STARK AND ANTI-KICKBACK LAWS P. 15 • GLAUCOMA INFLOW ABLATIVE PROCEDURES P. 18 A NEW DRUG TOXICITY REPORTED P. 50 • RESEARCH NEWS P. 47 CROSS-LINKING IN CHILDREN P. 54 • WILLS RESIDENT CASE REPORT P. 63 Review of Ophthalmology Vol. XXVI, No. 7 • July 2019 How to Manage Postop • Refractive Surgery in Patients Surprises Over 50 • Ocular Trauma

JulyJuly 20192019

reviewofophthalmology.comreviewofophthalmology.com

REFRACTIVE-CATARACT FOCUS HOW TO DEAL WITH THE UNEXPECTED

Experts share their tips for dealing with postop refractive surprises. P. 28

ALSO INSIDE: • Refractive Surgery in the Patient Over 50 P. 36 • How to Manage Ocular Trauma P. 42

001_rp0719_fc.indd 1 6/28/19 12:13 PM Less stress, pure success ...in your O.R. day1 ™

OMIDRIA® (phenylephrine and ketorolac intraocular solution) 1% / 0.3% is added to ophthalmic irrigating solution used during cataract surgery or intraocular lens replacement and is indicated for maintaining pupil size by preventing intraoperative miosis and reducing postoperative ocular pain.

The data are compelling and consistent—OMIDRIA makes cataract surgery better for you and your patients Published and presented clinical studies and manuscripts in press and/or in preparation report that in post-launch (i.e., not included in current labeling), prospective and retrospective, double-masked and open-label, cohort and case-controlled, single- and multi-center analyses, the use of OMIDRIA, compared to the surgeons’ standard of care, statistically significantly: • Prevents Intraoperative Floppy Iris Syndrome (IFIS)2 • Delivers NSAID to the anterior chamber and related structures • Reduces complication rates (epinephrine comparator)3 better than routine preoperative topical drug administration, • Decreases use of pupil-expanding devices resulting in effectively complete postoperative inhibition of 10,11 (epinephrine comparator)3-8 COX-1 and COX-2 • Reduces surgical times (epinephrine comparator)3,5,7,8 • Reduces the incidence of rebound iritis, postoperative pain/ photophobia, and cystoid macular edema (CME) in patients without • Prevents miosis during femtosecond laser-assisted surgery preoperative vitreomacular traction (VMT), when used with a (epinephrine comparator)6,9 postoperative topical NSAID (compared to postoperative topical • Improves uncorrected visual acuity on day after surgery NSAID + corticosteroid without OMIDRIA)12 (epinephrine comparator)3 OMIDRIA inhibits prostaglandin release, reducing intraoperative inflammation, to prevent miosis and reduce postoperative pain13 OMIDRIA is separately reimbursed under Medicare Part B and by many Medicare Advantage and commercial payers.* Contact your OMIDRIA representative today or visit omidria.com to learn more.

*Based on currently available information and subject to change without notice. Individual plan coverage, policies, and procedures may vary and should be confirmed. Omeros does not guarantee coverage or payment.

IMPORTANT SAFETY INFORMATION OMIDRIA must be added to irrigating solution prior to intraocular use. OMIDRIA is contraindicated in patients with a known hypersensitivity to any of its ingredients. Systemic exposure of phenylephrine may cause elevations in blood pressure. Use OMIDRIA with caution in individuals who have previously exhibited sensitivities to acetylsalicylic acid, phenylacetic acid derivatives, and other nonsteroidal anti-inflammatory drugs (NSAIDs), or have a past medical history of asthma. The most commonly reported adverse reactions at ≥2% are eye irritation, posterior capsule opacification, increased intraocular pressure, and anterior chamber inflammation. Please see the Full Prescribing Information for OMIDRIA at www.omidria.com/prescribinginformation. You are encouraged to report Suspected Adverse Reactions to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

References: 1. Omeros survey data on file. 2. Silverstein SM, Rana V, Stephens R, Segars L, Pankratz J, Shivani R, et al. Effect of phenylephrine 1.0%-ketorolac 0.3% injection on tamsulosin-associated intraoperative floppy-iris syndrome. J Cataract Refract Surg. 2018;44(9):1103-1108. 3. Rosenberg ED, Nattis AS, Alevi D, et al. Visual outcomes, efficacy, and surgical complications associated with intracameral phenylephrine 1.0%/ketorolac 0.3% administered during cataract surgery. Clin Ophthalmol. 2018;12:21-28. 4. Bucci FA Jr, Michalek B, Fluet AT. Comparison of the frequency of use of a pupil expansion device with and without an intracameral phenylephrine and ketorolac injection 1%/0.3% at the time of routine cataract surgery. Clin Ophthalmol. 2017;11:1039-1043. 5. Visco D. Effect of phenylephrine/ketorolac on iris fixation ring use and surgical times in patients at risk of intraoperative miosis. Clin Ophthalmol. 2018;12:301-305. 6. Walter K, Delwadia N. Miosis prevention in femtosecond cataract surgery using a continuous infusion of phenylephrine and ketorolac. Presented at: 2018 American Society of Cataract and Refractive Surgery (ASCRS) and American Society of Ophthalmic Administrators (ASOA) Annual Meeting; April 13-17, 2018; Washington, DC. 7. Matossian C. Clinical outcomes of phenylephrine/ketorolac vs. epinephrine in cataract surgery in a real-world setting. Presented at: American Society of Cataract and Refractive Surgery (ASCRS) and American Society of Ophthalmic Administrators (ASOA) Annual Meeting; April 13-17, 2018; Washington, DC. 8. Al-Hashimi S, Donaldson K, Davidson R, et al. Medical and surgical management of the small pupil during cataract surgery. J Cataract Refract Surg. 2018;44:1032-1041. 9. Gayton JL. E-poster presented at: 15th International Congress on Vision Science and Eye; 2017 Aug 10-11; London, UK. 10. Katsev DA, Katsev CC, Pinnow J, Lockhart CM. Intracameral ketorolac concentration at the beginning and end of cataract surgery following preoperative topical ketorolac administration. Clin Ophthalmol. 2017;11:1897-1901. 11. Waterbury LD. Alternative drug delivery for patients undergoing cataract surgery as demonstrated in a canine model. J Ocul Pharmacol Ther. 2018;34:154-160. 12. Visco D. et al. Study to evaluate patient outcomes following cataract surgery when using OMIDRIA with postoperative topical NSAID administration versus a standard regimen of postoperative topical NSAIDs and steroids. Presented at: 28th Annual Meeting of the American College of Eye Surgeons (ACES), the American Board of Eye Surgery (ABES), and the Society for Excellence in Eyecare (SEE), Caribbean Eye Meeting; February 1-5, 2019; Cancún, Mexico. 13. OMIDRIA [package insert]. Seattle, WA: Omeros Corporation; 2017. OMIDRIA® and the OMIDRIA logo® are registered trademarks of Omeros Corporation. © Omeros Corporation 2019, all rights reserved. 2019-004

RP0719_Omeros.indd 1 6/17/19 10:18 AM REVIEW NEWS Volume XXVI • No. 7 • July 2019 Studies Shed Light on Postop Cataract Complications

Two groups of international researchers cent fl are-up, and three (5.3 per- recently published studies that may cent) had surgery fewer than three help cataract surgeons minimize months after the last recurrence. complications. After the group’s cataract surger- A group composed of researchers ies, the HZO recurred in 23 patients from the New Zealand National Eye (40.4 percent), with recurrences in Center at the University of Auckland the fi rst two years postop being the and the Greenlane Clinical Centre at most common. Three patients de- the Auckland District Health Board veloped band keratopathy after re- say that cataract surgeons may be peated infl ammation, and one had able to take certain measures preop a neurotrophic keratitis with a per- to help minimize the recurrence of were HIV-positive. sistent epithelial defect. There was herpes zoster-related ocular disease. At presentation, the researchers a severe recurrence of herpes kera- In what the researchers deem say that 55 patients (96.5 percent) titis with corneal melt in the eye of the largest study to date examining had a typical clinical presentation a Crohn’s-disease patient which ulti- the outcomes of cataract surgery in of HZO, with unilateral rash. Fifty- mately required evisceration. eyes with a history of herpes zoster four patients were taking antivirals, The study’s corresponding au- keratitis and uveitis, the researchers and 48 of them (88.9 percent) re- thor, Rachael L. Niederer, MB ChB, retrospectively studied 57 cases (57 ceived seven to 10 days of oral anti- PhD, FRANZCO, of the Depart- eyes of 57 patients) in which patients viral therapy. The median corrected ment of Ophthalmology at Green- with herpes zoster-related keratitis distance visual acuity at presentation lane Clinical Centre, says a couple and/or uveitis had cataract surgery was 20/30 (range: 20/25 to 20/60). things stood out to her from the in the affected eye.1 Patients were Thirty-seven patients (64.9 percent) study’s fi ndings. “Cataract surgery in included if they had clinical presen- had corneal disease at presentation, subjects with previous HZO is com- tation of HZO with keratitis or an- with pseudodendrites in 21 cases plicated by corneal scars (43.9 per- terior uveitis, or if they had anterior (36.8 percent) and disciform kerati- cent), atrophic fl oppy iris (5.3 per- uveitis consistent with a viral picture tis in 19 (33.3 percent). Forty-eight cent) and posterior synechiae (8.8 that was confi rmed to be varicella patients (84.2 percent) had anterior percent),” she says. “I was surprised zoster virus on aqueous humor tap. uveitis at presentaton. that despite this more complex sur- The median age at the time of In terms of herpes recurrence gery, the early postoperative compli- HZO diagnosis was 71.4 years preop, 38 patients (66.7 percent) cations were low, with few subjects (range: 65.9 to 76.8), and 34 patients had recurrent disease, with 28 (49.1 experiencing cystoid macular edema (59.6 percent) were men. Nine pa- percent) having recurrent corneal or prolonged postoperative infl am- tients were immunosuppressed at disease and 25 having recurrent mation. What really stood out from the time of presentation, includ- uveitis. The patients had a median the study, was the very high rate of ing two with Crohn’s disease, one of two recurrences before surgery, recurrence of zoster keratitis and/or with rheumatoid arthritis, two with and the median time from the last uveitis over the fi rst year following chronic lymphocytic leukemia, two recurrence to surgery was 1.2 years surgery, often with a reduction in vi- on low-dose prednisone for poly- (range: 0.7 to 2.4 years). Twenty-two sion to below preoperative levels.” myalgia rheumatica and two with a patients (38.6 percent) had surgery Seven patients (12.3 percent) saw solid organ transplant. No patients less than a year after their most re- a decline in their 12-month CDVA

July 2019 | reviewofophthalmology.com | 3

003_rp0719_news.indd 3 6/28/19 3:49 PM REVIEW News E DITORIAL STAFF

Editor in Chief compared to their preop level. A (p=0.727).” Walter C. Bethke poor visual outcome was more com- Dr. Niederer says surgeons can (610) 492-1024 mon in patients with a central scar, take steps to possibly decrease the [email protected] and complications during the sur- risk of a postop fl are-up. “Normally gery didn’t correlate with decreased in subjects with uveitis, we advo- Senior Editor acuity afterward. cate three months of disease quies- Christopher Kent At this point, the researchers can’t cence prior to considering cataract (212) 274-7031 say for sure what it is about phaco surgery,” she says. “However, in [email protected] that triggers a higher rate of HZO the current study, the highest rates recurrence. “An increase in recur- of recurrence of herpes zoster eye Senior Editor Sean McKinney rence of herpes zoster and herpes disease were seen in those with less (610) 492-1025 simplex has been noticed by a few than one year of quiescence. We [email protected] researchers following other surgery,” therefore recommend a longer pe- Dr. Niederer says. “The mechanisms riod of quiescence (ideally one year) Associate Editor are unclear, but could include local where possible in those with herpes Christine Leonard trauma, release of sequestered virus, zoster. The role of antivirals in de- (610) 492-1008 or the stress of the surgery. Herpes creasing disease recurrence in zos- [email protected] simplex virus has previously been ter is currently unknown and we are isolated from the lens in a patient eagerly awaiting the results of the Chief Medical Editor with previous acute retinal necrosis, Zoster Eye Disease Study (ZEDS) Mark H. Blecher, MD so it seems plausible that seques- to provide more guidance on this. Art Director tered virus may exist in patients with In our personal practice, we use Jared Araujo herpes zoster. We have a further three months of antiviral prophy- (610) 492-1032 study under way to examine this link laxis, starting on the day of surgery, [email protected] in more detail. There was no differ- for those with simple previous her- ence in the rate of recurrence fol- pes zoster eye involvement, and one Senior Graphic Designer lowing complicated cataract surgery year of antiviral prophylaxis for those Matt Egger (610) 492-1029 Corrections [email protected]

Graphic Designer In the May 2019 article, “EHR Sys- Ashley Schmouder tems: Room For Improvement?” the (610) 492-101048 physician in this image on the left was incorrectly identifi ed as Jennifer Lim. [email protected] It is actually Davis Eye Center’s Lily Koo Lin, MD. Review regrets the error. International coordinator, Japan Mitz Kaminuma In the June installment of Glaucoma [email protected] Management, “Easing Your Patients’ Financial Burden,” the pricing data in Business Offi ces the table on p. 62 wasn’t accurate. 11 Campus Boulevard, Suite 100 Specifi cally, the per-day price shown Newtown Square, PA 19073 for latanoprostene bunod was for a (610) 492-1000 larger 5 ml bottle, not 2.5 ml, leading Fax: (610) 492-1039 to a higher per-day price. The cor- Subscription inquiries: rected table using a 30-day supply for the drugs appears below. United States — (877) 529-1746 Outside U.S. — (845) 267-3065 E-mail: Per-day Glaucoma Drug Price Comparison* [email protected] BB AA CAI PGA BB+CAI BB+AA LBN Netarsudil Website: www.reviewofophthalmology.com $0.38 $0.97 $1.04 $1.62 $1.83 $5.29 $6.41 $8.52 * Numbers from GoodRx.com, Accessed 27 June 2019. BB=beta blocker; AA=alpha agonist; CAI=carbonic anhydrase inhibitor; PGA=prostaglandin analogue; LBN=latanoprostene bunod.

4 | Review of Ophthalmology | July 2019

003_rp0719_news.indd 4 6/28/19 4:01 PM FDA APPROVED. UNIQUE BILLING CODE C9048 EFFECTIVE JULY 1. BIG TIME INNOVATION1 THE FIRST AND ONLY OPHTHALMIC STEROID INSERT DEXTENZA is an advancement in steroid treatment

• Resorbable, so no need for removal2 • Designed to deliver a tapered dose1 • Insert can be removed via saline irrigation • Contains fluorescein for visualization2 or manual expression, if necessary2 • No additional components or • Physicians rated DEXTENZA as easy assembly required2 to insert3*

LEARN MORE AT DEXTENZA.COM

INDICATION Use of ocular steroids may prolong the course and may exacerbate the severity of many viral infections of DEXTENZA is a corticosteroid indicated for the the eye (including herpes simplex). treatment of ocular pain following ophthalmic surgery. Fungus invasion must be considered in any persistent IMPORTANT SAFETY INFORMATION corneal ulceration where a steroid has been used or is in CONTRAINDICATIONS use. Fungal culture should be taken when appropriate. Use of steroids after cataract surgery may delay DEXTENZA is contraindicated in patients with healing and increase the incidence of bleb formation. active corneal, conjunctival or canalicular infections, including epithelial herpes simplex keratitis (dendritic ADVERSE REACTIONS keratitis), vaccinia, varicella; mycobacterial infections; The most common ocular adverse reactions that fungal diseases of the eye, and dacryocystitis. occurred in patients treated with DEXTENZA were: WARNINGS AND PRECAUTIONS anterior chamber inflammation including iritis and iridocyclitis (9%); intraocular pressure increased (5%); Prolonged use of corticosteroids may result in glaucoma visual acuity reduced (2%); eye pain (1%); cystoid with damage to the optic nerve, defects in visual acuity macular edema (1%); corneal edema (1%); and and fields of vision. Steroids should be used with caution conjunctival hyperemia (1%). in the presence of glaucoma. Intraocular pressure should be monitored during treatment. The most common non-ocular adverse reaction that occurred in patients treated with DEXTENZA was Corticosteroids may suppress the host response headache (1%). and thus increase the hazard for secondary ocular infections. In acute purulent conditions, steroids may Please see brief summary of full Prescribing mask infection and enhance existing infection. Information on adjacent page.

*73.6% of physicians in Study 1 and 76.4% in Study 2 rated DEXTENZA as easy to insert.

References: 1. Sawhney AS et al, inventors; Incept LLC, assignee. US patent 8,409,606 B2. April 2, 2013. 2. DEXTENZA [package insert]. Bedford, MA: Ocular Therapeutix, Inc; 2018. 3. Walters T et al. J Clin Exp Ophthalmol. 2016;7(4):1-11.

© 2019 Ocular Therapeutix, Inc. All rights reserved. DEXTENZA is a registered trademark of Ocular Therapeutix, Inc. PP-US-DX-0071 02/2019

RP0719_ Ocular.indd 1 6/17/19 10:12 AM DEXTENZA was studied in three randomized, REVIEW vehicle-controlled studies (n = 351). The News mean age of the population was 68 years (range 43 to 87 years), 62% were female, and 85% were white. Forty-six percent had brown iris color and 31% had blue iris with recurrent episodes of infl ammation.” color. The most common ocular adverse BRIEF SUMMARY: Please see the reactions that occurred in patients treated Researchers in New Delhi, India, say that the timing DEXTENZA Package Insert for full with DEXTENZA were: anterior chamber prescribing information for DEXTENZA inflammation including iritis and iridocyclitis of cataract surgery appears to be a key factor for patients (11/2018) (9%); intraocular pressure increased (5%); 1 INDICATIONS AND USAGE visual acuity reduced (2%); eye pain (1%); with chorioretinal coloboma. cystoid macular edema (1%); corneal edema DEXTENZA® (dexamethasone ophthalmic (1%); and conjunctival hyperemia (1%). In the largest case series of cataract surgery in patients insert) is a corticosteroid indicated for the treatment of ocular pain following ophthalmic The most common non-ocular adverse with chorioretinal coloboma, the researchers reviewed surgery (1). reaction that occurred in patients treated with DEXTENZA was headache (1%). the medical records of patients with chorioretinal colo- 4 CONTRAINDICATIONS 8 USE IN SPECIFIC POPULATIONS boma who had cataract surgery between January 2016 DEXTENZA is contraindicated in patients with 2 active corneal, conjunctival or canalicular 8.1 Pregnancy and May 2018. The study comprised 39 eyes of 38 pa- infections, including epithelial herpes simplex Risk Summary keratitis (dendritic keratitis), vaccinia, tients. There were 14 women and 24 men, with a mean varicella; mycobacterial infections; fungal There are no adequate or well-controlled diseases of the eye, and dacryocystitis. studies with DEXTENZA in pregnant women age of 36.74 ±15.24. to inform a drug-associated risk for major 5 WARNINGS AND PRECAUTIONS birth defects and miscarriage. In animal 5.1 Intraocular Pressure Increase reproduction studies, administration of topical ocular dexamethasone to pregnant Prolonged use of corticosteroids may result mice and rabbits during organogenesis in glaucoma with damage to the optic nerve, produced embryofetal lethality, cleft palate defects in visual acuity and fields of vision. and multiple visceral malformations Steroids should be used with caution in the [see Animal Data]. “There was a marked difference presence of glaucoma. Intraocular pressure should be monitored during the course of Data in the baseline visual acuity of the treatment. Animal Data 5.2 Bacterial Infection Topical ocular administration of 0.15% our cases compared to other Corticosteroids may suppress the host dexamethasone (0.75 mg/kg/day) on response and thus increase the hazard gestational days 10 to 13 produced for secondary ocular infections. In acute embryofetal lethality and a high incidence studies reporting cataract surgery purulent conditions, steroids may mask of cleft palate in a mouse study. A daily infection and enhance existing infection dose of 0.75 mg/kg/day in the mouse is [see Contraindications (4)]. approximately 5 times the entire dose of outcome in chorioretinal coloboma. dexamethasone in the DEXTENZA product, 5.3 Viral Infections on a mg/m2 basis. In a rabbit study, topical ocular administration of 0.1% This could have resulted in the Use of ocular steroids may prolong the dexamethasone throughout organogenesis course and may exacerbate the severity of (0.36 mg /day, on gestational day 6 followed many viral infections of the eye (including by 0.24 mg/day on gestational days 7-18) suboptimal outcome.” herpes simplex) [see Contraindications (4)]. produced intestinal anomalies, intestinal 5.4 Fungal Infections aplasia, gastroschisis and hypoplastic kidneys. A daily dose of 0.24 mg/day is — Praful Maharana, MD Fungus invasion must be considered in any approximately 6 times the entire dose of persistent corneal ulceration where a steroid dexamethasone in the DEXTENZA product, has been used or is in use. Fungal culture on a mg/m2 basis. should be taken when appropriate [see Contraindications (4)]. 8.2 Lactation 5.5 Delayed Healing Systemically administered corticosteroids appear in human milk and could suppress The use of steroids after cataract surgery growth and interfere with endogenous may delay healing and increase the corticosteroid production; however the Preop, the mean best-corrected vision of the group incidence of bleb formation. systemic concentration of dexamethasone 6 ADVERSE REACTIONS following administration of DEXTENZA is low was 1.83 logMAR (slightly worse than 20/800). Colobo- [see Clinical Pharmacology (12.3)]. There The following serious adverse reactions are is no information regarding the presence of ma involving the macula was present in 46.5 percent of described elsewhere in the labeling: DEXTENZA in human milk, the effects of the drug on the breastfed infant or the effects the cases. The cataracts were grade 2 in fi ve cases (12.8 • Intraocular Pressure Increase [see of the drug on milk production to inform risk Warnings and Precautions (5.1)] of DEXTENZA to an infant during lactation. percent), grade 3 in seven (17.9 percent) and grade 4 in • Bacterial Infection [see Warnings and The developmental and health benefits of Precautions (5.2)] breastfeeding should be considered along 17 cases (43.6 percent). with the mother’s clinical need for DEXTENZA • Viral Infection [see Warnings and and any potential adverse effects on the Other morphologies in the study included six cortical Precautions (5.3)] breastfed child from DEXTENZA. cataracts, two total cataracts, one posterior subcapsular • Fungal Infection [see Warnings and 8.4 Pediatric Use Precautions (5.4)] cataract and one congenital nuclear cataract. Safety and effectiveness in pediatric patients • Delayed Healing [see Warnings and have not been established. For the procedure itself, surgeons performed phaco Precautions (5.5)] 8.5 Geriatric Use 6.1 Clinical Trials Experience in 22 eyes (56 percent), lens aspiration in fi ve cases (12.8 No overall differences in safety or Because clinical trials are conducted effectiveness have been observed between percent), extracap in fi ve cases, intracap in four eyes under widely varying conditions, adverse elderly and younger patients. reaction rates observed in the clinical trials (10.3 percent), small-incision cataract surgery in two of a drug cannot be directly compared to 17 PATIENT COUNSELING INFORMATION cases (6.7 percent) and pars plana lensectomy in one rates in the clinical trials of another drug Advise patients to consult their surgeon if and may not reflect the rates observed pain, redness, or itching develops. case (2.6 percent). in practice. Adverse reactions associated with ophthalmic steroids include elevated Immediately postop, eyes with increased intraocular intraocular pressure, which may be associated with optic nerve damage, pressure were managed with glaucoma drops. Eleven visual acuity and field defects, posterior subcapsular cataract formation; delayed cases had corneal edema, which resolved with conser- wound healing; secondary ocular infection MANUFACTURED FOR: vative therapy in nine cases; the remaining two needed from pathogens including herpes simplex, Ocular Therapeutix, Inc. and perforation of the globe where there is thinning of the cornea or sclera [see Bedford, MA 01730 USA endothelial keratoplasty. At one year, data was available Warnings and Precautions (5)]. PP-US-DX-0072 for 13 cases (14 eyes). The mean vision at that time was 1.51 ±0.58 logMAR (slightly better than 20/800).

0003_rp0719_news.indd03_rp0719_news.indd 6 66/28/19/28/19 3:503:50 PMPM Looking at the study’s results in re- says. “In our area, the greatest dif- fest refraction, slit-lamp exams and lation to similar studies, the authors fi culty in decision making is the un- Scheimpfl ug tomography—the latter say that the patient age at the time predictable follow-up pattern of the of which was evaluated by two masked of surgery likely dictates the type patient after the surgery. Hence, cornea and refractive surgeons. of surgery that’s performed. In one most surgeons avoid cataract surgery The researchers found the to- study composed of relatively young while the patient has some reason- mography data showed 17.5 percent patients (mean age: 27.7), phaco was able vision. However, the result of participants had keratoconus, while performed in all cases. In this study our study suggests that the surgery 19.1 percent were labeled as having and another in which patients were should be done early. keratoconus by objective analysis. older (mean age: 37.6), some cases “The standard practice of being The team found that 11.5 percent required ECCE, ICCE or lensec- prepared with capsular supporting to 15.5 percent of patients with tomy through the pars plana, which devices such as CTR/Cionni, using keratoconus were younger than 11, might invite complications that capsulorhexis forceps for CCC, low with steepest anterior curvature and wouldn’t be as likely to occur with and slow phacoemulsifi cation, use of thinnest pachymetry values of 44.8 phaco. The researchers also point viscodispersive viscoelastics, and per- ±6.5D and 515.9 ±39.2 µm. The 18 out that the outcomes of surgery in forming pupilloplasty at the end of percent between the ages of 12 and younger patients were better; spe- surgery should be kept in mind. Care- 15 with keratoconus had values of cifi cally the proportion of uneventful ful follow-up is essential as the com- 47.34 ±3.4D and 496.1 ±37.9 µm, surgeries, IOL implantation rate and plication rate is high and the majority while the 25.5 percent of keratoco- the rate of posterior capsule rupture of patients requires laser delimitation nus patients between 16 and 18 had were all better in the series with in the postoperative period.” 49.7 ±6.1 D and 486.0 ±66.5 µm.

younger patients. 1. Lu L, McGhee C, Sims J, Niederer R. High rate of recurrence of They add that 37.5 percent of kera- Praful Maharana, MD, one of herpes zoster-related ocular disease after phacoemulsifi cation toconus patients were unilateral as cataract surgery. J Cataract Refract Surg 2019;45:810-815. the study’s authors, says some other 2. Sahay P, Maharana P, Mandal S, et al. Cataract surgery evaluated by tomography alone. outcomes in eyes with chorioretinal coloboma. J Cataract factors may have impacted the sub- 1. Awwad ST, Yehia M, Mehanna CJ, et al. Tomographic and Refract Surg 2019;45:630-638. optimal outcomes. “The macular refractive characteristics of pdiatric fi rst-degree relatives of keratoconus patients. Am J Ophthalmol. June 10, 2019. [Epub involvement rate was signifi cantly ahead of print]. more in our series (45.2 percent),” he notes. “In fact, there was a marked Keratoconus’ difference in the baseline visual acu- ity of our cases compared to other AbbVie to studies reporting cataract surgery Genetic outcome in chorioretinal coloboma. Acquire This could have resulted in the sub- Connection optimal outcome. The second major cause could be the associated am- New data adds some weight to the Allergan blyopia. “Most of the cases of CRC theory that keratoconus is driven, have had some refractive error since in part, by genetics. Researchers AbbVie and Allergan announced the early part of their lives,” Dr. Ma- recently evaluated the tomographic that the companies have entered into harana continues. “Due to poor ac- and refractive characteristics of sib- a defi nitive transaction agreement cess to health care or lack of knowl- lings of pediatric patients with kera- under which AbbVie will acquire Al- edge on the part of the primary care toconus or the children of adults lergan in a cash and stock transaction physician, refractive error, especially with keratoconus and found that the for a transaction equity value of ap- irregular astigmatism, often goes un- prevalence of keratoconus was high, proximately $63 billion, based on the corrected. This could lead to ambly- warranting screening in this high- closing price of AbbVie’s common opia and subsequent poor outcomes risk group.1 stock of $78.45 on June 24, 2019. In following cataract surgery.” This cross-sectional study evalu- the offi cial announcement of the ac- Dr. Maharana says the main thing ated 183 pediatric fi rst-degree rela- quisition, AbbVie describes the deal he learned from the study was re- tives of patients with keratoconus as, a “transformational transaction garding surgical timing. “One should and included both eyes of all partici- for both companies” that “achieves not delay cataract surgery in patients pants between the ages of six and 18. unique and complementary strategic with chorioretinal coloboma,” he The participants underwent mani- objectives.”

