An Update on New Tools and Tactics in the OR

JANUARY/FEBRUARY 2020 VOL. 15, NO. 1 | RETINATODAY.COM Techniques and Technologies

An update on new tools and tactics in the OR

CLOSING A MACULAR HOLE WITH CAN OCTA REDUCE THE NEED FOR WHAT’S NEW FOR BILLING DROPS INSTEAD OF SURGERY FACEDOWN POSITIONING? AND CODING IN 2020?

0120rt_Cover.indd 1 1/30/20 2:20 PM This is

Laser-ablated micro-surface is designed to support atraumatic ILM peel initiation1

Optimized grasping platform and angled tip closure to help mitigate membrane shredding2

GRIESHABER® DSP IMPORTANT PRODUCT INFORMATION Caution: Federal (USA) law restricts this device to sale by, or on the order of, a physician. Indications for Use: GRIESHABER® DSP instruments are a line of single-use vitreoretinal microinstruments which are used in ophthalmic surgery, for cases either in the anterior or the posterior segment. The GRIESHABER® Advanced Backflush Handles DSP are a family of instruments for fluid and gas handling in vitreoretinal surgery. Warnings and Precautions: • Potential risk from reuse or reprocessing GRIESHABER® DSP instruments include: foreign particle introduction to the eye; reduced cutting or grasping performance; path leaks or obstruction resulting in reduced fluidics performance. • Verify correct tip attachment, function and tip actuation before placing it into the eye for surgery. • For light fiber instruments: Minimize light intensity and duration of exposure to the retina to reduce risk of retinal photic injury. The light fiber instruments are designed for use with an ALCON® illumination source. • Good clinical practice dictates the testing for adequate irrigation and aspiration flow prior to entering the eye. If stream of fluid is weak or absent, good fluidics response will be jeopardized. • Use appropriate pressure supply to ensure a stable IOP. • If unwanted tissue gets engaged to the aspiration port, it should be released by interrupting aspiration before moving the instrument. Attention: Please refer to the product labeling for a complete listing of indications, warnings, and precautions.

Reference: 1. Data on File. Alcon Laboratories Inc; May 2018. 2. Data on File. Alcon Laboratories Inc; September 2017.

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Designed to: Enhance stability with a continuously open port and CONSTELLATION® Vision System’s IOP compensation1 Reduce pulsatile traction with 20 000 cuts per minute using 25+® and 27+® gauge probes*, 2,3 Improve vitreous flow4 Enable closer access to tissue plane with beveled tip5

*At similar single-blade flow rates

MIVS IMPORTANT PRODUCT INFORMATION Caution: Federal law restricts this device to sale by, or on the order of, a physician. Indications for Use: The CONSTELLATION® Vision System is an ophthalmic microsurgical system that is indicated for both anterior segment (i.e., phacoemulsification and removal of cataracts) and posterior segment (i.e., vitreoretinal) ophthalmic surgery. The ULTRAVIT® Vitrectomy Probe is indicated for vitreous cutting and aspiration, membrane cutting and aspiration, dissection of tissue and lens removal. The valved entry system is indicated for scleral incision, canulae for posterior instrument access and venting of valved cannulae. The infusion cannula is indicated for posterior segment infusion of liquid or gas. Warnings and Precautions: • The infusion cannula is contraindicated for use of oil infusion. • Attach only Alcon supplied products to console and cassette luer fittings. Improper usage or assembly could result in a potentially hazardous condition for the patient. Mismatch of surgical components and use of settings not specifically adjusted for a particular combination of surgical components may affect system performance and create a patient hazard. Do not connect surgical components to the patient’s intravenous connections. • Each surgical equipment/component combination may require specific surgical setting adjustments. Ensure that appropriate system settings are used with each product combination. Prior to initial use, contact your Alcon sales representative for in-service information. • Care should be taken when inserting sharp instruments through the valve of the Valved Trocar Cannula. Cutting instrument such as vitreous cutters should not be actuated during insertion or removal to avoid cutting the valve membrane. Use the Valved Cannula Vent to vent fluids or gases as needed during injection of viscous oils or heavy liquids. • Visually confirm that adequate air and liquid infusion flow occurs prior to attachment of infusion cannula to the eye. • Ensure proper placement of trocar cannulas to prevent sub-retinal infusion. • Leaking sclerotomies may lead to post operative hypotony. • Vitreous traction has been known to create retinal tears and retinal detachments. • Minimize light intensity and duration of exposure to the retina to reduce the risk of retinal photic injury. ATTENTION: Please refer to the CONSTELLATION® Vision System Operators Manual for a complete listing of indications, warnings and precautions.

References: 1. Irannejad A, Tambat S, Abulon DJK. Retropulsion and mass flow of 27-gauge vitrectomy probes: comparison of dual-blade/flat-tipped probes and single-blade/beveled probes. Poster presented at: 18th Congress of the European Society of Retina Specialists; September 20–23, 2018; Vienna, Austria. 2. Alcon data on file. Alcon Laboratories, Inc; June 2018. 3. Alcon data on file. Alcon Laboratories, Inc; June 2018. 4. Alcon data on file. Alcon Laboratories, Inc; June 2018. 5. Alcon data on file. Alcon Laboratories, Inc; May 2017.

US-GAU-19-E-0842 RT.indd 1 1/8/20 10:05 AM EDITORIAL ADVISORY BOARD CHIEF MEDICAL ASSOCIATE Thomas Albini Pravin U. Dugel John W. Kitchens Elias Reichel EDITOR MEDICAL EDITOR Miami, FL Phoenix, AZ Lexington, KY Boston, MA Allen C. Ho Robert L. Avery J. Fernando Arevalo Jay S. Duker Derek Y. Kunimoto Carl D. Regillo Philadelphia, PA Santa Barbara, CA Baltimore, MD Boston, MA Phoenix, AZ Philadelphia, PA Carl C. Awh Jorge Fortun Baruch Kuppermann Kourous A. Rezaei Nashville, TN Miami, FL Irvine, CA Chicago, IL SECTION EDITORS G. William Aylward Thomas R. Friberg Rohit Ross Lakhanpal Philip J. Rosenfeld RETINA PEARLS GLOBAL PERSPECTIVES London, UK Pittsburgh, PA Owings Mills, MD Miami, FL Dean Eliott Albert J. Augustin Caroline R. Baumal Julia A. Haller Theodore Leng Steven D. Schwartz Boston, MA Karlsruhe, Germany Boston, MA Philadelphia, PA Palo Alto, CA Los Angeles, CA Ingrid U. Scott Ehab El Rayes Rubens Belfort Jr. Tarek S. Hassan Xiaoxin Li Carol L. Shields Hershey, PA Cairo, Egypt São Paulo, Brazil Royal Oak, MI Beijing, China Philadelphia, PA Audina M. Berrocal Stanislao Rizzo Miami, FL Jeffrey Heier Jordi M. Mones Richard F. Spaide BUSINESS MATTERS Boston, MA Barcelona, Spain New York, NY Florence, Italy María H. Berrocal Alan Ruby S.K. Steven Houston III Andrew A. Moshfeghi Ramin Tadayoni Royal Oak, MI San Juan, Puerto Rico Lihteh Wu Lake Mary, FL Los Angeles, CA Paris, France San José, Costa Rica David M. Brown MEDICAL RETINA Houston, TX Jason Hsu Timothy G. Murray Sjakon George Tahija Philadelphia, PA Miami, FL Jordana G. Fein FELLOWS’ FOCUS David S. Boyer Jakarta, Indonesia Fairfax, VA Thomas Jenkins Los Angeles, CA Michael Ip Anton Orlin Nadia Waheed Los Angeles, CA New York, NJ Boston, MA Heeral R. Shah Philadelphia, PA Robison V. Paul Chan Chicago, IL Glenn J. Jaffe Yusuke Oshima Joplin, MO George A. Williams Ravi Pandit Steve Charles Durham, NC Osaka, Japan Royal Oak, MI EYETUBE RETINA CHIEF Philadelphia, PA Memphis, TN Kazuaki Kadonosono Kirk H. Packo Charles C. Wykoff Michael A. Klufas David Xu Allen Chiang Yokohama City, Japan Chicago, IL Houston, TX Philadelphia, PA Philadelphia, PA Philadelphia, PA Peter K. Kaiser Jonathan L. Prenner Young Hee Yoon David R. Chow Cleveland, OH New Brunswick, NJ Seoul, South Korea VISUALLY SPEAKING Mississauga, Canada Richard S. Kaiser Aleksandra Rachitskaya Manish Nagpal Kim Drenser Philadelphia, PA Cleveland, OH Gujarat, India Royal Oak, MI Szilárd Kiss Ehsan Rahimy New York, NY Palo Alto, CA BUSINESS David Levine, Executive Vice President, Stephen Daily, Executive Editor, News Digital & Custom Media +1 484 581 1871; [email protected] David Cox, President/Cofounder +1 609 933 6799; [email protected] +1 484 581 1814; [email protected] Cara Deming, Director, Special Projects Laura O’Connor, Director, +1 484 581 1889; [email protected] Adam Krafczek Jr, Esq, Cofounder Market Analysis & Strategy +1 484 581 1815; [email protected] +1 484 581 1860; [email protected] ART/PRODUCTION Tamara Bogetti, MBA Alvin Fu, Senior Director, Analytics & Technology Executive Vice President/Group Publisher +1 484 581 1888; [email protected] John Follo, Creative/Production Director +1 714 878 0568; [email protected] +1 484 581 1811; [email protected] Janet Burk, Publisher Dominic Condo, Art/Production Director +1 214 394 3551; [email protected] EDITORIAL +1 484 581 1834; [email protected] Gaynor Morrison, Scott Krzywonos, Editor-in-Chief Joe Benincasa, Digital Art Director Vice President, Sales +1 484 581 1880; [email protected] +1 484 581 1822; [email protected] +1 484 581 1836; [email protected] Katie Herman, Associate Editor Rachel McHugh, Associate Art Director Barbara Bandomir, Vice President, Operations +1 484 581 1897; [email protected] +1 484 581 1853; [email protected] +1 484 581 1810; [email protected] Tim Donald, ELS, Consulting Editor Camela Pastorius, CMP, Vice President, [email protected] Meetings & Events, Gillian McDermott, MA, Editor-in-Chief, Clinical Bryn Mawr Communications Group Content, Anterior Segment +1 484 581 1807; [email protected] +1 484 581 1812; [email protected]

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4 RETINA TODAY | JANUARY/FEBRUARY 2020

0120RT_Edboard/Staff.indd 4 1/31/20 10:25 AM New permanent YUTIQ® J code: J7314 Reimbursement just got easier...... New permanent J code effective October 2019 INDICATIONS AND USAGE YUTIQ® (fluocinolone acetonide intravitreal implant) 0.18 mg is indicated for the treatment of chronic non-infectious uveitis affecting the posterior segment of the eye. IMPORTANT SAFETY INFORMATION CONTRAINDICATIONS Ocular or Periocular Infections: YUTIQ is contraindicated in patients with active or suspected ocular or periocular infections including most viral disease of the cornea and conjunctiva including active epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, varicella, mycobacterial infections and fungal diseases. Hypersensitivity: YUTIQ is contraindicated in patients with known hypersensitivity to any components of this product. WARNINGS AND PRECAUTIONS Intravitreal Injection-related Effects: Intravitreal injections, including those with YUTIQ, have been associated with endophthalmitis, eye inflammation, increased or decreased intraocular pressure, and choroidal or retinal detachments. Hypotony has been observed within 24 hours of injection and has resolved within 2 weeks. Patients should be monitored following the intravitreal injection. Steroid-related Effects: Use of corticosteroids including YUTIQ may produce posterior subcapsular cataracts, increased intraocular pressure and glaucoma. Use of corticosteroids may enhance the establishment of secondary ocular infections due to bacteria, fungi, or viruses. Corticosteroids are not recommended to be used in patients with a history of ocular herpes simplex because of the potential for reactivation of the viral infection. Risk of Implant Migration: Patients in whom the posterior capsule of the lens is absent or has a tear are at risk of implant migration into the anterior chamber. ADVERSE REACTIONS In controlled studies, the most common adverse reactions reported were cataract development and increases in intraocular pressure. Please see next page for Brief Summary of full Prescribing Information.

©2019, EyePoint Pharmaceuticals, Inc. All rights reserved. 480 Pleasant Street, Suite B300, Watertown, MA 02472 08/2019 YUTIQ is a registered trademark and the YUTIQ logo and the EyePoint logo are trademarks of EyePoint Pharmaceuticals, Inc. US-YUT-1900098

YTQ190023_J-Code_Retina Today_Ad_2019_FSU_v3 final.indd 1 9/11/2019 11:49:56 AM YUTIQ® (fluocinolone acetonide intravitreal implant) 0.18 mg, Table 1: Ocular Adverse Reactions Reported in ≥ 1% of Subject Eyes and for intravitreal injection Non-Ocular Adverse Reactions Reported in ≥ 2% of Patients Initial U.S. Approval: 1963 Ocular BRIEF SUMMARY: Please see package insert for full prescribing information. YUTIQ Sham Injection 1. INDICATIONS AND USAGE. YUTIQ® (fluocinolone acetonide intravitreal implant) 0.18 mg is indicated for the treatment of chronic non-infectious uveitis affecting ADVERSE REACTIONS (N=226 Eyes) (N=94 Eyes) the posterior segment of the eye. n (%) n (%) 4. CONTRAINDICATIONS. 4.1. Ocular or Periocular Infections. YUTIQ is contra- Vitreous Hemorrhage 4 ( 2%) 0 indicated in patients with active or suspected ocular or periocular infections includ- Iridocyclitis 3 ( 1%) 7 ( 7%) ing most viral disease of the cornea and conjunctiva including active epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, varicella, mycobacterial infec- Eye Inflammation 3 ( 1%) 2 ( 2%) tions and fungal diseases. 4.2. Hypersensitivity. YUTIQ is contraindicated in Choroiditis 3 ( 1%) 1 ( 1%) patients with known hypersensitivity to any components of this product. Eye Irritation 3 ( 1%) 1 ( 1%) 5. WARNINGS AND PRECAUTIONS. 5.1. Intravitreal Injection-related Effects. Intravitreal injections, including those with YUTIQ, have been associated with Visual Field Defect 3 ( 1%) 0 endophthalmitis, eye inflammation, increased or decreased intraocular pressure, Lacrimation Increased 3 ( 1%) 0 and choroidal or retinal detachments. Hypotony has been observed within 24 hours of injection and has resolved within 2 weeks. Patients should be monitored follow- Non-ocular ing the intravitreal injection [see Patient Counseling Information (17) in the full YUTIQ Sham Injection prescribing information]. 5.2. Steroid-related Effects. Use of corticosteroids ADVERSE REACTIONS (N=214 Patients) (N=94 Patients) including YUTIQ may produce posterior subcapsular cataracts, increased intraocu- n (%) n (%) lar pressure and glaucoma. Use of cortico steroids may enhance the establishment of secondary ocular infections due to bacteria, fungi, or viruses. Corticosteroids are Nasopharyngitis 10 ( 5%) 5 ( 5%) not recommended to be used in patients with a history of ocular herpes simplex Hypertension 6 ( 3%) 1 ( 1%) because of the potential for reactivation of the viral infection. 5.3. Risk of Implant Migration. Patients in whom the posterior capsule of the lens is absent or has a Arthralgia 5 ( 2%) 1 ( 1%) tear are at risk of implant migration into the anterior chamber. 1. Includes cataract, cataract subcapsular and lenticular opacities in study eyes 6. ADVERSE REACTIONS. 6.1. Clinical Studies Experience. Because clinical trials that were phakic at baseline. 113 of the 226 YUTIQ study eyes were phakic at are conducted under widely varying conditions, adverse reaction rates observed in baseline; 56 of 94 sham-controlled study eyes were phakic at baseline. the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adverse reac- Table 2: Summary of Elevated IOP Related Adverse Reactions tions associated with ophthalmic steroids including YUTIQ include cataract forma- YUTIQ Sham tion and subsequent cataract surgery, elevated intraocular pressure, which may be ADVERSE REACTIONS (N=226 Eyes) (N=94 Eyes) associated with optic nerve damage, visual acuity and field defects, secondary ocu- n (%) n (%) lar infection from pathogens including herpes simplex, and perforation of the globe IOP elevation ≥ 10 mmHg where there is thinning of the cornea or sclera. Studies 1 and 2 were multicenter, 50 (22%) 11 (12%) randomized, sham injection-controlled, masked trials in which patients with non- from Baseline infectious uveitis affecting the posterior segment of the eye were treated once with IOP elevation > 30 mmHg 28 (12%) 3 (3%) either YUTIQ or sham injection, and then received standard care for the duration of the study. Study 3 was a multicenter, randomized, masked trial in which patients Any IOP-lowering medication 98 (43%) 39 (41%) with non-infectious uveitis affecting the posterior segment of the eye were all Any surgical intervention treated once with YUTIQ, administered by one of two different applicators, and then for elevated IOP 5 (2%) 2 (2%) received standard care for the duration of the study. Table 1 summarizes data available from studies 1, 2 and 3 through 12 months for study eyes treated with YUTIQ Figure 1: Mean IOP During the Studies (n=226) or sham injection (n=94). The most common ocular (study eye) and non- ocular adverse reactions are shown in Table 1 and Table 2. Table 1: Ocular Adverse Reactions Reported in ≥ 1% of Subject Eyes and Non-Ocular Adverse Reactions Reported in ≥ 2% of Patients Ocular YUTIQ Sham Injection ADVERSE REACTIONS (N=226 Eyes) (N=94 Eyes) n (%) n (%) Cataract1 63/113 (56%) 13/56 (23%) Visual Acuity Reduced 33 ( 15%) 11 (12%) Macular Edema 25 ( 11%) 33 (35%) Uveitis 22 ( 10%) 33 (35%) Conjunctival Hemorrhage 17 ( 8%) 5 ( 5%) Eye Pain 17 ( 8%) 12 (13%) 8. USE IN SPECIFIC POPULATIONS. 8.1 Pregnancy. Risk Summary. Adequate and well-controlled studies with YUTIQ have not been conducted in pregnant women to Hypotony Of Eye 16 ( 7%) 1 ( 1%) inform drug associated risk. Animal reproduction studies have not been conducted Anterior Chamber Inflammation 12 ( 5%) 6 ( 6%) with YUTIQ. It is not known whether YUTIQ can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Corticosteroids have been Dry Eye 10 ( 4%) 3 ( 3%) shown to be teratogenic in laboratory animals when administered systemically at Vitreous Opacities 9 ( 4%) 8 ( 9%) relatively low dosage levels. YUTIQ should be given to a pregnant woman only if the Conjunctivitis 9 ( 4%) 5 ( 5%) potential benefit justifies the potential risk to the fetus. All pregnancies have a risk of birth defect, loss, or other adverse outcomes. In the United States general population, Posterior Capsule Opacification 8 ( 4%) 3 ( 3%) the estimated background risk of major birth defects and miscarriage in clinically rec- Ocular Hyperemia 8 ( 4%) 7 ( 7%) ognized pregnancies is 2% to 4% and 15% to 20%, respectively. 8.2 Lactation. Risk Summary. Systemically administered corticosteroids are present in human milk and Vitreous Haze 7 ( 3%) 4 ( 4%) can suppress growth, interfere with endogenous corticosteroid production. Clinical or Foreign Body Sensation In Eyes 7 ( 3%) 2 ( 2%) nonclinical lactation studies have not been conducted with YUTIQ. It is not known Vitritis 6 ( 3%) 8 ( 9%) whether intravitreal treatment with YUTIQ could result in sufficient systemic absorption to produce detectable quantities of fluocinolone acetonide in human milk, or Vitreous Floaters 6 ( 3%) 5 ( 5%) affect breastfed infants or milk production. The developmental and health benefits of Eye Pruritus 6 ( 3%) 5 ( 5%) breastfeeding should be considered, along with the mother’s clinical need for YUTIQ and any potential adverse effects on the breastfed child from YUTIQ. 8.4 Pediatric Conjunctival Hyperemia 5 ( 2%) 2 ( 2%) Use. Safety and effectiveness of YUTIQ in pediatric patients have not been estab- Ocular Discomfort 5 ( 2%) 1 ( 1%) lished. 8.5 Geriatric Use. No overall differences in safety or effectiveness have been Macular Fibrosis 5 ( 2%) 2 ( 2%) observed between elderly and younger patients. Glaucoma 4 ( 2%) 1 ( 1%) Manufactured by: Photopsia 4 ( 2%) 2 ( 2%) EyePoint Pharmaceuticals US, Inc., 480 Pleasant Street, Watertown, MA 02472 USA (continued) Patented.

YTQ190023_J-Code_Retina Today_Ad_2019_FSU_v3 final.indd 2 9/11/2019 11:49:56 AM MEDICAL EDITORS’ PAGE s TRICKS OF THE TRADE

n Retina Today’s 5Q column, found on the final page of involve IOLs. John W. Kitchens, MD, shares a technique for each issue, we often ask retina surgeons what drew them removing dropped IOLs that minimizes the risk of creat- to the specialty. Read enough of those interviews and a ing iatrogenic injury. Second-year Wills Eye Hospital fel- pattern emerges. Synonyms for elegance appear. The word lows Thomas L. Jenkins, MD; Ravi R. Pandit, MD, MPH; and puzzle is used. Passionate phrases such as fell in love with David Xu, MD, provide an introduction to secondary IOLs Iand was mesmerized by emerge in drafts. that is a great place to start for anyone who needs a survey We understand where they’re coming from: there’s a of the latest technology. romance to surgery. A marriage of engineering, medical sci- Some of the topics in this issue take place outside of ence, and talent converge in the OR and buttress each other. the OR. Ragui W. Sedeek, MD, makes the case for why laser New tools allow gifted surgeons to become more precise therapy ought to play a large role in the management of with their movements. Advances in anatomic understanding patients with diabetic eye disease. Michael C. Renfroe, BSA; fuel the need for better equipment. Superior training in fel- Gowtham Jonna, MD; Yong Ren, MMS; Saradha Chexal, MD; lowship motivates surgeons to collaborate with industry to and Chirag D. Jhaveri, MD, explore how use of OCT angiog- craft more advanced instruments. raphy could affect the duration of facedown positioning for This issue of Retina Today explores how our field thinks patients who underwent macular hole surgery. about surgery, both inside and outside the OR. And what about avoiding the OR altogether? Madeleine Michael A. Klufas, MD, highlights some of the latest videos Webb, BA, BS; and Brian C. Joondeph, MD, MPS, profile a on Eyetube, the online depot of surgical videos that even case in which surgery for a macular hole was obviated by a the best surgeons use to keep track of the field’s trends. course of topical NSAID drops. By relying on outside-the-box Ashley M. Crane, MD; and David A. Eichenbaum, MD, thinking, the risks of surgery were avoided. share pearls for Dutch Ophthalmic’s EVA surgical plat- This issue is our gift to retina surgeons. We hope you form, shedding light on how this growing technology find it useful. n has improved their OR. In a review of their favorite tools, Peter A. Karth, MD, MBA; and Rahul K. Reddy, MD, MHS, review Alcon’s HyperVit Dual Blade Vitrectomy Probe and ALLEN C. HO, MD ROBERT L. AVERY, MD Bausch + Lomb’s Bi-Blade Cutter, respectively. As retina surgeons, we’re often managing cases that CHIEF MEDICAL EDITOR ASSOCIATE MEDICAL EDITOR

From the Cover John W. Kitchens, MD, wrote an article in this issue about a technique for remov- A B C ing dropped plate haptic IOLs. By using a soft-tip cannula for removal of the IOL, he mitigates the risk of iatrogenic injury (A). Dr. Kitchens describes moving the IOL to the middle of the vitreous cavity, where safe manipulation is possible (B). The large incision required to remove the IOL doubles as an entry point for an anterior chamber IOL or other large IOL (C). Want to know how Donald J. D’Amico, MD; María H. Berrocal, MD; and Timothy G. Murray, MD, MBA, reacted to the technique shared by Dr. Kitchens? Read his article in this issue’s cover focus to find out.

JANUARY/FEBRUARY 2019 | RETINA TODAY 7

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Cover image credit: ©iStockphoto.com JANUARY/FEBRUARY 2020 • VOLUME 15, NO. 1 FEATURES 26 Eyetube Retina Channel Update 42 Avoiding Iatrogenic Injury During IOL Removal By Michael A. Klufas, MD By John W. Kitchens, MD 28 Surgical Pearls for the EVA Platform 44 An Elusive Macular Hole Closed by Eye Drops Alone By Ashley M. Crane, MD; and David A. Eichenbaum, MD By Madeleine Webb, BA, BS; and Brian C. Joondeph, MD, MPS 30 Introduction to Secondary IOLs 46 The Beauty of a Dual-Blade Vitrectomy Probe By Thomas L. Jenkins, MD; Ravi R. Pandit, MD, MPH; and David Xu, MD By Peter A. Karth, MD, MBA 34 The Case for Modern Lasers in Diabetic Eye Disease 47 Bi-Blade Cutter Provides Fast Speeds, Improved Fluidics By Ragui W. Sedeek, MD By Rahul K. Reddy, MD, MHS 38 OCT Angiography to Confirm Macular Hole Closure and Reduce Facedown Positioning By Michael C. Renfroe, BSA; Gowtham Jonna, MD; Yong Ren, MMS; Saradha Chexal, MD; and Chirag D. Jhaveri, MD

DEPARTMENTS UP FRONT MEETING MINUTES 7 Medical Editors’ Page 22 VBS at Mediterranean Retina By Allen C. Ho, MD; and Robert L. Avery, MD By R. Ross Lakhanpal, MD, FACS 9 Retina News SPECIAL REPORT VISUALLY SPEAKING 50 Widefield Multimodal Imaging 10 Widefield Fluorescein Angiography in Coats Disease By Manish Nagpal, MS, DO, FRCS(Edin); Gayathri Mohan, MS; By Boontip Tipsuriyaporn, MD; and Yoshihiro Yonekawa, MD Akshar Soni, MS; Sham Talati, DO; and Navneet Mehrotra, DNB, MNAMS GLOBAL PERSPECTIVES 54 Visual Disturbances in Headache 14 Ophthalmic Manifestations of Neurosyphilis: By Kimberly M. Winges, MD A Case Report By Sukumaran Ramanathan, MB, BS, FRCSEd, DO; PA AVENUE UPDATES and Agata Nizankowska, MB, BS 57 Cost Effectiveness Analysis in Retina ONCOLOGY By Thomas A. Ciulla, MD, MBA 17 Uveal Effusion Secondary to Hyperviscosity CODING ADVISOR From Chronic Lymphocytic Leukemia 62 What’s New in 2020 for Retina Coding and Reimbursement By Sunidhi Ramesh, BS; Min Kim, MD; By Joy Woodke, COE, OCS, OCSR and Carol L. Shields, MD IN THE BACK 65 Ad Index 66 5Q With Dilraj Grewal, MD

8 RETINA TODAY | JANUARY/FEBRUARY 2020

0120RT_TOC.indd 8 1/31/20 10:49 AM JANUARY/FEBRUARY 2020 RT NEWS VOL. 15, NO. 1 | RETINATODAY.COM SIX-MONTH DATA REPORTED FROM ONGOING PHASE 1/2 CLINICAL TRIAL IN X-LINKED RETINITIS PIGMENTOSA

Gene therapy company Applied Genetic Technologies s WATCH IT NOW Corporation (also called AGTC) reported positive interim 6-month data from its ongoing phase 1/2 clinical program in X-linked retinitis pigmentosa (XLRP). Patients treated centrally with the product candidate demonstrated durable improvement in visual function 6 months after dosing. These data reinforce the promising efficacy and safety results reported in September 2019 and will help investigators to design an XLRP pivotal trial that the company plans to initiate by the end of 2020, according to a company news release. Data from 17 of the 25 patients were reported in September and suggested a favorable safety profile. Of the 17 patients, eight peripherally treated patients had stable visual function through bit.ly/Eyewire0120 6 months, and nine centrally treated patients experienced an patients, measurable improvements were observed in visual improvement in visual function as measured by microperimetry sensitivity for four of the evaluable eight patients. All nine and/or BCVA through 3 months. patients demonstrated stable or improved visual acuity, with At the 6-month time point for those nine centrally dosed 78% experiencing an improvement of at least 5 letters. n NEWS BRIEFS Read Eyewire’s latest retina news at Eyewire.news/interests/retina. > US FDA APPROVES FIRST TREATMENT FOR THYROID The Pagoda trial is a phase 3, multicenter, randomized, active-comparator, noninferiority study that will evaluate the efficacy, safety, and pharmacokinet- EYE DISEASE ics of the PDS for the treatment of DME. Nearly 550 patients with DME will The US FDA approved teprotumumab-trbw (Tepezza, Horizon Therapeutics) for the be randomly assigned to receive either the PDS 100 mg/mL refilled at fixed treatment of adults with thyroid eye disease, a rare condition in which the muscles and 6-month intervals or monthly intravitreal injections of ranibizumab 0.5 mg. The fatty tissues behind the eye become inflamed, pushing the eye forward and causing it to primary endpoint of the Pagoda trial is the change in BCVA from baseline aver- bulge outwards. This is the first drug approved for the treatment of thyroid eye disease. aged over weeks 48 and 50. Teprotumumab is a fully human monoclonal antibody and a targeted inhibitor of the insulin-like growth factor-1 receptor. It is administered to patients once >>> OERTLI LAUNCHES THE VIPER ILLUMINATED every 3 weeks for a total of eight infusions. SCLERAL INDENTOR FOR RETINAL SURGERY >> PHASE 3 TRIAL OF THE PORT DELIVERY SYSTEM FOR Oertli Instrumente announced the launch of the ViPer illuminated scleral indentor for retinal surgery. The ViPer facilitates work in the periphery of the posterior seg- DIABETIC MACULAR EDEMA BEGINS ment thanks to its ability to indent and illuminate transsclerally at the same time, Genentech and Roche have initiated a new phase 3 clinical trial of the Port according to the company. Delivery System (PDS) with ranibizumab (Lucentis, Genentech) in patients with The tool is semitransparent and therefore an antiglare and backscatter-free diabetic macular edema (DME). The PDS is an investigational, first-of-its-kind, instrument. The consistent illumination of the indented tissue improves the user’s refillable implant designed to continuously release a customized formulation of view of the retinal periphery, while the rounded 360° tip ensures its easy applica- ranibizumab into the eye over a period of months. tion and excellent mobility, according to the company.

