 541 C PMS 908 C PMS 137 C PMS 908 CCustomer Service 1-866-600-4799

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 ® Give Ptosis Patients an EYE-OPENING Lift UUPNEEQ With a Daily Drop of Upneeq® (oxymetazoline 1 (oxymetazoline hydrochloride hydrochloride ophthalmic solution), 0.1% * The only FDA-approved prescription eyedrop proven to ophthalmic solution), 0.1% lift upper eyelids in adults with acquired blepharoptosis *Each mL of Upneeq contains 1 mg of oxymetazoline hydrochloride, equivalent to 0.9 mg (0.09%) of oxymetazoline free base. (low-lying lids)1 Learn more at Upneeq.com. Eye-Opening Possibilities

ADVERSE REACTIONS Adverse reactions that occurred in 1-5% of subjects treated with Upneeq were punctate keratitis, conjunctival hyperemia, dry eye, blurred vision, instillation site pain, eye irritation, and headache. DRUG INTERACTIONS • Alpha-adrenergic agonists, as a class, may impact blood pressure. Caution in using drugs such as beta blockers, anti-hypertensives, and/or cardiac glycosides is advised. Caution should also be exercised in patients receiving alpha adrenergic receptor antagonists such as in the treatment of cardiovascular disease, or benign prostatic hypertrophy. • Caution is advised in patients taking monoamine oxidase inhibitors which can affect the metabolism and uptake of circulating amines. To report SUSPECTED ADVERSE REACTIONS or product complaints, contact RVL Pharmaceuticals at 1-877-482-3788. You may also report SUSPECTED ADVERSE REACTIONS to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. Please see next page for Brief Summary of full Prescribing Information.

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

TM Learn more at Upneeq.com UU 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 0.9 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 birth defect, 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 If more than one topical ophthalmic drug is being used, the drugs 15-20%, 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, mydriasis, 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 Get the latest at news review www.reviewofoptometry.com/news Clinical, legislative and practice development updates for ODs. Stories post every weekday

SmartPhone Apps and Vision Testing, p. 6 >> POAG Conversion RAte, p. 8 >> Tanning Beds Cause Ocular Harm, p. 10 >> SPEEDY DEQ-5 vs. OSDI, p. 10 >> Screen Time aFfects MG, p. 13

No Clinical Advantage to Femto Cataract Surgery Study finds equal levels of vision, safety and patient-perceived quality vs. traditional methods.

emtosecond laser–assisted Photo: Derek Cunningham, OD, and Walter Whitley, OD “Our results indicated that both cataract surgery (FLACS) has groups had excellent visual and Freceived much buzz since it refractive outcomes at 12 months was introduced over a decade ago, but with no statistically significant dif- there is uncertainty about whether this ference in any of the tested param- high-tech, high-price approach offers eters,” the authors explained in their any clinical benefits over conventional study. “Although validated cataract surgery using manual techniques. For surgery-specific PROMs at one month this reason, researchers from London postoperatively have been reported, decided to study and report 12-month this is the first time the same PROMs outcomes of a randomized controlled at 12 months postoperatively have trial comparing FLACS with conven- become available” for a study of femto tional methods. cataract vs. conventional approaches. Visual acuity, refraction, central The authors concluded that FLACS was not “In contrast with other studies, we did corneal thickness, endothelial cell loss, superior to conventional phaco, as it did not find that FLACS resulted in more adverse events, quality of life out- not provide any benefits in outcomes and it predictable refractive outcomes.” comes and patient-reported outcome incurred higher costs. Visual outcomes remain unchanged measures (PROMs) were recorded for and 0.13 logMAR for conventional and, moreover, the femto approach 400 patients (single eye surgery for phaco. Rates of spherical equivalent wasn’t any safer, they found. “The each). There were no differences in refraction within 0.5D of target were rate of onset of new visually significant corrected or uncorrected visual acuity, 78% for FLACS and 81% for conven- comorbidities in the fellow eye be- corneal thickness (compared to pre- tional phaco. tween four weeks and 12 months was op), endothelial cell loss (compared The authors concluded that FLACS not significantly different between the to pre-op and one month post-op), was not superior to conventional pha- FLACS group and the [conventional residual refractive cylinder, spherical co, as it did not provide any benefits in phaco] group.” equivalent refractive error from target outcomes and it incurred higher costs. Stanojcic N, Roberts HW, Wagh VK, et al. A randomised con- refractions or changes in PROM indi- A little more than half (58.5%) of the trolled trial comparing femtosecond laser-assisted cataract ces. Mean uncorrected distance visual 400 patients attended a 12-month surgery versus conventional phacoemulsification surgery: acuity was 0.12 logMAR for FLACS follow-up exam. 12-month results. Br J Ophthalmol. 2021;105(5):631-8.

encounter complications if they had g New research suggests greater neuritis had higher BMI (31.26 vs. IN BRIEF BCVA of 1logMAR or greater, were BMI may be linked with higher 25.73), greater serum estrogen lev- acute optic neuritis severity in g Patients who underwent intra- older than 90, male or diabetic or els (32.24nmol/L vs. 23.06nmol/L) vitreal therapy have an increased had pseudoexfoliation, glaucoma or males with multiple sclerosis. The and enhanced serum leptin rates risk of intraoperative complications previous intravitreal therapy. Other investigation also reports that (12.29ng/mL vs. 4.1ng/mL) com- during cataract surgery. A new predictors included surgeon experi- the hormones estrogen and leptin pared with male subjects with mild model can predict the risk of com- ence (fewer than 600 surgeries), appeared to influence the ocular acute optic neuritis. plications such as posterior capsule use of rhexis hooks, blue staining condition in men with MS. Of note: the researchers didn’t rupture and zonular dehiscence. and mechanical pupil dilation. The study enrolled 61 MS observe these same findings in This large-scale study included patients whose acute optic neuritis female patients. 900,000 eyes from the Swedish Na- Af Segerstad PH. Risk model for intraoperative severity and recovery (based on tional Cataract Register. Overall, the complication during cataract surgery based on data VA) was evaluated before, during Chu DT, Rosso M, Gonzalez CT, et al. Obesity is from 900,000 eyes: previous intravitreal injection is association with the optic neuritis severity in male rate of intra-op complications was a risk factor. Br J Ophthalmol. April 22, 2021. [Epub and after the relapse. Males with patients with multiple sclerosis. Mult scler relat 0.86%. Patients were more likely to ahead of print]. moderate/severe acute optic disord. March 21, 2021. [Epub ahead of print].

MAY 15, 2021 | REVIEW OF OPTOMETRY 5 NEWS REVIEW | Get the latest at www.reviewofoptometry.com/news Smartphone Apps Fare Poorly at Vision Testing Researchers identified three as the best of the bunch, yet stressed these too had limitations.

isual acuity apps aren’t in the Photo: Bisant Labib, OD the device is being held from the face ballpark of comparability to when measuring near VA, using the Vin-person refractions, but new Landolt C or tumbling E optotype. research that analyzed 24 currently The testing process involves the user available platforms suggests three that identifying the direction of the opto- seem to perform the best if an office type of increasing or decreasing size visit isn’t feasible, such as when offer- depending on the user response. This ing remote screenings for telehealth is a test of monocular VA, and acuity is consults. presented as a Snellen imperial. “A growing number of ophthalmic This novel technique of calibra- health tool apps are available for both Variables can impact smartphone apps’ tion has not been employed by any patients and clinicians, which may accuracy compared with printed optotypes. of the other apps tested; however, address the increasing demand for there are some inherent limitations, eye care in the future. As they are a and this can be switched to Snellen the investigators said. The method relatively new form of technology, they metric (6/6) or Snellen imperial (20/20). relies on detecting facial landmarking, are not without disadvantages,” the Peek Acuity has been clinically vali- which varies greatly depending on the research team from the UK wrote in dated and shown to produce accurate optics of the camera being used, most their paper. and repeatable acuity measurement notably the focal length. Additionally, Compared with traditional VA test- compared with conventional acuity the LooC–Mobile eye test hasn’t been ing that relies on printed optotypes, charts in peer-reviewed research, the clinically validated. Still, the app has smartphone apps suffer from a range researchers noted. been created according to the Interna- of variables that can influence the ac- tional Organization for Standardization curacy of results. This includes screen Peek Acuity Pro (Peek Vision) criteria for VA testing and has been size, aspect ratio, pixel density, contrast The Pro version of the app is a CE- implemented in individual ophthal- and screen brightness, the study noted. registered, class 1, medical device mology clinics in Berlin with good With these limitations in mind, here available in certain countries, and results, the researchers said. are the three apps the authors said both versions (Peek Acuity and Peek The team started by conducting a would be suitable for clinical practice Acuity Pro) are available for free on systemic search for VA testing apps on under appropriate circumstances: the Google Store. The two apps have the Google Play and Apple App stores. methods for calibrating both optotype They narrowed it down to 16 (67%) Peek Acuity (Peek Vision) size and brightness. that tested near vision, five (21%) that The standalone app measures VA using The limitation of these two apps is measured distance and three (13%) the tumbling E test and includes an the inability for users to self-test, since that offered both. Out of the 24 apps, interactive guide on proper usage. The the test requires a second person to act only five (21%) offered a method of app begins by measuring VA monocu- as the device operator. In the context calibration of optotype size, while the larly at a 2m distance. The optotype of ophthalmic telehealth consults, this three previously mentioned (13%) decreases in size as the patient cor- would limit the suitability of the app demonstrated evidence of clinical rectly identifies its direction until the to patients living with friends or family validation. final VA is reached. If the patient is members who can accurately operate More work is needed in vision unable to identify the direction of the the device, the authors noted. testing smartphone applications, optotype at 2m, the user is prompted to including the clinical validation of decrease the test distance to 1m. If the Looc-Mobile Eye Test (Looc GmbH) individual apps, improved governance patient fails to identify the optotype at When testing near vision, the calibra- of health apps and cohort management 1m, the user is instructed to decrease tion stage of this app involves using systems for the integration of these the test distance to 30cm. a mirror and the phone’s front facing programs into existing care pathways, The app offers two additional camera to estimate the user’s interpu- the study concluded. prompts corresponding to decrease VA, pillary distance, which takes around 30 including a moving target, and abil- seconds to complete. The app uses a Kawamoto K, Stanojcic N, Olivia J P, Thomas PBM. Visual acuity apps for rapid integration in teleconsultation services in all ity to perceive the phone’s torchlight. phone’s front-facing camera and face resource settings: a review. Asia Pac J Ophthalmol. February 9, Final VA is expressed as logMAR (0.0), detection to determine the distance 2021. [Epub ahead of print].

6 REVIEW OF OPTOMETRY | MAY 15, 2021 Journey to a world WHERE A LOSS OF TEAR FILM HOMEOSTASIS LEADS TO DRY EYE 1

When it comes to dry eye disease and the loss of tear film homeostasis, there’s a broader integrated system that needs exploring. We call it Dry Eyeland.2,3

Come travel this anatomical landscape, where: • Loss of tear film homeostasis is the unifying characteristic of all dry eye1 • The parasympathetic nervous system plays a major role in tear film homeostasis2 • The lacrimal functional unit (LFU) is far more than just the lacrimal gland3

Allow us to be your guide to dry eye—visit DryEyeland.com to see the sights. Because a whole world awaits beyond the ocular surface.

References: 1. Craig JP, Nelson JD, Azar DT, et al. Ocul Surf. 2017;15(4):802-812. 2. Efron N, Jones L, Bron AJ, et al. Invest Ophthalmol Vis Sci. 2013;54(11):TFOS98-TFOS122. 3. Ocul Surf. 2007;5(2):75-92.

© 2021 Oyster Point Pharma, Inc. Oyster Point™ and the Oyster Point logo are trademarks of Oyster Point Pharma, Inc. OP-COM-000083 NEWS REVIEW | Get the latest at www.reviewofoptometry.com/news

Ocular Hypertension to POAG Recombinant Herpes Vaccine Effective But Conversion Rate Low, Study Finds Not Popular ptometrists have long known of POAG in one or both eyes was While prevention can be the best that ocular hypertension is a 45.6% among all participants, 49.3% medicine, sometimes the battle begins Orisk factor for development of among participants in the observation even earlier; namely, in helping those primary open-angle glaucoma (POAG), group and 41.9% among participants who need it to take the first step. The but anticipating disease manifestation in the medication group. The 20- relatively recent recombinant vaccine is a perennial problem for doctors moni- year cumulative incidence of POAG for herpes zoster virus has been toring such cases. In a recent study, was 55.2% among African American proven to reduce the incidence rate researchers determined the cumula- participants and 42.7% among partici- of herpes zoster ophthalmicus (HZO), tive incidence and severity of POAG pants of other races, but the authors but researchers have uncovered a low after 20 years of follow-up among noted “when patients are stratified by vaccination rate and highlight the public health need to increase herpes zoster participants in the Ocular Hyperten- baseline risk, Black/African American vaccination in eligible patients. sion Treatment Study (OHTS). The individuals and others in the same risk To assess HZO incidence in the United data from this long-term follow-up can category have similar outcomes.” States in vaccinated vs. unvaccinated be used to inform ocular hypertension “In total, 199 participants devel- individuals, the study included 4.8 million management. oped optic disc POAG deterioration in people who were age-eligible for herpes In phase one of the seminal study, one or both eyes without visual field zoster vaccination (≥50 years old). Those participants were randomized to abnormality,” the authors noted in their with a diagnosis of herpes zoster or an receive either topical ocular hypoten- study. “As a group, these participants immunocompromising condition within sive therapy (medication group) or had few differences from those who did one year prior to study inclusion were close observation (observation group). not develop POAG when comparing excluded. The researchers found that In phase two, both groups received the last-assessed visual field mean de- 177,289 (3.7%) received two valid doses medication. In phase three, participants viation or pattern standard deviation vi- of the recombinant vaccine. The second received eye exams and visual function sual acuity, contrast sensitivity or foveal dose was considered valid only if it oc- curred 30 to 210 days after the first dose. assessments. sensitivity. Greater functional differenc- The incidence rate of HZO was 25.5 Over 1,600 individuals were random- es might have been detected with more cases per 100,000 person-years in the ized in phase one of the trial. Of those, rigorous psychophysical, performance vaccinated group compared with 76.7 483 participants (29.5%) developed or electrophysiologic tests that were not in the unvaccinated group. The overall POAG in one or both eyes (unadjusted performed in the OHTS.” adjusted effectiveness of the vaccine incidence). After adjusting for exposure Over the course of the study, 515 against HZO was 89.1%. The vaccinated time, the 20-year cumulative incidence participants died, which alarmed the group in the study was also older than authors. “It is concerning that the num- the unvaccinated group, highlighting the Photo: Justin Cole, OD, and Jarett Mazzarella, OD ber of participants who died and the need to improve vaccination efforts in number who developed POAG were eligible younger patients. approximately the same,” they noted. “By focusing on the ocular benefits “The incidence of POAG appeared to of vaccination, clinicians could play a bigger role in the public health sphere be generally linear over 20 years, with a by championing vaccination efforts to possible modest increase in the rate of prevent a debilitating eye disease,” the conversion after 15 years. ” researchers noted. The authors noted some factors that Nevertheless, the study also could may have implicated the results. For not assess waning of the recombinant example, participants may have a lower vaccine’s effectiveness, since it was only risk of developing POAG because introduced in late 2017, and individuals volunteers in most studies may be more had relatively short post-vaccination fol- likely to return for follow-up visits and low-up time. The researchers suggested adhere to medication. a future study with a longer study period could confirm long-term effectiveness. Kass MA, Keuer DK, Higginbotham, EJ, et al. Assessment Lu A, Sun Y, Porco TC, et al. Effectiveness of the of cumulative incidence and severity of primary open-angle Only one-fourth of participants developed glaucoma among participants in the ocular hypertension recombinant zoster vaccine for herpes zoster ophthal- visual field loss in either eye over a 20- treatment study after 20 years of follow-up. JAMA Ophthal- micus in the United States. Ophthalmology. April 20, mol. April 15, 2021. [Epub ahead of print]. 2021. [Epub ahead of print]. year follow-up.

8 REVIEW OF OPTOMETRY | MAY 15, 2021 Helping Heroes See Clear And Stay Safe

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Tanning Beds Induce Ocular Surface Changes

here are a number of clinical and endothelial cell counts when studies demonstrating ocular compared with age-matched popula- Tsurface damage from natural tions, but exposure to UV light also UV exposure, but there’s limited damages notably the epithelium of evidence of the experience of indoor the cornea immediately after several sun tanning sessions. In a new study, tanning sessions. researchers evaluated the ocular “Although the overall corneal surface clinically and at a microstruc- damage cannot be directly correlated tural level using in vivo confocal to the UV damage, the short-term, microscopy. reversible epithelial damage has no Female participants between ages Sun tanning leads to clinically undetectable, other common causative agent in our microstructural changes affecting the 20 and 29 were enrolled into a study study group,” the authors explained cornea and the bulbar conjunctiva. group with a history of UV indoor tan- in their paper. “The number of con- ning and a control group with no prior pate in tanning sessions. junctival cystic lesions was greatest in history. The study subjects partici- No clinically significant changes the superior and inferior conjunctiva.” pated in voluntary tanning sessions were observed in either group over The study concluded that sun tan- performed with standard equipment time using slit lamp biomicroscopy; ning leads to clinically undetectable, and maintained their usual routine for however, statistically significant dif- microstructural changes affecting the eye protection. Slit lamp biomicros- ferences were observed between the cornea and the bulbar conjunctiva. copy and in vivo confocal microscopy study and the control group for all The long-term effect of those changes were performed at baseline before corneal layers imaged using confo- would lead to “UV aging of the an- undertaking a series of sun tanning cal microscopy. Characteristic cystic terior ocular surface,” which appears sessions (10 sessions of 10-minute conjunctival lesions with dark centers to be similar to microstructural skin duration over a 15-day period), within and bright borders were observed in damage from UV exposure. three days and four weeks after the 95% of the study group before and in last session. Control group partici- 100% after the sun tanning sessions. Grupcheva CN, Radeva MN, Grupchev DI. Damage of the ocular surface from indoor suntanning—Insights from in vivo pants were examined at baseline and This study found that the corneas confocal microscopy. Cont Lens Anterior Eye. April 8, 2021. eight weeks later and did not partici- of sunbed users had lower keratocyte [Epub ahead of print]. Speedy DEQ-5 Comparable to OSDI iven the chronic nature of dry used to evaluate the OSDI and DEQ-5 naire only measures frequency of dry eye, it’s often helpful to track questionnaires. The reliability of the eye symptoms and their effects on Gsymptoms over time using overall OSDI and DEQ-5 scores were vision-related functioning. The DEQ- standardized questionnaires, but the 0.919 and 0.819, respectively. The au- 5 questionnaire, in addition to assess- experience can be time-consuming thors noted the DEQ-5 questionnaire ing frequency of dry eye symptoms, for patients and practice alike. The had good concurrent validity, based is also sensitive to dry eye symptom most frequently used question- on the relatively strong correlation be- intensity.” naire—the Ocular Surface Disease tween its overall score and the overall Despite this, the authors concluded Index (OSDI)—contains 12 items and score of the OSDI questionnaire. the performance of the DEQ-5 ques- uses three subscales to assess dry eye “However, there wasn’t a perfect tionnaire in discriminating symptoms symptoms. correlation between the two question- of dry eye is comparable to the OSDI. The Dry Eye Questionnaire (DEQ- naires, indicative of the fact that either The DEQ-5 questionnaire is a valid 5) is a simplified version of the original questionnaire might capture unique as- measure of dry eye symptoms and DEQ, but compared to the OSDI, it pects of dry eye disease that the other can be used as a dry eye symptom has not been well studied. In a cross- might not,” the authors explained in assessment tool in both studies and in sectional study conducted in Ghana, their study. “An imperfect correlation practice, they argued. researchers compared the performance between the two questionnaires was Akowuah PK, Adjei-Anang J, Nkansah, EK, et al. Com- of both questionnaires. expected, owing to the difference in parison of the performance of the dry eye questionnaire Various statistical measures of reli- the structure and content of the two (DEQ-5) to the ocular surface disease index in a non-clinical population. Cont Lens Anterior Eye. April 6, 2021. [Epub ability, sensitivity and specificity were questionnaires. The OSDI question- ahead of print].

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Available by INDICATIONS AND USAGE prescription only ZERVIATE® (cetirizine ophthalmic solution) 0.24% is a histamine-1 (H1) receptor antagonist indicated for treatment of ocular itching associated with allergic conjunctivitis. Formulated with HYDRELLA™ for comfort.1 IMPORTANT SAFETY INFORMATION Visit MyZERVIATE.com for more information. ADVERSE REACTIONS References: 1. ZERVIATE [package insert]. Fort Worth, TX: Eyevance The most commonly reported adverse reactions occurred Pharmaceuticals LLC; 2018. 2. Malhotra RP, Meier E, Torkildsen G, in approximately 1%-7% of patients treated with either et al. Safety of cetirizine ophthalmic solution 0.24% for the treatment ZERVIATE or vehicle. These reactions were ocular hyperemia, of allergic conjunctivitis in adult and pediatric subjects. Clin Ophthalmol. 2019;13:403-413. 3. Meier EJ, Torkildsen GL, Gomes PJ, instillation site pain, and visual acuity reduced. et al. Phase III trials examining the eff icacy of cetirizine ophthalmic solution 0.24% compared to vehicle for the treatment of allergic Please see brief summary of Full Prescribing Information conjunctivitis in the conjunctival allergen challenge model. Clin on the adjacent page. Ophthalmol. 2018;12:2617-2628.

© 2021 Eyevance Pharmaceuticals LLC. All rights reserved. ZERVIATE® is a registered trademark and HYDRELLA™ is a trademark of Eyevance Pharmaceuticals LLC. *All other trademarks are the property of their respective owners. ZER-21-AD-106-02 ZERVIATE™ (cetirizine ophthalmic solution) 0.24% There is no adequate information regarding the e€ects of cetirizine on breastfed infants, or the e€ects on milk Brief Summary production to inform risk of ZERVIATE to an infant during INDICATIONS AND USAGE lactation. The developmental and health benefits of ZERVIATE (cetirizine ophthalmic solution) 0.24% is a breastfeeding should be considered along with the mother’s histamine-1 (H1) receptor antagonist indicated for treatment of clinical need for ZERVIATE and any potential adverse e€ects ocular itching associated with allergic conjunctivitis. on the breastfed child from ZERVIATE. DOSAGE AND ADMINISTRATION Pediatric Use: The safety and e€ectiveness of ZERVIATE Recommended Dosing: Instill one drop of ZERVIATE in has been established in pediatric patients two years of age each a€ected eye twice daily (approximately 8 hours apart). and older. Use of ZERVIATE in these pediatric patients is The single-use containers are to be used immediately after supported by evidence from adequate and well-controlled opening and can be used to dose both eyes. Discard the studies of ZERVIATE in pediatric and adult patients. single-use container and any remaining contents after Geriatric Use: No overall di€erences in safety or administration. The single-use containers should be stored in e€ectiveness have been observed between elderly and the original foil pouch until ready to use. younger patients. CONTRAINDICATIONS NONCLINICAL TOXICOLOGY None. Carcinogenesis, Mutagenesis, Impairment of Fertility WARNINGS AND PRECAUTIONS Carcinogenicity Contamination of Tip and Solution: As with any eye drop, In a 2-year carcinogenicity study in rats, orally administered care should be taken not to touch the eyelids or surrounding cetirizine was not carcinogenic at dietary doses up to areas with the dropper tip of the bottle or tip of the single- 20 mg/kg (approximately 550 times the MRHOD, on a use container to avoid injury to the eye and to prevent mg/m2 basis). In a 2-year carcinogenicity study in mice, contaminating the tip and solution. Keep the multi-dose bottle cetirizine caused an increased incidence of benign liver closed when not in use. Discard the single-use container after tumors in males at a dietary dose of 16 mg/kg (approximately using in each eye. 220 times the MRHOD, on a mg/m2 basis). No increase in the incidence of liver tumors was observed in mice at a dietary Contact Lens Wear: Patients should be advised not to wear dose of 4 mg/kg (approximately 55 times the MRHOD, on a contact lens if their eye is red. a mg/m2 basis). The clinical significance of these findings ZERVIATE should not be instilled while wearing contact during long-term use of cetirizine is not known. lenses. Remove contact lenses prior to instillation of Mutagenesis ZERVIATE. The preservative in ZERVIATE, benzalkonium Cetirizine was not mutagenic in the Ames test or in an in vivo chloride, may be absorbed by soft contact lenses. Lenses may micronucleus test in rats. Cetirizine was not clastogenic in the be reinserted 10 minutes following administration human lymphocyte assay or the mouse lymphoma assay. of ZERVIATE. Impairment of Fertility ADVERSE REACTIONS In a fertility and general reproductive performance study in Clinical Trials Experience: Because clinical trials are mice, cetirizine did not impair fertility at an oral dose of conducted under widely varying conditions, adverse reaction 64 mg/kg (approximately 875 times the MRHOD, on a rates observed in the clinical trial of a drug cannot be directly mg/m2 basis). compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. PATIENT COUNSELING INFORMATION Risk of Contamination: Advise patients not to touch In 7 clinical trials, patients with allergic conjunctivitis or those dropper tip to eyelids or surrounding areas, as this may at risk of developing allergic conjunctivitis received one contaminate the dropper tip and ophthalmic solution. Advise drop of either cetirizine (N=511) or vehicle (N=329) in one or patients to keep the bottle closed when not in use. Advise both eyes. The most commonly reported adverse reactions patients to discard single-use containers after each use. occurred in approximately 1%–7% of patients treated with either ZERVIATE or vehicle. These reactions were ocular Concomitant Use of Contact Lenses: Advise patients not hyperemia, instillation site pain, and visual acuity reduced. to wear contact lenses if their eyes are red. Advise patients that ZERVIATE should not be used to treat contact lens– USE IN SPECIFIC POPULATIONS related irritation. Advise patients to remove contact lenses Pregnancy prior to instillation of ZERVIATE. The preservative in ZERVIATE Risk Summary solution, benzalkonium chloride, may be absorbed by soft There were no adequate or well-controlled studies with contact lenses. Lenses may be reinserted 10 minutes following ZERVIATE in pregnant women. Cetirizine should be used in administration of ZERVIATE. pregnancy only if the potential benefit justifies the potential risk to the fetus. Administration: Advise patients that the solution from one single-use container is to be used immediately after opening. Data Advise patients that the single-use container can be used Animal Data to dose both eyes. Discard the single-use container and Cetirizine was not teratogenic in mice, rats, or rabbits remaining contents immediately after administration. at oral doses up to 96, 225, and 135 mg/kg, respectively (approximately 1300, 4930, and 7400 times the maximum Storage of Single-use Containers: recommended human ophthalmic dose (MRHOD), on a Instruct patients to store single-use containers in the original mg/m2 basis). foil pouch until ready to use. Lactation Rx Only Risk Summary Distributed by: Eyevance Pharmaceuticals LLC. Fort Worth, Cetirizine has been reported to be excreted in human breast TX 76102 milk following oral administration. Multiple doses of oral dose cetirizine (10 mg tablets once daily for 10 days) resulted in systemic levels (Mean Cmax = 311 ng/mL) that were 100 times higher than the observed human exposure (Mean Cmax = 3.1 ng/mL) following twice daily administration of cetirizine ophthalmic solution 0.24% to both eyes for 1 week. Comparable bioavailability has been found between the tablet and syrup dosage forms. However, it is not known whether the systemic absorption resulting from topical © 2020 Eyevance Pharmaceuticals LLC. All rights reserved. ocular administration of ZERVIATE could produce detectable ZERVIATE™ is a trademark of Eyevance Pharmaceuticals LLC. quantities in human breast milk. ZER-04-20-MS-44

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Important Safety Information: ACUVUE® Contact Lenses are indicated for vision correction. As with any contact lens, eye problems, including corneal ulcers, can develop. Some wearers may experience mildirritation, itching or discomfort. Lenses should not be prescribed if patients have any eye infection, or experience eye discomfort, excessive tearing, vision changes, redness or other eye problems. Consult the package insert for complete information. Complete information is also available from Johnson & Johnson Vision Care, Inc. by calling 1œ800œ843œ2020, or by visiting JNJVISIONPRO.com. © Johnson & Johnson Vision Care, Inc. 2021 | PP2021AVO4115v2 | MBœ00551B CATCH UP ON THE LATEST NEWS features Stories post online every weekday Weekly recap emailed every Sunday REVIEW OF OPTOMETRY • Vol. 158, No. 5 • MAY 15, 2021 70 Take the Fear Out of Comanaging Neuro Cases Many patients are best served through a partnership between primary care optometrists and appropiate subspecialists. By Catlin Nalley, Contributing Writer

14th Annual Pharmaceuticals Report

34 56 Stay Alert For Systemic Managing Miotics and Med Surprises Mydriatics 78 EARN 2 CE CREDITS Many ocular adverse effects may be Take a closer look at old, new and future Get to Know HZO hiding inside your patient’s pill bottle. uses of these drugs. Here’s a new way to think about them. By Paymaun Asnaashari, OD Gain a comprehensive understanding of the various treatment options to By Aaron Case, OD, Joy Kerns, OD, and effectively manage this condition. Sara Weidmayer, OD By Aaron Bronner, OD 50 62 Using Antibiotics in Make Glaucoma Therapy Anterior Segment Care More Patient-Friendly Bacterial ocular and periocular Here’s how to better ensure patient infections are common in adults and adherence to treatment. children, but choosing an effective By Michael Dorkowski, OD, Shaleen treatment strategy relies on more than Ragha, OD, and Jennifer Sanderson, OD an accurate clinical diagnosis. By Jessica Steen, OD

MAY 15, 2021 | REVIEW OF OPTOMETRY 15 departments REVIEW OF OPTOMETRY • MAY 15, 2021 5 28 NEWS REVIEW THE ESSENTIALS Surveying the Cavern Take a closer look at how the features that 20 make up this sinus function—and can lead to OUTLOOK dysfunction. The Force Awakens Bisant A. Labib, OD In-person conferences are coming back, slowly and fitfully, but with momentum and goodwill on their side. Jack Persico, Editor-in-Chief 32 CODING CONNECTION 22 Spring Renewal 94 THROUGH MY EYES With the change of the seasons comes RETINA QUIZ opportunity. Dose Escalation John Rumpakis, OD, MBA Persistent Proliferation A number of new and exciting pharmaceuticals Solve this patient’s cloudy vision with fundus to help manage ocular disease are on the photography. horizon. Get to know them here. Rami Aboumourad, OD Paul M. Karpecki, OD 88 Mark Dunbar, OD 24 CORNEA AND CONTACT LENS Q+A CHAIRSIDE Sidestep Side Effects Here’s how to minimize the potential 100 Looking to Be a complications of a KPro. CLASSIFIED ADVERTISING Trendsetter? Yeah, Me Too Joseph P. Shovlin, OD I may not have a million followers on Instagram—or even have an account—but I do know a thing or two about things. 104 Montgomery Vickers, OD 90 PRODUCT REVIEW URGENT CARE 26 From Dislocation to CLINICAL QUANDARIES Restoration 105 Blindsided This patient had to undergo IOL replacement ADVERTISERS INDEX A thorough, dilated examination of the surgery to finally achieving satisfactory retina is necessary to diagnose retinitis vision. pigmentosa. Leonid Skorin, Jr., DO, OD, MS Paul C. Ajamian, OD Richard Mangan, OD 106 VISIT US ON SOCIAL MEDIA DIAGNOSTIC QUIZ Game Over Facebook: www.facebook.com/revoptom An anxious patient presents complaining of Twitter: twitter.com/revoptom recent-onset blurred vision at distance. Are his fears warranted? Instagram: www.instagram.com/revoptom Andrew S. Gurwood, OD

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Editorial Offices 19 Campus Blvd., Suite 101 Newtown Square, PA 19073 The Force Awakens EDITOR-IN-CHIEF JACK PERSICO In-person conferences are coming back, slowly and fitfully, (610) 492-1006 • [email protected] but with momentum and goodwill on their side. SENIOR EDITOR JULIE SHANNON (610) 492-1005 • [email protected] hose of us who are regular travel- I have to admit that streaming the ASSOCIATE EDITOR ers on the educational conference lectures to my living room was aw- CATHERINE MANTHORP (610) 492-1043 • [email protected] circuit will probably always think fully convenient, but it wasn’t always of SECO 2020 when we reflect on engrossing. In fact, it felt a lot like ASSOCIATE EDITOR T MARK DE LEON the COVID pandemic lockdown. That watching TV: comfortable, passive and (610) 492-1021 • [email protected] was the last big meeting to happen prone to distraction. Emails and texts, SPECIAL PROJECTS MANAGER before the profession, and pretty much social media feeds and a boisterous JILL GALLAGHER (610) 492-1037 • [email protected] the entire world, retreated from society five-year-old son who knows no work/ for a year or so. home boundaries all competed with SENIOR ART DIRECTOR JARED ARAUJO This magazine hosts a big recep- SECO for my attention. The content (610) 492-1032 • [email protected] tion at SECO each year, where over was as great as always; my couch potato DIRECTOR OF CE ADMINISTRATION 100 people gather to talk and eat and experience, not so much. REGINA COMBS (212) 274-7160 • [email protected] laugh together, elbow-to-elbow, for TV binge-watching exploded during three hours. You couldn’t ask for a the pandemic as people found them- more convivial atmosphere. Less than selves with few options for their leisure Clinical Editors two weeks after last year’s event, I was time. Turn on the TV or flip open your Chief Clinical Editor • Paul M. Karpecki, OD literally wearing surgical gloves and a laptop and hundreds of choices are Associate Clinical Editors Joseph P. Shovlin, OD, Christine W. Sindt, OD mask in the grocery store. Quite a 180 instantly at your fingertips. But so are Clinical & Education Conference Advisor from SECO! all the others if your attention drifts. Paul M. Karpecki, OD So, like many others, I was encour- The day SECO ended, the ARVO Case Reports Coordinator • Andrew S. Gurwood, OD aged to see SECO’s 2021 meeting hap- conference began—all virtual this year. Clinical Coding Editor • John Rumpakis, OD, MBA pen live in-person. Kudos to them for Just another TV show to watch. putting in the tremendous additional Contrast TV with the experience of Columnists effort it took to pull it off (on top of the seeing a movie—critically, in a theater. Chairside – Montgomery Vickers, OD Clinical Quandaries – Paul C. Ajamian, OD already heavy lift of running a large, That’s an immersive, compelling ex- Coding Connection – John Rumpakis, OD complex meeting). Organizers heeded perience that you actively must create Cornea and Contact Lens Q+A – Joseph P. Shovlin, OD all the necessary protocols to ensure a for yourself by traveling to the location Diagnostic Quiz – Andrew S. Gurwood, OD safe event. Attendees dutifully wore and making other logistical arrange- The Essentials – Bisant A. Labib, OD masks and abided by the social distanc- ments. A night out at the movies used Focus on Refraction – Marc Taub, OD, Paul Harris, OD ing requirements. It all looked very to sometimes feel like a chore. (Child- Glaucoma Grand Rounds – James L. Fanelli, OD functional—but, without the personal care hassles! Overpriced popcorn!) And Ocular Surface Review – Paul M. Karpecki, OD Retina Quiz – Mark T. Dunbar, OD connection, more somber this year. yet, that’s what people seem to really Surgical Minute – Derek Cunningham, OD, Walter Whitley, OD The evident desire to be back together crave after 14 months of isolation. Therapeutic Review – Joseph W. Sowka, OD ran smack into the reality that the All year, it’s been an open question of Through My Eyes – Paul M. Karpecki, OD pandemic circumstances, while much whether or not in-person meetings will Urgent Care – Richard B. Mangan, OD improved, are not yet resolved. rebound once safety concerns abate. Our editorial staff produced the Streaming CE’s convenience, some say, daily newspaper for SECO 2021, as we demands inclusion regardless. Maybe have for many years. Like the confer- so. It got us by when we needed it. But