July 2019 | reviewofophthalmology.com | 7

0003_rp0719_news.indd03_rp0719_news.indd 7 66/28/19/28/19 3:503:50 PMPM Editorial

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8 | Review of Ophthalmology | July 2019

0003_rp0719_news.indd03_rp0719_news.indd 8 66/28/19/28/19 3:503:50 PMPM

BRIEF SUMMARY OF PRESCRIBING INFORMATION produced malformations when administered orally to pregnant rabbits at doses 4.2 times the recommended human ophthalmic dose (RHOD) and to This Brief Summary does not include all the information needed to use pregnant rats at doses 106 times the RHOD. In pregnant rats receiving oral LOTEMAX® SM safely and effectively. See full prescribing information ® doses of loteprednol etabonate during the period equivalent to the last for LOTEMAX SM. trimester of pregnancy through lactation in humans, survival of offspring was ® reduced at doses 10.6 times the RHOD. Maternal toxicity was observed in LOTEMAX SM (loteprednol etabonate ophthalmic gel) 0.38% rats at doses 1066 times the RHOD, and a maternal no observed adverse For topical ophthalmic use effect level (NOAEL) was established at 106 times the RHOD. The Initial U.S. Approval: 1998 background risk of major birth defects and miscarriage for the indicated population is unknown. However, the background risk in the U.S. general INDICATIONS AND USAGE ® population of major birth defects is 2 to 4%, and of miscarriage is 15 to 20%, LOTEMAX SM is a corticosteroid indicated for the treatment of post- of clinically recognized pregnancies. Data: Animal Data. Embryofetal studies operative inflammation and pain following ocular surgery. were conducted in pregnant rabbits administered loteprednol etabonate by DOSAGE AND ADMINISTRATION oral gavage on gestation days 6 to 18, to target the period of organogenesis. Invert closed bottle and shake once to fill tip before instilling drops. Apply one Loteprednol etabonate produced fetal malformations at 0.1 mg/kg (4.2 times drop of LOTEMAX® SM into the conjunctival sac of the affected eye three the recommended human ophthalmic dose (RHOD) based on body surface times daily beginning the day after surgery and continuing throughout the first area, assuming 100% absorption). Spina bifida (including meningocele) was 2 weeks of the post-operative period. observed at 0.1 mg/kg, and exencephaly and craniofacial malformations were observed at 0.4 mg/kg (17 times the RHOD). At 3 mg/kg (128 times the CONTRAINDICATIONS ® RHOD), loteprednol etabonate was associated with increased incidences of LOTEMAX SM, as with other ophthalmic corticosteroids, is contraindicated abnormal left common carotid artery, limb flexures, umbilical hernia, scoliosis, in most viral diseases of the cornea and conjunctiva including epithelial and delayed ossification. Abortion and embryofetal lethality (resorption) herpes simplex keratitis (dendritic keratitis), vaccinia, and varicella, in occurred at 6 mg/kg (256 times the RHOD). A NOAEL for developmental mycobacterial infection of the eye and fungal diseases of ocular structures. toxicity was not established in this study. The NOAEL for maternal toxicity in WARNINGS AND PRECAUTIONS rabbits was 3 mg/kg/day. Embryofetal studies were conducted in pregnant Intraocular Pressure (IOP) Increase: Prolonged use of corticosteroids may rats administered loteprednol etabonate by oral gavage on gestation days 6 result in glaucoma with damage to the optic nerve, defects in visual acuity to 15, to target the period of organogenesis. Loteprednol etabonate produced and fields of vision. Steroids should be used with caution in the presence of fetal malformations, including absent innominate artery at 5 mg/kg (106 times glaucoma. If this product is used for 10 days or longer, intraocular pressure the RHOD); and cleft palate, agnathia, cardiovascular defects, umbilical should be monitored. hernia, decreased fetal body weight and decreased skeletal ossification at 50 Cataracts: Use of corticosteroids may result in posterior subcapsular mg/kg (1066 times the RHOD). Embryofetal lethality (resorption) was cataract formation. observed at 100 mg/kg (2133 times the RHOD). The NOAEL for Delayed Healing: The use of steroids after cataract surgery may delay developmental toxicity in rats was 0.5 mg/kg (10.6 times the RHOD). healing and increase the incidence of bleb formation. In those diseases Loteprednol etabonate was maternally toxic (reduced body weight gain) at 50 causing thinning of the cornea or sclera, perforations have been known to mg/kg/day. The NOAEL for maternal toxicity was 5 mg/kg. A peri-/postnatal occur with the use of topical steroids. The initial prescription and renewal of study was conducted in rats administered loteprednol etabonate by oral the medication order should be made by a physician only after examination gavage from gestation day 15 (start of fetal period) to postnatal day 21 (the of the patient with the aid of magnification such as slit lamp biomicroscopy end of lactation period). At 0.5 mg/kg (10.6 times the clinical dose), reduced and, where appropriate, fluorescein staining. survival was observed in live-ERUQRIIVSULQJ'RVHV•PJNJ WLPHVWKH Bacterial Infections: Prolonged use of corticosteroids may suppress the RHOD) FDXVHGXPELOLFDOKHUQLDLQFRPSOHWHJDVWURLQWHVWLQDOWUDFW'RVHV• host response and thus increase the hazard of secondary ocular infections. mg/kg (1066 times the RHOD) produced maternal toxicity (reduced body In acute purulent conditions of the eye, steroids may mask infection or weight gain, death), decreased number of live-born offspring, decreased birth enhance existing infection. weight, and delays in postnatal development. A developmental NOAEL was Viral infections: Employment of a corticosteroid medication in the treatment not established in this study. The NOAEL for maternal toxicity was 5 mg/kg. of patients with a history of herpes simplex requires great caution. Use of Lactation: There are no data on the presence of loteprednol etabonate in ocular steroids may prolong the course and may exacerbate the severity of human milk, the effects on the breastfed infant, or the effects on milk many viral infections of the eye (including herpes simplex). production. The developmental and health benefits of breastfeeding should Fungal Infections: Fungal infections of the cornea are particularly prone to EHFRQVLGHUHGDORQJZLWKWKHPRWKHU¶VFOLQLFDOQHHGIRU/27(0$;® SM and ® develop coincidentally with long-term local steroid application. Fungus any potential adverse effects on the breastfed infant from LOTEMAX SM. invasion must be considered in any persistent corneal ulceration where a Pediatric Use: Safety and effectiveness of LOTEMAX® SM in pediatric steroid has been used or is in use. Fungal cultures should be taken when patients have not been established. appropriate. Geriatric Use: No overall differences in safety and effectiveness have been Contact Lens Wear: Contact lenses should not be worn when the eyes are observed between elderly and younger patients. inflamed. NONCLINICAL TOXICOLOGY ADVERSE REACTIONS Carcinogenesis, Mutagenesis, Impairment of Fertility: Long-term animal Because clinical trials are conducted under widely varying conditions, studies have not been conducted to evaluate the carcinogenic potential of adverse reaction rates observed in the clinical trials of a drug cannot be loteprednol etabonate. Loteprednol etabonate was not genotoxic in vitro in directly compared to rates in the clinical trials of another drug and may not the Ames test, the mouse lymphoma tk assay, or in the chromosomal reflect the rates observed in practice. Adverse reactions associated with aberration test in human lymphocytes, or in vivo in the mouse micronucleus ophthalmic steroids include elevated intraocular pressure, which may be assay. Treatment of male and female rats with 25 mg/kg/day of loteprednol associated with infrequent optic nerve damage, visual acuity and field etabonate (533 times the RHOD based on body surface area, assuming defects, posterior subcapsular cataract formation, delayed wound healing 100% absorption) prior to and during mating caused preimplantation loss and and secondary ocular infection from pathogens including herpes simplex, and decreased the number of live fetuses/live births. The NOAEL for fertility in perforation of the globe where there is thinning of the cornea or sclera. There rats was 5 mg/kg/day (106 times the RHOD). were no treatment-emergent adverse drug reactions that occurred in more than 1% of subjects in the three times daily group compared to vehicle. LOTEMAX is a trademark of Bausch & Lomb Incorporated or its affiliates. © 2019 Bausch & Lomb Incorporated USE IN SPECIAL POPULATIONS Bausch + Lomb, a division of Valeant Pharmaceuticals North America LLC Pregnancy: Risk Summary: There are no adequate and well controlled Bridgewater, NJ 08807 USA studies with loteprednol etabonate in pregnant women. Loteprednol etabonate produced teratogenicity at clinically relevant doses in the rabbit LSM.0091.USA.19 and rat when administered orally during pregnancy. Loteprednol etabonate Based on 9669600-9669700 Revised: 02/2019

RRP0719_BLP0719_BL LotemaxLotemax PI.inddPI.indd 1 66/17/19/17/19 10:3810:38 AMAM SUBMICRON STRONG Engineered with SM Technology™ for effi cient penetration at a low BAK level (0.003%)1,2 GREATER PENETRATION ~2× to the aqueous humor2* * Compared to LOTEMAX® GEL (loteprednol etabonate ophthalmic gel) 0.5%. Clinical signifi cance of these preclinical data has not been established.

SMALL & MIGHTY SUBMICRON PARTICLES

PROVEN STRENGTH Important Safety Information (cont.) • The use of steroids after cataract surgery may delay healing and increase • 30% of LOTEMAX® SM patients had complete ACC resolution the incidence of bleb formation. In those with diseases causing thinning of the cornea or sclera, perforations have been known to occur with the use of vs vehicle (15%) at Day 8 (N=371, P<0.0001)1,3† topical steroids. The initial prescription and renewal of the medication order • 74% of LOTEMAX® SM patients were completely pain-free should be made by a physician only after examination of the patient with the vs vehicle (49%) at Day 8 (N=371, P<0.0001)1,3‡ aid of magnifi cation such as slit lamp biomicroscopy and, where appropriate, fl uorescein staining. † Pooled analysis of Phase 3 clinical studies. Study 1: 29% LOTEMAX® SM (N=171) vs • Prolonged use of corticosteroids may suppress the host response and 9% vehicle (N=172). Study 2: 31% LOTEMAX® SM (N=200) vs 20% vehicle (N=199); thus increase the hazard of secondary ocular infections. In acute purulent P <0.05 for all. conditions, steroids may mask infection or enhance existing infections. ‡ Pooled analysis of Phase 3 clinical studies. Study 1: 73% LOTEMAX® SM (N=171) • Employment of a corticosteroid medication in the treatment of patients with vs 48% vehicle (N=172). Study 2: 76% LOTEMAX® SM (N=200) vs 50% vehicle a history of herpes simplex requires great caution. Use of ocular steroids may (N=199); P<0.05 for all. prolong the course and may exacerbate the severity of many viral infections of the eye (including herpes simplex). Indication • Fungal infections of the cornea are particularly prone to develop coincidentally with long-term local steroid application. Fungus invasion must be considered LOTEMAX® SM (loteprednol etabonate ophthalmic gel) 0.38% is a corticosteroid in any persistent corneal ulceration where a steroid has been used or is in use. indicated for the treatment of post-operative infl ammation and pain following Fungal cultures should be taken when appropriate. ocular surgery. • Contact lenses should not be worn when the eyes are infl amed. Important Safety Information • There were no treatment-emergent adverse drug reactions that occurred in • LOTEMAX® SM, as with other ophthalmic corticosteroids, is contraindicated in more than 1% of subjects in the three times daily group compared to vehicle. most viral diseases of the cornea and conjunctiva including epithelial herpes You are encouraged to report negative side eff ects of prescription drugs simplex keratitis (dendritic keratitis), vaccinia, and varicella, and also in to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088. mycobacterial infection of the eye and fungal diseases of ocular structures. • Prolonged use of corticosteroids may result in glaucoma with damage to the Please see brief summary of Prescribing Information on adjacent page. optic nerve, defects in visual acuity and fi elds of vision. Steroids should be References: 1. LOTEMAX SM Prescribing Information. Bausch & Lomb, Incorporated. 2. Cavet ME, Glogowski S, DiSalvo C, Richardson ME. Ocular pharmacokinetics of submicron loteprednol etabonate ophthalmic gel, used with caution in the presence of glaucoma. If LOTEMAX® SM is used for 10 0.38% following topical administration in rabbits. Poster presented at 2015 ARVO Annual Meeting; May 4, days or longer, IOP should be monitored. 2015; Denver, Colorado. 3. Data on fi le. Bausch & Lomb, Incorporated. • Use of corticosteroids may result in posterior subcapsular cataract formation.

®/TM are trademarks of Bausch & Lomb Incorporated or its affi liates. © 2019 Bausch & Lomb Incorporated or its affi liates. All rights reserved. Printed in USA. LSM.0176.USA.19 Visit www.LOTEMAXSM.com

RP0719_BL Lotemax.indd 1 6/17/19 10:37 AM July 2019 • Volume XXVI No. 7 | reviewofophthalmology.com Cover Story 28 | Refractive Surprises: What To Do Next Christopher Kent, Senior Editor Surgeons offer advice for those times when your cataract surgery outcome isn’t on target.

Feature Articles

36 | Refractive Surgery for Patients Over 50 Sean McKinney, Senior Editor It appears there’s one central question for this group: lens- or cornea-based refractive surgery?

42 | Tips for Treating Ocular Trauma Michelle Stephenson, Contributing Editor Generally, the type of injury—globe laceration vs. blunt trauma—will dictate the outcome.

July 2019 | reviewofophthalmology.com | 11

011_rp0719_toc.indd 11 6/28/19 12:18 PM Departments

3 | Review News 50 15 | Medicare Q & A Understanding Stark and Kickback Laws What you need to know about laws governing such things as “self-referrals” and financial arrangements between practices.

18 | Glaucoma Management Working with Inflow Ablative Procedures An experienced glaucoma surgeon discusses the pros and cons of three commonly used forms of cyclophotocoagulation.

54 47 | Research Review The Ischemic Index in CRVO

50 | Retinal Insider Clinical Pearls for a New Condition Pentosan polysulfate therapy, a common treatment for interstitial cystitis, is associated with a maculopathy.

54 | Pediatric Patient Corneal Cross-linking in Pediatric Patients Early intervention is key to preventing progression and the need for corneal transplantation.

61 | Product News 63 62 | Classifieds

63 | Wills Eye Resident Case Series

65 | Advertiser Index

12 | Review of Ophthalmology | July 2019

011_rp0719_toc.indd 12 6/28/19 12:18 PM The first and only FDA-approved, single-dose, NEW sustained-release, intracameral steroid for the treatment of postoperative inflammation1-3

For Post-Cataract Surgery Inflammation Target Within1-3

With a single injection at the end of cataract NOW AVAILABLE surgery, anti-inflammatory efficacy begins as early as day 1 and continues through day 301* • The percentage of patients who received DEXYCU (517 mcg) who had anterior chamber cell clearing on day 8 was 60% (n=94/156) vs 20% (n=16/80) in the placebo group1 • The cumulative percentage of subjects receiving rescue medication of ocular steroid or nonsteroidal anti-inflammatory drug (NSAID) at day 30 was significantly lower in the DEXYCU (517 mcg) treatment group (20%; n=31/156) compared to placebo (54%; n=43/80)1

*DEXYCU was studied in a randomized, double-masked, placebo-controlled trial. Patients received either DEXYCU or a vehicle administered by a physician at the end of the surgical procedure. The primary endpoint was the proportion of patients with anterior chamber cell clearing (cell score=0) on postoperative day 8.

INDICATION AND USAGE DEXYCU™ (dexamethasone intraocular suspension) 9% is indicated . Use of a corticosteroid in the treatment of patients with a history of for the treatment of postoperative inflammation. herpes simplex requires caution and may prolong the course and may exacerbate the severity of many viral infections IMPORTANT SAFETY INFORMATION . Fungal infections of the cornea are particularly prone to coincidentally CONTRAINDICATIONS develop with long-term local steroid application and must be None. considered in any persistent corneal ulceration where a steroid has WARNINGS AND PRECAUTIONS been used or is in use. Fungal culture should be taken when appropriate Increase in Intraocular Pressure . Prolonged use of corticosteroids may suppress the host response . Prolonged use of corticosteroids, including DEXYCU, may result in and thus increase the hazard of secondary ocular infections. In glaucoma with damage to the optic nerve, defects in visual acuity acute purulent conditions, steroids may mask infection or enhance and fields of vision . existing infection Steroids should be used with caution in the presence of glaucoma Cataract Progression Delayed Healing . The use of corticosteroids in phakic individuals may promote the . The use of steroids after cataract surgery may delay healing and development of posterior subcapsular cataracts increase the incidence of bleb formation ADVERSE REACTIONS . In those diseases causing thinning of the cornea or sclera, perforations . The most commonly reported adverse reactions occurred in 5-15% have been known to occur with the use of corticosteroids of subjects and included increases in intraocular pressure, corneal Exacerbation of Infection edema and iritis . The use of DEXYCU, as with other ophthalmic corticosteroids, is not recommended in the presence of most active viral diseases of the Please see brief summary of full Prescribing Information cornea and conjunctiva including epithelial herpes simplex keratitis on adjacent page. (dendritic keratitis), vaccinia, and varicella, and also in mycobacterial infection of the eye and fungal disease of ocular structures

References: 1. DEXYCU™ (dexamethasone intraocular suspension) 9% full U.S. Prescribing Information. EyePoint Pharmaceuticals, Inc. December 2018. 2. Donnenfeld E, Holland E. Dexamethasone intracameral drug-delivery suspension for inflammation associated with cataract surgery: a randomized, placebo-controlled, phase III trial. Ophthalmology. 2018;125(6):799-806. 3. Data on file. EyePoint Pharmaceuticals, Inc.

DEXYCU and the EyePoint logo are trademarks of EyePoint Pharmaceuticals, Inc. ©2019 EyePoint Pharmaceuticals, Inc. All rights reserved. 01/2019 480 Pleasant Street, Suite B300, Watertown, MA 02472 US-DEX-1900045

RP0319_Eyepoint.indd 1 2/13/19 9:59 AM DEXYCU (dexamethasone intraocular suspension) 9%, 6.1 Clinical Trials Experience for intraocular administration Because clinical studies are conducted under widely varying conditions, Initial U.S. Approval: 1958 adverse reaction rates observed in the clinical studies of a drug cannot BRIEF SUMMARY: Please see package insert for full prescribing information. be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice. 1 INDICATIONS AND USAGE DEXYCU (dexamethasone intraocular suspension) 9% is indicated The following adverse events rates are derived from three clinical trials for the treatment of postoperative inflammation. in which 339 patients received the 517 microgram dose of DEXYCU. The most commonly reported adverse reactions occurred in 5-15% of subjects 4 CONTRAINDICATIONS and included increases in intraocular pressure, corneal edema and iritis. None. Other ocular adverse reactions occurring in 1-5% of subjects included, 5 WARNINGS AND PRECAUTIONS corneal endothelial cell loss, blepharitis, eye pain, cystoid macular edema, 5.1 Increase in Intraocular Pressure dry eye, ocular inflammation, posterior capsule opacification, blurred vision, Prolonged use of corticosteroids including DEXYCU may result in glaucoma reduced visual acuity, vitreous floaters, foreign body sensation, photophobia, with damage to the optic nerve, defects in visual acuity and fields of vision. and vitreous detachment. Steroids should be used with caution in the presence of glaucoma. 8 USE IN SPECIFIC POPULATIONS 5.2 Delayed Healing 8.1 Pregnancy The use of steroids after cataract surgery may delay healing and increase the Risk Summary incidence of bleb formation. In those diseases causing thinning of the cornea There are no adequate and well-controlled studies of DEXYCU or sclera, perforations have been known to occur with the use of corticosteroids. (dexamethasone intraocular suspension) in pregnant women. Topical ocular 5.3 Exacerbation of Infection administration of dexamethasone in mice and rabbits during the period The use of DEXYCU, as with other ophthalmic corticosteroids, of organogenesis produced cleft palate and embryofetal death in mice and is not recommended in the presence of most active viral diseases of the malformations of abdominal wall/intestines and kidneys in rabbits at doses cornea and conjunctiva including epithelial herpes simplex keratitis 7 and 5 times higher than the injected recommended human ophthalmic dose (dendritic keratitis), vaccinia, and varicella, and also in mycobacterial (RHOD) of DEXYCU (517 micrograms dexamethasone), respectively infection of the eye and fungal disease of ocular structures. [see Data in the full prescribing information]. Employment of a corticosteroid medication in the treatment of patients In the US general population the estimated background risk of major birth with a history of herpes simplex requires caution. Use of ocular steroids may defects and miscarriage in clinically recognized pregnancies is 2 to 4% prolong the course and may exacerbate the severity of many viral infections and 15 to 20%, respectively. of the eye (including herpes simplex). Fungal infections of the cornea are 8.2 Lactation particularly prone to develop coincidentally with long-term local steroid Risk Summary application. Fungus invasion must be considered in any persistent corneal Systemically administered corticosteroids are present in human milk and ulceration where a steroid has been used or is in use. Fungal culture should can suppress growth, interfere with endogenous corticosteroid production, be taken when appropriate. or cause other unwanted effects. There is no information regarding the Prolonged use of corticosteroids may suppress the host response and presence of injected DEXYCU in human milk, the effects on breastfed infants, thus increase the hazard of secondary ocular infections. In acute purulent or the effects on milk production to inform risk of DEXYCU to an infant during conditions, steroids may mask infection or enhance existing infection. lactation. The developmental and health benefits of breastfeeding should be considered, along with the mother’s clinical need for DEXYCU and any 5.4 Cataract Progression potential adverse effects on the breastfed child from DEXYCU. The use of corticosteroids in phakic individuals may promote the development of posterior subcapsular cataracts. 8.4 Pediatric Use Safety and effectiveness of DEXYCU in pediatric patients have not 6 ADVERSE REACTIONS been established. The following adverse reactions are described elsewhere in the labeling: 8.5 Geriatric Use ҹ Increase in Intraocular Pressure [see Warning and Precautions (5.1)] No overall differences in safety or effectiveness have been observed ҹ Delayed Healing [see Warnings and Precautions (5.2)] between older and younger patients. ҹ Infection Exacerbation [see Warnings and Precautions (5.3)] ҹ Cataract Progression [see Warnings and Precautions (5.4)] Manufactured for: EyePoint Pharmaceuticals US, Inc. Watertown, MA 02472

DEX0019

RRP0319_EyepointP0319_Eyepoint PI.inddPI.indd 1 22/13/19/13/19 9:579:57 AMAM 015_rp0719_mqa.indd 15 And Kickback Laws Kickback And Understanding Stark A that important? is Why violations. Law” “Stark entity fromsubmittingclaims this law“…prohibitsthe… ments. Theyalsonotethat compensation arrange- vestment interestsand both ownership/in- relationships include plies. Financial an exceptionap- tionship, unless a financialrela- family memberhas cian oranimmediate with whichthephysi- Medicaid fromentities able byMedicareor health services’pay- receive ‘designated referring patientsto its physiciansfrom Stark Law“prohib- OIG notesthatthe Q This articlehasnocommercial sponsorship. should knowabout. the topfivethingsallphysicians Services notesthatStarkisoneof “self-referrals” andfi nancial arrangementsbetweenpractices. What youneedtoknowaboutlawsgoverningsuchthingsas REVIEW Paul M. Larson, MBA, MMSc, COMT, COE, CPC, CPMA Medicare Q&A General forHealthandHuman The OfficeoftheInspector about avoiding possible possible avoiding about talk people of alot I hear 1

the PhysicianSelf-ReferralLaw, Another namefortheStarkLawis Security Act[42U.S.C.§1395nn]. found insection1877oftheSocial is about“youreferringtoyou.”It’s so it’s usefultorememberthatthis to Medicareforthoseservices….”

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15 6/28/19 11:53 AM Medicare

REVIEW Q&A

tests don’t have a Technical Compo- well as the recipients of kickbacks …”1 was medically necessary.”1 nent/Modifi er 26 split and the entire AKS is not a “strict liability” stan- Importantly, there are some spe- allowed amount is subject to Stark dard like Stark. To be found guilty of cifi c, published ways that ensure that DHS if it appears on the list. The list AKS, you have to be proven to have you don’t violate AKS; the law refers of DHS services for 2019 includes intent (i.e., you are knowingly and to these as “safe harbors.” OIG notes1 the following things that are done willingly in violation). that “Safe harbors protect certain fairly commonly in eye care (the full payment and business practices that list is much longer): could otherwise implicate the AKS • ultrasound tests: The A- and from criminal and civil prosecution. B-scan tests done in the offi ce (CPT To be protected by a safe harbor, an codes 76510-76519); “The Government arrangement must fi t squarely in the • OCT tests (CPT 92132, 92133, safe harbor and satisfy all of its re- and 92134); does not need to quirements. Some safe harbors ad- • tear testing (CPT codes 0330T, prove patient harm dress personal services and rental 83516, 83861); and agreements, investments in ambula- • remote imaging (CPT 92227 and or fi nancial loss to tory surgical centers, and payments 92228). to bona fi de employees.”1 While some The list of codes subject to DHS the programs to show practices don’t fit squarely under a regulations may change from year that a physician safe harbor, they may not rise to the to year. It’s usually published for the level of enforcement, or are consid- upcoming year in late November of violated the AKS. A ered low-risk. the preceding year. physician can be guilty of violating the AKS How do I fi nd out if I have What is the Anti-kickback Q a potential issue under QStatute? Does it have the even if the physician either Stark Law or the Anti- same concerns for me as does kickback Statute? the Stark Law? actually rendered the service and the If you are concerned in any way While being in violation of either A about specifi c referral, legal or Ais certainly bad, the Anti-kickback service was medically fi nancial arrangements that might vio- Statute is much broader in scope than 1 late either of these important regula- Stark. AKS is not about “you benefi t- necessary.” tions, get advice from an attorney who ting from referring to yourself” (that’s is well-versed in this area. It could be Stark Law)—it’s about “relationships money well-spent. between entities” in which a fi nancial benefit that might accrue to either Mr. Larson is a senior consultant party might not be above board. OIG Are there penalties under at the Corcoran Consulting Group. notes “The AKS is a criminal law that Q the AKS? Contact him at plarson@corcoranc- prohibits the knowing and willful pay- cg.com. ment of ‘remuneration’ to induce or Yes, and they can be severe. CMS 1. OIG. Compliance. Physician Education. A Roadmap for New reward patient referrals or the genera- Anotes that violators can “face pen- Physicians. Fraud & Abuse Laws. https://oig.hhs.gov/compli- tion of business involving any item or alties of up to $50,000 per kickback ance/physician-education/01laws.asp. Accessed 06/01/19. 2. OIG. Comparison of the Antikickback Statute and Stark Law. service payable by the Federal health plus three times the amount of the re- https://oig.hhs.gov/compliance/provider-compliance-training/ care programs (e.g., drugs, supplies, muneration.” You can even run afoul fi les/StarkandAKSChartHandout508.pdf. Accessed 06/01/19. 3. CMS. Fraud and Abuse. Physician Self Referral. https://www. or health care services for Medicare of AKS and “the Government does cms.gov/Medicare/Fraud-and-Abuse/PhysicianSelfReferral/ index.html?redirect=/physicianselfreferral/. Accessed 06/01/19. or Medicaid patients). Remuneration not need to prove patient harm or 4. Social Security Act. Limitation on Certain Physician Referrals. includes anything of value … in the fi nancial loss to the programs to show https://www.ssa.gov/OP_Home/ssact/title18/1877.htm. Ac- cessed 06/01/19. Federal health care programs, paying that a physician violated the AKS. A 5. Barrett & Singal. The Stark Law. https://barrettsingal.com/ for referrals is a crime. The statute physician can be guilty of violating services/the-stark-law. Accessed 06/01/19. 6. CMS. Code List for Certain Designated Health Services (DHS). covers the payers of kickbacks—those the AKS even if the physician actually https://www.cms.gov/Medicare/Fraud-and-Abuse/PhysicianSelf- who offer or pay remuneration—as rendered the service and the service Referral/List_of_Codes.html. Accessed 06/01/19.