JANUARY/FEBRUARY 2020 | RETINA TODAY 9

0120rt_News.indd 9 1/30/20 2:11 PM s VISUALLY SPEAKING WIDEFIELD FLUORESCEIN ANGIOGRAPHY IN COATS DISEASE Imaging was essential in guiding the treatment for this pediatric patient.

BY BOONTIP TIPSURIYAPORN, MD; AND YOSHIHIRO YONEKAWA, MD

3-year-old girl presented with A leukocoria in the left eye. The anterior segment in each eye was normal. Fundus examination of the left eye showed Aextensive exudates in the posterior pole, subretinal fluid from arcade to arcade, retinal hemorrhages, and extensive telangiectatic vessels throughout the periphery with aneurysmal lesions superiorly (Image A). No mass lesions were observed. Widefield fluorescein angiography (WFA; RetCam 3, Natus) demonstrated diffuse vascular leakage, telangiectasia, aneurysms in the periphery, and large areas of capillary dropout and nonperfusion (Image B). The vascular findings on WFA were classic for Coats disease. Laser photocoagulation, intravitreal B bevacizumab (Avastin, Genentech), and sub-Tenon triamcinolone were administered. The laser was used to photocoagulate the nonperfused retina, to apply long duration laser burns to close the aneurysms, and to paint the incompetent vessels. The patient required three more treatment sessions before the vascular leakage resolved and there was substantial improvement of the exudation and resolution of the subretinal fluid. Coats disease is a retinal vascular abnormality characterized by idiopathic retinal vascular telangiectasia and microvascular aneurysmal changes that can cause exudation and exudative retinal detachment.1

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0120rt_Visually Speaking_Yonekawa.indd 10 1/30/20 3:08 PM VISUALLY SPEAKING s

COATS DISEASE IS A RETINAL VASCULAR ABNORMALITY CHARACTERIZED BY IDIOPATHIC RETINAL VASCULAR TELANGIECTASIA AND MICROVASCULAR ANEURYSMAL CHANGES THAT CAN CAUSE EXUDATION AND EXUDATIVE RETINAL DETACHMENT.

The mainstay of management of Coats disease is photoco- 4. Kusaka S. Surgical management of Coats disease. Asia Pac J Ophthalmol. 2018;7(3):156-159. 5. Yonekawa Y, Chan RVP. Widefield imaging-guided treatment of pediatric vitreoretinal diseases. Retina Today. March 2014: agulation to treat the nonperfused retina and to obliterate 54-57. the aneurysms and leaking vessels.1,2 Anti-VEGF injections and periocular steroids are not routinely administered but BOONTIP TIPSURIYAPORN, MD may be used as adjunctive treatments for severe disease.3 n Department of Ophthalmology, Faculty of Medicine, Ramathibodi Hospital, Vitreoretinal surgery may be necessary for extensive retinal Mahidol University, Bangkok detachment; in that event, we recommend an external n [email protected] drainage approach.4 WFA imaging is essential to identify n Financial disclosure: None all vascular pathology that must be lasered, and it can also provide data on when to stop treatment and be used for YOSHIHIRO YONEKAWA, MD n follow-up surveillance.5 n Adult and Pediatric Retina Surgeon, Wills Eye Hospital/Mid Atlantic Retina, Philadelphia 1. Shields JA, Shields CL, Honavar SG, Cater J. Classification and management of Coats disease: the 2000 Proctor Lecture. n Assistant Professor of Ophthalmology, Sidney Kimmel Medical College, Thomas Am J Ophthalmol. 2001;131(5):572-583. 2. Ong SS, Buckley EG, McCuen BW 2nd, et al. Comparison of visual outcomes in Coats’ disease: a 20-year experience. Jefferson University, Philadelphia Ophthalmology. 2017;124(9):1368-1376. n [email protected] 3. Sein J, Tzu JH, Murray TG, Berrocal AM. Treatment of Coats’ disease with combination therapy of intravitreal bevacizum- n ab, laser photocoagulation, and sub-Tenon corticosteroids. Ophthalmic Surg Lasers Imaging Retina. 2016;47(5):443-439. Financial disclosure: Consultant (Alcon)

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0120rt_Visually Speaking_Yonekawa.indd 11 1/30/20 3:08 PM I AM MODERNIZING RETINA CARE WITH AN ALL-IN-ONE EHR SOLUTION

You may have heard that our EHR is so smart that it actually learns how you diagnose retinal detachment or perform treatments with anti-VEGF injections. But did you know that it’s also part of an all-in-one, ophthalmology-specific platform designed to give you greater clinical, financial and operational visibility into your practice? And with the improved communication and fewer redundancies of an integrated solution, you can spend more time focusing on your patients.

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Untitled-2 12 1/29/20 10:44 AM I AM MODERNIZING RETINA CARE WITH AN ALL-IN-ONE EHR SOLUTION

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Untitled-2 13 1/29/20 10:44 AM 1/31/20 10:27 AM - Positive Positive (Ref.Lab.) >1:10240 (Ref.Lab.) Positive disease research laboratory/rapid plasmalaboratory/rapid research disease g screen: Tryponemal screen (enzyme immunoas- (enzyme screen Tryponemal screen: Positive g haemagglutination testhaemagglutination pallidum yponema g IgM pallidum yponema Syphilis say) Tr (TPHA) Tr Venereal

Figure 1. An all-over erythematous rash that was present for more than 7 weeks for more than 7 weeks Figure 1. An all-over erythematous rash that was present before onset of visual deterioration. Fluorescein angiography (FA) showed fluorescent mottlingfluorescent showed (FA) angiography Fluorescein presentation:on results investigation Relevant • • • • ing of the retinal pigment epithelium (RPE) layer, hyper- layer, (RPE) epithelium pigment retinal the of ing theof obliteration and layer, nuclear outer the of reflectivity eye.each of region macular the in membrane limiting outer fluid subretinal of evidence showed also OD macula The 5).and 4 (Figures fovea the at (SRF) frames,late the in leakage by followed OS region macular the of theto inferior and superior areas circumscribed fairly involving hyperfluores diffuse of area an showed OD fundus The fovea. foveathe to superior localized FA, on frames late the in cence 7). and 6 (Figures diameters disc 2 about of area an involving and

1-4

as well as rare manifestations such as gummaas such manifestations rare as well as 5 These disorders can occur due to other etiologies,other to due occur can disorders These

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Reported ophthalmic manifestations of syphilis includesyphilis manifestationsof ophthalmic Reported reti- acute chorioretinitis, uveitis, keratitis, interstitial opticand nerve cranial and vasculitis, retinal nitis, everal recent reports have indicated a resurgence of theof resurgence a indicated have reports recent everal world. the of regions some in syphilis of prevalence Spectral-domain OCT showed irregularity and thicken- and irregularity showed OCT Spectral-domain On examination, BCVA was 0.70 logMAR in the right eyeright the in logMAR 0.70 was BCVA examination, On A 49-year-old white woman presented with rapid deterio- rapid with presented woman white 49-year-old A In this article we report a case of acute placoid retinalplacoid acute of case a report we article this In Highlighting the characteristics of this condition that is experiencing a resurgence in some parts of the world. parts of in some a resurgence experiencing this condition that is of characteristics Highlighting the FRCSED, DO; AND AGATA NIZANKOWSKA, MB, BS BY SUKUMARAN RAMANATHAN, MB, BS, of the superior orbital muscle bundle and anterior nodularanterior and bundle muscle orbital superior the of scleritis. (OD) and 0.90 in the left eye (OS) logMAR. The anteriorThe logMAR. (OS) eye left the in 0.90 and (OD) showedexamination Fundus eye. each in quiet was chamber thein edema retinal subtle of areas placoid circumscribed 3).and 2 (Figures eye each in region macular ration of vision in both eyes of 3 days’ duration. Occasionalduration. days’ 3 of eyes both in vision of ration painless,reported patient The reported. also was photpsia andupper her over rash reddish-brown rough, non-itchy, 1).(Figure weeks several for present torso and limbs lower Hervoice. of hoarsenessand ulcers mouth had also She hypertension,for treatment included history medical bilateraland hysterectomy, abdominal total previous ramipril,included medications Her salpingo-oophorectomy. hormonefor estrogens conjugated and omeprazole, therapy. replacement CASE REPORT CASE REPORT

NEUROSYPHILIS: A CASE REPORT REPORT CASE A NEUROSYPHILIS: OPHTHALMIC MANIFESTATIONS OF OF MANIFESTATIONS OPHTHALMIC neuropathies, pigment epitheliopathy secondary to tertiary syphilis, withsyphilis, tertiary to secondary epitheliopathy pigment Treatmentcomplaint. presenting the as vision of loss acute discussed.are outcome clinical and so a high index of clinical suspicion is required to identifyto required is suspicion clinical of index high a so agent.causative the as pallidum Treponema S RETINA TODAY

GLOBAL PERSPECTIVES s 14 0120rt_Global_Ramanathan.indd 14 GLOBAL PERSPECTIVES s

Figure 2. Color photo of the fundus OD showing an area of subtle retinal elevation Figure 3. Color photo of the fundus OS showing area of subtle retinal elevation superior to the fovea (arrows), due to chorioretinitis. superior to the fovea (arrows), due to chorioretinitis.

Figure 4. OCT showing irregularity and thickening of the RPE and obliteration of the Figure 5. OCT showing irregularity and thickening of the RPE and obliteration of outer outer limiting membrane in the macular region OD. The macula showed evidence of limiting membrane in the macular region OS. subfoveal fluid.

reagin (VDRL/RPR) g Positive titre 1:32 0.06 logMAR OS. Fundus examination showed no significant • Cerebrospinal fluid polymerase chain reaction abnormality in either eye. OCT showed reduced irregularity (PCR) g Positive for Treponema pallidum and thickening of the RPE layer and a well-defined outer lim- • HIV g Negative iting membrane in each eye. There was complete resolution Treatment was initiated with a 14-day course of benzyl- of SRF OD (Figures 8 and 9). penicillin (2.4 g intravenous six times daily), along with oral prednisolone 20.0 mg for 4 days, 15.0 mg for 7 days, 10.0 mg DISCUSSION for 7 days, and 5.0 mg for 7 days. The patient’s partner tested The British Ocular Syphilis Study reported findings in 63 eyes positive for syphilis and was also treated appropriately. Oral of 41 patients during a 2-year surveillance.8 Bilateral involve- thrush was treated with nystatin (100,000 units/mL) 1 mL ment was noted in 56% of patients. After treatment, mean orally for 7 days and benzydamine HCl 0.15% w/v (Difflam, VA improved, with 92.1% of eyes achieving VA of 0.3 logMAR Difflam) oral rinse four times daily for 4 weeks. or better. Average duration of symptoms was 1 month. After the course of penicillin, the patient’s vision recovered Moradi et al, in a study including 61 eyes of 35 patients seen at a and the rashes resolved. BCVA was 0.00 logMAR OD and referral center, reported stable visual outcomes with treatment

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0120rt_Global_Ramanathan.indd 15 1/30/20 2:04 PM 1/31/20 10:27 AM Figure 9. OCT showing reduced irregularity and thickening of the RPE layer and Figure 9. OCT showing reduced irregularity and thickening of the RPE layer and well-defined outer limiting membrane OS. Figure 7. FA showing fluorescent mottling of the macular region OS followed by region OS followed by Figure 7. FA showing fluorescent mottling of the macular areas superior and diffuse leakage in the late frames, involving fairly circumscribed inferior to the fovea. Consultant Ophthalmic Surgeon, Pilgrim Hospital, Boston, United Kingdom [email protected] Financial disclosure: None House Officer (Foundation Year 2), Pilgrim Hospital, Boston, United Kingdom Financial disclosure: None

SUKUMARAN RAMANATHAN, MB, BS, FRCSED, DO Critical Care Medicine. 2017;195:A5585. 7. Casey R, Flowers CW Jr, Jones DD, Scott L. Anterior nodular scleritis secondary to syphilis. Arch Ophthalmol. 1996;114(8):1015-1016. 8. Mathew RG, Goh BT, Westcott MC. British Ocular Syphilis Study (BOSS): 2-year national surveillance study of intraocular inflammation secondary to ocular syphilis. Invest Ophthalmol Vis Sci. 2014;55(8):5394-5400. 9. Moradi A, Salek S, Daniel E, et al. Clinical features and incidence rates of ocular complications in patients with ocular syphilis. Am J Ophthalmol. 2015;159(2):334-343.e1. n n n AGATA NIZANKOWSKA, MB, BS n n

9 n

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In the case reported here, the patient presented withinpresented patient the here, reported case the In Figure 8. OCT showing reduced irregularity and thickening of the RPE layer and a Figure 8. OCT showing reduced irregularity and thickening of the RPE layer and a well-defined outer limiting membrane OD. There was complete resolution of SRF. Figure 6. FA showing diffuse leakage OD, localized superior to the fovea. Figure 6. FA showing diffuse leakage OD, localized superior 3 days of onset of visual deterioration, and features of plac- of features and deterioration, visual of onset of days 3 compre- a prompted epitheliopathy pigment retinal oid anddiagnosis rapid in resulting investigations, of set hensive aplayed have may treatment of initiation Prompt treatment. patient. this in recovery visual impressive the in role in 33.3% of eyes and deterioration of vision in 13% of eyes. of 13% in vision of deterioration and eyes of 33.3% in 1. Furtado JM, Arantes TE, Nascimento H, et al. Clinical manifestations and ophthalmic outcomes of ocular syphilis at a time of re-emergence of the systemic infection. Sci Rep. 2018;8(1):12071. Erratum in: Sci Rep. 2018;8(1):15902. 2. Mustapha M, Abdollah Z, Ahem A, Mohd Isa H, Bastion MC, Din NM. Ocular syphilis: resurgence of an old disease in modern Malaysian society. Int J Ophthalmol. 2018;11(9):1573-1576. 3. Oliver SE, Aubin M, Atwell L, et al. Ocular syphilis - eight jurisdictions, United States, 2014-2015. MMWR Morb Mortal Wkly Rep. 2016;65(43):1185-1188. 4. Clinical Advisory: Ocular Syphilis in the United States. Centers for Disease Control and Prevention. Updated March 24, 2016. https://www.cdc.gov/std/syphilis/clinicaladvisoryos2015.htm. Accessed January 14, 2020. 5. Kiss S, Damico FM, Young LH. Ocular manifestations and treatment of syphilis. Semin Ophthalmol. 2005;20(3):161-167. 6. Chandar P, Kulandaisamy S, Shenoy MA, et al. An unusual case of ocular syphilis. American Journal of Respiratory and RETINA TODAY

GLOBAL PERSPECTIVES s 16 0120rt_Global_Ramanathan.indd 16 OCULAR ONCOLOGY s UVEAL EFFUSION SECONDARY TO HYPERVISCOSITY FROM CHRONIC LYMPHOCYTIC LEUKEMIA

Partial spontaneous resolution was documented over 30 months in this case report.

BY SUNIDHI RAMESH, BS; MIN KIM, MD; AND CAROL L. SHIELDS, MD

hronic lymphocytic leukemia a case of uveal effusion secondary to treated with thyroidectomy and radio- (CLL) is a B-cell malignancy char- hyperviscosity from CLL. active iodine; squamous cell carcinoma acterized by an accumulation of of the right arm, which was surgically functionally incompetent mono- CASE REPORT excised; and CLL diagnosed 11 years clonal lymphocytes in the bone A 67-year-old white woman with a before presentation and followed with Cmarrow, blood, and lymph nodes. This 2-month history of a blind spot in the observation. At the time of presenta- condition is known for its slow rate of left eye (OS) was referred to the Ocular tion, the patient reported no meta- cell division and disease progression, Oncology Service at Wills Eye Hospital static disease and noted long-standing and, for this reason, CLL is often fol- for evaluation of a possible intraocular hypertension. lowed conservatively.1 mass. She had previously been seen by VA was 20/25 in the right eye A sequela of CLL is hyperviscosity several retina specialists who had sus- (OD) and 20/40 OS on examination. syndrome. This occurs when the blood pected a retinal detachment, posterior Tortuosity of the retinal veins was becomes hyperviscous secondary to scleritis, or tumor. observed OD, but there was no sign an increase in immunoglobulins or Ocular history included LASIK in of intraretinal, subretinal, or choroidal the hyperproliferation of blood com- each eye 17 years before her presenta- fluid or mass. The macula OD was ponents.2 Ultimately, hyperviscosity tion to us and cataract surgery in each intact. Similar retinal venous tortuos- may lead to a series of hematologic, eye. Medical history included several ity was noted OS, but with shallow cardiovascular, neurologic, and renal previous cancers, including a basal cell subretinal fluid and a smooth, brown, complications, as well as bleeding from carcinoma of the right brow, which peripheral choroidal area that may mucous membranes.3 was surgically excised; thyroid cancer, have been presumed to be a mass in all Ophthalmic manifestations associated with hyperviscosity syndrome AT A GLANCE are not common but can manifest as venous distention or tortuosity, s Hyperviscosity syndrome, in which blood becomes hyperviscous, is a local areas of beading and dilatation of retinal vessels creating a string-of- common sequela of chronic lymphocytic leukemia.

sausage appearance, and flame-shaped s hemorrhages.3 Uveal effusion as a In this case study, hyperviscosity led to uveal effusion. The patient was manifestation of hyperviscosity is quite followed for 30 months. uncommon. In this article we describe

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4 /µL) was/µL) In theIn 3 4 /µL). Given the underlyingthe Given /µL). 3 The most important scleropathy isscleropathy important most The Choroidal effusion represents anrepresents effusion Choroidal At 30 months, the eye demon- eye the months, 30 At Hydrodynamic factors that canthat factors Hydrodynamic nanophthalmos. Nanophthalmos isNanophthalmos nanophthalmos. mm20 of length axial an by defined complicated be often can and less or exu- and glaucoma angle-closure by detachment. retinal dative to 10.5 x 10 x 10.5 to accumulation of fluid in the supra- the in fluid of accumulation variousare There space. choroidal including notably most etiologies, acquired),or (congenital scleropathies either(through factors hydrodynamic uvealelevated or hypotony ocular fac- inflammatory pressure), venous conditions. neoplastic and tors, DISCUSSION DISCUSSION presence of suprachoroidal fluid. The fluid. suprachoroidal of presence suspectedwas effusion uveal of cause sec- hyperviscosity to related be to whitepatient’s the as CLL, to ondary 10 x (22.9 count cell blood moderately elevated (normal 4.5 x 10 x 4.5 (normal elevated moderately conditions and intact macula, a perioda macula, intact and conditions advised. was observation of spontaneouscomplete nearly strated ODFundoscopy effusion. of resolution persistentshowed and normal was Fundoscopytortuosity. vascular retinal of resolution dramatic showed OS residualminimal with effusion the retinaldiffuse and elevation choroidal temporally.epitheliopathy pigment decreasedhad thickness choroidal The with ultrasonography on mm 3.3 to OCTon undulation choroidal trace sub- no was There 2). (Figure imaging edema.macular no and fluid retinal improvedhad and OD 20/40 was VA OS.20/25 to patient described in this article, thearticle, this in described patient outruling mm, 23.2 was length axial nanophthalmos. includehypotony ocular to lead sur- or trauma ocular leak, wound anddysfunction, body ciliary gery, detachment.retinal rhegmatogenous tolead can that factors Hydrodynamic includepressure venous uveal elevated globeand syndrome Sturge-Weber At this point, a diagnosis of choroi- of diagnosis a point, this At B B lation of the choroidal surface withoutsurface choroidal the of lation OS.edema macular or fluid subretinal intactotherwise was OS macula The 1C). (Figure givenbut, suspected, was effusion dal malignancy,of history patient’s the con- test This performed. was MRI an theand detachment choroidal firmed | JANUARY/FEBRUARY 2020

C C A A OCT imaging showed shallow undu- shallow showed imaging OCT Ultrasonography confirmed the sus- the confirmed Ultrasonography - Figure 2. At 30 months, a marked reduction in the choroidal effusion was observed OS (A, arrow). Choroidal detach ment was measured at 3.28 mm elevation on ultrasound (B). OCT imaging showed fewer, minimally perceptible choroidal undulations (C, arrows). Figure 1. This is a case of choroidal effusion in a 67-year-old woman with CLL. At presentation, the left eye demonstrated woman with CLL. At presentation, the left eye demonstrated Figure 1. This is a case of choroidal effusion in a 67-year-old in the nasal quadrant (A, arrow). Ultrasonography dilated tortuous retinal veins and a large orange-brown “mass” (B). OCT showed shallow choroidal undulations (C, arrows). documented choroidal detachment with 4.75 mm elevation pected mass to be choroidal detach- choroidal be to mass pected inmm 4.8 (effusion)measuring ment andOD mm (23.4 length Axial height. limitsnormal within was OS) mm 23.2 1B).(Figure four quadrants but was most notablemost was but quadrants four 1A).(Figure nasally RETINA TODAY

18 s OCULAR ONCOLOGY 0120rt_Oncology.indd 18 OCULAR ONCOLOGY s

OUR STRATEGY IS TYPICALLY TO OBSERVE MILD CASES AND TRIAL ALL OTHERS ON ORAL OR PERIOCULAR CORTICOSTEROIDS. PATIENTS WHO DO NOT RESPOND TO CORTICOSTEROIDS ARE THEN ADVISED TO

UNDERGO SCLEROTOMY, IF NECESSARY.

globulin abnormalities. Semin Hematol. 1973;10(2):113-24. 4. Carricondo PC, Andrade T, Prasov L, Ayres BM, Moroi SE. Nanoph- compression from orbital mass or of the eye in eight patients (8.3%) and thalmos: a review of the clinical spectrum and genetics. J Ophthalmol. hemorrhage. In our patient, we specu- indirect involvement of the eye from 2018;2018:2735465. 5. Shields CL, Roelofs K, Di Nicola M, et al. Uveal effusion syndrome in 104 late that the effusion was related to a anemia, thrombocytopenia, hyper- eyes: Response to corticosteroids - The 2017 Axel C. Hansen Lecture. Indian J hydrodynamic process of hyperviscos- viscosity, total body irradiation, and Ophthalmol. 2017;65(11):1093-1104. 6. Mansour A, Stewart MW, Shields CL, et al. Extensive circumferential partial- ity from her elevated white blood cell immunosuppression in 42 patients thickness sclerectomy in eyes with extreme nanophthalmos and spontaneous count, leading to sludging of vascular (43.8%).10 The other patients in the uveal effusion. Br J Ophthalmol. 2019;103(12):1862-1867. 7. Reddy SC, Jackson N, Menon BS. Ocular involvement in leukemia – a study flow and raised venous pressure. series showed no evidence of ocular of 288 cases. Ophthalmologica. 2003;217:441-445. The treatment of uveal effusion changes due to leukemia. The authors 8. Omoti CE, Awodu OA, Bazuaye GN. Chronic lymphoid leukaemia: clinico- haematological correlation and outcome in a single institution in Niger Delta typically involves corticosteroid (oral, noted that ocular involvement was region of Nigeria. Int J Lab Hematol. 2007;29:426-432. periocular, or intraocular) therapy or more often found in patients with 9. Leonardy NJ, Rupani M, Dent G, et al. Analysis of 135 autopsy eyes for ocular involvement in leukemia. Am J Ophthalmol. 1990;109:436-444. surgical sclerotomy (either partial or acute and myeloid leukemia and 10. Koshy J, John MJ, Thomas S, et al. Ophthalmic manifestations of acute full-thickness scleral resection). In 2017, was relatively uncommon in cases of and chronic leukemias presenting to a tertiary care center in India. Indian J Shields et al reviewed 104 eyes with chronic and lymphocytic leukemia. Ophthalmol. 2015;63(8):659. non-nanophthalmic uveal effusion treated with corticosteroids and found CONCLUSION that control was achieved in 95% of This article described a patient with eyes, and scleral window surgery was uveal effusion as a rare manifestation MIN KIM, MD required in only 5% of cases.5 of hyperviscosity syndrome from CLL. n Fellow, Ocular Oncology Service, Wills Eye Sclerotomy is a technique designed In this patient, partial spontaneous Hospital, Thomas Jefferson University, Philadelphia to create a scleral window to allow resolution was documented over n Associate Professor, Department of drainage of suprachoroidal and supra- 30 months. n Ophthalmology, Yonsei University College of ciliary fluid. Mansour et al published a Medicine, Seoul, Korea case series in which uveal effusion was Support provided in part by the n [email protected] treated in eight nanophthalmic eyes Eye Tumor Research Foundation, n Financial disclosure: None of five patients using sclerotomy. In Philadelphia, PA (CLS). The funders that series, all effusions resolved within had no role in the design and conduct SUNIDHI RAMESH, BS an average of 14 days.6 Our strategy is of the study, in the collection, analysis n Sidney Kimmel Medical College, Thomas Jefferson typically to observe mild cases and trial and interpretation of the data, and in University, Philadelphia all others on oral or periocular cortico- the preparation, review or approval of n [email protected] steroids. Patients who do not respond the manuscript. Carol L. Shields, MD, n Financial disclosure: None to corticosteroids are then advised to has had full access to all the data in the undergo sclerotomy, if necessary. study and takes responsibility for the CAROL L. SHIELDS, MD Leukemia can affect the eye in integrity of the data. n Director, Ocular Oncology Service, Wills Eye several ways.7-9 Koshy et al described Hospital, Thomas Jefferson University, Philadelphia 1. Chiorazzi N, Rai KR, Ferrarini M. Chronic lymphocytic leukemia. N Engl J Med. n Editorial Advisory Board Member, Retina Today ophthalmic manifestations of acute 2005;352(8):804-815. and chronic leukemias in 96 patients 2. Buchan J, McKibbin M, Burton T. The prevalence of ocular disease in chronic n [email protected] lymphocytic leukaemia. Eye (Lond). 2003;17(1):27-30. n Financial disclosure: None and found direct leukemic infiltration 3. Bloch KJ, Maki DG. Hyperviscosity syndromes associated with immuno-

JANUARY/FEBRUARY 2020 | RETINA TODAY 19

0120rt_Oncology.indd 19 1/30/20 4:07 PM Sponsored by

SS-OCT: Clinical Applications for Diagnosing and Following Ocular Pathology Faster scanning speed provides clear images that aid in identifying pathology while greater penetrance allows the ability to understand changes in deeper tissues, such as the choroid and lamina cribrosa.