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Subscription inquiries: (877) 529-1746 Atlanta; the editors were working from many post-pandemic events will be Continuing Education inquiries: (800) 825-4696 home, viewing video feeds of the pre- blockbusters. As Siskel and Ebert used

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References: 1. Torkildsen GL, et al. Clin Ther. 2008;30(7):1272-1282. doi:10.1016/s0149-2918(08)80051-3 2. Data on fi le. Alaway is a trademark of Bausch & Lomb Incorporated or its a‹ liates. © 2021 Bausch & Lomb Incorporated or its a‹ liates. PN09876 APF.0015.USA.21 By Paul M. Karpecki, OD Chief Clinical Editor Through my eyes

Thyroid Eye Disease Dose Escalation Another 2020 approval was Tepezza A number of new and exciting pharmaceuticals to help manage (teprotumumab-trbw) from Horizon Therapeutics for the treatment of ocular disease are on the horizon. Get to know them here. thyroid eye disease (TED). The treat- ment involves a series of eight infu- e’re currently in a growth Eysuvis for Dry Eye Flares sions of a human monoclonal antibody phase for pharmaceutical Having an FDA approval for dry eye and a specific growth factor receptor management of eye disease. In flares using this new agent from Kala inhibitor. It is the only therapeutic wthe last month, two companies in is not only significant in helping for this indication. Prior to Tepezza, announced positive Phase III results DED patients but also validates our patients experienced the severe reper- on novel drugs for dry eye/MGD and long-standing approach to the man- cussions of Graves’ ophthalmopathy, allergic conjunctivitis. The newest agement of this disease. The approval including eye dryness, proptosis and FDA-approved drugs include a drop provides us an on-label loteprednol eventual nerve compression, along for ptosis and dry eye flares, an infusion 0.25% eye drop for short-term therapy with the negative cosmesis associated therapy for thyroid eye disease and a that improves dry eye signs and with TED. Decompression surgery glaucoma implant. Getting to know symptoms. In fact, 91% of patients on is painful and difficult, so having a these new meds can greatly improve chronic immunomodulators admit to highly effective (though pricey) alter- your care of ocular disease patients. experiencing flares and the average native treatment has done wonders for dry eye patient has between four and patients with TED. Two Future Therapies six of such incidents per year. Bausch + Lomb, with partner Novaliq, Sustained-release Bimatoprost announced top-line results from the The FDA also approved Allergan’s first Phase III trial of NOV03. This Decompression surgery Durysta (bimatoprost) implant in 2020. perfluorohexyloctane agent works to is painful and difficult, so An inserter placed at the limbus allows solubilize lipids for the treatment of the eyecare provider to easily deliver having a highly effective MGD and evaporative dry eye disease a biodegradable, sustained-release (DED). It achieved a statistically sig- (though pricey) alternative glaucoma implant into the anterior nificant improvement over vehicle for treatment has done wonders chamber. The device sits in the lower both signs (total corneal staining) and for patients with TED. angle and is evident for about three symptoms (eye dryness score). Most months before dissolving. What has impressive: improvement on both been interesting is that a lowered IOP measures was noted as soon as day 15. Blepharoplasty in a Bottle equivalent to using topical drops re- Even more recently, and closer to Shy of surgical options, there was mains for between 18 and 24 months. FDA approval, Aldeyra Therapeutics little that could be done to improve This treatment is ideal for many pa- announced a novel allergy medication the appearance or functioning of a tients, particularly those with dexterity called reproxalap. Reactive aldehyde ptosis. Upneeq (oxymetazoline 0.1%) issues or ocular surface disease. species levels are highly elevated in was recently FDA-approved as a once There are numerous exciting and ef- allergic conjunctivitis and dry eye daily drop for the treatment of ac- fective pharmaceuticals at our disposal, disease. Positive, statistically signifi- quired blepharoptosis. It is an α1 and including new mechanisms of action cant top-line results from the Phase partial α2 adrenergic agonist capable and first-in-class therapeutics. They III clinical trial were observed in the of contracting Müller’s muscle. The can greatly help our patients with primary pre-specified endpoint and treatment elevated the upper eyelid ocular surface disease, glaucoma, TED all secondary endpoints. In the last about 2mm and statistically improved and even ptosis. It’s time to get famil- 20 years, only the steroid Alrex has the superior visual field, making this iar with these new medications that go achieved a sign-and-symptom label therapy an effective nonsurgical treat- far in helping us effectively manage for allergic conjunctivitis. ment for upper lid ptosis. our patients. ■

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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wear a whole bunch of masks. You have to admire his patience. So, load up. Looking to Be a Trendsetter? Cover up. All the cool kids are doing it. 6. Speaking of pandemics, I got my two vaccines. They may be protecting Yeah, Me Too me, but more important is that they’re I may not have a million followers on Instagram—or even have also a trend. “You haven’t had your vac- cines? Ewwwww!” Feeling superior to an account—but I do know a thing or two about things. others is the first step to feeling trendy. 7. I’ve noticed if a patient opts out nyone who knows me knows who want you to pay them to develop of widefield fundus photography and I am not at all trendy. Perhaps and maintain your full-service website. chooses dilation instead, they tend to that’s what has stifled every one Smart people. Trendy people. Now, not buy from your optical. Then they Aof my attempts to become a social websites are better than phone books, have to see you again before they leave influencer, which I’m told is a thing but they still need to hold a millennial’s the office, taking up more valuable time these days. Even though all you have to attention for longer than the time it and resources and offering next to noth- do to be a social influencer is say you are takes them to check a text while driving ing in return. It’s your call, but I would a social influencer, I still cannot succeed on (and sometimes off) the interstate. urge you to strongly encourage them to as one. That tells you something. But this whole trend of scheduling, come in yearly. And I personally would So, it should come at no surprise at all buying and sometimes even having an never be so presumptuous as to pre- that no one comes to me to learn about eye exam through a website is just plain appoint them. They’ll call, right? By the latest trends in optometry (or in any creepy. I can’t practice in Florida, but the way, three or four drops of atropine other area of interest for that matter, someone in Florida can check my Texas really dilate well. although I do know a lot about sneaking patient’s eyes and sell them glasses and 8. I guess the use of scribes is a trend. cookies past my wife). contacts! Where’s the Board? You see, we all have our charts on com- Still, I am undeterred. My crack team 4. Leasing cool, overpriced luxury puters in the exam rooms. Marketing of investigators assures me the list of vehicles is definitely a trend, companies have convinced us that trends I’ve put together is “in,” so here even for ODs. It’s okay. You having our records on comput- are “our” findings: should get to decide where ers is just wonderful. It is kinda 1. There is a growing glut in IT. to spend whatever little bit nice, but it takes us twice as Every freakin’ kid in the universe is go- of cash our benevolent long to complete ing to school to study IT. The more IT government decides the chart so we professionals there are, the less they’ll you get to keep (for need scribes to be paid. Perhaps your kid should be a now). But I always get it right. I like plumber. That’s the next trend because thought living in a having scribes for who wants to fix toilets? People who hut to give off the scribe purposes and want to get rich, that’s who. illusion that you can to blame dilation 2. In spite of our every attempt afford to drive an unaf- issues on (see #7). to keep patients from making grave fordable car was overrated. I also like hav- errors, giant glasses are coming back. 5. Wearing more masks ing scribes to see if I can find It’s a trend. What’s next? Crown glass? than anyone else is trendy. It’s diagnoses that aren’t found Executive trifocals in a +7 hyperope? hard for me to believe some anywhere in the EHR Say goodbye to each of your patient’s 80-year-old guy who sat quietly checklists they use. Makes nose and ears. for 50 years in a little office me feel superior/trendy. 3. ODs share a similar mindset by in Washington, DC, and Don’t follow every trend. Be thinking the only thing we have to do was paid to work crossword yourself. And don’t post stupid stuff. to stay in the game is have a full-service puzzles is now trending Nobody will stop following Dua Lipa to website. This trend was started by folks because he says you should make room for you anyway. 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.

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spicules noted in this case (Figure 2). Comanaging with a retina specialist Blindsided is not always necessary. However, A thorough, dilated examination of the retina is necessary to documenting the degree of vision and visual field loss as a baseline diagnose retinitis pigmentosa. is critical to monitor progression. Fundus photos, visual field testing and A 32-year-old mother of three electrodiagnostic testing if available Q came in for a routine exam with are other essential components of no complaints. Vision was 20/20, but diagnosis, according to Dr. Miller. confrontation fields were dramatically Electroretinograms (ERGs) measure constricted. The fundus exam confirmed the electrical response of the photo- retinitis pigmentosa (RP). How do I receptors and can help detect early deliver the news, and what are the next disease as well as distinguish between steps? retinal disease and optic nerve disease. A “Breaking this news to patients The multifocal ERG can measure is often more of a challenge than Fig. 1. VF reveals peripheral vision loss. responses in the fovea, which is more reaching the proper diagnosis,” says beneficial in later stages of R P. Chelsea Miller, OD, of Athens Family Vision Clinic in Athens, GA. In many Testing Responsibilities RP patients there is a known history, Referring a patient and their family and family members have a clear members for genetic testing is impor- understanding of the condition and tant. “The genetics of RP can vary, and its inheritance pattern. However, in a testing by a trained counselor may offer patient like ours, who presented for a information in terms of inheritance routine eye exam, this conversation can patterns and gene mutations as well as be a lot more difficult. Fig. 2. Bone spicules are a common a prognosis,” Dr. Miller says. After discussing a potentially devas- finding of most RP patients. There are risks and benefits to pre- tating diagnosis like RP with a patient, dicting the future of RP in asymptom- Dr. Miller believes ongoing support is less dense. Because rods are more af- atic family members without clinical important. They will have more ques- fected, complaints of difficulty seeing signs—either a false sense of security tions after they do their own research. in dim/dark lighting are common. In that they will never get it or a lifetime “In my experience, let the patient its end stages, RP can also causes a of fear that they will. One pro to ge- know that you are available to answer loss of cones and affect central vision netic testing in children of RP patients any further questions via phone, email and best-corrected visual acuity. The is that it may qualify them for clinical or future appointments,” she recom- inheritance pattern can be autosomal trials. Gene therapy research for certain mends. “Patients who know their eye dominant (30% to 40%), autosomal types of RP is currently underway, giv- care provider is reliable and accessible recessive (50% to 60%) or X-linked ing hope to patients in the future.2 will be very appreciative.” recessive (5% to 15%). RP can also In this specific case, genetic testing be associated with Leber’s congenital was performed using the patient’s RP Refresher amaurosis and Usher syndrome.1 saliva, which confirmed RP and will Retinitis pigmentosa is a progressive A thorough, dilated retinal also help determine the risk factors for condition that causes retinal degen- examination can determine if there is her children. g eration at the photoreceptor level. It any alteration in pigmentation and also 1. Natarajan S. Retinitis pigmentosa: a brief overview. Indian J affects rods initially and more severely detect the presence of bone spicules, Ophthalmol. 2011;59(5):343-6. than cones. Vision loss will begin in a common finding in RP patients. 2. Huang H, Chen Y, Chen H, et al. Systematic evaluation of a targeted gene capture sequencing panel for the periphery and gradually progress Considering the degree of field molecular diagnosis of retinitis pigmentosa. PLoS One. into the central vision, where rods are loss (Figure 1), there were few bone 2018;13(4):e0185237.

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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allowing the parasympathetic system to dominate, resulting in a miotic pupil Surveying the Cavern and ptosis. These features, with the addition of anhidrosis on the affected Take a closer look at how the features that make up this sinus side, constitute Horner’s syndrome.4 function—and can lead to dysfunction. Oculomotor nerve (CN III). Running along the superior-lateral wall of the cavernous sinus is CN III. In conjunc- he eye is an extension of the Deep Dive tion with the aforementioned sympa- brain and central nervous system. Often, observable ocular abnormalities thetic stimulation of the upper eyelid, Through a simple ocular exami- on clinical exam aid in identifying the CN III innervates the levator palpe- Tnation, we can glean significant source, if not also the etiology, of a pa- brae superioris, contributing to the insight into complex neurological pro- tient’s condition. Here’s what disrup- majority of eyelid elevation. Addition- cesses. Ophthalmologic examinations tions to the features of the cavernous ally, it innervates many ocular muscle thus serve as conduits through which sinus look like and tell us. branches, such as the superior rectus, we can detect and diagnose many ICA. The common carotid artery inferior rectus, medial rectus and infe- underlying neurologic conditions.1 (CCA) arises directly from the aorta rior oblique. Fibers also extend to the One of the anatomic conduits that on the left and indirectly on the right pupillary sphincter. As such, a lesion in connects the eye to the brain is the through the brachiocephalic artery. the cavernous sinus affecting the third cavernous sinus. This structure is one The CCA bifurcates within the neck, nerve causes ptosis that is more signifi- of two paired intracranial dural venous giving rise to the ICA, which contin- cant than in sympathetic dysfunction. sinuses located posterior to the orbit ues intracranially and gives off several Additionally, patients may have a and on either side of the sella turcica smaller branches.3 Surrounding the resting position where their eye is sit- of the sphenoid bone. Anteriorly, the ICA are postganglionic, sympathetic ting “down and out” due to the lack of cavernous sinus communicates directly fibers. The sympathetic system affects muscular innervation. If pupil involve- with the superior and inferior orbital many ocular structures and is respon- ment is present, dilation would be evi- fissures and indirectly with the ptery- sible for innervating the superior tarsal dent. A patient with CN III palsy may gopalatine fossa. muscle of the upper eyelid and the report symptoms of diagonal, binocular Its primary function is the transport pupil dilator. Sympathetic disruption diplopia and a drooping eyelid, among of deoxygenated blood. As such, it may occur in cavernous sinus disease, other side effects.5 communicates with numerous venous structures, including the superior and inferior ophthalmic veins, basal venous plexus, superficial middle cerebral vein and superior and inferior petrosal sinuses. The cavernous sinus is so much more than a simple vein. Many im- portant neurovascular structures travel through it due to its location between the orbit and brain proper. These in- clude the internal carotid artery (ICA), cranial nerve (CN) III, CN IV, two divisions of CN V (1 and 2) and CN VI. All the constituents of the cavern- MRI imaging of the brain through the cavernous sinus shows the lateral border of the right ous sinus are related to and have an cavernous sinus (blue), cavernous segment of the right ICA (red), left CN III (orange), left 2 B effect on ocular function. As such, it is CN IV (yellow) and left CN VI (green). The left CN V-1 and left CN V-2 are not well resolved important we understand them. (purple).

About Dr. Labib graduated from Pennsylvania College of Optometry, where she now works as an associate professor. She completed her residency in primary care/ocular Dr. Labib disease and is a fellow of the American Academy of Optometry and a diplomate in the Comprehensive Eye Care section. She has no financial interests to disclose.

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Trochlear nerve (CN IV). ing from the cavernous ICA Subadjacent to CN III The Function and Dysfunction of Cavernous Sinus Structures or venous thrombosis of within the lateral wall of the the cavernous sinus itself. Structure Ocular Function Ocular Dysfunction cavernous sinus is CN IV. Numerous tumors may arise This nerve, after exiting the ICA • Superior tarsal muscle • Horner’s syndrome from or invade the cavernous cavernous sinus, continues of upper eyelid (miosis, small ptosis, sinus, including schwan- anhidrosis) on its course to eventually in- • Pupil dilator noma, meningioma, extra- nervate the superior oblique CN III • Levator palpebrae • Larger ptosis medullary plasmacytoma, (SO) muscle. The SO is superioris • Diagonal binocular pituitary macroadenoma and the sole extraocular muscle • Superior rectus diplopia metastasis.9 Trauma may lead that is innervated by CN IV • Inferior rectus • Mydriasis to the formation of a cavern- and functions primarily as • Medial rectus ous-carotid fistula. Finally, a depressor. Secondary and inflammation may affect the • Inferior oblique tertiary functions include cavernous sinus in the form abduction and intorsion of • Pupillary sphincter of idiopathic orbital inflam- the eye. Patients with SO CN IV • Superior oblique • Diagonal binocular mation, also called Tolosa- palsies may report vertical diplopia worse on Hunt syndrome.2 or diagonal diplopia that is downgaze Pathology within the worse on downgaze. They • Head tilt cavernous sinus can lead may also have a compensa- CN V-1 • Sensory input orbital • Decreased sensation to many vision-threatening tory head tilt to balance out and supraorbital of the forehead and scenarios. But more than the torsional effect.6 portion above the eye that, these ocular signs and Trigeminal nerve (CN • Ciliary muscle symptoms may often be V). CN V consists of three • Lacrimal gland the initial heralds of a life- branches on either side to • Conjunctiva threatening cavernous sinus provide sensory and motor • Cornea syndrome. It is imperative function to the entire face. to identify and appropriately Only the first two of these CN V-2 • Sensory input to • Decreased sensation work up suspected cavernous branches, the ophthalmic infraorbital portion below the eye to sinus pathology with timely extending above the above the mouth (V-1) and maxillary (V-2), are mouth diagnostic neuroimaging and contained within the inferior referrals. aspect of the cavernous sinus. CN VI • Lateral rectus • Horizontal binocular In the event that multiple diplopia These two divisions are cranial nerves are implicated primarily sensory in func- on clinical examination, it is tion. The ophthalmic division provides positioned cranial nerve within the necessary to keep in mind this special- sensory innervation to the orbital and cavernous sinus, located just slightly ized intracranial compartment. g supraorbital portion of the face. It also inferior to the cavernous ICA. After 1. Yap TE, Balendra SI, Almonte MT, et al. Retinal cor- supplies various ocular structures, exiting the cavernous sinus, it even- relates of neurological disorders. Ther Adv Chronic Dis. such as the lacrimal gland, ciliary body, tually innervates the lateral rectus 2019;10:2040622319882205. cornea and conjunctiva. The maxil- muscle within the orbit. 2. Kuybu O, Dossani RH. Cavernous Sinus Syndromes. In: StatPearls [Internet]. Treasure Island, FL: StatPearls lary division innervates the infraorbital Patients with CN VI dysfunction Publishing; 2020. portion of the face above the mouth, as may report horizontal, binocular diplo- 3. von Arx T, Tamura K, Yukiya O, et al. The face—a vascular perspective. A literature review. Swiss Dent J. well as the maxillary teeth and sinuses. pia due to their inability to abduct the 2018;128(5):382-92. 8 Cavernous sinus pathology that af- eye. 4. Khan Z, Bollu PC. Horner Syndrome. In: StatPearls [Inter- fects the area housing these branches net]. Treasure Island, FL: StatPearls Publishing; 2020. 5. Margolin E, Freund P. Third nerve palsies: review. Int reduces sensation on the ipsilateral Take-home Message Ophthalmol Clin. 2019;59(3):99-112. 7 side of the face. This can be tested With a clear understanding of cavern- 6. Kim SY, Motlagh M, Naqvi IA. Neuroanatomy, Cranial clinically using the end of a tissue ous sinus anatomy, we can see how Nerve 4 (Trochlear). In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2020. or cotton wisp to stroke the area of pathology in and around the structure 7. Huff T, Daly DT. Neuroanatomy, Cranial Nerve 5 (Trigemi- distribution on either side while the leads to a myriad of ocular manifesta- nal). In: StatPearls [Internet]. Treasure Island, FL: StatPearls patient has their eyes closed, to check tions. These pathologic conditions of Publishing; 2020. 8. Graham C, Mohseni M. Abducens Nerve Palsy. In: Stat- for symmetry. the cavernous sinus typically fall into Pearls [Internet]. Treasure Island, FL: StatPearls Publishing; Abducens nerve (CN VI). Cranial one of four categories: vascular, tumor, 2020. nerve VI is responsible for the abduc- trauma or inflammation.2 Vascular 9. Labib ML, Som PM. Unusual extramedullary plasmacy- toma of the head and neck: a case series. Neurographics. tion of the eye. It is the most medially conditions include aneurysms aris- 2017;7(2):115-20.

30 REVIEW OF OPTOMETRY | MAY 15, 2021 IRIS/

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not necessarily relating to the primary diagnosis. If that isn’t the case, a Spring Renewal 992XX code is the way to go. The new With the change of the seasons comes opportunity. E&M code definitions make coding much easier since we have to provide a “medically appropriate history and pring hits different this year— coding for ocular surface disease. Keep examination,” but they can complicate one can sense the feeling of in mind that the CC must be stated in the medical necessity requirements renewal and optimism that comes terms of “complaints or symptoms of since it is now more subjective. Swith the rollout of the COVID an eye disease or injury” to meet the Personally, I prefer the 992XX codes vaccines and communities reopen- standard of invoking a patient’s medi- for medically related eye care visits. ing. How different from last year. One cal insurance benefits, and we want Think of them as structure- and func- thing, however, isn’t different. Spring- to be specific about these signs and tion-based coding hierarchy rather than time in the world of eye care brings symptoms particularly since we may the general overall evaluation a 920XX another feeling: the itch and discomfort be diagnosing and treating multiple code provides. Always code each pa- of ocular surface disease (OSD). concurrent conditions. If providing a tient encounter by the individual case physician-directed return office visit, presentation, as well as the individual Beware Allergy Season the CC should be implicit; e.g., “patient patient you are examining and treating, OSD is a broad and common presen- returning for physician directed visit using the choices that you have using tation in our offices. We often think secondary to findings consistent with either total time or medical decision about dry eye when we hear OSD, but (insert signs and symptoms here).” making as your coding criterion. don’t forget that OSD incorporates lid When doing ancillary testing, most disease as well as other conjunctival of the additional tests that you perform and corneal issues. OSD also often While some conditions, such will be incidental to the office visit occurs with other disease states, such as seasonal allergies, are and not separately billable. Measur- as ocular allergy. When we think about acute, many are chronic and ing tear volume whether by evaluat- proper diagnosis and treatment of the ing the meniscus or by Schirmer are require continuing care. entire ocular surface, it is critical that not separately billable procedures. our medical record keeping maintains Standing orders for clinical lab tests proper detail to support our billings. Once the CC requirement has been for inflammation (MMP-9) and tear Understanding the fundamentals of met, then you can proceed with your osmolarity are common if the patient determining the proper type of medical evaluation. Be mindful that the level of has documented signs and symptoms office visit (920XX or 992XX) is essen- the office visit must be proportional to from a qualified questionnaire. How- tial for proper medical record compli- the level of the disease state. Never as- ever, adjunctive items like photos, lid ance and patient management. While sume or code an office visit based upon debridement and meibography must some conditions that we treat, such as the patient diagnosis but rather on the have a clear path of medical necessity seasonal allergies, are acute, many are medically necessary individual compo- established in the record in order for chronic and require continuing care. nents that you performed. Don’t forget: them to be legitimately performed— Set expectations with these patients, with the change in 2021 E&M coding and don’t forget the interpretation and as this is not a one- or two-visit process rules, you can choose to use either total report requirement with any special but ongoing management. By most time or medical decision making to ophthalmic testing. OSD protocols, you may be seeing this determine the office visit level. Diseases that affect the ocular patient two to four times per year in ad- When differentiating between a surface can be seasonally acute or dition to their general refractive care. 920XX code and a 992XX code, a chronic, but pollen isn’t the only thing 92012 requires that the patient present in the air this spring—it’s optimism and Proper Protocol with a new condition or an existing opportunity. ■ The chief complaint becomes the condition complicated with a new Send your coding questions to epicenter of our medical record when diagnostic or management problem [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 | MAY 15, 2021 ™ SCLERALAtlantis

© 2021 X-Cel Specialty Contacts Feature SYSTEMIC MEDICATIONS PEER REVIEWED

Stay Alert for Systemic Med Surprises

Many ocular adverse effects may be hiding inside your patient’s pill bottle. Here’s a new way to think about them.

AARON case, od Photo: Jay Pepose, MD, PhD Photo: Sara Weidmayer, OD fort wayne, in joy kerns, od wyoming, mi sara weidmayer, od grand rapids, mi he list of systemic drugs that may have ocular effects is enormous. While perusing a patient’s medi- tcation list and considering all the possible effects can be daunting, it is Fig. 1. Amiodarone causes corneal whorl Fig. 2. Early subepithelial refractile important to be watchful and educate keratopathy, or corneal verticillata, visible deposits in a patient on macrolide therapy the patient about any concerning ocular at the level of the basal epithelium. for chronic obstructive pulmonary disease. complications that could potentially arise. However, rather than the typi- grouping the findings by ocular location starts at approximately three weeks and cal “this medication can cause these or function to help allow that “retrace is generally reversible within months of effects” mentality, it’s often more clini- your steps” approach to connecting discontinuation of the medicine. Vortex cally relevant to think of it the other presentations to medications. keratopathies rarely have any effect on way around: “With this clinical finding, acuity but can cause blurry vision or, on could one of the patient’s medications Cornea rare occasions, even corneal ulceration. be causing the problem?” This sort Some of the most readily apparent Drug-related keratopathies generally of effectgcause rather than causegeffect effects of systemic meds appear in the resolve with discontinuation of the of- thinking can help you when you’re cornea, given the structure’s ease of fending agent. confronting a clinical finding in your observation to patient and doctor alike. Drugs causing vortex epithelial chair and need to think backwards to Many drugs allow drug penetrance into deposits include amiodarone, hydroxy- determine the source. cells with the potential for phospho- chloroquine, chlorpromazine, tamoxi- Here, we’ll touch on some of the lipid accumulation intracellularly. This fen, nonsteroidal anti-inflammatory more commonly encountered ocular manifests in the eye as vortex (or whorl) drugs, atovaquone, suramin, perhexi- side effects related to systemic meds, keratopathy (Figure 1). The finding line maleate and aminoglycosides.1

Dr. Case is an attending and residency director at the Fort Wayne VA NIHCS Eye Clinic, an adjunct assistant professor with Indian University and a clinical associate professor with the Michigan College of Optometry. Dr. Kerns practices at the Wyoming VA Community Based Outpatient Clinic in About the authors Wyoming, Michigan, and is on clinical faculty for the Michigan College of Optometry, Illinois College of Optometry and Pennsylvania College of Optometry. Dr. Weidmayer practices at the VA Ann Arbor Healthcare System and is a clinical assistant professor for the University of Michigan’s Department of Ophthalmology & Visual Sciences. None of the authors have any financial interests to disclose.

34 REVIEW OF OPTOMETRY | MAY 15, 2021 Similarly, many drugs are subject to system. Whether systemic, topical, in- the medication. Patients should have a lysosomal sequestration or drug precipi- halant, nasal spray or injected, they can baseline dilated fundus exam prior to tation, which can lead to a crystalline produce posterior subcapsular cataract initiating INF-α therapy, then follow- keratopathy. These often begin as a (PSC) in both adults and children, and up every three to six months through- diffuse punctate subepithelial deposit, do appear to be dose- and time-depen- out the course of treatment. The which may become more linear. In dent. While the lenticular changes may finding of retinopathy is not typically a contrast to whorl forms, crystalline-like progress or remain stationary, they will reason to discontinue treatment unless keratopathies are more likely to elicit rarely reverse with discontinuation of there’s associated acute vision loss, and a decrease in acuity, especially when the medication. The cataract typically the retinopathy most often resolves less caused by antineoplastic agents. begins as a PSC but can gradually prog- than one month after completion of Inciting agents include benoquine, ress to appear similar to other types, treatment.5 tilorone, macrolide antibiotics, clofazi- including senile cataract.2 Patients on Tamoxifen (Soltamox). This anti- mine, gold salts and multiple antineo- corticosteroids should be educated on estrogen medication is used to treat plastic agents, including vandetanib, the possibility of cataract formation and estrogen receptor–positive breast can- osimertinib, cytarabine and emtansine have routine eye evaluations. cer, ovarian cancer, pancreatic cancer (Figure 2).1 While discontinuing the and malignant melanoma.6 The retinal offending agent may be impossible, it’s Retina findings most often associated with it important to identify the correlation Access to the vasculature makes the include small refractive bodies in the and communicate with the prescribing retina fertile ground for complications inner retina, which appear like dot-like physician to consider titrating to a toler- of systemic med use. yellowish deposits surrounding the able dose. Interferon (Intron A, Roferon-A). The macula.2 Patients may also be at risk for While any topical ophthalmic drug interferons (IFNs) are glycoproteins development of pseudocystic cavitary containing the common preservative classified as cytokines and used primar- spaces—without macular edema— benzalkonium chloride (BAK) can ily for hepatitis C virus (HCV). Specifi- which may only be visible on SD-OCT independently elicit corneal edema, cally, INF-α used to treat HCV that is imaging. as can several topical antiseptics, it is associated with ocular manifestations. The OCT appearance of the condi- a very rare complication of systemic The most common finding is INF-α tion appears very similar to that of medications. Most notably, amanta- associated retinopathy, predominantly idiopathic macular telangiectasia type dine—an anti-Parkinson’s drug—has with cotton wool spots and flame- 2 and has been found to occur early in been demonstrated to reversibly pro- shaped hemorrhages in the posterior treatment, at low doses of the drug; it voke corneal edema in rare cases. pole radiating from the optic nerve is irreversible.7 There is also a more (Figure 3). These findings rarely cause severe form of retinopathy that can Lens significant visual disturbance and may include cystoid macular edema, retinal Early cataract formation is the most go undetected due to lack of patient hemorrhages and optic nerve edema, likely drug-related effect we commonly symptoms. Risk factors include type and is associated with vision loss. This see in practice. 2 diabetes, systemic hypertension, in- more acute form of toxicity is most Phenothiazines (chlorpromazine, thiorid- creasing age and duration of treatment. likely to occur only after a few weeks of azine). This is a group of psychotropic Retinal changes usually occur by starting therapy whereas the less severe medications used to treat serious men- week 12 of therapy but can take as form usually occurs after more than one tal disorders including schizophrenia long as 28 weeks to manifest. Typi- year of treatment, when a total of more and psychoses. These drugs, specifi- cally, the retinopathy will resolve on its than 100 grams of the drug has been cally chlorpromazine and thioridazine, own, even with the continued use of dosed.6 are associated with cataract formation in Photo: Sara Weidmayer, OD the anterior subcapsular layers and are nearly always associated with pigment accumulation.2 Over time, this pigment can become arranged in a stellate pat- tern, but is rarely associated with visual impairment.3 These opacities are rarely bilateral but are typically asymmetric when they are, and are not likely to re- verse with cessation of the medication.4 Glucocorticoids. These are a group of corticosteroid hormones used to reduce inflammation and suppress the immune Fig. 3. Interferon retinopathy with cotton wool spots.

MAY 15, 2021 | REVIEW OF OPTOMETRY 35 Help your patients with DIABETIC RETINOPATHY (DR), and HELP DRIVE PATIENT OUTCOMES Through early detection, monitoring, and timely referral, you can play a pivotal role in managing your DR patients’ vision1-3

IF YOU SEE OR SUSPECT DR:

Educate your patients Refer Follow up about living with DR and DR patients for timely to ensure they potential treatment options2,3 intervention have visited a • According to the AOA, you retina specialist should refer patients with2,3 – Severe nonproliferative DR (NPDR) within 2 to 4 weeks – Proliferative DR (PDR) within 1 week

INDICATIONS AND IMPORTANT SAFETY INFORMATION EYLEA® (aflibercept) Injection 2 mg (0.05 mL) is indicated for the treatment of patients with Neovascular (Wet) Age-related Macular Degeneration (AMD), Macular Edema following Retinal Vein Occlusion (RVO), Diabetic Macular Edema (DME), and Diabetic Retinopathy (DR). CONTRAINDICATIONS • EYLEA is contraindicated in patients with ocular or periocular infections, active intraocular inflammation, or known hypersensitivity to aflibercept or to any of the excipients in EYLEA. WARNINGS AND PRECAUTIONS • Intravitreal injections, including those with EYLEA, have been associated with endophthalmitis and retinal detachments. Proper aseptic injection technique must always be used when administering EYLEA. Patients should be instructed to report any symptoms suggestive of endophthalmitis or retinal detachment without delay and should be managed appropriately. Intraocular inflammation has been reported with the use of EYLEA.

References: 1. Early Treatment Diabetic Retinopathy Study Research Group. Fundus photographic risk factors for progression of diabetic retinopathy. ETDRS report number 12. Ophthalmology. 1991;98(5 suppl):823-833. 2. Care of the Patient With Diabetes Mellitus: Quick Reference Guide. American Optometric Association website. http://bit.ly/2M22OUJ. Accessed August 7, 2019. 3. Ferrucci S, Yeh B. Diabetic retinopathy by the numbers. Rev Optom. June 15, 2016. http://bit.ly/2KNNJ4E. Accessed August 7, 2019.

EYLEA is a registered trademark of Regeneron Pharmaceuticals, Inc.

© 2020, Regeneron Pharmaceuticals, Inc. All rights reserved. 777 Old Saw Mill River Road, Tarrytown, NY 10591 Brought to you by REGENERON

Visit diabeticretinaldisease.com for additional information and useful patient resources

Continue to monitor The more you know about emerging clinical your patients with DR2,3 science about anti-VEGF and other potential therapies • The AOA recommends frequent for DR, the better you can help inform your patients monitoring of patients2 about how treatment may be able to help – At least every 6 to 8 months in Refer patients to a retina specialist patients with moderate NPDR who can treat DR2,3 and more frequently for patients with greater disease severity2

WARNINGS AND PRECAUTIONS (cont’d) • Acute increases in intraocular pressure have been seen within 60 minutes of intravitreal injection, including with EYLEA. Sustained increases in intraocular pressure have also been reported after repeated intravitreal dosing with VEGF inhibitors. Intraocular pressure and the perfusion of the optic nerve head should be monitored and managed appropriately. • There is a potential risk of arterial thromboembolic events (ATEs) following intravitreal use of VEGF inhibitors, including EYLEA. ATEs are defined as nonfatal stroke, nonfatal myocardial infarction, or vascular death (including deaths of unknown cause). The incidence of reported thromboembolic events in wet AMD studies during the first year was 1.8% (32 out of 1824) in the combined group of patients treated with EYLEA compared with 1.5% (9 out of 595) in patients treated with ranibizumab; through 96 weeks, the incidence was 3.3% (60 out of 1824) in the EYLEA group compared with 3.2% (19 out of 595) in the ranibizumab group. The incidence in the DME studies from baseline to week 52 was 3.3% (19 out of 578) in the combined group of patients treated with EYLEA compared with 2.8% (8 out of 287) in the control group; from baseline to week 100, the incidence was 6.4% (37 out of 578) in the combined group of patients treated with EYLEA compared with 4.2% (12 out of 287) in the control group. There were no reported thromboembolic events in the patients treated with EYLEA in the first six months of the RVO studies. ADVERSE REACTIONS • Serious adverse reactions related to the injection procedure have occurred in <0.1% of intravitreal injections with EYLEA including endophthalmitis and retinal detachment. • The most common adverse reactions (≥5%) reported in patients receiving EYLEA were conjunctival hemorrhage, eye pain, cataract, vitreous detachment, vitreous floaters, and intraocular pressure increased. Please see Brief Summary of Prescribing Information on the following pages.