16 | Review of Ophthalmology | July 2019

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RP0319_Focus.indd 1 2/26/19 3:17 PM Glaucoma Management

REVIEW Edited by Kuldev Singh, MD, MPH, and Peter A. Netland, MD, PhD

Working with Infl ow Ablative Procedures A surgeon discusses the pros and cons of three commonly used forms of cyclophotocoagulation.

Jeffrey Kammer, MD, Nashville, Tennessee

s you know, our primary way approach, along with pearls to help mologists have waited until patients A of preventing glaucoma pro- you make the most of whichever one had end-stage disease to perform gression is by reducing intraocular you may be using. cyclophotocoagulation. End-stage pressure. Most procedures, inclu- patients—particularly those with ding trabeculectomy, tube shunt Transscleral CPC neovascular glaucoma—tend to do implantation and most minimally in- poorly regardless of how you treat vasive glaucoma surgeries (MIGS), When performing transscleral them. reduce IOP by increasing the outfl ow cyclophotocoagulation—lasering For example, one study of patients of aqueous from the eye. The most from outside the eye—the three risks with advanced neovascular glaucoma notable exception has always been that we’re primarily concerned about compared the effectiveness of a cyclophotocoagulation of the ciliary are hypotony, phthisis and vision loss. cyclodestructive procedure and a body (CPC), which alters this tissue These complications are rare, but Baerveldt tube shunt.1 Both groups and reduces its secretion of aqueous they’ve been an issue since people had similar rates of complications; humor. (It may also increase outfl ow; started performing cyclodestructive in both groups, vision decreased by more on that later.) For many years, procedures almost 100 years ago. almost 40 percent despite treatment, this has been accomplished using That’s because, historically, ophthal- and both groups had an 8-percent either external lasers (transscleral cy- clophotocoagulation, or TSCPC), or an endoscopic probe to target the Eyes Receiving Primary Treatment for POAG Using Diode Laser tissue from inside the eye (endoscop- TSCPC, Compared to the Fellow Medically Treated Eye (n=47) ic cyclophotocoagulation, or ECP). TSCPC-treated eye Fellow medically P value More recently, the use of a non-con- treated eye tinuous-wave laser pattern has created Decrease in IOP (mmHg); mean 2.7 ±11.2 -0.60 ±6.6 0.2 a new, less-tissue-altering way to ac- ±SD (range) (+28 to -29) (+16 to -20) complish this from outside the eye Change in visual acuity (micropulse cyclophotocoagulation, (number [%]): or MPCPC). Decrease 9 (20) 10 (23) >0.25 All three are effective at lowering No change 31 (70) 30 (68) >0.25 IOP, and all three have benefi ts and Increase 4 (9) 4 (9) >0.25 risks associated with them. Here, A study conducted in Ghana using transscleral CPC as a primary treatment for POAG found I’ll share the pros and cons of each it practical and well-tolerated, with few serious complications.4

18 | Review of Ophthalmology | July 2019 This article has no commercial sponsorship.

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RP0319_Keeler Slit.indd 1 2/14/19 3:16 PM Glaucoma

REVIEW Management

Analysis of Risk Factors for Hypotony after Transscleral Diode years of follow-up reported an IOP spike incidence of 14.1 percent.6 Cyclophotocoagulation A study conducted by the ECP Factor Odds Ratio 95%CI P value Collaborative Study Group involving Rubeotic glaucoma 9.17 1.85 – 45.36 0.002 5,824 eyes with a mean follow-up of Total energy >90 J 0.737 0.181 – 2.995 0.668 5.2 years found an IOP spike rate of Age >50 years 0.537 0.145 – 1.988 0.347 14.5 percent. The data were reported Earlier operations 0.295 0.036 – 2.431 0.232 at the American Society of Cataract Repeat TCP 1.69 0.319 – 8.954 0.534 and Refractive Surgery Symposium In a study of 90 eyes that underwent TSCPC at the Singapore National Eye Center between on Cataract, IOL and Refractive 2005 and 2007, an underlying diagnosis of neovascular (rubeotic) glaucoma was found to Surgery in San Diego in May 2007. be a signifi cant risk factor for postoperative hypotony. Because in the past TSCPC was To minimize the likelihood of often reserved for advanced glaucoma cases, fi ndings such as this may partially explain an IOP spike following ECP, it’s 2 why hypotony has been thought of as a frequent side effect of TSCPC. important to understand the etiology of the problem. There are four main risk of phthisis. So a tube shunt also start with patients who have better reasons for an IOP spike in this sit- produced less-than-ideal results in prognoses, they’ll do better regardless uation: excessive inflammation; re- these patients. of which therapy regimen you choose, tained viscoelastic; excessive treat- In fact, other studies have shown and TSCPC is an option worth con- ment; and steroid response. Let’s that neovascular glaucoma—i.e., sidering. discuss each of these in detail. advanced disease—is far and away • Infl ammation. ECP causes some the largest risk factor for developing Endoscopic CPC coagulative changes to the tissue, and hypotony following CPC.2 (See table, that incites an infl ammatory response. above.) As Harry Quigley, MD, noted I think of endoscopic cyclophoto- This can be addressed prophylac- in one of his studies involving TCP, coagulation as the forgotten MIGS tically, both before and after the pro- “Although phthisis and enucleation procedure. (I know some doctors cedure. Postoperatively, I always occurred, they were uncommon and don’t consider ECP to be MIGS, perform a subconjunctival injection frequently associated with severe but I believe it fits the description of dexamethasone (Decadron), and baseline status and complex additional of a MIGS procedure quite well.) I slowly taper the topical steroids ocular problems.”3 It doesn’t get the attention that the over a month to minimize any severe The fact that this procedure is safer more recent MIGS procedures get; infl ammatory response. If the patient than its reputation suggests has been they’re new and exciting and have has signifi cant infl ammation or fi brin confirmed by a number of studies. company reps promoting them, on postoperative day one, I can aug- In studies in which TCP is used to while ECP has been around for ment that with oral steroids for fi ve treat glaucoma patients at an earlier 10 or 12 years. Nevertheless, the to seven days. That usually gets rid stage of disease, not only is it effective, clinical data show that it has effi cacy of any excessive anterior chamber but patients tend to do quite well. and a favorable side-effect profile. infl ammation. You can also transiently For example, in one study, TPC was In addition, it’s reusable and doesn’t increase the topical glaucoma drops compared to traditional glaucoma leave any hardware inside the eye, regimen and/or add some oral car- drops as primary treatment in fellow and it can be used in a large number bonic anhydrase inhibitors such as eyes.4 Researchers found that in the of patients. In particular, it can be acetazolamide or methazolamide. 19 eyes that had baseline good vision, used as an adjunctive treatment, • Retained viscoelastic. This is only one experienced a decrease in because it combines well with other probably the most common cause vision over the course of the study, and MIGS. Most MIGS increase outfl ow; of a postoperative IOP spike. When there was no significant difference ECP helps to decrease infl ow, making performing ECP, we have to infl ate in visual acuity between the fellow them symbiotic. the ciliary sulcus with viscoelastic eyes at the final visit. (See table, p. One thing we have to be concerned to give the probe room to reach the 18.) Also, TCP can be effective as an about with ECP is IOP spikes. ciliary processes. Then, at the end of adjunctive treatment in patients with Two separate studies found almost the case, we have to be very mindful glaucoma drainage implants, with a the same incidence of IOP spikes to remove all of the viscoelastic, not low rate of complications.5 associated with ECP. A 2010 study just from the anterior chamber (as we The implication is clear: If you involving 368 eyes with at least two usually do) but also from the ciliary

20 | Review of Ophthalmology | July 2019

0018_rp0719_gm18_rp0719_gm (1).indd(1).indd 2020 66/28/19/28/19 10:5410:54 AMAM SUBSTITUTEGENERICNO FOR INVELTYS INVELTYS The ƼVWXERHSRP] corticosteroid FDA approved for &-(XVIEXQIRX of post-operative inflammation and pain following ocular surgery

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Indication -2:)08=7 PSXITVIHRSPIXEFSREXISTLXLEPQMGWYWTIRWMSR  MWMRHMGEXIHJSVXLIXVIEXQIRXSJTSWXSTIVEXMZIMRƽEQQEXMSR and pain following ocular surgery. Important Safety Information INVELTYS is contraindicated in most viral diseases of the cornea and conjunctiva including epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, and varicella, and also in mycobacterial infection of the eye and fungal diseases of ocular structures. Prolonged use of corticosteroids may result in glaucoma with damage to the optic nerve, defects in visual acuity and ƼIPHWSJZMWMSR-JXLMWTVSHYGXMWYWIHJSVHE]WSVPSRKIV-34WLSYPHFIQSRMXSVIH Use of corticosteroids may result in posterior subcapsular cataract formation. Use of steroids after cataract surgery may delay healing and increase the incidence of bleb formation. In those diseases causing thinning of the cornea or sclera, perforations have been known to occur with the use of topical steroids. The initial prescription and renewal of the medication order should be made by a physician only after examination of the patient with XLIEMHSJQEKRMƼGEXMSRWYGLEWWPMXPEQTFMSQMGVSWGST]ERH[LIVIETTVSTVMEXIƽYSVIWGIMRWXEMRMRK Prolonged use of corticosteroids may suppress the host response and thus increase the hazard of secondary ocular infections. In acute purulent conditions, steroids may mask infection or enhance existing infection. Use of a corticosteroid medication in the treatment of patients with a history of herpes simplex requires great caution. Use of ocular steroids may prolong the course and may exacerbate the severity of many viral infections of the eye (including herpes simplex). Fungal infections of the cornea are particularly prone to develop coincidentally with long-term local steroid application. Fungus invasion must be considered in any persistent corneal ulceration where a steroid has been used or is in use. In clinical trials, the most common adverse drug reactions were eye TEMR  ERHTSWXIVMSVGETWYPEVSTEGMƼGEXMSR  8LIWIVIEGXMSRW may have been the consequence of the surgical procedure. Please see Brief Summary of Prescribing Information for INVELTYS on the next page. (loteprednol etabonate ophthalmic suspension) 1%

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RP0719_Kala.indd 1 6/17/19 9:49 AM INVELTYSTM (loteprednol etabonate ophthalmic suspension) 1%, ADVERSE REACTIONS for topical ophthalmic use Adverse reactions associated with ophthalmic steroids include elevated intraocular pressure, which may be associated with BRIEF SUMMARY OF FULL PRESCRIBING INFORMATION infrequent optic nerve damage, visual acuity and field defects, posterior subcapsular cataract formation, delayed wound healing INDICATIONS AND USAGE and secondary ocular infection from pathogens including herpes INVELTYS is a corticosteroid indicated for the treatment of simplex, and perforation of the globe where there is thinning of the post-operative inflammation and pain following ocular surgery. cornea or sclera.

CONTRAINDICATIONS Clinical Trial Experience—Because clinical trials are conducted INVELTYS is contraindicated in most viral diseases of the cornea and under widely varying conditions, adverse reaction rates observed conjunctiva including epithelial herpes simplex keratitis (dendritic in the clinical trials of a drug cannot be directly compared to rates keratitis), vaccinia, and varicella, and also in mycobacterial infection in the clinical trials of another drug and may not reflect the rates of the eye and fungal diseases of ocular structures. observed in practice. The most common adverse drug reactions in the clinical trials with INVELTYS were eye pain and posterior capsular WARNINGS AND PRECAUTIONS opacification, both reported in 1% of patients. These reactions may Intraocular Pressure (IOP) Increase—Prolonged use of corticosteroids have been the consequence of the surgical procedure. may result in glaucoma with damage to the optic nerve, as well as defects in visual acuity and fields of vision. Steroids should be used USE IN SPECIFIC POPULATIONS with caution in the presence of glaucoma. If this product is used for Pregnancy—Risk Summary: INVELTYS is not absorbed systemically 10 days or longer, intraocular pressure should be monitored. following topical ophthalmic administration and maternal use is not expected to result in fetal exposure to the drug. Cataracts—Use of corticosteroids may result in posterior subcapsular cataract formation. Lactation—Risk Summary: INVELTYS is not absorbed systemically by the mother following topical ophthalmic administration, and Delayed Healing—Use of steroids after cataract surgery may delay breastfeeding is not expected to result in exposure of the child healing and increase the incidence of bleb formation. In those to INVELTYS. diseases causing thinning of the cornea or sclera, perforations have been known to occur with the use of topical steroids. The Pediatric Use—Safety and effectiveness in pediatric patients have initial prescription and renewal of the medication order should be not been established. made by a physician only after examination of the patient with the aid of magnification such as slit lamp biomicroscopy and, where Geriatric Use—No overall differences in safety and effectiveness appropriate, fluorescein staining. have been observed between elderly and younger patients.

Bacterial Infections—Prolonged use of corticosteroids may suppress NONCLINICAL TOXICOLOGY the host response and thus increase the hazard of secondary ocular Carcinogenesis, Mutagenesis, Impairment of Fertility— infections. In acute purulent conditions of the eye, steroids may Long-term animal studies have not been conducted to evaluate mask infection or enhance existing infection. the carcinogenic potential of loteprednol etabonate. Loteprednol etabonate was not genotoxic in vitro in the Ames test, the mouse Viral Infections—Use of corticosteroid medication in the treatment lymphoma thymidine kinase (tk) assay, or in a chromosome of patients with a history of herpes simplex requires great aberration test in human lymphocytes, or in vivo in the single dose caution. Use of ocular steroids may prolong the course and mouse micronucleus assay. may exacerbate the severity of many viral infections of the eye (including herpes simplex). For a copy of the Full Prescribing Information, please visit www.INVELTYS.com. Fungal Infections—Fungal infections of the cornea are particularly prone to develop coincidentally with long-term local steroid Manufactured for: application. Fungus invasion must be considered in any persistent Kala Pharmaceuticals, Inc. Waltham, MA 02453 corneal ulceration where a steroid has been used or is in use. Marks designated by TM and ® are owned by Fungal cultures should be taken when appropriate. Kala Pharmaceuticals, Inc. Patented. See www.kalarx.com/patents Contact Lens Wear—The preservative in INVELTYS may be © 2018 Kala Pharmaceuticals, Inc. All rights reserved. absorbed by soft contact lenses. Contact lenses should be removed US-INV-1800055 December 2018 prior to instillation of INVELTYS and may be reinserted 15 minutes following administration.

RRP0719_KalaP0719_Kala PI.inddPI.indd 1 66/17/19/17/19 9:519:51 AMAM Glaucoma

REVIEW Management

sulcus. If I have any concern that Micropulse CPC Versus Continuous Wave Transscleral CPC in there may still be viscoelastic left in Refractory Glaucoma the sulcus, I’ll go in with a cannula and manually inject BSS into the Micropulse TSCPC TSCPC sulcus to make sure I’ve cleared the Number of patients 24 24 sulcus of all viscoelastic. Preop IOP 36.5 mmHg 35 mmHg On postoperative day one, if the Average follow-up 17.5 months 17.5 months IOP is elevated and I believe that IOP reduction 45 percent 45 percent residual viscoelastic is the problem, Success rate ( ≤21 mmHg 52 percent 30 percent at 12 months) I’ll burp the wound, being sure to Prolonged hypotony 0 5 (20 percent) place a drop of ophthalmic betadine Phthisis bulbi 0 1 (4 percent) on the area first to minimize the Mean number of treatments 1.6 (retreatment rate: 1.3 (retreatment rate: risk of infection. If I’ve done this 47 percent) 46 percent) two or three times within 24 hours A randomized study of 48 patients with refractory glaucoma, conducted in Singapore, and the pressure still hasn’t gone found that both TSCPC and MPCPC were effective at lowering IOP, but MPCPC had a more down enough, and extra glaucoma consistent and predictable effect, with minimal ocular complications.8 medications don’t seem to be helping, I’ll consider taking the patient back know, some glaucoma patients are is uncommon following CPC, al- to the OR to remove residual visco- steroid responders. If your patient though it’s not as rare as aqueous elastic. has a history of steroid response, don’t misdirection. It probably occurs in • Pigmentary debris from over- overtreat, and avoid using stronger fewer than 1 percent of patients. treatment. Retained pigmentary de- steroids like difuprednate (Durezol). Nevertheless, CPC incites a post- bris, caused by treating ciliary tissue When I’m treating a steroid re- operative inflammatory reaction, until it makes an audible pop, can lead sponder, I’ll use my regular postop- so the patient has some risk of to IOP spikes. The popping sound erative regimen—prednisolone developing CME—especially if indicates that tissue has exploded, four times a day. Sometimes I’ll use the patient is diabetic. You want to releasing pigment; the pigment de- loteprednol instead of predniso- stymie any potential postoperative bris can then block the trabecular lone, but I’ll often augment it with infl ammation as much as possible to meshwork and cause a rise in IOP. postoperative topical NSAIDs to minimize this risk. Obviously, the best way to deal with minimize the postoperative inflam- I minimize the risk by treating this is by preventing the explosions matory response. I taper the patient prophylactically with subconjunctival in the fi rst place, which can be done off the topical steroids as soon as dexamethasone, and when I’m going by titrating power appropriately. (See possible. to perform ECP, I treat both preop- the tips on p. 25.) However, if you do Other less-common causes of eratively and postoperatively with cause popping, you’ll need to spend pressure spikes following ECP in- topical NSAIDs. If CME does de- a fair amount of time performing clude: velop postoperatively, I’ll increase irrigation and aspiration to clear out • Aqueous misdirection. Aqueous the topical steroid regimen and I’ll the debris. If that happens, you should misdirection, or malignant glaucoma, seriously consider using sub-Tenon’s be aggressive with postoperative is extremely rare in this situation— steroids to ameliorate the edema. steroids; you can give subconjunctival I’ve only seen one case in my career— dexamethasone and/or increase the but it can occur following any type Micropulse CPC frequency of postoperative topical of intraocular surgery, including steroids. ECP. Unfortunately, it’s easy to miss The latest iteration of CPC, Usually, the pressure will return because we typically consider aqueous micropulse cyclophotocoagulation, to normal (or even lower) within misdirection as a process only seen or MPCPC, minimizes the elevation five to seven days. Needless to say, after trabeculectomies or tube shunt of temperature inside the targeted prevention is the better approach. implantation. We need to remember tissue by dividing a continuous-wave • Steroid response. IOP can that if the patient develops a shallow beam of energy into a series of short also spike in response to steroid use. anterior chamber and elevated IOP pulses. As a result, the targeted tis- Obviously we’re being aggressive with postoperatively, aqueous misdirection sue cools back down before any co- steroids after ECP to try to decrease is a possible etiology. agulation takes place. This has the any inflammatory response. As you • Cystoid macular edema. CME effect of altering the tissue without

July 2019 | reviewofophthalmology.com | 23

0018_rp0719_gm18_rp0719_gm (1).indd(1).indd 2323 66/28/19/28/19 10:5410:54 AMAM Glaucoma

REVIEW Management

about how to hold the P3 Probe is Safety Profi le: Micropulse CPC Versus Continuous-wave TSTCP so widespread, when people tell me 8 in Refractory Glaucoma they’re not getting much response to treatment, that’s the fi rst thing I tell Outcome Measure MPCPC TSCPC Number of patients 23 23 them to try changing. Number of patients with ocular complications 20 (88%) 9 (40%) • When sweeping the probe Prolonged anterior chamber infl ammation 1 (4%) 7 (30%) along the eye, try doing shorter Phthisis bulbi 0 1 (4%) segments at a time. When you’re Scleral thinning 1 (4%) 4 (17%) sweeping across 180 degrees, the Visual acuity decline 1 (4%) 2 (9%) probe tip may get stuck on the conjunctiva, particularly if the ocular surface isn’t well lubricated. I prefer destroying it. For that reason, I like way you’d hold the G-Probe. sweeping across shorter 90-degree to refer to this as “cyclomodifi cation,” Occasionally, surgeons report a lack segments; I fi nd the probe tip is less rather than cyclodestruction. of good response to treatment with likely to get stuck, making treatment This lack of destruction has been MPCPC. In my experience, this is less awkward. demonstrated in several studies. One usually the result of a simple technique • Don’t be afraid to use MPCPC study reported by Murray Johnstone, problem involving how the probe is in cases of refractory glaucoma. MD, at the 2017 meeting of the being held against the eye. Surgeons Given that micropulse minimizes the American Glaucoma Society, found who’ve used the G-Probe to perform tissue damage, surgeons may worry that tissue treated with MPCPC transcleral CPC are accustomed to that it won’t be effective in refractory showed no sign of ciliary epithelium placing that probe positioned at the individuals. One excellent study coagulative damage or motion. Only limbus, held parallel to the visual axis. looked at that, comparing micropulse subtle changes could be seen upon Because of the design of the G-Probe, CPC to traditional continuous wave evaluation. including the off-center positioning diode CPC in 48 end-stage glaucoma This raises an interesting question: of the laser inside the probe and the patients.8 The groups had nearly The traditional assumption about curved tip designed to hug the globe, identical IOPs before treatment: the mechanism of action of CPC this delivers the laser energy to the 36.5 mmHg vs. 35 mmHg, and both has been that it causes damage that correct area inside the eye. approaches produced a 45-percent prevents the ciliary processes from The P3 Probe used for micropulse reduction in IOP. In fact, in this study creating aqueous, thus helping to CPC is designed differently. It has the micropulse group had a slightly lower pressure by lessening “input” a more rounded tip, with the laser greater success rate, based on the rather than enhancing outflow. If coming out at the center, so it should definition of success used in the this version of CPC isn’t causing any be positioned about 1 mm back from study—pressures between 6 and 21 visible damage, why does intraocular the limbus and held perpendicular mmHg and a 30-percent reduction in pressure drop after treatment? to the surface of the globe in order IOP at 18 months. (See table, p. 23.) The answer may lie in an older study for the laser to treat the correct area The only signifi cant tradeoff was a published in 1994.7 This study found inside the eye. If it’s held the same slightly higher retreatment rate. Here that TSCPC causes enlargement of way as the G-Probe—which surgeons it was an average of 1.6 treatments the extracellular space in the stroma may instinctively do—the treatment to achieve success, vs. 1.3 treatments and separation of the ciliary muscles will have little effect. (See sample for the continuous wave group. (In from the sclera. This suggests that the pictures, p. 26.) our experience it can sometimes be decrease in IOP may have resulted The other factor that can cause a more than that. In my practice the from both reduced aqueous secretion surgeon to hold the probe incorrectly mean number of treatments is closer and enhanced uveoscleral outflow. is a tight orbit. If there’s not much to two, particularly for patients with Given that MPCPC minimizes dam- room around the globe, it’s challenging advanced disease.) So, you’re trading age to the tissue, this may explain why to hold the probe perpendicular to a little convenience for the safety and it’s nonetheless effective at reducing the eye, 1 mm back from the limbus. effi cacy you gain with MPCPC. IOP. This encourages the surgeon to hold it Here are some pearls for making more like the G-Probe, with the same Three Key Strategies the most of MPCPC: less-than-excellent results. • Don’t hold the P3 Probe the Because this misunderstanding The following strategies will help

24 | Review of Ophthalmology | July 2019

0018_rp0719_gm18_rp0719_gm (1).indd(1).indd 2424 66/28/19/28/19 11:4011:40 AMAM VisiPlug is the only one for me… minimize any complications when performing CPC: No pop-out! • Avoid causing the popping sound. The audible “pop” you may hear during TPC or ECP is the sound of tissue exploding. Exploding tissue is never a good thing, so this is something you want to avoid. (You can see ciliary processes popping—on camera—in a video by Craig Chaya, MD’s group in Salt Lake City, at youtube.com/ watch?v=OKMR3tCenlk. The footage of ciliary processes popping starts about 2:45 into the video.)

Hopefully, more ophthalmic surgeons will realize the advantages of this approach to lowering IOP—the avoidance of patient adherence issues, the cost- effectiveness, and the benefi ts for the patient’s quality of life, Lacrimedics’ VisiPlug is not like to name a few. “other” punctum plugs. We have no reported “pop-outs” since VisiPlug’s introduction in 2003… and it’s There are two protocols for avoiding causing the ciliary distributed in over forty countries! processes to explode. Historically, surgeons started between 1,750 and 2,250 mW of energy applied for 2,000 mS, and would turn up the power until a little crackle was FDA approved for the treatment audible; at that point, you’d back off the power a little bit of the Dry Eye components of and proceed with treatment. I would typically perform 12 varying Ocular Surface Diseases spots of treatment per hemisphere, skipping the 3 o’clock (OSD), after surgery to prevent and 9 o’clock positions (see the explanation below). complications due to Dry Eye However, in the past couple of years I’ve been using Disease, and to enhance the the Gaasterland “slow coagulation technique” which efficacy of topical medications. involves starting with a lower power and applying it over a longer duration. Again, I increase power until I hear a little crackle and then treat using slightly less than that amount. This method has resulted in a higher degree of VisiPlug® – effi cacy with a better side-effect profi le: less edema; less infl ammation; and less discomfort postoperatively. (In a visibly better plug either technique the important thing is to avoid reaching to treat dry eye! the level at which you hear a loud pop. If you hear that, you’re more likely to get signifi cant postoperative infl am- mation, fi brin and possibly even hypotony.) • Avoid performing CPC at the 3 and 9 o’clock positions inside the eye. The long, posterior ciliary vessels, including the arteries, typically enter the eye at (800) 367-8327 the 3 and 9 o’clock positions. For that reason, performing E-mail: [email protected] CPC at those locations means a higher risk of causing www.lacrimedics.com ischemia, hypotony and all of the other negative sequelae

that we’re concerned about. 1Dramatization. Not a real patient. ©2017 Lacrimedics, Inc.

018_rp0719_gm (1).indd 25 6/28/19 10:57 AM Glaucoma

REVIEW Management Iridex

Surgeons who’ve used the G-Probe to perform transscleral CPC are accustomed to placing that probe at the limbus, held parallel to the visual axis (above, left). Because of the different design of the P3 Probe used for micropulse CPC, it has to be positioned about 1 mm back from the limbus and held perpendicular to the surface of the globe in order for the laser to treat the correct area inside the eye (above, right).

