and done ONE CYPASS MICRO-STENT IS ALL IT TAKES TO CONNECT TO SAFE, CONSISTENT, LONG-TERM IOP CONTROL

Transcription

1 FOR THE REDUCTION OF IOP IN MILD TO MODERATE PRIMARY OPEN-ANGLE GLAUCOMA AT THE TIME OF CATARACT SURGERY and done ONE CYPASS MICRO-STENT IS ALL IT TAKES TO CONNECT TO SAFE, CONSISTENT, LONG-TERM IOP CONTROL IN THE COMPASS STUDY AT TWO YEARS 1,2 : 72.5% of patients achieved a 20% reduction in IOP (n=374) 93% of patients were medication free* Safety profile similar to cataract surgery alone FOR AN EXPERIENCE LIKE NO OTHER, CONNECT WITH AN ALCON REPRESENTATIVE TODAY. *Those patients who attained an unmedicated mean diurnal IOP reduction of 20% or more as compared to baseline in the absence of IOP-affecting surgery during the study. References: 1. CyPass Micro-Stent Instructions for Use. 2. Vold S, Ahmed IIK, Craven ER, et al. Two-year COMPASS trial results: supraciliary microstenting with phacoemulsification in patients with open-angle glaucoma and cataracts. Ophthalmology. 2016;123(10): Novartis 09/17 US-CYP-17-E-2272 IMPORTANT PRODUCT INFORMATION CAUTION: FEDERAL (USA) LAW RESTRICTS THIS DEVICE TO SALE BY OR ON THE ORDER OF A PHYSICIAN. INDICATION: The CyPass Micro-Stent is indicated for use in conjunction with cataract surgery for the reduction of intraocular pressure (IOP) in adult patients with mild to moderate primary open-angle glaucoma (POAG). CONTRAINDICATIONS: Use of the CyPass Micro-Stent is contraindicated in the following circumstances or conditions: (1) in eyes with angle-closure glaucoma; and (2) in eyes with traumatic, malignant, uveitic, or neovascular glaucoma or discernible congenital anomalies of the anterior chamber angle. MRI INFORMATION: The CyPass Micro-Stent is magnetic resonance (MR) Safe: the implant is constructed of polyimide material, a non-conducting, non-metallic, non-magnetic polymer that poses no known hazards in all magnetic resonance imaging environments. WARNINGS: Gonioscopy should be performed prior to surgery to exclude peripheral anterior synechiae (PAS), rubeosis, and other angle abnormalities or conditions that would prohibit adequate visualization of the angle that could lead to improper placement of the stent and pose a hazard. PRECAUTIONS: The surgeon should monitor the patient postoperatively for proper maintenance of intraocular pressure. The safety and effectiveness of the CyPass Micro- Stent has not been established as an alternative to the primary treatment of glaucoma with medications, in patients 21 years or younger, in eyes with signifi cant prior trauma, chronic infl ammation, eyes with an abnormal anterior segment, eyes with chronic inflammation, eyes with glaucoma associated with vascular disorders, pseudophakic eyes with glaucoma, eyes with uveitic glaucoma, eyes with pseudoexfoliative or pigmentary glaucoma, eyes with other secondary open-angle glaucomas, eyes that have undergone prior incisional glaucoma surgery or cilioablative procedures, eyes with laser trabeculoplasty performed 3 months prior to the surgical screening visit, eyes with unmedicated IOP less than 21 mmhg or greater than 33 mmhg, eyes with medicated IOP greater than 25 mmhg, in the setting of complicated cataract surgery with iatrogenic injury to the anterior or posterior segment, and when implantation is without concomitant cataract surgery with IOL implantation for visually signifi cant cataract. The safety and effectiveness of use of more than a single CyPass Micro-Stent has not been established. ADVERSE EVENTS: In a randomized, multicenter clinical trial comparing cataract surgery with the CyPass Micro-Stent to cataract surgery alone, the most common postoperative adverse events included: BCVA loss of 10 or more letters at 3 months after surgery (8.8% for the CyPass Micro-Stent vs. 15.3% for cataract surgery only); anterior chamber cell and fl are requiring steroid treatment 30 or more days after surgery (8.6% vs. 3.8%); worsening of visual fi eld mean deviation by 2.5 or more decibels (6.7% vs. 9.9%); IOP increase of 10 or more mmhg 30 or more days after surgery (4.3% vs. 2.3%); and corneal edema 30 or more days after surgery, or severe in nature (3.5% vs. 1.5%). ATTENTION: PLEASE REFER TO THE INSTRUCTIONS FOR A COMPLETE LIST OF CONTRAINDICATIONS, WARNINGS, PRECAUTIONS, AND ADVERSE EVENTS.