03/2020 anti-VEGF = anti–vascular endothelial growth factor; AOA = American Optometric Association. EYL.20.02.0082 BRIEF SUMMARY—Please see the EYLEA Table 2: Most Common Adverse Reactions (≥1%) in RVO Studies full Prescribing Information available CRVO BRVO on HCP.EYLEA.US for additional EYLEA Control EYLEA Control Adverse Reactions (N=218) (N=142) (N=91) (N=92) product information. Eye pain 13% 5% 4% 5% Conjunctival hemorrhage 12% 11% 20% 4% Intraocular pressure increased 8% 6% 2% 0% 1 INDICATIONS AND USAGE Corneal epithelium defect 5% 4% 2% 0% EYLEA is a vascular endothelial growth factor (VEGF) inhibitor indicated for the treatment of: Vitreous floaters 5% 1% 1% 0% Neovascular (Wet) Age-Related Macular Degeneration (AMD); Macular Edema Following Retinal Vein Occlusion (RVO); Diabetic Ocular hyperemia 5% 3% 2% 2% Macular Edema (DME); Diabetic Retinopathy (DR). Foreign body sensation in eyes 3% 5% 3% 0% 4 CONTRAINDICATIONS Vitreous detachment 3% 4% 2% 0% 4.1 Ocular or Periocular Infections Lacrimation increased 3% 4% 3% 0% EYLEA is contraindicated in patients with ocular or periocular infections. Injection site pain 3% 1% 1% 0% 4.2 Active Intraocular Inflammation Vision blurred 1% <1% 1% 1% EYLEA is contraindicated in patients with active intraocular inflammation. Intraocular inflammation 1% 1% 0% 0% 4.3 Hypersensitivity Cataract <1% 1% 5% 0% EYLEA is contraindicated in patients with known hypersensitivity to aflibercept or any of the excipients in EYLEA. Hypersensitivity Eyelid edema <1% 1% 1% 0% reactions may manifest as rash, pruritus, urticaria, severe anaphylactic/anaphylactoid reactions, or severe intraocular inflammation. Less common adverse reactions reported in <1% of the patients treated with EYLEA in the CRVO studies were corneal edema, retinal 5 WARNINGS AND PRECAUTIONS tear, hypersensitivity, and endophthalmitis. 5.1 Endophthalmitis and Retinal Detachments. Intravitreal injections, including those with EYLEA, have been associated with endophthalmitis and retinal detachments [see Adverse Diabetic Macular Edema (DME) and Diabetic Retinopathy (DR). The data described below reflect exposure to EYLEA in 578 patients Reactions (6.1)]. Proper aseptic injection technique must always be used when administering EYLEA. Patients should be instructed with DME treated with the 2-mg dose in 2 double-masked, controlled clinical studies (VIVID and VISTA) from baseline to week 52 and to report any symptoms suggestive of endophthalmitis or retinal detachment without delay and should be managed appropriately from baseline to week 100. [see Patient Counseling Information (17)]. Table 3: Most Common Adverse Reactions (≥1%) in DME Studies 5.2 Increase in Intraocular Pressure. Acute increases in intraocular pressure have been seen within 60 minutes of intravitreal injection, including with EYLEA [see Adverse Baseline to Week 52 Baseline to Week 100 Reactions (6.1)]. Sustained increases in intraocular pressure have also been reported after repeated intravitreal dosing with vascular EYLEA Control EYLEA Control endothelial growth factor (VEGF) inhibitors. Intraocular pressure and the perfusion of the optic nerve head should be monitored and Adverse Reactions (N=578) (N=287) (N=578) (N=287) managed appropriately. Conjunctival hemorrhage 28% 17% 31% 21% 5.3 Thromboembolic Events. There is a potential risk of arterial thromboembolic events (ATEs) following intravitreal use of VEGF inhibitors, including EYLEA. ATEs Eye pain 9% 6% 11% 9% are defined as nonfatal stroke, nonfatal myocardial infarction, or vascular death (including deaths of unknown cause). The incidence of Cataract 8% 9% 19% 17% reported thromboembolic events in wet AMD studies during the first year was 1.8% (32 out of 1824) in the combined group of patients Vitreous floaters 6% 3% 8% 6% treated with EYLEA compared with 1.5% (9 out of 595) in patients treated with ranibizumab; through 96 weeks, the incidence was Corneal epithelium defect 5% 3% 7% 5% 3.3% (60 out of 1824) in the EYLEA group compared with 3.2% (19 out of 595) in the ranibizumab group. The incidence in the DME Intraocular pressure increased 5% 3% 9% 5% studies from baseline to week 52 was 3.3% (19 out of 578) in the combined group of patients treated with EYLEA compared with 2.8% (8 out of 287) in the control group; from baseline to week 100, the incidence was 6.4% (37 out of 578) in the combined group of Ocular hyperemia 5% 6% 5% 6% patients treated with EYLEA compared with 4.2% (12 out of 287) in the control group. There were no reported thromboembolic events Vitreous detachment 3% 3% 8% 6% in the patients treated with EYLEA in the first six months of the RVO studies. Foreign body sensation in eyes 3% 3% 3% 3% 6 ADVERSE REACTIONS Lacrimation increased 3% 2% 4% 2% The following potentially serious adverse reactions are described elsewhere in the labeling: Vision blurred 2% 2% 3% 4% • Hypersensitivity [see Contraindications (4.3)] Intraocular inflammation 2% <1% 3% 1% • Endophthalmitis and retinal detachments [see Warnings and Precautions (5.1)] • Increase in intraocular pressure [see Warnings and Precautions (5.2)] Injection site pain 2% <1% 2% <1% Eyelid edema <1% 1% 2% 1% • Thromboembolic events [see Warnings and Precautions (5.3)] 6.1 Clinical Trials Experience. Less common adverse reactions reported in <1% of the patients treated with EYLEA were hypersensitivity, retinal detachment, retinal Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug tear, corneal edema, and injection site hemorrhage. cannot be directly compared to rates in other clinical trials of the same or another drug and may not reflect the rates observed Safety data observed in 269 patients with nonproliferative diabetic retinopathy (NPDR) through week 52 in the PANORAMA trial were in practice. consistent with those seen in the phase 3 VIVID and VISTA trials (see Table 3 above). A total of 2980 patients treated with EYLEA constituted the safety population in eight phase 3 studies. Among those, 2379 patients 6.2 Immunogenicity. were treated with the recommended dose of 2 mg. Serious adverse reactions related to the injection procedure have occurred in <0.1% As with all therapeutic proteins, there is a potential for an immune response in patients treated with EYLEA. The immunogenicity of intravitreal injections with EYLEA including endophthalmitis and retinal detachment. The most common adverse reactions (≥5%) of EYLEA was evaluated in serum samples. The immunogenicity data reflect the percentage of patients whose test results were reported in patients receiving EYLEA were conjunctival hemorrhage, eye pain, cataract, vitreous detachment, vitreous floaters, and considered positive for antibodies to EYLEA in immunoassays. The detection of an immune response is highly dependent on the intraocular pressure increased. sensitivity and specificity of the assays used, sample handling, timing of sample collection, concomitant medications, and underlying Neovascular (Wet) Age-Related Macular Degeneration (AMD). The data described below reflect exposure to EYLEA in 1824 patients disease. For these reasons, comparison of the incidence of antibodies to EYLEA with the incidence of antibodies to other products with wet AMD, including 1223 patients treated with the 2-mg dose, in 2 double-masked, controlled clinical studies (VIEW1 and VIEW2) may be misleading. for 24 months (with active control in year 1). In the wet AMD, RVO, and DME studies, the pre-treatment incidence of immunoreactivity to EYLEA was approximately 1% to 3% across Safety data observed in the EYLEA group in a 52-week, double-masked, Phase 2 study were consistent with these results. treatment groups. After dosing with EYLEA for 24-100 weeks, antibodies to EYLEA were detected in a similar percentage range of patients. There were no differences in efficacy or safety between patients with or without immunoreactivity. Table 1: Most Common Adverse Reactions (≥1%) in Wet AMD Studies Baseline to Week 52 Baseline to Week 96 8 USE IN SPECIFIC POPULATIONS. 8.1 Pregnancy Active Control Control Risk Summary EYLEA (ranibizumab) EYLEA (ranibizumab) Adequate and well-controlled studies with EYLEA have not been conducted in pregnant women. Aflibercept produced adverse Adverse Reactions (N=1824) (N=595) (N=1824) (N=595) embryofetal effects in rabbits, including external, visceral, and skeletal malformations. A fetal No Observed Adverse Effect Level Conjunctival hemorrhage 25% 28% 27% 30% (NOAEL) was not identified. At the lowest dose shown to produce adverse embryofetal effects, systemic exposures (based on AUC for Eye pain 9% 9% 10% 10% free aflibercept) were approximately 6 times higher than AUC values observed in humans after a single intravitreal treatment at the recommended clinical dose [see Animal Data]. Cataract 7% 7% 13% 10% Animal reproduction studies are not always predictive of human response, and it is not known whether EYLEA can cause fetal harm Vitreous detachment 6% 6% 8% 8% when administered to a pregnant woman. Based on the anti-VEGF mechanism of action for aflibercept, treatment with EYLEA may Vitreous floaters 6% 7% 8% 10% pose a risk to human embryofetal development. EYLEA should be used during pregnancy only if the potential benefit justifies the Intraocular pressure increased 5% 7% 7% 11% potential risk to the fetus. Ocular hyperemia 4% 8% 5% 10% All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth Corneal epithelium defect 4% 5% 5% 6% defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Detachment of the retinal pigment epithelium 3% 3% 5% 5% Data Injection site pain 3% 3% 3% 4% Animal Data Foreign body sensation in eyes 3% 4% 4% 4% In two embryofetal development studies, aflibercept produced adverse embryofetal effects when administered every three days Lacrimation increased 3% 1% 4% 2% during organogenesis to pregnant rabbits at intravenous doses ≥3 mg per kg, or every six days during organogenesis at subcutaneous Vision blurred 2% 2% 4% 3% doses ≥0.1 mg per kg. Intraocular inflammation 2% 3% 3% 4% Adverse embryofetal effects included increased incidences of postimplantation loss and fetal malformations, including anasarca, umbilical hernia, diaphragmatic hernia, gastroschisis, cleft palate, ectrodactyly, intestinal atresia, spina bifida, encephalomeningocele, Retinal pigment epithelium tear 2% 1% 2% 2% heart and major vessel defects, and skeletal malformations (fused vertebrae, sternebrae, and ribs; supernumerary vertebral arches Injection site hemorrhage 1% 2% 2% 2% and ribs; and incomplete ossification). The maternal No Observed Adverse Effect Level (NOAEL) in these studies was 3 mg per kg. Eyelid edema 1% 2% 2% 3% Aflibercept produced fetal malformations at all doses assessed in rabbits and the fetal NOAEL was not identified. At the lowest Corneal edema 1% 1% 1% 1% dose shown to produce adverse embryofetal effects in rabbits (0.1 mg per kg), systemic exposure (AUC) of free aflibercept was Retinal detachment <1% <1% 1% 1% approximately 6 times higher than systemic exposure (AUC) observed in humans after a single intravitreal dose of 2 mg. 8.2 Lactation Less common serious adverse reactions reported in <1% of the patients treated with EYLEA were hypersensitivity, retinal tear, and Risk Summary endophthalmitis. There is no information regarding the presence of aflibercept in human milk, the effects of the drug on the breastfed infant, or the effects of the drug on milk production/excretion. Because many drugs are excreted in human milk, and because the potential for Macular Edema Following Retinal Vein Occlusion (RVO). The data described below reflect 6 months exposure to EYLEA with a absorption and harm to infant growth and development exists, EYLEA is not recommended during breastfeeding. monthly 2 mg dose in 218 patients following CRVO in 2 clinical studies (COPERNICUS and GALILEO) and 91 patients following BRVO in The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for EYLEA and any one clinical study (VIBRANT). potential adverse effects on the breastfed child from EYLEA. 8.3 Females and Males of Reproductive Potential Contraception Females of reproductive potential are advised to use effective contraception prior to the initial dose, during treatment, and for at least 3 months after the last intravitreal injection of EYLEA. Infertility There are no data regarding the effects of EYLEA on human fertility. Aflibercept adversely affected female and male reproductive systems in cynomolgus monkeys when administered by intravenous injection at a dose approximately 1500 times higher than the systemic level observed humans with an intravitreal dose of 2 mg. A No Observed Adverse Effect Level (NOAEL) was not identified. These findings were reversible within 20 weeks after cessation of treatment. 8.4 Pediatric Use. The safety and effectiveness of EYLEA in pediatric patients have not been established. 8.5 Geriatric Use. In the clinical studies, approximately 76% (2049/2701) of patients randomized to treatment with EYLEA were ≥65 years of age and M¨nufactured by: approximately 46% (1250/2701) were ≥75 years of age. No significant differences in efficacy or safety were seen with increasing age Regeneron Pharmaceuticals, Inc. Issue Date: 08/2019 in these studies. 777 Old Saw Mill River Road Initial U.S. Approval: 2011 Tarrytown, NY 10591 17 PATIENT COUNSELING INFORMATION Based on the August 2019 In the days following EYLEA administration, patients are at risk of developing endophthalmitis or retinal detachment. If the EYLEA ©s a registered trademark of Regeneron EYLEA® (aflibercept) Injection full eye becomes red, sensitive to light, painful, or develops a change in vision, advise patients to seek immediate care from an Pharmaceuticals, Inc. Prescribing Information. ophthalmologist [see Warnings and Precautions (5.1)]. © 2019, Regeneron Pharmaceuticals, Inc. Patients may experience temporary visual disturbances after an intravitreal injection with EYLEA and the associated eye examinations All rights reserved. EYL.19.07.0306 [see Adverse Reactions (6)]. Advise patients not to drive or use machinery until visual function has recovered sufficiently. Feature SYSTEMIC MEDICATIONS Photo: Sara Weidmayer, OD Patients should have a baseline eye exam and yearly screening with a dilat- ed fundus examination and SD- OCT imaging. If ocular manifestations are present, it is recommended to consult with the patient’s oncologist as a change in dosage or discontinuation of the drug may be indicated.7 Canthaxanthine (Orobronze). A naturally occurring carotenoid whose oral consumption may cause bronzing of the skin, canthaxanthine is sold over the counter as a tanning agent. This substance has been FDA approved for use as an artificial food coloring agent but not for any other use. Fig. 4. Classic advanced hydroxychloroquine-induced toxic maculopathy showing parafoveal Orobronze deposits in all layers of the RPE/outer retinal loss (yellow arrows on OCT), hypoAF on FAF imaging and corresponding paracentral visual field defects. retina with a preference for the more superficial layers and will appear as Monitoring should include a baseline and has subsequently been bolstered very small, gold-like particles near the exam within one year of initiating thera- by larger population studies. Current macula.6 The associated retinopathy py, then biannual exams after five years evidence suggests a dose-dependent does appear to be dose-dependent, and of use including OCT and 10-2 thresh- pattern of damage with caution in is found in 50% of patients who have old visual fields. FAF and mfERG may anyone with a cumulative exposure taken at least 37 grams and nearly 100% have utility in early detection. Early of greater than 500g. Color fundus of those who have consumed at least 60 findings in OCT may show disruption photos, OCT, FAF and near-infrared grams of the drug. Most patients will be of the outer ellipsoid zone and parafo- reflectance (nearIR) imaging are key asymptomatic; however, occasionally veal thinning of the outer nuclear layer, to detection. Fundus evaluation will it can cause abnormal dark adaptation. which may progress to “flying saucer” demonstrate yellow deposits at the The retinal deposits do resolve with the sign with advanced toxicity. level of the retinal pigmented epithe- discontinuation of the drug.8 FAF may demonstrate early patchy lium (RPE), which correlate to hyper- hyperautofluorescence (hyperAF) cir- reflective focal RPE thickening via Macula cumferentially around the fovea, which OCT. Similarly, these deposits correlate Here we encounter some of the heavy- may coalesce to a ring in advanced dis- to hyperAF on FAF and hyperreflec- hitters most familiar to optometrists, ease. mfERG studies are sensitive but tive patches on nearIR imaging, which especially Plaquenil, with which we widely variable and are of limited value show highly disorganized patterns and have a long history. in isolation. Threshold visual fields will irregularity in excess of what might be Hydroxychloroquine (Plaquenil). The similarly show patchy shallow depres- predicted by fundus evaluation. choloroquines are a class of chemo- sions circumferentially about the fovea A hyperAF halo may be evident in therapeutic agents and a mainstay as which will coalesce into continuous, the peripapillary region (Figure 5).9 both treatment and prophylaxis against deeper scotomas in advanced disease. The clinical course and endpoints are malarial disease and Q fever. Hydroxy- Of note, Asian patients tend to have unknown, but maculopathy can evolve chloroquine is effective in managing defects more peripherally in the macula after discontinuation and patients various autoimmune conditions, includ- and should be evaluated with a 24-2 should be followed at regular intervals. ing rheumatoid arthritis, Sjögren’s, visual field. The chance of retinal toxic- Phenothiazines (multiple trade names). lupus and porphyria cutanea tarda. ity increases with time and has as high This drug class encompasses a larger The ophthalmic complications as a 20% risk at 20 years.9 Concurrent group of antipsychotic agents in which primarily lie in its ability to produce a use of tamoxifen increases the risk of thioridazine and chlorpromazine are toxic maculopathy in a dose-dependent maculopathy fivefold. the most prescribed. They have been manner. Findings include a bull’s-eye Pentosan polysulfate sodium (Elmiron). largely supplanted by newer medica- maculopathy in the late stages, as- PPS is an oral medication approved for tions— especially in chronic therapy— sociated with more subtle findings on the relief of bladder pain or discomfort but are still commonly used. OCT, fundus autofluorescence (FAF), associated with interstitial cystitis/pain- In contrast to most toxic maculopa- multifocal electroretinogram (mfERG) ful bladder syndrome. thies, the macular toxicity seen here is and threshold perimetry findings in the A unique pigmentary maculopathy more dependent on daily doses rather early stages (Figure 4). was only recently elucidated in 2018 than a cumulative one. The mechanism

MAY 15, 2021 | REVIEW OF OPTOMETRY 39 Feature SYSTEMIC MEDICATIONS Photo: Sara Weidmayer, OD which makes it very difficult to estab- lish a definite association between the two.2 It is recommended that these drugs be avoided in patients who have experienced NAION in one eye, as they may be more likely to develop the condition in the same or fellow eye.6 Amiodarone (Pacerone). An anti-ar- rhythmic drug, amiodarone is one of the most effective medications available to treat various cardiac arrhythmias. While the exact mechanism is unknown, there is a probable associa- tion between amiodarone use and optic neuropathy. However, note that the neuropathy secondary to amiodarone Fig. 5. Multimodal imaging demonstrating collocated yellow deposits, RPE thickening, near use differs from typical NAION in that infrared hyper-reflectance and hyperAF on FAF imaging in advanced Elmiron maculopathy. the condition is bilateral, associated vi- sion loss progresses slowly over several of damage is not completely under- established, there are multiple case months and the degree of vision loss stood, but they are thought to disrupt reports describing acute-onset bilateral tends to be less severe. The disc edema rhodopsin synthesis.11 maculopathies in otherwise healthy is also much slower to improve when Onset of visual symptoms typi- eyes following initiation of therapy at compared to NAION, which can help cally occurs within weeks of initiating standard doses, whose findings closely distinguish between the two. therapy in doses greater than 800mg mimic those in advanced hydroxychlo- Patients on amiodarone should have a daily of thioridazine and 1200mg daily roquine toxicity.13 While maculopathies baseline exam with follow-up every 12 of chlorpromazine. In the early stages, appear infrequently, the reported cases months, or immediately should visual course granular pigmentation occurs, are profound, so be aware of this poten- symptoms occur. followed by patchy RPE loss with a tial adverse effect given the widespread If optic neuropathy is suspected, it’s characteristic ovoid shape extending to use of this medication. recommended that the decision to dis- the midperipheral retina. In late stages, continue the medication be discussed widespread areas of depigmentation Optic Nerve with that patient’s prescribing cardiolo- and hyperpigmented plaques are vis- As we encounter neuro-ophthalmic gist. Once the drug has been discontin- ible, followed by geographic atrophy. involvement, the potential for serious ued, it may take several months for the At most doses, benign pigmented vision loss escalates. edema to resolve, ultimately leaving the corneal and anterior lens opacities can Phosphodiesterase Type 5 (PDE5) patient with optic atrophy (Figure 6).6 also occur. OCT can reveal photore- Inhibitors (Viagra, Levitra, Cialis). This Vigabatrin (Sabril). An anticonvul- ceptor loss, which may span the fovea class of drugs is used to treat erectile sant used in the treatment of seizures, extending far into the arcades. There is dysfunction (ED). There has been an vigabatrin is most often used to manage typically some measure of visual recov- association between PED5 inhibitors drug-resistant partial seizures and infan- ery upon discontinuation.12 In standard and non-arteritic anterior ischemic tile spasms. doses, routine exams are sufficient optic neuropathy (NAION); however, It has been associated with vi- for monitoring, while symptomatic there has been no evidence confirming sual field loss and optic nerve atrophy, individuals should be examined within a cause-effect relationship. The clinical although the exact mechanism is un- the week. Alternate meds should be picture of NAION in patients taking known. These complications are typi- discussed with the prescribing practitio- these medications is the same as one cally irreversible and occur in approxi- ner at the first sign of toxicity. that occurs spontaneously: edematous mately 45% of patients treated with this Sertraline (Zoloft, Celexa, Lexapro, Pro- and hyperemic optic disc, relative af- medication. Exam shows a bilateral, zac, Paxil). This a commonly prescribed ferent pupil defect and painless loss of symmetric, concentric peripheral field selective serotonin reuptake inhibitor vision. defect with no central involvement. (SSRI) for depressive and anxiety disor- It’s important to note that most Retinal nerve fiber layer (RNFL) analy- ders and more infrequently for bulimia patients who require the use of ED sis with OCT shows thinning, with cor- nervosa and anorexia nervosa. medications have the same risk factors responding pallor of the optic nerves. While the link between sertraline (older age, vascular risk factors such as Even in severe case of visual field and maculopathy has yet to be firmly hypertension and diabetes) for NAION, loss and optic atrophy, visual acuity can

40 REVIEW OF OPTOMETRY | MAY 15, 2021 TREAT OCULAR INFLAMMATION AND INFECTION, AND... TURN ON RELIEF

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Indications and Usage WARNINGS & PRECAUTIONS: • Viral infections – Use with history of The development of secondary infection • IOP increase – Prolonged use may result herpes simplex requires great caution. has occurred. Fungal infections of the For steroid responsive infl ammatory ocular The course and severity of many viral cornea may occur. Secondary bacterial conditions of the palpebral and bulbar in glaucoma with damage to the optic conjunctiva, cornea, and anterior segment nerve, defects in visual acuity and fi elds infections of the eye (including herpes ocular infection following suppression of the globe and chronic anterior uveitis, of vision. IOP should be monitored. simplex) may be exacerbated. of host responses also occurs. corneal injury from chemical, radiation or • Aminoglycoside sensitivity – Sensitivity • Fungal infections – Fungal infections Non-ocular adverse events (0.5% to 1%) thermal burns, or penetration of foreign of the cornea may occur and should included headache and increased bodies for which a corticosteroid is to topically applied aminoglycosides may occur. be considered in any persistent blood pressure. indicated and where the risk of superfi cial corneal ulceration. Please see Brief Summary bacterial ocular infection is high or where • Cataracts – Posterior subcapsular there is an expectation that potentially • Use with systemic aminoglycosides – of Full Prescribing Information cataract formation may occur. dangerous numbers of bacteria will be Total serum concentration of on the adjacent page. present in the eye. • Delayed healing – May delay healing tobramycin should be monitored. and increase the incidence of bleb a ADVERSE REACTIONS: Randomized, investigator-masked, active-controlled, formation. Perforations of the cornea parallel-group trial conducted at 7 private practice The most frequent adverse reactions Important Safety or sclera have occurred. Slit lamp clinical sites in the United States with 122 adult Information (<4%) to topical ocular tobramycin are patients who had moderate to severe blepharitis/ biomicroscopy, and fl uorescein staining hypersensitivity and localized ocular blepharoconjunctivitis.1 CONTRAINDICATIONS: should be conducted. toxicity, including eye pain, eyelid pruritus, bMulticenter, double-blind, parallel-group, single-dose Most viral disease of the cornea and eyelid edema, and conjunctival hyperemia. study of 987 patients receiving a single dose of • Bacterial infections – May suppress 2 conjunctiva including epithelial herpes TOBRADEX ST or TobraDex ophthalmic suspension. host response and increase secondary simplex keratitis (dendritic keratitis), The reactions due to the steroid References: 1. Torkildsen GL, Cockrum P, Meier E, et al. vaccinia, and varicella, and also in ocular infections. In acute purulent component are increased intraocular Curr Med Res Opin. 2011;27(1):171-178. 2. Scoper SV, mycobacterial infection of the eye conditions, steroids may mask infection pressure with possible development Kabat AG, Owen GR, et al. Adv Ther. 2008;25(2):77-88. and fungal disease of ocular structures. or enhance existing infection. If signs and of glaucoma, and infrequent optic Hypersensitivity to any components symptoms fail to improve after 2 days, nerve disorder; subcapsular cataract; of the medication. the patient should be re-evaluated. and impaired healing.

© 2020 Eyevance Pharmaceuticals LLC. All rights reserved. TOBRADEX® ST and XanGen™ are trademarks of Eyevance Pharmaceuticals LLC. All other trademarks are the property of their respective owners. TST-01-20-AD-04 TOBRADEX® ST (tobramycin/dexamethasone Delayed healing: May delay healing and increase the ophthalmic suspension) 0.3%/0.05% incidence of bleb formation after cataract surgery. In those diseases causing thinning of the cornea or sclera, Brief Summary perforations have been known to occur with the use of topical steroids. This Brief Summary does not include all the information needed to use TOBRADEX ST safely and Bacterial infections: May suppress the host response and effectively. Please see Full Prescribing Information thus increase the hazard of secondary ocular infections. In acute purulent conditions, steroids may mask infection for TOBRADEX ST at MyTobraDexST.com. or enhance existing infection. If signs and symptoms fail to improve after 2 days, the patient should be re-evaluated. INDICATIONS AND USAGE Viral infections: Treatment in patients with a history of TOBRADEX ST is a topical antibiotic and corticosteroid herpes simplex requires great caution. Use of ocular steroids combination for steroid-responsive inflammatory ocular may prolong the course and may exacerbate the severity of conditions for which a corticosteroid is indicated and where many viral infections of the eye (including herpes simplex). superficial bacterial ocular infection or a risk of bacterial ocular infection exists. Fungal infections: Fungal infections of the cornea are particularly prone to develop with long-term use. Ocular steroids are indicated in inflammatory conditions Fungal invasion must be considered in any persistent of the palpebral and bulbar conjunctiva, cornea and anterior corneal ulceration. segment of the globe where the inherent risk of steroid use in certain infective conjunctivitides is accepted to obtain Use with systemic aminoglycosides: Use with systemic a diminution in edema and inflammation. They are also aminoglycoside antibiotics requires monitoring for total indicated in chronic anterior uveitis and corneal injury from serum concentration of tobramycin. chemical, radiation or thermal burns, or penetration of foreign bodies. ADVERSE REACTIONS The use of a combination drug with an anti-infective The most frequent adverse reactions to topical ocular ® component is indicated where the risk of superficial ocular tobramycin (TOBREX ) are hypersensitivity and localized infection is high or where there is an expectation that ocular toxicity, including eye pain, eyelids pruritis, eyelid potentially dangerous numbers of bacteria will be present edema, and conjunctival hyperemia. These reactions occur in the eye. in less than 4% of patients. Similar reactions may occur with the topical use of other aminoglycoside antibiotics. DOSAGE AND ADMINISTRATION Non-ocular adverse events occurring at an incidence of 0.5% Recommended Dosing: Instill one drop into the to 1% included headache and increased blood pressure. conjunctival sac(s) every four to six hours. During the initial The reactions due to the steroid component are: increased 24 to 48 hours, dosage may be increased to one drop every intraocular pressure (IOP) with possible development of 2 hours. Frequency should be decreased gradually as glaucoma, and infrequent optic nerve disorder; subcapsular warranted by improvement in clinical signs. Care should be cataract; and impaired healing. taken not to discontinue therapy prematurely. Secondary Infection. The development of secondary infection has occurred. Fungal CONTRAINDICATIONS infections of the cornea are particularly prone to develop with Nonbacterial Etiology: TOBRADEX ST is contraindicated long-term use. Fungal invasion must be considered in any in most viral diseases of the cornea and conjunctiva persistent corneal ulceration. Secondary bacterial ocular including epithelial herpes simplex keratitis (dendritic infection following suppression of host responses also occurs. keratitis), vaccinia, and varicella, and also in mycobacterial infection of the eye and fungal diseases of ocular structures. USE IN SPECIFIC POPULATIONS Pregnancy and Nursing Mothers Hypersensitivity: Hypersensitivity to any component of There are no adequate and well controlled studies in the medication. pregnant women. TOBRADEX® ST ophthalmic suspension should be used during pregnancy only if the potential benefit WARNINGS AND PRECAUTIONS justifies the potential risk to the fetus. Caution should be IOP increase: Prolonged use of corticosteroids may result exercised when TOBRADEX® ST is administered to a nursing in glaucoma with damage to the optic nerve, defects in woman. visual acuity and fields of vision. IOP should be monitored. Pediatric Use: Safety and effectiveness in pediatric Aminoglycoside sensitivity: Sensitivity to topically patients below the age of 2 years have not been established. applied aminoglycosides may occur. Geriatric Use: No overall differences in safety or Cataracts: May result in posterior subcapsular effectiveness have been observed between elderly and cataract formation. younger patients. Rx Only Distributed by: Eyevance Pharmaceuticals LLC. Fort Worth, TX 76102

© 2020 Eyevance Pharmaceuticals LLC. All rights reserved. TOBRADEX® ST is a trademark of Eyevance Pharmaceuticals LLC. All other trademarks are the property of their respective owners. TST-01-20-MS-05 Feature SYSTEMIC MEDICATIONS

Photo: Sara Weidmayer, OD has been associated with optic neuritis. Visual symptoms are like those seen with other optic neuropathies and include decreased vision, loss of color vision and either a bitemporal or cen- trocecal visual field defect. The optic nerves appear hyperemic with blurred margins, though rarely may appear normal. The condition is reversible, and improvement can begin as early as four days after discontinuing the medi- cation, with complete recovery taking anywhere from four to six months. Fig. 6. Late stage, severe optic atrophy OS in a patient on chronic amiodarone therapy. Continuation of treatment may lead to optic atrophy.16 be normal and the patient asymptom- are taking greater than 15mg/kg/day, Tetracyclines. Part of a group of com- atic. The damage does appear to be it is recommended they have monthly monly prescribed antibiotics that also dose-dependent and irreversible with follow-ups. Those taking lower doses includes doxycycline, minocycline and the first signs of RNFL thinning show- may need to be followed closely if they oxytetracycline, these meds are used ing around 1000 grams cumulative dose have any conditions that may put them to treat conditions like acne, rosacea, and worsening as that dose increases.14 at higher risk for toxicity, such as diabe- blepharitis and dry eye syndrome. Patients should have a comprehen- tes, chronic renal failure or alcoholism. While there is currently no evidence sive eye exam within four weeks of The medication should be discon- that they cause intracranial hyperten- starting the medication, every three tinued, at the discretion of the treating sion, they have long been associated months during treatment and three to physician, if there is any evidence of with it. Patients with this condition six months once treatment has been vision loss, visual field or color vision most often present with headache, discontinued. If vision loss is confirmed defect.6 pulsatile tinnitus, transient visual or suspected, the prescribing physician Isoniazid (Nydrazid). Another pul- obscurations or diplopia. should be consulted and the medica- monary tuberculosis drug, this one is Exam findings include bilateral op- tion should be discontinued.15 commonly prescribed in combination tic disc edema and possibly decreased Ethambutol (Myambutol). This drug with other meds due to concern of drug visual acuity. While obese women in treats pulmonary tuberculosis and there resistance to monotherapy. Isoniazid their childbearing years are at higher is significant evidence of optic neuropa- has also been associated with optic risk in general for the development of thy associated with its use (Figure 7). neuropathy; therefore, when used with idiopathic intracranial hypertension The condition is typically bilateral but ethambutol, it can be difficult to deter- (IIH), when associated with tetracy- can be asymmetric or unilateral. mine the causative agent. cline use the condition tends to occur The most common clinical findings Optic neuropathy from isoniazid in even younger age groups (teens) include a decrease in visual acuity, color tends to occur less frequently, is less and patients are less likely to be obese. vision loss or central scotoma on visual severe and is reversible with medica- Average duration of antibiotic use field testing. Ethambutol may also af- tion discontinuation.6 Rarely, the drug before symptom onset can range from

fect the optic chiasm and cause bitem- Photo: Sara Weidmayer, OD poral visual field defects. The adverse ocular effects appear to be related to dose, with those taking 60-100 mg/kg/ day at the highest risk of 50%. At the recommended dose of 15mg/kg/day or less, the risk goes down to 1%. Patients prescribed this medication should be made aware of the poten- tial for severe, irreversible vision loss and a baseline exam, including visual field and color vision testing should be performed. RNFL OCT analysis is also recommended, as it could possibly de- tect early stages of toxicity. If patients Fig. 7. Optic neuropathy with pallor OD>OS due to ethambutol.