BY RUBENS BELFORT, MD, PHD; PEARSE KEANE, MD; AND KI HO PARK, MD, PHD

wept-source OCT (SS-OCT) represents available for clinical use. The DRI OCT Triton, 6 x 6 mm macular cube scan were performed a variation on a technology that has which also includes a non-mydriatic color with SD-OCT, and a 12 x 9 mm widefield become indispensable for imaging the fundus camera and a monochrome camera scan was performed with SS-OCT. Detection anterior and posterior segments— for fluorescein angiography and fundus of RNFL defect from thickness and deviation one with technological advances autofluorescence, achieves a scanning speed maps was assessed by three independent Sthat confer distinct benefits for identifying of 100,000 A Scans/sec to provide superior glaucoma specialists. Diagnostic power for pathology and monitoring ocular tissues. visualization of the vitreous and choroid detecting glaucoma was also compared using At the 3rd International Swept-Source in the same scan. Meanwhile, the intuitive circumpapillary RNFL thickness at 3.4 mm; OCT & Angiography Conference, three oph- IMAGEnet 6 software enables dynamic GCIPL map on SD-OCT versus Macular GCL+ thalmologists discussed how they are using viewing of OCT data—providing 3D, 2D, map on SS-OCT; and GCIPL on SD-OCT this technology in clinical practice. Following and fundus images simultaneously—and versus Macular GCL ++ thickness on SS-OCT. is a summary of their lectures, focusing on Pin-Point Registration identifies an exact For the diagnostic accuracy of myopic how SS-OCT improves diagnostic accuracy pathological location across all imaging glaucoma, wide GCL ++ and GCL+ thickness and facilitates clinical decision-making in a modalities available within the Triton. maps showed higher accuracy compared broad range of clinical settings. to GCIPL thickness for both inferotemporal SS-OCT IS MORE SENSITIVE FOR DETECTING and superotemporal defects. Additionally, ABOUT SS-OCT MYOPIC GLAUCOMA the wide GCL+ superpixel map showed Similar to spectral-domain OCT (SD-OCT), The faster scan speed, wider scan area, and significantly higher accuracy compared to SS-OCT imaging relies on backscattered higher penetration associated with SS-OCT the GCIPL deviation map for inferotemporal light that is compared to a reference beam relative to SD-OCT would seem to allow for defects, with borderline significance for that, when superimposed, creates an more accurate depiction of retinal nerve fiber superotemporal defects. In the comparison interference pattern—a principle known layer (RNFL) defects in myopic glaucoma. analysis of area under the receiver operating as low-coherence interferometry. Each Ki Ho Park, MD, PhD, performed a characteristic curve (AUROC) for glaucoma technology employs principles of Fourier prospective observation study in 150 eyes between SS-OCT and SD-OCT, SS-OCT transformation to measure simultaneous with myopic glaucoma (n = 104 perimetric showed significantly larger AUROC in the sources of backscattered light. However, there and 46 pre-perimetric) and 50 healthy eyes superior and 11-o’clock sectors of RNFL are some important differences in how these with myopia to understand the diagnostic thickness compared to SD-OCT. In addition, technologies work, with implications for the accuracy of SS-OCT vs SD-OCT.1 Glaucoma the AUROC for glaucoma was significantly types of images they produce. was defined as neuroretinal rim change larger for GCL+ thickness from SS-OCT The Topcon DRI OCT Triton is one of the and/or RNFL defect by photography. For all compared to GCIPL thickness from SD-OCT most advanced SS-OCT devices to become eyes, a 6 x 6 mm optic disc cube scan and a in average, superior temporal, inferonasal, and inferior sectors. SD-OCT SS-OCT Based on the results, Dr. Park concluded Broadband light source Narrow bandwidth laser that rapidly sweeps over a broad range of that SS-OCT showed better accuracy for wavelengths—provides greater penetrance to choroidal layers detection of RNFL defects in myopic eyes, which corresponded with better diagnostic Uses a spectrometer to detect returning Uses a point photodetector, allowing faster scanning speeds and accuracy for detection of glaucoma in myopic wavelengths reduced signal-to-noise ratio degradation over imaging depth eyes. He also emphasized that the wide scan

20 INSERT TO RETINA TODAY | JANUARY/FEBRUARY 2020 The views, thoughts, and opinions expressed in the article belong solely to the authors.

0120RT_Topcon ISSOCT #1_ROB v2.indd 20 1/30/20 2:45 PM range of SS-OCT has an advantage in detect- thereby providing insight on the activity of was discontinued after further examination ing RNFL defects that may have been missed the disease. of OCT imaging. Subsequent laboratory test- in the conventional SD-OCT scan range. Dr. Keane emphasized that such an ing instead revealed a diagnosis of cat scratch approach is an emerging paradigm for disease. In this patient, despite the presence A POTENTIAL ROLE FOR SS-OCTA IN following DR, and until more data are available, of frank retinal changes, the choroid was MANAGEMENT OF DR clinicians should be cautious in interpreting the relatively unaffected. The treatment paradigm for diabetic kinds of findings he described. Nevertheless, retinopathy (DR) is changing in light of the combined use of OCT and OCTA, particu- CONCLUSION data from recently completed clinical trials larly with SS-OCT technology, appears to be a SS-OCT has a broad range of potential showing the benefit of anti-VEGF therapy promising approach for monitoring neovascu- applications for discovering pathology for proliferative DR (PDR), and perhaps in larization at the disc. and following it over time. Ultimately, the some cases of nonproliferative DR (NPDR) as increased sensitivity, particularly of the well. Analogous to how the PrONTO study CHOROIDAL CHANGES MAY HELP choroid and deep structures of the eye, impacted the use of OCT for disease moni- DISTINGUISH UVEITIC SUBTYPES provides new information that assists the toring in age-related macular degeneration There is increasing evidence that the clinician in making decisions. Meanwhile, the (AMD), widefield OCT and OCT angiography extent and degree of choroidal involvement idea of using multiple imaging modalities (OCTA) are poised to be similarly integral seen on SS-OCT may help distinguish to discern disease features is an emerging mechanisms for objective quantitative uveitic etiologies. According to Rubens paradigm across all sectors of eye care. With analysis of PDR, monitoring the status of the Belfort, MD, PhD, several forms of uveitis the potential to perform multiple imaging retina structure and function, and ultimately, have similar retinal findings, which may studies on a single platform, coupled with for making decisions about treatment and lead to them being classified as idiopathic, correlation to anatomic markers across determining its effect. if additional testing and diagnostics do not various imaging modalities, the Topcon In his presentation, Pearse Keane, MD, said reveal an obvious cause.3 This may delay the DRI OCT Triton is poised to be a powerful that he performs a line scan, a 3D volume initiation of appropriate treatment, with clinical tool for anterior and posterior seg- scan (which he compared to macular OCT potential to lead to incomplete resolution of ment ophthalmologists. n on SD-OCT), and a 6 x 6 mm angio disc scan inflammation. On the other hand, the deeper 1. Park KH. Role of SSOCT in diagnosis of myopic glaucoma. Presented at Topcon’s 3rd centered on the optic disc for all patients penetration capability of SS-OCT is improving International Swept Source OCT & Angiography Conference. July 26-30, 2019; Fort 2 Myers, Florida. entering with DR. In situations where there the ability to appreciate subtle choroidal 2. Keane P. SSOCTA in proliferative diabetic retinopathy. Presented at Topcon’s 3rd is concern over peripheral regions, additional changes associated with uveitic subtypes that International Swept Source OCT & Angiography Conference. July 26-30, 2019; Fort Myers, Florida. scans may be ordered. provide insight on the diagnosis, prognosis, 3. Belfort R, Novaes E, Andrade G, et al. Swept Source OCT Angiography in chorio-retinal inflammatory diseases. Presented at Topcon’s 3rd International Swept Source OCT & How’s this approach making an impact and response to treatment. Angiography Conference. July 26-30, 2019; Fort Myers, Florida. in the clinic? A 62-year-old woman with Dr. Belfort highlighted a number of cases type 2 diabetes and a history of prior from his clinic that demonstrate the potential panretinal photocoagulation presented role of SS-OCT imaging in managing uveitis. RUBENS BELFORT, MD, PHD for a consultation. Line scan OCT revealed A 29-year-old woman with toxoplasmosis n Head professor of ophthalmology at the Federal diabetic macular edema. In addition, areas that was confirmed with IgM testing with University of Sao Paulo and Vision Institute, Brazil of preretinal hyper-reflectance were visible, decreased vision of 20/40 in the right eye was n [email protected] suggesting neovascularization in that region. successfully treated with anti-toxoplasmic n Financial Disclosures: Speaker (Topcon) Superimposing the structural OCT over the drugs, with visual acuity resolving to 20/20. PEARSE KEANE, MD angio disc scan in this case helped to confirm However, the patient discontinued therapy on n Consultant Ophthalmologist/NIHR Clinician Scientist, the presence of neovascularization, with her own and returned to the clinic 9 months Moorfields Eye Hospital/Institute of Ophthalmology red dots in the preretinal hyper-reflected later with recurrence and visual acuity of University College material suggesting perfusion within that 20/160. SS-OCT imaging performed during this n [email protected] tissue. According to Dr. Keane, such findings visit showed an apparent artifact above the n Financial Disclosures: Speaker (Allergan, Bayer, Carl Zeiss are often missed during clinical examination sclero-choroidal junction. After reviewing other Meditec, Haag-Streit, Heidelberg Engineering, Novartis, or on SD-OCT imaging. Additional use of en imaging, Dr. Belfort said it became clear that Topcon); Advisory Board (Bayer, Novartis); Consultant face imaging may be additive in discovering there was choroidal involvement, which was (Apellis, DeepMind Technologies, Novartis, Roche) neovascularization at the disc, he said. In this confirmed by the choroidal thickening over case, fibrous tissue was apparent on the disc the site of the pathology. KI HO PARK, MD, PHD despite the history of previous laser. Following In another example, a 17-year-old n Professor and chairman of ophthalmology at Seoul anti-VEGF treatment, repeat imaging did not patient with HM vision was referred National University and current President of the Korean show the same preretinal hyper-reflective to Dr. Belfort’s clinic for suspected Ophthalmology Society material, while OCTA showed no presence toxoplasmosis. The patient was initially n [email protected] of blood flow in the corresponding region, started on anti-toxoplasmic drugs, but that n Financial Disclosures: None

JANUARY/FEBRUARY 2020 | INSERT TO RETINA TODAY 21

0120RT_Topcon ISSOCT #1_ROB v2.indd 21 1/30/20 2:45 PM 1/30/20 2:08 PM

CASE No. 3: CASE 3: No. MD FORLINI, MATTEO (ITALY) In this situation, some surgeons maysurgeons some situation, this In meritsthe debated panelists The impor- the discussed also panel The Dr. Forlini began his presentation onpresentation his began Forlini Dr. opt for silicone oil removal, secondaryremoval, oil silicone for opt replacementand peel, membrane PPV, Quiroz-Mercado,Dr. oil. silicone the of mem- a perform to decided however, withoil silicone under peel brane placenot did and cutter vitreous the 25-gaugeused He eye. the in infusion instrumentation. thisin instrumentation 27-gauge of outpointed I debate, this During case. would instrumentation 27-gauge that betweenintervene to surgeon a allow casethis in membranes tractional the 25-gaugeor 23- than effectively more instrumentation. thisfor removal oil silicone of tance complica- potential the and patient hemostasis.to related tions ocular trauma surgery by pointing outpointing by surgery trauma ocular vitreoretinalmany cases, such in that, per- of challenge the face surgeons cor- opacified an through PPV forming fundusthe of visualization making nea, duebe may opacities Media difficult. Mediterranean Retina 2019 meeting in Mediterranean Retina 2019 meeting in

HUGO QUIROZ- MD MERCADO, CASE No. 2: CASE 2: No. (MEXICO) (MEXICO) The VBS hosted a panel at the Dubrovnik, Croatia, that sparked discussion about surgical techniques. The international RRD. chronic trauma, and vitrectomy, complicated cases involving VBS paneldiscussed AT A GLANCE s s Dr. Quiroz-Mercado shared a casea shared Quiroz-Mercado Dr. (Bausch + Lomb) to the sulcus duringsulcus the to Lomb) + (Bausch timewhich at procedure, second a of reconstruction perform would he videoa shared Coney Dr. pupil. the fortechniques multiple demonstrating iridodialysistraumatic a with dealing laterthen and RD an of repair and maximizeto lens secondary a placing debatedpanelists The potential. visual of complexity the on based whether, scleral-fixateda procedure, first the choicebetter a been have would IOL TheyIOL. chamber anterior an than scleral- general, in that, out pointed fewerpotentially have IOLs fixated as(such complications long-term syndrome), uveitis-glaucoma-hyphema in advances recent that noted and havetechnology IOL chamber anterior complication. of risk the decreased involving a patient with a diabetic trac- diabetic a with patient a involving PPV,undergone had who RD tional place- oil silicone and peel, membrane remainedtraction surgery, After ment. patientthe and macula, central the on metamorphopsia. reported

CASE No. 1: CASE 1: No. MD JOSEPH CONEY, STATES) (UNITED Debates were frequent at the VBS panel at the Mediterranean Retina 2019 meeting. meeting. Retina 2019 at the Mediterranean VBS panel at the Debates were frequent MD, FACS BY R. ROSS LAKHANPAL,

JANUARY/FEBRUARY 2020 | s president of the Vit-Bucklethe of president s tohonored was I (VBS), Society sym- a moderate and attend Mediterraneanthe at posium in meeting 2019 Retina

He planned to suture an Akreos IOLAkreos an suture to planned He Dr. Coney presented a case ofcase a presented Coney Dr. I moderated a panel on surgical chal- surgical on panel a moderated I

a 65-year-old aphakic man with awith man aphakic 65-year-old a planapars a received who hyphema scleral-fixeda and (PPV) vitrectomy cataractcomplicated a following IOL evacuation,hyphema After procedure. 4-clock-houra surgeonidentified the andmaterial, lens retained iridodialysis, (RD). detachment retinal inferior an vitrectomyposterior and Anterior werefragments lens performed, was performed, was repair RD removed, tech- machine sewing modified a and iridodi- the repair to used was nique dem- video a showed Coney Dr. alysis. machine sewing the how onstrating rootiris the reattached technique sclera. the to VBS AT MEDITERRANEAN RETINA MEDITERRANEAN AT VBS lenges that included Joseph Coney, MD;Coney, Joseph included that lenges Quiroz- Hugo MD; Forlini, Matteo MD. Lazic, Ratko and MD; Mercado, inthat, case a presented panelistEach Meeting,Annual VBS the of spirit the newwelcomed and debate sparked cases.those summarize I Here, ideas. Dubrovnik, Croatia. Several societ- Several Croatia. Dubrovnik, meeting,the at represented were ies Vitreoretinal European the including ofSociety Vitreoretinal the and Society thathonored and humbled was I India. of group this in included was VBS the societies. distinguished A RETINA TODAY

22 s MEETING MINUTES 0120rt_Meeting Minutes_Lakhanpal.indd 22 For your appropriate patients with severe acute or chronic uveitis, keratitis, or scleritis

STEROIDS BIOLOGICS

Envision another way to treat ocular inflammatory disease

For more information, visit actharophthalmology.com

Indication Acthar® Gel (repository corticotropin injection) is indicated for severe acute and chronic allergic and inflammatory processes involving the eye and its adnexa such as: keratitis, iritis, iridocyclitis, diffuse posterior uveitis and choroiditis, optic neuritis, chorioretinitis, anterior segment inflammation. Important Safety Information • Acthar may be associated with central nervous system effects Contraindications ranging from euphoria, insomnia, irritability, mood swings, • Acthar should never be administered intravenously personality changes, and severe depression, and psychosis. • Administration of live or live attenuated vaccines is Existing conditions may be aggravated contraindicated in patients receiving immunosuppressive doses • Patients with comorbid disease may have that disease of Acthar worsened. Caution should be used when prescribing Acthar in • Acthar is contraindicated where congenital infections are patients with diabetes and myasthenia gravis suspected in infants • Prolonged use of Acthar may produce cataracts, glaucoma and • Acthar is contraindicated in patients with scleroderma, secondary ocular infections. Monitor for signs and symptoms osteoporosis, systemic fungal infections, ocular herpes simplex, • Acthar is immunogenic and prolonged administration of Acthar recent surgery, history of or the presence of a peptic ulcer, may increase the risk of hypersensitivity reactions. Neutralizing congestive heart failure, uncontrolled hypertension, primary antibodies with chronic administration may lead to loss of adrenocortical insufficiency, adrenocortical hyperfunction or endogenous ACTH activity sensitivity to proteins of porcine origins • There is an enhanced effect in patients with hypothyroidism and in those with cirrhosis of the liver Warnings and Precautions • Long-term use may have negative effects on growth and • The adverse effects of Acthar are related primarily to its physical development in children. Monitor pediatric patients steroidogenic effects • Decrease in bone density may occur. Bone density should be • Acthar may increase susceptibility to new infection or monitored for patients on long-term therapy reactivation of latent infections • Pregnancy Class C: Acthar has been shown to have an • Suppression of the hypothalamic-pituitary-axis (HPA) may embryocidal effect and should be used during pregnancy only if occur following prolonged therapy with the potential for adrenal the potential benefit justifies the potential risk to the fetus insufficiency after withdrawal of the medication. Adrenal insufficiency may be minimized by tapering of the Adverse Reactions dose when discontinuing treatment. During recovery of the • Common adverse reactions for Acthar are similar to those of adrenal gland patients should be protected from the stress corticosteroids and include fluid retention, alteration in glucose (e.g. trauma or surgery) by the use of corticosteroids. tolerance, elevation in blood pressure, behavioral and mood Monitor patients for effects of HPA suppression after changes, increased appetite and weight gain stopping treatment • Specific adverse reactions reported in IS clinical trials in • Cushing’s syndrome may occur during therapy but generally infants and children under 2 years of age included: infection, resolves after therapy is stopped. Monitor patients for signs hypertension, irritability, Cushingoid symptoms, constipation, and symptoms diarrhea, vomiting, pyrexia, weight gain, increased appetite, • Acthar can cause elevation of blood pressure, salt and water decreased appetite, nasal congestion, acne, rash, and cardiac retention, and hypokalemia. Blood pressure, sodium and hypertrophy. Convulsions were also reported, but these may potassium levels may need to be monitored actually be occurring because some IS patients progress to • Acthar often acts by masking symptoms of other diseases/ other forms of seizures and IS sometimes mask other seizures, disorders. Monitor patients carefully during and for a period which become visible once the clinical spasms from IS resolve following discontinuation of therapy • Acthar can cause GI bleeding and gastric ulcer. There is also Other adverse events reported are included in the full an increased risk for perforation in patients with certain Prescribing Information. Please see Brief Summary of full gastrointestinal disorders. Monitor for signs of bleeding Prescribing Information on the adjacent page.

Mallinckrodt, the “M” brand mark and the Mallinckrodt Pharmaceuticals logo are trademarks of a Mallinckrodt company. Other brands are trademarks of a Mallinckrodt company or their respective owners. © 2019 Mallinckrodt. US-1900690 07/19

Untitled-1 45 7/16/19 12:27 PM

1500638-Acthar_Journal Ad_Rv4.indd 1 7/10/19 12:21 PM Perigord US www.perigord-as.com [email protected] PGD #: 500843 Acthar Gel Brief Summary Language(s): English Black Proof #: 5 14 Jun 2019 Part no.: US-1900771 Size: 7.375 in x 10.375 in Fonts: Helvetica Neue Lt Std Condensed, Condensed Oblique, Bold Condensed; Symbol Regular Minimum font size: 5.2 point

BRIEF SUMMARY - Consult full Patients should be monitored carefully during and for a period Recommended 150 U/ complete cessation of spasms and elimination of hypsarrhythmia. prescribing information before use. following discontinuation of therapy for signs of infection, abnormal 75 U/m2 bid m2 qd Safety in the pediatric population for infantile spasms was cardiac function, hypertension, hyperglycemia, change in body System Organ Class n=122, (%) n=37 (%) evaluated by retrospective chart reviews and data from non-sponsor weight and fecal blood loss. Acthar® Gel (repository corticotropin injection) INJECTION, GEL Metabolism and nutrition disorders conducted clinical trials [see Adverse Reactions (6.1.1)]. While Gastrointestinal Perforation and Bleeding the types of adverse reactions seen in infants and children under for INTRAMUSCULAR | SUBCUTANEOUS use Increased appetite 0 5 Initial U.S. Approval: 1952 Acthar Gel can cause GI bleeding and gastric ulcer. There is also an 2 years of age treated for infantile spasms are similar to those seen increased risk for perforation in patients with certain gastrointestinal Decreased appetite 3 3 in older patients, their frequency and severity may be different due INDICATIONS AND USAGE disorders. Signs of gastrointestinal perforation, such as peritoneal Nervous system disorders to the very young age of the infant, the underlying disorder, the Infantile spasms: irritation, may be masked by the therapy. Use caution where there duration of therapy and the dosage regimen. Effects on growth are Convulsion† 12 3 Acthar Gel (repository corticotropin injection) is indicated as is the possibility of impending perforation, abscess or other pyogenic of particular concern [see Warnings and Precautions (5.12)]. Serious monotherapy for the treatment of infantile spasms in infants and infections, diverticulitis, fresh intestinal anastomoses, and active or Respiratory, thoracic and mediastinal disorders adverse reactions observed in adults may also occur in children [see children under 2 years of age. latent peptic ulcer. Nasal Congestion 1 5 Warnings and Precautions (5)]. Multiple Sclerosis: Behavioral and Mood Disturbances Skin and subcutaneous tissue disorders OVERDOSAGE Acthar Gel (repository corticotropin injection) is indicated for the Use of Acthar Gel may be associated with central nervous system Acne 0 14 While chronic exposure to Acthar Gel at high doses can be treatment of acute exacerbations of multiple sclerosis in adults. effects ranging from euphoria, insomnia, irritability (especially in associated with a variety of potential serious adverse effects, Controlled clinical trials have shown Acthar Gel to be effective in Rash 0 8 infants), mood swings, personality changes, and severe depression, it is not expected that a single high dose, or even several large speeding the resolution of acute exacerbations of multiple sclerosis. to frank psychotic manifestations. Also, existing emotional instability Vascular disorders doses, has the potential for serious adverse effects compared to However, there is no evidence that it affects the ultimate outcome or psychotic tendencies may be aggravated. Hypertension 11 19 a standard dose. There have been no reports of death or acute or natural history of the disease. Comorbid Diseases *Specific infections that occurred at≥ 2% were candidiasis, otitis overdose symptoms from Acthar Gel in clinical studies or in the Rheumatic Disorders: Patients with a comorbid disease may have that disease worsened. media, pneumonia and upper respiratory tract infections. †In the published literature. As adjunctive therapy for short-term administration (to tide the Caution should be used when prescribing Acthar Gel in patients with treatment of Infantile Spasms, other types of seizures/convulsions The intramuscular route of administration makes it unlikely that patient over an acute episode or exacerbation) in: Psoriatic arthritis; diabetes and myasthenia gravis. may occur because some patients with infantile spasms progress an inadvertent acute overdose will occur. The typical daily dose Rheumatoid arthritis, including juvenile rheumatoid arthritis Ophthalmic Effects to other forms of seizures (for example, Lennox-Gastaut of Acthar Gel to treat an infant that has a BSA of 0.4 m2 would (selected cases may require low-dose maintenance therapy), Syndrome). Additionally the spasms sometimes mask other be 60 U/day. Using the 1-cc syringe supplied with Acthar Gel, the Ankylosing spondylitis. Prolonged use of Acthar Gel may produce posterior subcapsular cataracts, glaucoma with possible damage to the optic nerves and seizures and once the spasms resolve after treatment, the other maximum amount that can be injected is 80 U/injection, which is a Collagen Diseases: may enhance the establishment of secondary ocular infections due seizures may become visible. well-tolerated single dose. During an exacerbation or as maintenance therapy in selected to fungi and viruses. cases of: systemic lupus erythematosus, systemic dermatomyositis These adverse reactions may also be seen in adults and children HOW SUPPLIED / STORAGE AND HANDLING (polymyositis). Immunogenicity Potential over 2 years of age when treated for other purposes and with Acthar Gel (repository corticotropin injection) is supplied as 5 mL Acthar Gel is immunogenic. Limited available data suggest that different doses and regimens. multi-dose vial (63004-8710-1) containing 80 USP Units per mL. Dermatologic Diseases: a patient may develop antibodies to Acthar Gel after chronic Postmarketing Experience Acthar Gel (repository corticotropin injection) should be warmed to Severe erythema multiforme, Stevens-Johnson syndrome. administration and loss of endogenous ACTH and Acthar Gel activity. The following adverse reactions associated with the use of room temperature before using. Do not over pressurize the vial prior Allergic States: Prolonged administration of Acthar Gel may increase the risk of Acthar Gel have been identified from postmarketing experience with to withdrawing the product. Serum sickness. hypersensitivity reactions. Sensitivity to porcine protein should Acthar Gel. Only adverse events that are not listed above as adverse Store Acthar Gel (repository corticotropin injection) under be considered before starting therapy and during the course of events reported from retrospective chart reviews and non-sponsor refrigeration between 2° to 8°C (36° to 46°F). Product is stable Ophthalmic Diseases: treatment should symptoms arise. Severe acute and chronic allergic and inflammatory processes conducted clinical trials and those not discussed elsewhere in for the period indicated on the label when stored under the involving the eye and its adnexa such as: keratitis; iritis, iridocyclitis, Use in Patients with Hypothyroidism or Liver Cirrhosis labeling, are listed in this section. Because the adverse reactions conditions described. There is an enhanced effect in patients with hypothyroidism and in are reported voluntarily from a population of uncertain size, it is not diffuse posterior uveitis and choroiditis, optic neuritis, chorioretinitis; PATIENT COUNSELING INFORMATION anterior segment inflammation. those with cirrhosis of the liver. always possible to estimate their frequency or establish a causal Caretakers of patients with infantile spasms should be informed of Negative Effects on Growth and Physical Development relationship to use with Acthar Gel. Events are categorized by Respiratory Diseases: system organ class. Unless otherwise noted these adverse events the availability of a Medication Guide, and they should be instructed Long-term use of Acthar Gel may have negative effects on growth Symptomatic sarcoidosis. have been reported in infants, children and adults. to read the Medication Guide prior to administering Acthar Gel. and physical development in children. Changes in appetite are seen Patients should be instructed to take Acthar Gel only as prescribed. Edematous State: with Acthar Gel therapy, with the effects becoming more frequent Allergic Reactions To induce a diuresis or a remission of proteinuria in the nephrotic They should not stop treatment suddenly unless instructed by their as the dose or treatment period increases. These effects are Allergic responses have presented as dizziness, nausea and shock physician to do so. syndrome without uremia of the idiopathic type or that due to reversible once Acthar Gel therapy is stopped. Growth and physical (adults only). lupus erythematosus. Patients, their caregivers and families should be advised as to the development of pediatric patients on prolonged therapy should be Cardiovascular carefully monitored. importance of the need for careful monitoring while on and during CONTRAINDICATIONS Necrotizing angitis (adults only) and congestive heart failure. titration from Acthar Gel treatment and the importance of not Acthar Gel is contraindicated for intravenous administration. Decrease in Bone Density Dermatologic missing scheduled doctor’s appointments. Decrease in bone formation and an increase in bone resorption both Acthar Gel is contraindicated where congenital infections are Skin thinning (adults only), facial erythema and increased sweating Patients, their caregivers and families should be advised that if suspected in infants. through an effect on calcium regulation (i.e. decreasing absorption (adults only). and increasing excretion) and inhibition of osteoblast function may the patient develops an infection or fever they should contact their Administration of live or live attenuated vaccines is contraindicated occur. These, together with a decrease in the protein matrix of the Endocrine physician. They should be educated that a fever may not necessarily in patients receiving immunosuppressive doses of Acthar Gel. bone (secondary to an increase in protein catabolism) and reduced Decreased carbohydrate tolerance (infants only) and hirsutism. be present during infection. The patient should also try to limit contact with other people with infections to minimize the risk of Acthar Gel is contraindicated in patients with scleroderma, sex hormone production, may lead to inhibition of bone growth in Gastrointestinal infection while taking Acthar Gel. osteoporosis, systemic fungal infections, ocular herpes simplex, children and adolescents and to the development of osteoporosis [see Warnings and Precautions Pancreatitis (adults only), abdominal distention and ulcerative (5.1) and Adverse Reactions (6.1.1)] recent surgery, history of or the presence of a peptic ulcer, at any age. Special consideration should be given to patients at esophagitis. congestive heart failure, uncontrolled hypertension, primary increased risk of osteoporosis (i.e., postmenopausal women) before Patients, their caregivers and families should be advised that if adrenocortical insufficiency, adrenocortical hyperfunction or initiating therapy, and bone density should be monitored in patients General Disorders and Administration Site Conditions the patient experiences an increase in blood pressure they should sensitivity to proteins of porcine origin. on long term therapy. Injection site reactions. contact their physician. [see Warnings and Precautions (5.3) and Metabolic Adverse Reactions (6.1.1)] WARNINGS AND PRECAUTIONS Use in Pregnancy Acthar Gel has been shown to have an embryocidal effect. Hypokalemic alkalosis (infants only). Patients, their caregivers and families should be advised that if the The adverse effects of Acthar Gel are related primarily to its patient or the caregiver notices blood or a change in color of the steroidogenic effects. Not all of the adverse events described below Apprise women of potential harm to the fetus. [see Use in Specific Musculoskeletal patient’s stool they should contact their physician. [see Warnings have been seen after treatment with Acthar Gel, but might be Populations (8.1)] Muscle weakness and vertebral compression fractures (infants and Precautions (5.6)] expected to occur. [see Adverse Reactions (6.3)] ADVERSE REACTIONS only). Caregivers and families of infants and children treated with Infections Please refer to Adverse Reactions in Infants and Children Under Neurological Headache (adults only), vertigo (adults only), subdural hematoma, Acthar Gel should be informed that the patient may show signs of Acthar Gel may increase the risks related to infections with 2 Years of Age (Section 6.1.1) for consideration when treating irritability and sleep disturbances. These effects are reversible once patients with Infantile Spasms. The adverse reactions presented in intracranial hemorrhage (adults only), and reversible brain any pathogen, including viral, bacterial, fungal, protozoan or Acthar Gel therapy is stopped. [see Warnings and Precautions (5.7) Section 6.2 are primarily provided for consideration in use in adults shrinkage (usually secondary to hypertension) (infants only). helminthic infections. Patients with latent tuberculosis or tuberculin and Adverse Reactions (6.1.1)] reactivity should be observed closely, and if therapy is prolonged, and in children over 2 years of age, but these adverse reactions Possible Additional Steroidogenic Effects Patients, their caregivers and families should be advised that chemoprophylaxis should be instituted. should also be considered when treating infants and children Based on steroidogenic effects of Acthar Gel certain adverse changes in appetite, most often leading to weight gain, are seen under 2 years of age. events may be expected due to the pharmacological effects of Cushing’s Syndrome and Adrenal Insufficiency Upon with Acthar Gel therapy, becoming more frequent as the dose corticosteroids. The adverse events that may occur but have not Withdrawal Acthar Gel causes the release of endogenous cortisol from the or treatment period increases. These effects are reversible once adrenal gland. Therefore all the adverse effects known to occur been reported for Acthar Gel are: Treatment with Acthar Gel can cause hypothalamic-pituitary-axis Acthar Gel therapy is stopped. [see Warnings and Precautions (5.12) with elevated cortisol may occur with Acthar Gel administration as (HPA) suppression and Cushing’s syndrome. These conditions Dermatologic and Adverse Reactions (6.1.1)] should be monitored especially with chronic use. well. Common adverse reactions include fluid retention, alteration in Impaired wound healing, abscess, petechiae and ecchymoses, and glucose tolerance, elevation in blood pressure, behavioral and mood Patients, their caregivers and families should be advised that the Suppression of the HPA may occur following prolonged therapy suppression of skin test reactions. changes, increased appetite and weight gain. patient may be monitored for signs of adrenal insufficiency such with the potential for adrenal insufficiency after withdrawal of the Endocrine as weakness, fatigue, lethargy, anorexia, weight loss, hypotension, medication. Patients should be monitored for signs of insufficiency Clinical Studies Experience Menstrual irregularities. abdominal pain or hyperpigmentation (adults only) after treatment such as weakness, hyperpigmentation, weight loss, hypotension Because clinical trials are conducted under widely varying Metabolic has stopped. Since the recovery of the adrenal gland varies from and abdominal pain. conditions, adverse reaction rates observed in the clinical trials of days to months, patients may need to be protected from the stress Negative nitrogen balance due to protein catabolism. The symptoms of adrenal insufficiency in infants treated for infantile a drug cannot be directly compared to rates in the clinical trials of of trauma or surgery by the use of corticosteroids during the period spasms can be difficult to identify. The symptoms are non-specific another drug, and may not reflect the rates observed in practice. Musculoskeletal of stress. [see Warnings and Precautions (5.2)] and may include anorexia, fatigue, lethargy, weakness, excessive Adverse Reactions in Infants and Children Under 2 Years of Age Loss of muscle mass and aseptic necrosis of femoral and humeral Patients should be advised not to be vaccinated with live or live weight loss, hypotension and abdominal pain. It is critical that While the types of adverse reactions seen in infants and children heads. attenuated vaccines during treatment with Acthar Gel. Additionally, parents and caregivers be made aware of the possibility of under age 2 treated for infantile spasms are similar to those seen Neurological other immunization procedures in patients or in family members adrenal insufficiency when discontinuing Acthar Gel and should in older patients, their frequency and severity may be different due Increased intracranial pressure with papilledema, (pseudo-tumor who will be in contact with the patient should be undertaken with be instructed to observe for, and be able to recognize, these to the very young age of the infant, the underlying disorder, the cerebri) usually after treatment, and subdural effusion. caution while the patient is taking Acthar Gel. [see Warnings and symptoms. [see Patient Counseling Information (17)] duration of therapy and the dosage regimen. Below is a summary Ophthalmic Precautions (5.4)] The recovery of the adrenal gland may take from days to months so of adverse reactions specifically tabulated from source data derived from retrospective chart reviews and clinical trials in children under Exophthalmos. Patients, their caregivers and families should be advised that patients should be protected from the stress (e.g. trauma or surgery) prolonged use of Acthar Gel in children may result in Cushing’s by the use of corticosteroids during the period of stress. 2 years of age treated for infantile spasms. The number of patients DRUG INTERACTIONS in controlled trials at the recommended dose was too few to provide syndrome and associated adverse reactions, may inhibit skeletal Formal drug-drug interaction studies have not been performed. The adrenal insufficiency may be minimized in adults and infants by meaningful incidence rates or to permit a meaningful comparison growth, and may cause osteoporosis and decreased bone tapering of the dose when discontinuing treatment. to the control groups. Acthar Gel may accentuate the electrolyte loss associated with density. If prolonged use is necessary, Acthar Gel should be given intermittently along with careful observation. Signs or symptoms of Cushing’s syndrome may occur during diuretic therapy. [see Warnings and TABLE: Incidence (%) of Treatment Emergent Adverse Precautions (5.2), (5.12), and (5.13) and Adverse Reactions (6.1.1)] therapy but generally resolve after therapy is stopped. Patients Events Occurring in ≥ 2% of Acthar Gel USE IN SPECIFIC POPULATIONS Patients, their caregivers and families should be informed that should be monitored for these signs and symptoms such as (repository corticotropin injection) Infants and Pregnancy deposition of adipose tissue in characteristics sites (e.g., moon Acthar Gel may mask symptoms of other diseases/disorders without Children under 2 years of Age Pregnancy Class C: Acthar Gel has been shown to have an face, truncal obesity), cutaneous striae, easy bruisability, decreased altering the course of the other disease/disorder. The patient will embryocidal effect. There are no adequate and well-controlled bone mineralization, weight gain, muscle weakness, hyperglycemia, Recommended 150 U/ need to be monitored carefully during and for a period following 2 2 studies in pregnant women. Acthar Gel should be used during and hypertension. 75 U/m bid m qd discontinuation of therapy for signs of infection, abnormal cardiac System Organ Class n=122, (%) n=37 (%) pregnancy only if the potential benefit justifies the potential risk function, hypertension, hyperglycemia, change in body weight, and Elevated Blood Pressure, Salt and Water Retention and to the fetus. fecal blood loss. Hypokalemia Cardiac disorders [see Warnings and Precautions (5.5)] Nursing Mothers Acthar Gel can cause elevation of blood pressure, salt and water Cardiac Hypertrophy 3 0 In the treatment of Infantile Spasms, other types of seizures may It is not known whether this drug is excreted in human milk. retention, and increased excretion of potassium and calcium. occur because some patients with infantile spasms progress to Endocrine disorders Because many drugs are excreted in human milk and because of Dietary salt restriction and potassium supplementation may be other forms of seizures (for example, Lennox-Gastaut Syndrome). Cushingoid 3 22 the potential for serious adverse reactions in nursing infants from necessary. Caution should be used in the treatment of patients Additionally the spasms sometimes mask other seizures and once Acthar Gel, when treating a nursing mother, a decision should be with hypertension, congestive heart failure, or renal insufficiency. Gastrointestinal disorders the spasms resolve after treatment with Acthar Gel, the other made whether to discontinue nursing or to discontinue the drug, Constipation 0 5 seizures may become visible. Parents and caregivers should inform Vaccination considering the risk and benefit to the mother. their physician of any new onset of seizures so that appropriate Administration of live or live attenuated vaccines is contrain dicated Diarrhea 3 14 Pediatric Use management can then be instituted. [see Adverse Reactions (6.1.1)] in patients receiving immunosuppressive doses of Acthar Gel. Vomiting 3 5 Acthar Gel is indicated as monotherapy for the treatment of infantile Killed or inactivated vaccines may be administered; however, the Mallinckrodt, the “M” brand mark, the Mallinckrodt Pharmaceuticals General disorders and administration site conditions spasms in infants and children less than 2 years of age. Both logo and other brands are trademarks of a Mallinckrodt company. response to such vaccines can not be predicted. Other immunization serious and other adverse reactions in this population are discussed Irritability 7 19 procedures should be undertaken with caution in patients who are in Warnings and Adverse Reactions in Infants and Children Under © 2019 Mallinckrodt receiving Acthar Gel, especially when high doses are administered, Pyrexia 5 8 2 Years of Age [see Sections 5 and 6.1.1]. because of the possible hazards of neurological complications and Manufactured for: lack of antibody response. Infections and infestations The efficacy of Acthar Gel for the treatment of infantile spasms in Mallinckrodt ARD LLC. infants and children less than 2 years of age was evaluated in a Bedminster, NJ 07921 USA Masking Symptoms of Other Diseases Infection* 20 46 Investigations randomized, single blinded (video EEG interpreter blinded) clinical Acthar Gel often acts by masking symptoms of other diseases/ trial and an additional active control supportive trial [see Clinical US-1900771 disorders without altering the course of the other disease/disorder. Weight gain 1 3 Studies (14)]. A responding patient was defined as having both Rev 03/2019