Many surgeons are aware of this shift one way or the other.9 this approach to lowering IOP— and try to avoid these areas when Given that we still don’t get about 10 the avoidance of patient adherence treating, but if the eye has been anes- percent of our patients within 0.5 D of issues, the cost-effectiveness, and thetized using a retrobulbar block our target, it’s easy to overlook asym- the benefi ts for the patient’s quality it may cyclorotate, changing the lo- metric ECP treatment as a possible of life, to name a few. In terms of cation of 3 and 9 o’clock. (Even with- explanation for a slight, consistent outcomes, close attention to detail, out a block, eyes may cyclorotate a refractive surprise. However, if you’re as well as taking advantage of some little when the patient lies down.) performing EPC, there could be a of the pearls provided here, should For that reason, I mark the eye at 3 connection. So, try to perform a uni- prevent untoward complications and and 9 o’clock preoperatively, to avoid form, diffuse application across the ensure excellent results. inadvertently treating those areas. ciliary processes—not too anterior or Although I’ve seen videos in which posterior. Then, be sure to track your Dr. Kammer is an associate professor surgeons using micropulse CPC don’t refractive outcomes postoperatively of ophthalmology at Vanderbilt Eye skip the 3 and 9 o’clock sections, I still and adjust your technique accordingly Institute in Nashville, Tennessee. He believe that it’s a good idea to skip if you fi nd that your refractive results has consulted for Allergan, Aerie, these locations, even with this less- are a little bit off. Iridex and New World Medical. destructive technology. Theoretically 1. Eid TE, Katz LJ, Spaeth GL, Augsburger JJ. Tube-shunt the laser doesn’t penetrate as deeply, A Valuable Option surgery versus neodymium:YAG cyclophotocoagulation in and it might not hit those deeper the management of neovascular glaucoma. Ophthalmology 1997;104:10:1692-700. vessels, but I’m not going to take that Today, doctors treating glaucoma 2. Ramli N, Htoon HM, Ho CL, Aung T, Perera S. Risk factors chance. I don’t think skipping two are more comfortable using CPC for hypotony after transscleral diode cyclophotocoagulation. J Glaucoma 2012;21:3:169-73. clock hours of treatment is going to earlier in the treatment course than 3. Quigley HA. Improved outcomes for transscleral have a major impact on the outcome, they were in the past. I think this is cyclophotocoagulation through optimized treatment parameters. J Glaucoma 2018;27:8:674-681. so I err on the side of caution. true for two reasons: First, surgeons 4. Egbert PR, Fiadoyor S, Budenz DL, Dadzie P, Byrd S. Diode • When using ECP, be aware younger than 45 have seen their laser transscleral cyclophotocoagulation as a primary surgical treatment for primary open-angle glaucoma. Arch Ophthalmol that inaccurate placement of the attendings use CPC earlier in the 2001;119:3:345-50. treatment can lead to a refractive course of the glaucomatous disease 5. Semchyshyn TM, Tsai JC, Joos KM. Supplemental transscleral diode laser cyclophotocoagulation after aqueous shunt placement shift. Not many surgeons realize it, process, with good results. Thus, they in refractory glaucoma. Ophthalmology 2002;109:6:1078-84. but if you laser the ciliary processes a feel more comfortable incorporating 6. Lima FE, Carvalho DM, Avila MP. Phacoemulsifi cation and endoscopic cyclophotocoagulation as primary surgical procedure little too anteriorly, the tissue changes it earlier in their treatment paradigm. in coexisting cataract and glaucoma. Arq Bras Oftalmol can cause forward movement of the The second factor increasing the use 2010;73:5:419-22. 7. Liu GJ, Mizukawa A, Okisaka S. Mechanism of intraocular iridozonular complex, resulting in a of CPC is the arrival of micropulse pressure decrease after contact transscleral continuous- small myopic shift. Likewise, if you CPC. This has shifted the risk/benefi t wave Nd:YAG laser cyclophotocoagulation. Ophthalmic Res 1994;26:2:65-79. apply the laser a little too posteriorly, ratio even more in the direction of 8. Aquino MC, Barton K, Tan AM, Sng C, Li X, Loon SC, Chew the tissue changes can pull the safety, and that makes surgeons more PT. Micropulse versus continuous wave transscleral diode cyclophotocoagulation in refractory glaucoma: A randomized complex posteriorly, causing a small comfortable about using CPC earlier exploratory study. Clin Exp Ophthalmol 2015;43:1:40-6. hyperopic shift. If this is happening, in the game. 9. Sheybani A, Saboori M, Kim JM, Gammon H, Lee AY, Bhorade AM. Effect of endoscopic cyclophotocoagulation on refractive it’s likely to be a consistent problem, Hopefully, more ophthalmic sur- outcomes when combined with cataract surgery. Can J resulting in a consistent refractive geons will realize the advantages of Ophthalmol 2015;50:3:197-201.

26 | Review of Ophthalmology | July 2019

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RP0719_Compulink.indd 1 6/10/19 3:45 PM Refractive Surprises REVIEW Cover Story Refractive Surprises: What To Do Next

Christopher Kent, Senior Editor

Surgeons offer hen performing refractive want to end up on-target.” cataract surgery, a perfect When a patient’s outcome isn’t what advice for those Woutcome is always the goal, was hoped for, the surgeon has to and the number of patients hitting make a number of decisions. Is the times when your their refractive target has increased refractive miss signifi cant enough to steadily over the years. However, require correcting? What, exactly, is cataract surgery the challenges inherent in operating the cause of the less-than-ideal out- within a complex, living system have come? And if I’m going to correct the outcome isn’t on kept the success rate from reaching refractive result, which method makes 100 percent. As a result, surgeons still the most sense for this patient? target. have to deal with cases of postopera- tive refractive surprise. Should You Correct It? “Tools such as intraoperative aber- rometry and better power calculation “Not all refractive misses have to formulas, like Hill RBF and Graham be surgically corrected,” notes Dean Barrett’s formulas, have made refrac- Ouano, MD, a cornea and anterior tive misses less common,” notes John segment specialist at the Coastal Eye Berdahl, MD, a corneal, refractive and Clinic in New Bern, North Carolina. glaucoma surgeon at Vance Thomp- “Despite advances in optical biom- son Vision in Sioux Falls, South Da- etry and IOL formulas, a signifi cant kota, and associate clinical professor percentage of patients fail to achieve at the University of South Dakota. emmetropia. If you look at the Swed- “Nevertheless, today we still enhance ish National Registry study published 10 to 15 percent of our patients that in 2012, 17,000 patients were targeted have a refractive endpoint in mind.” for emmetropia in cataract surgery, William B. Trattler, MD, director of but only 55 percent of them actually cornea at the Center for Excellence in achieved it.1 So deciding to correct Eye Care in Miami, and a volunteer a refractive surprise is a question of faculty member at the Herbert Wert- degree. The patient has to be symp- heim College of Medicine at Florida tomatic, and the refractive miss has International University, agrees. “Re- to be large enough to justify surgical fractive surprises are definitely less intervention. frequent, but they still do happen,” he “Deciding to explant or exchange says. “Premium IOL patients, in par- a lens shouldn’t be done lightly,” he ticular, have high expectations. They continues. “Before you surgically in-

28 | Review of Ophthalmology | July 2019 This article has no commercial sponsorship.

0028_rp0719_f1.indd28_rp0719_f1.indd 2828 66/28/19/28/19 1:391:39 PMPM Dean Ouano, MD tervene in a refractive miss you have gery, and those can be worsened by to fi gure out several things. How big all the drops associated with surgery. is the miss? Will the patient tolerate That can impact postoperative quality the residual refractive error if it’s cor- of vision and the refractive error. Eye- rected by spectacles or contact lenses? care providers can focus on reducing Have you ruled out any other coexist- postoperative infl ammation, and at the ing problems such as macular disease, same time treat the underlying ocular ocular surface disease or irregular surface condition. astigmatism? I think each case has to “The impact of a condition such as be examined on its own merits.” dry eye may not be that obvious, but To be certain that you really do need you’ll be surprised when you treat to make a refractive adjustment, sur- A piggyback IOL is sometimes a good postoperative patients for dry eye,” choice for correcting a refractive surprise, geons emphasize two points: First, but anatomical issues always need to be he continues. “Some patients may im- make sure you understand exactly considered. Here, the sharp edge of the prove enough that they won’t need what’s causing the refractive issue. optic is causing pigment dispersion. further surgery to improve their vi- Second, make sure to wait an appro- sion—even though you thought they priate amount of time before drawing patient unhappy.” did. For example, let’s say you have a any fi nal conclusions about the size of Surgeons also agree that in most patient who is 20/30 with -0.75 D of the miss. cases it’s crucial to wait before making cylinder. The patient may say, ‘My vi- “There are a couple of things you a fi nal determination about the extent sion isn’t what I expected.’ While one need to check out,” says Dr. Berdahl. of a refractive miss. “I won’t usually might believe the patient’s complaint “Is there other pathology going on, make a refractive miss call until three is due to the small amount of residual such as posterior capsule opacity or months after surgery, when I feel sure astigmatism, further questioning may a retinal problem? Is the lens tilted? the eye is entirely stable,” says Dr. reveal that it’s actually the result of Also, keep in mind that some prob- Berdahl. “You’re probably on reason- fl uctuating vision caused by dry eye. lems can’t be corrected by adjusting ably safe ground if you decide as early In my experience, treating dry eye the refraction. Let’s say you implanted as three weeks out, but I want the next can eliminate 60 to 70 percent of the a bilateral extended-depth-of-focus move I make to be defi nitive. For that patients who initially seem to need an lens and the patient’s main complaint reason, I prefer to wait at least three enhancement following cataract or is inadequate near vision. Adjusting months for the refraction to settle.” lens replacement surgery. the refraction isn’t necessarily going “It’s important not to make that “Make no mistake, patients don’t to solve that problem. You need to decision too early,” agrees Dr. Lee. want to undergo more surgery, so understand the nature of the problem “You need to give the patient at least they’ll be happy if you can resolve the before you try to solve it.” a couple of weeks to be refractively problem without it,” he says. “That’s Bryan Lee, MD, JD, in private prac- stable, and some patients may need why if the patient is unhappy, my tice at Altos Eye Physicians in Los Al- even more time to get where they’re protocol is to first treat for dry eye tos, California, agrees that sometimes supposed to be. You don’t want to cor- and meibomian gland disease, even the nature of the IOL is the problem. rect something prematurely.” if these conditions aren’t obvious. In- “If the patient’s unhappy after you put creasing tear quality—even if it wasn’t in a multifocal or extended-depth-of- Minimizing Alternate Factors terrible before—can signifi cantly im- focus lens, one of the things you have prove their vision.” to fi gure out is whether the problem is Given that issues besides a refrac- Dr. Berdahl agrees. “The fi rst thing residual refractive error or an optical tive power miss can affect vision, and to examine and treat is the ocular sur- problem relating to the IOL design,” additional surgery should ideally be face,” he says. “Whatever target you’re he says. “Figuring that out may re- avoided, you can take several steps to shooting for, you don’t want it to be a quire having the patient wear a pair ensure that a surgical adjustment is re- moving target. As we all know, dryness of glasses or contact lenses to make ally necessary. and ocular surface disease are com- sure they’re actually happy when the “One of the things that impacts the mon in these patients, and those con- refractive error is corrected. If they fi nal refractive outcome is the ocular ditions can affect the refraction. If the are, then laser vision correction makes surface,” notes Dr. Trattler. “Many ocular surface isn’t OK, then we need sense. The main point is that you have patients have mild dry eye or meibo- to treat it and rehabilitate it.” to fi gure out exactly what’s making the mian gland dysfunction before sur- Dr. Trattler says a second concern

July 2019 | reviewofophthalmology.com | 29

028_rp0719_f1.indd 29 6/28/19 1:39 PM 028_rp0719_f1.indd 30 30 “Then weseehowhe’s doingandre- him throughthefi course ofpostoperativedrops andget following surgery, wefi a patientisunhappywithhisvision in termsoftiming.“Onceit’s clearthat gical enhancement.” like tofollowbeforemovingonsur- he concludes.“That’s theprotocolI their postoperativevisualoutcomes,” many patientswillbehappierwith ocular surfaceandperformYAG— optimize thepatient’s vision. of therefractivefeebecauseIwantto patient either. Ijustincludeitaspart cant PCO,andIwouldn’t chargethe this withoutthepresenceofsignifi- Again, youcan’t chargeinsurancefor we reallyoptimizethepatient’s vision. through allofthesestepstomakesure YAG wouldbequicker, butwework more stablelong-term.Skippingthe sion correction,thevisionisalittlebit performed aYAG priortothe laservi- shift theirrefractiveerror. Ifyou’ve rience capsularcontraction,whichcan patient’s PCOworsensandtheyexpe- continues. “Threemonthslaterthe perform laservisioncorrection,”he is, let’s sayyoudon’t YAG andyou difference. this protocolsometimesmakesareal of bestcorrectedvisualacuity. But treating somethingthat’s causingaloss don’t chargeforthisbecauseI’mnot surgery enhancement.“Ofcourse,I outcome andhe’s planningarefractive when apatientisunhappywiththe tler saysheroutinelyperformsaYAG tuning.” With thisinmind,Dr. Trat- cases, thismayavoidanyneedforfi improving vision.Insomeborderline ing therefractiveoutcomealittleand lens mayevenshiftalittlebit,chang- eliminate theproblem,”hesays.“The sule, visionisimprovedjustenoughto sion. “Sometimesifwelaserthecap- fi is thatmildposteriorcapsularopaci- cation canalsoimpactqualityofvi- REVIEW Dr. Trattler explains howthisworks “If youdoboththings—treatthe “The otherthingthatcanhappen |

Story Cover Review ofOphthalmology

rst month,” he says. rstmonth,”hesays. Refractive Surprises rst fi rst nish the nish | July2019 ne- ReSure tissueadhesiveonthewound. A postopcataract patientwithpriorRKand surprise following cataract surgery. Above: be more likely toendupwitharefractive Patients withpriorradial keratotomy may no furthercorrectionisnecessary.” enough thatthepatientishappy. Ifso, just, andoftenthingshaveimproved tocol givestheeyetimetohealandad- tively fi nal,” heconcludes.“Thispro- two wecheckeverythingagain. capsulotomy. After anotherweekor two tothreemonthswemaydoaYAG also checktheposteriorcapsule.At the patientreturns,were-refract.We give thepatientanothermonth.When may alsoplacepunctalplugs.Thenwe with eitherRestasisorXiidra,andwe we oftenstartatopicalsteroid,along In casesofaqueous-defi ciency dryeye, three-week courseofatopicalsteroid. tic spraysfortheeyelashesandoftena treat withwarmcompresses,antisep- to bemeibomianglanddisease,we’ll initiate dry-eyetherapy;ifitappears try tooptimizetheocularsurface.We refract. Ifhe’s stillunhappy, thenwe’ll with corneallasersurgery requires and laserrefractiveprocedures. the IOLoraddingapiggybacklens— IOL-based changes—i.e.,replacing broadly dividedintotwocategories: rection isnecessary, thechoicescanbe refraction, ifyou’vedecidedthatacor- Should You UsetheLaser? “At thispointtherefractionisrela- Deciding whether or not to proceed Deciding whetherornottoproceed When choosingawaytoadjustthe

Dean Ouano, MD Ouano, Dean notes Dr. Ouano. an IOLexchangeorapiggybacklens,” astigmatism andrefractiveerrorsthan to moreaccuratelycorrectresidual that laserrefractivesurgeryisable Journal ofRefractiveSurgeryshowed +1 Doff-target.” accurate thanlaseringsomeonewhois one whois-1Deasierandmore error,” notesDr. Lee.“Laseringsome- count isthedirectionofrefractive ment. you havealotofoptions.” If thepatientisa-2Dmyopicmiss, smaller refractivemissisagrayzone. not agoodidea.Ontheotherhand, dure onanolderpatientisgenerally D hyperopickeratorefractiveproce- solution,” hesays.“Forexample,a+4 refractive misscallsforanIOL-based most surgeonswouldagreethatalarge surgery tomakeacorrection.“Ithink direction, youshouldavoidusinglaser cal errorismorethan4Doffineither Ouano saysthatifthepatient’s spheri- considering numerousfactors: “If thepatienthashadprior LASIK from refractivesurgery.” and howeasilythepatientwillrecover have toconsiderhowdrytheeyesare a worseocularsurface,”hesays.“You tients areolder, andtheyoftenhave ease anddryeye.” patients havemoreocularsurfacedis- 25-year-old,” notesDr. Ouano.“Older much differenthealingprocessthana 75-year-old undergoingLASIKhasa age hastobeconsidered,becausea avoid anotherintraocularprocedure.” procedure couldbe.Inaddition,you’d ing thecylinder, butaLASIKorPRK going tobeveryreliableforcorrect- -2 Dcylinder. An IOLexchangeisn’t suppose yourmissis-3Dsphereand signed tobeaccurate.Forexample, because LASIKandPRKwerede- • • • • Dr. Leeagrees.“Cataract-agepa- • Age ofthepatient.“Thepatient’s The sizeoftheadjustment.Dr. Prior laserrefractivesurgery. Accuracy. The directionoftheadjust- “Another thingtotakeintoac- “A 2013 study in the “A 2013studyinthe 2 “That makes sense, “Thatmakessense, 6/28/19 1:39 PM COMBOCOMBO SELECTSELECT YYOUROUR CCHAIRHAIR

or PRK, I typically wouldn’t want to PRK or another procedure such as do further laser correction on that pa- SMILE. tient,” says Dr. Lee. “Doing PRK over “If the patient ends up on the myo- a LASIK flap is less accurate. So in pic side, I typically perform laser vi- general, if the patient has had laser re- sion correction,” says Dr. Trattler. fractive surgery I’ll do a lens exchange. “We don’t have access to SMILE, I think it’s more accurate in that situ- but we perform both LASIK and ation.” PRK—mostly PRK, although LASIK • Contraindications. Performing is certainly an option for myopic or 1000-CH LASIK or PRK on a patient under any astigmatic fine-tuning.” Dr. Trattler Examination circumstances requires that the cor- uses epi-Bowman’s keratectomy, per- Chair nea meet appropriate specifi cations. formed with a device called EpiClear “You have to consider the normal con- (ORCA Surgical), which removes the traindications for LASIK or PRK— epithelium and collects discarded cells things like corneal thickness and kera- into its tip without touching Bowman’s toconus,” Dr. Ouano points out. membrane. Dr. Trattler says that in his • Practical issues, including ac- experience this is more comfortable 1800-CH18000 CH cess to the technology. “Logistics, for patients than traditional epithelial Manual availability and reimbursement are debridement with alcohol. Recline all issues with PRK and LASIK,” says Dr. Berdahl says he prefers to do a Dr. Ouano. “For one thing, not every refractive correction with LASIK rath- offi ce has access to an excimer laser.” er than PRK. “I think the results are a Dr. Lee agrees. “If you don’t have little bit better in an older population,” access to an excimer laser, that may he says. “Because these patients are push you towards doing an IOL ex- older, their epithelium can be more change or piggyback in these situa- irregular. Doing a low-correction PRK tions,” he says. “On the other hand, if can unmask that irregular epithelium, you operate in a hospital setting and leading to more variable results. In the cost of doing an IOL exchange fact, epithelial mapping can be very is outside of your control, that might helpful when trying to decide whether push you towards doing an excimer you should do LASIK or PRK. laser treatment. Either choice is prob- “It’s kind of a conundrum,” he con- ably fi ne, because clinically, one way tinues. “If the epithelium is very ir- 2000-CH0000-CH isn’t necessarily better than the other.” regular, that might indicate anterior CCradleradle TilTiltt Dr. Berdahl says he believes resid- basement membrane disease, which ual refractive error is probably un- probably should have been treated dertreated in general, simply because prior to cataract surgery. But if you’re many surgeons don’t have access to faced with a very irregular epithelium 2500-CH an excimer laser. “If you don’t have postoperatively, you should do a super- Motorized access to a laser, you should consider fi cial keratectomy or phototherapeutic Recline developing a relationship with some- keratectomy and see how it heals; then one in your community who does,” he come back and do LASIK or PRK. says. “Try to work out a system where If the epithelium is mildly irregular, you either can use their technology, which is true for a lot of patients, then or they’ll do enhancements on your I’d probably do LASIK. I don’t want to patients for you.” unmask that irregular epithelium with PRK, causing it to be translated into LASIK or PRK? the refractive outcome. If the patient has a very regular epithelium, than If an adjustment by excimer laser either LASIK or PRK is OK. seems like the best choice, the next “I think an irregular epithelium is question is whether to opt for LASIK, one of the things that cataract sur- 250 Cooper Ave., Suite 100 Tonawanda NY 14150 www.s4optik.com I 888-224-6012 Sensible equipment. Well made, well priced.

028_rp0719_f1.indd 31 6/28/19 1:40 PM 0028_rp0719_f1.indd 32 2 8 _ r p 0 7 1 9 _ f 1 32 at usingitastimegoesby.” cedure, andwe’regoingtogetbetter he says.“SMILEisaveryyoungpro- refractive, includingenhancements,” holds alotofpromiseforallthings SMILE lenticulecanbechallenging. corrections. Removingaverysmall is thattheseareusuallyverysmall SMILE tocorrectarefractivemiss able. Thebiggestconcernwithusing ness—although thatmaybedebat- there’s alittlelesspostoperativedry- like aboutSMILEisthatperhaps ments,” saysDr. Berdahl.“Whatwe will begreatforrefractiveenhance- it’s tooearlytotellwhetherSMILE refractive IOLandanenhancement.” dissatisfi the mainreasonssurgeonshavesome easy tooverlook.Ithinkit’s oneof geons frequentlymiss,”headds.“It’s Laser orIOL-basedCorrection? . i n d “Nevertheless, IthinkSMILE What aboutusingSMILE?“Ithink Alternatives tolaserrefractive cor- REVIEW d the lenswillbecomemuchmorechallenging.” If wewait, willcontractaroundtheIOLandrotating thecapsule itgoesovertime.we makethecorrectionandnotwaittoseehow thelensalittlebit.tate case, Inthat that I’dsuggesttothepatient tellsmehisvisionwouldbesignificalculator cantly betterifIro- tism. anyway, ishappy Sometimesthepatient butmyastigmatism toric lensandit’s notintheidealpositiontocorrecthisastigma- forfiwindow xing things,” hecontinues. “Let’s sayI’veimplanteda something weshouldprobablyadjust, becausethere’s atime- ishappy. ifthepatient do anything inspiteofthat, willbehappy thepatient andIwouldn’t sible that IOL, aimingforplano, -0.75D. endsupat butthepatient It’s pos- correction orpresbyopiacorrection. Perhaps youimplantedatoric surgery,type ofrefractivecataract whetherthat’s astigmatism some haselectedtohave “This isespeciallytruewhenthepatient practiceat in private Altos EyePhysiciansinLos Altos, California. isanimportantconsideration,”happiness Lee, saysBryan MD, JD, thetearfitreated lm andtheocularsurfacelooksOK—patient correction. you’vegotastablerefraction—you’ve “Assuming that andcomfortwithyourpreferredmethodformakinga satisfaction all—willdependpartlyonthepatient’sa refractiveadjustmentat | Accommodating thePatient

Story Cover Review ofOphthalmology

3 Whatever courseofactionyouchoose—includingWhatever notmaking “However, thisis that therearetimeswhenI’lltellthepatient 2 ed patientsafterreceivinga

Refractive Surprises | July2019 is equal,Ithinkinmostcases theex- have theotheroption.Butif allelse exchange simplybecausethey don’t an excimerlaser, sothey’lldoanIOL many surgeonsdon’t haveaccessto with apreviousLASIKfl too, ifI’mnotcomfortabledealing may betrueforpost-LASIKpatients, exchange makesthemostsense.That notes. “Inthatsituation,IthinkIOL refractive-enhancement options,”he RK patient,Iwon’t havegoodlaser- ity isamajorconcern.“Ifit’s apost- to exchangetheIOL,cornealstabil- when he’s consideringwhetherornot sults.” However, Dr. Berdahlsaysthat “That approachcangiveyougoodre- facile withIOLexchanges,”hesays. exchange. “That’s reasonableifyou’re geons prefertogorightanIOL corneal lasercorrection. based changewillworkbetterthana them—determine whetheranIOL- factors—surgeon preferenceamong or addingapiggybacklens.Several rection includeanIOLexchange Dr. Berdahlobservesthatsomesur- make thebestchoice.” further, it’s andhelpthem toinformthemofthat myobligation just forme.‘20-happy’ Icanimprovethepatient’s IfIknow vision improvement ispossible. that knows sure thepatient Soit’s not all, thenI’llsay, ‘I thinkIcanmakeyouevenhappier.’ I’llmake he says. signofdiffi any indicates patient “But ifahappy culty at wellenoughalone,” thegoalhasbeenachievedandleave that they wanttodoeasilyandwithoutannoyance, thenImayagree fractive misshasoccurred. saytheycandoeverything “If patients are- reactionwhenheknows careful ifhegetsapositivepatient at Vance Thompson Vision inSiouxFalls, SouthDakota, sayshe’s pretty satisfi ed.” mend tweakingoradjustingtheIOLposition, is evenifthepatient patient. scenarioinparticular, Inthat I’dbemorelikelytorecom- all,at additionalchargetothe andtypicallytherewouldn’tbeany fi rst eyewhileyou’rethere. Itdoesn’tinconveniencethepatient todothesecondeye.OR anyway Itmakessensetotweakthe the toriclensinfi rst eyebetter, andyou’regoingtobeinthe the fi rst andsecondeye,” hesays. “You youcanposition know in somesituations. “Let’s between sayyou’reseeingapatient JohnBerdahl, MD, acorneal, refractiveandglaucomasurgeon Dr. easy anIOLisrelatively thedecisiontorotate Leenotesthat ap. Of course, ap. Ofcourse, Piggyback orLensExchange? Piggyback exchange.” bag ismorepliableandamenableto he says.“Inearlylensexchanges,the lens hasn’t beenintheretoolong,” with alensexchange,aslongthe was averylargesphericalmiss,I’dgo tient’s overallrefractiveerror. “Ifit situation woulddependonthepa- cases,” heexplains. with IOLexchangethanPRKinmany more comfortableandfasterrecovery exchange. “Thepatientwillhavea he maydecidetoperformanIOL is acandidateforPRKbutnotLASIK, exchange. Dr. Leesaysthatifapatient a shifttoanalternativesuchasIOL the patient,that’s suffi surgeon believeswillbeeasiestfor for thespecificlaserprocedure correct arefractivemiss.” cimer laseristhemostprecisewayto If lasercorrectionisoffthe table, Dr. Ouanosayshisapproachinthis Sometimes ifapatientisn’t eligible cient to cause to cient — CK 66/28/19 1:40 PM / 2 8 / 1 9

1 : 4 0

P M EXAMINATIONEXAMINATION STAND

should you opt for exchanging the IOL power lenses from Johnson & John- or adding a piggyback lens? son Vision within a certain range. But “A straightforward lens exchange is the lack of an ideal sulcus-fi xated IOL appealing to me, because you’re going is a disadvantage for the piggyback to maintain the desired anatomy of the option. eye—switching an in-the-bag lens for “The biggest problem,” he adds, “is an in-the-bag lens,” says Dr. Ouano. that if you have a large myopic miss—

“You’re not going to have two lenses let’s say -9 D—you’re not going to 2000-ST inside the eye, and you’re not going to solve that with LASIK or PRK, and disrupt the corneal surface. You can you can’t get an IOL that high. You usually use the same entry wound, can use an implantable contact lens and it’s a straightforward, safe surgery off-label; they come in powers up to if it’s done in the early postoperative -16 D. But it raises a big fi nancial is- period, as long as you have an intact sue: Who pays for the ICL? It’s quite rhexis and intact posterior capsule and a bit more expensive than a standard zonules. An early IOL exchange for a IOL. So piggybacking in that situation refractive miss after cataract surgery, isn’t a good option.” is, in my opinion, a good procedure. Dr. Ouano admits, however, that if Furthermore, in our experience, the you’re contemplating a lens exchange reimbursement pathway for an IOL instead, timing is a major concern. exchange after a refractive miss is also “Opening a capsular bag late, let’s say straightforward. So if there’s a refrac- six months to a year after the surgery, tive miss following cataract surgery my is more difficult,” he notes. “There preference is to do an IOL exchange are risks involved, depending on the during the early postoperative period.” status of the zonules and the poste- Dr. Ouano says he doesn’t favor rior capsule, so exchanging the lens the piggyback option, although some isn’t necessarily a slam dunk. It’s not surgeons in his practice prefer it. “I impossible, but it’s more difficult to understand why they like it,” he says. manage.” “Number one, it’s technically easy to Dr. Lee says that in his experience do. Two, selecting the lens implant is implanting a piggyback lens usually easy to do because it’s based on the works well. “Calculating the power is Modern design, postoperative refractive error. Three, straightforward, and the procedure the reimbursement pathway is reason- is straightforward as well,” he says. built to last. able. The fi nancial barriers are not as “However, not every patient can toler- insurmountable as they can be if you ate a piggyback lens, depending on Add a superior achievement do a LASIK procedure on a 75-year- the anatomy of the anterior segment. in engineering to your old patient. So the piggyback option That’s not totally predictable, so if you has some advantages. put in a piggyback IOL, sometimes practice with the S4OPTIK “However, I think the disadvan- it will have to come out later. If I’m 2000-ST Instrument Stand tages are also signifi cant,” he contin- planning to use a piggyback lens, I’ll ues. “The patient might have a very always mention preoperatively that shallow anterior chamber, in which occasionally these piggyback lenses with logically positioned, case there’s a real possibility of iris have to be explanted. Fortunately, it’s durable membrane switches chafi ng, pigment dispersion or UGH very straightforward to remove a pig- for chair up/ down control syndrome. And a big downside is that gyback IOL. and main power. we don’t have a lot of choices for a sul- “I think in general a piggyback lens cus-fi xated IOL in the United States. is a good way to correct refractive er- We currently have two silicone three- ror,” he continues. “Again, it depends piece lenses for the plus powers: the on the clinical situation. You might Bausch + Lomb Sofport LI61AO and have a patient with bad zonules, or the Tecnis Z9002. There are minus- one who’s uncooperative during the 250 Cooper Ave., Suite 100 Tonawanda NY 14150 www.s4optik.com I 888-224-6012 Sensible equipment. Well made, well priced.