MAY 15, 2021 | REVIEW OF OPTOMETRY 43 Feature SYSTEMIC MEDICATIONS Photo: Sara Weidmayer, OD Topiramate (Topamax). An oral sulfamate originally approved as an anticonvulsant, topiramate has more recently been expanded for use for migraines, weight loss, depression and ethanol dependence. The drug may induce uveal ef- fusions, which result in ciliary body edema and forward rotation of the lens-iris diaphragm and angle closure glaucoma. Myopic shifts average under Fig. 8. Findings due to chronic anterior uveitis associated with Keytruda use. one diopter but have been reported at greater than eight. 14.4 to 18.9 weeks.17 IIH is a diagnosis These conditions can be unilateral Adverse events are rare, but typi- of exclusion and additional testing, or bilateral and the onset of symptoms cally occur within two weeks of start- neuroimaging and cerebrospinal fluid is two days to two weeks after start- ing the medication. Much rarer cases evaluation must be performed for con- ing treatment. In almost all cases of of ciliary body effusion have been re- firmation.18 The condition does tend inflammation, the alendronate must be ported with other sulfa drugs including to improve with discontinuation of the discontinued for the condition to fully acetazolamide, sulfamethoxazole, pro- medication, and recurrence—while resolve and reinitiating any bispho- methazine, spironolactone, isosorbide rare—is typically less severe than the sphate prompts recurrence of the dinitrate and bromocriptine.22 Isolated original presentation.17 inflammation.6,20 cases have also been reported with It is recommended that patients Pembrolizumab (Keytruda). This is a tetracyclines, bupropion, oseltamivir, taking tetracyclines be educated about cancer immunotherapy drug that works duloxetine and aspirin. the possible side effects and have an by increasing the natural immune sys- Recognition of the inciting medica- eye exam after one month of treat- tem’s ability to detect and fight cancer tion is critical, as the treatment differs ment. Patients who experience any of cells. Due to the increased immune from a primary angle closure and the common IIH symptoms should be response, this drug has been associated includes the use of cycloplegics and a instructed to seek prompt care with an with ocular inflammation, specifically topical steroid with discontinuation of eye care provider.19 anterior uveitis or panuveitis (Figure 8). the inciting medication. Classic uveitis symptoms include Alpha-1 blockers (Flomax, Uroxatral, Inflammatory Changes pain, redness, photophobia and de- Rapaflo). These treat symptoms of For the remainder of our discussion, creased vision present, typically with benign prostatic hyperplasia (BPH). we’ll shift emphasis from anatomical mild to moderate cells in the anterior The presence of alpha-adrenocep- changes to those affecting multiple chamber. It is possible, however, to tors in mediating the contraction of structures and/or functions, beginning have a more severe reaction with vitre- the dilator pupillae muscle leads to a with the effects of inflammation. ous involvement. The condition is generalized miosis and the potential Alendronate (Fosamax, Actonel, almost always bilateral and will occur of intraoperative floppy iris syndrome Boniva, Reclast, Prolia, Evista, Duavee). within the first six months of therapy. (IFIS). This condition shows a billow- Bisphosphonates inhibit bone resorp- Most patients respond well to tradi- ing iris, rapid progressive intraopera- tion and are most used to treat or pre- tional topical uveitis treatment; in rare tive miosis and protrusion of iris tissue vent osteoporosis in post-menopausal cases, long-term inflammation and/or through surgical incisions. The effect women. severe vision loss have been reported. tends to occur in as little as two weeks The most common ocular side Patients on pembrolizumab should after initiation of therapy and remains effect is uveitis or scleritis. Patients have a baseline exam and be educated even when discontinued. Severe IFIS with uveitis will typically present with on ocular side effects. Routine monitor- occurs in roughly one-third of those severe pain, redness, sensitivity to ing once treatment has been started is taking Flomax and Rapaflo, while the light and decreased vision. There will acceptable but may not be necessary effect is less pronounced with Uroxa- be cell in the anterior chamber and oc- unless patients become symptomatic.21 tral.23 casionally keratic precipitates. Scleritis Although the challenges surround- will cause a severe deep pain, often Mechanical Changes ing IFIS cannot be eliminated with that awakens the patient at night. The Ocular effects in this category can discontinuation of the drug, the intra- sclera can have a deep purple hue complicate surgical procedures and, operative risks can be mitigated with with vessel engorgement, and scleral in severe presentations, expose the intracameral epinephrine, preoperative edema and thinning can occur. patient to risk of angle closure. atropine, intraoperative trypan blue

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and iris retractors. As such, simply recognizing the risk and Table 1. Ocular Adverse Effects of Systemic Medications appropriate preoperative planning should minimize IFIS. Finding/Association Medication or Drug Class Cornea Vortex/whorl keratopathy • Aminoglycosides Perceptual Changes • Amiodarone These adverse effects may be particularly troubling to • Atovaquone • Chlorpromazine patients without necessarily representing high-risk events • Hydroxychloroquine that jeopardize eye health. • NSAIDs Color Changes (multiple classes). PDE5 inhibitors dem- • Perhexiline maleate • Suramin onstrate mild cross-reactivity with PDE6 receptors in the • Tamoxifen retina. Changes in color perception are a common side Crystalline keratopathy • Antineoplastic agents (cytarabine, effect, with a blue tint being the most common. The effect emtansine, osimertinib, vandetanib) occurs in a dose-dependent manner with a 5% chance of • Benoquine • Clofazimine side effects at a standard dose. Voriconazole—a common • Gold salts antifungal—has a similar cross reactivity and may elicit • Macrolide antibiotics similar changes in perception.11 Fosamax and digoxin are • Tilorone commonly associated with a yellow or gold color distur- Pigmented keratopathy • Phenothiazines bance. Corneal Edema • Amantadine • Antiseptics Palinopsia (multiple classes). Defined as isochromatic • BAK afterimages which last following the removal of a stimulus, Sclera Scleritis • Alendronate palinopsia can be caused by a wide variety of medications. Lens Anterior subcapsular cataract • Phenothiazines Razadone, clomiphene, risperidone, topiramate and mir- tazapine have been associated with these manifestations.12 Posterior subcapsular cataract • Glucocorticoids The mechanism of action is unclear, but effects on poste- Uvea Intraoperative floppy iris syndrome (IFIS) • -1 blockers α rior cortical matter are implicated. Mydriasis and/or cycloplegia • SSRIs Blurred vision/diplopia (multiple classes). Blurred vision Uveitis • Alendronate and diplopia can occur with a wide variety of oral meds. • Pembrolizumab The most common classes include alpha-blockers, second Uveal effusion • Topiramate • Sulfa-based medications generation fluoroquinolones, statins, PDE5 inhibitors and bisphosphonates. The practitioner should investigate each Retina Retinopathy • Interferon-α • Tamoxifen case to rule out the more common etiologies and medica- Intraretinal deposits • Tamoxifen tions cross-referenced with known side effects. • Canthaxanthine Macula Macular edema • Tamoxifen Functional Changes Toxic maculopathy • Chloroquines Another patient-forward category of effects, these changes • Phenothiazines are often amenable to mitigation with discontinuation of • Setraline the drug. Pigmentary maculopathy • Pentosan polysulfate sodium Phenytoin (Dilantin). Phenytoin is a commonly prescribed • Phenothiazines antiseizure medication and has been associated with ocu- Optic Edema • Tamoxifen Nerve lomotor disturbances including gaze-evoked nystagmus, Intracranial hypertension • Tetracyclines downbeat nystagmus, periodic alternating nystagmus and NAION • PDE5 inhibitors partial or complete ophthalmoplegia. These findings can Optic neuritis • Isoniazid take place in the normal therapeutic range, but are much Optic neuropathy/Atrophy • Amiodarone more common in overdosed/ and toxic levels. Consider- • Ethambutol ing the oculomotor findings could suggest a structural • Isoniazid • Vigabatrin brainstem lesion rather than a drug-induced side effect, it Functional Abnormal dark adaptation • Canthaxanthine is important to review all medications to determine if a full neurologic work-up, including neuroimaging, is indicated. Perceptual Color perception changes • PDE5 inhibitors • Voriconazole The clinical findings do improve and resolve once the dose • Alendronate is decreased or the drug is discontinued.24 • Digoxin Selective serotonin reuptake inhibitors (Prozac, Zoloft, Paxil, Oculomotor dysfunction • Phenytoin Lexapro, Celexa). SSRIs are psychiatric medications used to Palinopsia • Clomiphene treat anxiety disorders. • Mirtazapine • Risperidone These drugs are known to cause changes to the accom- • Topiramate modative status due to their anticholinergic effects. They • Trazadone cause both mydriasis by stimulating the alpha receptors

46 REVIEW OF OPTOMETRY | MAY 15, 2021 located on the radial dilator muscle of the iris, and cyclople- gia due to the paretic effect on the ciliary muscle. Patients experiencing these effects will likely complain of blur— mostly at near—and occasionally glare. Eye care providers should consider prescribing appropriate spectacle correction to alleviate symptoms. The conditions are reversible once the medication is discontinued.25

Keep a Watchful Eye As we’re reminded all the time in clinical practice, the eyes are not an island and are very susceptible to medication- induced side effects. Being aware of these possible effects can help providers educate their patients, quickly recognize and mitigate unwanted side effects, and avoid costly and time-consuming workups. ■

1. Raizman MB, Hamrah P, Holland EJ, Kim T, et al. Drug-induced corneal epithelial changes. Surv Ophthalmol. 2017-05-01;62(3):286-301. 2. Li J, Tripathi RC, Tripathi BJ. Drug-induced ocular disorders. Drug Saf. 2008;31(2):127-41. 3. McCarty CA, Wood CA, Fu CL, Livingston PM, et al. Schizophrenia, psychotropic medication, and cataract. Ophthalmology. 1999 Apr;106(4):683-7. 4. Minhas B. The mind’s eye: ocular complications of psychotropic medications. Review of Optometry. 2016 Jan 15; 153(1): 42-49. 5. Rentiya ZS, Wells M, Bae J, Chen KJ, et al. Interferon-α-induced retinopathy in chronic hepatitis C treatment: summary, considerations, and recommendations. Graefes Arch Clin Exp Ophthalmol. 2019 Mar;257(3):447-52. 6. Santaella RM, Fraunfelder FW. Ocular adverse effects associated with systemic medications: recognition and management. Drugs. 2007;67(1):75-93. 7. Doshi RR, Fortun JA, Kim BT, Dubovy SR, Rosenfeld PJ. Pseudocystic foveal cavitation in tamoxifen retinopathy. Am J Ophthalmol. 2014 Jun;157(6):1291-1298. 8. Espaillat A, Aiello L P, Arrigg PG, Villalobos R, et al. Canthaxanthine retinopathy. Arch Ophthal- mol. 1999 Mar;117(3):412-3. 9. Melles RB, Marmor MF. The risk of toxic retinopathy in patients on long-term hydroxychloro- ELEVATE PATIENT quine therapy. JAMA Ophthalmol. 2014 Dec;132(12):1453-60. 10. Barnes AC, Hanif AM, Pentosan NJ. Polysulfate Maculopathy versus inherited macular EXPERIENCE dystrophies: comparative assessment with multimodal imaging. Ophthalmol Retina. 2020 Dec;4(12):1196-1201. 11. Garg P, Yadav S. Ocular side effects of systemic drugs. Era J Med Res. 2019;6(1):1-9. 12. Blomquist PH. Ocular complications of systemic medications. Am J Med Sci. 2011 Jul;342(1):62-9. 13. Ewe S, Abell R, Vote B. Bilateral maculopathy associated with sertraline. Australas Psychia- try. 2014 Dec;22(6):573-5. 14. Clayton LM, Devile M, Punte T, de Haan GJ, et al. Patterns of peripapillary retinal nerve fi ber layer thinning in vigabatrin-exposed individuals. Ophthalmology. 2012 Oct;119(10):2152-60. 15. Vigabatrin: Medline Plus Drug Information. US National Library of Medicine. medlineplus. gov/druginfo/meds/a610016.html. Accessed 23 March 2021. 16. Kulkarni HS, Keskar VS, Bavdekar SB, Gabhale Y. Bilateral optic neuritis due to isoniazid (INH). Indian Pediatr. 2010 Jun;47(6):533-5. 17. Orme D, Vegunta S, Miller M, Warner J, et al. A comparison between the clinical features of pseudotumor cerebri secondary to tetracyclines and idiopathic intracranial hypertension. Am J Ophthalmol. 2020; 220:177-182. 18. Thurtell M, Wall M. Idiopathic intracranial hypertension (pseudotumor cerebri): recognition, treatment and ongoing management. Curr Treat Options Neurol. 2013 Feb;15(1):1-12. 19. Kesler A, Goldhammer Y, Hadayer A, Pianka P. The outcome of pseudotumor cerebri induced by tetracycline therapy. Acta Neurol Scand. 2004;110:408-411. 20. Samalia P, Sims J, Niederer R. Drug-induced ocular infl ammation. N Z Med J. 2020 Dec 18;133(1527):83-94. 21. Sun M, Levinson R, Filipowicz A, Anesi S, et al. Uveitis in patients treated with CTLA-4 and PD-1 checkpoint blockade inhibition. Ocul Immunol Infl amm. 2020;28(2):217-27. 22. Chen TC, Chao CW, Sorkin JA. Topiramate induced myopic shift and angle closure glau- coma. Br J Ophthalmol. 2003;87(5):648-649. 23. Handzel DM, Briesen S, Rausch S, Kälble T. Cataract surgery in patients taking alpha-1 antagonists: know the risks, avoid the complications. Dtsch Arztebl Int. 2012;109(21):379-384. BOOTH 24. Praveen-kumar S, Desai M. Ocular motor abnormalities in a patient with phenytoin toxicity- -case report and minireview. Clin Neurol Neurosurg. 2014 Dec;127:116-7. TF233 25. Minhas B. The Mind’s Eye: Ocular complications of psychotropic medications. Review of Optometry. 2016 Jan 15; 153(1): 42-49. Remote Refraction New remote diagnostic technology allows refractions from anywhere

Evolving Refraction Capabilities By H. Jay Wisnicki, MD

ven before COVID was an issue, our New York City- Topcon RDx® and the CV-5000S based eye care practice of optometrists and ophthal- Digital Phoropter Benefi ts the Emologists had been doing an increasing amount of virtual work. This has been the case for many of us in eye- Patient and the Practice care; we have been outsourcing our billing operations, front Topcon RDx®, an ocular telehealth platform desk services, human resources, and a variety of administra- enables eye care providers to connect to their tive and clerical functions for many years. o ces remotely and conduct portions of the At the same time, the introduction of electronic medical comprehensive eye exam. Topcon’s CV-5000S records (EMRs) has increased the level of medical device automated phoropter integrates with RDx integration and the exchange of clinical information across remotely, so practitioners can perform refractions the spectrum of eyecare. For example, image management from anywhere. software has made it possible for us to view fundus and OCT images, in addition to fi ndings from corneal topogra- phy, biometry, ultrasound, and other digital devices be- tween our o† ces and networks. In the clinical realm, while medical specialties such as radiology, pathology and behavioral health have been con- ducting some form of telemedicine for years, other areas of medicine such as optometry and ophthalmology requiring a ter so practitioners can virtually perform refractions, view close-up view of the patient, have had a slower time making supplementary diagnostic information through Topcon’s the same leap. A few areas of eyecare have successfully Harmony data management software, and video consult used telemedicine to some degree to monitor patients with, with the patient in real time. or at risk of retinal pathologies such as diabetic retinopathy This new capability o• ers the patient and provider more or age-related macular degeneration. However, eyecare exam fl exibility, e† ciency and an increased level of safety. in general has not utilized remote capabilities to perform The doctor and patient are able to virtually meet for the portions of the comprehensive eye examination or conduct patient’s eye exam, which helps to ensure the patient is diagnostic evaluations and tests. presented with timely, high quality eye care while reducing That is all changing with the introduction of new software the number of people and touch points encountered during technology enabling clinicians to perform remote diag- an exam. Imagine how much more comfortable the patient nostics, refractions and eye examinations without being might feel in a room with just one technician, while the per- physically in front of the patient. son performing the exam is in a di• erent location. From a practice standpoint, this technology has trans- Advancing Refraction Capabilities formed our busy urban clinics. Our remote optometrists There has been an evolution of refraction technology over are able to quickly move from patient to patient, serving the years, from conventional subjective refraction to com- patients in both of our o† ce locations from essentially puterized or digital phoropters and now remote operation. anywhere. In December 2020, Topcon Healthcare (Tokyo, Japan) introduced Topcon RDx®, an ocular telehealth platform H. Jay Wisnicki, MD, is a professor of ophthalmology at enabling eye care providers to remotely connect to their the Icahn School of Medicine at Mount Sinai, and founder o† ces to conduct portions of the comprehensive eye exam. and medical director of Union Square Eye Care, all in New RDx integrates with Topcon’s CV-5000S digital phorop- York City.

Sponsored by 48 • REVIEW OF OPTOMETRY Benefi ts of Remote Refraction By Ryan Ngo, OD

s an optometrist who has spent years manually and of the main drawbacks digitally refracting patients, heading into a virtual of being an eyecare pro- Arealm has required a slightly di erent approach to fessional was that you the way I practice; however, the remote refraction process couldn’t provide care is not that di erent from using the CV-5000S digital pho- to patients and work ropter in the o ce. The main di erence is that rather than from home at the same using a manual control panel in the examination room, the time. Now that we have clinician is instead using a computer interface and mouse the ability to remotely at a remote location to control the phoropter head. conduct eye exams, including refractions, that opens up I like that the Topcon RDx platform is intuitive and easy options for doctors who may mix in-person and remote to start using. A technician is still needed to set up and work, switching between the two to suit their personal align the patient before the refraction starts, but once needs and allowing a better quality of life. the program is up and running, the sequence of steps is the same as an in-person refraction. The more we use the Utilization Today technology, the more seamless and integrated it’s becom- In addition to its potential use for many of our routine ing in our day-to-day clinical examinations. evaluations, I think remote refraction can help improve access to vision care and fi ll in service gaps for large and Patient & Provider Benefi ts of RDx Technology small practices. For example, a patient who has an urgent In practice, we have found that the patients’ early ex- need for glasses but can’t schedule a live visit with a doc- perience with this new way of refracting has been over- tor nearby, could schedule an appointment at a practice whelmingly positive. After a recent remote refraction on o ering remote refractions, and quickly obtain a prescrip- a patient, the young woman gave us her impression of tion through this virtual service. In addition, high-volume the process: “I was told prior to my exam that I would be specialty practices that don’t do refractions might consid- getting a remote refraction from a clinician that would be er adding remote capabilities to o er a more comprehen- o site. This new examination process was so easy and was sive eye exam for their patients. Another application could as if the doctor was still in the room with me!” be for small optical shops that can’t a ord a full-time She liked the e ciency that remote refraction o ered, optometrist but could hire someone part-time to manage noting: “It’s nice just to be able to walk in, have a seat, remote refractions. video connect with the doctor and start the refraction While remote refraction is an excellent fi t for many process. I really liked that I didn’t have to wait. Sometimes patients, certain patients might not be ideal candidates. in busy practices the doctors are running behind schedule, Those individuals could include patients with large de- but with the remote refraction, I was able to get in front of grees of astigmatism, or those who have conditions such the video screen with Dr. Ngo right away and he quickly as keratoconus or more complicated pathologies that refracted me and provided a new prescription.” require in-person or follow-up evaluations. Young children This patient also appreciated the additional fl exibility or elderly patients may not be as well-suited for remote and convenience that remote refraction o ered. She said, refraction. “You have more choices now based on your schedule or I estimate that 60% to 70% of my patient population what doctor you prefer to see, because the doctor does might enjoy utilizing this new technology, in particular, not have to physically be in the o ce to see you. For “computer-age” patients like Millennials, Generations X and people who are super busy and have fast-paced lifestyles, Z who have a comfort level with innovation and virtual tech- I think the convenience and time savings with remote re- nology. In all cases, it will be exciting to see where remote fraction is going to be a big value moving forward.” refraction will take eye care now and into the future. As an eye care provider, I also value fl exibility in my professional life. Remote eye exams and refractions are es- Ryan Ngo, OD, is an optometrist at Denny Eye & Laser pecially helpful if I am travelling, unable to make it into one Center in San Francisco; he formerly practiced at Union of our o ces or need to work from home. In the past, one Square Eye Care in New York City.

REVIEW OF OPTOMETRY • 49 Feature ANTIBIOTICS PEER REVIEWED

Using Antibiotics in Anterior Segment Care

Bacterial ocular and periocular infections are common in adults and children, but choosing an effective treatment strategy relies on more than an accurate clinical diagnosis.

The chosen route of treatment typi- days. Considering their self-limiting By Jessica Steen, OD cally depends on the tissue involved: nature, topical antibiotics may not be Fort Lauderdale, FL soft tissue infections such as preseptal prescribed; however, they modestly cellulitis and dacyrocystitis require improve (by approximately two days) cular and periocular infections antimicrobial drug levels at the site the time to resolution compared with present in a variety of locations of infection, which typically requires supportive therapy alone.1 Interest- from a variety of causes. The ap- oral administration. Conjunctival and ingly, nearly 60% of patients with acute propriate treatment course varies corneal disease is most commonly conjunctivitis in the United States fill O 4 from observation to non-pharmacologic treated efficiently with topical agents, prescriptions for topical antibiotics. measures to the prescription of topical while externally pointed hordeola may The gap between the number of or oral anti-infective agents.1-3 In the respond well to topical ointments and cases of conjunctivitis that may benefit absence of the need for a bacterial hot compresses.1-3 from topical antibiotic therapy and the culture, which is generally reserved for number of prescriptions filled high- vision-threatening conditions, a care- The Dangers of Overtreatment lights the concern of over-prescribing ful history and thorough examination While most anti-infective agents used antibiotics when not clinically indicat- guides the clinician to determine the in periocular infection management ed, a driver of antibiotic resistance. most likely underlying cause that can are considered to be broad-spectrum, The concept of a pre-determined inform treatment. emerging trends in pathogen resistance set course of antibiotic therapy as a To muddy the waters further, nar- have resulted in the need for under- broad prescribing strategy aims to rowing down the diagnosis to suspect- standing most common underlying ensure complete eradication of disease- ing a bacterial etiology leaves the pathogens likely to cause infection and causing bacteria.5 But a one-size-fits-all clinician with a broad range of treat- their susceptibility to commonly pre- treatment approach ignores a central ment strategies. Known patterns of scribed antibiotics. However, overtreat- component to patient care: the patient. resistance, allergy history and systemic ment through unnecessary prescribing The fear of undertreatment has led history complicate the choice between as well as undertreatment of antibiotics prescribers to generally prescribe the antibiotics in clinical practice. While persists. same duration of treatment regardless treatment failure may be caused by Up to 80% of uncomplicated acute of the patient’s response to therapy.5 inaccurate diagnosis, the cause may conjunctivitis in adults are viral in If our goal of appropriate antibiotic also be inadequate dosing, organism nature. In those where bacterial infec- prescribing is centered on limiting resistance, development of toxicity or tion is the underlying cause, cases are antibiotic use based on necessity and allergy or nonadherence. typically self-limiting within seven minimizing side effects to reach clini-

About Dr. Steen is an attending optometrist and assistant professor of ocular pharmacology at Nova Southeastern University College of Optometry. She has no the author financial interests to disclose.

50 REVIEW OF OPTOMETRY | MAY 15, 2021 cal efficacy, antibiotic therapy discon- flora of the eyelids and conjunctiva. The study also found that more tinuation should differ based on the Common pathogens include gram- than half of all S. aureus isolates were patient’s response and how follow-up positive cocci, such as Staphylococcus resistant to azithromycin, and 33.3% care goes. One should only continue epidermidis, Staphylococcus aureus and were resistant to ciprofloxacin. MRSA treatment with topical ocular antibiot- streptococcus species as well as Proteus isolates were nearly all resistant to ics for the prophylaxis of infection—for miribalis, Serratia marcenas and gram- azithromycin. Importantly, MRSA example, in cases of corneal abrasion, negative Pseudomonas species.2.3,7,8 isolates were determined to be highly while the increased risk is present— In children, Haemophilus influenzae susceptible to trimethoprim and tet- while epithelial damage exists rather and Streptococcus pneumoniae are the racycline, but a high percentage of than for a pre-determined course. most common ocular isolates in isolates displayed resistance to fluoro- The minimum inhibitory concen- conjunctivitis cases.8,9 quinolones other than besifloxacin.8 S. tration (MIC) value describes the in A basic understanding of the trends pneumoniae isolates were most likely vitro susceptibility or resistance levels of resistance of common ocular isolates to be resistant to azithromycin (36.3%) of bacteria to an antibiotic and serves forms the basis for antibiotic selec- and penicillin (32.2%). P. aureginosa as the basis for assessing whether an tion for treatment with topical ocular isolates displayed the lowest MIC with antibiotic may be effective in a clinical antibiotics and oral medications to treat ciprofloxacin.8 setting. Undertreatment of an infection periocular infections. The Antibi- In general, azithromycin shows can cause failure to reach the MIC, otic Resistance Monitoring in Ocular widespread resistance to the common resulting in bacteria survival, mutation Microorganisms (ARMOR) study ocular isolates implicated in ocular and and replication during treatment, in- surveyed antibiotic resistance patterns periocular disease, including MRSA, creasing the likelihood of development of common ocular isolates.8 Its 10-year which is likely a result of the wide- of a drug-resistant population.6 Never results showed that while there was no spread use of the medication. Specific taper antibiotic agents below their significant increase in the rates of re- resistance strategies of macrolides may equivalent MIC, which is often clini- sistance during the study period, there be compounded by the medication’s cally represented by FDA-approved was generally increased resistance with long half-life and make azithromycin a dosing. In order to taper a steroid in a age.8 A significant proportion of S. au- non-preferred choice for the treatment topical antibiotic and steroid combina- reus isolates were resistant to oxacillin/ of soft tissue infections or bacterial tion, first switch the patient to a steroid methicillin (MRSA) and at least three conjunctivitis.8,10 agent alone, rather than taper the classes of antibiotics, termed to be Pertinent to infections in children, combination agent. “multi-drug resistant.” Many believe nearly all H. influenzae isolates were resistance and susceptibility patterns to susceptible to all antibiotics evalu- A Better Understanding closely mirror patterns in systemic in- ated including ofloxacin, ciprofloxacin, The main source of bacteria causing fections, so we can apply these findings moxifloxacin, azithromycin and tetracy- periorbital soft tissue infection or to treatment of ocular infections with cline.8 conjunctivitis in adults is the natural systemic and topical antibiotics.8 The ARMOR trial also determined resistance to besifloxacin to be negli- gible. Besifloxacin has no systemic for- mulation, and due to its mechanism of action, the development of resistance requires mutation in both DNA gyrase and DNA topoisomerase IV. 8 While community-acquired rates of MRSA have increased over time, individuals in healthcare settings, those recently released from the hospital, incarcerated patients and patients with a history of MRSA carry a greater possibility of harboring MRSA and therefore developing a bacterial infection due to MRSA.3 Based on the ARMOR data on treating bacte- rial infections in patients who may be at increased risk of MRSA, a topical agent containing trimethoprim, such as Bacterial keratitis in a soft contact lens wearer. trimethoprim sulfate and polymyxin B

MAY 15, 2021 | REVIEW OF OPTOMETRY 51 Feature ANTIBIOTICS

Photo: Greg Caldwell, OD rent punctal occlusion of any topical ophthalmic agent is low, many consider topical ophthalmic antibiotic agents to be safe for use in pregnant individuals. Still, take additional clinical risk-bene- fit consideration for topical ophthalmic fluoroquinolones due to the risk that systemically applied agents pose.

Adverse Effects Review When discussing the risks, benefits and expected effects of a prescribed oral antibiotic with patients, do devote a part of the conversation to likely and possible side effects. Due to orally administered antibiotics’ disruption of disease-causing flora and natural gastrointestinal flora, antibiotic- This internally pointed hordeolum of the upper eyelid may respond well to topical associated diarrhea is common and can ointments and hot compresses. be expected in approximately 30% of individuals—one of the most common sulfate or besifloxacin, is preferred.8 For viduals, which resulted in the difficulty reasons for nonadherence to antibiotic the treatment of infections requiring of inclusion of pregnant individuals in treatment.19 oral medication, consider trimethoprim clinical trials. This resulting lack of data Probiotics are ingested microorgan- 160mg and sulfamethaxazole 800mg, may make both the prescriber and the isms, including Lactobacillus, Bifido- or for sulfonamide allergic patients, patient reluctant to treat the underlying bacterium and others, that may help to doxycycline 100mg. condition.15 maintain or restore the natural gastroin- For the treatment of bacterial Taking medications during pregnan- testinal flora and ecosystem during and conjunctivitis in children, where the cy or during lactation is common, with after antibiotic treatment; however, not gram-negative bacteria H. influenzae is an estimated 90% of individuals taking all patients will respond favorably, with a common underlying cause, consider an over-the-counter or prescription a determined number of 13 individual fluoroquinolones such as ciprofloxacin medication during pregnancy, which species that need to be treated in order 0.3%, moxifloxacin 0.5% and ofloxacin means that 5.4 million pregnancies to improve one case of antibiotic-asso- 0.3% ophthalmic solution. The safety are exposed to medications annually.16 ciated diarrhea.20 and efficacy of these medications have When treating pregnant individuals, While reconstitution of the natural been evaluated in children one year of make note of alcohol use, drug use and gut flora is often slow following age and older.11-13 smoking as well as inappropriately pre- antibiotic treatment, probiotics may For children younger than one scribed medications. Consider the risks further delay the reconstitution to a year old, researchers have evaluated and benefits of therapy for the patient natural gastrointestinal microbiome. polymyxin B sulfate and trimethoprim and fetus.17 Notably, gastrointestinal flora is unique sulfate in children as young as two In general, penicillins and cephalo- to individuals. By ingesting a large months. While trimethoprim is not ef- sporins are safe to use during pregnan- amount of specific probiotic organisms, fective against H. influenzae, polymyxin cy. 18 Of the macrolides, azithromycin is which are often not an exact reflection B can provide coverage against this generally safe to use, while one should of the composition of an individuals’s specific organism.14 use erythromycin and clarithromycin flora, the introduced species may with caution and only when the benefit dominate and delay recolonization Pregnancy Considerations of treatment outweighs the risk.18 Tet- of natural flora by up to five months, Every prescribing decision is based on racyclines have proven teratogenicity compared with individuals who did not a careful understanding and discussion in humans, and fluoroquinolones have use probiotics.21 with the patient of the risks, benefits concerns of fetal malformation in ani- While warnings about taking anti- and expected result of treatment. The mals and therefore should be avoided. biotics with alcohol are often added to lack of data regarding prescription Avoid trimethoprim and sulfamethoxa- prescription bottles, the evidence for medication safety in pregnant individu- zole in the first trimester of pregnancy reduced efficacy for most antibiotics is als stems from protections implement- and after 32 weeks of gestation.18 While lacking. Erythromycin, which may be ed to limit the study of pregnant indi- systemic absorption with concur- prescribed in the context of periocular

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Digital chart Feature ANTIBIOTICS disease treatment, should not be taken with alcohol due to the potential for reduced efficacy and potential systemic toxicity.22 Also, cephalosporins and sulfon- amide antibiotics carry a specific adverse effect that patients should be advised of. A “disulfiram-like” reaction describes specific symptoms that mimic the effect of disulfiram, a medication used for the treatment of alcohol dependency disorder. Patients may experience dizziness, sweating, Hypersensitivity reaction of the left eye secondary to topical brimonidine use. headache, nausea, weakness, vomiting Differentiating between a true type-1 hypersensitivity reaction or an IgE-mediated response and another type of adverse effect requires a careful discussion of symptoms the patient and hypotension—symptoms often de- experienced with each reported adverse event. scribed to be similar to the exacerbated effects of a hangover. While disulfiram- Differentiating between a true type-1 The practice of avoiding cephalospo- like reactions are well-documented hypersensitivity reaction or an IgE- rins in penicillin-allergic patients stems with cephalosporin and alcohol use, mediated response and another type from the potential for cross-reactivity only isolated case reports have been of adverse effect requires a careful due to their structurally similar R1 described following the administration discussion of symptoms the patient side-chain of first- (i.e., cephalexin) of trimethoprim-sulfamethaxazole.23,24 experienced with each reported and second-generation cephalosporins. While azithromycin is a commonly adverse event. The risk of allergy to a cephalosporin prescribed oral antibiotic, recent re- Urticaria, anaphylaxis, in a penicillin-allergic patient due to ports note an increased risk of sudden bronchospasm, laryngospasm and cross-reactivity is much less than the cardiac death due to prolongation of angioedema are all signs of true allergy, historically understood 10%.29 How- the QT interval in individuals with car- while gastrointestinal upset is a sign ever, avoid cephalexin in patients with diovascular event risk factors that later of an expected adverse effect of orally known penicillin hypersensitivity due prompted the FDA to include a black administered antibiotics.26,27 While to the approximate 1% cross-reactivity box warning for the drug.25 Individuals approximately 10% of the population with first-generation cephalosporins.29 most at risk are those with underlying have reported an allergy to penicillin, When patients have a true allergy arrhythmia termed torsades de pointes.25 less than 5% have a true allergy.26 to one type of drug—for instance, to The allergic potential of sulfonamide a sulfonamide non-antibiotic such as Allergy Perils antibiotics carries a similar risk, with a thiazide diuretic—is there potential Prior to prescribing any medication, approximately 3% of the population for allergy to a structurally similar drug perform a careful review of history of having experienced a true allergic class, such as a sulfonamide antibiotic? adverse drug reactions and allergies. reaction.28 While the potential exists for allergic reaction in both classes, it appears to Photo: Greg Caldwell, OD not be due to structural similarity and development of cross-reactivity but rather increased propensity to allergic reaction in general. Pay particular attention to patients with an atopic history or pre-existing asthma diagnosis, especially when they have a history of penicillin or sulfonamide antibiotic allergy. Either of these can suggest that multiple allergies may exist across non- structurally similar drug categories.27

Takeaways Optimal prescribing for the treatment of bacterial infections requires careful Mucopurulent discharge characteristic of bacterial conjunctivitis. clinical examination, a thorough

54 REVIEW OF OPTOMETRY | MAY 15, 2021 8. Asbell PA, Sanfilippo CM, Sahm DF, et al. Trends in 18. Lamont HF, Blogg HJ, Lamont RF. Safety of antimicrobial history and an understanding of the antibiotic resistance among ocular microorganisms in treatment during pregnancy: a current review of resistance, microbiome of periocular tissues, the United States from 2009 to 2018. JAMA Ophthalmol. immunomodulation and teratogenicity. Expert Opin Drug Saf. 2020;138(5):439-50. resistance and susceptibility patterns 2014;13(12):1569-81. 9. Cavuoto K, Zutshi D, Karp CL, et al. Update on 19. Szajewska H, Mrukowicz JZ. Probiotics in prevention and risk of potential adverse effects. bacterial conjunctivitis in South Florida. Ophthalmology. of antibiotic-associated diarrhea:meta-analysis. J Pediatr. Using the right antibiotic at the right 2008;115(1):51-6. 2003;142(1):85. time, dose and duration will ensure that 10. Food and Drug Administration. Highlights of prescribing 20. Hempel S, Newberry SJ, Maher AR, et al. Probiotics information: Zithromax. 2019. www.accessdata.fda.gov/ for the prevention and treatment of antibiotic-associated your patient is appropriately managed drugsatfda_docs/label/2019/050710s049,050711s047,050 diarrhea: a systematic review and meta-analysis. JAMA. 784s034lbl.pdf. Accessed April 9, 2021. while minimizing the risk of adverse 2012;307(18):1959-69. 11. Novartis Pharma AG. Prescribing information: Ciloxan. 21. Suez J, Zmora N, Zilberman-Schapira G, et al. Post- effect to your patient and the greater 2013. www.novartis.com.sg/system/files/product-info/ antibiotic gut mucosal microbiome reconstitution is impaired community. ■ CILOXAN%20STERILE%20OPHTHALMIC%20AND%20 by probiotics and improved by autologous FMT. Cell. OTIC%20SOLUTION%200.3%25.pdf. Accessed April 9, 2021. 2018;174(6):1406-23.e16. 1. Azari AA, Barney N P. Conjunctivitis: a systematic review 12. Food and Drug Administration. Highlights of prescribing 22. Mergenhagen KA, Wattengel BA, Skelly MK, et al. Fact information: Vigamox. 2020. www.accessdata.fda.gov/ of diagnosis and treatment. JAMA. 2013; 310(16):1721-9. versus fiction: a review of the evidence behind alcohol drugsatfda_docs/label/2020/21598s024lbl.pdf. Accessed and antibiotic reactions. Antimicrob Agents Chemother. 2. Mannis MJ, Plotnick RD. Bacterial conjunctivitis. In: Tas- April 9, 2021. man W, Jaeger EA, ed. Duane’s Clinical Ophthalmology. Vol. 2020;64(3):e02167-19. 13. Allergan. Prescribing Information: Ocuflox. 4. Philadelphia: Lipencott-Raven; 2004:1-7. 2016. www.accessdata.fda.gov/drugsatfda_docs/ 23. Barth KS, Malcolm RJ. Disulfiram: an old therapeutic 3. Charalampidou S, Connell P, Fennell J, et al. Preseptal label/2016/019921s021lbl.pdf. Accessed April 9, 2021. with new applications. CNS Neurol Disord Drug Targets. cellulitis caused by community acquired methicillin resis- 2010;9(1):5-12. 14. Allergan. Prescribing Information: Polytrim. 2018. tant Staphylococcus aureus (CAMRSA). Br J Ophthalmol. media.allergan.com/actavis/actavis/media/allergan-pdf- 24. Heelon MW, White M. Disulfiram-cotrimoxazole reaction. 2007;91(12):1723-4. documents/product-prescribing/20180622-POLYTRIM-USPI- Pharmacotherapy. 1998;18(4):869-70. 4. Shekhawat NS, Shtein RM, Blachley TS, et al. Antibiotic 1-0USPI7824.pdf. Accessed April 9, 2021. 25. Ray WA, Murray KT, Hall K, et al. Azithromycin and the risk prescription fills for acute conjunctivitis along enrollees in a 15. van der Graaf R, van der Zande ISE, den Ruijter HM, et al. of cardiovascular death. N Engl J Med. 2012; 366(20):1881-90. large United States managed care network. Ophthalmology. Fair inclusion of pregnant women in clinical trials: an inte- 2017;124(8):1099-1107. 26. Shenoy ES, Macy E, Rowe T, et al. Evaluation and manage- grated scientific and ethical approach. Trials. 2018;19(1):78. ment of penicillin allergy: a review. JAMA. 2019;321(2):188-99. 5. Llewelyn MJ, Fitzpatrick JM, Darwin E, et al. The antibi- 16. Mitchell AA, Gilboa SM, Werler MM, et al. National birth otic course has had its day. BMJ. 2017;358;j3418. 27. Strom BJ, Schinnar R, Apter AJ, et al. Absence of cross- defects prevention study. Medication use during pregnancy, reactivity between sulfonamide antibiotics and sulfonamide 6. Kowalska-Krochmal B, Dudek-Wicher R. The minimum with particular focus on prescription drugs: 1976-2008. Am nonantibiotics. N Engl J Med. 2003;349(17):1628-35. inhibitory concentration of antibiotics: methods, interpreta- J Obstet Gynecol. 2011;205(1):51.e1-8. tion, clinical relevance. Pathogens. 2021;10(2):165. 28. Lieberman P, Anderson JA, eds. Allergic diseases: diagno- 17. Genetic Alliance; District of Columbia Department of sis and treatment. Totowa, NJ:Humana Press; 1997:289. 7. Ratnumnoi R, Keorochana N, Sontisomabat C. Normal Health. Understanding genetics: a District of Columbia flora of conjunctiva and lid margin, as well as its antibiotic guide for patients and health professionals. Washington 29. Campagna JD, Bond MC, Schabelman E, et al. The use sensitivity, in patients undergoing cataract surgery at Phra- (DC): Genetic Alliance; 2010 Feb 17. Appendix D, Terato- of cephalosporins in penicillin-allergic patients: a literature mongkutklaoReview Hospital. of Optometry_Bruder Clin Ophthalmol. 2017;11:237-41. Kit_Karpecki_Maygens/Prenatal 2021 Substance Abuse. review. J Emerg Med. 2012;42(5):612-20.