Untitled-1 46 7/16/19 12:27 PM

1500638-Acthar_Journal Ad_Rv4.indd 2 7/10/19 12:21 PM MEETING MINUTES s

MANY SURGEONS FROM EUROPE STATED THAT PHACOVITRECTOMY AND PLACEMENT OF A POSTERIOR CHAMBER IOL IS THE STANDARD OF CARE, WHEREAS SURGEONS FROM THE UNITED STATES NOTED THAT PPV AND FLUID-GAS EXCHANGE IS THE STANDARD OF CARE.

to corneal wounds secondary to the surgeon must be proficient at both peripheral retinal tissue necessary to ocular trauma itself. procedures. It should be noted that flatten the retina. He then performed In his video, Dr. Forlini demon- many retina surgeons do not routinely endolaser photocoagulation for 360° at strated some tips and tricks for PPV in perform cataract surgery. the edges of the retinectomy. these difficult scenarios. He performs International differences in the man- A complete fluid-air exchange was surgery without removing the clouded agement of cases in which visualiza- initiated while PFO kept the central cornea, thereby avoiding corneal tion through the cataract is possible macula flat. This was followed by transplantation at the time of PPV. became clear. Many surgeons from removal of the PFO, more endolaser The panel’s debate during and after Europe stated that phacovitrectomy photocoagulation, and reapplication of the video concerned whether it would and placement of a posterior chamber silicone oil to address the chronic RRD. have been better to combine PPV with IOL is the standard of care, whereas The panel had many opinions about penetrating keratoplasty (PK) instead surgeons from the United States noted the steps necessary to flatten the of performing PPV alone. The major- that PPV and fluid-gas exchange is the retina in this case of chronic RRD with ity of the audience thought that the standard of care. subretinal silicone oil. Some attendees visualization through the hazy cornea wondered whether fluid-air exchange was adequate to perform PPV. Some CASE No. 5: and subretinal silicone oil removal audience members noted that a PK MANISH NAGPAL, MS, could be a better solution than PFO would be necessary after PPV anyway, DO, FRCS(EDIN) application. In this case, Dr. Nagpal and that perhaps a PK before or at the (INDIA) used PFO because he did not want any time of PPV would have been a better I had the honor of presenting a case residual subretinal silicone oil or resid- choice. The patient did well after the submitted by Manish Nagpal, MS, DO, ual subretinal fluid during the repair, as PPV, according to Dr. Forlini. FRCS(Edin). these would ultimately have affected Dr. Nagpal’s case concerned a chronic the patient’s postoperative recovery CASE No. 4: total RRD in a patient with proliferative and visual prognosis. RATKO LAZIC, MD vitreoretinopathy and subretinal silicone (CROATIA) oil 360° that was present after an unsuc- MORE INTERNATIONAL VBS PANELS? Dr. Lazic presented a case of a cessful attempt at total RRD repair. The VBS–Mediterranean Retina macula-on rhegmatogenous RD (RRD) First, he initiated silicone oil removal symposium sparked the type of dis- with a nuclear sclerotic cataract. He from the vitreous cavity via a silicone cussion that the VBS is known for. I performed PPV with an endolaser and oil–fluid exchange. After the exchange, was honored to represent the VBS at fluid-gas exchange. Dr. Lazic pointed the entire retina remained detached, this meeting, and the VBS team looks out that phacoemulsification is often and he observed that the peripheral forward to collaboration with interna- performed during PPV. The positives retina was chronically detached and tional societies in the coming years. n and negatives of combined surgery ischemic. He placed PFO on the sur- were the subject of a lively debate. face of the retina out to the periphery On the positive side, a single surgi- and then performed a 270° retinec- R. ROSS LAKHANPAL, MD, FACS cal session is optimal, especially if the tomy to flatten the retina centrally. He n Vitreoretinal Surgeon, The Retina Care Center, desired outcome is achieved. However, could remove the remaining subretinal Baltimore depending on the complexity of the silicone oil only after PFO installation. n President, Vit-Buckle Society RD, some believe that it is better to Dr. Nagpal performed endocautery at n Editorial Advisory Board Member, Retina Today address the RD and then do a staged the edge of the ischemic retina, again n [email protected] procedure for the cataract extraction. injected PFO, and performed a PPV n Financial disclosure: Consultant (Alcon, Allergan, To complete a combined surgery, the using scissors mode to remove the Genentech, Novartis); Speaker (Alcon, Novartis)

JANUARY/FEBRUARY 2020 | RETINA TODAY 25

0120rt_Meeting Minutes_Lakhanpal.indd 25 1/30/20 2:08 PM Eyetube Retina Channel Update A number of videos recently uploaded to Eyetube show innovative, cutting-edge techniques.

BY MICHAEL A. KLUFAS, MD

s the Retina Chief for Eyetube, I am on the lookout for Case No. 2: Internal Limiting Membrane Peeling videos that show innovative procedures from surgical pioneers and outside-the-box thinkers. For this issue’s for Macular Hole With the Awh Micro Vacuum Pick cover focus on surgical techniques and technologies, From Carl C. Awh, MD: This is one of the I selected five videos that I think illustrate the field’s first macular hole cases I performed using Aingenuity and creativity in the OR, and here I offer com- the micro vacuum pick (Awh MVP; Katalyst ments on some of the questions these procedures raise. Surgical). I make a firm stroke to incise the ILM at the start of surgery. After I have an edge, I lift it with a spatula.

Case No. 1: Endolaser-Assisted Scleral Buckle Commentary from Dr. Klufas: New surgical devices con- From David Xu, MD; and tinue to push our field forward. Clinical series have reported Jason Hsu, MD: We perform visual field defects and scotomas resulting from pinch-and- a scleral buckle for a patient peel techniques. Could the Awh MVP help lead the way to with a retinal detachment. The an era of less traumatic ILM peeling? patient also has extensive lattice in four quadrants, which we treat with a lighted endolaser probe. This provides widefield microscope visualization during the application of the laser and cryotherapy.

Commentary from Dr. Klufas: Scleral buckling is still an important procedure, and this is a nifty little trick to avoid cryotherapy and further modification of the chandelier- assisted scleral buckle. A case such as this one raises a compelling question worthy of study: Does endolaser provide better clinical outcomes than cryotherapy in cases of retinal detachment? VIEW AT: bit.ly/Awh0120

Case No. 3: Dexamethasone Intravitreal Implant 0.7 mg Under the Retina From Federic Aissani, MD: A 70-year-old patient presented with a dexamethasone intravitreal implant 0.7 mg (Ozurdex, Allergan) under the retina. The patient’s VIEW AT: bit.ly/Hsu0120 surgical history included two surgeries for

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0120rt_Cover_Klufas.indd 26 1/30/20 2:02 PM TECHNIQUES AND TECHNOLOGIES s

retinal detachment in the left eye and one surgery for reti- Case No. 5: Repair of a Chronic Macular Hole nal detachment in the right eye. I operated on the patient because the retina was detached; had the retina been From Diana V. Do, MD; and attached, I would not have operated. Peter H. Tang, MD, PhD: We present a case of a 62-year-old Commentary from Dr. Klufas: We have heard of ste- pseudophakic woman with roid implant migration to the anterior segment in aphakic counting fingers vision and patients, but this one takes the cake. Consider the choices stable diabetic retinopathy who presented for treatment of Dr. Aissani makes, including the decision to leave the a large, persistent macular hole in her right eye. There had implant in the eye. been three attempts at repair prior to her presentation. Autologous serum and amniotic membranes were used to close the macular hole.

Commentary from Dr. Klufas: Should we try to close holes with retinal grafts? With autologous serum and amniotic membrane? If so, is one preferred over the other? Some argue that retinal grafting is more effective. Others note that application of autologous serum and amniotic membrane is easier to perform. n VIEW AT: bit.ly/Aissani0120

Case No. 4: Unimanual 27-Gauge Vitrectomy for Tractional Retinal Detachment From Gurkan Erdogan, MD: This video presents unimanual (one-handed) 27-gauge vitrectomy for tractional retinal detachment surgery. This surgical technique minimizes the forces applied on the retinal surface, eliminates the need for chandelier illumination, and reduces the number of instrument exchanges during surgery. VIEW AT: bit.ly/Tang0120

Commentary from Dr. Klufas: Is a 27-gauge cutter all you need for diabetic tractional retinal detachment surgery? This MICHAEL A. KLUFAS, MD instrument can be like a magic eraser for removing tightly n Vitreoretinal Surgeon, Mid Atlantic Retina; Assistant Professor of Ophthalmology, Thomas adherent membranes. Because of its small sphere of influ- Jefferson University, both in Philadelphia ence and limited flow, it reduces the chance of iatrogenic n Retina Chief, Eyetube.net breaks (even in cases of bullous detached retina). n [email protected] n Financial disclosure: Consultant (Allergan, Novartis, Genentech), Speaker (Genentech. Regeneron)

VIEW AT: bit.ly/Erdogan0120

JANUARY/FEBRUARY 2020 | RETINA TODAY 27

0120rt_Cover_Klufas.indd 27 1/31/20 10:28 AM Surgical Pearls for the EVA Platform Improved fluidics and illumination are features of this vitrectomy system.

BY ASHLEY M. CRANE, MD; AND DAVID A. EICHENBAUM, MD

he Enhancing Visual Acuity working closer to the retina, however, PEARL No. 2: ILLUMINATION (EVA) vitrectomy system (Dutch it is advantageous to switch to flow The EVA system also incorporates Ophthalmic) can be used for mode. In vacuum mode, the vacuum LEDStar Illumination LED technology. vitreoretinal surgery, cataract rate is constant but flow fluctuates These LED bulbs are known for their surgery, and combined anterior- depending on the viscosity of the long life, minimizing the frequency of posteriorT segment surgery. The system fluid. When working closer to the bulb changes. The technology includes has gained widespread use due to retina, this may cause inadvertent updated LED light fibers that provide its safety and efficiency and its lower contact by the cutter, resulting in better visualization in 27-gauge surgery. price point compared with other iatrogenic breaks. Transient hypotony The color of the light can be varied similar systems. may also occur. from white to yellow or amber. Some The EVA incorporates an innovative When flow mode is activated, the surgeons like to use the yellow or amber fluidics system and a twin duty cycle flow at the tip of the cutter (or other light while working under air or during cutter, and it works with a variety instrument) is kept constant with the long cases. of peripheral accessories. This article assistance of VTi, often resulting in The EVA’s light pipe incorporates a describes three posterior segment sur- safer and more effective shaving, espe- directional light, minimizing glare and gical pearls relating to the EVA system. cially over detached retina or during a allowing the surgeon to efficiently visu- posterior membrane peel. alize the vitreous and retina. Of note, it PEARL No. 1: FLUIDICS Furthermore, the surgeon can toggle may take a couple of surgeries for the The EVA system’s most distinctive among customized preset flows using user to get accustomed to directing this feature is its VacuFlow Valve Timing the footpedal, based on the mobility light pipe posteriorly when it is intro- Intelligence (VTi) vacuum control of the retina or the desired proximity duced through the trocar. system. In traditional venturi pump of the cutter to the retinal surface. A Light pipes in all gauges also come systems, a flow of air is used to create common setting for peripheral vitrec- with a clear cap that can be fitted over a vacuum. The surgeon controls the tomy, for example, is to use flow mode the light pipe so that it can be used as vacuum, and the flow depends on with a low-vacuum shave setting. an illuminated scleral depressor. This several factors, including the amount of vacuum, the gauge of instrumentation, and the viscosity of fluid or AT A GLANCE tissue. In a peristaltic system, a rotary

wheel compresses the tubing system s to displace fluid. The surgeon controls The EVA system’s VTi system pump can be used in vacuum or in flow mode, the flow, and vacuum can also be con- depending on the surgical scenario. trolled independently. s The LED illumination system offers improved visualization with 27-gauge The EVA system’s VTi system pump can be used in vacuum or in flow instrumentation. mode. Core vitrectomy is typically s A high-flow infusion system can provide high infusion pressure in performed in vacuum mode, as it allows quick and efficient removal of small-gauge surgeries. core vitreous. When the surgeon is

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0120rt_Cover_Crane Eichenbaum.indd 28 1/30/20 1:58 PM TECHNIQUES AND TECHNOLOGIES s

LIGHT PIPES IN ALL GAUGES ALSO COME WITH A CLEAR CAP THAT CAN BE FITTED OVER THE LIGHT PIPE SO THAT IT CAN BE USED AS AN ILLUMINATED SCLERAL DEPRESSOR. THIS FEATURE IS BEST USED ON LIGHTLY PIGMENTED EYES AND MAY NOT PROVIDE SUFFICIENT TRANSSCLERAL ILLUMINATION IN SOME CASES.

feature is best used on lightly pigmented removed, and the infusion is changed compatible with the EVA trocars eyes and may not provide sufficient from one that is fitted inside the trocar in order to maximize their surgical transscleral illumination in some cases. cannula to one that fits around the efficiency. n trocar. This allows full use of the entire PEARL No. 3: CANNULAS lumen of the trocar for infusion, and AND INFUSION therefore lower infusion pressures. ASHLEY M. CRANE, MD The trocars and cannulas of the When the high-flow infusion system n Retina Vitreous Associates of Florida, St. Petersburg, EVA system have both pluses and is used, the surgeon must be mind- Florida minuses. The trocars are fitted with ful to decrease the upper limit of the n [email protected] transparent, removable, silicone valved automatic infusion control in order to n Financial disclosure: None cannulas that provide a watertight avoid excessively high infusion pres- seal. The funnel-shaped metal trocar sures in comparison with those of DAVID A. EICHENBAUM, MD makes insertion of rigid instruments standard infusion systems. n Partner and Director of Clinical Research, Retina easy. However, care must be taken Conversely, when standard infusion Vitreous Associates of Florida, St. Petersburg, Florida when choosing soft tip instruments, as is used, the surgeon must be careful n Clinical Associate Professor of Ophthalmology, some soft silicone soft tips will adhere not to overpower the infusion with University of South Florida, Tampa, Florida to the silicone valves, impeding their excessive vacuum, which can result n [email protected] entry into the cannulas. This is a com- in hypotony. Getting used to one’s n Financial disclosure: Consultant, Speaker (Dutch mon problem across platforms with own individual infusion, flow, and Ophthalmic) silicone valves. Some widely used soft vacuum settings is easy and intuitive tip cannulas may be difficult to intro- on the EVA system, but each surgeon duce into the EVA’s trocar-cannulas. should work with his or her com- Stabilizing the cannula with forceps pany representative to customize the can often solve this difficulty. In our machine’s setup. experience, the soft tip cannula manufactured by Vortex Surgical, with its CONCLUSION slightly shorter and more rigid silicone The EVA system offers significant tip, is significantly easier to introduce advantages over traditional systems, into the EVA trocar-cannula than especially with regard to its innovative other soft tip cannulas. Vortex also fluidics system. We recommend the offers 23- and 25-gauge retractable soft use of flow mode when the cutter is tip cannulas, which basically eliminate coming into close contact with mobile this issue. retina or when preretinal membranes The removable valved cannula also are being removed with the vitreous allows the EVA system to be used cutter. The EVA illumination system with an alternative high-flow infusion allows greater customization and system, which is optional in 23- and broader use of 27-gauge instrumenta- 25-gauge systems and is used in all tion than other lighting systems. It is 27-gauge systems. For use of this sys- important for surgeons to familiarize tem, the translucent valved cannula is themselves with the accessories most

JANUARY/FEBRUARY 2020 | RETINA TODAY 29

0120rt_Cover_Crane Eichenbaum.indd 29 1/30/20 1:58 PM Introduction to Secondary IOLs

Scleral fixation of a lens with two eyelets requires precise sclerotomy placement and suture management to avoid rotation.

BY THOMAS L. JENKINS, MD; RAVI R. PANDIT, MD, MPH; AND DAVID XU, MD

here are multiple options for vitrectomy and ab externo scleral its hydrophilic properties.6-9 Given the secondary IOL implantation in fixation of posterior chamber IOLs frequent comorbid factors that place aphakic eyes, including the use of with PTFE suture after a minimum aphakic patients at high risk of requir- anterior chamber IOLs, iris-fixated of 1-year follow-up with no docu- ing retinal surgery (eg, previous trau- IOLs, or scleral-fixated IOLs.1 In mented instances of suture breakage ma, retinal damage from dislocated youngT patients or patients with insuffi- or lens dislocation.3 IOL, vitreous traction), the Akreos lens cient iris support, narrow anterior cham- may be seen as inappropriate for use bers, corneal endothelial disease, or other LENS TYPES in some patients. anterior segment pathology, scleral fixa- Many models of foldable acrylic The enVista MX60 IOL (Bausch + tion of a posterior chamber IOL should IOLs have been used for scleral suture Lomb) is a one-piece hydrophobic be considered. fixation. The Akreos AO60 (Bausch acrylic IOL with two eyelets. In con- This article describes considerations + Lomb) is a one-piece, foldable trast to the Akreos lens, no cases of pertinent to suture type, lens selection, hydrophilic acrylic IOL with four eye- opacification have been reported with and surgical technique when implanting lets through which sutures can be this lens. It may, therefore, represent a a scleral-fixated IOL. We also describe passed. This lens is commonly used more versatile option in a vitreoretinal the technique used at our institution as a secondary IOL, but there have surgical context in which intraocular for scleral fixation with one particular been well-documented reports of air or gas tamponade is likely to be combination of IOL and suture material. optic opacification with calcium salt used. Despite the two-eyelet design of deposition after air or gas fill due to the MX60 IOL, with proper technique SUTURE TYPES Multiple authors have demonstrated excellent IOL positioning and stabil- AT A GLANCE ity with sutured scleral-fixated lenses

using a variety of suture types, includ- s ing 10-0 polypropylene, 9-0 polypro- Options for secondary IOL implantation in aphakic eyes include the use of pylene, and polytetrafluoroethyl- anterior chamber IOLs, iris-fixated IOLs, or scleral-fixated IOLs. ene (PTFE; Gore-Tex, W.L. Gore & Associates) suture materials.2-5 s Polytetrafluoroethylene (PTFE) suture, also known as Gore-Tex suture, is an PTFE is a nonabsorbable mono- attractive option for scleral IOL fixation because of its durability and low rate filament suture with high tensile strength. It is an attractive option for of suture-related complications.

scleral fixation of IOLs due to its dura- s bility and low rate of suture-related A one-piece foldable hydrophobic acrylic IOL may be preferred for patients in complications. In 2018, Khan et al, at whom intraocular air or gas tamponade is likely to be needed. our institution, reported favorable outcomes of combined pars plana

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0120rt_Cover_Jenkins_Sedeek.indd 30 1/30/20 2:28 PM TECHNIQUES AND TECHNOLOGIES s

and suture placement it has been shown to result in surgically induced astigmatism similar to that of other IOL models.10 The CZ70BD (Alcon) is a one-piece PMMA lens with two eyelets that are suitable for suture fixation. However, this lens requires a larger scleral tunnel incision, as the optic is not foldable. At our institution, we have had the most experience with the Akreos and the enVista.