028_rp0719_f1.indd 33 6/28/19 1:40 PM Cover Refractive Surprises

REVIEW Story

surgery. Factors like these might push • First, let the patient know the parts of their visual outcome they you towards thinking about implanting you’re on the case. “When you have already like, which isn’t the case. a piggyback lens instead of performing a refractive surprise, be sure the pa- “For example, let’s say we have a an IOL exchange, but the anatomy tient knows that you care about this, patient who ends up a little on the will still be a factor. Just a few weeks and that you’re going to work to get nearsighted side,” he continues. “They ago I had a patient who’d had prior them where they want to be,” says Dr. have good computer vision and read- LASIK and was off-target. That pa- Berdahl. ing vision, but they want better dis- tient had already had a YAG laser, so • Don’t shy away from rotating a tance vision. I’ll have them demo a I didn’t want to laser or do an IOL misaligned toric IOL. Dr. Lee notes contact lens to make sure this change exchange. I did a piggyback, and he’s that whether or not a toric lens rota- in their vision is really what they want, done very well so far.” tional adjustment should be made in a because if they realize what the trade- Dr. Trattler says he doesn’t often borderline case depends on numerous off is—getting better distance at the exchange IOLs. “If the patient’s hy- factors. “If someone has a very high- expense of near—they may decide peropic, I prefer to implant a piggy- powered toric lens implanted, like a they don’t want to have the refractive back lens,” he says. “Implanting a pig- T6, and the lens is 7 degrees off, that outcome adjusted after all. That’s why gyback lens is very simple. You make a patient’s vision will be affected a lot a contact lens trial prior to performing tiny incision, insert the lens, put Mio- more than a patient who has a T3 lens an enhancement is helpful. That trial chol in the eye, and you’re done. It’s but is rotationally further off-target,” educates the patient about what to very fast and patients have very good he says. “So it depends on the clini- expect.” outcomes. In contrast, if you have to cal situation—as well as the patient’s “When the patient has a presby- free-up an IOL, bring it into the an- personality. opia-correcting IOL, I wouldn’t make terior chamber, bisect it with scissors “I know that some surgeons hesitate any decision about how to proceed inside the AC, remove the IOL frag- to go back in to rotate a toric IOL,” he without correcting the refractive miss ments and then place a second lens adds. “Aside from having to re-enter fi rst,” says Dr. Lee. “This can be done inside the capsular bag, there’s a little the eye, you’re telling the patient that with a pair of glasses or contact lenses. more surgery and risk. Of course, you you want to take him back to the OR, I’ve had many unhappy patients re- may have to perform an exchange if and there could be a cost associated ferred to me two or three months after you implanted a toric lens with the with it, depending on whether you surgery who had never tried a pair of wrong astigmatic power, or the patient operate in a hospital or in a surgery glasses. That’s kind of the fi rst step in is unhappy with the glare and haloes center where you have more control. fi guring out what to do: Correct the caused by a multifocal lens. But if ev- But surgically it’s not too diffi cult to residual refractive error. Sometimes if erything’s fi ne other than the patient rotate a lens, as long as you’re doing you give them a pair of glasses they’re being a little hyperopic, then a piggy- it within three or four weeks after the so happy they can see clearly that they back lens can work very nicely.” initial surgery. It’s pretty straightfor- don’t want anything else. And if they Dr. Trattler adds, however, that he ward, and it can help the patient.” still want to have their refractive error generally reserves the piggyback op- • Keep the lines of communica- corrected, this gives you confi dence tion for refractive surprises that are tion open. “Be sure to continue to that the thing that’s making them un- signifi cantly hyperopic. “For myopia, communicate with the patient postop- happy really is the refractive error.” PRK and LASIK are very effective,” eratively, especially if the patient is un- Sometimes the refractive miss is he says. “If we’re talking about 1.5 D happy,” says Dr. Lee. “You have to take very small, but the patient is still un- of hyperopia or higher, laser vision the initiative to follow-up and keep the happy. “Suppose a patient ends up correction has been a little under- communication lines open so you have +0.25 -0.5,” says Dr. Berdahl. “The whelming. Of course, if it’s a hyperopic as good a relationship as possible.” first thing I want to do in that situ- refractive surprise of 0.5 or 0.75 D, • Perform a trial correction be- ation is simulate the adjustment I’d then LASIK or PRK is fine. But if fore proceeding. “Before I actually be making, using glasses or contact more than 1 D of treatment is needed, perform the procedure, whether it’s lenses. The glasses might take the pa- I’ll typically use a piggyback lens.” PRK, LASIK or a piggyback lens, I tient from 25/25+1 to 20/15 solid. The typically have the patient undergo a patient may put the glasses on and say, Some General Advice … contact lens trial to demo what their ‘Yes, this is what I want.’ In that case, corrected vision will be like,” says Dr. I’ll do the enhancement. But I want to Surgeons offer these suggestions to Trattler. “Patients often assume that help things go smoothly: altering the outcome won’t change (Continued on page 45)

34 | Review of Ophthalmology | July 2019

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RP0719_Imprimis.indd 1 6/17/19 3:45 PM Refractive Surgery REVIEW Feature Refractive Surgery for Patients over 50

Sean McKinney, Senior Editor

You may now be our fastest growing patient dividualizing refractive surgery rec- population and the field of ommendations for patients over 50. grappling with one Yrefractive surgery are reach- David R. Hardten, MD, FACS, ing their prime at the same time. who is in private practice at Min- central question With more surgical options available nesota Eye Consultants in Minne- than ever, more patients over the apolis, looks carefully at health his- for this group: age of 50 are fl ooding ophthalmol- tories. For example, increased risks ogy practices, seeking new ways to of early cataracts could raise second lens- or cornea- correct presbyopia and other re- thoughts about refractive surgery fractive errors.1 This growing trend for these patients. The following are based refractive has established a paradigm shift in such risk factors: history of smoking; surgery? preoperative planning. Increased diabetes; asthma; chronic bronchitis screening takes precedence over and cardiovascular disease. Inhaled promoting the benefits of LASIK, and oral corticosteroids, oral chlor- LASEK, Epi-LASIK, bladeless promazine and oral multivitamin/ LASIK, wavefront LASIK, PRK, mineral intake add to the risk.2 corneal inlays, implantable lenses He also aggressively treats dry-eye and clear lens exchange. disease before considering refractive “More than ever, we need to ask surgery. “Ocular surface disease is ourselves one simple question,” more common in the older patient,” says George Waring IV, MD, FACS, he notes. “It will get worse year by founder and medical director of the year, even after refractive surgery. Waring Vision Institute in Mount Helping patients understand this is Pleasant, South Carolina. “What important.” makes more sense–addressing the William D. Wiley, MD, medical cornea or the lens?” director, Cleveland Eye Clinic and In this report, experts discuss the Clear Choice LASIK Center, holds best answer to this question for a off on LASIK and SMILE in the variety of patient types. presence of contraindications com- monly found in the over-50 popula- Ruling Patients In or Out tion. “We won’t go through with it if a patient has keratoconus, age- Surgeons accustomed to routine related macular degeneration, cor- screening of younger patients need neal scars, early signs of cataract, to evaluate more factors when in- acute eye disease and other contra-

36 | Review of Ophthalmology | July 2019 This article has no commercial sponsorship.

0036_rp0719_f2.indd36_rp0719_f2.indd 3636 66/27/19/27/19 3:573:57 PMPM David R. Hardten, MD, FACS indications, such as unstable refrac- tive values, astigmatism over 5 D, suspicious corneal topography and thinner-than-average corneas.” Dr. Wiley emphasizes scrutinizing the lens, the progression of nuclear sclerosis, and the condition of the cornea. “The cornea might not be in the best shape for refractive sur- gery,” he notes. “They could have other conditions, such as Fuchs’ endothelial corneal dystrophy, Sal- This Pentacam scan shows moderate nuclear sclerosis, which should be closely evaluated zmann’s nodular degeneration, pte- along with other factors when deciding whether LASIK or other corneal procedures are worth performing on a patient over 50, say physicians. rygium and corneal stromal fi brosis. We need to get any disease under control before proceeding with re- helped the husband-and-wife surgi- these patients that this and other fractive surgery. Some may require cal team increase their percentage new advanced IOLs are currently chronic treatment. Others, such as of premium cataract-refractive cases being evaluated that might be able nodules, can be treated [before sur- from 30 percent to more than 75 to provide even better vision than gery], allowing us to stabilize the percent in recent years. Dr. Aker ex- IOLS that are currently approved. underlying condition and proceed plains that the femtosecond laser is Sometimes it’s best to wait. We feel with refractive surgery.” attractive to the over-50 set because, it’s important to share this option among other things, its precise, bl- with our patients.” “Younger Elderly Patients” adeless cutting minimizes postop- erative cornea issues and allows for The Refractive Gamble An increasing number of baby correction of corneal astigmatism. boomers and Generation X patients “For patients of this age who are Uncertainty can be a challenge want visual improvement that will interested in LASIK, we go into a when caring for these patients. help keep them gainfully employed, lengthy discussion of the impact of Some surgeons feel like they need attractive and vital well into their se- LASIK and cornea-based refractive a diagnostic crystal ball of sorts to nior years. By 2020, an estimated 1.4 surgery on their future cataract sur- determine if a refractive procedure billion people will turn presbyopic gery,” says Dr. Aker. “We explain after age 50 might actually be too across the world.3 And the number that following a LASIK procedure, close to a patient’s eventual cata- of patients in need of ophthalmic the calculations for the appropriate ract surgery. “These days, I do see care will increase markedly during IOL power can be more challeng- too many patients who have had re- the next 20 years, primarily because ing.” fractive surgery only a year or two of the aging of the U.S. population.4 Dr. Aker also informs over-50 before they come to us in need of Alan Aker, MD, who runs the patients seeking LASIK that, after cataract surgery,” says Dr. Aker. “It Aker-Kasten Eye Center with his some LASIK procedures, because would seem that lens-based refrac- wife, Ann Kasten, MD, in Boca of resulting spherical aberration, tive surgery would have been a bet- Raton, Florida, has always attracted they may not be good candidates for ter choice for them. First of all, lens- seniors in need of cataract surgery. some of the more advanced presby- based surgery spares the patient the Now, he has noticed increased de- opia-correcting implants. “We also expense of a LASIK procedure. In mand for “premium solutions with explain to these younger patients addition, it leaves the patient with a specific refractive outcomes” ex- presenting with minimal lens chang- pristine, untouched cornea, enabling pressed by “our younger elderly pa- es that youth and technology are on us to provide them with the best tients.” their side. We are currently involved possible outcome following cataract- He and Dr. Kasten offer lens- in an FDA study evaluating the in- refractive surgery with the appropri- based refractive procedures, and vestigational SC9 IOL produced by ate premium IOL.” they say they’ve achieved success the CORD Group LLC (Hammond, Dr. Hardten evaluates every fac- using the femtosecond laser. The ad- Louisiana). This is an extended- tor when deciding if a patient is too dition of the femtosecond laser has depth-of-focus IOL. We explain to close to needing cataract surgery.

July 2019 | reviewofophthalmology.com | 37

036_rp0719_f2.indd 37 6/27/19 3:57 PM 0036_rp0719_f2.indd 38 3 6 _ r p 0 7 1 9 _ f 2 38 points out. be avoidedbecauseofdryeye,”he sibly, ifacorneal approachshould if dry-eyetherapyisbestor, pos- breakup time.“We candetermine strument alsomeasurestear-film based proceduresarebest.Thein- determine ifcornea-basedorlens- by evaluatinglightscatter, helping which identifi lyzer (Visiometrics; Terrassa, Spain), history overtimeiscritical.” signifi enced amyopicshift,thatcanbe presbyopia. that beginbeforeandduring changes inthecrystallinelens possible onsetofcataractsand presbyopia, nuclearsclerosis, alone,” saysDr. Hardten. ing cornealrefractivesurgery needed tomakeitworthdo- fore cataractsurgeryislikely stay thesamelongenoughbe- out iftherefractiveerrorwill clear sclerosis,wetrytofi including theamountofnu- “When weanalyzethelens, hne, a Dri, D and MD, Durrie, Dan changes, In anattempttocharacterize these of thecrystallinelensover years. He hasevaluatedtheagingchanges tionality, accordingtoDr. Waring. cess, guidedbystagesofdysfunc- multifactorial decision-makingpro- cornea orcrystallinelensinvolvesa no answer.” health. It’s neveranautomaticyesor needs, cornealhealthandoverall picture analysisofthepatient’s visual decision ondiagnosticsandabig- according toDr. Wiley. “Ibasemy outside oftheeyeisajudgmentcall, correct apatient’s visioninsideor Inside Versus Outside . i n

d REVIEW Dr. Wiley alsousestheHDAna- “If thepatienthasexperi- Dr. Wiley assessesapatient’s Deciding whethertoaddressthe Deciding whethertosurgically d |

Feature

Review ofOphthalmology

3 cant factor,” headds.“Patient 8 essubclinicalcataracts

Refractive Surgery gure | July2019 50 which requires treatment before refractive surgery. ment membrane dystrophy, acommonfinding inpatientsover topography mapshowsThis corneal signsofepithelialbase- opia istheinsertionof donut- Stage II.” Stage IDLSand,inselectcases, detachment inpatientsover50 ogy andotherriskfactorsforretinal ope withperipheralretinalpathol- contact lenses“inthehighaxialmy- still utilizesLASIKorimplantable preventing cataracts.”Dr. Waring could occur. Simplystated,weare cataract, whenasecondintervention eventual degradationprocessintoa thermore, wearepreventingthe ity andmaintainbinocularity. Fur- scatter, improveretinalimagequal- can’t,” hesays.“We canreducelight improves visioninwaysLASIK ment inpatientswithStageIIDLS an insurance-basedprocedure. sponds withcataractsthatqualifyfor daily activities.Thisstagecorre- signifi and lightscatteremerge. increased higher-order aberrations with presbyopia. rigid andlessfl as follows: functional LensSyndrome,staged Dr. Waring suggestedthetermDys- Vision inOverlandPark,Kansas,and Jason E.Stahl,MD,bothofDurrie One surgicaloptionforpresby- “We havefoundthatlensreplace- Stage III: Stage II: Stage I: cant enoughtointerferewith Thelensbecomesmore Contrast sensitivityloss, Lensopacitiesarenow exible, corresponding tissue arealsobeingevaluated. genic cornealinlaysfrom opia eyedrops.Furthermore,allo- and excimerlasers,suchaspresby- treatments beyondlenstechnology a numberofemergingpresbyopia of upto2.5D.” nitely, offeringa fullrangeoffocus conceivably remaininthereindefi extend theintermediatevisionand -1 D,”hesays.“We inserttheinlayto plano andthenon-dominanteyefor “We cantargetthedominanteyefor with LASIKforpresbyopicpatients. near vision.” some extradistancewhileimproving -0.75, heorshecanadditionallygain a refractiveerrorofabout-0.5to says Dr. Hardten. “Ifthepatienthas emmetropic presbyopicpatients,” viding enhancedrangeoffocusfor 55 isthesweetspotforKamra,pro- the patient’s lensisclear, ages50to pocket inthenon-dominanteye.“If tients, we the time,”hesays.“Onyounger pa- approach tothecornealsurface. ways prompthimtotakeacautious says apatient’s olderagedoesn’t al- When AgeIsn’taFactor

Dr. Waring isalsoinvolvedwith Dr. Wiley combinesKamrainlays “We doLASIKandSMILEall Unlike somesurgeons,Dr. Wiley David R. Hardten, MD, FACS MD, Hardten, R. David via afemto-createdstromal minimum depthof200µm monocular implantationata of focus.It’s designedfor system toenhancedepth rays oflightintothevisual sion, allowingonlycentral effect toenhancenearvi- Kamra reliesonapinhole a 1.6-mmaperture.The 3.8 mmindiameterwith polyvinylidene fluoride,is The inlay, madeofadark in thefrontofcornea. Gen, Seattle)cornealinlay shaped Kamra(Cornea- know theyalsowillneed - 66/27/19 3:57 PM / 2 7 / 1 9

3 : 5 7

P M ProvenProven Stability.Stability. PredictablPredictablee PerfoPerformance.rmance

Optically Advanced1 | Rotationally Stable1 | Exceptional Outcomes1 Let’s be clear about enVista toric. enVistatoric.com • 800.338.2020

INDICATIONS: IIndidicated for primary implantationo ini the cac psular baag of the eye iin adult patieientsn for the visual correction of aphakkia in addult patientnts and corneal astigmatism folllowing removal of a cataraactous lens for immproved uncorrrected distance visionn. WARARNNINGS: Physiciana s considering lens immplap ntation in patit ente s withitt pre-exxisting condditioons, orri in the event of suurgiccala difficulultiees at the timme of catataractte extracaction, should wweight the poteential rrisk/ benefit ratio. Rotation of enVista® toric IOL awayy from ththe inntended axiss cancan reduce the assttigmgmatic correcte ion. Misalilignmenent greatere than 30° may iincrease poostoperattive rerefraccttive cylindder. PREP CAUCA TIOIONS: Do noot attttempt tot resterrilize this lens. Do not use if the packaging iss damagagede or if theh re are signsnsns ofof leeakagge. Do not store lensess at ttempem rattuures oveer 43°C (110°F) or lower than 0°C (3232°F). Doo notno reuuse thhe lens. Safetyty annd effectivveeness of the enVVista toric IOL have not been subbstantiated in patients with conditions and intraaoperative complications as outu lined in the enVistat toricc IOLIO Directions for Use. ADVERSE EVEVENTSS: As witht any surgiicacal procedure, risk is involved. Potentiala adverse events accomppanying cataraact oro implantt sursu gery may inccludude,e but are not limited to, the follol wing: corneal endotheh llial damage, infecction (endophthalmiitis), retinaldl detachmhment, vitritis, cystoid macular edema, corneeall edema, pupillary block, cyclitic memmbrane, iris prolappse,, hypopopyon,t, transieient or persistent glaucoma, acute corneaealdl dececompensation, toxic anterioro segment syndrome (TASS). Secondary surgical interventions innclude, butb aare not limited to: lens repopositiooningg, leens replacement, vitrtreoous asspiratatioion oor iridectotomym for pupillary block, wound leak repair, and retinal detachmeent reppaira . CAUTIU ON: Federal law restricts this device to sale by or on ththe order oof a physician. ATTENTIONON: This is not all you need to knowno . Pleeasee rer ferer to the Directionsns For Use labeling for a complete listing of indications, full risk and safety infnfoormation, clinical study information, etc. 1. enVVistis a toric Directions for Use. ®®/™ are trademaarksrk of Bauscch&h & Lombm IncIn orporated or its affiliffi ates. © 2018 Bausch & Lomb Incorporated. EVT.0026.USA.1818

RP0119_BL IOL.indd 1 12/20/18 10:07 AM 036_rp0719_f2.indd 40 40 category.” to highhyperopiawouldfallintothis Any presbyopicpatientwithmoderate sider lensreplacementforover+1D. lenses keepimproving,wemaycon- correction ashigh+4Dormore.As considered LASIKforpatientswitha intraocular lenstechnology. We once of theimprovementthat’s occurredin procedures becomelessviablebecause placement. LASIKandothercorneal correction istrendingtowardlensre- for them,”heconceded.“Hyperopia time. “Lensreplacementmaybebest may havelessrefractivestabilityover neal surfaceproceduresonhyperopes after it’s implanted.” tomized throughapoweradjustment approved IOLthatcanbecus- California), theonlyFDA- Lens (RxSight;AlisoViejo, usage oftheLightAdjustable looking forwardtoincreased do aclearlensexchange.Iam wants refractivecorrection,I aract extractionandheorshe year awayfromneedingacat- “If Iclearlyseeapatientis Wiley ishardlyanabsolutist. have thesamerisks.” 55-year-old, asIseeit.Both A 20-year-old isthesameasa cataract moval of the lenticule-shaped disc of moval ofthelenticule-shaped discof younger patients.With SMILE,re- characteristics arebettertolerated by 50. SomeofLASIK’s biomechanical cially advantageousforpatientsover and minimizesdryeye,whichisespe- sive, doesn’t severthecornealnerves, tients,” henotes.“SMILEislessinva- cornea strong,whichhelpsthesepa- ing ofthecornealtissuemakes for patientsover50. SMILE proceduremorefrequently More SMILESforOlderPatients Dr. Wiley hasalsofoundthatcor- Like manysurgeons,Dr. “The naturallyoccurringcross-link- Dr. Wiley hasstartedusingthe REVIEW |

Feature Review ofOphthalmology surgery at some point. surgery atsomepoint.

Refractive Surgery | July2019 patient’s nearvision. created pocket inthenon-dominanteye inorder toimprove a The Kamra inlayisplacedinafemtosecond- intracorneal Clear LensExchange sion youprovidethepatient,however, and visualquality. Themorenearvi- halos, andnotasmuchlossof contrast “Patients experiencelessglare,fewer add lensesofthepast,”saysDr. Wiley, create thesideeffectsofhigher tifocal IOL. sign fortheAcrySofIQReSTORmul- by Alcon’s newActivefocusopticalde- uses theTecnis lensesandisimpressed patient,” Dr. Hardtensays. modation, especiallyinthehyperopic replacement toaddresslackofaccom- candidate forsurgery, Iconsiderlens options,” hesays. focus, alloftheselensescanbegood patient’s desiredsecondnearpointof +3.25 Dor+4D.“Dependingonthe Tecnis multifocalIOLsfor+2.75D, the AcrySof.Dr. Hardtenfavorsthe technology suchastheSymfonyand eye morebecauseofadvancedlens correcting refractiveerrorinsidethe lent of-8.25D.” manifest refractionsphericalequiva- have 3Dofastigmatismorlessanda 50 whoarebetween-2and-8D patient. IuseSMILEonpatientsover tissue islesstraumaticfortheolder “The lowaddpowerlensesdon’t For lensreplacement,Dr. Wiley also “For anolderpatientwhoisagood Like Dr. Wiley, manysurgeonsare tients’ visualexperiences.” far orfornear, dependingonthepa- Offer theBest report norelevantfi RxSight. Drs.HardtenandWaring ceives researchcompensationfrom J&J Vision, AlconandZeiss,re- Dr. Wiley consultsforCorneaGen, cal MonitorfortheCORDGroup. & Lomb.HealsoservesasMedi- son &JohnsonVision andBausch geons.” opportunity forthesepatientsandsur- creates atimeofgreatexcitementand all ofthenewtechnology. Overall,it the testandkeepsusonourtoeswith notes. “Itputsourdiagnosticskillsto and moreoptionstoofferthem,”he to grow. “We willhavemorepatients over-50 population,sinceit continues the needtobemorefl Wiley andothersurgeonsemphasize inside theeyeoroncornea,Dr. States. Arch Ophthalmol2004;122:4:477-85. prevalence ofvisualimpairmentamongadults intheUnited 4. CongdonN, O’ColmainB, CC, Klaver etal. Causesand 2015;122:8:1706-10. Ophthalmology potential productivitylossfromuncorrected presbyopia. 3.Frick KD, SM, Joy Wilson DA, etal. The globalburdenof 2013:91: 5:395-405. 2012Jun20. and preventioninEurope: review. aliterature Acta Ophthalmol. 2. ProkofyevaE, Wegener A, ZrennerE. prevalence Cataract Ophthalmol. 2016;2016:5263870. Epub2016Mar9. inpseudophakicpatients. andtheir application J therapies 1.Paley GL, ChuckRS, Tsai LM. Corneal-basedsurgicalpresbyopic

Dr. AkerisaspeakerforJohn- Whether you’redoingaprocedure Majid Moshirfar, MD Moshirfar, Majid with a power suited more for with apowersuitedmorefor correct lensfortheothereye, them returnandputinthe one tothreeweeks,thenhave one lens,letthemdrivefor reduce sideeffects.Iwilldo issue withlessnearpowerto effects. Sowewilladdressthat driving mightcreateadverse want,’” saysDr. Wiley. “Night near visionisn’t quitewhatI “The patientmightsay, ‘my by varyingthelenspowers. fi the highersideeffectpro- le will be.” le willbe.” He addressestheseissues nancial interests. exible with the the with exible 6/27/19 3:58 PM There’s used. And there’s ÕİļõţÕÑ|İÕʴcŖčÕÑʣ Unlimited peace-of-mind with high-qualityuality performance

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RP0719_Lombart.indd 1 6/13/19 4:54 PM Ocular Trauma REVIEW Feature Tips for Treating Ocular Trauma

Michelle Stephenson, Contributing Editor

Generally, the type hough conditions like age- went through his lower eyelid, through related macular degeneration his eyeball, and through his upper eye- of injury—globe Tand glaucoma are scourges lid all in one millisecond. Another guy upon patients and doctors, nothing was exercising at a gym using a bun- laceration vs. robs patients of vision as suddenly or gee cord apparatus. He was sitting in shockingly as ocular trauma. To make the rowing position, holding the two blunt trauma— matters worse, trauma cases often rubber straps away from the wall ap- have to be evaluated under duress, paratus, and somehow both bungee will dictate the sometimes with a tight time window cord hooks came loose at exactly the in order to avoid further damage. In same time. They hit him in both of his outcome. this article, experts outline how to eyes simultaneously. He went from a deal with these cases. high-functioning executive to being basically blind in both eyes.” A Range of Injuries Blunt trauma is also common. In- juries include fi st injuries, racquetball Ocular trauma is relatively common. injuries or just getting hit in the eye According to Thomas John, MD, who with a cabinet door or table edge. is in practice in Chicago, there are There are also projectile injuries, more than 2.4 million eye injuries in such as fl ying glass during automobile the United States annually. “Ninety accidents, and gunshot wounds. “A lot percent of these are preventable, and of people try to kill themselves by put- more than 20,000 eye injuries occur in ting a gun up to the side of their tem- the workplace,” he says. ple,” Dr. Miller says. “When they pull Kevin M. Miller, MD, who is in the trigger, the bullet goes through practice in Los Angeles, says that he both eyes, but doesn’t kill them. There sees bungee cord injuries more than are quite a variety of injuries.” any other injury. “They are incredibly He says that people who suffer common,” he says. “One of my pa- ocular injuries rarely lose their sight tients had taken his boat out of the wa- or their eye. “In the majority of open ter and put it on a trailer. He and an- globe injuries, people retain vision,” other person were securing a tarp over Dr. Miller says. “It may not be the the boat, when a bungee cord came greatest vision, however. It depends on loose. The cord came fl ying under the how badly damaged the retina is. They boat and around to the side where he might end up going through a couple was standing. The metal hook portion of years of reconstructing the ante-

42 | Review of Ophthalmology | July 2019 This article has no commercial sponsorship.