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Managing Miotics and Mydriatics

Take a closer look at old, new and future uses of these drugs.

neuron begins in the hypothalamus synapse with postganglionic neurons By Paymaun Asnaashari, OD and descends through the midbrain in the ciliary ganglion. Postganglionic sacramento to synapse onto a specific area of the neurons leave the ciliary ganglion to spinal cord, known as the ciliospi- innervate the iris sphincter.1,3 ptometrists are well-acquainted nal center of Budge. This synapse Mydriatic drops work by either in- with the two opposing muscles is located between the C8 and T2 hibiting the parasympathetic pathway in the iris, the sphincter and vertebrae. The second neuron, which to the iris sphincter or by promot- Othe dilator, as we witness their is the preganglionic neuron, exits ing the sympathetic pathway to the effects daily in clinical practice. Pupil the spinal cord, ascends through the iris dilator. Drops that antagonize constriction (miosis) can either be thorax and synapses near the apex the parasympathetic pathway block stimulated by contraction of the iris of the lung into the superior cervical acetylcholine, a neurotransmitter of sphincter or by relaxation of the iris ganglion. The third postganglionic the autonomic nervous system, from dilator. On the other hand, pupil dila- neuron travels to the cavernous sinus reaching muscarinic receptors, which tion (mydriasis) can either be stimu- and enters the orbit through the short are located within the iris sphincter.1,4 lated by contraction of the iris dilator and long ciliary nerves, synapsing to This leads to relaxation of the iris or by relaxation of the iris sphincter. the iris dilator.1,2 sphincter and promotes mydriasis. Miotic and mydriatic drops work by Contrarily, the parasympathetic On the other hand, mydriatic drops acting on these different muscles of pathway is mainly responsible for that promote the sympathetic path- the iris. The drops are able to control pupil miosis.1,3 Pupil constriction way prevent the reuptake of norepi- pupil size by targeting two parts of starts when light enters the retina nephrine, another neurotransmitter the autonomic nervous system: the and activates the retinal ganglion of the autonomic nervous system, sympathetic and parasympathetic sys- cells—the beginning of the affer- from the synapse.1 This allows more tems. Let’s review their function and ent arm—which then transmit their norepinephrine to bind to alpha-one clinical role to better understand their impulses into the optic nerve. This adrenergic receptors on the iris dilator, present uses and why some of these stimulus travels to the optic chiasm, stimulating the activation of the iris agents are undergoing re-evaulation through the optic tract and eventually dilator and leading to mydriasis. for potential new ones. reaches the pretectal nucleus. The Miotic drops work by either pro- impulses from the pretectal nucleus moting the parasympathetic pathway Behind the Scenes begin the efferent arm, which projects to the iris sphincter or by inhibiting The sympathetic pathway, mainly re- to the Edinger-Westphal nucleus. The the sympathetic pathway to the iris sponsible for pupil mydriasis, involves Edinger-Westphal nucleus gives rise dilator.1,5 Taking the former route, a three-neuron pathway.1,2 The first to preganglionic fibers, which then these drops mimic the activity of

About Dr. Asnaashari graduated from the UC Berkeley School of Optometry in 2018. He is a therapeutic- and glaucoma-certified optometrist in Sacramento, CA, and the author a Fellow of the American Academy of Optometry. One of his areas of expertise is specialty contact lenses. He has no financial interests to disclose.

56 REVIEW OF OPTOMETRY | MAY 15, 2021 ever, it can also induce myopic shifts in those who have anatomically nar- and precipitate retinal detachments. row angles. The following are several For these reasons, pilocarpine is not established drops and associated clini- commonly used in general practice. cal pearls of each: Pilocarpine is a direct muscarinic Parasympatholytics. Tropicamide, acetylcholine agonist, or a parasympa- cyclopentolate and atropine are all thomimetic. It binds to the M3 mus- mydriatic drops that are traditionally carinic receptor, an excitatory receptor used for dilated fundus examination, in the iris sphincter and ciliary body. paralysis of accommodation, anterior This leads to an upregulation of cal- uveitis treatment, myopia control cium and smooth muscle contraction and pharmacological penalization for of the iris sphincter and ciliary body. amblyopia treatment.8-10 The contraction of the iris sphincter Tropicamide is typically used for causes the pupil to decrease in size, dilated fundus exam, paralysis of and the contraction of the ciliary accommodation and anterior uveitis body opens the trabecular meshwork, treatment. It has a strong mydriatic ef- decreasing IOP by enhancing aqueous fect, rapid onset and shorter duration outfl ow. of action in comparison with cyclo- Sympathomimetics. Brimonidine and pentolate and atropine. Its disadvan- apraclonidine are miotic drops that tages include its ineffectiveness at Tropicamide has a strong mydriatic effect. are typically used to lower IOP and inhibiting accommodation and its side assist with post-surgical glare, ocular effects of light sensitivity and blurred acetylcholine, and when they bind to redness and diagnosis of pupil abnor- vision. muscarinic receptors, the iris sphincter malities (e.g., Horner’s syndrome).7 Cyclopentolate is commonly used contracts and pupil size decreases. These drops are able to rapidly lower to inhibit accommodation and treat Drops that inhibit the sympathetic IOP and are readily available. They amblyopia and anterior uveitis. It is pathway can also stimulate pupil mio- are contraindicated in patients with effective at accommodation paralysis. sis. These drops selectively bind to underlying asthma and those taking On the other hand, it has a long onset alpha-two adrenergic receptors, which MAO inhibitors. They are also more of action, long duration of action and are responsible for decreasing the strongly associated with allergic reac- sympathetic tone. These receptors are tions. located on the iris dilator, which when Both of these drops exhibit selec- activated leads to a decrease in the tive alpha-two adrenergic agonist amount of norepinephrine released activity. They bind directly to alpha- into the synapse. This reduces the two adrenergic receptors, which are sympathetic tone on the iris dilator inhibitory receptors of the sympa- and encourages pupil miosis. thetic system. These receptors are present on the iris dilator, ciliary body Miotic Drops and conjunctival blood vessels. They These drops can be used for a number cause a downregulation of cAMP of things, including diagnosis of pupil and a decrease in the sympathetic abnormalities (e.g., Adie’s tonic pupil) tone, leading to iris dilator relaxation, and treatment of ocular hypertension, increasing uveoscleral outfl ow and acute angle closure, dry eye and post- decreasing aqueous production and surgical glare.3 Exercise caution or vasoconstriction. avoid use altogether in patients who are pregnant, breastfeeding or at risk Mydriatic Drops of retinal detachment. The following These drops can be used to perform are several established drops and as- dilated fundus examination, diagnose sociated clinical pearls of each: pupil abnormalities (e.g., Horner’s Parasympathomimetics. Pilocarpine syndrome), treat anterior uveitis and is a miotic drop that is used primarily engage in pharmacological penaliza- to treat ocular hypertension.6 It can tion for amblyopia.2 Exercise caution Cyclopentolate can effectively inhibit effectively lower intraocular pressure or completely avoid use in patients accommodation to help treat amblyopia (IOP) and is easily accessible. How- who are pregnant or breastfeeding and and anterior uveitis.

MAY 15, 2021 | REVIEW OF OPTOMETRY 57 Feature PUPIL CONTROL

has a weak mydriatic effect and should fectiveness of low-dose atropine. The not be used alone for dilated fundus investigators found that if the con- examination. centration of atropine is low enough, Phenylephrine promotes the sympa- it is possible to avoid side effects of thetic pathway as a selective alpha-one photophobia and blurred vision while adrenergic receptor agonist. Alpha-one still controlling myopic progression.13,14 receptors are excitatory receptors of The Low-Concentration Atropine for the sympathetic system and reside in Myopia Progression (LAMP) study the iris dilator and conjunctival blood showed that 0.05% atropine had the vessels. Activation of these recep- most profound effect on minimiz- tors causes an upregulation of cAMP, ing myopic progression and axial which leads to iris dilator contraction elongation compared with 0.01% and and vasoconstriction. 0.025%.15 Sympathomimetics and parasympatho- Furthermore, new clinical studies lytics. Paremyd (hydroxyamphetamine are looking into the effectiveness of 1% and tropicamide 0.25%, Akorn) is combination treatments for myopia a mydriatic that is traditionally used control. The Bifocal and Atropine for dilated fundus examination.12 It in Myopia (BAM) study is assessing has a rapid onset of action, reduced the pharmacological effect of 0.01% effect on accommodation and shorter atropine with the optical effect of soft 16 Phenylephrine should not be the sole drop duration of action. Its disadvantages bifocal contact lenses. Studies like used for dilated fundus examination, as it include a reduced mydriatic effect on these could lead to additional novel has a weaker mydriatic effect. dark irides, decreased ability to inhibit strategies to either optimize or provide accommodation and a side effect pro- greater slowing of myopia progression side effect profi le that includes light fi le that includes light sensitivity and than single-treatment strategies. sensitivity and blurred vision. The blurred vision. Presbyopia. Another area of focus for long duration of action makes this Hydroxyamphetamine acts as an pharmaceutical companies has been a viable drop of choice for anterior adrenergic agonist and blocks the developing noninvasive treatments for uveitis treatment to prevent anterior breakdown of norepinephrine. This presbyopia. The race to develop ef- synechiae. increases the sympathetic tone and in- fective treatments for the underlying Similar to cyclopentolate, atropine directly initiates contraction of the iris cause of symptoms is underway. is traditionally used to inhibit accom- dilator. Tropicamide has antimuscarin- One of the most interesting avenues modation, manage amblyopia, treat ic activity and inhibits the muscarinic of presbyopia treatment involves the anterior uveitis and provide myopia receptors on the iris sphincter, leading use of topical drops to alter the pupil control. It has a strong mydriatic effect to pupil dilation. size to aid near vision. The challenge and is effective at inhibiting accom- with miotic drops is avoiding too much modation and slowing the progression In the Pipeline pupil constriction, as this can have a of myopia. Its disadvantages mirror The exploration of pharmaceutical negative impact on distance vision, those of cyclopentolate. advancements in the areas of myopia night vision and even visual fi eld. The The mechanism of action of each of control, presbyopia and dilation is on key to a productive presbyopia drop is these drops is identical: they all have the rise. fi nding the miosis “sweet spot.” direct antimuscarinic activity. They Myopia. The increasing prevalence Allergan is in the process of devel- competitively bind to muscarinic re- of myopia worldwide and its associ- oping a presbyopic drop known as ceptors on the iris sphincter and ciliary ated risk factors have led to a public AGN-190584, which consists of an body and inhibit their activity. This health crisis. Historically, orthokera- optimized formulation of pilocarpine, results in a downregulation of calcium tology has been a leading option for a muscarinic receptor agonist, the and induces smooth muscle relaxation slowing myopic progression, but activation of which causes the iris of the iris sphincter and ciliary body. ophthalmic drops are catching up and sphincter and ciliary body to contract. Sympathomimetics. Phenylephrine may potentially surpass this modal- This can enhance depth of focus and is a mydriatic drop that is traditionally ity. Treatment with low-dose atropine promote accommodation.17 used for dilated fundus examination, has been increasing in popularity as Another company, Orasis, is also de- ocular redness relief and diagnosis of more evidence continues to show its veloping a miotic drop to constrict the pupil abnormalities (e.g., Horner’s syn- effectiveness. The Atropine for the pupil, known as CSF-1. Its complete drome).11 It has a rapid onset of action Treatment of Myopia studies (ATOM composition has not yet been released, and is easily accessible. However, it 1 and ATOM 2) demonstrated the ef- but it appears to be a combination of

58 REVIEW OF OPTOMETRY | MAY 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 keratoconjunctivitis 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 blepharitis, 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 PUPIL CONTROL a parasympathomimetic agent and a fects of routine pupil dilation. The nonsteroidal anti-infl ammatory agent drop, Nyxol (phentolamine 0.75%), is in an oil-based vehicle.18 currently undergoing clinical trials to In addition, Presbyopia Therapies is determine its safety and effi cacy. developing a presbyopic drop, called With a drop like this, subjects may Liquid Vision, that produces miosis be able to return to near baseline pupil without stimulating accommodation. diameter and accommodation within Rather than using pilocarpine, the ac- two hours, independent of the myd- tive ingredient is aceclidine, which has riatic agent used. Patients commonly a different mechanism of action that defer routine dilation due to the long- may provide a greater depth of fi eld lasting and disruptive side effects. If than pilocarpine.19 Nyxol shows promise, it could offer a Visus Therapeutics is using a novel solution to signifi cantly improve combination of ingredients to achieve the patient experience when it comes a similar effect. Brimochol is a once- to routine dilation.23 daily drop that combines carbachol Paremyd is commonly the drop of choice and brimonidine tartrate to provide Take-home Message for pupil dilation. functional near vision for at least eight The autonomic nervous system plays hours.20 10. Li FF, Yam JC. Low-concentration atropine eye drops an important role in managing pupil for myopia progression. Asia Pac J Ophthalmol (Phila). While recent pharmaceutical strate- size. Parasympathetic and sympathetic 2019;8(5):360-5. gies for presbyopia focus on altering innervation compete for control over 11. Matsumoto S, Tsuru T, Araie M, et al. Pharmacokinetics of topical phenylephrine hydrochloride in the normal human pupil size and the ciliary body, others the pupil. The sympathetic system eye. Jap J Ophthalmol. 1981;26(3):338-44. are investigating targeted approaches dilates it, while the parasympathetic 12. Bartlett JD, Janus SD. Clinical Ocular Pharmacology. 5th to alter the crystalline lens. Studies system constricts it. The diameter edition. St. Louis, MO: Butterworth-Heinemann; 2008. have suggested that the formation 13. Chua WH, Balakrishnan V, Chan YH, et al. Atropine of the pupil at any time refl ects the for the treatment of childhood myopia. Ophthalmology. of disulfi de bonds within the crystal- balance of these two forces acting 2006;113:2285-91. line lens restricts the ability of the simultaneously. 14. Chia A, Chua WH, Cheung YB, et al. Atropine for the treatment of childhood myopia: safety and effi cacy of 0.5%, lens to change shape in response to The pupil response to miotic and 0.1%, and 0.01% doses (atropine for the treatment of myopia ciliary muscle contraction.21 Due to its mydriatic drops is directly dependent 2). Ophthalmology. 2012;119:347-54. decline in fl exibility with age, alter- 15. Yam JC, Jiang Y, Tang SM, et al. Low-Concentration on which of these two autonomic sys- Atropine for Myopia Progression (LAMP) study: a random- ing the lens shape could be a future tems is activated or inhibited. These ized, double-blinded, placebo-controlled trial of 0.05%, avenue for novel treatment strategies. 0.025%, and 0.01% atropine eye drops in myopia control. drops continue to play a pivotal role in Ophthalmology. 2018;126(1):113-24. Routine dilation. Newer mydriatic clinical practice, with new alternatives 16. Huang J, Mutti DO, Jones-Jordan LA, et al. Bifocal & atro- drops for routine dilation did not ex- paving the way for treatments that pine in myopia study: baseline data and methods. Optom Vis ist until recently. Eyenovia is near- Sci. 2019;96(5):335-44. were previously unavailable. ■ 17. Phase 3 effi cacy study of AGN-190584 in participants ing FDA approval for its new drop, with presbyopia. Allergan. www.allerganclinicaltrials.com/ MydCombi, which contains a fi xed 1. McDougal DH, Gamlin PD. Autonomic control of the eye. en/trial-details/?id=1883-301-013. Accessed March 23, Compr Physiol. 2015;5(1):439-73. 2021. combination of phenylephrine and 2. Lykstad J, Reddy V, Hannah A. Neuroanatomy, Pupillary 18. CSF-1 overview. Orasis. www.orasis-pharma.com/our- tropicamide. The drop would be the Dilation Pathway. In: StatPearls [Internet]. Treasure Island, solution/csf-1-overview/. Accessed March 23, 2021. fi rst microdosed ocular therapeutic FL: StatPearls Publishing; 2020. 19. Lipner M. A unique drop. EyeWorld. October 2014. www. 3. Belliveau A P, Somani AN, Dossani RH. Pupillary Light Re- eyeworld.org/article-a-unique-drop. Accessed March 23, that contains a smart delivery system. fl ex. In: StatPearls [Internet]. Treasure Island, FL: StatPearls 2021. According to the company, Eyeno- Publishing; 2020. 20. Visus Therapeutics announces FDA acceptance of IND via’s Optejet dispenser is designed to 4. Smith SV, Dake BA, Panneerselvam S. Pharmacologic to proceed with clinical development of presbyopia-correct- dilation of pupil. EyeWiki. eyewiki.aao.org/Pharmacologic_di- ing eye drop. Eyewire News. March 16, 2021. eyewire.news/ provide a consistent, effi cient and easy lation_of_pupil. December 29, 2020. Accessed March 17, articles/visus-therapeutics-announces-fda-acceptance-of- 2021. ind-for-presbyopia-correcting-eye-drop/. Accessed March touchless application of two mydriatic 23, 2021. 5. Harvey RD. Muscarinic receptor agonists and antagonists: medications. The bottle design of effects on cardiovascular function. Handb Exp Pharmacol. 21. Garner WH, Garner MH. Protein disulfi de levels and lens MydCombi contains no protruding 2012;(208):299-316. elasticity modulation: applications for presbyopia. Invest Ophthalmol Vis Sci. 2016;57(6):2851-63. parts, which can help prevent ac- 6. Panarese V, Moshirfar M. Pilocarpine. In: StatPearls [Inter- net]. Treasure Island, FL: StatPearls Publishing; 2020. 22. Eyenovia announces FDA acceptance of the MydCombi NDA. Business Wire. March 2, 2021. www.businesswire. cidental interaction with the ocular 7. Yüksel N, Karabaş L, Altintaş O, et al. A comparison of the com/news/home/20210302005329/en/. Accessed March 22 short-term hypotensive effects and side effects of unilateral surface. 23, 2021. brimonidine and apraclonidine in patients with elevated intra- Reverse dilation. Currently, there are ocular pressure. Ophthalmologica. 2002;216:45-9. 23. Ocuphire announces publication of MIRA-1 Phase 2b results demonstrating reduction of pharmacologically no FDA-approved drops to reverse 8. Alimgil ML, Erda N. The cycloplegic effect of atropine in induced mydriasis by Nyxol. Eyewire News. March 5, 2021. comparison with the cyclopentolate-tropicamide-phenyleph- pharmacological dilation. Ocuphire eyewire.news/articles/ocuphire-announces-publication- rine combination. Klin Monbl Augenheilkd. 1992;201(1):9-11. Pharma is currently developing an of-mira-1-phase-2b-results-demonstrating-reduction-of- 9. Wallace DK, Repka MX, Lee KA, et al. Amblyopia preferred pharmacologically-induced-mydriasis-by-nyxol/. Accessed option that counteracts the side ef- practice pattern. Ophthalmology. 2018;125(1):P105-42. March 23, 2021.

MAY 15, 2021 | REVIEW OF OPTOMETRY 61 Feature GLAUCOMA TREATMENT PEER REVIEWED

Make Glaucoma Therapy More Patient-Friendly

Here’s how to better ensure patient adherence to treatment.

By Michael Dorkowski, OD, Helping pa- Photo: The Eye Center at SCO Shaleen Ragha, OD, and tients understand Jennifer Sanderson, OD memphis the disease, set long-term expec- t is estimated that glaucoma affects tations, embrace over three million Americans and various thera- over 76 million adults over the age of peutic options I40 worldwide.1,2 By 2050, glaucoma and anticipate is expected to impact nearly eight potential hurdles million adults in the United States and plays an essential over 110 million around the globe.3 role in success- Glaucoma is a leading cause of blind- ful outcomes; ness, and the only proven therapy that namely, slowing has been shown to decrease the risk the progression of progression is reducing intraocular of the disease pressure (IOP).4,5 and reducing Glaucomatous optic nerve. Historically, topical medications vision loss. This were the mainstay therapy; now the article focuses on the specifi c factors tics indicates roughly 10% of the US most effective management involves optometrists should address with their population was uninsured in the fi rst a continuum of both medical and patients for the best results with topi- quarter of 2020.11 With the COVID-19 surgical treatments.6,7 Multiple factors cal therapy. pandemic, these statistics are ex- determine which treatment paradigm pected to worsen as loss of jobs means bests suits each patient. Details such Price and Acquisition loss of employer-provided insurance.12 as the disease severity at the time of Cost is one of the most important Even having insurance or a Medicare diagnosis, rate of disease progression, things to keep in mind to encourage plan does not necessarily guarantee age of the patient, ocular and sys- adherence to therapy and patient an associated drug benefi t. Sampling temic comorbidities, allergies, previous compliance.9,10 Financial constraints a new drop is only effective if the therapy, cost of treatment, target IOP are a real issue many patients face in patient can afford it, let alone locate it and other patient-specifi c issues and today’s healthcare system. Data from at a nearby pharmacy and tolerate its preferences must be considered.8 the National Center for Health Statis- side effects.

Dr. Dorkowski is an associate professor at the Southern College of Optometry (SCO). Clinically, he works in the advanced care ocular disease and the adult primary care clinics and is coordinator of the nursing home and assisted living programs at the Eye Center at SCO. Dr. Ragha is a clinical instructor at SCO. She About the authors sees patients and supervises students in a clinical setting at the Eye Center, in the primary care, ocular disease and fl uorescein angiography departments, and at the Focal Point at Crosstown Concourse in Memphis. Dr. Sanderson is an associate professor and the assistant director of residency programs at SCO. The authors have no fi nancial interests to disclose.

62 REVIEW OF OPTOMETRY | MAY 15, 2021 Lifetime medication use is ex- Table 1. Combination Medications Commercially Available in the United States pensive, especially if the disease progresses and the patient requires Name (Manufacturer) Ingredients additional therapy. This factor must CoSopt/CoSopt PF (Akorn) timolol maleate 0.5% + dorzolamide hydrochloride 2% be weighed against surgical interven- tion and the associated set of fees and Combigan (Allergan) timolol maleate 0.5% + brimonidine tartate 0.2% adverse effects. After taking all costs Simbrinza (Novartis) brinzolamide 1% + brimonidine tartate 0.2% into consideration, one study found that selective laser trabeculoplasty Rocklatan (Aerie) netarsudil 0.02% + latanoprost 0.005% (SLT) is typically less expensive than most long-term brand name medica- access to manufacturer-sponsored of patients who start topical glaucoma tions.13 Another study reported that patient assistance programs, coupons, therapy are noncomplaint or have S LT effectively maintained IOP in rebate programs and even drug de- completely discontinued their pre- newly diagnosed glaucoma and ocular livery. Discussing all of these options scribed medications by six months.20 hypertensive patients over a 36-month with patients can help them under- An additional study analyzed dispens- period.14 Patients who had S LT were stand their choices and how to best ing records to determine the degree at or below target IOP readings for afford their care.15 of adherence for glaucoma medication more follow-ups than their counter- To that end, online formulary search refi lls at community pharmacies and parts on topical therapy.14 tools can ensure the recommended found that over a 12-month period, Prescribing generic medications therapy is cost effective for each pa- only about 57% of patients had the when possible can also be a less tient. Many insurance providers post proper amount of medication to last costly alternative. However, the cost their medication formularies online the year.19 In addition to cost and of generic medications is set by each through easily accessible platforms. accessibility, several other factors can individual pharmacy, so price may There are also several search engines help us avoid these outcomes. vary widely, even within the same and associated cell phone apps that community. Two optometrists started offer information on medication Routine and Regimen werx.org to help patients determine coverage for a multitude of insurance Patients often have diffi culty fi tting the cost analysis of medications across providers in a region. Such resources glaucoma drops into their established local pharmacies for both name brand include www.formularylookup.com, routine due to forgetfulness.21-23 Ask- and generic medications. A similar lookup.decisionresourcesgroup.com, ing patients about the details of their feature is offered on www.goodrx.com. www.epocrates.com and www. daily routine, such as when they wake Many pharmacies and other organiza- healthcare.gov.16 up, work, eat and sleep, can assist in tions (including ScriptSave WellRx) Insurance considerations and fi nan- drop integration. When a patient’s have membership plans that offer cial concerns can be a limiting factor lifestyle needs dictate an atypical opportunities for reduced medica- to medication compliance, yet optom- dosing schedule, optometrists must tion cost. It would be benefi cial for etrists spend little time discussing the understand how to best accommodate prescribers to review local providers to cost of therapy with their patients—a the patient. For example, patients evaluate what ophthalmic drugs may barrier that we can easily over- who have evening or overnight work be available and at what cost. come.17,18 Even if the patient is able schedules may benefi t from altering Additional web-based resources to afford and obtain the prescribed the typical nightly dosing regimen and such as www.needymeds.org and medication, non-adherence is one of instead take prostaglandin analogs in www.blinkhealth.com offer ways to the most important and costly world- the morning in conjunction with their assist patients in navigating the cost of wide healthcare problems.19 A recent sleep schedule to maintain IOP. One their medications, including one-stop study demonstrated that roughly half study showed that mean 24-hour IOP control was equivalent when compar- ing travoprost dosed in the morning Table 2. Compounded Combination Medications Available Through ImprimisRx vs. in the evening.24 brimonidine (0.15%) + dorzolamide (2%) If a patient is already compliant with other regimens such as oral med- timolol (0.5%) + brimonidine (0.15%) + dorzolamide (2%) + latanoprost (0.005%) ications and self-care routines such as timolol (0.5%) + brimonidine (0.15%) + dorzolamide (2%) brushing teeth, placing the eye drops near their medication or toothbrush timolol (0.5%) + dorzolamide (2%) + latanoprost (0.005%) may improve compliance with ther- apy. To optimize the 12- or 24-hour timolol (0.5%) + latanoprost (0.005%) effect of the bulk of glaucoma drops,

MAY 15, 2021 | REVIEW OF OPTOMETRY 63 Feature GLAUCOMA TREATMENT

Instillation tors observed similar reductions in Administering the drop IOP with this method compared with itself can be exceedingly direct instillation onto the cornea.33 difficult for some pa- Directing your patient to resources tients with limited mo- on drop administration such as www. bility or arthritis. Poor glaucoma.org and www.aoa.org can be aim, inability to extend beneficial in giving them a reference their neck and dexter- point and tips on how to apply the ity issues can all add up medication to the eye.34,35 to cause an undesirable result. In fact, one study Complications found that nearly nine Side effects of medications are another out of every 10 glau- common barrier to drug adherence coma patients were un- encountered by patients with glau- able to instill eye drops coma. These patients overcome the correctly.28 Another obstacles of obtaining and instill- found that patients ing the drop only to be thwarted by administer an average intolerable adverse events, which can of seven drops before be temporary or persistent. Stinging, they feel confident in redness and burning are common the instillation process.29 sequelae of drop instillation. Storing The author of the latter the drop in the refrigerator can help The Autodrop Eye Drop Guide (Maddak) can help patients study published a video alleviate these complaints and helps with drop instillation. titled “Glaucoma Drop the patient with proper administration Operator Error” that onto the ocular surface as the drop is setting reminders can be beneficial. can be found at eyetube.net/videos/ easier to detect.34 Cell phone alarms, calendar alerts glaucoma-drop-operator-error. Another consideration is the effect and app reminders are all options. A Finally, other researchers concluded these medications have on pre- study showed that 72.9% of glaucoma that despite excellent confidence in existing ocular conditions or diseases, patients expressed interest in using an their ability, patients rarely adminis- especially when it comes to dry eye.36 app, one of the more popular routes ter topical ophthalmic drops without Controlling and treating the underly- that we can take advantage of.25 Along touching the bottle to their eye, which ing disease concurrently with glau- with these recommendations, phar- increases risk of infection.30 Punctal coma treatment can help prevent macy auto-refills or mail orders are also occlusion or eyelid closure for three ocular discomfort. Preservatives advised so that patients do not run out to five minutes post-instillation is an that are inherent in topical therapy of their medications. important final step of the process that can exacerbate discomfort, specifi- The complexity of the dosing regi- many patients miss, as it can have the cally benzalkonium chloride (BAK).37 men can also affect adherence. Simply intended effect of increasing ocular To alleviate this dilemma, use of adding a second eye drop to the penetrance and decreasing systemic preservative-free medication—Zi- regimen can increase dosing errors by absorption.31 optan (tafluprost, Akorn), CoSopt PF nearly 400%.15,26 There are a multitude In-office training, including watch- (dorzolamide hydrochloride-timolol of combination agents available com- ing the patient administer a drop maleate, Akorn), Timoptic in Ocudose mercially and through compounding to their eye, can help mitigate and (timolol maleate, Bausch + Lomb)— pharmacies that can make treatment correct many instillation mistakes. To or alternatives to BAK-preserved coordination and adherence easier for aid in the instillation process, there medication—Travatan Z (travoprost, patients (Tables 1 and 2).27 are several different types of auto Novartis), Alphagan P (brimonidine, Adherence to follow-up appoint- drop mechanisms and guides on the Allergan), Xelpros (latanoprost, Sun ments is still necessary to complete di- market.32 Some are pharmaceutical Pharmaceutical)—are recommended, agnostic testing to ensure the patient’s company-specific, and others can be especially for those who require ad- daily routine and glaucoma medication obtained online for use with a variety ditional therapy.38 are sufficient in disease control, and of different-sized bottles. One study Requesting the patient bring their pre-appointing follow-up exams helps proposed using an alternate instillation medication bottle with them to subse- ensure patients return for their on- technique into the medial canthal area quent appointments may be necessary going assessments. over a closed eyelid.33 The investiga- when attempting to decipher patient

64 REVIEW OF OPTOMETRY | MAY 15, 2021

complaints and confirm they are taking the correct drug in the first place.

Patient Education Upon prescribing a new medication, effective education can help guide patient expectations moving forward.39 Patients may notice mild momentary blurring or clearing of their vision from the effect of the drop on the ocular surface and assume it is a problem with the efficacy of the medication rather than a temporary adverse effect.21 We can resolve this popular misconception with clear communication prior to the patient beginning their regimen. If side effects persist and are intolerable, however, patients must understand the importance of calling the office, as the medication may be substituted. Glaucoma management can be fraught with miscommunication, and health literacy plays an important role in patient compliance and disease treatment.22 A study found that 44% of patients in an urban American set- ting did not have an acceptable idea of what the term “glaucoma” means Glaucomatous visual defects tend to appear as negative scotomas, but rather than and that 30% were unsure as to why presenting as dark or blurred, the brain creates an inaccurate but believable image in the they were taking medications in the defective visual field using surrounding retinal images. By late stages of the disease, the first place.40 Without appropriate brain no longer receives sufficient visual input to compose an image. understanding of their disease or its management, patients lose motivation 45% of patients were completely un- matous risks or signs when a previous and can progress to advanced stages aware of the true nature of their vision provider did not, the patient may of glaucoma due to poor adherence to loss.42 The survey showed that patients question their judgment. Patients may treatment and follow-up.41 do not have tunnel vision or perceive also assume their glaucoma is similar to Many individuals may not even want black spots in their vision; rather, they an acquaintance’s, but glaucoma status to pursue treatment until symptoms see blurred patches. Patients should varies based on type of glaucoma, rate present; hence, doctors must advise be informed that glaucoma is slowly of progression and treatment history. that the associated vision loss is irre- progressive and they will likely be Written instructions as a follow-up versible. Patients should be reminded asymptomatic until advanced visual to verbal education can help alleviate that treatment is not geared toward field loss occurs. Hence the importance misunderstandings the patient may prevention of glaucoma, but rather of treatment continuation despite per- encounter. A study showed that even prevention of vision loss. Along these ceived subjective improvements. after a patient has been successful lines, patients should not get into the Some patients rarely participate with their drug regimen for over a year, habit of assuming a lower IOP read- in preventive care or routine screen- continued education and positive rein- ing equates to adequate control and ings or physicals to begin with. These forcement have ongoing benefits.44 An- stop using their drops or only use them patients may only seek medical care other confirmed positive reinforcement prior to an appointment. if any problems or symptoms that do increases short-term improvements in Patients should also be informed of arise fail to improve. On the other measures regarding adherence.15 As op- their test findings and rate of progres- hand, some patients are too discour- tometrists, it is our job to continuously sion, when applicable. Perceptual visu- aged to seek out medical care, whether educate our glaucoma patients on the al field loss can be vastly different from due to trust issues with the physician purpose of their therapy and follow- what doctors observe on automated or unfavorable practice conditions.22,43 ups, and the risks of abstinence and visual field testing. One study found If one optometrist discovers glauco- progressive visual loss.23,45

MAY 15, 2021 | REVIEW OF OPTOMETRY 67 Feature GLAUCOMA TREATMENT Photos: The Eye Center at SCO

The PanoMap feature on the Zeiss Cirrus OCT (left) exhibits thinning of both the retinal nerve fi ber layer and ganglion cell layer- inner plexiform layer complex with a corresponding visual fi eld result (right) showing a superior nasal step defect.