OUR TECHNIQUE Surgical placement of a PTFE scleral- fixated IOL can be challenging due Figure 1. Calipers are used to mark 3 mm posterior to the limbus and 2.5 mm above and below the posterior mark. to the need for precise sclerotomy placement and suture management to avoid rotation of the lens during intraocular insertion. The steps used for this surgery at our institution are described below. A toric lens marker is used to mark the cornea at two points 180° apart. Marking the 3 and 9 clock positions is the most common, but some surgeons choose 10 and 4 clock positioning to avoid the nasal bridge. Sectoral peritomies 3 clock hours in size are performed centered on the corneal marks, and hemostasis is maintained through the use of wet- field cautery. Calipers are used to Figure 2. A 23-, 25-, or 27-gauge needle is used to make sclerotomies, and sclerotomy ports of the corresponding mark 3 mm posterior to the limbus gauge are inserted at the superior scleral marks. and 2.5 mm above and below the posterior mark, such that the mark- ings are 3 to 5 mm apart on each side (Figure 1). The surgeon may adapt the precise posterior and intersclerotomy measurements based on his or her own surgical results. Depending on surgeon preference, a 23-, 25-, or 27-gauge needle is used to make sclerotomies at the inferior marks, and sclerotomy ports of the corresponding gauge are inserted at the superior scleral marks (Figure 2). An inferotemporal transconjunctival infusion cannula is inserted, and a standard three-port pars plana vitrectomy is performed. Figure 3. One half of an 8-0 PTFE suture with the needle removed is threaded through each eyelet of an MX60 IOL, The infusion is clamped, and the with both ends of the suture going over the haptic. anterior chamber is maintained with

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0120rt_Cover_Jenkins_Sedeek.indd 31 1/30/20 2:28 PM 1/30/20 2:28 PM

After

(Continued on page 36) (Continued One half of an 8-0 PTFE suturePTFE 8-0 an of half One temporarilytied is suture PTFE The appropriate tension has been placedbeen has tension appropriate confirmed,centration lens and use of an OVD. A 2.75-mm keratome iskeratome 2.75-mm A OVD. an of use incisioncorneal clear a create to used surgeonsSome limbus. superior the at corneoscleral a create to instead prefer knifecrescent angled an using tunnel chamberanterior the entering before keratome.the with threadedis removed needle the with IOL,MX60 an of eyelet each through goingsuture the of ends both with end Each 3). (Figure haptic the over lead- the from suture PTFE the of theinto passed then is haptic ing fromretrieved and chamber anterior usingsclerotomy corresponding the 4).(Figure forceps intraocular 27-gauge half,in folded is IOL the of optic The theinto tucked are haptics the and Kelman- curved using IOL folded thenis IOL The forceps. McPherson chamber anterior the into introduced 5).(Figure slipknot.a or throw three-loop a with sub- are suture the of ends other The oppositethe through passed sequently manner. similar a in sclerotomies MULTIPLE AUTHORS AUTHORS MULTIPLE HAVE DEMONSTRATED EXCELLENT IOL EXCELLENT IOL POSITIONING AND AND POSITIONING STABILITY WITH SUTURED SCLERAL- A VARIETY OF SUTURE TYPES. FIXATED LENSES USING FIXATED LENSES USING | JANUARY/FEBRUARY 2020

Figure 6. With appropriate tension placed and lens centration confirmed, the sutures are tied. Figure 5. The IOL optic is folded in half, the haptics are tucked into the folded IOL using curved Kelman-McPherson into the folded IOL using curved Kelman-McPherson Figure 5. The IOL optic is folded in half, the haptics are tucked forceps, and the IOL is introduced into the anterior chamber. Figure 4. Each end of the suture from the leading haptic of the IOL is passed into the anterior chamber and retrieved the IOL is passed into the anterior chamber and retrieved Figure 4. Each end of the suture from the leading haptic of from the corresponding sclerotomy using 27-gauge forceps. RETINA TODAY

32 s TECHNIQUES TECHNOLOGIES AND 0120rt_Cover_Jenkins_Sedeek.indd 32 A Brighter Vision on Illumination Enhanced Function and Directional Control

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BVI_1530380-02_Chandelier_retina.today_9x10.75_01.13.20.pdfx1a.indd 1 1/13/20 1:24 PM The Case for Modern Lasers in Diabetic Eye Disease

New laser technology may lead to increased use in some patients.

BY RAGUI W. SEDEEK, MD

n the days before the anti-VEGF era, Patients with diabetic eye disease of cataract formation in phakic patients focal laser application in patients with undergoing anti-VEGF therapy require and a risk of glaucoma development. diabetic macular edema (DME) was frequent treatment. Young, phakic, Using steroids in working-age, phakic an effective therapeutic option that working-age patients with bilateral patients, then, seems counterproduc- came with a price: The heavy burn disease are particularly affected by this tive: The need for frequent anti-VEGF Icreated by the laser blanched tissue and treatment burden. The need for frequent injections is eliminated but replaced by left permanent scarring. After anti-VEGF injections can be disruptive to patients’ potential ocular complications. agents were found to be effective in the lives and may lead to patients skipping Applications of subthreshold laser treatment of DME, many clinicians aban- treatments altogether. Some clinicians therapy (SLT) in young, phakic, working- doned focal laser in favor of pharmaco- may choose to employ steroid therapy, age patients can, in my experience, lower therapy for DME. but that strategy comes with a certainty the treatment burden for patients with

Figure 1. One month after subthreshold laser treatment in a diabetic patient with clinically significant macular edema, VA had improved from 20/30-2 to 20/25-2. Retinal thickness had decreased in areas treated with pattern subthreshold laser.

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DME without sacrificing efficacy. This SUBTHRESHOLD TECHNOLOGIES threshold laser platforms: MicroPulse has been particularly true in patients The evolution of lasers for retina on the IQ 532 and IQ 577 lasers (Iridex) who have non–center-involving DME. therapy has brought the field two sub- and Endpoint Management on the

Figure 2. At 3 months, retinal thickening had decreased and the patient’s VA had improved slightly, to 20/25.

Figure 3. At 6 months, the patient’s VA remained 20/25 and no recurring thickening was noted.

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0120rt_Cover_Jenkins_Sedeek.indd 35 1/30/20 2:28 PM 1/31/20 10:29 AM n

There are multiple options for placing a secondary IOL inIOL secondary a placing for options multiple are There The sclerotomy sites are closely inspected for leakage, andleakage, for inspected closely are sites sclerotomy The Second-Year Vitreoretinal Fellow, Wills Eye Hospital, Philadelphia Second-Year Vitreoretinal Fellow, Wills Eye Hospital, [email protected] Financial disclosure: None Second-Year Vitreoretinal Fellow, Wills Eye Hospital, Philadelphia [email protected] Financial disclosure: None Second-Year Vitreoretinal Fellow, Wills Eye Hospital, Philadelphia [email protected] Financial disclosure: Cofounder (EyeGuru.org)

(Continued from page 32) from (Continued SECTION EDITOR RAVI R. PANDIT, MD, MPH SECTION EDITOR DAVID XU, MD 1. Wagoner MD, Cox TA, Ariyasu RG, Jacobs DS, Karp CL; American Academy of Ophthalmology. Intraocular lens 1. Wagoner MD, Cox TA, Ariyasu RG, Jacobs DS, Karp CL; American Academy of of Ophthalmology. Ophthalmology. implantation in the absence of capsular support: a report by the American Academy 2003;110(4):840-859. chamber intraocular lenses using 2. Khan MA, Gerstenblith AT, Dollin ML, Gupta OP, Spirn MJ. Scleral fixation of posterior Gore-Tex suture with concurrent 23-gauge pars plana vitrectomy. Retina. 2014;34(7):1477-1480. and scleral fixation of an intraocular lens 3. Khan MA, Samara WA, Gerstenblith AT, et al. Combined pars plana vitrectomy using Gore-Tex suture: one-year outcomes. Retina. 2018;38(7):1377-1384. 4-point suture fixation of a foldable 4. Goel N. Clinical outcomes of combined pars plana vitrectomy and trans-scleral intraocular lens. Eye (Lond). 2018;32(6):1055-1061. as treatment for intraocular lens 5. Kim KH, Kim WS. Comparison of clinical outcomes of iris fixation and scleral fixation dislocation. Am J Ophthalmol. 2015;160(3):463-469.e1. after vitrectomy in a diabetic patient: a 6. Cao D, Zhang H, Yang C, Zhang L. Akreos Adapt AO intraocular lens opacification case report and review of the literature. BMC Ophthalmol. 2016;16:82. lens after vitrectomy with gas 7. Kalevar A, Dollin M, Gupta RR. Opacification of scleral-sutured Akreos AO60 intraocular Retin Cases Brief Rep. tamponade: case series [published online ahead of print September 27, 2017]. (Akreos AO MI60) optic opacification in 8. Park DH, Shin JP, Kim HK, Kim JH, Kim SY. Hydrophilic acrylic intraocular lens patients with diabetic retinopathy. Br J Ophthalmol. 2010;94(12):1688-1689. in a diabetic patient. Jpn J 9. Park DI, Ha SW, Park SB, Lew H. Hydrophilic acrylic intraocular lens optic opacification Ophthalmol. 2011;55(6):595-599. and scleral fixated intraocular lens 10. Su D, Stephens JD, Obeid A, et al. Refractive outcomes after pars plana vitrectomy with Gore-Tex suture. Ophthalmol Retina. 2019;3(7):548-552. aphakia. In the appropriate clinical context, a scleral-fixateda context, clinical appropriate the In aphakia. stablea offer can suture PTFE with IOL chamber posterior outcomes. refractive good with option SECTION EDITOR THOMAS L. JENKINS, MD SECTION EDITOR THOMAS L. JENKINS, MD n n n n n n n n n the sutures are tied using a 3-1-1 or slipknot techniqueslipknot or 3-1-1 a using tied are sutures the - scle the into rotated and trimmed are knots The 6). (Figure forceps.using rotomy - neces if suture polyglactin 8-0 an with closed be may they PTFEthe cutting avoid to care extraordinary taking sary, residualany of removal After pass. needle the during suture interruptedan with closed is incision corneal clear the OVD, closed.are peritomies conjunctival the and suture nylon 10-0 CONCLUSION n

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| JANUARY/FEBRUARY 2020

For clinicians concerned that their working-age patients working-age their that concerned clinicians For I treated the patient with subthreshold laser using theusing laser subthreshold with patient the treated I A 48-year-old woman with an 8-year history of type 2 diabe- 2 type of history 8-year an with woman 48-year-old A The patient is usually in the chair for about 5 minutes duringminutes 5 about for chair the in usually is patient The I target only microaneurysms found outside of the center,the of outside found microaneurysms only target I When applying subthreshold laser with the Pascal platform,Pascal the with laser subthreshold applying When In my experience, a number of patients with DME who DME with patients of number a experience, my In Retina Surgeon, Shepard Eye Center, Santa Maria, California [email protected] Financial disclosure: None disclosed

I suggest considering SLT on the Iridex or Pascal platforms. Pascal or Iridex the on SLT considering suggest I with DME may skip anti-VEGF therapy sessions due to treat- to due sessions therapy anti-VEGF skip may DME with literaturerecent about concerned are who (or burden ment injec- anti-VEGF frequent to development glaucoma linking degeneration macular age-related neovascular for tions Endpoint Management system. At 1 month follow-up, the follow-up, month 1 At system. Management Endpoint thick- retinal and 20/25-2 to improved had VA patient’s herAt 1). (Figure areas treated the in decreased had ness and20/25 to improved had VA the visit, follow-up 3-month identi- thickening of areas in noted were resolution of areas 20/25remained VA months, 6 At 2). (Figure previously fied 3).(Figure seen was thickening recurring no and tes mellitus presented with clinically significant macular edemamacular significant clinically with presented mellitus tes thick- perifoveal and Juxtafoveal 20/30-2. was VA eye. left her in micro- and exudates were as examination, on noted was ening angiogram. fluorescein on noted was Leakage aneurysms. n n n RAGUI W. SEDEEK, MD DON’T RULE OUT LASER DON’T RULE OUT LASER A RECENT CASE A RECENT CASE Pascal suite of lasers (Topcon). Subthreshold laser treatment has treatment laser Subthreshold (Topcon). lasers of suite Pascal without microaneurysms treating in effective be to shown been damage. tissue permanent causing vascular endothelial growth factor injections for macular degeneration. Clin Ophthalmol. a laser application session.application laser a 1. Scholz P, Altay L, Fauser S. A review of subthreshold micropulse laser for treatment of macular disorders. Adv Ther. 2017;34(7):1528-1555. 2. Wingard JB, and I avoid application of subthreshold laser directly to theto directly laser subthreshold of application avoid I and arather but microaneurysms, individual target not do I fovea. laser.the by generated pattern a with microaneurysms of region I test the laser intensity in an area outside the macula, usually macula, the outside area an in intensity laser the test I blanching, tissue no is there seconds, 10 after If, disc. the to nasal laser’sthe reduces which Management, Endpoint initiate then I microaneurysmstreat to laser the allows This 50%. by intensity damage. tissue permanent causing without received SLT have not needed subsequent anti-VEGF injec- anti-VEGF subsequent needed not have SLT received thatestimate I injections. of burden the reduced have or tions everyoffice the visit SLT after retreatment require who patients months. 3 patients with recurring or new microaneurysms.new or recurring with patients RETINA TODAY

36 s TECHNIQUES TECHNOLOGIES AND 0120rt_Cover_Jenkins_Sedeek.indd 36 Pub RT Easyret Mosar 012020.indd 1 24/12/2019 08:21:48 OCT Angiography to Confirm Macular Hole Closure and Reduce Facedown Positioning

This noninvasive, high-speed imaging technique can improve macular hole closure visualization and minimize discomfort for patients.

BY MICHAEL C. RENFROE, BSA; GOWTHAM JONNA, MD; YONG REN, MMS; SARADHA CHEXAL, MD; AND CHIRAG D. JHAVERI, MD

ntraocular gas tamponade creates a with clear visualization of the fovea and two physicians following the same surgi- gas-fluid interface in the eye, which closure status of MHs at postopera- cal protocol. Surgery included pars plana complicates adequate visualization tive day 1. We sought to evaluate the vitrectomy, internal limiting membrane of the fundus with spectral-domain effectiveness of OCTA in ascertaining (ILM) staining and peeling, and gas OCT. With lack of visual confirmation MH closure at postoperative day 1 in an tamponade. Iof macular hole (MH) closure, clinicians attempt to minimize cumbersome FDP The AngioVue OCTA imaging system have perpetuated excessive facedown regimens for patients. (Optovue) was used to perform the fol- positioning (FDP) regimens that can be lowing OCTA and OCT scan protocols arduous and may even be contraindicat- STUDY preoperatively and postoperatively, ed in some patients with comorbidities. Seven patients (three phakic, four contingent on sufficient view: OCTA The standard duration of FDP has pseudophakic) with idiopathic, unilat- (6.0 mm), 3D widefield volume OCT gradually decreased from as much as eral MHs stages 2 to 4 were treated by (12.0 x 9 mm), and retina cross-line 1 month to as little as 3 days.1-3 A pilot study demonstrated an 85% closure rate (28 of 33 eyes) with no FDP,4 challeng- AT A GLANCE ing its necessity altogether. Since then, multiple studies have confirmed compa- s Positioning regimens after surgery for MH closure can be distressing, rable efficacy of strict FDP and no-FDP highly uncomfortable, and even harmful for patients with comorbidities. regimens in MH closure.5,6 Although the evidence remains inconclusive on s OCT angiography can be used to assess gas-filled eyes and closure the impact of postoperative FDP on the outcome of MH surgery,7 two random- status of MHs on postoperative day 1.

ized, controlled trials have suggested a s benefit of FDP with higher closure rate Capturing a clear image of MH closure can facilitate decrease or in holes larger than 400 µm.8,9 discontinuation of positioning time for patients while maintaining OCT angiography (OCTA) can effec- surgical and visual outcomes. tively capture images in gas-filled eyes,

38 RETINA TODAY | JANUARY/FEBRUARY 2020

0120rt_Cover_Renfroe.indd 38 1/30/20 2:25 PM TECHNIQUES AND TECHNOLOGIES s

(10.0 mm) scan. All scans were performed by two experienced retinal photographers with the patient in an upright position. Patients were instructed to maintain FDP after surgery until their postoperative day 1 visit. If the MH was observed to be closed on OCTA, the patient was allowed to discontinue FDP but was instructed to avoid faceup positioning until clearance of the gas bubble. OCTA adequately visualized hole closure status in six of the seven Figure 1. Superficial en face OCTA images of a 74-year-old pseudophakic woman before surgery (left column), at post- patients. Four patients had apparent operative day 1 (middle column), and at postoperative week 1 (right column). The OCTA scan followed the course of total closure of the MH, and for them the retinal vessels, localized the fovea, and obtained the best quality images with gas in place. Although resolution was limited in the postoperative day 1 image, MH closure was evident, and FDP was discontinued. BCVA improved FDP was discontinued. Details for two from 20/200 before surgery to 20/40 at 6 months. of those patients are illustrated in Figures 1 and 2. The other two patients had adequate visualization of the fovea by OCTA, but only near-total closure was noted. They were instructed to continue FDP, typically for a total of 3 days. OCTA could not adequately document MH closure status in one patient. Mean visual gain from preoperative to postoperative was 27 (±7) letters. Two patients underwent cataract surgery with IOL implantation after the MH surgery. Two patients had visually significant cataracts at their most recent follow-up.

DISCUSSION Until 1996, strict postoperative FDP was thought to be critical for successful MH closure. Long periods of FDP are uncomfortable, may be painful in those with cervical and lumbar pathology, and can deter patients from opting for surgery Figure 2. Infrared imaging combined with dense raster scans (including the optic nerve) was used to localize the altogether. Furthermore, FDP has fovea and confirm MH closure in a 70-year-old pseudophakic woman. The preoperative image (top row) illustrates a full-thickness MH with associated intraretinal cystoid changes. Using the optic disc as a reference, infrared imaging been linked to ulnar neuropathy,10 11 was used along with the OCT component of the OCTA platform to localize the fovea and demonstrate closure of the decubitus ulcers, and, rarely, MH at postoperative day 1 (middle row) and postoperative week 1 (bottom row). BCVA improved from 20/100 before venous thrombotic/thromboembolic surgery to 20/25 at a postoperative visit 21.5 months later. disease.12,13 Given the numerous potential vari- ables—including MH size, chronicity strict FDP, 87% of US respondents to Fourier-domain OCT has been of MH, and surgeon-to-surgeon vari- a 2018 American Society of Retina used to discern MH closure as early as ability—the practice patterns for MH Specialists survey reported that they 24 hours after surgery, providing guid- surgery significantly vary.14 Despite recommend postoperative FDP ance to the surgeon regarding FDP reports of positive outcomes without for patients.15 duration.16-19 Microvascular features

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0120rt_Cover_Renfroe.indd 39 1/30/20 2:25 PM s TECHNIQUES AND TECHNOLOGIES

mol. 2017;255(10):1923-1924. and the potential for postoperative CONCLUSION 22. Cho JH, Yi HC, Bae SH, Kim H. Foveal microvascular features of surgically recovery due to neuronal and vascular With its superior axial resolution closed macular hole using OCT angiography. BMC Ophthalmol. 2017;17:217. 23. Demirel S, Değirmenci MFK, Bilici S, et al. The recovery of microvascular plasticity have been elucidated using and high scanning speed, OCTA may status evaluated by OCT angiography in patients after successful macular hole OCTA.20-23 However, to the best of our assist in confirming MH closure status surgery. Ophthalmic Res. 2018;59(1):53-57. knowledge, this is the first report of in gas-filled eyes in the immediate using features specific to OCTA to dis- postoperative period. Visual confirma- SARADHA CHEXAL, MD cern MH status in gas-filled eyes in the tion of MH closure on OCTA may be n Vitreoretinal Surgeon, Retina Consultants of immediate postoperative period. used as evidence to discontinue or Austin, Austin, Texas In our study, OCTA successfully reduce patients’ FDP regimens after n Investigator, Retina Research Center, Austin, Texas visualized the fovea in six of the seven MH surgery. Ultimately, this improves n [email protected] patients in our cohort (86%) on post- the patient experience and reduces n Financial disclosure: Financial Support (Alimera operative day 1. There was a 100% morbidity while maintaining good sur- Sciences, VisionCare Ophthalmic Technologies) MH closure rate at postoperative gical and visual outcomes. n week 1, despite discontinuation of CHIRAG D. JHAVERI, MD 1. Benson WE, Cruickshanks KC, Fong DS, et al. Surgical management n Vitreoretinal Surgeon, Retina Consultants of FDP in four (57%) patients who had of macular holes: a report by the American Academy of Ophthalmology. complete hole closure noted on post- Ophthalmology. 2001;108(7):1328-1335. Austin, Austin, Texas 2. Almeida DR, Wong J, Belliveau M, Rayat J, Gale J. Anatomical and visual n Investigator, Retina Research Center, Austin, Texas operative day 1. outcomes of macular hole surgery with short-duration 3-day face-down OCTA offers superior axial reso- positioning. Retina. 2012;32(3):506-510. n Clinical Assistant Professor, Dell Medical School, 3. Rayat J, Almeida DR, Belliveau M, Wong J, Gale J. Visual function and vision- The University of Texas at Austin, Austin, Texas lution (5 µm) and scanning speed related quality of life after macular hole surgery with short-duration, 3-day (70,000 A-scans per second) com- face-down positioning. Can J Ophthalmol. 2011;46(5):399-402. n Executive Committee Member, DRCR Retina 4. Tornambe PE, Poliner LS, Grote K. Macular hole surgery without face-down Network pared to previous spectral-domain positioning. A pilot study. Retina. 1997;17(3):179-185. OCT technologies. Visualization of 5. Forsaa VA, Raeder S, Hashemi LT, Krohn J. Short-term postoperative non- n Protocol Chair, DRCR Retina Network Protocol AC supine positioning versus strict face-down positioning in macular hole surgery. n [email protected] the fovea is more accurate because Acta Ophthalmol. 2013;91(6):547-551. the vessels can be easily identified 6. Alberti M, la Cour M. Face-down positioning versus non-supine positioning n Financial disclosure: Advisory Board Member in macular hole surgery. Br J Ophthalmol. 2015;99(2):236-239. (Allergan); Consultant (Novartis) using the angiography portion of the 7. Solebo AL, Lange CA, Bunce C, Bainbridge JW. Face-down position- OCTA scans. ing or posturing after macular hole surgery. Cochrane Database Syst Rev. 2011;(12):CD008228. GOWTHAM JONNA, MD For our study, at the day 1 postop- 8. Guillaubey A, Malvitte L, Lafontaine PO, et al. Comparison of face-down and n erative visit the automatic follow-up seated position after idiopathic macular hole surgery: a randomized clinical Vitreoretinal Surgeon, Retina Consultants of trial. Am J Ophthalmol. 2008;146(1):128-134. Austin, Austin, Texas option of the OptoVue device was 9. Lange CA, Membrey L, Ahmad N, et al. Pilot randomised controlled n disabled because the infrared view trial of face-down positioning following macular hole surgery. Eye (Lond). Investigator, Retina Research Center, Austin, Texas 2012;26(2):272-277. n [email protected] was significantly different compared 10. Holekamp NM, Meredith TA, Landers MB, et al. Ulnar neuropathy as a com- n with the preoperative scans and the plication of macular hole surgery. Arch Ophthalmol. 1999;117(12):1607-1610. Financial disclosure: None 11. Vincent JM, Peyman GA, Ratnakaram R. Bilateral ulnar decubitus as software would not allow automatic a complication of macular hole surgery. Ophthalmic Surg Lasers Imaging registration. The infrared view was 2003;34(6):485-486. YONG REN, MMS 12. Au Eong KG, Beatty S, Thomas W, Sen V, Turner GS. Pulmonary embolism n Head of Research Testing, Retina Research Center, used to visualize the macula, and then following head positioning for retinal reattachment surgery in a young patient the retinal vessels and optic nerve were with factor V leiden mutation. Arch Ophthalmol. 2000;118(9):1300-1301. Austin, Texas used to assist in locating the fovea. To 13. Starr MR, Iezzi R. Mesenteric venous thrombosis after face-down position- n [email protected] ing for retina detachment surgery. Ophthalmol Retina. 2018;2(11):1174-1175. n successfully acquire the best available 14. Patel S, Sternberg, P. Face-down positioning following macular hole Financial disclosure: None OCTA image quality and position, surgery: pros and cons. J Vitreoretin Dis. 2017;1(5):331-333. 15. Singh RP, Stone TW, eds. 2018 Global Trends in Retina Survey. MICHAEL C. RENFROE, BSA the automatic adjustment function American Society of Retina Specialists 2018. https://www.asrs.org/content/ n (a combination of auto Z, auto F, and documents/2018-global-trends-in-retina-survey-highlights-website.pdf Clinical Research Coordinator, Retina Research Accessed September 20, 2019. Center, Austin, Texas auto P) was performed twice, followed 16. Muqit MM, Akram I, Turner GS, Stanga PE. Fourier-domain OCT imaging n by manual adjustment of the focus of gas tamponade following macular hole surgery. Ophthalmic Surg Lasers [email protected] Imaging. 2010;41(online):e1-6. n Financial disclosure: None and scan position by the photogra- 17. Eckardt C, Eckert T, Eckardt U, Porkert U, Gesser C. Macular hole surgery with air tamponade and OCT-based duration of face-down positioning. Retina. pher. The 3D widefield volume OCT 2008;28(8):1087-1096. and cross-line scans were also obtained 18. Masuyama K, Yamakiri K, Arimura N, Sonoda Y, Doi N, Sakamoto T. Postur- ing time after macular hole surgery modified by OCT images: a pilot study. Am following these specified adjustments. J Ophthalmol. 2009;147(3):481-488.e2. Image quality was found to be bet- 19. Zhang Y, Chen X, Hong L, et al. Facedown positioning after vitrectomy will not facilitate macular hole closure based on swept-source OCT imaging in ter in pseudophakic patients than gas-filled eyes: a prospective, randomized comparative interventional study. in phakic patients overall. The pres- Retina. 2019;39(12):2353-2359. 20. Shahlaee A, Rahimy E, Hsu J, Gupta OP, Ho AC. Preoperative and postop- ence of cataract may have prevented erative features of macular holes on en face imaging and optical coherence adequate visualization of the fundus in topography angiography. Am J Ophthalmol Case Rep. 2016;5:20-25. 21. Yun C, Ahn J, Kim M, et al. Characteristics of retinal vessels in surgically one patient. closed macular hole: an OCT angiography study. Graefes Arch Clin Exp Ophthal-

40 RETINA TODAY | JANUARY/FEBRUARY 2020

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06.01.2020 19:20:03 Avoiding Iatrogenic Injury During IOL Removal A pearl for this not uncommon occurrence could reduce the risk of patient injury.

BY JOHN W. KITCHENS, MD

econdary surgical removal of a dropped IOL from the posterior segment carries a risk of iatrogenic injury, and plate-haptic IOLs in particular elevate this Srisk. The silicone material of these IOLs makes them difficult to grasp, and forceps must come very close to the retinal tissue to grasp the IOL during removal, risking a retinal injury or tear. In addition, this technique allows wide-angle viewing to be used for the entire case, as opposed to switching from a high-magnification contact lens Figure 1. A soft-tip cannula can be used to grasp a plate-haptic IOL that has fallen into the posterior segment. when grasping the IOL on the surface of the retina to a wide-angle lens when creating a large incision (Figure 3), I prefer larger lenses in most of my removing it from the eye. Over the which some surgeons wish to avoid. cases due to familiarity with the proce- years, I have found this technique to However, because I usually implant a dure, stability of these larger and rigid be particularly useful for safely and replacement IOL that requires a large IOLs, and the age and corneal status effectively removing these lenses from incision such as an anterior chamber of the patients. Plate haptics can easily the posterior segment. IOL or a large rigid PMMA IOL such as be cut or folded and removed from I start with 25-gauge chandelier light- the CZ70BD (Alcon), the large incision smaller incisions should surgeons pre- ing (Alcon) and perform a full vitrec- is needed to insert the new IOL. fer to go that route. tomy, ensuring that a posterior vitreous detachment has occurred. Then, with a 25-gauge soft-tip aspiration cannula (Alcon), I use suction to engage the AT A GLANCE IOL on the optic surface. With suction applied and a vacuum created, I lift the s Use of a soft-tip cannula and chandelier lighting during removal of a fallen IOL to the middle of the vitreous cavity (Figure 1). With the IOL safely away from plate-haptic IOL may reduce the risk of creating a posterior break during the retina, I can then use either 20-gauge surgery. reusable IOL forceps or 25-gauge Max- s Removing the IOL intact requires a large incision that can accommodate Grip Forceps (Alcon) to grasp the IOL in my other hand and to maneuver it into insertion of a large IOL. the anterior chamber (Figure 2). s Presenting this case to a panel of experts allowed the author to tease out I do not cut the lens during this details of the technique. procedure, but rather remove the IOL from the eye intact. This requires

42 RETINA TODAY | JANUARY/FEBRUARY 2020

0120rt_Cover_Kitchens.indd 42 1/30/20 2:00 PM TECHNIQUES AND TECHNOLOGIES s

RETINA TODAY ON THE ROAD This article is adapted from a lecture the author presented at the Alcon Retina Film Festival during the AAO Annual Meeting. To watch Dr. Kitchens’s video presentation, visit bit.ly/Kitchens0120.

María H. Berrocal, MD, agreed with my assessment that plate-haptic IOLs Figure 2. After the IOL is lifted from the surface of the retina with a soft-tip cannula, it is brought to the middle of the are difficult to cut because the mate- vitreous cavity, where it can be more safely maneuvered. rial is hard and the lens is slippery. She noted that she cuts flexible acrylic IOLs when she removes them. Timothy G. Murray, MD, MBA, agreed that creating a large incision is appropriate for extraction if another large lens will have to pass through the wound. He said that, rather than cutting an acrylic IOL before removal, he folds the lens and removes it through a small incision. He noted that he does so only in cases in which he will then implant a foldable acrylic lens through the same incision.