0042_rp0719_f4.indd42_rp0719_f4.indd 4242 66/28/19/28/19 12:0212:02 PMPM rior segment of the eye. The surgeon All images: Darren Gregory, MD might have to do a corneal transplant, implant a glaucoma tube device, and/ or implant an artifi cial iris. But, if the retina comes through okay, they can actually maintain pretty good vision.”

Assessing the Injury

The fi rst step with any type of ocular injury is to determine the mechanism of injury, if possible. “Sometimes, the Figure 1. A massive subconjunctival Figure 2. A large circumferential rupture of patient knows exactly what happened,” hemorrhage in a 30-year-old following an the superior sclera 3 mm posterior to the says Darren Gregory, MD, who is in assault (the amount of hemorrhaging is limbus in the same patient. practice in Aurora, Colorado. “Some- very suggestive of a globe rupture even times, it’s the middle of the night, the though there is no visible rupture). patient’s drunk, and you can’t get a good story. They know they were beat- en up, but they don’t know what they were hit with.” The next step is to evaluate the extent of the injury. A computed tomography scan can be performed very quickly in the ER. “This can show you details about what’s going on in the eye,” ex- plains Uday Devgan, MD, who is in practice in Los Angeles and teaches UCLA ophthalmology residents at Ol- ive View-UCLA Medical Center. “You Figure 3. The suture repair of the patient’s Figure 4. The same eye following closure can have a ruptured globe and the lids laceration. of the conjunctiva over the scleral defect. are so swollen and the [patient’s eye] so The patient had a retinal detachment that tender, it’s hard to examine him or her. recommends fi rst checking a patient’s was repaired a week later, but vision only But a CT scan will tell you if any of the vision. “Then, you can examine the recovered to the 20/200 range. orbital bones are broken. It can tell you front of the eye and the lid to make if there’s a posterior rupture. The eye sure there are no signifi cant issues or plugs up the leak, the iris can plug up is like a round ball, but if somebody lacerations there,” he says. “A slit-lamp an anterior segment leak or rupture,” hits the front of the eye really bluntly, microscope can be used to look at the he says. “If the eye has a rupture, the like with a knuckle, it may blow out the front of the eye. It’s important to know iris will be peaked and pointed toward back of the globe. So, you can have a where the eye typically ruptures and the area of the rupture. If possible, get posterior rupture, which can easily be look there. For example, one of the a view of the back of the eye. If the eye seen on a CT scan. A CT scan can also places is where the extraocular muscles is full of blood, a B scan ultrasound can show you if there is a retained intra- attach to the sclera. The sclera tends to be used to look back there, as well.” ocular foreign body.” be a little thinner there and can rip Dr. Miller adds that it can often be It’s important to get both an axial in those areas. If the patient has had difficult to assess a patient’s ocular scan and a direct coronal scan. “Make cataract surgery, the eye can rupture at trauma immediately after an accident sure the slices are thin enough. If you the site of the phaco incisions, even if because he or she may have injuries only get scans every 5 mm, you’ll miss it’s 10 or more years later.” to other parts of the body that are also a lot of details. You want somewhere in Dr. Devgan also recommends exam- being evaluated. the 1 to 2 mm range for the slices,” Dr. ining the iris, which has the ability to Devgan says. plug up a leak. “Much like when you An Intact Globe After the CT scans, the patient can have a stab wound or a bullet wound be examined clinically. Dr. Devgan in your abdomen and the omentum Treatment can typically be delayed

July 2019 | reviewofophthalmology.com | 43

042_rp0719_f4.indd 43 6/28/19 12:02 PM Feature Ocular Trauma REVIEW

if the patient has an intact globe. “It back in a few days or weeks and fix often doesn’t require immediate sur- the traumatic cataract or retinal de- gery that day or night,” Dr. Devgan ex- tachment. “During the initial surgery, plains. “With anterior segment trauma our goal is to remove any intraocular that’s not rupturing, you’ll typically see foreign body and close the globe,” he damage to the iris and lens. Posterior adds. “If we can fi x other damage at the trauma can include damage to the reti- same time, we will, but it depends on na, the choroid, and the other layers of the severity of the trauma.” the posterior segment, as well. Those usually can be fixed a little bit later; Chemical Burns [the repair] doesn’t have to happen right away.” Fifteen percent of eye injuries are Figure 5. A 9-year-old boy who was stabbed in the eye with a pencil. The a result of burns. “With chemical in- A Ruptured Globe suture repair of the corneal laceration is juries, alkali is the worst because it shown. There was also violation of the lens can penetrate the ocular structures A ruptured globe is a severe injury. capsule. A cataract and elevated IOP soon much faster than acid,” notes Dr. John. It’s sight-threatening, and there is the developed. The cataract was removed three “Alkali rapidly disrupts the cell mem- potential that the patient could lose the to four weeks following the initial injury. branes and penetrates into the tissues. eye. “Patients with ruptured globes, Due to iris and zonular damage, the patient Acid is usually less damaging due to such as those who have been in a car was left aphakic, but he has achieved the binding and buffering of the acid 20/30 vision with a soft contact lens. This crash, may also have severe head and/ by the corneal protein. When that hap- and the Case on p. 47 show how the visual or brain trauma,” Dr. Devgan says. prognosis with a globe laceration from a pens, the coagulated tissue can act as “When you’re called to the ER to see sharp object is generally better than with a a barrier and prevent further penetra- a patient with a ruptured globe, you globe rupture from blunt trauma. tion. The most important thing is to must determine the extent of the trau- irrigate as soon as possible.” ma. Is it limited to the eye and the ruptured globe, there is a lifetime risk Chemical ocular injuries can range orbit, or does it also involve other body of sympathetic ophthalmia. “Because from very mild to very serious. “In parts? With the brain particularly, it of the rupture, some of the antigens Grade 1, the injury is very superfi cial,” can be life-threatening.” that are present in the eye, which are Dr. John explains. “With such minor Besides car accidents, ruptured normally never seen by the immune injuries, there is little ischemia, and the globes are typically the result of assault system, are now presented to the im- cornea is completely clear. With Grade or industrial accidents. “Then, there’s mune system,” Dr. Devgan says. “The 2, there is minor corneal haze and lo- the wild card: Every July 4th, we get immune system can attack not only calized focal limbal ischemia. In Grade patients with combined hand and eye the bad eye, but the good eye, months 3, there is pronounced corneal haze, injuries,” Dr. Devgan says. “They light or even years later. Because this is a and the view of the anterior chamber up their fi rework and if it doesn’t work, lifetime risk once you have a ruptured is compromised. There is significant they pick it up and look at it, and it goes globe, it has to be in the consent form ischemia of the limbus. The worst is off in their hand toward their face.” for the procedure to repair the rup- Grade 4, where the cornea is opaque Ocular trauma with a ruptured globe tured globe. It’s critical for the patient and porcelainized. It’s extremely prone is less frequently seen in private prac- to know that it’s very diffi cult to return to melting in the acute or intermediate tice, according to Dr. Devgan. “I’ve an eye that has suffered a ruptured time frames after injury. Depending been in practice 20 years, and I’ve seen globe back to normal. The goal is just on the extent of the injury, the visual one ruptured globe in my private sub- to close the globe today, not to restore loss can be mild, or there can be total specialty clinic,” he says. “At the coun- sight. In fact, this patient may never loss of vision.” ty hospital where we do our residency get useful sight back out of the eye. training, we see at least one ruptured There’s always the risk that you may Enucleation of the Eye globe a week. On July 4th weekend, lose the whole eye. We must manage it will probably be two or three. One expectations and paint a realistic pic- Surgeons typically don’t perform a year, we had six in one weekend.” ture before performing surgery.” primary enucleation of the eye im- When treating these patients, ex- Especially if it’s in the middle of the mediately after the injury. “We usually perts say it’s important to manage pa- night, the goal is just to close the eye. try to let patients come to terms with tient expectations. If a patient has a Dr. Devgan says the surgeon can come the severity of their injury,” says Dr.

44 | Review of Ophthalmology | July 2019

042_rp0719_f4.indd 44 6/28/19 12:02 PM Cover Refractive Surprises

REVIEW Story

Gregory. “If they have a blind, painful eye or a severely dis- (Continued from page 34) fi gured eye, they may choose to have it removed. However, that’s usually diffi cult psychologically. And it’s surprising how simulate the adjustment fi rst to make sure I’m not doing many cases that look almost hopeless end up with more vi- unnecessary surgery. sion than you initially anticipated.” “We do a fair number of those simulations,” he adds. He believes that it’s best to close the hole as well as you • Take the age of the patient into account. “I would can to stabilize the eye, “let the dust settle” a little bit, and definitely perform a refractive correction on younger monitor for signs of infection or problems with the intra- patients in their 40s and 50s,” notes Dr. Trattler. “Those ocular pressure either being too high or too low. “If the eye patients have very high expectations, so if we’re off-target begins to stabilize, then you can start looking at repairing the with one of these patients, we follow our process. We damage that’s occurred inside the eye, whether it’s removal treat their dry eye, perform the YAG capsulotomy, then of vitreous hemorrhage and repair of a retinal detachment undergo a contact lens trial, and fi nally perform the re- or replacement of the lens,” Dr. Gregory says. “Especially fractive enhancement. As far as which option to use for with ruptures from blunt trauma there’s often prolapse of the adjustment, younger patients are eligible for all of the the lens out of the eye, whether it’s an artifi cial lens or a options; any of them are appropriate.” natural lens. If it ruptures anteriorly, there’s often damage Dr. Berdahl notes that—for better or worse—older to the iris and the pupil, which may require some repair at a patients seem more willing to accept imperfection than later date, as well.” younger patients. “In general, I fi nd that older patients are easier to work with than younger patients,” he says. The Million Dollar Eye “They’ve had a number of procedures over the course of their lives, and not all of them have turned out perfectly. When a patient has undergone ocular trauma in one eye, As a result, they’re more willing to accept imperfection it’s important to turn your attention to the fellow eye. “There than younger patients who haven’t been through multiple is the concept of the million dollar eye and the hundred dol- diagnoses and medical treatments.” lar eye,” Dr. Devgan says. “The eye that’s already severely damaged is the hundred dollar eye, and the better eye is the It’s All Good million dollar eye. You don’t want to lose a good eye, right? So, the million dollar eye should not be neglected. For ex- Surgeons note that the good thing about most instances ample, if a patient has a ruptured globe from grinding metal, of refractive surprise is that multiple corrective options a little fragment of metal could be in the fellow eye without will work, giving the surgeon some leeway. us knowing it. So, you have to examine what you think is the “The good news is that all of the technologies available non-traumatized eye in great detail, as well.” to us—IOL exchange, piggyback lens and laser refractive Dr. Devgan says the number one risk factor for a ruptured surgery—can be used in almost any refractive-surprise globe is a previous ruptured globe, because the patient may situation,” says Dr. Trattler. “So although I have my own continue to do the high-risk activities that caused the injury preferences, I wouldn’t fault someone who has a different the fi rst time. “Let’s say you’re a gardener and there are tree preference. If a surgeon wants to use a piggyback lens branches on the left side of your face, but you’ve lost vision on a -2-D patient, that’s OK. If you want to do PRK on a in your left eye and can’t see them,” he says. “You turn your +1.5-D patient, that could also work. It’s not like anything head, and the branches poke you in the good eye. This is is set in stone. The bottom line is that we’re using a vari- why people with a ruptured globe need to be in protective ety of technologies and procedures to make our patients glasses and have monocular precautions for the rest of their happy.” lives. If the patient feels that it looks goofy to wear safety goggles every day, we can even place polycarbonate lenses Dr. Trattler has consulted for VISX, Johnson & Johnson in Ray-Ban frames, so the patient will look cool while being Vision, ORCA Surgical and Bausch + Lomb. Dr. Ber- protected.” dahl has consulted for Astigmatismfi x, Alcon, Johnson & Though dealing with an ocular injury demands a lot Johnson Vision, Bausch + Lomb and RxSight. Drs. Lee from the clinician and surgeon, physicians say that moving and Ouano report no fi nancial ties to any product dis- quickly—but not rushing—and taking a logical approach cussed.

can often lead to the best possible outcomes. 1. Behndig A, Montan P, Stenevi U, Kugelberg M, Zetterström C, Lundström M. Aiming for emmetropia after cataract surgery: Swedish National Cataract Register study. J Cataract Refract Surg 2012;38:7:1181-6. None of the physicians interviewed have any fi nancial 2. Fernández-Buenaga R, Alió JL, Ardoy ALP, et al. Resolving refractive error after cataract surgery: interest to disclose. IOL exchange, piggyback lens, or LASIK. J Refract Surg 2013;29:10:676-683.

July 2019 | reviewofophthalmology.com | 45

0042_rp0719_f4.indd42_rp0719_f4.indd 4545 66/28/19/28/19 12:0312:03 PMPM Monthly MACKOOL ONLINE CME CME SERIES | SURGICAL VIDEOS

MackoolOnlineCME.com MONTHLY Video Series We are excited to continue into our fourth year of Mackool Online CME. With the generous support of several ophthalmic companies, I am honored to have our To view CME video viewers join me in the operating room as I demonstrate go to: the technology and techniques that I have found to be www.MackoolOnlineCME.com most valuable, and that I hope are helpful to many of my colleagues. We continue to edit the videos only to either change camera perspective or to reduce down time – allowing you to observe every step of the procedure. Richard J. Mackool, MD Episode 43: As before, one new surgical video will be released monthly, “Modifi ed Yamane Technique” and physicians may earn CME credits or just observe the case. New viewers Surgical Video by: are able to obtain additional CME credit by reviewing previous videos that are Richard J. Mackool, MD located in our archives. I thank the many surgeons who have told us that they have found our CME program to be interesting and instructive; I appreciate your comments, Video Overview: suggestions and questions. Thanks again for joining us on Mackool Online CME. In one of our most requested videos, I use a modifi ed Yamane technique for scleral fi xation of CME Accredited Surgical Training Videos Now a posterior chamber IOL. Available Online: www.MackoolOnlineCME.com

Richard Mackool, MD, a world renowned anterior segment ophthalmic microsurgeon, has assembled a web-based video collection of surgical cases that encompass both routine and challenging cases, demonstrating both familiar and potentially unfamiliar surgical techniques using a variety of instrumentation and settings. This educational activity aims to present a series of Dr. Mackool’s surgical videos, carefully selected to address the specifi c learning objectives of this activity, with the goal of making surgical training available as needed online for surgeons motivated to improve or expand their surgical repertoire. Learning Objective: After completion of this educational activity, participants should be able to: • employ techniques that simplify scleral fi xation of a posterior chamber lens (Yamane technique)

Satisfactory Completion - Learners must pass a post-test and complete an evaluation form to receive a certifi cate of completion. You must listen to/view the entire video as partial credit is not available. If you are seeking continuing education credit for a specialty not listed below, it is your responsibility to contact your licensing/certifi cation board to determine course eligibility for your licensing/certifi cation requirement.

Physicians - In support of improving patient care, this activity has been planned and implemented by Amedco LLC and Postgraduate Healthcare Education. Amedco LLC is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team

JOINTLY ACCREDITED PROVIDERTM Credit Designation Statement - Amedco designates this enduring material activity for a maximum of .25 AMA PRA Category 1 INTERPROFESSIONAL CONTINUING EDUCATION CreditsTM. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Additionally Supported by: Endorsed by: Jointly provided by: Supported by an unrestricted independent Glaukos In Kind Support: Review of Ophthalmology® medical educational grant from: MST Sony Healthcare Video and Web Production by: REG & (Review Education Group) Alcon Crestpoint Management Solutions JR Snowdon, Inc Carl Zeiss Meditec Research Review REVIEW

The Ischemic Index In CRVO Cases

n a single-center, retrospective emic CRVO in the one-year follow- bleeding disorders, and/or history of Icohort study of 60 treatment-naïve up timeframe. The researchers also trauma or surgery to the nondominant central retinal vein occlusion patients, found that eyes with an IsI ≥35 per- hand. The primary outcome was rest- researchers sought to understand the cent were 100 times as likely to be ing capillary blood fl ow at the nailfold relationship between baseline isch- classified as ischemic and six times of the fourth digit of the nondominant emic index (IsI) values calculated with as likely to have fi nal acuity of 20/200 hand in patients with XFG, NTG, ultra-widefi eld fl uorescein angiogra- or worse in the fi rst year of follow-up HTG and controls, using nailfold cap- phy (UWFFA) and classifi cation as an compared to eyes with an IsI <35 per- illaroscopy. ischemic CRVO. cent. Observed differences in vision Ultimately, two participants were Researchers identified 60 eyes of were attributed in part to a greater exluded due to poor nailfold image 60 patients who were diagnosed with prevalence of ischemic maculopathy quality, leaving 109 patients for the fi - a CRVO between 2009 and 2016. and foveal avascular zone enlarge- nal analysis. Sixty-two participants (57 The criteria for an ischemic CRVO ment in eyes with an IsI ≥35 percent. percent) were women and 79 (72 per- included having an afferent pupillary Retina 2019;39:6:1033-8. cent) were white. The average age of defect and counting fi ngers vision or Thomas AS, Thomas MK, Finn AP, Fekrat S. the participants was 67.9 ±11.7 years. worse and/or neovascularization not Mean resting peripheral cap- attributable to another disease. Lo- Nailfold Capillary Blood Flow illary blood flow at the nailfold for gistic regression was used to evaluate And Exfoliation Glaucoma controls was 70.9 ±52.4 picoliters/s the relationship between IsI and the Researchers from New York, Bos- (pL/s); HTG: 47.5 ±41.9 pL/s; NTG: clinical outcomes. ton and Chiang Mai, Thailand, say 40.1 ±16.6 pL/s; and XFG: 30.6 ±20 The study found that patients with that, since analyzing patients’ blood pL/s. Multivariable analysis of the dif- an IsI ≥35 percent were signifi cantly fl ow using nailfold capillaroscopy has ferences of flow in HTG vs control more likely to become ischemic dur- demonstrated alterations associated participants showed values of -18.97 ing the first year of follow-up than with high-tension glaucoma and nor- (95% CI, -39.22 to 1.27; p=0.07) pL/s, those with an IsI <35 percent (83.3 mal-tension glaucoma, it’s possible NTG vs. controls of -25.17 (95% CI, versus 13.9 percent, odds ratio 111, that exfoliation glaucoma may also -45.92 to -4.41; p=0.02) pL/s, and p<0.00001). In eyes with an IsI ≥35 cause such changes. They undertook a XFG vs. controls of -28.99 (95% CI, percent, baseline and fi nal logarithm study to try to fi nd a connection. -51.35 to -6.63; p=0.01) pL/s. of the minimum angle of resolution The cross-sectional, clinic-based The researchers say the study hints (logMAR) acuity were worse than study was carried out at the New York at the systemic nature of glaucoma, those with IsI <35 percent (1.18 [a Eye and Ear Infi rmary of Mount Sinai since the resting peripheral capillary little better than 20/400] versus 0.46 from July 6, 2017, to May 18, 2018. blood fl ow decreased in patients with [a little worse than 20/50], p<0.001 The researchers studied 111 patients exfoliation and normal-tension glau- and 1.26 versus 0.45, p<0.001). (30 XFG, 30 NTG, 30 HTG, and 21 coma. For eyes with IsI ≥35 percent, the controls). Exclusion criteria were the JAMA Ophthalmol 2019;137:6:618- researchers calculated a 50-percent presence of connective tissue dis- 625. Kertes PJ, Galic IJ, Greve M, et al. FUS and the Rubella Virus- probability of classification as isch- ease, uncontrolled diabetes, history of Associated Uveitis

This article has no commercial sponsorship. July 2019 | reviewofophthalmology.com | 47

0047_rp0719_rr.indd47_rp0719_rr.indd 4747 66/28/19/28/19 3:243:24 PMPM Research

REVIEW Review

Groen-Hakan F, Van de Laar S, Van der Eijk-Baltissen A, Ten Dam- FUS and Rubella Virus- Van Loon N, De Boer J, Rothova A. The researchers concluded that these Associated Uveitis monthly maintenance procedures can Researchers in the Netherlands Survivor: Goldmann Tonometer save time and money. sought to investigate and expand Because calibration error (CE) is J Glaucoma 2019;28:6:507-11 Choudhari NS, Richhariya A, Wadke V, Deshmukh SP, George R, knowledge of ocular manifestations one of the most common sources of Senthil S, Sekhar GC. and complications of RV-associated error for Goldmann applanation to- uveitis and to demonstrate its relation nometers, researchers implemented to rubella vaccination and Fuchs uve- a preventative maintenance program Restrictive Strabismus After itis syndrome. for 190 tonometers to measure sur- Pterygium Excision A retrospective study of 144 eyes vival rates and report maintenance Researchers from San Diego and of 127 uveitis patients RV-positive in outcomes. the Tel Aviv, Israel, conducted a study aqueous humor analysis was carried The prospective cohort study was to report characteristics of restrictive out. Patients were chosen from be- carried out at two tertiary eye care re- strabismus and diplopia development tween January 2010 and October 2016. ferral centers on slit-lamp-mounted in patients following pterygium exci- The average age at presentation was GATs (Model AT 900 C/M; Haag-Stre- sion and approaches to treating post- 37, and no cystoid macular edema was it). The maintenance program consist- operative restrictive strabismus. encountered preoperatively. None of ed of monthly testing by ophthalmolo- The retrospective interventional the patients was vaccinated against RV. gists for one year. Reported repairs case series was carried out at a single Uveitis was classifi ed mainly as anteri- were fi xed within 24 hours. Only CE academic institution on 15 patients or uveitis or panuveitis, despite vitritis at the clinically signifi cant level of 20 (mean age 49) who developed restric- in 103 (81 percent) patients. mmHg was reported. tive diplopia after pterygium excision. During the study, cataracts affected Acceptable CE level was deemed ±2 Inclusion criteria for diplopia on pre- 67 percent of patients and five eyes mmHg at all levels of testing. Instru- sentation was a history of ≥1 pteryg- presented with glaucoma at the end ments were considered faulty if the ium excision procedures before pre- of follow-up. Thirty-nine patients pre- CE exceeded this limit at any testing sentation of diplopia. Cases of diplopia sented with complete FUS phenotype, level. Failure was defined as having due to other reasons were excluded. with 37 testing positive for RV (95 developed an unacceptable CE be- The researchers report that all pa- percent) and two patients (5 percent) yond the third repair. The outcome tients had an esotropia after excision of testing negative. No alternative cause measures included frequency of CE pterygium, which caused the diplopia. of uveitis was found in the two RV- and the survival rate of the tonometer. The mean time for diplopia onset after negative FUS patients. Sixty-three tonometers (33.1 per- the last surgery was six months. The researchers conclude that RV- cent) needed more than one repair. A combined procedure to remove associated uveitis and FUS aren’t ex- The remaining 127 instruments (66.8 scar tissue formation and improve dip- changeable. RV-associated uveitis has percent) required no repairs. Of the lopia was performed by a strabismolo- a wider spectrum of clinical signs than GATs requiring repair, 49 (77.7 per- gist and an oculoplastic surgeon. Am- typical features of FUS phenotype. cent) needed one repair, five (7.9 niotic membrane grafts secured with This study supports the finding that percent) needed two repairs, two (3.1 sutures rather than fi brin glue were FUS is mostly caused by RV in Eu- percent) required three and seven used on all 15 patients. At 24 months rope. However, the researchers note (11.1 percent) developed unaccept- of follow-up, only two patients re- that FUS has other causes such as able CE after the third repair and were quired surgical intervention, which CMV, T. gondii, and trauma, and not removed from the program. led the researchers to believe that all RV-associated uveitis cases exhibit Among tonometers requiring one securing AMGs with sutures was less classical features of FUS. In this study, CE repair, the survival rate was 100 inflammatory than glue, though no RV occurred in the aqueous humor of percent. For those requiring more direct comparison was done. nearly all FUS patients, but RV pre- than one repair, the survival rate was Given the frequency of pterygium sented as FUS only in a minority. 0.64 after three months, dropping to excision and AMG placement with The researchers say that with cor- 0.40 at the end of the study. The main- glue, the researchers say that it’s im- rect diagnosis of RV-associated uveitis tenance program didn’t halt the de- portant to be aware of the possibility patients can avoid unnecessary immu- cline of units requiring maintenance, of postoperative restrictive strabismus nosuppressive therapies and cortico- and the researchers reported that the and its correction potential. steroids. number of repairs rather than the Am J Ophthalmol 2019;202:6-14 Am J Ophthalmol 2019;202:37-46 age of the unit determined survival. Baxter S, Nguyen B, Kinori M, Kikkawa D, Robbins SL, Granet DB.

48 | Review of Ophthalmology | July 2019

0047_rp0719_rr.indd47_rp0719_rr.indd 4848 66/28/19/28/19 3:563:56 PMPM The Rick Bay Foundation for Excellence in Eyecare Education www.rickbayfoundation.org Support the Education of Future Healthcare & Eyecare Professionals

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2015_rickbay_housead.indd 1 7/5/17 3:00 PM Retinal Insider

REVIEW Edited by Carl Regillo, MD, and Yoshihiro Yonekawa, MD

Clinical Pearls for a New Condition Pentosan polysulfate therapy, a common treatment for interstitial cystitis, has been associated with a maculopathy.