Health Statistics. February 2021. www.cdc.gov/nchs/data/nhis/ 28. Gupta R, Patil B, Shah BM, et al. Evaluating eye drop Takeaways earlyrelease/insur202102-508.pdf. Accessed March 11, 2021. instillation technique in glaucoma patients. J Glaucoma. 2012;21(3):189-92. Glaucoma patients are in it for the long 12. McDermott D, Cox C, Rudowitz R, et al. How has the pandemic affected health coverage in the U.S.? KFF. December 29. Robin AL. Instilling drops. Glaucoma Today. September haul. Place an emphasis on clear, direct 9, 2020. www.kff.org/policy-watch/how-has-the-pandemic- 2010. [Epub ahead of print]. affected-health-coverage-in-the-u-s/. Accessed March 11, 2021. instructions to aid in manageable, 30. Stone JL, Robin AL, Novack GD, et al. An objective evalu- patient-friendly care. Be supportive 13. Seider MI, Keenan JD, Han Y. Cost of selective laser ation of eyedrop instillation in patients with glaucoma. Arch trabeculoplasty vs topical medications for glaucoma. Arch Ophthalmol. 2009;127(6):732-6. and empathetic while actively listening Ophthalmol. 2012;130(4):529-30. 31. Flach AJ. The importance of eyelid closure and naso- and providing solutions to patient con- 14. Gazzard G, Konstantakopoulou E, Garway-Heath D, lacrimal occlusion following the ocular instillation of topical et al. Selective laser trabeculoplasty versus eye drops for glaucoma medications, and the need for the universal inclusion cerns regarding possible barriers to ef- fi rst-line treatment of ocular hypertension and glaucoma of one of these techniques in all patient treatments and clinical fective treatment. Advocating for your (LiGHT): a multicentre randomised controlled trial. Lancet. studies. Trans Am Ophthalmol Soc. 2008;106:138-45. 2019;393(10180):1505-16. patient and helping them overcome 32. Davies I, Williams AM, Muir KW. Aids for eye drop adminis- 15. Robin AL, Muir KW. Medication adherence in patients with tration. Surv Ophthalmol. 2017;62(3):332-45. the challenges they may face will assist ocular hypertension or glaucoma. Expert Rev Ophthalmol. 2019;14(4-5):199-210. 33. Freddo TF, Ho DY, Steenbakkers M, et al. Validation of a in ensuring a successful partnership in more reliable method of eye drop self-administration. Optom 16. Davison R. Making drug formulary search tools better for Vis Sci. 2020;97(7):496-502. their long-term care.  patients. The Catalyst. September 7, 2016. catalyst.phrma. org/making-drug-formulary-search-tools-better-for-patients. 34. Gudgel DT. How to put in eye drops. American Academy of Accessed March 11, 2021. Ophthalmology. March 10, 2021. www.aao.org/eye-health/treat- 1. Vajaranant TS, Wu S, Torres M, et al. The changing face ments/how-to-put-in-eye-drops. Accessed March 11, 2021. of primary open-angle glaucoma in the United States: demo- 17. Slota C, Davis SA, Blalock SJ, et al. Patient-physician com- graphic and geographic changes from 2011 to 2050. Am J munication on medication cost during glaucoma visits. Optom 35. Robin AL. Glaucoma eye drops: suggestions on use. Glau- Ophthalmol. 2012;154(2):303-14. Vis Sci. 2018;95(6):554. coma Research Foundation. October 29, 2017. www.glaucoma. 2. Tham YC, Li X, Wong TY, et al. Global prevalence of org/treatment/glaucoma-eye-drops-suggestions-on-use.php. 18. Rylander NR, Vold SD. Cost analysis of glaucoma medica- Accessed March 11, 2021. glaucoma and projections of glaucoma burden through 2040: tions. Am J Ophthalmol. 2008;145(1):106-13. a systematic review and meta-analysis. Ophthalmology. 36. Zhang X, Vadoothker S, Munir WM, et al. Ocular surface 2014;121(11):2081-90. 19. Feehan M, Munger MA, Durante R, et al. Adherence to disease and glaucoma medications: a clinical approach. Eye glaucoma medications over 12 months in two US community Contact Lens. 2019;45(1):11-8. 3. Vajaranant TS, Wu S, Torres M, et al. A 40-year forecast of pharmacy chains. J Clin Med. 2016;5(9):79. the demographic shift in primary open-angle glaucoma in the 37. Rosin LM, Bell N P. Preservative toxicity in glaucoma medica- united states. Invest Ophthalmol Vis Sci. 2012;53(5):2464-6. 20. Nordstrom BL, Friedman DS, Mozaffari E, et al. Persistence tion: clinical evaluation of benzalkonium chloride-free 0.5% and adherence with topical glaucoma therapy. Am J Ophthal- 4. Weinreb RN, Aung T, Medeiros FA. The pathophysiology and timolol eye drops. Clin Ophthalmol. 2013;7:2131-5. mol. 2005;140(4):598-606. treatment of glaucoma: a review. JAMA. 2014;311(18):1901-11. 38. Yadgarov A, Garg RA. Preservative-free alternatives. Glau- 21. Taylor SA, Galbraith SM, Mills R P. Causes of non-compliance 5. Flaxman SR, Bourne RRA, Resnikoff S, et al. Global causes coma Today. November/December 2016. [Epub ahead of print]. of blindness and distance vision impairment 1990–2020: a with drug regimens in glaucoma patients: a qualitative study. J Ocul Pharmacol Ther. 2002;18(5):401-9. 39. Budenz DL. A clinician’s guide to the assessment and systematic review and meta-analysis. Lancet Glob Health. management of nonadherence in glaucoma. Ophthalmology. 2017;5(12):e1221-34. 22. Newman-Casey PA, Robin AL, Blachley T, et al. The most 2009;116(11):S43-7. 6. European Glaucoma Society Terminology and Guidelines for common barriers to glaucoma medication adherence: a cross- 40. Costa V P, Spaeth GL, Smith M, et al. Patient education in Glaucoma, 4th Edition - Part 1. Br J Ophthalmol. 2017;101(4):1- sectional survey. Ophthalmology. 2015;122(7):1308-16. glaucoma: what do patients know about glaucoma? Arq Bras 72. 23. MacKean JM, Elkington AR. Compliance with treatment of Oftalmol. 2006;69(6):923-7. 7. Preferred practice patterns committee G P. Chicago, IL: patients with chronic open-angle glaucoma. Br J Ophthalmol. American Academy of Ophthalmology; 2010. 1983;67(1):46-9. 41. Miller NH. Compliance with treatment regimens in chronic asymptomatic diseases. Am J Med. 1997;102(2A):43-9. 8. Fingeret M. Optometric clinical practice guideline, care of 24. Konstas AGP, Mikropoulos D, Kaltsos K, et al. 24-Hour the patient with open angle glaucoma. St. Louis, MO: American intraocular pressure control obtained with evening- versus 42. Crabb D P, Smith ND, Glen FC, et al. How does glaucoma Optometric Association; 2010. morning-dosed travoprost in primary open-angle glaucoma. look?: patient perception of visual fi eld loss. Ophthalmology. Ophthalmology. 2006;113(3):446-50. 2013;120(6):1120-6. 9. Tsai JC, McClure CA, Ramos SE, et al. Compliance barri- ers in glaucoma: a systematic classifi cation. J Glaucoma. 25. Waisbourd M, Dhami H, Zhou C, et al. The Wills Eye 43. Taber JM, Leyva B, Persoskie A. Why do people avoid medi- 2003;12(5):393-8. glaucoma app: interest of patients and their caregivers in a cal care? A qualitative study using national data. J Gen Intern smartphone-based and tablet-based glaucoma application. J Med. 2015;30(3):290-7. 10. Feldman RM, Cioffi GA, Liebmann JM, et al. Current knowl- Glaucoma. 2016;25(9):e787-91. edge and attitudes concerning cost-effectiveness in glaucoma 44. Curtis C, Lo E, Ooi L, et al. Factors affecting compliance pharmacotherapy: a glaucoma specialists focus group study. 26. Robin AL, Novack GD, Covert DW, et al. Adherence in glau- with eye drop therapy for glaucoma in a multicultural outpatient Clin Ophthalmol. 2020;14:729-39. coma: objective measurements of once-daily and adjunctive setting. Contemp Nurse. 2009;31(2):121-8. medication use. Am J Ophthalmol. 2007;144(4):533-40. 11. Cohen RA, Terlizzi E P, Cha AE, et al. Health insurance 45. McDonald JE, Dickinson JK. A novel approach to helping coverage: early release of estimates from the National Health 27. ImprimisRx. www.imprimisrx.com/search/ophthalmology. people with glaucoma use their drops routinely. Optom Vis Sci. Interview Survey, January-June 2020. National Center for Accessed March 11, 2021. 2019;96(5):331-4.

68 REVIEW OF OPTOMETRY | MAY 15, 2021 OCULAR RESPONSE ANALYZER® G3

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CATS® Tonometer Prism is the new shape of IOP. The patented, CATS Tonometer Prism’s dual-curved design successfully reduces measurement errors caused by corneal biomechanics, corneal thickness, and tear fi lm, which a ect a large percentage of patients.4-7 Modernize your Goldmann tonometer today with CATS Tonometer Prism.5-7

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· © 2021 AMETEK, Inc. & Reichert, Inc. (04-2021) · Ocular Response Analyzer is a registered trademark of Reichert, Inc. · Designed & assembled in USA · References: 1. Medeiros FA, Meira-Freitas D, Lisboa R, Kuang TM, Zangwill LM, Weinreb RN. Corneal hysteresis as a risk factor for glaucoma progression: a prospective longitudinal study. Ophthalmology. 2013 Aug;120(8):1533-40. 2. De Moraes CV, Hill V, Tello C, Liebmann JM, Ritch R. Lower corneal hysteresis is associated with more rapid glaucomatous visual fi eld progression. J Glaucoma. 2012 Apr-May;21(4):209-13. 3. Susanna CN, Diniz-Filho A, Daga FB, Susanna BN, Zhu F, Ogata NG, Medeiros FA. Am J Ophthalmol. A Prospective Longitudinal Study to Investigate Corneal Hysteresis as a Risk Factor for Predicting Development of Glaucoma. 2018 Mar;187:148-152. doi: 10.1016/j. ajo.2017.12.018. 4. McCa¥ erty S, Lim G, Duncan W, et al. Goldmann tonometer prism with an optimized error correcting applanation surface. Transl Vis Sci Technol 2016; 5:4–5. 5. McCa¥ erty S, Tetrault K, McColgin A, Chue W, Levine J, Muller M. Modifi ed Goldmann prism intraocular pressure measurement accuracy and correlation to corneal biomechanical metrics: multicentre randomised clinical trial. Br J Ophthalmol. 2019 Dec;103(12):1840-1844. doi: 10.1136/bjophthalmol-2018-313470. 6. McCa¥ erty S, Lim G, Duncan W, et al. Goldmann tonometer error correcting prism: clinical evaluation. Clin Ophthalmol 2017;11:835–40. 7. McCa¥ erty S, Enikov E, Schwiegerling J, et al. Goldmann tonometry tear-fi lm error and partial correction with a shaped applanation surface. Clin Ophthal 2018;12:71–8.*CATS® Tonometer Prism is distributed by Reichert Techonologies · CATS and CATS logo are trademarks of CATS Tonometer, LLC. Series COMANAGEMENT CONNECTIONS Part 3 of 6

Take the Fear out of comanaging neuro cases

Many patients are best served through a partnership between primary care optometrists and appropiate subspecialists.

By catlin nalley ing of these conditions. A prospective, Michael DelGiodice, OD, PhD, contributing writer cross-sectional study of cases sent to who practices in New Jersey, has neuro-ophthalmology subspecialists access to neuro-ophthalmologists; omanagement, a key aspect of (from both optometrists and general however, it can still be challeng- optometric practice, can take ophthalmologists) found that the re- ing to get appointments for patients many forms and this is especially ferral diagnosis was incorrect in 49% of quickly. “I typically always comanage Ctrue for neuro-ophthalmic cases. cases.1 The researchers reported that with neurology,” he explains, noting These complex conditions, which can 26% of misdiagnosed patients suffered that neuro-ophthalmologists usually be vision- or life-threatening, require harm, which could have been prevent- work with neurology as well. “As timely collaboration across various ed by earlier referral. In 23% of cases, optometrists, we have the knowledge specialties. patients experienced inappropriate and skills to work directly with these While challenging, these conditions laboratory testing, diagnostic imaging specialists.” can be comanaged successfully and or treatment prior to referral. Comfort level plays a key role in optometrists are in the perfect position Clearly, there’s plenty of headroom the referral pathway an optometrist to take a leadership role in the care of for optometry to grow its capabilities chooses to follow, notes Kelly Malloy, this patient population. in triaging neuro cases. OD, professor and chief of neuro- “It’s important to recognize that Given the seriousness of these ophthalmic disease at Pennsylvania there are too few neuro-ophthal- conditions, tackling the management College of Optometry. “If an optom- mologists to effectively manage the of neuro-ophthalmic patients can etrist has the confidence to do so, they number of patients that present with be overwhelming. As a part of our can directly handle imaging and refer- neuro-ophthalmic disorders,” notes comanagement series, this article will ral to neurology and neurosurgery,” Leonard Messner, OD, an optometric help lay the framework for a strong she says. “Since timely intervention is expert in care of neuro-ophthalmic referral relationship as well as offer critical for many neurologic conditions, disease and vice president for pa- clinical pearls and practical advice to it is important to take the most direct tient care services at Illinois College give ODs the confidence to take on referral route whenever possible.” of Optometry. “Therefore, it is very these patients. That isn’t to say that neuro-oph- important that the general optometrist thalmology has no role to play. For has a fundamental knowledge and Determining the Referral Pathway non-urgent cases, they can serve as a understanding of these disorders to Unlike other areas of optometry, such second opinion or additional resource, ensure comprehensive patient care.” as cataract or cornea care, the referral notes Dr. DelGiodice. In emergency Recent research highlights the pathway for neuro-ophthalmic cases is situations, waiting for an appointment important role ODs can play in the not always straightforward. Therefore, with a specialist—whether that’s the management of these patients and the it is important for ODs to have a clear neuro-ophthalmologist or neurolo- need for a comprehensive understand- plan on when and to whom they refer. gist—is not always an option. Those

70 REVIEW OF OPTOMETRY | MAY 15, 2021 cases require the ODs to make a judg- Direct, consistent communication three main components of the eye ment call and send their patient to the helps take the guesswork out of case examination (afferent assessment, emergency department for immediate management. “Nothing can replace efferent assessment and ocular health care. Once admitted to the hospital, picking up the phone and communi- assessment) and these conditions the patient will then be able to more cating peer-to-peer. This ensures the often have features that overlap with acutely benefit from the knowledge relationship is a two-way street and ev- a variety of other ocular and systemic and expertise of neuro-ophthalmolo- eryone is on the same page,” empha- conditions. Determining when and gists, neurologists and other specialists sizes Dr. Messner. “That is the art and when not to refer can be a difficult as needed, according to Dr. Malloy. science of medicine. It is the essence task. In some cases, the best specialist of taking care of people properly.” Common neurologic complaints may not be neurology related. For Given the complex, and often optometrists may encounter include instance, Dr. DelGiodice will refer a subtle, nature of neuro-ophthalmic diplopia, vision loss or visual distur- patient with unilateral disc edema or conditions, ODs must feel comfort- bances, and headaches. Facial and lid signs suggestive of incipient disc ede- able working collaboratively, but abnormalities, such as ptosis, propto- ma to a retina specialist for immediate, finding the right specialist can be a sis, facial weakness, head turn or tilt, same-day fluorescein angiography challenge. Visiting physicians at their and blepharospasm, can also indicate (FA). “These cases obviate the need office, whether by appointment or neurologic eye disease.2 for neuro-ophthalmic referral because dropping off your resume and making As with any type of condition, a the FA will elucidate the seat of the a quick introduction, can be a good detailed history is a vital first step, fol- pathology,” he notes. way to build connections, according to lowed by a comprehensive eye exam. Dr. DelGiodice. This should include blood pressure Fostering Strong Relationships “Writing comprehensive letters is measurement, relative afferent pupil- Like any comanagement relation- another way to enhance the referral lary defect assessment, measuring ship, building a partnership based on relationship,” he says, noting that this pupils and eyelids, visual field testing mutual trust and respect is vital to suc- is an effective approach to showcase and OCT.3 In addition, a cursory cess. This begins by finding special- your own skills and knowledge of neu- neurologic examination can also help ists who not only have strong clinical rologic conditions. Dr. DelGiodice also significantly with localization of the skills but also value the important suggests taking it a step further and abnormality. role optometry plays. Without this, a calling the office to discuss the case as “Optometrists should always con- true comanagement relationship that well. “Comanagement becomes easier sider that every patient might have a benefits both patients and providers is as you build that trust and both pro- neuro-ophthalmic disease process,” not possible. viders are confident in one another’s suggests Dr. Malloy, who notes that “Effective comanagement requires abilities.” while it may be obvious among a high level of coordination be- patients who present urgently, ODs tween providers, whether that is the Optimizing the Approach to also need to pay attention for signs of neuro-ophthalmologist, neurologist Neuro-Ophthalmic Care neuro-ophthalmic disease in patients or primary care provider,” notes Dr. Understandably, many neuro-ophthal- who present for routine care without Messner. “Building and maintaining a mic conditions can pose a challenge any specific complaints. “It is impor- strong relationship depends on com- for optometrists. Neuro abnormali- tant to comprehensively assess the munication.” ties can present within any of the afferent and efferent visual systems Photo: Kelly Malloy, OD Photo: Christopher Suhr, OD

The appearance of optic neuritis on MRI. Optometrists should be As many as 60% of myasthenia gravis patients, such as this one, comfortable knowing when and why to order neuroimaging work. present with ptosis and diplopia.

MAY 15, 2021 | REVIEW OF OPTOMETRY 71 Series COMANAGEMENT CONNECTIONS

Photo: Joseph Sowka, OD ment include aneurysm, giant cell arteritis, acute stroke, papilledema, pituitary apoplexy and carotid artery dissection.3 In these cases, timing is critical; ODs need to be ready to take imme- diate action and send their patients to the emergency department. Referring to their primary care provider or an- other specialist could cost the patient valuable time. “Optometrists have a significant role to play in recognizing Idiopathic intracranial hypertension is fairly commonly diagnosed by optometrists—and it’s emergency cases and acting according- incumbent on them to coordinate care, says Dr. Messner. ly,” explains Dr. Malloy, who suggests that ODs stay current on the latest as well as the ocular health status of optometrist’s role ends with the refer- recommendations as well as partici- every patient.” ral. Someone still needs to be fol- pate in ongoing continuing education Navigating when a referral is neces- lowing the patient’s vision and doing to ensure they have the confidence to sary and when it isn’t depends on a regular visual fields and OCTs, notes make these calls. fundamental understanding of these Dr. Messner. “Neurologists, to a large Recommendations and standards conditions as well as the necessary extent, do not have the fundamen- of care can change from the time an testing. “ODs must be able to recog- tal knowledge of the visual field or OD graduates from optometry school, nize the signs and symptoms of under- OCT interpretation, and this is where notes Dr. Malloy. “More recently, lying neurologic disease and conduct optometry must take the lead. This is we have seen this with how acute appropriate tests,” Dr. Messner says. comanagement in its truest sense.” transient vision loss and symptomatic “And, when needed, work hand in When a condition necessitates a retinal emboli are managed,” she hand with either neuro-ophthalmology referral, optometrists should maintain says. “We now understand that these or neurology for the betterment of the relationships with both the specialist conditions should be treated the same patient.” and patient to ensure they continue to as acute stroke, requiring the patient For example, there are number of take a leadership role in care. Com- be sent immediately to an emergency vision and eye movement problems munication with the neurologist or department of a hospital with a dedi- associated with multiple sclerosis, other specialists is crucial throughout cated stroke center.” including optic neuritis and brainstem follow up. motility abnormalities. The general “I make a point to schedule an ap- Effective Patient Communication optometrist should be able to recog- pointment with my patient after they A sometimes difficult but important nize these issues and work with neu- see the neurologist and I will continue aspect of comanagement is patient rology to evaluate and manage these to manage their visual challenges,” communication. This involves not individuals effectively. explains Dr. DelGiodice. “This can only explaining a diagnosis or reason Once patients have been diagnosed include, for example, running OCTs for referral, but helping them through with multiple sclerosis, the OD con- or visual field tests. The results of all the process of seeing a specialist. tinues to play a role in their long-term of those images and testing are then comanagement. For example, com- sent to the neurologist. While they CONDUCTING A COMPREHENSIVE municating follow-up OCT and visual are taking care of the chronic man- NEURO EXAM4 field findings to neurology can help agement of a patient’s disease, I am them determine stability and adjust following the patient and continuing The neurologic exam is a vital part of comanaging neuro-ophthalmic conditions treatment plans as needed. to manage their visual needs.” and can easily be conducted in the A condition that Dr. Messner sees One of the most challenging—and optometry office. Key components of the frequently is idiopathic intracranial potentially daunting—aspects of exam, include: hypertension. “A key finding associ- neuro-ophthalmic comanagement is 1. Mental status ated with this disease is papilledema,” the life-threatening implications some 2. Cranial nerve testing he says. “So, these are individuals conditions may have. Optometrists 3. Motor/reflex examination that invariably are initially seen by must be able to recognize when a situ- 4. Coordination/gait optometrists with comanagement by ation is an emergency and when it is neurology.” not. Conditions that require immedi- 5. General sensory exam However, this does not mean the ate referral to the emergency depart-

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TABLE 1. COMMUNICATION GOALS AND TECHNIQUES FOR NEURO-OPHTHALMIC REFERRALS WHAT TO COMMUNICATE HOW TO COMMUNICATE THIS INFORMATION COMMUNICATE Why referring to emergency • Explain reasoning to both patient and family/support system (in person or via phone) that they need WITH department or specialist more evaluation to rule out or prevent a particular problem, or to find out the etiology of their signs/ PATIENT/FAMILY symptoms. • Ask what questions they have to help them better understand the reason for referral. • Give them a way to contact you if they think of additional questions later. • Emphasize that keeping this appointment is in their best interest. How to prepare for the • Write out details of upcoming appointment (date, time, exact location). referred visit/referral • Write out doctor/facility NPI number and tell the patient to call their PCP for a referral if necessary. • Write out instructions on what to bring with them to the appointment (test results, MRI disc, medications). • If they need to have outpatient testing prior to referred appointment, give them any necessary scripts and write out timeline of when testing should be done/is scheduled. • Explain what to expect at upcoming appointment or emergency department visit. • Give them an appointment card for a follow-up visit with you. COMMUNICATE Key history and/or in-office • Phone call preferred, especially for emergent or urgent referrals, or when sending to ED. WITH clinical findings • Comprehensive letter, including clinical findings to back up phone conversation should be faxed or sent PROVIDER TO via secure email to avoid delay. WHOM YOU ARE REFERRING • VF, OCT and/or optic disc photos sent to highlight significant clinical findings and demonstrate interval change. • Be sure the provider has a way to reach you to further discuss he patient during the visit, if needed. External testing/work-up • Phone call and/or letter indicating testing OD deems necessary for provider to perform/order. • Phone call and/or letter indicating outpatient or inpatient testing that has been previously obtained. • Send copies of all reports to provider via fax or secure email to avoid delay. Conditions that need to be • Phone call and/or letter indicating conditions of concern and any noted signs or symptoms consistent ruled out with each. When patient should return • Make it clear that you plan to continue to comanage the patient, and include the date of follow-up to see the OD appointment with you. • Each time the patient does see you in follow-up, communicate (via a comprehensive letter) with all of their providers to keep them updated regarding patient progress. This will prompt the other providers to regularly communicate with you as well as you continue to comanage the patient.

When discussing neurological the lead in coordinating their care, ing quickly is in the best interest of concerns, ODs must strike a balance they tacitly acknowledge that your their health and overall well-being. between conveying the seriousness role in their care will continue even as Dr. DelGiodice goes the extra mile of a condition without unduly alarm- other doctors become involved. to make sure his patients have sup- ing their patient. “You don’t want to “There’s a tendency to think that port, especially when they have to overstate the diagnosis,” suggests Dr. if you scare someone [with a dramatic contend with a visit to the emergency DelGiodice, “because the majority of description of the condition], they’re department. He provides them with the time you’re not going to have a actually going to follow through” and a note for the doctor as well as his definitive answer yet.” urgently see a specialist, Dr. Del- phone number and tells them to call if Using words like proactive or preven- Giodice continues. “However, in my they have any questions or need help. tive while describing your recom- experience, it has the opposite effect. The optometrist should also call mendations and actions can be a good Often, the patient will shut down and the hospital and, if possible, speak approach with patients. “The key is to won’t process what you are saying.” with either the neurologist on call, communicate,” says Dr. DelGiodice. Handling emergency cases requires emergency department doctor or at “Explain the process and let them a nuanced approach, he notes. An least the triage nurse to explain the know that you will be following up emergent situation still doesn’t mean patient’s presentation and why it war- with them after they see the special- you should scare your patients, but rants emergency evaluation, suggests ist.” When patients hear you taking you do need to emphasize that mov- Dr. Malloy.

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When a patient adamantly refuses terpret visual field and OCT findings will grow, and they will become more to go to the emergency room, Dr. for patients with neuro-ophthalmic comfortable reading the scans. Some DelGiodice will follow up with the disorders, notes Dr. Messner, who may ask, is this a necessary step? “I patient as well as connect with one of emphasizes the importance of keep- think it is important because it is their other providers. This may not be ing up with the latest technologies. our field,” notes Dr. DelGiodice. “If their PCP but rather the person they “It’s fascinating to see how technol- you’re comanaging with a neurologist, see most frequently, such as their car- ogy is evolving, particularly in the you want to know what you are look- diologist. “In these situations, send- area of OCT,” he says. “We’re able ing at. This step may be less neces- ing your patient back to a provider to look at the structure of the optic sary if you are working with a neuro- they haven’t seen in two years is not nerve and retina almost down to a cel- ophthalmologist; however, I believe an effective approach,” he notes. lular level. It’s been said now that we improving your skills in this area will Table 1, developed by Dr. Malloy, really need to be looking at OCTs the only enhance your practice.” lists many specific points to com- same way that neuroradiology looks at Dr. DelGiodice makes a point to municate to patients and comanaging the MRI and I think that is absolutely request the discs and review all of providers. true.” the scans. If questions arise, he will Another key component related to connect with the neuroradiologist. Ongoing Education & Growth the care and comanagement of these He acknowledges that not everyone Given the wide range of neuro- patients is knowing which neuroim- has direct access to this specialty. ophthalmic conditions as well as their aging studies to perform. Any OD However, the OD should always complex nature, continuing education who wants to take this aspect of their have the ability to call and speak with and professional growth is necessary practice to the next level must devote the reading radiologist regardless of for the ongoing enhancement of your significant time to honing these skills. where they work and/or where the practice. As mentioned above, optometrists study was performed. In addition, One way to build your confidence should play a central role in the man- comanaging with neurology or neuro- when assessing these cases is through agement of these patients, including ophthalmology can allow for another mentorship. “Fostering a mutual ordering imaging. With a shortage of opinion regarding neuroimaging find- relationship with someone who does neuro-ophthalmologists, especially ings when needed. neuro work, ideally a fellow optom- in more rural areas, ODs should be With limited access to neuro- etrist, is an excellent way to grow your prepared to take charge of these ophthalmologists as well as cases that skills,” notes Dr. DelGiodice. “This patients. “The optometrist should be often require timely intervention, will help you become more comfort- fundamentally involved in ordering it is critical that ODs be positioned able with timing and diagnosis of neuroimaging studies, MRI and CT as leaders in care for patients with these conditions.” scans,” explains Dr. Messner. neuro-ophthalmic conditions. Effec- An area where mentorship could be “We don’t want to abrogate this tive comanagement begins with ODs very useful is double vision, accord- responsibility to the primary care and their desire to explore what are ing to Dr. DelGiodice, who notes that physician or the general ophthalmolo- often complex and challenging cases. given the subtlety of this issue, build- gist,” he continues. “As optometrists, “Most patients present with subtle ing up skills on your own can be very we are the ones seeing the patient clinical signs, so you have to be able challenging. Optometrists should also and we have the greatest understand- to carve out the time to carefully continue to develop their ability to in- ing of their clinical manifestations; evaluate these cases and you have therefore, it is our responsibility to to be curious,” concludes Dr. Del- take the lead.” Giodice. “Curiosity is paramount KEY TAKEAWAYS Optometrists need to know which when it comes to managing these • Establish strong referral pathways imaging studies correlate with which conditions.” ■ depending on the condition. conditions. Who needs a CT? Does • Determine the urgency of the clinical the patient require an MRI with or 1. Stunkel L, Sharma RA, Mackay DD, et al. Patient harm presentation. due to diagnostic error of neuro-ophthalmologic condi- without contrast? Once you have tions. Ophthalmology. March 10, 2021. [Epub ahead of • Maintain open lines of communication identified the condition, ODs must print]. with comanaging specialists. 2. Trottini M, DelGiodice M. An Intro to Neuro. Review of feel comfortable directing the imag- Optometry. 2015. www.reviewofoptometry.com/article/ • Take the lead on neuroimaging and ing center. “Proving localization and an-intro-to-neuro. patient management. directions for the proper imaging 3. Malloy K. 10 Tips and Helpful Hints for Neuro- ophthalmic Disease. Review of Optometry. 2018. www. • Support patients through clear, study is crucial,” says Dr. DelGiodice. reviewofoptometry.com/article/10-tips-and-helpful-hints- consistent communication. “The final part, which can be more for-neuroophthalmic-disease. • Take advantage of CE and mentors to 4. Maglione AK, Seidler K. The Neurologic Exam, Step-by- challenging, is reviewing the scans.” step. Review of Optometry. 2019. www.reviewofoptom- hone your skills. Over time, the OD’s experience etry.com/article/the-neurologic-exam-stepbystep.

76 REVIEW OF OPTOMETRY | MAY 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 Optometric Study Center HERPES ZOSTER OPHTHALMICUS PEER REVIEWED

Earn 2 CE Credits (COPE APPROVED) Get to Know HZO

Gain a comprehensive understanding of the various treatment options to effectively manage this condition.

gets its name—the most frequently one to three days’ time, these lesions involved cranial nerve is the trigeminal either regress or coalesce to form By AARON BRONNER, od nerve (CN V). When the ophthal- pseudodendrites.1,5 Despite similar Kennewick, Wa mic branch of the CN V is affected, names and gross appearance, pseu- the condition may affect the ocular dodendrites, which appear in 50% to etermining the right avenue of structures, at which point it may be de- 75% of cases of HZO corneal disease, treatment for herpes zoster oph- scribed as HZO, an entity accounting are readily distinguished from the thalmicus (HZO), which occurs for 10% to 20% of all cases of zoster.1,2 HSV dendritic equivalents primarily Dwhen the varicella-zoster virus The cornea is among the most though lack of ulceration and second- (VZV) is reactivated in the ophthalmic frequently involved ocular tissues in arily through lack of terminal end- section of the trigeminal nerve, can be HZO. Keratitis occurs in up to 65% bulbs.3,4,6,7 Because of the absence of a challenge. While antiviral use during of HZO cases and has varied mani- ulceration in either forms of varicella the acute, infectious stage is common, festations.3,4 In seeking to distinguish zoster ophthalmicus (VZO) epithelial treatment in later, post-infectious this from its cousin HSV keratitis, it’s keratitis, neither pseudodendrites nor stages can vary. With the potential for useful to point out that while HSV their vesicular precursors stain with chronic and recurrent disease, it can be corneal disease may vacillate from one fluorescein, though staining with rose difficult for clinicians to identify the manifestation to the next without any bengal is reported variably.3-5,7 right management approach. particular chronology, HZO seems to Stromal/endothelial keratitis. In The purpose of this article is to follow a sequential chronology with general, it’s thought that HZO stromal review what we do know about HZO, some manifestations possible in the keratitis represents an inflammatory including its clinical manifestations. first few days and weeks after the manifestation of the disease rather We will also delve into its treatment initial infection and others only mani- than a true infection, though there is and where these concepts diverge festing months to years following the some controversy surrounding this. from its cousins herpes simplex virus episode.1,5 A form of deep keratitis follows the (HSV) 1 and 2, with which HZO is Infectious epithelial keratitis. As with infectious episode in around 40% sometimes mistakenly blended in our HSV, true infection of the corneal epi- to 50% of cases.3,4 The early form of education. thelium sets the stage for other corneal this with HZO, known as nummular manifestations, and with VZV this corneal infiltrates, occurs immediately Clinical Manifestations initial infection begins as focal patches below the previous pseudodendrite While shingles lesions occur most of coarse vesicular epithelial kerati- within the anterior corneal stroma and commonly on the trunk and abdo- tis. There are often multiple lesions follows the infectious episode by a pe- men—which is where the disease scattered across the cornea. Within riod of seven to 14 days.5-7 More rarely,

About the Dr. Bronner is an attending optometrist at Pacific Cataract and Laser Institute in Kennewick, WA. He has no financial interests to disclose. author

78 REVIEW OF OPTOMETRY | MAY 15, 2021 an acute form of endotheliitis may also the mechanical Photo used with permission of Brian Johnson, OD develop within this same timeframe shearing forces and may cause signifi cant corneal on the corneal edema and subsequent disruption epithelium. Cul- to vision. Depending on the severity ture and cytology of the attack, this endotheliitis could show no viral result in corneal decompensation and activity.10,11 As the need for endothelial transplanta- these are not in- tion.3,5 Both nummular and endothe- fectious, steroids lial keratitis are frequently paired with may be con- anterior uveitis.5 While stromal disease sidered. Their typically follows infectious epitheli- effi cacy, however, opathy, it may occur without history of is variable from a previous epithelial episode in 10% of study to study.4,7,9 patients.7 The lesions can Corneal mucous plaques. A late be manually corneal manifestation of HZO is removed, leaving mucous plaque keratitis (MPK). The behind intact incidence varies but is estimated at epithelium, but 4% to 13% and typically develops one tend to recur. to three months after an infectious The develop- episode, though occasionally its ap- ment of MPK 5,8,9 Fig. 1. A severe episode of HZO affecting the nasociliary branch of pearance may be delayed by years. may be linked the fi fth cranial nerve. The patient has profound ocular involvement The lesions of MPK are coarse, to more serious and already has a total corneal epithelial defect. The severity grayish fi lamentous elevations weakly ocular events, increases the likelihood of complex and chronic ocular involvement. adherent to epithelium, and may be but their own linear or dendriform in appearance.8 presence is transitory, with a natural tion or limbal vasculitis. Serpiginous As these are actually mucous deposits history characterized by gradual reso- keratitis manifests as a peripheral and not epithelial ulcerations, they lution leaving behind a mild underly- arcuate-shaped area of corneal ulcer- stain negatively with fl uorescein but ing stromal haze.11,12 ation and infi ltration. It is often paired vigorously with rose bengal. Marginal keratitis. Sclerokeratitis with localized corneal edema. As the Some sources report the lesions as and serpiginous keratitis are uncom- condition progresses, thinning and having a predilection for prior foci mon, late manifestations of HZO, vascularization take place, which may of epithelial or stromal disease, and occurring one to four months after the ultimately lead to perforation. The others report them as freely migra- infectious episode.5 These are each lesions have been described as similar tory.4,5,8 Patients will be symptomatic presumed to be infl ammatory respons- to a Mooren’s-type ulceration. Sclero- with red, irritated eyes as a result of es secondary to a stromal infl amma- keratitis results as an infl ammatory

Release Date: May 15, 2021 Accreditation Statement: In support of improving patient care, this activity Expiration Date: May 15, 2024 has been planned and implemented by the Postgraduate Institute for Medicine and Review Education Group. Postgraduate Institute for Medicine is jointly Estimated Time to Complete Activity: 2 hours accredited by the Accreditation Council for Continuing Medical Education, Jointly provided by Postgraduate Institute for Medicine the Accreditation Council for Pharmacy Education, and the American Nurses (PIM) and Review Education Group Credentialing Center, to provide continuing education for the healthcare team. Postgraduate Institute for Medicine is accredited by COPE to provide Educational Objectives: After completing this activity, the participant should continuing education to optometrists. be better able to: Reviewed by: Salus University, Elkins Park, PA • Understand the current standard of care for herpes zoster ophthalmicus. Faculty/Editorial Board: Aaron Bronner, OD, Pacific Cataract and Laser • Understand the importance of early detection to initiate timely treatment. Institute, Kennewick, WA • Determine when to use different treatment modalities. Credit Statement: This course is COPE approved for 2 hours of CE credit. • Prescribe topical steroids/antivirals appropriately. Activity #121689 and course ID 72517-SD. Check with your local state licens- ing board to see if this counts toward your CE requirement for relicensure. • Recognize the role of oral antivirals in herpes zoster ophthalmicus treat- Disclosure Statements: Author: Dr. Bronner has no financial interests to ment. disclose. Managers and Editorial Staff: The PIM planners and managers have Target Audience: This activity is intended for optometrists engaged in routine nothing to disclose. The Review Education Group planners, managers and edi- eye care and primary care of ocular disease. torial staff have nothing to disclose.