Figure 3. The large incision (red circle) used to remove the intact plate-haptic IOL accommodates insertion of an AVOIDING RISK, anterior chamber IOL or a rigid PMMA lens. NOT SLOWING DOWN SURGERY Reducing the risk of iatrogenic injury is paramount during secondary surgery to remove a dropped IOL. However, we must also prioritize efficiency and efficacy. Use of the soft-tip cannula, in my hands, is safer and more efficient than using forceps to directly grab the IOL off the surface of the retina, and it has no observed effect on the final efficacy of the intervention. The technique described here may be appropriate for Figure 4. The panel of surgeons who reviewed this video at the Alcon Film Festival included Donald J. D’Amico, MD; cases in which the surgeon wishes to María H. Berrocal, MD; and Timothy G. Murray, MD, MBA. The author is seated on the right side of the stage. reduce the risk of iatrogenic injury during IOL retrieval and replacement. n EXPERT PANEL COMMENTS regrasp the IOL and try again. The light When I presented this procedure at pipe or another instrument can be the Alcon Retina Film Festival, a panel used to help manipulate the IOL when JOHN W. KITCHENS, MD of surgical experts weighed in (Figure 4). lifting it into the anterior chamber. But n Partner, Retina Associates of Kentucky, Lexington, Donald J. D’Amico, MD, inquired in my experience, dropping the IOL in Kentucky about the risk of damaging the retina this situation does not present much n Editorial Advisory Board Member, Retina Today by dropping the IOL after grasping it risk to the patient. I have not seen iat- n [email protected] with the soft-tip cannula. This does rogenic injury secondary to a dropped n Financial disclosure: Consultant (Alcon) occur, in which case it is necessary to IOL during secondary surgery.

JANUARY/FEBRUARY 2020 | RETINA TODAY 43

0120rt_Cover_Kitchens.indd 43 1/30/20 2:00 PM An Elusive Macular Hole Closed by Eye Drops Alone Although no major studies have analyzed this phenomenon, anecdotal evidence can be instructive.

BY MADELEINE WEBB, BA, BS; AND BRIAN C. JOONDEPH, MD, MPS

64-year-old man presented with a 1-month history of reduced subfoveal fluid and unchanged visual acuity or blurred vision in his right eye (OD). His medical and symptoms (Figure 4). ocular histories were unremarkable. On exam of his right eye and left eye (OS), VA was 20/40 and 20/20, COMMENTARY respectively. Borderline high IOPs, mild nuclear sclerosis, MHs are believed to form due to tractional forces at Aand otherwise normal anterior segments were noted. the vitreoretinal interface. In 2003, Tornambe proposed a His fundus exam revealed macular edema OD; it was normal OS. Spectralis OCT (Heidelberg Engineering) high-speed A 25-raster macular scans through, above, and below the fovea OD revealed macular edema and subretinal fluid (Figure 1). As the appearance was suggestive of a macular hole (MH), a high- density OCT scan was performed, revealing a small MH missed during the standard OCT scan (Figure 2).

THERAPY AND RESULT Given the small size of the MH and presence of edema at its edges, medical treatment with a topical NSAID was offered as an alternative to surgery. B The patient was prescribed ketorolac eye drops 0.5% three times a day OD. After 6 weeks, the MH closed and a small pocket of subfoveal fluid persisted, but no macular edema was noted. The patient’s visual acuity and symptoms had not changed (Figure 3). Over the next 4 months, the drops were gradually tapered. At the patient’s last visit, at which point he was using ketorolac once daily, the MH remained closed with C AT A GLANCE s Small MHs detected on high-density OCT scans might be missed on standard OCT scans.

s A course of NSAID drops may be a nonsurgical option for patients who present with small MHs. Figure 1. Standard OCT scan through the fovea (A), above it (B), and below it (C).

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0120rt_Cover_Joondeph.indd 44 1/30/20 2:00 PM TECHNIQUES AND TECHNOLOGIES s

IT STANDS TO REASON THAT, IF THE RETINAL HYDRATION CAN BE REDUCED MEDICALLY, THE MACULAR HOLE SHOULD Figure 2. High-density OCT scan through the fovea demonstrating a small MH. CLOSE WITHOUT SURGERY. In the case presented here, the subfoveal fluid was improving at the patient’s most recent visit, similar to what is seen in surgically closed MHs, but it may take a year or longer to fully resolve. Our choice of ketorolac was based on insurance formulary coverage and the cost to the patient. Any of the available NSAID drops would be suitable for a similar patient.

Figure 3. High-density OCT scan through the fovea 6 weeks after starting NSAID LESSONS TO LEARN treatment showing a closed MH with subfoveal fluid pocket. Although prospective randomized clinical trials are the gold standard for validating treatments, new treatment modalities can be introduced to the retina community based on anecdotal experience shared with others. Two lessons can be drawn from this case. First, standard OCT scans can miss a small MH. If there is a high degree of clinical suspicion that an MH is present based on other clinical features, a high-density scan through the fovea may reveal the hole. Second, for small MHs with some degree of retinal edema, a trial of NSAID drops is a reasonable initial treatment option, avoiding the potential adverse effects and patient Figure 4. High-density OCT scan through the fovea 4 months after starting treatment showing a closed MH with a slightly smaller subfoveal fluid pocket. inconvenience of surgical treatment without compromising future surgical treatment if needed. n hydration theory of MH formation,1 whereby posterior hya- 1. Tornambe PE. Macular hole genesis: the hydration theory. Retina. 2003;23(3):421-424. loid traction creates a small inner foveal retinal defect which 2. Ehlers JP, Han J, Petkovsek D, Kaiser PK, Singh RP, Srivastava SK. Membrane peeling-induced retinal alterations on intra- then absorbs vitreous cavity fluid, causing retinal swelling operative OCT in vitreomacular interface disorders from the PIONEER study. Invest Ophthalmol Vis Sci. 2015;56(12):7324- around the defect. As the inner retina swells, it retracts ante- 7330. riorly, widening the hole. This theory suggests that reversing the hydration process may lead to hole closure. Surgery with internal limiting BRIAN C. JOONDEPH, MD, MPS membrane peeling and gas bubble tamponade accomplishes n Partner, Colorado Retina Associates, Denver this with a high degree of success. n Clinical Professor of Ophthalmology, Rocky Vista University College of It stands to reason that, if the retinal hydration can be Osteopathic Medicine, Parker, Colorado reduced medically, the MH should close without surgery, n [email protected]; Twitter: @retinaldoctor which it did in the case presented here. The hole closed, n Financial disclosure: None and likely over time the subfoveal fluid pocket will reab- sorb. In an analysis of OCT findings in surgically closed MADELEINE WEBB, BA, BS MHs in the PIONEER study, subfoveal fluid was present in n Ophthalmic Technician, Colorado Retina Associates, Denver 49% of eyes at 1 month after surgery, decreasing to 37% at n [email protected] 6 months.2 n Financial disclosure: None

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0120rt_Cover_Joondeph.indd 45 1/30/20 2:00 PM The Beauty of a Dual-Blade Vitrectomy Probe A new probe makes a big leap.

BY PETER A. KARTH, MD, MBA

We are called vitreo- ous is aspirated into the port; when the MY FAVORITE retinal surgeons, but, port closes, there is turbulent retropul- INSTRUMENT for the most part, we sion and vitreous recoil, which turns vit- are vitreous surgeons. reous strands into whips and transfers Membrane peels are kinetic energy back to the retina. We an important part of our skill set, but I see this most clearly when performing would venture to say that most of our peripheral vitreous shaves on detached surgical time is spent dealing with vit- retinas, scenarios in which we often see reous. Even straightforward surgery for iatrogenic retinal breaks (secondary to an epiretinal membrane may take an retropulsion and vitreous recoil). unwanted turn if a retinal tear occurs, which is nearly always caused by vit- DUAL-BLADE SYSTEMS reoretinal traction. Vitrectomy probes that are always Figure. The dual-blade design of this probe allows Retinal detachment surgery, too, is open allow continuous and constant constant vitreous aspiration, reducing retropulsion and all about the vitreous. The vitrectomy flow, free from retropulsion. Fluid and vitreous recoil during vitrectomy. cutting probe is front and center dur- vitreous are constantly aspirated into ing this important task. We have seen the port, allowing smooth aspiration Blade Vitrectomy Probe represents a huge improvements in vitrectomy without turbulence and traction on the huge leap forward from the 25-gauge probe cut speed and gauge size in the retina. This allows me to move the probe systems I previously used, and even the past decade. To me, the biggest leap in directly onto the detached retina with- 27-gauge 10,000 cpm system. n development has arrived in the form out the fear of creating a break. I no lon- of the HyperVit Dual Blade Vitrectomy ger see turbulent vitreous whipping. This Probe (Alcon), which has quickly has led to fewer iatrogenic breaks, even PETER A. KARTH, MD, MBA become my favorite instrument for in surgical cases involving the macula. n Vitreoretinal Surgeon, Oregon Eye Consultants, vitreoretinal surgery (Figure). With this higher flow, a dual-blade Eugene, Oregon port allows me to quickly remove vitre- n [email protected]; PeterKarthMD on social media USER EXPERIENCE ous, and the 27-gauge port practically n Financial disclosure: None In my experience, this probe has dra- eliminates any wound leak. Overall, I matically reduced vitreous movement believe the 27-gauge HyperVit Dual (due to constant vitreous flow) and nearly eliminated retropulsion. These innovations have led to a decrease in vitreous turbulence, which reduces vit- AT A GLANCE reous traction on the retina. s An important difference between single-blade and dual-blade vitrectomy SINGLE-BLADE SYSTEMS probes is the rate and constancy of vitreous flow during vitrectomy. In a single-blade system, turbulent s A dual-blade system facilitates safer, more efficient removal of vitreous due to a retropulsion occurs each time the port design that constantly keeps the port open, allowing constant even flow. is closed. When the port is open, vitre-

46 RETINA TODAY | JANUARY/FEBRUARY 2020

0120rt_Cover_Karth.indd 46 1/30/20 1:59 PM Bi-Blade Cutter Provides Fast Speeds, Improved Fluidics The 100% duty cycle allows constant aspiration with a consistent flow rate.

BY RAHUL K. REDDY, MD, MHS

Over the past decade available in 23-, 25-, and 27-gauge MY FAVORITE we have seen unprec- platforms. The efficiency of the cutter INSTRUMENT edented advances in is based on a double-cut mechanism, the field of surgical with a completely open port and 100% retina. The surgi- duty cycle. The cutter achieves speeds cal landscape continues to expand of 15,000 cuts per minute. Its design and evolve, with emphasis placed on allows constant aspiration with a con- outcomes, efficiency, and cost. As we sistent flow rate, resulting in efficient strive to provide the best possible vitreous removal. Figure. A close-up shot of the dual-port Bi-Blade cutter care for our patients, surgeons have a Because of the importance of efficiency (Bausch + Lomb). variety of options with regard to sur- in central vitreous removal, perhaps the the system’s shave mode to address gical platforms and vitreous cutters. greatest advantage of the Bi-Blade cutter thick preretinal bands, facilitating access However, we face challenges including is the fluidic predictability that surrounds to dissection planes. increasing costs of instrumentation the cutter port. This predictability gives I cannot overemphasize the benefit and decreasing reimbursements. the surgeon an intuitive ease of move- of the predictability of this cutter probe In this economic environment, it ment within the vitreous and promotes a and the surrounding flow, providing the is vital for surgeons to determine the high level of confidence as the cutter port surgeon with a high degree of control. optimal vitrectomy platform to suit can shave near the surface of retina to The Bi-Blade vitreous cutter has become their purposes. The ideal system is a perform a variety of maneuvers. With the integral in my OR, as it enables me to platform that maximizes fluidics while superior fluidics of the system, delicate maintain quality, improve efficiency, and exerting minimal retinal traction. With maneuvers can be accomplished with minimize risk of complications. n the introduction of dual cutting, modern minimal retinal traction. surgical platforms have maximized the I have noted minimal turbulence at speed with which central vitreous can be the tip of this cutter probe as com- RAHUL K. REDDY, MD, MHS removed, and we are reaching the ceiling pared with other platforms. In par- n Vitreoretinal Surgeon, Associated Retina with current pneumatic cutter designs. ticular, I can more efficiently and safely Consultants, Scottsdale, Arizona I am a surgical retina specialist in perform segmentation and delamina- n Assistant Clinical Professor of Ophthalmology, Phoenix in a large academic private tion of diabetic membranes as well University of Arizona College of Medicine, Phoenix practice with two fellows, nine providers, as removal of peripheral vitreous on n [email protected] and 13 locations. With a busy surgical mobile retina. I particularly like to use n Financial disclosure: Consultant (Bausch + Lomb) practice operating out of ambulatory surgery centers, our vitreous cutter must be chosen to facilitate efficiency and excel- AT A GLANCE lent outcomes. The dual-port Bi-Blade vitreous cutter of the Stellaris Elite Vision s The Bi-Blade cutter on the Bausch + Lomb Stellaris achieves high cutting Enhancement System (Bausch + Lomb) speeds and optimized fluidics. enables us to achieve a high degree of s efficiency in the OR (Figure). Maneuvers close to the retina can be accomplished safely and with confidence. The dual-port Bi-Blade cutter is

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0120rt_Cover_Reddy.indd 47 1/30/20 2:04 PM rt_house spread_2020.indd 48 1/30/20 4:11 PM Log on now at www.retinatoday.com

rt_house spread_2020.indd 49 1/30/20 4:11 PM 1/30/20 3:14 PM . 1. SILICONE OIL–FILLED BUCKLED EYE . 1. SILICONE OIL–FILLED BUCKLED EYE o Figure 1. Widefield color fundus photo montage OS of a buckled eye with silicone oil Figure 1. Widefield color fundus photo montage OS of a buckled eye with silicone oil reflex. The retina is well settled, and laser marks can be seen nasally. A 36-year-old man presented for routine postoperativeroutine for presented man 36-year-old A The capabilities of the Mirante make it useful in a num- a in useful it make Mirante the of capabilities The follow-up 3 months after pars plana vitrectomy with scleral with vitrectomy plana pars after months 3 follow-up undergone had He detachment. retinal total a for buckle sili- and vitrectomy plana pars 25-gauge with encirclage 6/18was BCVA His (OS). eye left the in injection oil cone 360°a showed montage photo color fundus Widefield OS. wellwas retina The reflex. oil silicone a and effect buckle seen be can site retinotomy the around marks Laser settled. 1). (Figure o’clock 10 at ber of scenarios. Here we present case examples in whichin examples case present we Here scenarios. of ber onimaging widefield for modalities more or one used we device. the CASE N Devices that perform widefield imagingwidefield perform that Devices 1

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he peripheralretinalin involved commonly is retina occlu- vein retinopathy, diabetic as such pathologies Ultra-widefielduveitis. and detachments, retinal sions, assess- retinal of part essential an becoming is imaging ofdocumentation and screening facilitates it as ment, The Mirante’s spectral-domain OCT (SD-OCT) captures (SD-OCT) OCT spectral-domain Mirante’s The According to Nidek, the Mirante is the only device thatdevice only the is Mirante the Nidek, to According Themodalitiesimaging multiple provides Mirante SLO-based BY MANISH NAGPAL, MS, DO, FRCS(EDIN); GAYATHRI MOHAN, MS; AKSHAR SONI, MS; SHAM TALATI, DO; DO; MS; AKSHAR SONI, MS; SHAM TALATI, MS, DO, FRCS(EDIN); GAYATHRI MOHAN, BY MANISH NAGPAL, DNB, MNAMS AND NAVNEET MEHROTRA, Documenting the periphery is vital in many retinal pathologies. periphery Documenting the T the retinal periphery. retinal the 85,000 A-scans per second. It can obtain macula maps thatmaps macula obtain can It second. per A-scans 85,000 assess- detailed facilitating area, 12-mm by 16.5-mm a include singlea in choroid the to vitreous the from field wide a of ment otheron possible is than field imaging OCT wider a is This shot. mm.16.5 at devices includes four separate lasers, each of which penetrates to differ- to penetrates which of each lasers, separate four includes fibernerve the by reflected is which nm, (480 blue depths: ent redlayer), cell ganglion the by reflected nm, (532 green layer), nm,(790 infrared and retina), the through penetrates nm, (670 canlasers the of Each layer). choroidal the through penetrates smalla with setup optical confocal a through retina the scan thefrom coming light only in lets that pinhole placed coaxially light.focal planes, while blocking backscattered and out-of-focus pseudocolorreproduce to Mirante the allow lasers multiple The fundus. the of colors natural the mimic almost that images in one device: high-definition OCT and confocal SLO (cSLO),SLO confocal and OCT high-definition device: one in fun- (OCTA); angiography OCT capabilities; widefield with both auto- fundus blue and green ICGA; and FA photography, dus widefieldadvanced optional An modes. retro and fluorescence; isattachment lens eye) the of center the from measured (163° device. this for available

FOUR LASERS, ONE DEVICE FOUR LASERS, ONE DEVICE WIDEFIELD MULTIMODAL IMAGING MULTIMODAL WIDEFIELD can capture images in a number of modalities, including colorincluding modalities, of number a in images capture can angiography ICG (FA), angiography fluorescein photography, thedevice, such one with experience Our OCT. and (ICGA), is(Nidek), Mirante (SLO) ophthalmoscope laser scanning article.this in detailed RETINA TODAY

50 s SPECIAL REPORT 0120rt_Special Report_Nagpal_PA Ave_Ciulla.indd 50 SPECIAL REPORT s

AT A GLANCE s The peripheral retina is usually involved in numerous frequent retinal pathologies.

s Ultra-widefield imaging facilitates screening and documentation of the retinal periphery.

s The Mirante SLO uses four lasers to capture images in a variety of modalities.

CASE No. 2. REDETACHMENT IN A BUCKLED EYE A 24-year-old man presented with decreased visual acuity OS that had persisted for 1.5 years. His ocular history included scleral buckling performed 2 years ago. Widefield fundus Figure 3. Widefield color fundus photo montage OS shows an elevated retinoblastoma color photo montage showed a subtotal retinal redetach- lesion nasally with cryo and laser marks. Sclerosed vessels are seen extending from ment involving the macula OS in a buckled eye with only the the disc to the lesion nasally. superonasal portion attached (Figure 2).

Figure 2. Widefield color fundus photo montage OS shows a subtotal retinal redetachment with superonasal portion attached.

CASE No. 3. LASERED RETINOBLASTOMA Figure 4. Widefield color fundus photo OD shows a myopic fundus with tessellated A 13-year-old girl presented for a routine follow-up. She background. A well-lasered horseshoe tear can be seen at 2:30 o’clock. had undergone chemotherapy plus laser ablation and cryotherapy for retinoblastoma 10 years ago. Widefield color and had used correction since childhood. He had undergone fundus montage OS showed sclerosed vessels extending prophylactic laser barrage OD 5 years ago. Widefield fundus nasally from the disc (Figure 3). An elevated mass was seen in photograph showed a myopic fundus with tessellated back- the nasal periphery with laser and cryo marks. The rest of the ground (Figure 4). A large disc with peripapillary atrophy was retina was normal with a good foveal reflex. No new lesions noted, along with pigmentary alterations at the macula. A were seen. well-barraged horseshoe tear can be seen at 2:30 o’clock.

CASE No. 4. LASERED HORSESHOE TEAR CASE No. 5. CENTRAL RETINAL VEIN OCCLUSION A 46-year-old man presented for a routine follow-up. A 52-year-old man with hypertension presented with BCVA in the right eye (OD) was 6/6. The patient was myopic decreased vision OD lasting 2 months. His BCVA was 6/12

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0120rt_Special Report_Nagpal_PA Ave_Ciulla.indd 51 1/30/20 3:14 PM s SPECIAL REPORT

A B CASE No. 7. MULTIFOCAL CHOROIDITIS A 60-year-old hypertensive woman presented with complaints of floaters and decreased vision OS for the past 10 days. Her BCVA OS was 6/12. Fundus examination revealed disc edema with vitritis and scattered multiple hypopigmented subretinal lesions (Figure 7A). On widefield ICGA, multiple hypofluorescent lesions in the posterior pole corresponded to the clinical picture (Figure 7B). These spots C D remained hypofluorescent thorough the mid and late phases (Figure 7C, D), indicating active lesions. A B

Figure 5. Fundus photo shows multiple hemorrhages, cotton wool spots with macular edema (A). FA widefield montage shows multiple hyperfluorescent dots with diffuse leakage at the macula (B). Retro mode infrared illumination shows multiple tiny elevations at the macula suggestive of edema (C). SD-OCT shows an altered foveal contour with cystoid spaces (D). C D with early cataractous changes. Fundus examination revealed multiple hemorrhages in all quadrants and cotton wool spots with macular edema (Figure 5A). FA widefield montage showed multiple hyperfluorescent dots with diffuse leakage at the macula (Figure 5B). Retro mode infrared illumination showed petaloid elevation at the macula suggestive of edema (Figure 5C). A 16-mm horizontal line scan on SD-OCT showed an altered foveal contour with cystoid Figure 7. Widefield color photo shows multiple hypopigmented patches in all spaces (Figure 5D). quadrants with vitritis and disc edema (A). Widefield ICGA in early phase shows multiple hypofluorescent lesions in all quadrants, suggestive of choroiditis (B). CASE No. 6. LASERED DIABETIC RETINOPATHY Hypofluorescence remained in mid (C) and late phase (D) ICGA, suggesting that the A 52-year-old man with diabetes presented with lesions were active. decreased visual acuity OS lasting 6 months. BCVA OS was 6/24. A 163° widefield fundus image showed a few hemor- CASE No. 8: VOGT-KOYANAGI-HARADA DISEASE rhages in the posterior pole and 360° laser marks (Figure 6A). A 32-year-old man had decreased vision in both eyes for Widefield FA revealed an altered foveal avascular zone (FAZ) the past 7 days. His BCVA was 6/36 in both eyes. Fundus and 360° staining from laser marks (Figure 6B). examination showed vitritis OD and disc edema with subretinal fluid pockets in all quadrants (Figure 8A). Widefield FA A B A B

Figure 8. Widefield color photo montage OD shows vitritis and disc edema with subretinal fluid pockets in all quadrants (A). Widefield FA montage reveals altered Figure 6. Fundus photo shows multiple hemorrhages along the posterior pole and FAZ with multifocal areas of pinpoint leakage, with leakage over disc with extensive superior arcade with 360° laser marks (A). Widefield FA shows altered FAZ and peripheral leakage visible in late phase (B). 360° laser staining marks (B). (Continued on page 60)

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0120rt_Special Report_Nagpal_PA Ave_Ciulla.indd 52 1/30/20 3:14 PM The podcast covering all the latest trends in retina.

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NRR_ad_full.indd 1 1/30/20 4:09 PM s SPECIAL REPORT VISUAL DISTURBANCES IN HEADACHE Just a pain for the patient or a canary in a coal mine?

BY KIMBERLY M. WINGES, MD

eadache syndromes often versus those who experience migraine AURA involve the visual system, without aura.4 Aura in migraine consists of recurrent and patients frequently seek Left untreated, the headache in attacks of unilateral, fully reversible eye care for symptoms that migraine lasts 4 to 72 hours and is visual, sensory, or other central nervous may or may not be related associated with at least two of the system symptoms that evolve over Hto migraine aura. Although it is following four characteristics: minutes and last less than an hour always important to evaluate these • Having a unilateral location; (most commonly 10–30 minutes). patients for ocular causes of visual • Exhibiting a pulsating quality; Aura is often unilateral and dynamic disturbances and to treat those causes, • Carrying a moderate or severe pain and involves at least one positive visual if present, ophthalmologists often face intensity; and phenomenon. It is usually followed by patients who are experiencing visual • Being aggravated by, or causing headache but can occur in isolation disturbances in the absence of visible avoidance of, routine physical without reported pain. The term ocular pathology. Primary headache activity (eg, walking or climbing ocular migraine is commonly used to disorders such as migraine with aura stairs). refer to painless, typical visual auras. produce positive visual phenomena, The headache is accompanied by More cautious usage of that term is and secondary headaches such as at least nausea and/or vomiting or by warranted, however, because it can compressive intracranial lesions photophobia and/or phonophobia.1 imply a visual migraine aura that cause visual changes due to increased intracranial pressure or mass effect on the intracranial visual pathways. It is important to distinguish between VISUAL SNOW primary and secondary headache syndromes because both the patient’s A persistent positive visual phenomenon health and peace of mind are at stake. associated with migraine but distinct from persistent migraine aura is known as visual snow.1 MIGRAINE This chronic illusion persists in the absence of Headaches come in many forms, as acute attacks and is more frequently found in described in International Headache patients with a history of migraine. They often Society guidelines.1 Migraine is the describe the phenomenon as looking through TV second most common form of primary static or snowfall. headache disorder, behind only Visual snow is distinct from persistent migraine tension-type headache. The Global aura (Figure). Positron emission tomography Burden of Disease Study of 2015 scan studies have linked this phenomenon to ranked migraine the third-highest Figure. Visual snow is one type of chronic altered hypermetabolism in the supplementary visual cor- perception commonly reported by patients with a history cause of disability worldwide in both tex (lingual gyrus).2 A similar link has been found of migraine. They describe a TV static-like disruption of men and women less than 50 years in patients with chronic photophobia, linking light their entire visual field that is constant and present even of age.2,3 Migraine is classified into sensitivity to migraine on a pathophysiologic level.3 in the absence of headache. migraine with aura (classic migraine) Although visual snow is harmless in isolation, any and without aura (common migraine). 1. Liu GT, Schatz NJ, Galetta SL, Volpe NJ, Skobieranda F, Kosmorsky positive visual phenomenon that is new should GS. Persistent positive visual phenomena in migraine. Neurology. This distinction is important because 1995;45(4):664-668. prompt visual field testing and further workup 2. Schankin CJ, Maniyar FH, Digre KB, Goadsby PJ. ‘Visual snow’ - a disorder several meta-analyses of the literature distinct from persistent migraine aura. Brain. 2014;137(pt 5):1419-1428. based on accompanying historical details as 3. Chong CD, Starling AJ, Schwedt TJ. Interictal photosensitivity associates have shown a twofold increase in the with altered brain structure in patients with episodic migraine. Cephalalgia. risk of ischemic stroke for patients described elsewhere in this article. 2016;36(6):526-533. who experience migraine with aura

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0120rt_Special Report_Winges.indd 54 1/30/20 4:07 PM SPECIAL REPORT s

HEADACHE AND DRY EYE debilitating, instilling fear in patients during highly demanding visual tasks By Gillian McDermott, MA, Editor-in-Chief, Clinical Content, Anterior Segment such as driving because these auras interfere with the visual field. Patients with migraine often experience aura, Questionnaire-25, the Headache Impact Test, the Although more than 90% of auras photophobia, and eye pain. Investigators for a Visual Aura Rating Scale, the Ocular Surface Disease are visual, patients may experience cross-sectional survey-based study evaluated visual Index, and the Utah Photophobia Score. Investigators other phenomena such as concurrent quality of life, headache impact, aura, dry eye, and looked for correlations between patients’ responses sensations of pins and needles photophobia in 62 patients with migraine.1 Of these to the questionnaires. The researchers found that dry emanating from a point to a side patients, 17 had episodic migraine and 45 had chronic eye had the greatest negative effect on visual quality of the body or face or, more rarely, migraine. Twenty-three of the patients reported of life and headache impact. aphasia or other speech disturbances. experiencing aura, and 39 did not report aura. Other prodromal symptoms (eg, blurry Patients completed several validated 1. Ozudogru S, Neufeld A, Katz BJ, et al. Reduced visual quality of life associated vision and fatigue) may signal an with migraine is most closely correlated with symptoms of dry eye. Headache. oncoming migraine 24 to 48 hours questionnaires, such as the Visual Functioning 2019;59(10):1714-1721. before headache onset.

DIAGNOSIS presents bilaterally with intracranial total loss of vision in either or both A thorough history provides pathology, or it can refer to a retinal eyes (Figure, center). critical guidance on the differential migraine with vasospastic vision loss diagnosis and workup. Neurologists in one eye. Visual disturbances seen s No. 3: Visual Distortions/ frequently ask patients to keep a in migraine aura may be divided into Illusions. The patient’s visual headache or headache aura journal three types. perception misrepresents reality or calendar. By documenting the (Figure, right). Examples include characteristics, timing, and evolution s No. 1: Positive Visual Phenomena/ bilateral metamorphopsia, micropsia of symptoms as well as any associated Hallucinations. The patient sees things or macropsia, halos, kaleidoscopic neurologic features, patients may that are not there, including lights, or fractured scenes, sensation of be able to identify environmental patterns, or something obstructing looking through waves of heat or triggers and gauge their responses to vision. These are the classic migraine water, persistence of visual imagery treatment more accurately. Common aura descriptions of scintillating (palinopsia), or loss of color vision environmental triggers include dietary scotoma or fortification spectra (achromatopsia). consumption of chocolate, red wine, (Figure, left). A migraine patient may experience sugar, or monosodium glutamate. any single or combined version of the High-stress environments, erratic s No. 2: Negative Visual Phenomena. aforementioned visual symptoms, sleep schedules, bright sunlight, strong Areas of vision are missing, such as which completely reverse, have a odors, extreme exertion, and/or homonymous field loss, constriction stereotyped pattern for each patient, medication use or overuse can also be of the visual field—often described and can change over a lifetime (see to blame. Triggers are individualized as tunnel vision—scotomas, or a Visual Snow). Visual auras can be and can change over time.