Adam M. Hanif, MD, and Nieraj Jain, MD, Atlanta

odern imaging and the relative Table 1: Consolidated Clinical Observations Mease of genetic testing have en- abled ophthalmologists to take great Median Age: 60 years (range: 37 to 79 years) strides forward. As these advance- Median Duration of PPS Intake: 14.5 years (range: 3 to 22 years) ments heighten diagnostic preci- Common Presenting Symptoms: Blurred vision while reading (48.6 percent) Prolonged dark adaptation (48.6 percent) sion, physicians are becoming better Metamorphopsia (11.4 percent) equipped to detect novel pathology. Median Duration of Visual Symptoms: 4 years (range: 1 to 9 years) We recently identifi ed a unique pig- Median Visual Acuity: OU: 20/25 mentary maculopathy in a cohort of OD Range: 20/20 to 20/300 patients who were receiving chronic OS Range: 20/15 to 20/400 pentosan polysulfate sodium therapy Data documented in a series of 35 confi rmed cases of PPS-associated maculopathy.12 (Elmiron, Janssen Pharmaceuticals, Titusville, New Jersey), a popular and pelvis that predominately affects unique macular pigment changes ob- medication for interstitial cystitis.1 females, manifesting with urinary ur- served in six patients receiving chronic Upon presentation to our clinic, these gency and dyspareunia.2 More than therapy for IC with oral PPS.1 Patients patients carried tentative diagnoses, 1 million people in the United States primarily identifi ed symptoms of blur- including age-related macular degen- are estimated to be affected by this ry vision and prolonged dark adapta- eration and pattern dystrophy. Our condition, which can also disrupt sleep tion. On dilated fundus exam, these subsequent investigations of this novel and lead to emotional stress.3 There patients exhibited subtle macular pig- phenotype are suggestive of a prevent- are only two FDA-approved therapies mentary changes, yet fundus autofl uo- able, vision-threatening medication for IC: intravesical dimethyl sulfoxide rescence and near infrared refl ectance

toxicity that could masquerade as other and oral pentosan polysulfate sodium.4 imaging of the posterior pole revealed known maculopathies. Here, we offer PPS is a semi-synthetic analogue of a striking pattern of abnormalities. a clinician’s primer on what is known biologic glycosaminoglycans, thought Despite a thorough review of medi- about this condition and how to avoid to act by binding to the bladder’s epi- cal history and comprehensive mo- missing it in the at-risk patient. thelial lining, regulating irritation and lecular testing, no known acquired cellular permeability.5-9 Although it has or inherited etiology accounted for Background been widely prescribed for decades, these fi ndings. This series presented no known ocular toxicity had previ- to us compelling evidence of a previ- Interstitial cystitis is a chronic re- ously been reported.10 ously unrecognized medication toxic- gional pain syndrome of the bladder In a 2018 report, we described ity, necessitating further investigation

50 | Review of Ophthalmology | July 2019 This article has no commercial sponsorship.

050_rp0719_retina.indd 50 6/28/19 11:35 AM of causality and phenotype. AB Investigation of Causality

Our subsequent investigations demonstrated that this unique macu- lopathy is strongly associated with chronic PPS exposure, not IC itself or its other therapies. In fact, this characteristic maculopathy has, to date, been exclusively diagnosed in patients reporting prior PPS expo- sure. To draw this conclusion, we C conducted a retrospective, cross- sectional study at our institution to evaluate risk factors for development of the maculopathy.11 All patients of the Emory Eye Center who had been diagnosed with IC within a four-year Figure 1: Representative images of a patient with PPS-associated maculopathy. period were included in the study. A. Color fundus photography reveals paracentral hyperpigmented spots and yellowish The medical charts and pharmacy subretinal deposits. The hyperpigmented spots appear to be an early manifestation of the condition; they are often absent in late, atrophic disease. B. Fundus autofl uorescence records of these patients were re- imaging reveals striking AF abnormality, with a fairly well-circumscribed, central patch of viewed for documentation of ex- hyper- and hypoautofl uorescent spots. C. Optical coherence tomography imaging reveals posure to IC therapies, including focal nodules of hyperrefl ectance at the level of the RPE, found to co-localize with hyper- PPS, hydroxyzine, tricyclic antide- pigmented spots. pressants, gabapentin, pregabalin, cyclobenzaprine, methenamine, for this grouping of patients was 2.3 Clinical Features phenazopyridine and oxybutynin. kg (range: 0.58 to 2.98 kg) across this Histories of hydroxychloroquine timespan. The largest case series to date ana- use and cigarette smoking were also lyzed 35 patients with a confi rmed included. Finally, expert reviewers Population at Risk diagnosis of PPS-associated maculopa- masked to medication history re- thy across four institutions, where the viewed ophthalmic images of all pa- As the only FDA-approved oral median age at the time of diagnosis tients to identify cases of this unique agent for IC, PPS has been a main- was 60 years (range: 37 to 79 years) maculopathy. stay of treatment for decades. Using (Table 1).13 The median PPS intake Of the 219 IC patients included in claims data from a national U.S. in- duration was 14.5 years (range: 3 to 22 the study, 80 (36.5 percent) had prior surer, we identifi ed practice patterns years), at a median daily dose of 300 documentation of exposure to PPS. suggesting hundreds of thousands of mg (range: 150 mg to 592 mg), consis- Masked reviewers identifi ed 14 cases individuals have likely been exposed tent with recommended therapeutic of the characteristic maculopathy, to the drug within the United States. regimens.9 Median cumulative intake each occurring among the 80 PPS- In a retrospective, matched co- per kilogram of body mass was 24.7 g/ exposed patients. hort study within this large database, kg (range: 9.83 to 61.9 g/kg). No patient exhibited this macu- PPS-exposed patients were found to Of note: Given the recent recogni- lopathy in the absence of PPS expo- have a signifi cantly increased risk of tion of this entity, this series likely sure. Among all potential risk factors being diagnosed with a new macular represents a group of patients with examined, PPS exposure emerged disease at seven years.12 relatively advanced disease, and it as the sole statistically signifi - This study also suggested that doesn’t fully capture the exposure cant predictor of this maculopathy chronicity of exposure plays a role; characteristics and clinical fi ndings of (p<0.0001). Median duration of PPS at the fi ve-year timepoint of con- those with incipient disease. intake among affected patients was tinuous treatment, there was a trend Patients most commonly had a 18.3 years (range: 3 to 21.9 years). for increased risk, although it wasn’t referral diagnosis of macular or pat- The cumulative medication exposure statistically signifi cant. tern dystrophy (45.7 percent) and/or

July 2019 | reviewofophthalmology.com | 51

050_rp0719_retina.indd 51 6/28/19 11:36 AM Retinal

REVIEW Insider

AMD (28.6 percent), and reported Table 2: Documented Imaging Discussion symptoms, including blurred vision while reading (48.6 percent), pro- Findings These fi ndings bolster growing con- longed dark adaptation (48.6 percent) cern about a newly described medica- and metamorphopsia (11.4 percent). Color Fundus Photography tion toxicity and raise signifi cant pub- Bilateral, symmetric pathology* The median visual symptom duration Centered on and involving the fovea* lic health implications. Thousands of was reportedly four years (range: 1 to Spots of hyperpigmentation (50 percent) unscreened patients may be at risk. 9 years). Visual acuity was relatively Importantly, many of these cases may well-preserved, with median loga- Fundus Autofl uorescence have masqueraded for years as similar- rithm of the minimum angle of resolu- Dense pattern of hyper-/hypoautofl uorescent appearing conditions, such as AMD spots* tion (logMAR) values from both eyes Well-circumscribed region of disease (>55 and pattern dystrophy. A unique pig- measured to be 0.10 (Snellen equiva- percent) mentary maculopathy is strongly asso- lent, 20/25; OD range: 0 to 1.18, OS RPE atrophy exceeding 1/3 disc diameter in ciated with chronic exposure to the IC range: -0.12 to 1.30, p=0.93). Only 10 size (40 percent) drug PPS. The fundus fi ndings in PPS- eyes (14.3 percent) had visual acuities Center-involving atrophy (9 percent) associated maculopathy are subtle, yet lower than 20/40, of which two (2.9 Optical Coherence Tomography exhibit a distinctive clinical phenotype percent) had visual acuities lower than Discrete lesions of RPE thickening* on multimodal imaging that’s best ap- 20/200. Humphrey visual fi eld testing Ill-defi ned irregularity in outer retinal bands* preciated by using FAF. Preliminary was typically fairly normal except in investigations of databases indicate * Observed in all affected eyes the setting of patchy atrophy of the that many thousands of patients may retinal pigment epithelium. Summary of imaging fi ndings organized be at risk. On examination, patients often had by modality, documented in a recent series Several possible explanations exist paracentral spots of hyperpigmentation of 35 confi rmed cases of PPS-associated for this condition’s recent discovery, accompanied by pale yellow or orange maculopathy (manuscript under review). relative to the FDA approval of PPS in deposits (Figure 1A; Table 2). Gener- 1996.14 First, chronic exposure gener- ally, these spots initially appear in the fl uorescent changes. ally seems a prerequisite for this con- parafoveal region and extend periph- OCT imaging (Figure 1C) reveals dition. We may only now be seeing the erally within the macula over time, nodular thickening of the RPE subset of patients who have exceeded indicating a dynamic disease process. that also co-localizes to the spots of the exposure threshold at which this RPE atrophy exceeding one-third of hyperpigmentation observed on color disease begins to manifest. Secondly, a disc diameter was observed in 39.4 fundus photography and as hyper- IC patients can be complex, harboring percent of cases, involving the central refl ectance on NIR imaging. The conditions that affect multiple organ fovea in 9.1 percent. Spots of hyper- yellow or orange deposits observed on systems treated with numerous medi- pigmentation occurred less often color fundus photography lack a clear cations. This can make identifying a in eyes with atrophy (23.1 percent) anatomic correlate on OCT imaging, drug-disease association diffi cult. than in those without atrophy (73.7 although similarly localized disrup- The presenting visual symptoms for percent, p<0.00007). tions in the outer retinal bands may these patients are vague, and retinal FAF (Figure 1B) imaging reveals the suggest that the deposits occupy the changes on conventional examination full extent of the fundus abnormal- subretinal space. are subtle. Modern retinal imaging ity, which typically centers on and All affected eyes in the cases contain modalities, including AF, recently ad- involves the fovea. Pathology is often regions with abnormality in the opted widely, can help detect changes. characterized by a fairly well-circum- interdigitation zone, or a confl uence Without referral to a specialist with scribed patch of affected retina involv- between the interdigitation zone and modern imaging instrumentation, PPS- ing the posterior pole, as was seen in ellipsoid zone bands. associated maculopathy may remain 56.1 percent of patients. Cystoid macular edema was ob- undetected. Many existing cases may However, in some cases, the FAF served in nine eyes of six patients. masquerade as similar-appearing con- abnormality exhibits a more diffuse These cases responded well to treat- ditions. Many patients with confi rmed pattern, extending into the retinal pe- ments, including topical dorzolamide, PPS-associated maculopathy are ini- riphery. Characteristic patterns within and intravitreal afi bercept and bevaci- tially diagnosed with AMD and macular these lesions resembled densely zumab. One eye in the series devel- or pattern dystrophies. They may never packed hyper- and hypoautofl uores- oped subretinal exudation attributed pursue comprehensive retinal diagnos- cent spots and reticular hyperauto- to choroidal neovascularization. tics, halting the diagnostic odyssey.15

52 | Review of Ophthalmology | July 2019

0050_rp0719_retina.indd50_rp0719_retina.indd 5522 66/28/19/28/19 11:3611:36 AMAM An underlying mechanism for this patients with comorbid macular dis- reoretinal Surgery and Disease at the condition hasn’t been fully elucidated. ease, such as AMD, which may confer Emory Eye Center. Fundus imaging suggests a primary a higher susceptibility to a toxic macu- Please direct correspondence to insult to the RPE or RPE-photore- lopathy. Patients with elevated risk, Nieraj Jain, MD, 1365B Clifton Road, ceptor interface. Similar to processes including those with an atypical dosing N.E., Suite 2400, Atlanta, GA 30322. observed in other macular dystro- regimen, those with a history of smok- Funding for this work has been pro- phies, the RPE lesions revealed by ing or macular disease and those with vided by a VitreoRetinal Surgery a OCT may represent dying RPE cells comorbidities involving renal, hepatic Foundation Research Grant (AH), that have accumulated pathologic or splenic function, may benefi t from Foundation Fighting Blindness Ca- levels of byproducts from the visual more frequent examinations. reer Development Award CD-C- cycle caused by an unknown, harmful For patients with PPS-associated 0918-0748-EEC (NJ) and a National interaction with PPS. The structural maculopathy, we recommend coordi- Institutes of Health Core Grant P30 homology between PPS and inter- nation with the patient and with the EY006360 (NJ). photoreceptor matrix components prescribing physician to fi nd an alter- The authors have no potential con- may permit such an interaction. The native regimen for IC management. fl icts of interest to disclose. interphotoreceptor matrix, an extra- Although we don’t fully understand 1. Pearce WA, Chen R, Jain N. Pigmentary maculopathy cellular scaffolding that mediates the the natural history of this condition, associated with chronic exposure to pentosan polysulfate sodium. Ophthalmology 2018;125:11:1793-1802. photoreceptor-RPE relationship, is we advise affected patients that visual 22.. McLennanMcLennan MT.M Interstitial cystitis: Epidemiology, composed primarily of glycosamino- symptoms may persist and possibly pathophysiology, and clinical presentation. Obstet Gynecol Clin 116-186-18 North Am. 2014;41:3:385-95. glycans. PPS, a glycosaminoglycan worsen, even after drug cessation. 3. Hanno PM, Erickson D, Moldwin R, Faraday MM. Diagnosis and treatment of interstitial cystitis/bladder pain syndrome: analogue, may somehow accumulate We expect to draw more conclusions AUA guideline amendment. J Jurol 2015;193:5:1545-1553. and disrupt the structure and function about the incidence and history of CP. 4. Nickel JC, Moldwin R. FDA BRUDAC 2018 Criteria for interstitial cystitis/bladder pain syndrome clinical trials: Future of this matrix. The nodular RPE ex- Investigations by our group and others direction for research. J Urol. 2018; 200:1:39-42. 5. Frileux C. [Thrombocid: a new synthetic anticoagulant]. crescences may indicate accumulation will examine this unique phenotype Presse Med. 1951;59:8:159. of PPS or one of its many metabolites longitudinally across multiple func- 6. Meng E, Hsu YC, Chuang YC. Advances in intravesical therapy for bladder pain syndrome (BPS)/interstitial cystitis in the RPE, as has been observed tional testing and imaging modalities to (IC). Low urin tract symptoms 2018;10:1:3-11. 19 7. Giusto LL, Zahner PM, Shoskes DA. An evaluation of

in the bladder’s urothelium. When provide guidance regarding long-term the pharmacotherapy for interstitial cystitis. Expert Opin radiolabeled PPS has been used to prognosis. Ongoing animal studies will Pharmacother. 2018;19:10:1097-1108. 8. Chen P, Yuan Y, Zhang T, et alXu B, Gao Q, Guan T. Pentosan study its distribution, it has been explore underlying mechanisms. polysulfate ameliorates apoptosis and infl ammation by suppressing activation of the p38 MAPK pathway in high primarily reported to deposit in the Given the emerging evidence linking glucose-treated HK2 cells. Int J Mol Med. 2018;41:2:908-914. urothelium and minimally in other PPS to macular disease, ophthalmolo- 9. Elmiron (R) [Package Insert]. Titusville, NJ: Jannssen 9 Pharmaceuticals, 2012. visceral organs. gists have a new role in protecting pa- 10. Al-Zahrani AA, Gajewski JB. Long-term effi cacy and tolerability of pentosan polysulphate sodium in the treatment of tients at risk for this vision-threatening bladder pain syndrome. Can Urol Assoc J. 2011;5:2:113-118. Recommendations condition. Many of us may unknow- 11. Hanif AM, Shah R, Yan J, et al. Strength of association between pentosan polysulfate and a novel maculopathy. ingly follow affected patients. Many Ophthalmology 2019 Apr 18 [Epub ahead of print]. 12. Li AL, Jain N, Yu Y, VanderBeek BL. Association of macular Although offi cial recommendations patients harboring this condition may disease with long-term use of pentosan polysulfate sodium: for evaluating at-risk patients are pre- either be undetected or misdiagnosed fi ndings from a large U.S. national insurance database. May 1, 2019. Association for Research in Vision and Ophthalmology. mature, our institution recommends with similar-appearing conditions. Vancouver, BC. 13. Hanif AM, Taylor S, Armenti S, et al. Expanded clinical discusing the lowest necessary dose As in cases involving hydroxychloro- spectrum of pentosan polysulfatesodium-associated and duration of treatment with long- quine and other drug-associated mac- pigmentary maculopathy. The Association for Research in Vision and Ophthalmology; April 30, 2019. Vancouver, B.C. term PPS therapy prescribers. We ulopathies, the use of modern fundus 14. Dell JR, Parsons CL. Multimodal therapy for interstitial cystitis. J Reprod Med. 2004;49:3 Suppl:243-52. suggest a baseline examination with imaging techniques will help identify 15. Hanif AM, Yan J, Jain N. Pattern dystrophy: an imprecise comprehensive fundus imaging (color affected patients. We look forward to diagnosis in the age of precision medicine. International ophthalmology clinics 20109;59:1:173-194. fundus photography, FAF imaging ongoing research developments that 16. Clark SJ, Keenan TD, Fielder HL, et al. Mapping the differential distribution of glycosaminoglycans in the adult and OCT), followed by annual exami- will improve our understanding of human retina, choroid, and sclera. Invest Ophtdhalmol Vis Sci. nations with fundus imaging, starting the pathobiology and prognosis of this 2011;52:9:6511-21. 17. Brandl C, Schulz HL, Charbel Issa P, et al. Mutations in the at fi ve years after initiation of therapy. unique maculopathy. genes for interphotoreceptor matrix proteoglycans, IMPG1 and IMPG2, in patients with vitelliform macular lesions. Genes FAF imaging is valuable for highlight- (Basel) 23;8:7. ing the characteristic early features of Dr. Hanif is a recent graduate of 18. Ishikawa M, Sawada Y, Yoshitomi T. Structure and function of the interphotoreceptor matrix surrounding retinal the condition. Emory University School of Medicine photoreceptor cells. Exp Eye Res. 2015;133:3-18. 19. Pantazopoulos D, Karagiannakos P, Sofras F, et al. Effect We recommend that providers ex- in Atlanta. Dr. Jain practices as an as- of drugs on crystal adhesion to injured urothelium. Urology. ercise caution in prescribing PPS for sistant professor in the Division of Vit- 1990;36:3:255-9.

July 2019 | reviewofophthalmology.com | 53

0050_rp0719_retina.indd50_rp0719_retina.indd 5533 66/28/19/28/19 11:3711:37 AMAM Pediatric Patient Edited by Wendy Huang, MD REVIEW

Cross-linking in Pediatric Patients Early intervention is key to preventing progression and the need for corneal transplantation. Benjamin B. Bert, MD, FACS Los Angeles

hough corneal collagen cross- ed States with FDA approval in the were based on corneal steepness on T linking has the potential to help spring of 2016 of the Avedro KXL sys- keratometry and the scissoring re- many patients with keratoconus, the tem and Photrexa ribofl avin solutions fl ex seen on retinoscopy. In more ad- patients likely to benefi t from it the for the treatment of progressive kera- vanced cases, the ectactic portion of most—children—may not receive toconus and corneal ectasia follow- the cornea—the cone itself—could it, for a variety of reasons. Here, I’ll ing refractive surgery.3 This approval be visualized at the slit lamp. review what we know about cross- means that it’s possible to administer Other fi ndings of keratoconus that linking in patients under the age of 14, the treatment right when ectasia be- can be seen at the slit lamp include: and look at ways the procedure might gins, which has been hypothesized to 1) Vogt’s striae: fi ne folds in Des- be able to help them. occur around the time of puberty. If cemet’s membrane at the apex of the it can be stopped at that point, that cone that fl atten with gentle pressure The Disease would prevent 21.6 percent of pa- on the globe; tients from progressing to the need 2) Kayser-Fleischer ring: iron de- Keratoconus is a progressive corne- for corneal transplantation.4 The chal- position into the corneal subepithelial al ectatic disease that thins the cornea lenge is that the original FDA studies layer at the base of the cone; and creates irregular astigmatism. In performed by Avedro didn’t include 3) corneal hydrops: a rupture of advanced stages, the disease can also any patients under the age of 14. So, Descemet’s membrane, leading to cause a reduction in the patient’s best- without safety data for the pediatric corneal edema and decreased vision; corrected visual acuity. population, the indication ultimately and Keratoconus remains fairly rare. Its approved by the FDA was for patients 4) apical scarring: this occurs as the prevalence varies in different parts of 14 or older.5,6 This is of course well cone becomes steeper, or after an epi- the world and by the criteria used to after most children have entered pu- sode of corneal hydrops. diagnose the condition. In the Unit- berty, since age 13 for girls and 14 for Everyone agrees on the diagnosis ed States the rate of keratoconus has boys is considered delayed puberty.7 of keratoconus in these late stages been reported as 54.5 per 100,000 in when there’s clear clinical evidence Minnesota,1 but can range anywhere Diagnosis of the disease. However, it’s the early from between 4 to 600 per 100,000 diagnosis of cases of forme fruste or depending on the diagnostic criteria The diagnosis of keratoconus is be- subclinical ectasia that remains con- used.2 coming more specifi c and more sensi- troversial. With the development of Keratoconus management under- tive as our ability to image the cornea topography and the progression to went a paradigm shift in the Unit- improves. Initially, diagnostic criteria multiple forms of tomography, our

54 | Review of Ophthalmology | July 2019 This article has no commercial sponsorship.

054_rp0719_peds.indd 54 6/28/19 12:08 PM attempts to diagnose keratoconus ear- rently the system is for epithelium-de- lier have become more successful. brided (a.k.a., “epi-off”) corneal col- In an effort to reach a consensus, lagen cross-linking, following what’s researchers surveyed corneal experts known as the Dresden protocol. The from around the world and then held Dresden protocol fi rst entails remov- a panel meeting to discuss the results ing the corneal epithelium. Then, you of the survey. In the debates that administer Photrexa Viscous at a rate followed, researchers and clinicians of one drop every two minutes over a came to some conclusions regarding “soaking” period of 30 minutes. Next, the diagnosis, monitoring and treat- Piggyback lenses (RGP on top of cosmetic examine the eye at the slit lamp for ment of keratoconus and other ectatic colored soft contact lens) in a patient with the presence of yellow flare in the diseases, even though the scientific keratoconus. anterior chamber. If fl are is present, evidence wasn’t clear-cut.8 Among then you proceed with the ultraviolet those conclusions was the impor- stromal ring segments, full thickness treatment. If there’s no fl are, then you tance of posterior corneal curvature penetrating keratoplasty, deep anteri- continue to administer one drop of measurements; the panel defi ned the or lamellar keratoplasty, and the trans- Photrexa Viscous every two minutes presence of abnormal posterior cor- plantation of Bowman’s layer. None of for two to three more doses before neal elevation as a requirement for these, however, adequately addressed checking for flare again. You then diagnosing early or subclinical kerato- the progressive nature of the disease. perform corneal pachymetry. If the conus.8 This makes corneal tomogra- Cross-linking, with its ability to halt cornea is at least 400 µm thick, you phy essential for the earliest diagnosis. progression, was a paradigm shift. proceed to ultraviolet treatment. If it’s Currently, imaging of the posterior Since most experts agree that there’s thinner than 400 µm, you administer corneal curvature is most often per- a much higher likelihood of kerato- two drops of Photrexa (NOT Viscous) formed using Scheimpfl ug technology conus progression in the younger age every five to 10 seconds until the or anterior segment OCT. Recently, group, the goal is to treat keratoconus pachymetric measurement is greater imaging of the corneal epithelium— at its earliest stages in the youngest than 400 µm. If the cornea can’t be primarily using OCT technology—in ages to prevent progression, reduced thickened to at least 400 µm, then order to create an epithelial thickness best-corrected visual acuity, and the it’s not advisable to proceed with the map has become an area of intense in- need for corneal transplantation. treatment. If you’re able to proceed to terest in the quest for another marker Since Avedro’s cross-linking system the ultraviolet treatment, then apply for early keratoconus.9 is the one that’s FDA-approved, I’ll 3 mW/cm2 of energy (wavelength of be discussing it exclusively here. Cur- 365 nm) to the cornea for 30 minutes, Treatment for a total energy of 5.4J/cm2. Dur- The treatment ing the 30 minutes of keratoconus has of UV treatment, undergone many apply one drop of changes over the Photrexa Viscous years, with the ap- every two min- proval of corneal utes.10 collagen cross- linking, both in the Outcomes United States and abroad, being the The goal of the most dramatic. pilot studies was to Before cross-link- show a reduction in ing, treatments for the maximum kera- keratoconus includ- tometry measure- ed glasses, contact ment (Kmax) of at lenses (soft, hybrid, least 1 D. All three rigid gas permeable studies (UVX-001, and scleral), intra- Tomography can be useful for catching the telltale signs of keratoconus. UVX-002 and UVX-

July 2019 | reviewofophthalmology.com | 55

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Satisfactory Completion - Learners must complete an evaluation form to receive a certifi cate of completion. Your chosen sessions must be attended in their entirety. Partial credit of individual sessions is not available. If you are seeking continuing education credit for a specialty not listed below, it is your responsibility to contact your licensing/certifi cation board to determine course eligibility for your licensing/certifi cation requirement. Physicians - In support of improving patient care, this activity has been planned and implemented by Amedco LLC and Postgraduate Healthcare Education. Amedco LLC is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team

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REVIEW Patient

003) met this endpoint. tions. Previously, Photrexa For keratoconus specifi- and Photrexa Viscous had cally (included in UVX-001 a miscellaneous J code. and UVX-002) there was a Recently, CMS issued a reduction in Kmax of -1.9 permanent J code, J2787, D and -2.3 D, respectively, effective January 1, 2019, at 12 months postop. which will help to stream- Looking specifically at line the process and avoid the pediatric population, the erroneous rejections a group of international that can occur with a man- researchers studied kera- ual review. Billing errors toconic patients ranging can also arise from the pro- from 10 to 17 years old.11 cedure code being a cate- They performed the stan- gory 3 code rather than the dard Dresden protocol normal category 1 code. The classic sign of inferior steepening on topography in a patient suffering treatment on them, and from keratoconus. The process of securing then followed them for an the CPT code is going to average of 7.5 years. Dur- take longer to fi nalize and ing that time, though the keratometry was 7.6 percent. They determined may be years away. The procedure is measurements didn’t improve, the that a high preoperative maximum also not reimbursed when used on pa- researchers did note stability of the keratometry reading was a signifi cant tients under the approved minimum keratoconus. risk factor for failure. Sterile infi ltrates age of 14. The long-term effect of cross-link- were seen in 7.6 percent of eyes and Since it’s a new procedure, and ing can be seen in the trends observed central stromal scars in 2.8 percent. many insurers are requiring manual internationally where cross-linking The researchers found that patient reviews, a lot of rejections have re- has been available for over a decade. age older than 35 years and preopera- sulted from an insurer’s staff not being There are a number of studies that tive corrected distance vision better properly informed about the status of show the rates of corneal transplants than 20/25 were signifi cant risk fac- cross-linking, which they mistakenly (PKP and DALK) for keratoconus tors for complications.13 think of as experimental. There’s been decreasing after the introduction of some improvement lately, however. cross-linking, intracorneal ring seg- Reimbursement Issues Avedro recently created a program ments and advanced contact lens called ARCH in order to provide technologies. In a study from Italy’s The biggest challenge with corneal information and resources for navi- Corneal Transplant Epidemiological collagen cross-linking in the United gating coverage problems with com- Study, there was a 27-percent reduc- States currently is the reimburse- mercial payers and improve patient tion in corneal grafting for keratoco- ment model. Initially, cross-linking access. nus from 2002 to 2008.12 Much of the was done as a cash-pay procedure, but In addition to the ARCH program, decline started after 2004 when cross- since FDA approval, more insurance Avedro has hired employees to pro- linking was becoming more common carriers have begun to cover it. I par- vide guidance in physicians’ offi ces, in Europe. ticipated in a telephone conference if need be. These new positions in- The complications that arise from with the Avedro team to discuss my clude payor relations directors who crosslinking are usually related to the experiences with the UCLA model as work with the insurance companies removal of the corneal epithelium; well as the steps Avedro has taken to to ensure coverage and positive reim- they include delayed healing, corneal help facilitate this shift. bursement, and fi eld reimbursement haze, scarring and infection. In one Avedro reported that in the second managers who are up-to-date on the study of cross-linking complications, half of 2018, coverage increased to 62 current regional payor landscape. The researchers studied 117 eyes of 99 health insurance plans. That coverage latter can work with a physician’s back patients. The percentage of eyes los- now includes 190 million patients, or offi ce and billing staff to ensure prop- ing two or more Snellen lines was more than 90 percent of U.S. covered er coding and submission, so reim- 2.9 percent. The failure rate of CXL lives. However, billing challenges re- bursements are processed correctly. (which they defi ned as the percentage main for both the procedure and re- There will certainly continue to of eyes with continued progression) imbursement for the ribofl avin solu- be hiccups along the way, but mov-