MAY 15, 2021 | REVIEW OF OPTOMETRY 79 Optometric Study Center HERPES ZOSTER OPHTHALMICUS spillover from a preceding episode Less common than disciform kera- Interstitial keratitis. The develop- of HZO-linked scleritis. It may be titis are corneal ring infiltrates.5,13 Ring ment of significant corneal haze, seen following cases of HZO scleritis infiltrates are most often described in vascularization and lipid deposition when corticosteroid therapy has been Acanthamoeba keratitis as one of the may follow any of the intense preced- too rapidly tapered. It also may cause late stromal manifestations of that dis- ing forms for HZO keratitis. Corneal stromal thinning and guttering of the ease, but they may also be part of the neovascularization following or as part peripheral cornea.4,5,7 clinical presentation of other sources of of herpetic eye disease seems to be Disciform keratitis/corneal immune microbial keratitis as well as with both mediated by T-cells and, as with other rings. These two forms of late stromal HSV and HZO keratitis. With viral forms of deep HZO keratitis, may be keratitis, which can occur within forms, corneal rings are most typically purely inflammatory or may be caused HZO, typically manifest months after thought to be composed of antigen- by a latent viral infection within the the infectious episode. Though often antibody complexes. When fronts of corneal stroma and may perpetuate for discussed part and parcel with each antigen migrating outward from the years.5 other, they probably result from quite nidus of involvement meet a front of Neurotrophic disease. Neurotrophy different immunologic scenarios.5,10,13 antibody migrating in from the limbus, of the cornea is a relatively common The etiology of disciform keratitis is the result is precipitate of an Ab-Ag manifestation of HZO, with an esti- debatable and not completely defined complex.11-13 Unlike microbial rings, mated 20% to 45% of patients exhib- as infectious or inflammatory, but the which are generally ulcerated and iting signs of neurotrophic disease target is most likely the endothelium apical, classic viral rings are usually not within the first year after infection, and and would probably be more accurate- ulcerated, and their location varies. with risk increasing following more se- ly described as disciform endotheliitis. It’s important to note that the clini- vere episodes of HZO.5,7,9 The clinical Clinically, disciform disease is char- cal appearance of many forms of HSV manifestation of corneal hypoesthesia acterized by a suddenly developing and HZO anterior segment disease is neurotrophic keratitis (NK), which circular form of corneal edema with are indistinguishable. Therefore, it is may be mild or very severe. Classifica- an intact epithelium and no clearly important to establish a prior history of tion of hypoesthesia can be performed definable infiltrate, which may have HZO in these cases, the timing from with an esthesiometer or, as in our underlying keratic precipitates.5,9,10 which will aid in the diagnosis. clinic, dental floss or cotton wisps. The clinical picture of HZO neuro- Natural History of HZO trophic disease is similar to that seen with herpes simplex, but is reported Varicella-zoster virus is a member of the alpha herpesviradae family of human as being more severe.5,7 Severe cases herpes viruses, which includes HSV 1 and 2, cytomegalovirus (CMV) and Epstein manifest as oval, “boggy” ulcerations Barr virus (EBV). Like all families, the viruses that make up this group share most commonly found in the central many core similarities; in the case of alpha herpesviradae, the ability to create of paracentral inferior cornea. Without latency, the inability of body to fully clear the virus once initial infection has oc- successful treatment, these ulcerations curred and periodic reactivation are shared. may develop scarring, secondary VZV causes disease during one of two states: the primary infection, known superinfection or progressive melting, as varicella (or, more commonly, chickenpox) and secondly, an endogenous thinning and perforation.7,9,10 reactivation of latent VZV in the form of herpes zoster or shingles. Primary Zoster-associated uveitis. This is the infection occurs as a result of direct contact with or via respiratory droplets from second-most common manifestation an infected individual. It manifests as chickenpox, the widely recognized itchy of HZO, developing in up to 40% of vesicular rash that spreads across the body.5 Though ocular involvement here is patients.5,9 A history of HZO increases unusual, lid and conjunctival vessels as well as dendriform corneal lesions are the risk for development of uveitis by all occasionally encountered.9 13 times compared with the patients Upon either vaccination or resolution of a varicella infection, the virus (the with shingles alone.14 And though wild type or the attenuated vaccine type, depending on the source of exposure) keratouveitis may develop twice as is transported to a dorsal root ganglion of sensory nerves where, in combination frequently as uveitis alone, HZO with host cellular immunity, it establishes latency. About 10% to 30% of infected remains an important cause of isolated individuals will have latency broken and the virus will migrate from one of the uveitis, particularly in an elderly popu- ganglion reservoirs, typically resulting in the classic shingles vesicular rash lation, where it may account for a high respecting a dermatome.1,5 The switch from latency to active disease seems to percentage of isolated uveitis cases.14-16 require some stress to host cell-mediated immunity, and the disease’s increasing When seen as an association with rate with advancing age may be tied directly to the immunosenescence, explain- HZO keratitis, the uveitis follows the ing the elevated risk with age.1,2,5,43 timeline for keratitis described above. As an isolated finding, however, it can

80 REVIEW OF OPTOMETRY | MAY 15, 2021 lag behind the acute HZO episode, in program, primarily some cases by years.16 the unknown impact When seen in combination with on the epidemiology keratitis, as a keratouveitis or endo- of the shingles. It’s theliitis plus uveitis, the diagnosis is speculated by some generally straightforward. In the case that widespread of delayed manifestation, its clinical di- vaccination may agnosis is more difficult. Any unilateral actually increase the uveitis in a patient over the age of 60 rate of herpes zoster should prompt questioning for a recent at least over the short or remote history of HZO or periocular term.19 Theoretically, shingles rash, among whom it accounts people who have for a high percentage of uveitis cases. latent, wild-type VZV Helpful ophthalmic clues may be infection will see a sectoral iris atrophy and subsequently reduction in their Fig. 2. Pseudodendrite seen with HZO. This occurred two weeks mild corectopia, and poor direct pupil- normal environmen- after the beginning of a shingles rash involving the brow of this lary response (with intact consensual tal exposures to VZV patient. Note that the lesion is not ulcerated and only stains response on fellow eye), diffusely as a wider percent- with rose bengal in a patchy manner. distributed, medium-sized keratitis age of children are precipitates and ocular hypertension, vaccinated. This then though studies vary on their incidence results in a reduction with HZO uveitis. Ocular hyperten- in immune boost- sion is also associated with a more ing to the virus that chronic course of disease.16,17 accompanies these Rarely, HZO can result in severe exposures and may panuveitis: acute retinal necrosis manifest as increasing (ARN) or progressive outer retinal rates of shingles and necrosis (PORN). Each of these enti- at younger ages.5,9,20,21 ties can progress to severe vision loss.18 While the jury is Among other sources of vision loss, out on the role of untreated cases of ARN or PORN Varivax in increas- will go on to have profound vision loss ing the prevalence from rhegmatogenous retinal detach- of shingles in an ment in up to 75% of cases, which at-risk population, Fig. 3. Mucous plaque keratitis with HZO. This patient had highlights the importance of dilating two things are not in a shingles episode four months prior to being referred in uveitis patients to make sure there is debate: (1) the aver- for eye pain. The patient did not feel the eye was involved with the initial episode. Note that these lesions, unlike the no posterior involvement.17,18 age age of patients pseudodendrite in Figure 2, stain vigorously with rose bengal. developing shingles Treatment Approaches is decreasing and (2) the incidence of post-herpetic neuralgia as well.25-27 Efforts to manage HZO can be broken shingles is going up.22-24 Detractors of Zostavax’s effectiveness, however, down into prevention of disease, treat- Varivax point this out as a cause-and- seems to vary with patient age. Those ment of active infection, treatment of effect relationship while supporters between 60 and 69 saw a reduction in post-infectious inflammatory events note these trends may have preceded disease of 60%, but only 40% when and treatment of corneal neurotrophy. widespread use of Varivax and can also dosed beyond the age of 70. Further, Vaccination. Prevention of varicella be seen in countries without varicella as a live virus, there is the slight risk zoster in its two forms has been accom- vaccination programs.22-24 of inducing zoster with the vaccine. plished with two related vaccinations. For patients at risk for shingles, Though the CDC recommended this The first, Varivax (Merck), is given Zostavax (Merck) or Shingrix (Glaxo- vaccine for all people over the age of to infants to reduce primary infec- SmithKline) should be used to reduce 60, its use has lagged way behind that tion, with good results. This vaccine risk. Zostavax is a smaller dose of the of Varivax, with only 31% of eligible has seen significant success and has same attenuated virus used in Varivax. adults receiving the vaccine.27 reduced the incidence of varicella in This vaccine reduces the develop- The more recently developed Shin- at-risk populations by 70%.5,19,20 ment of shingles by around 50%, and grix vaccine substitutes the live at- However, there are possible lowers the chances of developing tenuated virus of Varivax and Zostavax consequences of this vaccination severe disease and the potential for for a viral subunit. Though efficacy of

JANUARYMAY 2021 15, 2021| REVEW | REVIEW OF OPHTHALMOLOGY OF OPTOMETRY 81 Optometric Study Center HERPES ZOSTER OPHTHALMICUS

gles vaccination to our Though these groups of medications patients is within our are found to be effective in both HSV purview. Keeping in and VZV, the inhibitory concentration

mind that up to 20% of (IC50) of acyclovir is 3µg/mL for VZV all shingles cases may and somewhere between 0.5µl/ml and involve ocular struc- 2µl/ml for HSV 1 and 2.30 Due to this tures and each case greater concentration demand for VZV, carries the potential for all antivirals used in its treatment are debilitating, chronic dosed at higher levels than HSV-based or recurrent pathology disease. For example, the standard to the eye, it stands to dose of acyclovir or valacyclovir for reason that as provid- HSV is half that used for HZO (400mg ers on the forefront of five times per day for acyclovir or Fig. 4. A double corneal ring occurring four months following a the nation’s eye care, 500mg TID with valacyclovir for HSV shingles episode in a 42-year-old patient. The lesion does not we should be actively keratitis) compared with that used in stain with fluorescein or rose bengal. This issue resolved with taking a role in recom- HZO (800mg five times per day with treatment and the patient has had one further flare of HZO but mending our patients acyclovir/1000mg TID with valacyclo- has been quiet for three years. get this vaccine. Cur- vir). rently, the American The use of these medications in the Shringrix seems superior to Zostavax Academy of Ophthalmology recom- treatment of HZO is established based with 91% efficacy even beyond the age mends that all patients 50 and older on research with acyclovir in the 1980s, of 70—and, theoretically, using a viral receive one or the other vaccine.27 which showed benefit in reducing the subunit reduces potential for causing a Antivirals. In the late 1970s, acyclo- duration of viral shedding and symp- reactivation—it is a two-dose schedule vir was developed as a highly selective, toms, limiting the severity of disease and, perhaps partially as a result of minimally toxic antiviral nucleoside and reduction in late manifestations of this, has failed to gain wide penetrance analog effective in the treatment of the disease, and later studies show- into the at-risk population.26,27 both HSV 1 and 2 as well as VZV. The ing a reduction in PHN.32,33 Finally, Thus far, it seems logical that mechanism of acyclovir is to block gua- although there is good rationale to shingles vaccines are perhaps best nosine base pairing, thereby halting expect guanosine analogs to be useful suited for patients with elevated risk of DNA synthesis.29 Acyclovir’s selectiv- for VZO, the actual effectiveness of shingles but not an immediate history ity and subsequent safety is derived their use has been called into question. of it. That said, recent history of shin- from it being phosphorylated into its A large retrospective review found gles does not contraindicate a booster, active form by viral thymidine kinase, no evidence of reduction in severity which may still be beneficial to the and thus it only blocks DNA synthesis of the acute episode or in the reduc- patient; in fact, the CDC recommends in virally infected cells. Acyclovir’s tion of complications of the disease Zostavax in all people over the age of disadvantage is its poor bioavailability; in patients treated with oral acyclovir 60 regardless of previous episodes.25 possibly only 10% is absorbed follow- (800mg five times per day) vs. those Exactly how beneficial a vaccine ing an 800mg dose, the standard dose who were not treated.34 may be after a previous episode prob- for VZV treatment.30 Theoretically, it’s possible to expect ably relates to patient-specific factors From acyclovir, the prodrug valacy- that suppression dosing, found effec- such as immune status and the timing clovir, which shows improved bio- tive for HSV via the HEDS study, of vaccination relative to the episode. availability compared with its parent may also be helpful in cases of VZV, One author makes the case that the drug, was developed.29,30 Penciclovir, though it might be anticipated to immune boost following an episode of a later-developed antiviral drug, had be needed at higher dosages than shingles lasts for around three years, even poorer bioavailability than acyclo- those given with HSV.35 However, no so recommending the vaccine three vir and possibly a weaker mechanism general consensus or recommendation years after a flare seems reasonable.28 of action, but from penciclovir the on this matter exists and community Further, neither vaccine has a perma- prodrug famciclovir was developed, practice is divided.36 In the literature, nent effect and each can be repeated which shows a 77% bioavailability.29,30 I identified a couple of small reviews five years after a previous dose. Ganciclovir is a related guanosine that support the use of low-dose The lack of high utilization of these analog that has greater potential for chronic acyclovir. Both of these studies vaccines should be a concern within toxicity than the other antivirals when suggest that, in select populations the optometry and, though we generally dosed systemically and so remains a use of prophylactic therapy may result play little role in recommending vac- secondary option in all cases except in substantial reduction of recurrence, cinations, strongly advocating for shin- the treatment of cytomegalovirus.30,31 but both studies are too limited in

82 REVEWREVIEW OF OF OPHTHALMOLOGY OPTOMETRY | MAY | 15,JANUARY 2021 2021 design to broadly apply.22,37 The ongo- these manifestations on one hand, but cases should use long-term solutions, ing Zoster Eye Disease Study seeks to on the other recommends they should either a scleral contact lens, a conjunc- clarify some uncertainty with the use be avoided, when possible, given the tival flap (where the visual potential is of prophylactic antivirals but, to date, potential for extending the duration of limited), a partial or full tarsorrhaphy or no information has been published disease beyond its normal course.5 perhaps Oxervate. When considering and enrollment has been significantly Despite the mini controversy Oxervate for long-term management below expectation.38 surrounding their use, these recom- of NK, it’s important to recognize that At this time, despite the lack of mendations against their use do not it has not been shown to increase cor- good data on the topic, over half of the appear to be explicitly followed in neal sensitivity, the underlying mecha- cornea specialists polled in one review clinical practice. The most widely nism of NK, but only to speed the use long-term suppression therapy for used treatment modality for HZO is a healing of the ulcer itself.42 Our clinic chronic or recurrent HZO.36 combination of topical corticosteroids has used the medication in recalcitrant Topical antivirals. Topical acyclovir and oral antivirals, according to one cases of NK to good effect with posi- may have some effect on the corneal review on practice patterns among tive responses in both the acute phase infectious manifestations of VZV; cornea specialists.36 At our clinic, we (healing the ulcer) and the chronic however, the topical form of this drug treat cases of HZO with steroids when phase (preventing re-ulceration). is not available in the United States.5,29 reduction in vision is likely to occur in Trifluridine, an older antiviral, is their absence, which would be cases of Conclusion effective in the treatment of infec- significant stromal/interstitial disease, Herpes zoster is a systemic infectious tious ocular HSV, but is not effec- corneal endothelial disease and uveitis disease with a moderately high predi- tive against HZO and so should not but generally not epithelial disease. lection for the ocular and periocular tis- be used.5 Therefore, until recently The dosage of steroid varies on a case- sue. When the trigeminal nerve is af- there were no available products to by-case basis, but generally we will fected, ophthalmic findings frequently be used topically against HZO. This seek to use the lowest dose of steroid manifest. These manifestations are may have changed with the release of that allows total elimination of clinical extremely variable, though they seem Zirgan (ganciclovir 0.15% gel, Bausch inflammation. to follow a predictable timeline. Early- + Lomb). A small case series suggests Treatment of neurotrophic disease. NK stage findings such as epitheliopathy that the use of topical ganciclovir may may be one of the most troublesome may resolve and give way to mid-stage have shortened the duration of the and recalcitrant forms of zoster-related findings such as nummular keratitis. disease.39 While this study does not keratitis to manage. While ulcers and These in turn may become disciform provide extremely strong evidence epithelial disturbances associated keratitis, or in more serious cases ser- of effect, we know that ganciclovir with neurotrophy can wax and wane piginous disease. Within the eye, iritis does have efficacy against VZV, which over the disease course, unless the and panuveitis may develop. Essen- makes its topical use a reasonable underlying level of corneal hypoes- tially, any unusual unilateral red eye adjunct in some cases of HZO, par- thesia remits, the problems will recur. in a patient with a history of ipsilateral ticularly during the actively infectious Treatment varies and stage manifesting with pseudoden- can include lubrication, drites.30 punctal occlusion with Corticosteroids. The use of cortico- either plugs or cauter- steroids in cases of corneal HZO is ization, bandage con- an area of debate and is even more tact lenses—often used controversial than in HSV, where at chronically—amniotic least in stromal and endothelial disease membrane, autolo- it is felt to be a required component gous serum eye drops, of treatment as determined by the scleral contact lenses, HEDS study.40 In McGill’s article from Oxervate (cenegermin, 1987 on the uncertain mechanisms Dompé), tarsorrha- of both simplex and varicella zoster phy and conjunctival/ etiologies of stromal keratitis, the sug- Gunderson flaps.41,42 gestion is made that injudicious treat- While conservative Fig. 5. Iritis in HZO. The iritis in this eye developed about two ment with corticosteroids may prolong therapy is helpful in months after the episode of MPK seen in Figure 3. The patient 6 episodes and promote recurrence. mild and acute mani- had modest AC reaction, sectoral iris atrophy and a distorted, This advice is echoed in Holland’s festations, long-term poorly reactive pupil (this photo is in a non-dilated eye). Two Cornea; Dr. Lee acknowledges the management of NK in years later, the patient is still unable to come off of steroids effectiveness of corticosteroids to treat unremitting recurrent without a flare-up of their disease.

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Photo used with permission of Brian Johnson, OD 20. Seward JF, Watson BM, Peterson CL, et al. Varicella disease after introduction of varicella vaccine in the United States. JAMA. 2002;287(5):606-11. 21. Quirk M. Varicella vaccination reduces risk of herpes zoster. Lancet Infect Dis. 2002;2(8):454. 22. Miserocchi E, Fogliato G, Bianchi I, et al. Clinical features of ocular herpetic infection in an Italian referral center. Cornea. 2014;33(6):565-70. 23. Davies EC, Pavan-Langston D, Chodosh J. Herpes zoster ophthalmicus: declining age at presentation. Br J Ophthalmol. 2016;100(3):312-4. 24. Jeng B. Herpes zoster eye disease: new ways to combat an old foe. Ophthalmology. 2018;125(11):1671-4. 25. Centers for Disease Control and Prevention. Shingles vaccination: what you need to know: http://www.cdc. gov/vaccines/vpd-vac/shingles/vacc-need-know. htm#get-vaccine. 26. Gelb LD. Preventing herpes zoster through vaccina- tion. Ophthalmology. 2008;115:S35-8. 27. AOA Policy Statement: Recommendations for Herpes Zoster Vaccine for Patients 50 Years of Age and Older. Ophthalmology. 2018;125(11):1813-6. 28. Cohen J. Herpes zoster. New Engl J Med. Fig. 6. This is the patient from Figure 1. After years of dealing with unremitting 2013;369(18):1766-7. zoster-related inflammation, iritis and neurotrophy, the patient’s cornea opacified and 29. De Clercq ED, Field HJ. Antiviral prodrugs – the de- velopment of successful prodrug strategies for antiviral vascularized, and the pupil became irregular and non-responsive. His case illustrates the chemotherapy. Br J Pharmacol. 2006;147(1):1-11. potentially catastrophic impact of HZO on the visual system. 30. Gnann JW. Antiviral therapy of varicella-zoster virus infections. In: Arvin A, et al Eds. Human Herpesviruses: shingles in the preceding six months zoster ophthalmicus. Ophthalmology. 2008;115:S24-32. Biology Therapy and Immunoprophylaxis. Cambridge 4. Cobo LM. Corneal complications of herpes zoster University Press; 2007. should have HZO on the differential. ophthalmicus. Cornea. 1988;7(1):50-6. 31. Koyano S, Suzutani T, Yoshida I, et al. Analysis Though use of antivirals in the 5. Barry Lee W, Liesegang TJ. Herpes Zoster Keratitis. In: of phosphorylation pathways of antiherpesvirus acute, infectious stage is widespread, Krachmer JH, Mannis MJ, Holland EJ eds. Cornea. 4th ed. nucleosides by varicella-zoster virus specific enzymes. St Louis: Mosby; 2004:1075-90. Antimicrob Agents Chemother. 1996;40(4):920-3. treatment approaches in the later, post- 32. Cobo LM, Foulks GN, Liesegang T, et al. Oral acyclo- 6. McGill J. The enigma of herpes stromal disease. Br J vir in the treatment of acute herpes zoster ophthal- infectious stages are more varied. The Ophthalmol. 1987;71(2):118-25. micus. Ophthalmology. 1986;93(6):763-70. 7. Liesegang TJ. Corneal complications from herpes zos- potential for chronic and recurrent dis- 33. Hoang-Xuan T, Buchi ER, Herbort C P, et al. Oral acy- ter ophthalmicus. Ophthalmology. 1985;92(3):316-24. ease are particularly troublesome and clovir for herpes zoster ophthalmicus. Ophthalmology. 8. Marsh RJ, Cooper M. Ophthalmic zoster: mucous 1992;99(7):1062-71. can leave the clinician stumbling along plaque keratitis. Br J Ophthalmol. 1987;71(10):725-8. 34. Aylward GW, Claoue CM, Marsh RJ, et al. Influence a poorly defined treatment algorithm. 9. Rapuano C, Luchs JI, Kim T. Corneal Infections, Inflam- of oral acyclovir on ocular complications of herpes Further, for one reason or another, mations, and Surface Disorders. In: Anterior Segment; The zoster ophthalmicus. Eye. 1994;8:70-4. Requisites in Ophthalmology. Mosby; 2000:115-8. shingles is becoming more common 35. Acyclovir for the prevention of herpes simplex virus 10. Holland EJ, Brilakis HS, Schwartz GS. Herpes Simplex eye disease. Herpetic Eye Disease Study Group. N Engl J and occurring at a younger age. Keratitis. In: Krachmer JH, Mannis MJ, Holland EJ, eds. Med. 1998;339(5):300-6. This highlights perhaps the most Cornea. 2nd ed. St. Louis: Mosby; 2004:1043-74. 36. Sy A, McLeod SD, Cohen EJ, et al. Practice patterns 11. Mondion BJ, Rabin BS, Kessler E, et al. Corneal and opinions in the management of recurrent or chronic important thing optometrists can be rings with gram negative bacteria. Arch Opthalmol. herpes zoster ophthalmicus. Cornea. 2012;31(7):786-90. doing in the management of HZO— 1977;95(12):2222-5. 37. Seok JK, Kim K, Rok Do Y, et al. Low-dose acyclovir start helping to prevent the disease. As 12. Sery TW, Pinkes AH, Nagy RM. Immune corneal rings: is effective for prevention of herpes zoster in myeloma I. Evaluation of reaction to equine albumin. Invest Ophthal- patients treated with bortezomib: a report from the a profession, we need to be vocal with mol. 1962;1:672-85. Korean Multiple Myeloma Working Party (KMMWP) Retrospective Study. Jpn J Clin Oncol. 2011;41(3):353-7. our patients in promoting the use of 13. Sery TW, Pinkes AH, Nagy RM. Immune corneal rings: one of the two available shingles vac- III. Mechanism of local corneal ring formation. Invest 38. Cohen E, Jeng BH, Troxel AB, et al. Enrollment in The Ophthalmol. 1962;1:762-72. Zoster Eye Disease Study. Cornea. 2020;39(12):1480-4. cines. An ounce of prevention is worth 14. Wang TJ, Hu CC, Lin HC. Increased risk of anterior 39. Aggarwal S, Cavalcanti BM, Pavan-Langston a pound of cure after all, particularly uveitis following herpes zoster: a nationwide population- D P. Treatment of pseudodendrites in herpes zoster based study. Arch Ophthalmol. 2012;130(4):451-5. ophthalmicus with topical ganciclovir 0.15% gel. Cornea. when the “pound of cure” is not well 2014;33(2):109-13. 15. Chatzistefanou K, Markomichelakis NN, Christen W, et defined or even particularly effective, al. Characteristics of uveitis presenting for the first time in 40. Wilhelmus KR, Gee L, Hauck WW, et al. Herpetic Eye the elderly. Ophthalmology. 1998;105(2):347-52. Disease Study. A controlled trial of topical corticoste- as is the case with much of our man- roids for herpes simplex stromal keratitis. Ophthalmol- agement options with HZO once the 16. Tugal-Tutkum I, Cimino L, Aydin Akova Y. Review for ogy. 1994;101(12):1883-95. the disease of the year: varicella zoster virus-induced ante- disease has taken hold. g rior uveitis. Ocul Immunol Inflamm. 2018;26(2):171-7. 41. Dua HS, Gomes J, King AJ, et al. The amni- otic membrane in ophthalmology. Surv Ophthalmol. 17. Jap A, Chee S P. Viral anterior uveitis. Curr Opin Oph- 2004;49(1):51-77. 1. Liesegang TJ. Herpes Zoster Ophthalmicus: Natural thalmol. 2011;22(6):483-8. History, Risk Factors, Clinical Presentation and Morbidity. 42. Bonini S, Lambiase A, Rama P, et al. Phase II ran- 18. Duker JS, Blumenkranz MS. Diagnosis and manage- Ophthalmology. 2008;115:S3-S12. domized, double-masked vehicle-controlled trial of re- ment of the acute retinal necrosis syndrome. Surv combinant human nerve growth factor for neurotrophic 2. Borkar DS, Tham VM, Esterberg E, et al. Incidence of Ophthalmol. 1991;35(5):327-43. keratitis. Ophthalmology. 2018;125(9):1332-43. herpes zoster ophthalmicus: results from the pacific ocular inflammation study. Ophthalmology. 2013;120(3):451-6. 19. Brisson M, Edmunds WJ, Gay NJ, et al. Modelling the 43. Miller AE. Selective decline in cellular immune impact of immunization on the epidemiology of varicella response to varicella-zoster in the elderly. Neurology. 3. Kaufman SC. Anterior segment complications of herpes zoster virus. Epidemiol Infection. 2000;125(3):651-69. 1980;30(6):582-7.

84 REVEWREVIEW OF OF OPHTHALMOLOGY OPTOMETRY | MAY | 15,JANUARY 2021 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 from Pennsyl vania College of Optometry. Please check with your state licensing board to see if this approval counts toward your CE requirement for relicensure.

1. Which is NOT true of alpha herpes viruses? 7. Which is TRUE of pseudodendrites with HZO? 15. Which best describes the available shingles a. They target humans. a. They are a late manifestation of the disease. vaccination options? b. The body is able to effectively clear the virus. b. They will not clear without antiviral therapy. a. Both effectively reduce the incidence of shingles. c. Initial infection is followed by a period of latency. c. They lead to geographic ulceration if untreated. b. Shingrix has a higher rate of inducing an episode d. Broken latency results in recurrent disease. d. Unlike HSV dendrites, pseudodendrites are not of shingles than does Zostavax. true ulcerations. c. Zostavax is a two-step vaccine. 2. By what percent has Varivax reduced chickenpox d. Shingrix does not perform as well as Zostavax in in the US among the at-risk population? 8. Which is TRUE of stromal keratitis with HZO? patients over age 70. a. 30%. a. It is universally accepted to be an inflammatory b. 60%. manifestation. 16. Which is FALSE regarding the shingles vaccines? c. 70%. b. It is universally accepted to be an infectious a. The CDC recommends for all patients over age 60. d. 100%. manifestation. b. The American Academy of Ophthalmology c. It is frequently paired with anterior uveitis. recommends for all patients over age 50. 3. In the US over the last 25 years, what trends have d. It occurs in only 10% of patients with preceding c. The vaccines have been widely used by the been seen with shingles epidemiology? epithelial disease. susceptible population. a. Less frequent and occurring later in life than in d. The vaccines may reduce incidence of shingles by previous generations. 9. Mucous plaque keratitis in HZO ______. up to 90%. b. Less frequent but occurring earlier in life than in a. Often follows the original episode by months. previous generations. b. Can be permanently removed at the slit lamp. 17. Which is true regarding antivirals for HZO? c. More frequent and occurring earlier in life than in c. Is a reactivated viral process. a. Topical trifluridine is a front-line treatment. previous generations. d. Generally causes no symptoms. b. There is at least some evidence that oral d. More frequent but occurring later in life than in acyclovir is NOT effective in reducing severity and previous generations. 10. Which is FALSE regarding HZO-associated complication rates. marginal keratitis? c. There is no clinical or even theoretic support for 4. Which is NOT true regarding shingles? a. It is a late manifestation of HZO and typically the use of topical ganciclovir. a. The most frequently involved area is along the follows the initial episode by months. d. Acyclovir is a pro-drug of valacyclovir and trunk. b. It is due to an incompletely treated infection improves its bioavailability. b. The most frequently involved cranial nerve is the and represents reactivation of a perpetuating facial nerve. infection. 18. Which statement is FALSE regarding the role of c. Involvement of the nasociliary nerve increases the c. It may lead to perforation. acyclovir in prophylaxis of HZO? likelihood of ocular involvement. d. It is a severe manifestation and can behave a. Acyclovir may have a role in the management, but d. The incidence of shingles increases with somewhat like a Mooren’s ulcer. strong prospective evidence does not exist. increasing age. b. The HEDS study showed that low-dose oral 11. HZO disciform keratitis ______. acyclovir reduced the risk of recurrence of HZO. 5. Which statement most accurately conveys a. Clinically looks like HSV-linked disciform disease. c. Small retrospective reviews have shown some chronology-based differences between HSV and b. Generally, immediately follows epithelial keratitis. benefit of prophylactic acyclovir. VZV ocular disease? c. Will be paired with significant stromal infiltration. d. The ZEDS study is seeking to answer questions a. The varied ophthalmic manifestations of VZV d. Is caused by reduction in corneal sensitivity. surrounding the role of oral acyclovir in the follow a specific chronology relative to the time prophylaxis of HZO but is ongoing. from the original flare-up, while HSV does not. 12. Corneal rings from HZO ______. b. Neither VZV nor HSV follows a specific chronology a. Are generally ulcerated and apical. 19. Which best describes the role of steroids in with their ophthalmic effects. b. Are typically composed of infiltrating T-cells and management of HZO? c. The varied ophthalmic manifestations of both VZV virally infected cells. a. Always recommended for HZO corneal disease. and HSV follow a specific chronology relative to c. Usually occur within a few days of the initial b. Sometimes used in treatment of HZO corneal the time from the original flare-up. episode of HZO. disease. d. The varied ophthalmic manifestations of HSV d. Are a precipitate of antigen-antibody complex. c. Never recommended in treatment of HZO corneal follow a specific chronology relative to time from disease. the original flare-up, while those of VZV does not. 13. Which is TRUE regarding corneal neurotrophy d. There is a consensus of expert opinion on the role following HZO? of steroids in HZO. 6. Which of the following is FALSE in describing the a. 90% of patients will develop clinical signs of timing of the various manifestations of HZO? neurotrophy. 20. Which statement regarding the treatment options a. Epithelial disease is an early finding of the b. Is a mild form of the disease to treat. for neurotrophic keratitis following HZO is TRUE? disease. c. Seems related to the initial episode’s intensity. a. Amniotic membrane may be useful in healing b. Mucous plaque keratitis follows the initial d. Is less severe than HSV-induced neurotrophy. resultant corneal ulcers. infection days later. b. The nerve growth factor Oxervate has been proven c. Stromal disease may immediately follow epithelial 14. Which is FALSE about HZO-linked uveitis? to re-establish normal corneal sensitivity. disease. a. May lead to a retinal detachment. c. A conjunctival flap is considered front-line d. Interstitial keratitis may simmer for years b. May account for a significant percentage of all therapy. following the initial episode. uveitis cases among the elderly. d. Priming the ocular surface with preservative-free c. Corectopia may be a clue that an iritis is viral in tears, punctal occlusion and ointment is outdated origin. and no longer has a role in neurotrophic keratitis. d. Typically is both bilateral and granulomatous.

JANUARYMAY 2021 15, 2021| REVEW | REVIEW OF OPHTHALMOLOGY OF OPTOMETRY 85 Optometric Study Center HERPES ZOSTER OPHTHALMICUS

Mail to: Jobson Healthcare Information, LLC, Attn.: CE Processing, 395 Hudson Examination Answer Sheet Street, 3rd Floor New York, New York 10014 Get to Know HZO Payment: Remit $35 with this exam. Make check payable to Jobson Healthcare Valid for credit through May 15, 2024 Information, LLC. Credit: This course is COPE approved for 2 hours of CE credit. Course ID is 72517- Online: This exam can be taken online at revieweducationgroup.com. Upon passing SD. 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 current standard of care for herpes zoster ophthalmicus. 1 2 3 4 5 3. A B C D 4. A B C D 22. Understand the importance of early detection to initiate timely treatment. 1 2 3 4 5 A B C D 5. 23. Determine when to use different treatment modalities. 1 2 3 4 5 6. A B C D 24. Prescribe topical steroids/antivirals appropriately. 1 2 3 4 5 7. A B C D 8. A B C D 25. Recognize the role of oral antivirals in herpes zoster ophthalmicus treatment. 1 2 3 4 5 9. A B C D 26. Based upon your participation in this activity, do you intend to change your practice behavior? (Choose only one of the following options.) 10. A B C D A I do plan to implement changes in my practice based on the information presented. 11. A B C D B My current practice has been reinforced by the information presented. 12. A B C D 13. A B C D C I need more information before I will change my practice. 14. A B C D 27. Thinking about how your participation in this activity will influence your patient care, how many of your patients are likely to benefit? 15. A B C D (please use a number): 16. A B C D 28. If you plan to change your practice behavior, what type of changes do you plan to implement? (Check all that apply.) 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 ______29. How confident are you that you will be able to make your intended changes? A Very confident B Somewhat confident C Unsure D Not confident 30. Which of the following do you anticipate will be the primary barrier to implementing these changes? 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 ______31. Additional comments on this course: ______Please retain a copy for your records. Please print clearly.