Figure. Visual disturbances seen in migraine aura. Positive visual phenomena are the most common. An object in the way of the patient’s view moves from center to periphery in a centrifugal, spreading pattern (left). Negative visual phenomena such as a missing area of visual field develop, last for 10 to 30 minutes, and then resolve (center). Visual distortions or illusions happen when the patient perceives a normal scene as if it were fractured, underwater, or otherwise altered, often in a dynamic pattern (right).

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0120rt_Special Report_Winges.indd 55 1/30/20 4:07 PM s SPECIAL REPORT

By definition, the diagnosis symptoms, such as slurred speech, CONCLUSION of isolated migraine and other hemiparesis, Horner syndrome, Many eye care providers primary headache syndromes or cranial nerve palsy. Although are undertrained in headache requires that there be no causative complex migraine can produce classification, but knowing the basic pathology on diagnostic evaluation. these symptoms in a recurrent features common among patients The examination of a patient fashion, targeted neuroimaging with associated visual disturbances presenting with headache and visual and a neurology workup should be and recognizing the warning disturbances should therefore include performed to exclude ischemic or signs of secondary headache are careful documentation of BCVA and embolic stroke from carotid artery critical to making clinical decisions. color vision, assessment for a relative atherosclerosis, artery dissection, Prompt referral to an emergency afferent pupillary defect, and a dilated arteriovenous malformation, or department, a neurologist, or a fundus examination to identify retinal intracranial aneurysm; neuro-ophthalmologist may be or optic nerve pathology indicating • Persistent vision loss or positive visual necessary when the diagnosis or a causative structural lesion. Both phenomena that do not fully resolve; management strategy is uncertain. n confrontation and formal visual • Onset of migraines in patients older field testing is highly recommended than 50 years of age; 1. Headache Classification Committee of the International Headache Society (IHS): The International Classification of Headache Disorders, 3rd edition. to identify optic neuropathy or • Dramatic change in the character or Cephalalgia. 2018;38(1):1-211. homonymous defects, localizing the worsening severity of migraines or 2. Steiner TJ, Stovner LJ, Vos T. GBD 2015: migraine is the third cause of defect posterior to the chiasm. OCT migraine aura; disability in under 50s. J Headache Pain. 2016;17(1):104. 3. GBD 2015 Neurological Disorders Collaborator Group. Global, regional, imaging of the macular ganglion cell • Transient monocular vision loss, and national burden of neurological disorders during 1990-2015: a system- layer and retinal nerve fiber layer may often described as a curtain over atic analysis for the Global Burden of Disease Study 2015. Lancet Neurol. help to localize and obtain a baseline vision and usually lasting only a few 2017;16(11):877-897. 4. Hansen JM, Charles A. Differences in treatment response between migraine of optic nerve structural changes, minutes before complete resolution. with aura and migraine without aura: lessons from clinical practice and RCTs. especially if optic nerve atrophy is This phenomenon is indicative J Headache Pain. 2019;20(1):96. suspected. of amaurosis fugax and requires a retinal and cardiac workup for RED FLAGS embolic stroke; and KIMBERLY M. WINGES, MD When do a patient’s visual • Significant associated systemic n Comprehensive and Neuro-Ophthalmologist disturbances and headache warrant symptoms such as scalp tenderness, n Assistant Chief of Surgery for Clinical further workup? Several situations jaw claudication, and arthralgias that Operations, VA Portland Health Care System, should raise concern about a may accompany transient vision loss Portland, Oregon secondary headache syndrome: or diplopia with headache. These n Assistant Professor of Ophthalmology and • Homonymous visual field defects; require an emergency workup for Neurology, Casey Eye Institute, Oregon Health & • Loss or alteration of consciousness; giant cell arteritis and immediate Science University, Portland, Oregon • Concurrent neurologic signs or empiric steroid treatment. n [email protected] n Financial disclosure: None

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0120rt_Special Report_Winges.indd 56 1/30/20 4:07 PM PENNSYLVANIA AVENUE UPDATES s COST EFFECTIVENESS ANALYSIS IN RETINA New one-time treatments require new reimbursement models.

BY THOMAS A. CIULLA, MD, MBA

he economics of health care, which accounts now for the resulting CEAs, are complex and sometimes controver- 17% of the US gross domestic product, has become a sial, especially in determining appropriate indirect costs that topic of great debate. Medicare now monitors physi- address the high societal impact of blindness and in deter- cian costs of care under its Merit-Based Incentive mining the appropriately relevant health utilities to derive Payment System, and failure to participate in the pro- QALYs (See A Review of Terms). gramT results in meaningful reductions in physician payment for Medicare services.1 Direct Medical Costs Most physicians are familiar with the resource-based The direct medical costs of a new therapy can be com- relative value scale (RBRVS), the physician payment sys- pared to the existing standard of care. Interestingly, direct tem used by CMS, based on recommendations from medical cost offsets generated by a new therapy are minimal the AMA/Specialty Society Relative Value Scale Update for disorders with no existing therapy, such as many inher- Committee. The RBRVS ranks payments by resource ited retinal diseases. By contrast, direct medical cost offsets costs, including physician work, practice expense, and lia- can be substantial for disorders with costly existing therapy, bility insurance.2 such as hemophilia. However, most physicians are not familiar with cost-effectiveness analyses (CEA), the metrics used in health care eco- Indirect Medical Costs nomic assessment, which provide physicians with another Determination of indirect medical costs can be complex, common language to communicate the value of their work but it is important for ophthalmologists to understand the and therapies to insurance carriers, government regulators, and hospital administrators. This article reviews some of these metrics with particular emphasis on retinal therapies. AT A GLANCE s COST-EFFECTIVENESS ANALYSES IN RETINA Understanding health care economic analyses can provide Many payers perform CEA to evaluate the value for money physicians with a common language to communicate the value of different health interventions by comparing the costs and of their work and therapies. health outcomes of a new or proposed treatment relative s to standard treatment. In the United States, CEA is routinely There are unique challenges associated with one-time gene ther- performed by payers, as well as by independent organiza- apies, as some payers are reluctant to model lifetime treatment tions such as the Institute for Clinical and Economic Review. benefits and to consider the indirect cost offsets associated with In the United Kingdom, which has the publicly funded National Health Service, the National Institute for Health the high societal costs of blindness. and Care Excellence (NICE) routinely performs CEA. In the s The current health care system may readily value chronically future, health care resource allocation may increasingly be determined by CEA. administered medications but not properly value therapies that The value of a therapy generally derives from three major deliver long-lasting benefits with one administration. inputs: direct cost offsets (such as lowered cost of care com- s New reimbursement models tying payment to real-world pared to standard care), indirect cost offsets (such as lowered societal costs), and impact on quality-adjusted life years treatment effectiveness are being implemented. (QALYs). These inputs, which greatly affect the outcomes of

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9 Epiretinal membrane sur- membrane Epiretinal 8 incremental cost effectiveness ratio effectiveness cost incremental Consequently, interventions that restore that interventions Consequently, 7 transition model is often used. often is model transition state health A QALY is along years of life additional reflecting value added through factors. quality-of-life additional health-related with The - corre of 1.0 and a value to death value of 0.0 corresponding of perfect health. a year sponding to ICER the cost the difference in their QALYs, and it reflects divided by QALY gained. per s in discussionofhealthoutcomes, used a commonunit s QALYishealth utility, with a underlying measurementof s two therapies cost between difference in reflects the Health Utility ICER: Incremental Cost Effectiveness Ratio QALYs: Quality-Adjusted Life Years QALYs: Quality-Adjusted Studies have assessed the added QALYs resulting from resulting QALYs added the assessed have Studies In CEA, a CEA, In arepresent QALYs RBRVS, the to analogous Somewhat the term, Another A REVIEW OF TERMS A REVIEW profound loss of vision can be associated with significant with associated be can vision of loss profound QALYs. added example, For interventions. surgical ophthalmic common a over QALYs 1.62 conferred surgery cataract first-eye cata- Bilateral life. of quality in gain 20.8% a model, 13-year 36.2% a years, 13 over QALYs 2.82 conferred surgery ract life. of quality in improvement standard measure for comparing different treatments. Costtreatments. different comparing for measure standard compareto used sometimes is ratio) (cost-utility QALY per some- are prices threshold QALY per costs and therapies, Unitedthe In allocation. resource care health in used times for QALY per $50,000 from range can threshold the States, newa for QALY per $150,000 to $100,000 to therapy new a usestypically NICE Kingdom, United the In therapy. orphan thresholds. cost-per-QALY lower gery in the better-seeing eye compared with observation observation with compared eye better-seeing the in gery QALYs. discounted 0.755 of gain mean a in resulted respectively). COST UTILITY RATIO AND ICER Health states are identified that describe all of the relevant the of all describe that identified are states Health for in be could patient a that states economic and clinical and QALYs assigned are states These lifetime. her or his to used are probabilities transitional costs; medical direct back- time; over states health the through patients move all when ends model the and modeled, is mortality ground model. the exited have patients

3 4 health utility, health Vision loss to the level of hand hand of level the to loss Vision 7 The health utility literature in retina in literature utility health The 5

6 | JANUARY/FEBRUARY 2020 For example, vision loss to the level of finger count- finger of level the to loss vision example, For 5 A recent study illustrated how large indirect costs can becan costs indirect large how illustrated study recent A The underlying measurement of a QALY is QALY a of measurement underlying The A QALY is a common unit used in discussion of health of discussion in used unit common a is QALY A Health utilities are not vision-specific, and decreased and vision-specific, not are utilities Health for an inherited retinal disease (IRD) population, especiallypopulation, (IRD) disease retinal inherited an for loss. vision severe to lead and early present that IRDs for Furthermore, the loss of wages and tax payments from care- from payments tax and wages of loss the Furthermore, insignificant.not is givers with a value of 0.0 corresponding to death and a value of value a and death to corresponding 0.0 of value a with Time-tradeoff health. perfect of year a to corresponding 1.0 ask- by ophthalmology in assessed been has analysis utility theoreti- their of much how patients impaired visually ing return in trade to willing be would they life remaining cally vision. normal for outcomes, reflecting value added through additional years additional through added value reflecting outcomes, quality-of-life health-related additional with along life of substantial be can HRQL of Enhancement factors. (HRQL) therapeutics. retinal for QALY - blind of costs societal high the offsetting by created value substantial be can offsets cost indirect Specifically, ness. disorders.blinding serious address that therapies new for attain- educational increased from derive offsets These burden,caregiver reduced productivity, enhanced ment, 2016,In programs. governmental on reliance decreased and only Blind, the for Federation National the to according - bach a obtained disability visual a with individuals of 16% line;poverty the below lived 28% higher; or degree elor’s significant reported who adults working-age among and, full-time. employed not were 70% than more loss, vision has historically assessed visual impairment through visual through impairment visual assessed historically has age- with patients involving studies from derived as acuity, macular diabetic and (AMD) degeneration macular related (DME). edema visual acuity compares with very serious systemic disor- systemic serious very with compares acuity visual ders. motions compares to stroke with major residual deficits or deficits residual major with stroke to compares motions blad- and bowel and pain with cancer prostate advanced 0.35, and 0.34, 0.35, of utilities health (with dysfunction der Educational options become increasingly limited with pro- with limited increasingly become options Educational lowerwith associated is which impairment, visual of gression educationalfewer having of effect cumulative The earnings. orcollege to matriculating of likelihood lower a options, highand strata, educational across earnings reduced beyond, aproduces age, early an at beginning usually needs, caregiver thein Unfortunately, patient. per cost indirect lifetime large acknowl- fully not may insurers commercial States, United generallygovernments because offsets cost indirect edge costs.these bear ing compares to severe angina or end-stage renal disease disease renal end-stage or angina severe to compares ing 0.58, 0.52, of utilities health (with dialysis home requiring respectively). 0.56, and RE TINATODAY 58 s UPDATES AVENUE PENNSYLVANIA 0120rt_Special Report_Nagpal_PA Ave_Ciulla.indd 58 PENNSYLVANIA AVENUE UPDATES s

(referred to as ICER) describes the difference in cost between two interventions divided by the difference in their QALYs THE RECENT ECONOMIC and reflects the difference in cost per QALY gained. In retina care, payers likely perform this type of comparative CEA in justifying anti-VEGF step therapy for neovascular CHALLENGES RELATED AMD and DME. (As we well know, these are protocols that mandate trial and failure on certain less costly treatments before allowing access to other potentially more appropriate TO ONE-TIME RETINAL GENE treatments.) A basic understanding of these CEA analyses and their limitations better enables retina specialists to knowledgeably advocate for appropriate patient-centered THERAPY HAVE ACCELERATED medical decision-making.10

UNIQUE CHALLENGES DISCUSSION OF NEW One-time gene therapies have become an important topic in the retina community and in health care economics, REIMBURSEMENT MODELS. given the recent approval of voretigene neparvovec-rzyl (VN; Luxturna, Spark Therapeutics), the first US FDA–approved gene therapy for a genetic disorder. Other potential gene typically capture the value of the treatment over a patient’s therapies are at varied stages in the development pipeline. lifetime, gene therapy must capture the value of the benefit One-time gene therapies pose complex valuation chal- it provides coincident with one-time use. lenges.11 Specifically, retinal gene therapies could potentially enhance many patients’ quality of life while decreasing EVOLVING REIMBURSEMENT MODELS overall cost to society, given the previously discussed high The recent economic challenges related to one-time societal costs of blindness and visual impairment and the retinal gene therapy have accelerated discussion of new increasing life expectancy in the United States. However, reimbursement models. These models often involve install- payers are reluctant to model lifetime treatment benefits, ment payments or tie payment to real-world treatment given the limited long-term efficacy data of these novel ther- effectiveness. For example, Spark developed outcomes-based apies. Furthermore, in the United States, commercial insurers rebates for VN and an innovative contracting model that are reluctant to consider the indirect cost offsets associated supports patient access in the United States, while aiming with societal costs of blindness because, as mentioned above, to reduce risk and financial burden for payers and treat- governments generally bear these costs. ment centers. For VN, Spark offered to share risk with cer- Further, for IRD gene therapies, payers may not utilize tain health insurers by paying rebates if patient outcomes appropriate health utilities to derive QALYs, as the literature (full-field light sensitivity threshold testing scores) in both has historically assessed visual impairment through visual the short term and longer term failed to meet a specified acuity, as derived from studies involving patients with AMD threshold, thereby linking the payment for VN to both and DME.6,7 Only very recent literature has assessed health short-term efficacy (30-90 days) and longer-term durability utilities in IRDs.12 For example, the profound vision loss in (30 months) measures.14 RPE65 mutation–associated IRD is associated with a substan- As the retina community prepares to embrace the potential impact on health utilities, reflecting potential high value tial of gene therapy to treat common chronic retinal disor- for vision restoration by a one-time therapy.12 ders with large patient populations, such as AMD or DME, Finally, cost-effectiveness assessment is often biased reimbursement discussions will become even more complex. against one-time therapies due to the sequencing of cur- For example, if a novel one-time gene therapy prevented rent costs and future benefits, with costs incurred in the severe loss of vision in a patient who survived 10 or 20 more short term and benefits distributed over the long term. years, it could conceivably generate multiple additional In particular, the future benefits of one-time therapies are QALYs over existing therapies, especially given the poor real- disproportionally discounted when compared with their world outcomes associated with undertreatment.15-18 With current costs.13 cost-per-QALY threshold prices ranging from $50,000 to With respect to reimbursement, the current health care $150,000 per QALY (with greater thresholds for rare condi- system may readily value chronically administered medications), one can quickly estimate how these new therapies tions, but it may not properly value innovative therapies that should be valued by payers. Consequently, new reimburse- deliver long-lasting benefits in one administration. Unlike ment models could also be implemented for gene therapy other therapies developed to treat chronic diseases, which for common chronic retinal diseases.

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Retina Today Ultra-widefield imaging helps us to document peripheraldocument to us helps imaging Ultra-widefield bet- are periphery the in lesions choroiditis, multifocal In clinicalimportant an is imaging multimodal Ultra-widefield Peripheral leakage is a finding often missed during routineduring missed often finding a is leakage Peripheral SPECIAL REPORT Ahmedabad, India [email protected] Financial disclosure: None Vitreoretinal Fellow, The Retina Foundation, Ahmedabad, India [email protected] Financial disclosure: None Vitreoretinal Consultant, The Retina Foundation, Ahmedabad, India Vitreoretinal Consultant, The Retina Foundation, Ahmedabad, [email protected] Financial disclosure: None Vitreoretinal Fellow, The Retina Foundation, Ahmedabad, India [email protected] Financial disclosure: None Senior Consultant, Retina and Vitreous Services, The Retina Foundation, Editorial Advisory Board Member, [email protected] Financial disclosure: Consultant (Nidek) Vitreoretinal Fellow, The Retina Foundation, Ahmedabad, India

(Continued from page 52) from (Continued SHAM TALATI, DO GAYATHRI MOHAN, MS MANISH NAGPAL, MS, DO, FRCS(EDIN) AKSHAR SONI, MS 1. Staurenghi G, Sadda SR, Cozzi M, Corradetti G. Multimodal imaging: implications for clinical practice. Retina Today. 1. Staurenghi G, Sadda SR, Cozzi M, Corradetti G. Multimodal imaging: implications September 2019;[insert]:1-4. pathologies such as horseshoe tears and lattice degenera- lattice and horseshoetears as such pathologies withcases In retinoblastoma. as such tumors as well as tions retinal and retinopathy diabetic (eg, involvement vascular areascapture helps imaging ultra-widefield occlusions), vein extremethe in dropout capillary and neovascularization of missed been have would observations these Often, periphery. fields. central of imaging routine during alsoimaging This imaging. ultra-widefield on up picked ter Vogt- In progression. and activity disease monitoring in aids iden- helps imaging ultra-widefield disease, Koyanagi-Harada leakage.peripheral of areas tify modali- different from images combining By tool. research and - function of understanding detailed a develop can clinicians ties, diseases.retinal various of aspects morphologic and al n n n n n NAVNEET MEHROTRA, DNB, MNAMS n n n n n n n n n n n s with along disc hot a with FAZ altered an revealed montage Multifocal phase. late in visible leakage peripheral extensive 8B). (Figure seen are leakage pinpoint of areas Vogt-Koyanagi-Haradawith patients treating when imaging mayand success treatment measure to used be can It disease. steroids. of off patient a taper to decision the inform CONCLUSION

| JANUARY/FEBRUARY 2020 Despitereim- care health for future bleak seemingly the Board of Directors, Midwest Eye Institute, Indianapolis [email protected] Financial disclosure: Employee, Salary, Stock Options (Clearside Biomedical) Chief Medical Officer, Clearside Biomedical (Formerly) Vice President, Medical Strategy Lead, Spark Therapeutics Volunteer Clinical Professor of Ophthalmology, Indiana University School of Medicine, Indianapolis

bursement, the future for retina as a specialty is bright.is specialty a as retina for future the bursement, economic care health of understanding an with Armed highthe communicate better can specialists retina analysis, and HRQL, on impact large its blindness, of costs societal procedures.and therapies, services, retina of value high the fur- investment, continued foster will value for Advocating ultimately,cycle; virtuous potentially a and innovation, ther competitors new as commoditized, become innovations thera- biosimilar and generic lower-cost with arena the enter capi- freeing while patients for access enhancing further pies, innovations.retinal further into investment for tal n n n THOMAS A. CIULLA, MD, MBA n n n THE FUTURE THE FUTURE 1. MIPS: Merit-Based Incentive Payment System. American Society of Retina Specialists website. https://www.asrs.org/ 1. MIPS: Merit-Based Incentive Payment System. American Society of Retina Specialists advocacy/advocacy-mips-landing-page. Accessed December 13, 2019. website. https://www.ama-assn.org/ 2. RVS Update Committee (RUC): RBRVS overview. American Medical Association about/rvs-update-committee-ruc/rbrvs-overview. Accessed December 13, 2019. 2019. https://www.nfb.org/resources/ 3. Blindness Statistics. National Federation of the Blind website. Updated January blindness-statistics. Accessed December 13, 2019. of vision impairment in inherited 4. Jensen IS, Zacherle E, Blanchette C, Kay CN. Estimating the life-time indirect costs productivity, and tax loss for patients retinal degeneration: economic impact on education, government benefit programs, Annual Meeting; October 28-30, 2018; and caregiver burden. Paper presented at: American Academy of Ophthalmology Chicago, IL. loss: a time tradeoff utility analysis 5. Brown MM, Brown GC, Sharma S, Busbee B. Quality of life associated with visual comparison with medical health states. Ophthalmology. 2003;110(6):1076-1081. value-based medicine. Surv Ophthalmol. 6. Brown MM, Brown GC, Sharma S, Landy J. Health care economic analyses and 2003;48(2):204-223. a value-based medicine 7. Brown GC, Brown MM, Sharma S, et al. The burden of age-related macular degeneration: analysis. Trans Am Ophthalmol Soc. 2005;103:173-84; discussion 184-186. surgery cost utility revisited in 2012: a new 8. Brown GC, Brown MM, Menezes A, Busbee BG, Lieske HB, Lieske PA. Cataract economic paradigm. Ophthalmology. 2013;120(12):2367-2376. of idiopathic epiretinal membrane 9. Gupta OP, Brown GC, Brown MM. A value-based medicine cost-utility analysis surgery. Am J Ophthalmol. 2008;145(5):923-928. Accessed 10 . Step Therapy. American Society of Retina Specialists website. https://www.asrs.org/advocacy/step-therapy. December 13, 2019. in modeling the cost-effectiveness 11. Buessing M, O’Connell T, Johnson S, Pitluck S, Ciulla TA. Important considerations for future one-time therapies. Value for the first Food and Drug Administration-approved gene therapy and implications Health. 2019;22(8):970-971. inherited retinal disease on quality of life 12. Lloyd A, Piglowska N, Ciulla T, et al. Estimation of impact of RPE65-mediated and the potential benefits of gene therapy. Br J Ophthalmol. 2019;103(11):1610-1614. the ongoing debate. Value Health. 13. Severens JL, Milne RJ. Discounting health outcomes in economic evaluation: 2004;7(4):397-401. access to LUXTURNA (voretigene 14. Spark Therapeutics announces first-of-their-kind programs to improve patient 2018. Spark Therapeutics. http:// neparvovec-rzyl), a one-time gene therapy treatment [press release]. January 3, ir.sparktx.com/news-releases/news-release-details/spark-therapeutics-announces-first-their-kind-programs-improve#. Accessed December 13, 2019. 15. Ciulla TA, Bracha P, Pollack J, Williams DF. Real-world outcomes of anti-vascular endothelial growth factor therapy in diabetic macular edema in the United States. Ophthalmol Retina. 2018;2(12):1179-1187. 16. Ciulla TA, Huang F, Westby K, Williams DF, Zaveri S, Patel SC. Real-world outcomes of anti-vascular endothelial growth factor therapy in neovascular age-related macular degeneration in the United States. Ophthalmol Retina. 2018;2(7):645- 653. 17. Rao P, Lum F, Wood K, et al. Real-world vision in age-related macular degeneration patients treated with single anti- VEGF drug type for 1 year in the IRIS Registry. Ophthalmology. 2018;125(4):522-528. 18. Ciulla TA, Hussain RM, Pollack J, Williams DF. Visual acuity outcomes and anti-vascular endothelial growth factor therapy intensity in neovascular age-related macular degeneration patients - a real-world analysis of 49 485 eyes. Ophthalmol Retina. 2020;4(1):19-30. RE TINATODAY 60 s UPDATES AVENUE PENNSYLVANIA 0120rt_Special Report_Nagpal_PA Ave_Ciulla.indd 60 GO AHEAD. BE A SHOWOFF!

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Eyetube_Infographic_ad.indd 87 11/17/17 3:47 PM CODING ADVISOR CODINGADVISOR A Collaboration Between Retina Today and WHAT’S NEW IN 2020 FOR RETINA CODING AND REIMBURSEMENT Understanding the changes that occurred on January 1 can help prevent claim denials.

BY JOY WOODKE, COE, OCS, OCSR

ach new year sees changes in retina coding and reim- New Definitions bursement. In 2020, the most significant changes Along with these new codes come substantial modifica- relate to extended ophthalmoscopy (EO) and tions to the coding principles for EO. modifications of Medicare reporting requirements. The deleted EO codes were defined as initial (92225) or sub- A comprehensive knowledge of these changes may sequent (92226). These definitions were eliminated in the new Ehelp your practice prevent costly denials and receive EO codes, which are instead distinguished by the area examined appropriate reimbursement. by the doctor during the EO. CPT code 92201 indicates in the descriptor that the EO and retinal drawing of the periphery EXTENDED OPHTHALMOSCOPY must include scleral depression; this should be reflected in the The biggest changes that will affect retina practices were documentation. EO for the posterior pole with drawing of optic the deletion of CPT codes 92225 (extended ophthalmos- nerve or macula is now reported with CPT code 92202. copy with retinal drawing, initial) and 92226 (extended As with the eliminated codes, these new EO codes require ophthalmoscopy with retinal drawing, subsequent) and the the documentation of an interpretation and report. All EO addition of two new codes on January 1. The codes 92225 drawings should be legible and include clearly defined labels. and 92226 were eliminated because the Relative Value Scale Update Committee determined that initial and subsequent Reimbursement EOs involved similar physician work. The committee also The relative value unit and Medicare reimbursement for decided that peripheral and posterior examinations had EO in 2020 are shown in Table 1. Reimbursement for CPT distinct differences. code 92201 reflects approximately a 9% decrease in value The new EO codes are: compared with CPT 92225, and CPT 92202 reflects a 32% • 92201: Ophthalmoscopy, extended; with retinal draw- decrease compared with the deleted initial EO. The total ing and scleral depression of peripheral retinal disease decrease in value may vary by geographic region. (eg, for retinal tear, retinal detachment, retinal tumor) TABLE 1. NEW CODES AND REIMBURSEMENT RATES with interpretation and report, unilateral or bilateral; FOR EXTENDED OPHTHALMOSCOPY IN 2020 and • 92202: Ophthalmoscopy, extended; with drawing New CPT Code Relative Value Unit Medicare Allowable* of optic nerve or macula (eg, for glaucoma, macular 92201 0.71 nonfacility $25.85 pathology, tumor) with interpretation and report, uni- 92202 0.45 nonfacility $16.42 lateral and bilateral. *Based on the Medicare allowable in Dallas.

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Unilateral Versus Bilateral: compared with the previous, deleted National Correct Coding Initiative Bundles Avoid Claim Denials codes when billed bilaterally. According to the National Correct The 2020 EO codes are defined Due to these changes, the bilateral Coding Initiative (NCCI) Version 26.0, as “unilateral or bilateral” and may indicator 2, used to indicate a bilat- which became effective January 1, CPT be billed only once per examination eral payment adjustment, no longer codes 92201 and 92202 are bundled regardless of whether bilateral EO was applies. Applying modifiers -RT (right with all retinal laser procedures and performed. This CPT code indicator eye), -LT (left eye) or -50 (bilateral pro- surgeries when performed on the change represents a 50% reduction cedure) may cause a claim denial. same day. The new EO codes and CPT TABLE 2. CPT CODES 92201 AND 92202, NCCI BUNDLES, VERSION 26.0 Column 1 Column 2 Bundling Edit* 92201 92202 Indicator 0

99211 Indicator 1 92202 99211 Indicator 1 92250 92201 Indicator 0 92202 0465T, 67005, 67010, 67015, 67025, 67027, 67028, 67030, 67036, 67039, 67040, 67041, 92201 Indicator 1 67042, 67043, 67101, 67105, 67107, 67108, 67110, 67113, 67115, 67120, 67121, 67141, 92202 67145, 67208, 67210, 67218, 67220, 67221, 67225, 67227, 67228, 67229 *For bundling edits: Indicator 1 (Bundled): there are times when it is appropriate to unbundle the codes in Columns 1 and 2. Indicator 0 (Mutually exclusive): the codes in Columns 1 and 2 can never be unbundled. TABLE 3. RETINA DIAGNOSTIC TESTING SERVICES, NCCI BUNDLES, VERSION 26.0 EO Peripheral EO Posterior FA 92235 ICG 92240 FA/ICG 92242 FP 92250 Posterior Optic Nerve Retinal Pole 92202 Segment OCT OCT 92133 Disease 92201 92134 EO Peripheral Mutually Billable Billable Billable Mutually Billable Billable Retinal Exclusive Same Day Same Day Same Day Exclusive Same Day Same Day Disease 92201 EO Posterior Mutually Billable Billable Billable Mutually Billable Billable Pole 92202 Exclusive Same Day Same Day Same Day Exclusive Same Day Same Day FA 92235 Billable Billable Mutually Mutually Billable Billable Billable Same Day Same Day Exclusive Exclusive Same Day Same Day Same Day ICG 92240 Billable Billable Mutually Mutually Bundled Billable Billable Same Day Same Day Exclusive Exclusive Same Day Same Day FA/ICG 92242 Billable Billable Mutually Mutually Bundled Billable Billable Same Day Same Day Exclusive Exclusive Same Day Same Day FP 92250 Mutually Mutually Billable Bundled Bundled Bundled Bundled Exclusive Exclusive Same Day Posterior Billable Billable Billable Billable Billable Bundled Mutually Segment OCT Same Day Same Day Same Day Same Day Same Day Exclusive 92134 Optic Nerve Billable Billable Billable Billable Billable Bundled Mutually OCT 92133 Same Day Same Day Same Day Same Day Same Day Exclusive Abbreviations: EO, extended ophthalmoscopy; FA, fluorescein angiography; FP, fundus photography; ICG, indocyanine green angiography; OCT, optical coherence tomography.