July 2019 | reviewofophthalmology.com | 57

054_rp0719_peds.indd 57 7/1/19 9:17 AM Pediatric

REVIEW Patient

ing to an insurance payment model of Medicine. will make cross-linking available to a He has no financial interest in larger population, possibly including Avedro’s cross-linking products. the pediatric/adolescent population 1. Kennedy RH, Bourne WM, Dyer JA. A 48-year clinical who need the procedure the most, and epidemiologic study of keratoconus. Am J Ophthalmol but whose parents may not be able to 1986;101:3:267-73. afford the out-of-pocket cost. 2. McMahon TT, Shin JA, Newlin A, Edrington TB, Sugar J, Zadnik K. Discordance for keratoconus in two pairs of monozygotic twins. Cornea 1999;18:4:444-51. Future Directions 3. CDER Rare Disease And Orphan Drug Yellow/geen fl are in the anterior chamber Designated Approvals. https://www.fda.gov/ downloads/Drugs/DevelopmentApprovalProcess/ after the 30-minute “soaking” period during To avoid complications and in- HowDrugsareDevelopedandApproved/ cross-linking. DrugandBiologicApprovalReports/NDAandBLAApprovalReports/ crease patient comfort, especially in UCM544019.pdf Accessed November 2018. the pediatric population, there’s a lot 4. Tuft SJ, Moodaley LC, Gregory WM, Davison CR, Buckley of interest in developing an epitheli- ranging from as short as 10 minutes RJ. Prognostic factors for the progression of keratoconus. Ophthalmology 1994;101:3:439-47. um-on technique. The concern with to the normal 30 minutes. In a review 5. Center for Drug Evaluation and Research Application Number: this approach, however, is whether by Marcony Santhiago, MD’s group, 203324Orig2s000 Summary Review. https://www.accessdata. fda.gov/drugsatfda_docs/nda/2016/203324Orig2s000SumR.pdf the riboflavin solution can achieve they note that many of the studies Accessed November 2018. enough penetrance to fully saturate have a short follow-up period, so it’s 6. NDA 203324. https://www.accessdata.fda.gov/drugsatfda_ docs/label/2016/203324s000lbl.pdf Accessed November 2018. the cornea, and whether the UV light still difficult to assess the longevity 7. Palmert MR, Boepple PA. Variation in the timing of puberty: can penetrate adequately, as well.14 of the accelerated protocol. As an in- Clinical spectrum and genetic investigation. J Clin Endocrinol Metab 2001;86:2364-2368 To overcome this barrier, a couple of direct marker, the demarcation line 8. Gomes JA, Tan D, Rapuano CJ, Belin MW, Ambrósio R Jr, Guell different techniques have been at- has been used to signal the depth of JL, Malecaze F, Nishida K, Sangwan VS; Group of Panelists for tempted, including iontophoresis15 penetrance of the treatment and a the Global Delphi Panel of Keratoconus and Ectatic Diseases. Global consensus on keratoconus and ectatic diseases. Cornea and disrupting the epithelium with marker of successful treatment. In 2015;34:4:359-69. benzalkonium chloride.16 Studies the standard protocol, the demarca- 9. Li Y, Tan O, Brass R, Weiss JL, Huang D. Corneal epithelial thickness mapping by Fourier-domain optical coherence of epi-on crosslinking have thus far tion line is usually found around 300 tomography in normal and keratoconic eyes. Ophthalmology shown that corneal measurements to 350 µm deep. In accelerated treat- 2012;119:12:2425-33. 10. Wollensak G, Spoerl E, Seiler T. Ribofl avin/ultraviolet-A- stabilize for a period of time, but then ments the demarcation line can be as induced collagen crosslinking for the treatment of keratoconus. tend to progress after about a year.17 shallow as 100 to 150 µm, which Dr. Am J Ophthalmol 2003;135:5:620-7. A recent meta-analysis in the Journal Santhiago’s review found in a study of 11. Zotta PG, Diakonis VF, Kymionis GD, Grentzelos M, Moschou KA. Long-term outcomes of corneal cross-linking for of Cataract and Refractive Surgery the three-minute protocol. It was only keratoconus in pediatric patients. J AAPOS 2017;21:5:397-401. concluded that for now, epi-off cross- by expanding the total treatment to 14 12. Frigo AC, Fasolo A, Capuzzo C, et al. Corneal transplantation 2 activity over 7 years: Changing trends for indications, patient linking should remain the standard of minutes with a 9 mW/cm treatment demographics and surgical techniques from the Corneal care.18 delivering 7.5 J/cm2 that the acceler- Transplant Epidemiological Study (CORTES). Transplant Proc 2015;47:528–35. Another modifi cation to cross-link- ated protocols were able to deliver a 13. Koller T, Mrochen M, Seiler T. Complication and failure ing that would benefi t the pediatric demarcation line at depths compa- rates after corneal crosslinking. J Cataract Refract Surg 19 2009;35:8:1358-62. population is an accelerated protocol, rable to the Dresden protocol. 14. Li W, Wang B. Effi cacy and safety of transepithelial corneal so the entire procedure could be per- In conclusion, corneal collagen collagen crosslinking surgery versus standard corneal collagen formed in much less than the hour cross-linking is changing the para- crosslinking surgery for keratoconus: A meta-analysis of randomized controlled trials. BMC Ophthalmol 2017;17:1:262. currently required. The idea of the digm for the treatment of keratoco- 15. Bikbova G, Bikbov M. Standard corneal collagen crosslinking accelerated protocols is to deliver the nus and corneal ectatic disease. It’s versus transepithelial iontophoresis-assisted corneal crosslinking, 24 months follow-up: Randomized control trial. same amount of total energy (5.4 J/ crucial to treat patients at the young- Acta Ophthalmol 2016;94:7:e600-e606. cm2) but use higher ultraviolet inten- est age at which progressive kerato- 16. Rush SW, Rush RB. Epithelium-off versus transepithelial corneal collagen crosslinking for progressive corneal sity for shorter periods of time. This conus is diagnosed, to help prevent ectasia: A randomised and controlled trial. Br J Ophthalmol means that you would need 30 mW/ them from needing keratoplasty or 2017;101:4:503-508. cm2 for a three-minute treatment, 18 other advanced interventions in the 17. Shalchi Z, Wang X, Nanavaty MA. Safety and effi cacy of epithelium removal and transepithelial corneal collagen 2 mW/cm for a fi ve-minute treatment future. crosslinking for keratoconus. Eye (Lond) 2015;29:1:15-29. and 9 mW/cm2 for a 10-minute treat- 18. Kobashi H, Rong SS, Ciolino JB. Transepithelial versus 19 epithelium-off corneal crosslinking for corneal ectasia. J ment. Dr. Bert is an assistant professor Cataract Refract Surg 2018;44:12:1507-1516. Some of the studies looking into ac- of ophthalmology at the Doheny Eye 19. Medeiros CS, Giacomin NT, Bueno RL, Ghanem RC, Moraes HV Jr, Santhiago MR. Accelerated corneal collagen crosslinking: celerated protocols have also been ac- Center of UCLA, Doheny and Stein Technique, effi cacy, safety, and applications. J Cataract Refract companied by shorter soaking times, Eye Institutes, David Geffen School Surg 2016;42:12:1826-1835.

58 | Review of Ophthalmology | July 2019

054_rp0719_peds.indd 58 7/1/19 9:18 AM A Clear Vision For Life ®

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Her examdemonstratedbest-correctedvisualacuitiesof20/40ODand20/20OS.Pupils,intraocularpressuresmo- Her medicationsincludedlow-doseaspirin,atorvastatin,risedronate,estradiol,mometasonenasalsprayandfexofena- Her pastocularhistorywasnotableonlyformyopia.Pastmedicalremarkablearightbundlebranchblock, A 72-year-old womanpresentedwithathree-dayhistoryofblurredcentralvision,fl oaters consistingof“sprinklinglights” REVIEW ed). Socialhistorywassignifi cant foroccasionalalcoholconsumption,butshedeniedanyhistoryoftobaccoordrug the maculainrighteye. mild salt-and-pepperappearance of fluorescence images(C,D) show a macula inbotheyes. Fundusauto- atrophy,peripapillary butanormal (A) andleft(B)eyes demonstrate Figure 1.Fundusphotosoftheright Wills Eye Wills Eye Resident CaseSeries Edited byJasonFlamendorf, MD July 2019 | reviewofophthalmology.com |

63 6/28/19 1:44 PM Resident Case Series REVIEW

Workup, Diagnosis and Treatment

OCT demonstrated mild thinning of gadolinium, was unremark- the macula in both eyes, with possible able. A computed tomogra- abnormalities of the ellipsoid zone in phy scan of the chest, abdo- the right eye (Figure 2 A,B). Fluo- men and pelvis showed a rescein angiography was within nor- benign right lung nodule mal limits. Fundus autofl uorescence and small benign-appear- demonstrated a mild salt-and-pepper ing hepatic cysts, but no appearance in the right eye (Figure evidence of malignancy. 1 C,D). Humphrey perimetry of her C-reactive protein, eryth- right eye demonstrated superotem- rocyte sedimentation rate poral constriction, almost in the form and complete blood count of a superotemporal arcuate scotoma, were normal. An autoim- denser temporally, as well as an in- mune retinopathy panel ferior arcuate scotoma. This was re- was sent to the Casey Eye produced with Goldmann perimetry Institute and was pending (Figure 3 A,B). at the time of discharge. At this point, the differential diag- She was discharged after noses included the spectrum of acute 12 doses of IV steroids with Figure 3. Goldmann perimetry at initial presentation (A,B) zonal occult outer retinopathies, auto- an oral prednisone taper showed a superotemporal arcuate scotoma in the right immune retinopathy, and, less likely, (60 – 40 – 30 – 20 – 10 mg eye. Repeat Goldmann perimetry (C,D) two weeks after cancer-associated retinopathy. Given daily, tapered every three receiving intravenous steroids followed by an oral steroid the patient’s severe subjective visual days). taper showed a dramatic improvement in the defect. Ten fi eld worsening over a period of days, Two weeks after dis- weeks after initial presentation (E,F) the superotemporal she was admitted for intravenous charge, the patient’s symp- defect had worsened in the right eye with progression methylprednisolone 250 mg every six toms and Goldmann visual towards the central vision. hours and further work-up. Full-fi eld fi eld improved dramati cally ERG demonstrated cone dysfunction (Figure 3 C,D). Four weeks after ini- 3-phosphate dehydrogenase. Recov- in the right eye, but was normal in tial presentation, the autoimmune erin, PKM2, tubulin and carbonic an- the left eye. Visual evoked potential retinopathy panel arrived, showing hydrase II autoantibodies were ab- demonstrated a delay in the right eye positivity for several anti-retinal auto- sent. Based on the above fi ndings, the but was normal in the left. An MRI of antibodies, including HSP27, aldose, patient’s presentation was consistent the brain and orbits, with and without enolase, arrestin and glyceraldehyde with non-paraneoplastic autoimmune retinopathy. She received intravitreal triamcino- lone in the right eye, but denied any improvement with it. Her Goldmann visual fi eld 10 weeks after initial pre- sentation re-demonstrated a supero- temporal scotoma in her right eye with progression toward her central vision (Figure 3 E,F). Intravenous steroid therapy was reinitiated and followed with a slow oral steroid taper (methyl- prednisolone 1 g daily for three doses, then 60 – 40 – 20 – 10 mg daily, ta- pered every two weeks; then 10 mg ev- ery other day). This was administered Figure 2. (A,B) OCT demonstrates mild thinning of the macula in both eyes with possible in conjunction with starting mycophe- abnormalities of the ellipsoid zone in the right eye. OCT of the optic nerves (C) shows nolate mofetil 1,000 mg b.i.d. Assess- superotemporal thinning in the right eye but is otherwise normal. ment of treatment response is ongoing.

64 | Review of Ophthalmology | July 2019

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REVIEW Index

Discussion Bausch + Lomb 9, 10, 39 Phone (800) 323-0000 Fax (813) 975-7762 Autoimmune retinopathy describes dance between two laboratories for a diverse group of conditions with an- fi nding the presence of any antiretinal Compulink 27 tiretinal autoantibodies implicated in antibodies and 36 percent for having a Phone (800) 456-4522 www.compulinkadvantage.com the etiology. AIR is subdivided into positive result for a specifi c antiretinal paraneoplastic and nonparaneoplastic antibody. The potential for such dispa- EyePoint Pharmaceutical 13, 14 subtypes, depending on the presence rate results may lead clinicians to send Phone (617) 926-5000 3 Fax (617) 926-5050 or absence of concomitant malignan- serum samples to at least two labs. eyepointpharma.com cy. While universally-accepted diag- Evidence supporting the treatment nostic criteria for nonparaneoplastic of AIR is based largely on observation- Focus Laboratories, Inc. 17 AIR remain elusive, a recent expert al studies.4 One retrospective series of Phone (866) 752-6006 Fax (501) 753-6021 consensus-driven effort developed sev- 30 patients treated with systemic or lo- www.focuslaboratories.com eral essential diagnostic criteria (Table cal immunosuppression found that 70 1).1 These include: visual function ab- percent demonstrated improvement Imprimis Pharmaceuticals, Inc. 35 normality without apparent cause or in visual acuity or a visual fi eld defi cit.5 Phone (858) 704-4040 Fax (858) 345-1745 malignancy; absence of infl ammation; More recently, a majority of patients www.imprimispharma.com ERG abnormality with or without a with autoimmune retinopathy treated visual fi eld abnormality; and the pres- with rituximab demonstrated stable or Kala Pharmaceuticals 21, 22 ence of serum antiretinal antibodies. improved visual acuity six months after Phone (781) 996-5252 6 Fax (781) 642-0399 The differential diagnosis of non- therapy initiation. [email protected] paraneoplastic AIR includes drug tox- Our 72 year-old patient met the es- www.kalarx.com icity, vitamin defi ciencies, occult pos- sential diagnostic criteria developed by terior uveitis, acute zonal occult outer expert consensus.1 While her clinical Keeler Instruments 19 Phone (800) 523-5620 retinopathy, inherited retinal degen- exam was unrevealing, ancillary studies Fax (610) 353-7814 erations and carcinoma- or melano- were notable for cone dysfunction on ma-associated retinopathy. While drug ERG, visual fi eld defi cit on Humphrey Lacrimedics, Inc 25 toxicity and vitamin deficiency may and Goldmann perimetry, and ellip- Phone (800) 367-8327 Fax (253) 964-2699 be excluded with history, additional soid zone abnormalities on OCT. The [email protected] testing is often employed to investi- presence of serum antibodies was con- www.lacrimedics.com gate the cause. This testing includes fi rmed; however, due to a testing turn- OCT, fl uorescein angiography, fundus around time of two to four weeks and Lombart Instruments 41 Phone (800) 446-8092 autofl uorescence, genetic testing and evidence that a delay in treatment may Fax (757) 855-1232 malignancy evaluation in conjunction portend a worse prognosis,6 treatment with other specialists.1,2 with systemic steroids was initiated Ocular Therapeutix, Inc. 5, 6 Testing for serum antiretinal anti- prior to antiretinal autoantibody con- Phone (877) 628-8998 www.ocutx.com bodies remains non-standardized and fi rmation. While her visual fi eld defect commercially available on a limited improved with steroids, she relapsed Omeros 2 basis.1 Consequently, concordance be- while off them and is now currently Phone (206) 676-5000 tween laboratories may be low. One being treated with steroid-sparing im- Fax (206) 676-5005 study found only 64-percent concor- munosuppression. S4OPTIK 31, 33 Phone (888) 224-6012 1. Fox AR, Gordon LK, Heckenlively JR, et al. Consensus on the diagnosis and management of nonparaneoplastic autoimmune Table 1. Essential Diagnostic retinopathy using a modifi ed Delphi approach. Am J Ophthalmol Santen Inc. USA 59 2016;168:183–190. Phone (415) 268-9100 Criteria for Nonparaneoplastic 2. Sorbin L. Progress toward precisely diagnosing autoimmune Fax (510) 655-5682 retinopathy. Am J Ophthalmology 2018;188:xiv-xv. Autoimmune Retinopathy 3. Faez S, Loewenstein J, Sobrin L. Concordance of antiretinal www.santeninc.com antibody testing results between laboratories in autoimmune No apparent cause, lesion or dystrophy that may explain visual retinopathy. JAMA Ophthalmol 2013;131:113–115. Shire Ophthalmics 67, 68 function abnormality 4. Fox AR, Sen HN, Nussenblatt RB. Autoimmune retinopathies. In: www.shire.com Absence of overt intraocular infl ammation Ryan’s Retina, 6th ed. London: Elsevier, 2017:1562-1571. 5. Ferreyra HA, Jayasundera T, Khan NW, et al. Management ERG abnormality (with or without visual fi eld abnormality) of autoimmune retinopathies with immunosuppression. Arch This advertiser index is published as a convenience Presence of serum antiretinal antibodies Ophthalmol 2009;127:390–397. and not as part of the advertising contract. Every Absence of malignancy 6. Davoudi S, Ebrahimiadib N, Yasa C, et al. Outcomes in care will be taken to index correctly. No allowance autoimmune retinopathy patients treated with rituximab. Am J will be made for errors due to spelling, incorrect Adapted from Fox et al., 2016. Ophthalmol 2017;180:124–13. page number, or failure to insert.

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RP1218_House Fight Stars.indd 1 11/13/18 11:02 AM VGUVGFOIMIFC[ HQNFVJGJWOCPRNCUOCGZRQUWTGCV the recommended human ophthalmic dose [RHOD], based on VJGCTGCWPFGTVJGEWTXG=#7%?NGXGN 5KPEGJWOCPU[UVGOKE GZRQUWTGVQNKƂVGITCUVHQNNQYKPIQEWNCTCFOKPKUVTCVKQPQH:KKFTC Rx Only CVVJG4*1&KUNQYVJGCRRNKECDKNKV[QHCPKOCNƂPFKPIUVQVJG risk of Xiidra use in humans during pregnancy is unclear. Animal Data BRIEF SUMMARY: .KƂVGITCUVCFOKPKUVGTGFFCKN[D[KPVTCXGPQWU +8 KPLGEVKQP Consult the Full Prescribing Information for complete product VQTCVUHTQORTGOCVKPIVJTQWIJIGUVCVKQPFC[ECWUGF information. an increase in mean preimplantation loss and an increased INDICATIONS AND USAGE KPEKFGPEGQHUGXGTCNOKPQTUMGNGVCNCPQOCNKGUCVOIMI Xiidra® NKƂVGITCUVQRJVJCNOKEUQNWVKQP KUKPFKECVGFHQTVJG FC[TGRTGUGPVKPIHQNFVJGJWOCPRNCUOCGZRQUWTGCV VTGCVOGPVQHVJGUKIPUCPFU[ORVQOUQHFT[G[GFKUGCUG &'&  the RHOD of Xiidra, based on AUC. No teratogenicity was QDUGTXGFKPVJGTCVCVOIMIFC[ HQNFVJGJWOCP DOSAGE AND ADMINISTRATION RNCUOCGZRQUWTGCVVJG4*1&DCUGFQP#7% +PVJGTCDDKV Instill one drop of Xiidra twice daily (approximately 12 hours an increased incidence of omphalocele was observed at the CRCTV KPVQGCEJG[GWUKPICUKPINGWUGEQPVCKPGT&KUECTF NQYGUVFQUGVGUVGFOIMIFC[ HQNFVJGJWOCPRNCUOC VJGUKPINGWUGEQPVCKPGTKOOGFKCVGN[CHVGTWUKPIKPGCEJG[G GZRQUWTGCVVJG4*1&DCUGFQP#7% YJGPCFOKPKUVGTGFD[ Contact lenses should be removed prior to the administration +8KPLGEVKQPFCKN[HTQOIGUVCVKQPFC[UVJTQWIJ#HGVCN0Q QH:KKFTCCPFOC[DGTGKPUGTVGFOKPWVGUHQNNQYKPI 1DUGTXGF#FXGTUG'HHGEV.GXGN 01#'. YCUPQVKFGPVKƂGFKP administration. the rabbit. CONTRAINDICATIONS Lactation 6JGTGCTGPQFCVCQPVJGRTGUGPEGQHNKƂVGITCUVKPJWOCP Xiidra is contraindicated in patients with known hypersensitivity VQNKƂVGITCUVQTVQCP[QHVJGQVJGTKPITGFKGPVUKPVJG milk, the effects on the breastfed infant, or the effects on milk RTQFWEVKQP*QYGXGTU[UVGOKEGZRQUWTGVQNKƂVGITCUVHTQO formulation. ocular administration is low. The developmental and health ADVERSE REACTIONS DGPGƂVUQHDTGCUVHGGFKPIUJQWNFDGEQPUKFGTGFCNQPIYKVJ Clinical Trials Experience the mother’s clinical need for Xiidra and any potential adverse Because clinical studies are conducted under widely varying effects on the breastfed child from Xiidra. conditions, adverse reaction rates observed in clinical studies Pediatric Use of a drug cannot be directly compared to rates in the clinical 5CHGV[CPFGHƂECE[KPRGFKCVTKERCVKGPVUDGNQYVJGCIGQH VTKCNUQHCPQVJGTFTWICPFOC[PQVTGƃGEVVJGTCVGUQDUGTXGF years have not been established. KPRTCEVKEG+PƂXGENKPKECNUVWFKGUQHFT[G[GFKUGCUGEQPFWEVGF YKVJNKƂVGITCUVQRJVJCNOKEUQNWVKQPRCVKGPVUTGEGKXGFCV Geriatric Use NGCUVFQUGQHNKƂVGITCUV QHYJKEJTGEGKXGFNKƂVGITCUV  No overall differences in safety or effectiveness have been 6JGOCLQTKV[QHRCVKGPVU  JCFŰOQPVJUQHVTGCVOGPV observed between elderly and younger adult patients. GZRQUWTGRCVKGPVUYGTGGZRQUGFVQNKƂVGITCUVHQT NONCLINICAL TOXICOLOGY approximately 12 months. The majority of the treated patients Carcinogenesis, Mutagenesis, Impairment of Fertility YGTGHGOCNG  6JGOQUVEQOOQPCFXGTUGTGCEVKQPU Carcinogenesis: Animal studies have not been conducted TGRQTVGFKPQHRCVKGPVUYGTGKPUVKNNCVKQPUKVGKTTKVCVKQP VQFGVGTOKPGVJGECTEKPQIGPKERQVGPVKCNQHNKƂVGITCUV dysgeusia and reduced visual acuity. Other adverse reactions Mutagenesis: .KƂVGITCUVYCUPQVOWVCIGPKEKPVJGin vitro TGRQTVGFKPVQQHVJGRCVKGPVUYGTGDNWTTGFXKUKQP #OGUCUUC[.KƂVGITCUVYCUPQVENCUVQIGPKEKPVJGin vivo conjunctival hyperemia, eye irritation, headache, increased mouse micronucleus assay. In an in vitro chromosomal lacrimation, eye discharge, eye discomfort, eye pruritus and aberration assay using mammalian cells (Chinese sinusitis. JCOUVGTQXCT[EGNNU NKƂVGITCUVYCURQUKVKXGCVVJGJKIJGUV Postmarketing Experience concentration tested, without metabolic activation. 6JGHQNNQYKPICFXGTUGTGCEVKQPUJCXGDGGPKFGPVKƂGFFWTKPI Impairment of fertility: .KƂVGITCUVCFOKPKUVGTGFCV postapproval use of Xiidra. Because these reactions are KPVTCXGPQWU +8 FQUGUQHWRVQOIMIFC[ reported voluntarily from a population of uncertain size, it is not HQNFVJGJWOCPRNCUOCGZRQUWTGCVVJG always possible to reliably estimate their frequency or establish TGEQOOGPFGFJWOCPQRJVJCNOKEFQUG 4*1& QH a causal relationship to drug exposure. NKƂVGITCUVQRJVJCNOKEUQNWVKQP JCFPQGHHGEVQP Rare cases of hypersensitivity, including anaphylactic reaction, fertility and reproductive performance in male and bronchospasm, respiratory distress, pharyngeal edema, swollen female treated rats. tongue, and urticaria have been reported. Eye swelling and rash have been reported. USE IN SPECIFIC POPULATIONS Pregnancy /CPWHCEVWTGFHQT5JKTG75+PE5JKTG9C[.GZKPIVQP/# There are no available data on Xiidra use in pregnant women to (QTOQTGKPHQTOCVKQPIQVQYYY:KKFTCEQOQTECNN KPHQTOCP[FTWICUUQEKCVGFTKUMU+PVTCXGPQWU +8 CFOKPKUVTCVKQP Marks designated ®CPFvCTGQYPGFD[5JKTGQTCPCHƂNKCVGFEQORCP[ QHNKƂVGITCUVVQRTGIPCPVTCVUHTQORTGOCVKPIVJTQWIJ 5JKTG75+PE5*+4'CPFVJG5JKTG.QIQCTGVTCFGOCTMUQT IGUVCVKQPFC[FKFPQVRTQFWEGVGTCVQIGPKEKV[CVENKPKECNN[ TGIKUVGTGFVTCFGOCTMUQH5JKTG2JCTOCEGWVKECN*QNFKPIU+TGNCPF relevant systemic exposures. Intravenous administration of .KOKVGFQTKVUCHƂNKCVGU NKƂVGITCUVVQRTGIPCPVTCDDKVUFWTKPIQTICPQIGPGUKURTQFWEGF Patented: please see JVVRUYYYUJKTGEQONGICNPQVKEGRTQFWEVRCVGPVU an increased incidence of omphalocele at the lowest dose .CUV/QFKƂGF5

RRP0719_ShireP0719_Shire PI.inddPI.indd 1 66/17/19/17/19 9:549:54 AMAM THERE’S NO SUBSTIITUTE Xiidra is the only lymphocyte function-associated antigen-1 (LFA-1) antagonist treatment for Dry Eye Disease1,2

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For additional safety information, see accompanying Brief Summary of Safety Information on the adjacent page and Full Prescribing Information on Xiidra-ECP.com.

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