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86 REVEWREVIEW OF OF OPHTHALMOLOGY OPTOMETRY | MAY | 15,JANUARY 2021 2021 LIVE COPE*

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which is 67.5 times greater than the rate Sidestep Side Effects associated with cataract surgery.2 To de- crease endophthalmitis risk, a cocktail Here’s how to minimize the potential complications of a KPro. of medications is typically administered

Photo: Stephen Orlin, MD during surgery and continued prophy- I have a few patients with a kerato- lactically over a patient’s lifetime. Q prosthesis (KPro). What does this While there’s controversy over which procedure involve? What form of prophy- antibiotic should be taken long-term, a laxis is recommended to reduce risk of broad-spectrum, fourth-gen fl uoroqui- complications? nolone (moxifl oxacin or gatifl oxacin) is “The most common artifi cial most commonly used, says Dr. Zim- A cornea used today is the Boston prich. In autoimmune or monocular KPro,” says Larae Zimprich, OD, of patients, fortifi ed vancomycin is pre- Vance Thompson Vision. A KPro is in- scribed. These should be taken QD.4 dicated in poor candidates for PKP due Following surgery, patients require to reasons such as repeated graft failure, long-term bandage contact lens wear Retroillumination view of the fenestrated aniridia, Stevens-Johnson syndrome, back plate on the Boston KPro. to prevent surface dehydration and chemical burn and autoimmune dis- enhance graft retention, notes Dr. Zim- ease, in which there is often complete recipient’s cornea. A paracentesis is cre- prich. Consequently, fungal keratitis is or nearly complete stem cell defi ciency. ated for injection of viscoelastic into the more likely to occur. Prescribe patients Since FDA approval in 1992, more anterior chamber to maintain structure amphotericin B (0.15%) or natamycin than 12,000 patients have been implant- and stability. The KPro is then sutured (5%) to use as needed.4 Lens removal ed with a KPro.1 The most widely used into place with at least 12 uninterrupted and replacement every three months or (Type I) is for patients with adequate or running 9-0 nylon sutures. Once the so is crucial.4 Betadine is recommended or normal tear function.2 Type II is re- sutures are buried and Seidel-negative, before lens reinsertion. served for end-stage corneal disease and a bandage contact lens is placed on Lifelong topical steroids (e.g., prednis- requires a permanent tarsorrhaphy.2 the eye. Following surgery, an antibi- olone acetate) are required in all KPro The KPro Type I consists of a clear otic and a steroid are injected into the eyes, says Dr. Zimprich. After the initial PMMA front plate, a back plate of conjunctiva.2 post-op period, taper down to once titanium or PMMA that contains 16 fen- Post-surgical complications such as daily.4 Close monitoring is necessary, estrations to allow passage of nutrients, retroprosthetic membranes, glaucoma, as steroids can exacerbate infection. If and a locking ring behind the plates to cataracts, infection, retinal detachment, irritation occurs, patients should stop secure the system.2 The corneal graft is device extrusion and stromal necro- steroid use and see an eye specialist situated between the two plates.2 sis can occur. For this reason, other immediately. procedures can be combined with the Repeat all glaucoma tests every six The Procedure KPro, such as cataract removal or IOP- months, suggests Dr. Zimprich. The KPro insertion typically takes 1.5 hours. lowering device implantation. Educate central cornea is no longer intact; there- Patients are monitored under general patients on the risk of adverse effects fore, measure IOP every three months anesthesia or a retrobulbar block.3 First, and the associated prognosis. using a tactile approach. This is why a surgeon marks the center of the host many surgeons implant an IOP-lower- cornea by using a Sinskey hook and Follow-up ing device in glaucoma suspects.4  measures the cornea to determine the Long-term care by different special- 1. KPro Study Group. kpro.org. Accessed March 19, 2021. appropriate transplant size. Then, the ists, including cornea, glaucoma and 2. Boston keratoprosthesis (KPro). EyeWiki. eyewiki.aao.org/ KPro is assembled. A donor cornea retina, is required for patients with a Boston_Keratoprosthesis_(KPro). Accessed March 19, 2021. 3. Keratoprosthesis patient management. Mass Eye and Ear. www. with a 3mm central hole is sandwiched KPro, according to Dr. Zimprich. One masseyeandear.org/medical-professionals/keratoprosthesis. between the front and back plates. The of the most common complications is Accessed March 19, 2021. 4. Recommendations: Boston KPro follow-up. Harvard Medical locking ring binds the system together. endophthalmitis. To date, the overall School. eye.hms.harvard.edu/eyeinsights/2015-september/recom- Next, the surgeon trephines the incidence of endophthalmitis is 2.7%, mendations-for-boston-kpro-follow-up. Accessed March 19, 2021.

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.

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surement of 28.48mm (axial myopia defined as axial length >26.00mm). From Dislocation to Nowhere was there any indication of pseudoexfoliation (PEX) or uveitis history. The patient did not have any Restoration connective tissue disorders. This patient had to undergo IOL replacement surgery to finally Discussion achieve satisfactory vision. IOL dislocation is an uncommon complication following cataract sur- By Leonid Skorin, jr., do, od, ms pinhole, but he was still unable to see gery. With respect to time, posterior Minneapolis the near-point chart with his near- chamber IOL dislocation is divided corrected left eye. Manifest refraction into early and late cases. Early cases 75-year-old male presented with of the left eye yielded 20/20-2 with a occur within the first three months sudden vision loss in his left eye +6.00D sphere lens. Pupils, extraocular of cataract surgery, while late cases that had occurred earlier that motility and confrontation visual fields happen after.1,2 In general, early cases Asame day. He reported that his were normal. Intraocular pressures of PC-IOL dislocation are the result vision was somewhat clearer in the pe- were 13mm Hg OD and 14mm Hg of inadequate posterior chamber IOL riphery than centrally. There were no OS. fixation within the capsular bag but accompanying flashes and, although he The slit lamp exam showed a stable can also result from a zonular rupture had a history of floaters, they did not posterior chamber IOL in the right during a traumatic cataract surgery.3,4 increase in incidence with the loss of eye. There was an apparent void with Late cases result from progressive vision. He denied eye pain, new-onset no PC-IOL seen behind the pupil of zonular weakness and capsular bag headache and jaw claudication. He had the left eye. Otherwise, the anterior contraction years after even uncompli- not experienced any trauma. segments of both eyes were unremark- cated cataract surgery.5 able. The fundus exam found an optic More specifically, posterior chamber Case nerve cup-to-disc ratio of 0.75 but was IOL dislocation can be divided into The patient’s ocular history included otherwise unremarkable. The posterior five catagories:6 open-angle glaucoma, for which he was chamber IOL was not visible in the • A lens that is decentered within an using latanoprost 0.005% in each eye at vitreal cavity of the left eye; only when intact capsular bag. This is most often bedtime. He was also pseudophakic in the patient was placed in Trendelen- seen in patients with PEX. both eyes. He had phacoemulsification burg’s position did it finally emerge. • A lens that is partially subluxed cataract surgery with posterior chamber The PC-IOL was still within the out of the capsular bag, with one (PC) intraocular lens (IOL) implanta- capsular bag and attached by zonules haptic in the bag and one haptic out tion 27 years earlier. At that time, he at the six o’clock position, causing a or one haptic in and the optic and was corrected for monovision, with his hinge-like phenomenon. It positioned other haptic out. This can also result right eye set for distance and his left itself inferiorly when the patient sat in uveitis-glaucoma-hyphema (UGH) eye set for near. He noted that he had up. This was confirmed with ante- syndrome. never been satisfied with his monovi- rior segment B-scan ultrasonography • A lens that is in the ciliary sulcus. sion prescription. He also had YAG la- (Figure 1). An IOL is surgically positioned in ser capsulotomies in both eyes 16 years We were able to review the patient’s the sulcus if there is a compromised ago. His medical history was positive eye records from 32 years prior. He was capsular bag, meaning there is a tear in for benign prostatic hypertrophy, for a moderate myope in both eyes. His the posterior capsule or rupture of the which he was taking tamsulosin. pre-cataract surgery glasses correction equatorial capsule. Posterior chamber The patient’s entrance acuities with was -5.00+1.25x082 OS, and his kera- IOL dislocation in this case is referred his current glasses were 20/20-1 OD tometry measurement was 40.25x41.12 to as sunset (inferior displacement) and count-fingers at six feet OS. His OS. We found that he had significant or sunrise (superior displacement) vision improved to 20/175 OS with axial myopia OS, with an A-scan mea- syndrome.2

About Dr. Mangan is a board-certified consultative optometrist from Boulder, CO, and a fellow of the American Academy of Optometry. He is an assistant professor in the depart- Dr. Mangan ment of ophthalmology at the University of Colorado School of Medicine. His focus is on ocular disease and surgical comanagement. He has no financial interests to disclose.

90 REVIEW OF OPTOMETRY | MAY 15, 2021 LIVE COPE*

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Fig. 1. Reverberations of sound waves can be seen from the dislocated posterior chamber IOL/capsular bag complex behind the iris.

• A PC-IOL that’s in the capsular may include an anterior chamber IOL, At the three-month post-op visit, the bag, both of which are dislocated. This an iris-fixed IOL, a transscleral, sutured patient was no longer on any post-op is what our patient presented with. PC-IOL or a flanged, intrascleral PC- medications. His uncorrected distance • A PC-IOL dislocated into the vit- IOL fixation technique.9 In one study, vision was 20/30+2 OS. With a refrac- real cavity or sitting on the retina. dislocated, in-the-bag PC-IOLs were tion of -0.50 +0.50x174 OS, he was able The first three categories are usually replaced with anterior chamber IOLs to see 20/20-1 OS. A +2.50 add yielded seen within the first three months after in 60% of patients or repositioned or 20/20 OS at near. He was happy he did cataract surgery (early cases), while the exchanged and then fixed to the sclera not need distance glasses and satisfied last two usually occur in late cases. in 40% of patients.1 Surgeons usually that he only had to use simple reading Late, spontaneous PC-IOL disloca- try to reuse the current PC-IOL if it is glasses for near work. g tion occurs with a cumulative rate of not damaged and if the patient reacted 1. Gross JG, Kokame GT, Weinberg DV. In-the-bag intraocular 0.1% after 10 years and 1.7% after 25 well up until the dislocation.8 lens dislocation. Am J Ophthalmol. 2004;137(4):630-5. years.2 One study found late-case PC- Our patient was never satisfied with 2. Ascaso FJ, Huerva V, Grzybowski A. Epidemiology, etiology and prevention of late IOL-capsular bag complex dislocation: IOL dislocation occurred with virtually his monovision correction, so he chose review of the literature. J Ophthalmol. 2015;2015:805706. all posterior chamber IOL materials a lens exchange with the new posterior 3. Matsumoto M, Yamada K, Uematsu M, et al. Spontaneous 7 dislocation of in-the-bag intraocular lens primarily in cases and lens designs. The same series chamber IOL to be set for optimal with prior vitrectomy. Eur J Ophthalmol. 2012;22(3):363-7. found that PEX accounted for 50% of distance correction. 4. Wilson DJ, Jaeger MJ, Green WR. Effects of extracapsular all PC-IOL dislocations.7 The corrective surgery was per- cataract extraction on the lens zonules. Ophthalmology. 1987;94(5):467-70. Other causes included high myopia, formed with the assistance of a retina 5. Krėpštė L, Kuzmiene L, Miliauskas A, et al. Possible trauma, vitreoretinal surgery, retinitis surgeon. The surgeon performed a predisposing factors for late intraocular lens dislocation after pigmentosa, connective tissue dis- vitrectomy and prolapsed the dislo- routine cataract surgery. Medicina. 2013;49(5):229-34. 6. Stephenson M. How to manage dislocated IOLs. Rev orders, diabetes, atopic dermatitis, cated posterior chamber IOL/capsular Ophthalmol. 2018;25(10):54-60. previous angle-closure attacks and bag complex into the anterior cham- 7. Davis D, Brubaker J, Espandar L, et al. Late in-the-bag spontaneous intraocular lens dislocation. Ophthalmology. even older age, as zonules become ber. This lens/bag complex was then 2009;116(4):664-70. 2,7 more friable with age. Any condition, removed through a temporally placed 8. Stephenson M. How to handle dislocated IOLs. Rev Oph- including uveitis, that results in the scleral tunnel incision. A three-piece thalmol. 2020;27(11):76-8. breakdown of the blood-aqueous bar- acrylic monofocal posterior chamber 9. Yamane S, Sato S, Maruyama-Inoue M, et al. Flanged intra- scleral intraocular lens fixation with double-needle technique. rier is also likely to be associated with IOL was passed through this same Ophthalmology. 2017;124(8):1136-42. progressive zonulysis and potentially surgical incision and into the anterior late-case PC-IOL dislocation.8 chamber. It was then maneuvered into ABOUT THE AUTHOR the posterior chamber with its two hap- Dr. Skorin is a consultant in the Department Management tics externalized through the sclera and of Surgery, Community Division of Ophthalmology at the Mayo Clinic Health Surgery for secondary IOL implanta- secured using the flanged, intrascleral System in Albert Lea and Austin, MN. He tion in the absence of capsular support fixation technique.9 has no financial interests to disclose.

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c. Vitreous hemorrhage. d. None of the above; there is a 100% Persistent Proliferation success rate of RD repair. Solve this patient’s cloudy vision with fundus photography. 4. Which of the following is true of rhegmatogenous retinal detachment (RRD) By Rami Aboumourad, OD examination revealed a deep anterior repair? Houston chamber (AC) OU with rare cells and a. Smaller-gauge surgical instrumenta- 1+ fl are OS. Imaging of the posterior tion yields a better prognosis. 56-year-old Hispanic male pre- segment is shown below (Figure 1). b. Intravitreal steroid use yields a better sented with a two-week history prognosis. of “blurry vision” in his left eye. Take the Retina Quiz c. Cigarette smoking yields a poorer AHe described a cloudiness and 1. Which is seen in the fundus photo? prognosis. fogginess to his vision and a left-sided a. A retinal tear or retinal detachment d. Perfl uoropropane (C3F8) gas always dull, achy eye pain. Upon further (RD). yields a poorer prognosis than questioning, he endorsed a three-week b. A choroidal detachment. silicone oil. history of fl ashes and fl oaters in the left c. Pre-retinal membranes. eye. The right eye was asymptomatic d. All of the above. 5. What level of VA will most patients and he denied any similar previous achieve in the setting of postperative ana- episodes in either eye. His past ocular, 2. Which of the following is true of the mem- tomic success? medical and social histories were branes in the fundus photos? a. Approximately 20/50 BCVA. unremarkable. He had no known drug a. They are secondary to retinal pig- b. Ambulatory vision (approximately allergies and did not remember his last ment epithelial cell proliferation. 20/800). eye exam. b. They are secondary to chronic retinal c. Light perception. On examination, his best-corrected ischemia. d. No light perception. visual acuity (BCVA) was 20/25-1 OD c. They are fi brovascular in origin. For answers, see page 106. and hand motions OS. There was a d. They can be treated with intravitreal relative afferent pupillary defect in anti-VEGF therapy. Diagnosis the left eye. His extraocular motilities Slit lamp examination of the patient were full OU, and there was a signifi - 3. What is the strongest preoperative risk revealed positive Shafer sign in the cant constriction to his confrontation factor for surgical failure of RD repair? left eye with pigment clumping in the visual fi elds OS. His intraocular pres- a. Acute macular involvement. inferior vitreous and moderate vitreous sure (IOP) measured 18mm Hg OD b. Proliferative vitreoretinopathy haze. Fundus exam revealed a large and 4mm Hg OS. Anterior segment (PVR). radial superotemporal retinal tear with an adjacent smaller break at 12:30 in the left eye, with bullous surrounding subretinal fl uid (Figure 1). The macula was detached, and there were dif- fuse preretinal tractional membranes anterior and posterior to the equator. There remained only a small sector of attached retina inferotemporally (Fig- ures 1B and 2). Additionally, there were serous choroidal effusions nasally and temporally (Figure 1). We diagnosed an RRD with PVR OS. The size and chronicity of the large Fig. 1.Optos ultra-widefi eld (A) and Topcon (B) montage fundus images of the left eye. retinal tear led to secondary hypotony

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.

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Find your next hire at eyesoneyecare.com/hire-now RETINA QUIZ | Persistent Proliferation with choroidal effusions, AC inflam- ity.8 Reported anatomic success rate mation and ciliary body shutdown— in these cases is 60% to 80%.8 Of resulting in the patient’s eye pain. those that are anatomically success- ful, only 40% to 80% will recover Discussion ambulatory vision (5/200) or better.6,8 PVR is defined as the avascular pro- The patient in question was liferation and contraction of fibrocel- referred to our retina service. Un- lular retinal membranes associated derstanding the risks, benefits and with a rhegmatogenous retinal de- alternatives to treatment, the patient tachment.1,2 Despite surgical advanc- underwent 25-gauge PPV, endoscop- es, PVR remains the leading cause of ic laser photocoagulation, membrane rhegmatogenous retinal detachment peel, fluid-air exchange, cryotherapy Fig. 2. Ultra-widefield fundus image of the left eye (RRD) surgical failure at a rate of 5% at post-op month two. and insertion of 5000-centistoke to 10% (mean of 7%).1-4 Risk factors silicone oil. for PVR development include retinal ing the mobility and rigidity of the On the first day of post-op, the tear size, presence of vitreous hemor- retina, which can aid prognostication patient’s vision was counting fingers rhage, chronic intraocular inflammation, and surgical planning.5 Retinal rigid- at three feet and IOP was 4mm Hg. longstanding untreated RRD, unsuc- ity can also be assessed during scleral There was good silicone oil fill, and the cessful RRD repair and penetrating depression, and by evaluating retinal retina was grossly flat under the oil with ocular trauma.1,3-6 While its role is not mobility during saccades on indirect fresh laser surrounding the superotem- completely understood, smoking is the ophthalmoscopy.1,5 poral retinal breaks. The patient was only identified modifiable risk factor for Early PVR is characterized by vitre- then lost to follow-up until month two PVR development.7 ous haze, pigment clumping and retinal of post-op, at which his vision remained Disruption of the blood-retinal folds, and advanced PVR became at counting fingers and IOP was 17mm barrier—as in the case of a retinal break further subdivided in a more recent Hg. The retina remained attached or detachment, uveitis, cryotherapy classification after surgical success rates under oil with an epiretinal membrane and trauma—allows for the influx of were better for posterior than anterior along the inferior arcade inducing trac- inflammatory and retinal pigment PVR.3,4 Many clinicians still simply tion (Figure 2). ■ epithelial (RPE) cells into the vitreous grade PVR as mild, moderate or severe cavity.5,6 Once liberated, the prolifera- and acknowledge anterior/posterior 1. Yanoff M, Duker JS. Ophthalmology. 5th ed. Elsevier; 2018. 2. Pastor JC. Proliferative vitreoretinopathy: an overview. Surv tion of these cells leads to formation of extent of starfolds and traction. Ophthalmol. 1998;43(1):3-18. 2 preretinal and subretinal membranes. 3. Idrees S, Sridhar J, Kuriyan AE. Proliferative vitreoretinopa- Proliferative membranes, once formed, Treatment Options thy: a review. Int Ophthalmol Clin. 2019;59(1):221-40. 2 4. Coffee RE, Jiang L, Rahman SA. Proliferative vitreoretinopa- contract and induce retinal traction. Surgical intervention remains the thy: advances in surgical management. Int Ophthalmol Clin. The tractional forces exerted from primary treatment modalities for these 2014;54(2):91-109. these membranes can create secondary complex eyes.8 Pars plana vitrectomy 5. Schachat A P, Wilkinson C P, Hinton D, et al. Ryan’s Retina. 6th ed. Elsevier;2018. retinal breaks as well as reopen breaks (PPV) has been performed using 20-, 6. Pastor JC, de la Rúa ER, Martín F. Proliferative vitreoreti- that have already been treated.2 These 23-, 25- and 27-gauge instrumentation nopathy: risk factors and pathobiology. Prog Retin Eye Res. secondary breaks in the retina serve as with equivalent outcomes.3 A thorough 2002;21(1):127-44. 7. Xu K, Chin EK, Bennett SR, et al. Predictive factors for prolif- a conduit for further influx of catalytic vitrectomy with complete removal of erative vitreoretinopathy formation after uncomplicated primary RPE and inflammatory cells.2 As dem- the vitreous and any preretinal mem- retinal detachment repair. Retina. 2019;39(5):1488-95. 8. Sadaka A, Giuliari G P. Proliferative vitreoretinopathy: current onstrated, the pathogenesis of PVR is branes is necessary to achieve optimal and emerging treatments. Clin Ophthalmol. 2012;6:1325-33. 3 cyclic and self-propagating. outcomes. Comparison of intraocular 9. Abrams GW, Azen S P, McCuen BW, et al. Vitrectomy with Clinically, the retina takes on an tamponades revealed that silicone oil silicone oil or long-acting gas in eyes with severe proliferative vitreoretinopathy: results of additional and long-term follow-up: opaque appearance with wrinkles and and perfluoropropane (C3F8) gas are Silicone Study Report 11. Arch Ophthalmol. 1997;115(3):335- fixed folds.2 Due to gravity, PVR tends both equivalent to each other but supe- 44. 9,10 10. Diddie KR, Azen S P, Freeman HM, et al. Anterior proliferative to begin inferiorly with fine mem- rior to sulfur hexafluoride (SF6) gas. vitreoretinopathy in the Silicone Study: Silicone Study Report branes bridging the retinal folds as they Subgroup analysis, however, suggested number 10. Ophthalmology. 1996;103(7):1092-9. contract. Often, one can appreciate better visual prognosis with silicone oil proliferative membranes at the leading for eyes with anterior PVR.10 ABOUT THE AUTHOR edge of a retinal break, which causes Unfortunately, the prognosis for Dr. Aboumourad is an assistant stiffening of the torn retina and a rolled these complex RRDs remains poor professor of ophthalmology at Baylor posterior edge. Dynamic ultrasonog- despite best surgical efforts. The retinal College of Medicine in Houston. He also practices at the Jamail Specialty Care raphy remains a powerful tool for redetachment rate can be as high as Center of the Alkek Eye Center. He has identifying advanced PVR by evaluat- 75% depending on preoperative sever- no financial interests to disclose.

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104 REVIEW OF OPTOMETRY | MAY 15, 2021 ReviewCORNEA/ANTERIOR news SEGMENT | Conjunctivochalasis Surgical Techniques

1 Eyhance Intraocular Lenses studyCooperVisionTsuchihashi in ...... Frontiers Y. Clinicopathologic in Neurology study of reports.conjunc- 107 theMacuLogixOphthalmic study...... 23 Plast Reconstr Surg 2013;29:304–7. ADVERTISERfail, surgical options include INDEX shrink- ...... (800)tivochalasis.The multinational Cornea 2004;23:3:294-298. research team 341-2020 ...... (888)21.Following Liu D. Conjunctivochalasis: light exposure, A cause partici- of tear- 392-6801 Approved by FDA ...... www.coopervision.com 11. Francis IC, Chan DG, Kim P, Wilcsek G, Filipic M, ...... ing and its management. Ophthalmic Plasticwww.maculogix.com and (Continuedage of redundant from p. 16) tissue, removal composedYong J, Coroneo of researchersMT. Case-controlled from clinical Swit- and pantsReconstructive showed Surgery a much 1986;21:25-28. greater post- Eye Designs ...... 31 Thisof redundantindex is published tissue as a convenience and increased and not as part histopathologic study of conjunctivochalasis. Br J 22. Brodbaker E, Bahar I, Slomovic AR. Novel use of zerland,...... (800) the United Kingdom and 346-8890 illuminationOyster Point Pharma ...... 7 pupil response and had of the advertising contract. Every care will be taken to Ophthalmol 2005;89:302-305. fibrin glue in the treatment of phacoemulsifiadhesion cation. between Int Ophthalmol. conjunctiva 2021;41:1:273-282. and New...... Zealand suggests the changewww.eyedesigns.com better...... quality of sleep. Additionally,www.dryeyeland.com 12. Tong L, Lan W, Sim HS, Hou A. conjunctivochalasis. Cornea 2008;27:950-2. 2. indexMencucci correctly. R, Cennamo No allowance M, Venturi will D,be et made al. Visual for errors out- due sclera.  inConjunctivochalasis pupil response is themight precursor indicate to pterygium. that researchers23. Georgiadia report NS, Terzidou that CD. they Epiphora found caused no by come,to spelling, optical incorrectquality, and page patient number, satisfaction or failure with to insert.a new Eyevance ...... 11 & 12 Regeneron Pharmaceuticals, Inc...... 36 , 37 & 38 Medical Hypotheses 2013;81:927-930. conjunctivochalasis: Treatment with transplantation monofocal IOL, enhanced for intermediate vision: Prelimi- melanopsin...... (817) activity in viable intrinsi- 677-6120 signifi...... (914) cant changes in the participants’ 847-7000 Advancing Eyecare ...... 75 ...... 13. Li D, Meller D, Liu Y, Tseng SCG. Overexpressionwww.MyZerviate.com of preserved human amniotic membrane. Cornea nary...... (904)1. results.Elschnig J A.Cataract Beitrag Refract zur aetiologie Surg. 2020;46:3:378-387. und therapie der 997-4131 cally photosensitive retinal ganglion 24-hour...... rhythms or sleep parameters.www.regeneron.com 3. Eguileorchronischen B, Martinez-Indart konjunktivitis. L, Dtsch Alday Med N, et Wochenschr al. Differences of MMP-1 and MMP-3 by cultured conjunctivochala- 2001;20:6:619-621...... www.marco.com Eyevance ...... 41 & 42 in intermediate vision: Monofocal intraocular lenses vs. sis fibroblasts. IOVS 2000;41:2:404-410. 24. Meller D, Maskin SL, Pired RTF, Tseng SCG. 1908;34:1133-1155. cells...... (817) can adapt to different light lev- 677-6120 ReichertThe Technologies study ...... 69 demonstrated that even monofocal extended depth of focus intraocular lenses. 14. Acera A, Vecino E, Duran JA. Tear MMP-9 levels Amniotic membrane transplantation for symptomatic Akorn2. Hughes Pharmaceuticals WL. Conjunctivochalasis...... 27 Am J Ophthalmol els,...... if sustained over a periodwww.mytobradexst.com of time. a...... (888) relatively short duration of added 849-8955 Arch...... 1942;25:48-51. Soc Esp Oftalmol. 2020;95:11:523-527.www.MyAkornEyeCare.com as a marker of ocular surface inflammation in con- conjunctivochalasis refractory to medical treatments. junctivochalasis. IOVs 2013;54:13:8285-8291...... Cornea 2000;19:6:796-803.www.passionateabouteyecare.co /glaucoma 4. Yangzes3. Di Pascuale S, Kamble MA, N,Espana Grewal EM, S, et Kawakita al. Comparison T, Tseng EyevanceTheir ...... 65 study enrolled 20 glaucoma & 66 light exposure in a room is benefi cial of AlconanSCG. aspheric Laboratories Clinical monofocal characteristics ...... 108 intraocular of conjunctivochala- lens with the new ...... (817)15. Guo P, Xhang S, He H, Zhu Y, Tseng SCG. TSG-6 677-6120 25. Nakasato H, Uemoto R, Meguro A, et al. Treatment patients without severe vision loss andRVL Pharmaceuticals, also supports Inc...... 2 the general advice , 3 & 4 generation...... (800)sis with monofocalor without aqueouslens using tear defocus deficiency. curve. BrIndian J 451-3937 J ...... controls transcription and activation of www.eyevance.commatrix of symptomatic inferior conjunctivochalasis by liga- Ophthalmol...... Ophthalmol 2020;68:12:3025-3029. 2004;88:388-391. www.alcon.com andmetalloproteinase considered 1 inhow conjunctivochalasis. 30 minutes IOVSof that...... (866)tion. the Acta elderlyOphthalmol should 2014;92:e411-2. go outside 600-4799 5. Auffarth4. Balci O.GU, Clinical Gerl M, characteristics Tsai L, et al. Clinical of patients evaluation of Haag-Streit2012;53:3:1372-1380. USA ...... 17 ...... 26. Otaka I, Kyu N. A new surgical techniquewww.Upneeq.com for Alcon Laboratories Inc...... 45 daily bright light exposure from a for half an hour each morning, the a newwith monofocal conjunctivochalasis. intraocular lensClinical with Ophthalmology enhanced inter- ...... (866)16. Ward SK, Wakamatsu TH, Dogru M, Ibrahim OMA,769-1197 management of conjunctivochalasis. Brief Reports ...... (800) 451-3937 ...... www.xomasmartlane.com mediate2014;8:1655-1660. function in cataract patients. J Cataract Refract table-basedKaido M, Ogawa light Y, Matsumoto box placed Y, Igarashi in A, their Ishida researchersSun1999;129:3:385-387. Pharma ...... 59 suggest. & 60 Surg 2021;47:2:184-91. R, Shimazaki J, Schnider C, Negishi K, Katakami C, Allergan5. Meller, ...... Cover D, Tseng SC. Conjunctivochalasis: Literature Tip homes affected pupil constriction, ...... While glaucoma patients canwww.GetCequa.com never IcareTsubota USA ...... 29 K. The role of oxidative stress and inflam- ...... review and possible pathophysiology. Surveywww.allergan.com of circadian...... (888)mation in conjunctivochalasis. rest-activity cycles, IOVS 2010;51:4:1994- sleep, 389-4022 recover the vision lost from damaged Ophthalmology 1998;43:3:225-232...... www.icare-usa.com TopconDISCLOSURES ...... 48 & 49 Bausch6. Marmalidou + Lomb ...... A, Kheirkhah A, Dana R. 21 relaxation,2002. alertness and mood. retinal...... ganglion cells, theywww.topconhealthcare.com may be Bright Light May 17. Mamalidou A, Palioura A, Dana R, Kheirkhah A. Samantha Marek, MD, is a ...... (800)Conjunctivochalasis: A systematic review. Survey 871-1103 of Imprimis Pharmaceuticals, Inc...... 19 resident at the University of ...... www.alaway.com MedicalParticipants and surgical continuously management of conjunctivocha-wore an able to maintain a robust day–night Ophthalmology 2018;3:554-564...... (858) 704-4040 US Ophthalmic ...... 53Pennsylvania Department of ...... lasis. The Ocular Surface 2019;17:393-399.www.imprimisrx.com Help7. Mimura T, GlaucomaYamagami S, Usui T, et al. Changes of activity monitor and self-assessed cycle...... and concomitantOphthalmology. goodwww.usophthalmic.com circadian Bruder Ophthalmic Products ...... 55 18. Haefliger IO, Vysniauskiene I, Figueiredo AR, conjunctivochalasis with age in a hospital-based Stephen Orlin, MD, is the director ...... (888) 827-8337 sleepJohnsonPiffaretti &quality, Johnson JM. Superficial ...... 14 well-being conjunctiva and cauterization visual to entrainment which helps maintain study. Am J Ophthalmol 2009;147:1:171-77. X-cel Specialty ...... 33of the Cornea Department, chair Patients...... [email protected] comfort...... reduce moderate for several conjunctivochalasis. days beforewww.jnjvisionpro.com Klin Monatsbland high sleep quality, the investigators ...... 8. Mimura T, Mori M, Obata H, et al.www.bruderophthalmic.com ...... (800)of the Cornea Service, co-director 241-9312 GlaucomaConjunctivochalasis: patients Associations who are with exposed pinguecula in duringAugenheilkd the 2007;224:237-239.four weeks of daily 10,000 explain.  of the Refractive Surgery Service Keeler19. Trivle Instruments A, Dalianias ...... 9 G, Terzidou C. A quick surgical ...... [email protected] Coburna hospital-based Technologies ...... 47 study. Acta Ophthalmol 90:8:773-82...... (800) 523-5620 and an associate professor to bright light during the day may luxtreatment polychromatic of conjunctivochalasis bright usingwhite radiofrequen- light ...... www.xcelspecialtycontacts.com ...... (800)9. Tong L, Lan W, Sim HS. Conjunctivochalasis 262-8761 ...... www.keelerusa.com of ophthalmology at the Penn ...... is the precursor to pterygium. Medwww.coburntechnlogies.com Hypotheses cies. Healthcare 2018;6:14:1-5. 1. Kawasaki A, Udry M, WardaniPresbyterian ME, Münch Medical M. Center Can extra have improved sleep and an increased exposure. X-cel Specialty ...... 73 2013;81:5:927-30. Lacrimedics,20. Petris Inc.CK, ...... Holds JB. Medial conjunctival resec- 13 daytime light exposure improveof Philadelphia. well-being They and report sleep? no melanopsin-dependent pupil re- Individuals underwent pupillom- ...... (800) 241-9312 CooperVision10. Watanabe ...... 25 A, Yokoi N, Kinoshita S, Hino Y, ...... (800)tion for tearing associated with conjunctivochalasis. 367-8327 A pilot study of patients withrelated glaucoma. financial Front disclosures. Neurol sponse...... (800) after just four weeks, a pilot 341-2020 etry...... at baseline and on the [email protected] day of 2020;11:584479...... [email protected] ...... www.coopervision.com ...... www.lacrimedicsl.com ...... www.xcelspecialtycontacts.com

The Rick Bay Foundation for Excellence in Eyecare Education Support the Education of Future Healthcare & Eyecare Professionals Scholarships are awarded to advance the education of students in both Optometry and Ophthalmology, and are chosen by their school based on qualities that embody Rick’s commitment to the profession, including integrity, compassion, partnership and dedication to the greater good. Interested in being a partner with us? Visit www.rickbayfoundation.org (Contributions are tax-deductible in accordance with section 170 of the Internal Revenue Code.)

(The Rick Bay Foundation for Excellence in Eyecare Education is a nonprofi t, tax-exempt organization under section 501(c)(3) of the Internal Revenue Code.)

MAY 15, 2021 | REVIEW OF OPTOMETRY 105 30 70REVIEWREVIEW OF OF OPHTHALMOLOGY OPHTHALMOLOGY | MARCH | MAY 2021 2021 By Andrew S. Gurwood, OD diagnostic quiz

20/20 at near with a working distance of 10 inches. There was substantial Game Over improvement upon the pinhole at An anxious patient presents complaining of recent-onset distance. External examination was normal for color, brightness and blurred vision at distance. Are his fears warranted? extraocular motilities. Confrontation fields were normal and facial Amsler 55-year-old man reported to He explained further that every- grid was normal with no afferent the office emergently with a thing in the distance was blurry. The pupillary defect. chief complaint of blurry vi- patient was properly medicated for Refraction uncovered -0.75D Asion at distance in both eyes. hypertension and high cholesterol sphere, resulting in 20/20 vision at He explained in a panic that he had and denied trauma or allergies of any distance. Biomicroscopy showed woken up early that morning seeing kind. normal anterior segment structures, well, then played a game on his cell and Goldmann applanation tonom- phone and noticed that, after he Diagnostic Data etry recorded pressures of 16mm Hg stopped, he no longer needed his His best-corrected entering visual in each eye. Dilated exam uncovered reading glasses to read. acuities were 20/70 at distance and normal nerves with no evidence of maculopathy or disc edema.

Additional Testing The first important additional test is lensometry. This will permit an understanding of the previous refrac- tive error. It can then be matched against the refraction to understand how things have changed. A detailed history should include whether vi- sion is absent, distorted or blurry, and in which eye and when.

Your Diagnosis What would be your diagnosis in this case? What is the patient’s likely prognosis? To find out, please read The patient’s description of events: iPhone video play, followed by ability to read without the online version of this article at reading glasses but distance vision blur. 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 94)—Q1: d, Q2: a, Q3: b, Q4: c, Q5: b

Next Month in the Mag • Comanagement Series: Be a Retina Referral Rock Star In June, we present our annual retina report. Articles will include: • Assessing Macular Disorders and Dystrophies • The Retina Research Pipeline: Upcoming Advances to Look • Optometric Retina Society Annual Larry Alexander Case Report Forward to Contest Winner • How to Handle Central Serous Chorioretinopathy Also included in June: • Be Ready for Acute Retinal Ischemia • PAL Primer: How to Use New and Specialty Lens Designs

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1. CooperVision data on file 2021. Rx coverage database; 14 to 70 years. 2. CooperVision data on file, 2017-2019. Based on number of US soft contact lens fits. Includes CooperVision branded and customer-branded equivalent lenses. US industry reports and internal estimates. 3. Around the clock axis in 10° from Plano to -6.00DS in -0.75DC, 1.25DC and -1.75DC. 4. CVI data on file 2021. Based on number of prescription options available in the USA across all soft 1-day toric lenses as reported by the 4 main manufacturers and the SKU expansion for MyDay® toric (2H’21). 5. CooperVision data on file 2020. Kubic masked online survey; n=404 US ODs who prescribe toric soft CLs. ©2021 CooperVision 11006 04/21 Recommend long-lasting, preservative-free dry eye relief1*

Introducing HydroBoost Technology An exclusive combination that helps retain the lubricants, for relief to patients who need it most1

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HP-GUAR Forms a cross-linked meshwork on the surface of the eye to hold lubricants in place2

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SODIUM HYALURONATE Naturally occurring moisture substance found in tears that helps the lubricants to provide longer-lasting hydration1,3*

The Relief Is Real®

*Vs SYSTANE ULTRA Lubricant Eye Drops. References: 1. Mrukwa-Kominek E, Baranska K, Jadczyk K. First clinical reports on the application of the modern dual-polymer formula in aqueous defi ciency dry eye syndrome - Polish observations. Presented at the 20th European Society of Cataract & Refractive Surgery Winter Meeting; February 26-28, 2016; Athens, Greece. 2. Davitt WF, Bloomenstein M, Christensen M, Martin AE. E‘ cacy in patients with dry eye after treatment with a new lubricant eye drop formulation. J Ocul Pharmacol Ther. 2010;26:347-353. 3. Rah MJ. A review of hyaluronan and its ophthalmic applications. Optometry. 2011;82:38-43.

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