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TABLE 4. COMPARISON OF NEW AND DELETED EXTENDED OPHTHALMOSCOPY CODES FOR 2020 DELETED NEW IN 2020 92225 92226 92201 92202 CPT Definition Initial Subsequent Peripheral retina drawing with Optic nerve or macula drawing scleral depression Bilateral Rules Bilateral Bilateral Unilateral or bilateral Unilateral or bilateral Could be billed as –RT and -LT Could be billed as –RT and -LT Bill once with pathology in one Bill once with pathology in one with bilateral pathology with bilateral pathology or both eyes or both eyes Medicare Allowable $28.39 $26.20 $25.85 $16.42 Test Interpretation Required Required Required Required Documentation Initial diagnosis Progression of the initial Retinal drawing with labels Posterior pole drawing with Method of extended examination diagnosis Scleral depression labels (90 D lens, scleral depression) Method of extended examination Method of extended examination Method of extended examination Drawing with labels (90 D lens, scleral depression) Medical necessity Medical necessity Drawing with labels

TABLE 5. SUMMARY OF CHANGES TO MIPS IN 2020 TABLE 6. WEIGHT OF MIPS CATEGORIES IN 2020 2019 2020 Category Weight Performance Period Minimum Final MIPS Score to Avoid Penalty 30 points 45 points Quality 45% Calendar Year Exceptional Performance Bonus Score 75 points 85 points Promoting Interoperability 25% 90 days Penalty for Failing to Meet Minimum Final Score 7% in 2021 9% in 2022 Improvement Activities 15% 90 days Quality Data Completeness 60% 70% Cost 15% Calendar Year Abbreviation: MIPS, Merit-Based Incentive Payment System. Abbreviation: MIPS, Merit-Based Incentive Payment System.

92250 (fundus photography) are mutually exclusive, mean- denominator-eligible patients should have been included. In ing that the two codes may never be unbundled. See Table 2 2020, that requirement is increased to 70%. for more examples of bundled and mutually exclusive There are considerable changes to quality measures in coding sets. 2020, along with modifications to requirements promot- There are no new bundles related to retina diagnostic testing interoperability and improvement activity. These ing services and EO in NCCI Version 26.0, with the exception changes and other MIPS resources can be found online at of fundus photography. Table 3 provides a quick reference of aao.org/medicare. the updated bundles for the first quarter of 2020. Of note, the weight of each of the four MIPS categories is Adjustments in definitions, elimination of unilateral- unchanged in 2020 (Table 6). The performance period for bilateral distinctions, and reimbursement reductions are each category will not change. significant changes to EO coding in 2020. Table 4 provides a summary of the changes. MASTER CODING IN 2020 Throughout 2020, a commitment to mastering the new MIPS IN 2020 coding principles and MIPS changes will be key. The AAO Some changes to the Merit-Based Incentive Payment will provide education at aao.org/coding and at Codequest System (MIPS) will be implemented in 2020. Table 5 outlines coding courses around the country. The schedule for those these changes. courses may be found at aao.org/codequest. n The minimum final 2020 MIPS score to avoid penalty in 2022 will be 45 points, up from 30 points in 201. The exceptional performance bonus score rose 10 points this year to a JOY WOODKE, COE, OCS, OCSR total of 85. The stakes for achieving the minimum score are n Coding and Practice Management Executive, American Academy of higher, too: The penalty for failing to achieve the minimum Ophthalmology, San Francisco score is a 9% reduction in reimbursement. n [email protected] In 2019, in reporting a quality measure, at least 60% of n Financial disclosure: None

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JANUARY/FEBRUARY 2020 | RETINA TODAY 65

0120rt_Ad Index.indd 65 1/31/20 10:30 AM 1/30/20 1:56 PM . ISpeech. King’s The n

I plan to be more organized and efficient with my time.my with efficient and organized more be to plan I in VI George King as turn Firth’s Colin Dr. Grewal pictured on a hike of the Tour du Mont Blanc trail in Europe. Dr. Grewal pictured on a hike of the Tour du Mont Blanc trail I have research projects that I would like to see progress.see to like would I that projects research have I recentlythe at service uveitis the grow to trying also am I EyeDuke the at Center Inflammatory Ocular launched plannedtreks mountain some are there Personally, Center. complete.to hope I that WHAT WOULD YOU LIKE TO ACCOMPLISH IN 2020? WHAT WOULD YOU LIKE TO ACCOMPLISH WHAT FICTITIOUS CHARACTER DO YOU ADMIRE? think it’s a great role about the power of believing in yourselfin believing of power the about role great a it’s think impediments. your overcoming and | JANUARY/FEBRUARY 2020 DILRAJ GREWAL, MD GREWAL, DILRAJ I found vitreoretinal surgery interesting and challenging,and interesting surgery vitreoretinal found I During my residency at the Northwestern University Northwestern the at residency my During I worked on ocular imaging during a pre-residencya during imaging ocular on worked I It is a real privilege to be able to work with fellows, resi- fellows, with work to able be to privilege real a is It cular vital sign. vital cular and the overall breadth of pathology in retina fascinating.retina in pathology of breadth overall the and patient’sa affect treatment retina seeing residency, During toolsimaging with Working tremendous. was life of quality responseassessing and diagnosis for OR the and clinic the in clincher. final the was treatment to Feinberg School of Medicine, I worked with leading imag- leading with worked I Medicine, of School Feinberg andMD; Fawzi, A. Amani MD; Jampol, M. Lee experts ing pursueto me motivated They MD. Goldstein, A. Debra fel- vitreoretinal my During uveitis. and retina in imaging at fellowship uveitis my and University Duke at lowship theof some from learned I Hospital, Eye Moorfields the involvedbecame and imaging, ocular in leaders world’s developedfurther which Center, Reading Duke the with imaging. in interest my research fellowship at the Bascom Palmer Eye Institute,Eye Palmer Bascom the at fellowship research spectral-domaingeneration early to access me gave which exponentially,grown has field That prototypes. OCT antermed have some what considered is OCT now and o dents, and medical students. I think that when you areyou when that think I students. medical and dents, aand challenging both is it yourself, training of out recently - refin still are you hand, one On mentor. a being fun of lot theOn skills. research and surgical, clinical, own your ing mentorshipa into transition to trying are you hand, other complexsupervising and projects research leading by role andclinically both experience learning huge a is It surgeries. teachesalso It gratifying. incredibly is it and academically, and management time including skills, soft about lot a you skills. people WHAT DREW YOU TO RETINA? HOW DID YOU BECOME INTERESTED IN ADVANCED OCULAR OCULAR HOW DID YOU BECOME INTERESTED IN ADVANCED IMAGING FOR RETINAL DISEASES AND UVEITIS? PLEASE DESCRIBE THE EXPERIENCE OF BEING A MENTOR AS A A EXPERIENCE OF BEING A MENTOR AS PLEASE DESCRIBE THE YOUNG DOCTOR. RETINA TODAY

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6.2 Clinical Studies Experience 6.3 Immunogenicity Because clinical trials are conducted under widely varying conditions, adverse As with all therapeutic proteins, there is the potential for an immune response reaction rates observed in one clinical trial of a drug cannot be directly in patients treated with LUCENTIS. The immunogenicity data reflect the compared with rates in the clinical trials of the same or another drug and may percentage of patients whose test results were considered positive for not reflect the rates observed in practice. antibodies to LUCENTIS in immunoassays and are highly dependent on the The data below reflect exposure to 0.5 mg LUCENTIS in 440 patients with sensitivity and specificity of the assays. neovascular AMD in Studies AMD-1, AMD-2, and AMD-3; in 259 patients The pre-treatment incidence of immunoreactivity to LUCENTIS was 0%-5% with macular edema following RVO. The data also reflect exposure to 0.3 mg across treatment groups. After monthly dosing with LUCENTIS for 6 to 24 ® Brief summary–please see the LUCENTIS package LUCENTIS in 250 patients with DME and DR at baseline [see Clinical Studies (14 months, antibodies to LUCENTIS were detected in approximately 1%-9% of insert for full prescribing information. in the full prescribing information)]. patients. Safety data observed in Study AMD-4, D-3, and in 224 patients with mCNV The clinical significance of immunoreactivity to LUCENTIS is unclear at this time. 1 INDICATIONS AND USAGE were consistent with these results. On average, the rates and types of adverse Among neovascular AMD patients with the highest levels of immunoreactivity, LUCENTIS is indicated for the treatment of patients with: reactions in patients were not significantly affected by dosing regimen. some were noted to have iritis or vitritis. Intraocular inflammation was not 1.1 Neovascular (Wet) Age-Related Macular Degeneration (AMD) Ocular Reactions observed in patients with DME and DR at baseline, or RVO patients with the highest levels of immunoreactivity. 1.2 Macular Edema Following Retinal Vein Occlusion (RVO) Table 1 shows frequently reported ocular adverse reactions in LUCENTIS- treated patients compared with the control group. 6.4 Postmarketing Experience 1.3 Diabetic Macular Edema (DME) The following adverse reaction has been identified during post-approval use 1.4 Diabetic Retinopathy (DR) Table 1 Ocular Reactions in the DME and DR, AMD, and RVO Studies of LUCENTIS. Because this reaction was reported voluntarily from a population 1.5 Myopic Choroidal Neovascularization (mCNV) DME and DR AMD AMD RVO of uncertain size, it is not always possible to reliably estimate the frequency or 2-year 2-year 1-year 6-month establish a causal relationship to drug exposure. 4 CONTRAINDICATIONS • Ocular: Tear of retinal pigment epithelium among patients with 4.1 Ocular or Periocular Infections neovascular AMD LUCENTIS is contraindicated in patients with ocular or periocular infections. 7 DRUG INTERACTIONS Control Control Control Control 0.3 mg 0.5 mg 0.5 mg 0.5 mg

4.2 Hypersensitivity LUCENTIS LUCENTIS LUCENTIS LUCENTIS Drug interaction studies have not been conducted with LUCENTIS. LUCENTIS is contraindicated in patients with known hypersensitivity to Adverse Reaction n=250 n=250 n=379 n=379 n=440 n=441 n=259 n=260 LUCENTIS intravitreal injection has been used adjunctively with verteporfin ranibizumab or any of the excipients in LUCENTIS. Hypersensitivity reactions photodynamic therapy (PDT). Twelve (12) of 105 (11%) patients with may manifest as severe intraocular inflammation. Conjunctival hemorrhage 47% 32% 74% 60% 64% 50% 48% 37% neovascular AMD developed serious intraocular inflammation; in 10 of the 12 5 WARNINGS AND PRECAUTIONS patients, this occurred when LUCENTIS was administered 7 days (± 2 days) Eye pain 17% 13% 35% 30% 26% 20% 17% 12% 5.1 Endophthalmitis and Retinal Detachments after verteporfin PDT. Intravitreal injections, including those with LUCENTIS, have been associated Vitreous floaters 10% 4% 27% 8% 19% 5% 7% 2% 8 USE IN SPECIFIC POPULATIONS with endophthalmitis and retinal detachments. Proper aseptic injection Intraocular 8.1 Pregnancy technique should always be used when administering LUCENTIS. In addition, pressure increased 18% 7% 24% 7% 17% 5% 7% 2% Risk Summary patients should be monitored following the injection to permit early treatment Vitreous There are no adequate and well-controlled studies of LUCENTIS administration should an infection occur [see Dosage and Administration (2.6, 2.7) in the full detachment 11% 15% 21% 19% 15% 15% 4% 2% in pregnant women. prescribing information and Patient Counseling Information (17)]. Intraocular Administration of ranibizumab to pregnant monkeys throughout the period 5.2 Increases in Intraocular Pressure inflammation 4% 3% 18% 8% 13% 7% 1% 3% of organogenesis resulted in a low incidence of skeletal abnormalities at Increases in intraocular pressure have been noted both pre-injection and post- intravitreal doses 13-times the predicted human exposure (based on maximal injection (at 60 minutes) while being treated with LUCENTIS. Monitor intraocular Cataract 28% 32% 17% 14% 11% 9% 2% 2% serum trough levels [Cmax]) after a single eye treatment at the recommended pressure prior to and following intravitreal injection with LUCENTIS and manage Foreign body clinical dose. No skeletal abnormalities were observed at serum trough levels appropriately [see Dosage and Administration (2.7 in the full prescribing sensation in eyes 10% 5% 16% 14% 13% 10% 7% 5% equivalent to the predicted human exposure after a single eye treatment at the information)]. Eye irritation 8% 5% 15% 15% 13% 12% 7% 6% recommended clinical dose [see Animal Data]. 5.3 Thromboembolic Events Lacrimation Animal reproduction studies are not always predictive of human response, Although there was a low rate of arterial thromboembolic events (ATEs) increased 5% 4% 14% 12% 8% 8% 2% 3% and it is not known whether ranibizumab can cause fetal harm when observed in the LUCENTIS clinical trials, there is a potential risk of ATEs Blepharitis 3% 2% 12% 8% 8% 5% 0% 1% administered to a pregnant woman. Based on the anti-VEGF mechanism of following intravitreal use of VEGF inhibitors.ATEs are defined as nonfatal stroke, action for ranibizumab [see Clinical Pharmacology (12.1 in the full prescribing nonfatal myocardial infarction, or vascular death (including deaths of unknown Dry eye 5% 3% 12% 7% 7% 7% 3% 3% information)], treatment with LUCENTIS may pose a risk to human embryofetal cause). Visual disturbance development. Neovascular (Wet) Age-Related Macular Degeneration or vision blurred 8% 4% 18% 15% 13% 10% 5% 3% LUCENTIS should be given to a pregnant woman only if clearly needed. The ATE rate in the three controlled neovascular AMD studies (AMD-1, AMD-2, Eye pruritus 4% 4% 12% 11% 9% 7% 1% 2% AMD-3) during the first year was 1.9% (17 of 874) in the combined group of Data patients treated with 0.3 mg or 0.5 mg LUCENTIS compared with 1.1% (5 of Ocular hyperemia 9% 9% 11% 8% 7% 4% 5% 3% Animal Data 441) in patients from the control arms [see Clinical Studies (14.1 in the full Retinal disorder 2% 2% 10% 7% 8% 4% 2% 1% An embryo-fetal developmental toxicity study was performed on pregnant cynomolgus monkeys. Pregnant animals received intravitreal injections of prescribing information)]. In the second year of Studies AMD-1 and AMD-2, the Maculopathy 5% 7% 9% 9% 6% 6% 11% 7% ATE rate was 2.6% (19 of 721) in the combined group of LUCENTIS-treated ranibizumab every 14 days starting on Day 20 of gestation, until Day 62 at patients compared with 2.9% (10 of 344) in patients from the control arms. Retinal doses of 0, 0.125, and 1 mg/eye. Skeletal abnormalities including incomplete T:10.75" In Study AMD-4, the ATE rates observed in the 0.5 mg arms during the first degeneration 1% 0% 8% 6% 5% 3% 1% 0% and/or irregular ossification of bones in the skull, vertebral column, and S:10" and second year were similar to rates observed in Studies AMD-1, AMD-2, and Ocular discomfort 2% 1% 7% 4% 5% 2% 2% 2% hindlimbs and shortened supernumerary ribs were seen at a low incidence AMD-3. in fetuses from animals treated with 1 mg/eye of ranibizumab. The 1 mg/eye Conjunctival dose resulted in trough serum ranibizumab levels up to 13 times higher In a pooled analysis of 2-year controlled studies (AMD-1, AMD-2, and a study of hyperemia 1% 2% 7% 6% 5% 4% 0% 0% than predicted Cmax levels with single eye treatment in humans. No skeletal LUCENTIS used adjunctively with verteporfin photodynamic therapy), the stroke Posterior capsule abnormalities were seen at the lower dose of 0.125 mg/eye, a dose which rate (including both ischemic and hemorrhagic stroke) was 2.7% (13 of 484) in opacification 4% 3% 7% 4% 2% 2% 0% 1% resulted in trough exposures equivalent to single eye treatment in humans. patients treated with 0.5 mg LUCENTIS compared to 1.1% (5 of 435) in patients No effect on the weight or structure of the placenta, maternal toxicity, or in the control arms (odds ratio 2.2 (95% confidence interval (0.8-7.1))). Injection site hemorrhage 1% 0% 5% 2% 3% 1% 0% 0% embryotoxicity was observed. Macular Edema Following Retinal Vein Occlusion 8.2 Lactation The ATE rate in the two controlled RVO studies during the first 6 months was Non-Ocular Reactions Risk Summary 0.8% in both the LUCENTIS and control arms of the studies (4 of 525 in the Non-ocular adverse reactions with an incidence of ≥ 5% in patients receiving There are no data available on the presence of ranibizumab in human milk, the combined group of patients treated with 0.3 mg or 0.5 mg LUCENTIS and 2 LUCENTIS for DR, DME, AMD, and/or RVO and which occurred at a ≥ 1% higher effects of ranibizumab on the breastfed infant or the effects of ranibizumab on of 260 in the control arms) [see Clinical Studies (14.2 in the full prescribing frequency in patients treated with LUCENTIS compared to control are shown milk production/excretion. information)]. The stroke rate was 0.2% (1 of 525) in the combined group of in Table 2. Though less common, wound healing complications were also LUCENTIS-treated patients compared to 0.4% (1 of 260) in the control arms. Because many drugs are excreted in human milk, and because the potential for observed in some studies. absorption and harm to infant growth and development exists, caution should Diabetic Macular Edema and Diabetic Retinopathy be exercised when LUCENTIS is administered to a nursing woman. Safety data are derived from studies D-1 and D-2. All enrolled patients had Table 2 Non-Ocular Reactions in the DME and DR, AMD, and RVO Studies The developmental and health benefits of breastfeeding should be considered DME and DR at baseline [see Clinical Studies (14.3, 14.4 in the full prescribing DME and DR AMD AMD RVO along with the mother’s clinical need for LUCENTIS and any potential adverse information)]. 2-year 2-year 1-year 6-month effects on the breastfed child from ranibizumab. In a pooled analysis of Studies D-1 and D-2 [see Clinical Studies (14.3 in the full prescribing information)], the ATE rate at 2 years was 7.2% (18 of 250) with 8.3 Females and Males of Reproductive Potential 0.5 mg LUCENTIS, 5.6% (14 of 250) with 0.3 mg LUCENTIS, and 5.2% (13 of Infertility Control Control Control Control 0.3 mg 0.5 mg 0.5 mg 0.5 mg No studies on the effects of ranibizumab on fertility have been conducted. and it

250) with control. The stroke rate at 2 years was 3.2% (8 of 250) with 0.5 mg LUCENTIS LUCENTIS LUCENTIS LUCENTIS is not known whether ranibizumab can affect reproduction capacity. Based on LUCENTIS, 1.2% (3 of 250) with 0.3 mg LUCENTIS, and 1.6% (4 of 250) with Adverse Reaction n=250 n=250 n=379 n=379 n=440 n=441 n=259 n=260 control. At 3 years, the ATE rate was 10.4% (26 of 249) with 0.5 mg LUCENTIS the anti-VEGF mechanism of action for ranibizumab, treatment with LUCENTIS and 10.8% (27 of 250) with 0.3 mg LUCENTIS; the stroke rate was 4.8% (12 Nasopharyngitis 12% 6% 16% 13% 8% 9% 5% 4% may pose a risk to reproductive capacity. of 249) with 0.5 mg LUCENTIS and 2.0% (5 of 250) with 0.3 mg LUCENTIS. Anemia 11% 10% 8% 7% 4% 3% 1% 1% 8.4 Pediatric Use 5.4 Fatal Events in Patients with DME and DR at baseline Nausea 10% 9% 9% 6% 5% 5% 1% 2% The safety and effectiveness of LUCENTIS in pediatric patients have not been established. Diabetic Macular Edema and Diabetic Retinopathy Cough 9% 4% 9% 8% 5% 4% 1% 2% Safety data are derived from studies D-1 and D-2. All enrolled patients had 8.5 Geriatric Use DME and DR at baseline [see Clinical Studies (14.3, 14.4 in the full prescribing Constipation 8% 4% 5% 7% 3% 4% 0% 1% In the clinical studies, approximately 76% (2449 of 3227) of patients randomized information)]. Seasonal allergy 8% 4% 4% 4% 2% 2% 0% 2% to treatment with LUCENTIS were ≥ 65 years of age and approximately 51% A pooled analysis of Studies D-1 and D-2 [see Clinical Studies (14.3 in the full Hypercholesterolemia 7% 5% 5% 5% 3% 2% 1% 1% (1644 of 3227) were ≥ 75 years of age [see Clinical Studies (14 in the full prescribing information)]. No notable differences in efficacy or safety were seen prescribing information)], showed that fatalities in the first 2 years occurred in Influenza 7% 3% 7% 5% 3% 2% 3% 2% 4.4% (11 of 250) of patients treated with 0.5 mg LUCENTIS, in 2.8% (7 of 250) with increasing age in these studies. Age did not have a significant effect on of patients treated with 0.3 mg LUCENTIS, and in 1.2% (3 of 250) of control Renal failure 7% 6% 1% 1% 0% 0% 0% 0% systemic exposure. patients. Over 3 years, fatalities occurred in 6.4% (16 of 249) of patients treated Upper respiratory 10 OVERDOSAGE with 0.5 mg LUCENTIS and in 4.4% (11 of 250) of patients treated with 0.3 tract infection 7% 7% 9% 8% 5% 5% 2% 2% More concentrated doses as high as 2 mg ranibizumab in 0.05 mL have been mg LUCENTIS. Although the rate of fatal events was low and included causes Gastroesophageal administered to patients. No additional unexpected adverse reactions were of death typical of patients with advanced diabetic complications, a potential reflux disease 6% 4% 4% 6% 3% 4% 1% 0% seen. relationship between these events and intravitreal use of VEGF inhibitors cannot Headache 6% 8% 12% 9% 6% 5% 3% 3% 17 PATIENT COUNSELING INFORMATION be excluded. Advise patients that in the days following LUCENTIS administration, patients are 6 ADVERSE REACTIONS Edema peripheral 6% 4% 3% 5% 2% 3% 0% 1% at risk of developing endophthalmitis. If the eye becomes red, sensitive to light, The following adverse reactions are discussed in greater detail in other sections Renal failure chronic 6% 2% 0% 1% 0% 0% 0% 0% painful, or develops a change in vision, advise the patient to seek immediate of the label: Neuropathy care from an ophthalmologist [see Warnings and Precautions (5.1)]. • Endophthalmitis and Retinal Detachments [see Warnings and Precautions peripheral 5% 3% 1% 1% 1% 0% 0% 0% (5.1)] • Increases in Intraocular Pressure [see Warnings and Precautions (5.2)] Sinusitis 5% 8% 8% 7% 5% 5% 3% 2% • Thromboembolic Events [see Warnings and Precautions (5.3)] Bronchitis 4% 4% 11% 9% 6% 5% 0% 2% • Fatal Events in patients with DME and DR at baseline [see Warnings and Atrial fibrillation 3% 3% 5% 4% 2% 2% 1% 0% Precautions (5.4)] LUCENTIS® Arthralgia 3% 3% 11% 9% 5% 5% 2% 1% 6.1 Injection Procedure [ranibizumab injection] Serious adverse reactions related to the injection procedure have occurred Chronic obstructive Manufactured by: Initial US Approval: June 2006 pulmonary disease 1% 1% 6% 3% 3% 1% 0% 0% Genentech, Inc. Revision Date: LUC/021815/0050(4) 2017 in < 0.1% of intravitreal injections, including endophthalmitis [see Warnings ® and Precautions (5.1)], rhegmatogenous retinal detachment, and iatrogenic Wound healing A Member of the Roche Group LUCENTIS is a registered traumatic cataract. complications 1% 0% 1% 1% 1% 0% 0% 0% 1 DNA Way trademark of Genentech, Inc. South San Francisco, CA ©2017 Genentech, Inc. 94080-4990

11275068_wAMD_Efficacy_Delivered_Ad_B_SIZE_M2.indd 2 12/9/19 10:26 AM B:9.25" T:9" S:8.25"

LUCENTIS 0.5 MG PREFILLED SYRINGE EFFICACY DELIVERED The e cacy and safety of LUCENTIS 0.5 mg studied in 7 pivotal trials,*

1 T:10.75" B:11" available in a preﬁ lled syringe. S:10"

INDICATIONS ADVERSE EVENTS LUCENTIS® (ranibizumab injection) 0.5 mg is indicated for the treatment • Serious adverse events related to the injection procedure that occurred in of patients with: <0.1% of intravitreal injections included endophthalmitis, rhegmatogenous • Neovascular (wet) age-related macular degeneration (wAMD) retinal detachment, and iatrogenic traumatic cataract • Macular edema following retinal vein occlusion (RVO) • In the LUCENTIS Phase III clinical trials, the most common ocular side • Myopic choroidal neovascularization (mCNV) e ects included conjunctival hemorrhage, eye pain, vitreous ﬂ oaters, and increased intraocular pressure. The most common non-ocular side e ects IMPORTANT SAFETY INFORMATION included nasopharyngitis, anemia, nausea, and cough CONTRAINDICATIONS • LUCENTIS is contraindicated in patients with ocular or periocular Please see Brief Summary of LUCENTIS full Prescribing Information infections or known hypersensitivity to ranibizumab or any of the on next page. excipients in LUCENTIS. Hypersensitivity reactions may manifest as severe intraocular inﬂ ammation * The following randomized, double-masked pivotal trials were conducted for the wet AMD, macular edema following RVO, and mCNV LUCENTIS indications: wAMD: MARINA— WARNINGS AND PRECAUTIONS Phase III, multicenter, 2-year, sham injection–controlled study; primary end point at • Intravitreal injections, including those with LUCENTIS, have been associated 1 year. ANCHOR—Phase III, multicenter, 2-year, active treatment–controlled study; with endophthalmitis, retinal detachment, and iatrogenic traumatic cataract. primary end point at 1 year. PIER—Phase IIIb, 2-year, sham injection–controlled study; primary end point at 1 year. HARBOR—Phase III, multicenter, 2-year, active Proper aseptic injection technique should always be utilized when treatment–controlled dose-response study; primary end point at 1 year. RVO: administering LUCENTIS. Patients should be monitored following the BRAVO—Phase III, multicenter, 1-year, sham injection–controlled study; primary end injection to permit early treatment, should an infection occur point at 6 months. CRUISE—Phase III, multicenter, 1-year, sham injection–controlled • Increases in intraocular pressure (IOP) have been noted both pre- study; primary end point at 6 months. mCNV: RADIANCE—Phase III, multicenter, injection and post-injection (at 60 minutes) with LUCENTIS. Monitor 1-year, active-controlled study; key clinical outcomes at month 3.2-8 intraocular pressure prior to and following intravitreal injection with VEGF, vascular endothelial growth factor. LUCENTIS and manage appropriately REFERENCES: 1. LUCENTIS [package insert]. South San Francisco, CA: Genentech, Inc; 2017. • Although there was a low rate of arterial thromboembolic events (ATEs) 2. Rosenfeld PJ, et al; MARINA Study Group. N Engl J Med. 2006;355:1419-1431. 3. Brown DM, observed in the LUCENTIS clinical trials, there is a potential risk of ATEs et al; ANCHOR Study Group. Ophthalmology. 2009;116:57-65. 4. Regillo CD, et al; PIER Study Group. following intravitreal use of VEGF inhibitors. ATEs are defined as Am J Ophthalmol. 2008;145:239-248. 5. Busbee BG, et al; HARBOR Study Group. Ophthalmology. 2013;120:1046-1056. 6. Campochiaro PA, et al; BRAVO Investigators. Ophthalmology. 2010;117:1102- nonfatal stroke, nonfatal myocardial infarction, or vascular death 1112. 7. Brown DM, et al; CRUISE Investigators. Ophthalmology. 2010;117:1124-1133. 8. Data on file. (including deaths of unknown cause) Genentech, Inc. South San Francisco, CA.

11275068_wAMD_Efficacy_Delivered_Ad_B_SIZE_M2.indd 1 12/9/19 10:26 AM

PREPARED BY Studio Rx Express Releasing as: PDFx1A Production: Helen Sera n x3069 Job #: 11275068 Colors: 4C / 1C AD: Maria Vargas DeStefano Client: Genentech Ad P.I. AE: Brittany Benourida Product: Lucentis Bleed: 9.25"H x 11"W n/a Producer: Sozan Barzanje

Client Code: LUC/100316/0105(2)a Trim: 9"H x 10.75"W 9"H x 10.75"W Date: December 9, 2019 10:24 AM Safety: 8.25"H x 10"W 7"H x 10"W Digital Artist: ce, VA Proof: M2 Add’l Info: Path: PrePress:Genentech:LUCENTIS:11275068:11275068_wAMD_Ef cacy_Delivered_Ad_B_SIZE_M2 4C wAMD Ef cacy Delivered Ad: B SIZE