2 Glaucoma DECEMBER 2017 DETECTING AND TREATING OSD IN GLAUCOMA PATIENTS OCULAR SURFACE DISEASE AND GLAUCOMA Robert D. Fechtner, MD TELE-MEDICINE: THE NEXT FRONTIER Albert S. Khouri, MD WIDEFIELD OCT IMPROVES MANAGEMENT Robert Rothstein, MD FELLOWSHIPS: MOVING TO THE FRONT OF THE LINE Alena Reznik, MD ECP IN REFRACTORY GLAUCOMA PATIENTS Juan Carlos Izquierdo, MD

3 FOR THE REDUCTION OF IOP IN MILD TO MODERATE PRIMARY OPEN-ANGLE GLAUCOMA AT THE TIME OF CATARACT SURGERY and done ONE CYPASS MICRO-STENT IS ALL IT TAKES TO CONNECT TO SAFE, CONSISTENT, LONG-TERM IOP CONTROL IN THE COMPASS STUDY AT TWO YEARS1,2: 72.5% of patients achieved a 20% reduction in IOP (n=374) 93% of patients were medication free* Safety profile similar to cataract surgery alone FOR AN EXPERIENCE LIKE NO OTHER, CONNECT WITH AN ALCON REPRESENTATIVE TODAY. *Those patients who attained an unmedicated mean diurnal IOP reduction of 20% or more as compared to baseline in the absence of IOP-affecting surgery during the study. References: 1. CyPass Micro-Stent Instructions for Use. 2. Vold S, Ahmed IIK, Craven ER, et al. Two-year COMPASS trial results: supraciliary microstenting with phacoemulsification in patients with open-angle glaucoma and cataracts. Ophthalmology. 2016;123(10): Novartis 09/17 US-CYP-17-E-2272

4 NEWS BRIEFS CyPass Micro-Stent IMPORTANT PRODUCT INFORMATION CAUTION: FEDERAL (USA) LAW RESTRICTS THIS DEVICE TO SALE BY OR ON THE ORDER OF A PHYSICIAN. INDICATION: The CyPass Micro-Stent is indicated for use in conjunction with cataract surgery for the reduction of intraocular pressure (IOP) in adult patients with mild to moderate primary openangle glaucoma (POAG). CONTRAINDICATIONS: Use of the CyPass Micro-Stent is contraindicated in the following circumstances or conditions: (1) in eyes with angle-closure glaucoma; and (2) in eyes with traumatic, malignant, uveitic, or neovascular glaucoma or discernible congenital anomalies of the anterior chamber angle. MRI INFORMATION: The CyPass Micro-Stent is magnetic resonance (MR) Safe: the implant is constructed of polyimide material, a nonconducting, non-metallic, non-magnetic polymer that poses no known hazards in all magnetic resonance imaging environments. WARNINGS: Gonioscopy should be performed prior to surgery to exclude peripheral anterior synechiae (PAS), rubeosis, and other angle abnormalities or conditions that would prohibit adequate visualization of the angle that could lead to improper placement of the stent and pose a hazard. PRECAUTIONS: The surgeon should monitor the patient postoperatively for proper maintenance of intraocular pressure. The safety and effectiveness of the CyPass Micro-Stent has not been established as an alternative to the primary treatment of glaucoma with medications, in patients 21 years or younger, in eyes with significant prior trauma, chronic inflammation, eyes with an abnormal anterior segment, eyes with chronic inflammation, eyes with glaucoma associated with vascular disorders, pseudophakic eyes with glaucoma, eyes with uveitic glaucoma, eyes with pseudoexfoliative or pigmentary glaucoma, eyes with other secondary open-angle glaucomas, eyes that have undergone prior incisional glaucoma surgery or cilioablative procedures, eyes with laser trabeculoplasty performed 3 months prior to the surgical screening visit, eyes with unmedicated IOP less than 21 mmhg or greater than 33 mmhg, eyes with medicated IOP greater than 25 mmhg, in the setting of complicated cataract surgery with iatrogenic injury to the anterior or posterior segment, and when implantation is without concomitant cataract surgery with IOL implantation for visually significant cataract. The safety and effectiveness of use of more than a single CyPass Micro-Stent has not been established. ADVERSE EVENTS: In a randomized, multicenter clinical trial comparing cataract surgery with the CyPass Micro-Stent to cataract surgery alone, the most common postoperative adverse events included: BCVA loss of 10 or more letters at 3 months after surgery (8.8% for the CyPass Micro-Stent vs. 15.3% for cataract surgery only); anterior chamber cell and flare requiring steroid treatment 30 or more days after surgery (8.6% vs. 3.8%); worsening of visual field mean deviation by 2.5 or more decibels (6.7% vs. 9.9%); IOP increase of 10 or more mmhg 30 or more days after surgery (4.3% vs. 2.3%); and corneal edema 30 or more days after surgery, or severe in nature (3.5% vs. 1.5%). ATTENTION: PLEASE REFER TO THE INSTRUCTIONS FOR A COMPLETE LIST OF CONTRAINDICATIONS, WARNINGS, PRECAUTIONS, AND ADVERSE EVENTS. IOP-lowering Treatment Receives FDA Approval Last month, Bausch + Lomb and Nicox S.A. announced that the United States FDA approved the New Drug Application for Vyzulta (latanoprostene bunod ophthalmic solution, 0.024%), the first prostaglandin analog with one of its metabolites being nitric oxide (NO). Vyzulta is indicated for the reduction of intraocular pressure in patients with open-angle glaucoma or ocular hypertension. According to a company statement, following topical administration, Vyzulta, a once daily monotherapy with a dual mechanism of action, works by metabolizing into two moieties, latanoprost acid, which primarily works within the uveoscleral pathway to increase aqueous humor outflow, and butanediol mononitrate, which releases nitric oxide to increase outflow through the trabecular meshwork and Schlemm s canal. The most common ocular adverse events include conjunctival hyperemia, eye irritation, eye pain, and instillation site pain. Increased pigmentation of the iris and periorbital tissue and growth of eyelashes can occur. Vyzulta represents the first FDA-approved therapy developed through our proprietary NO-donating research platform, said Michele Garufi, chairman and CEO of Nicox, in recent a press release. We look forward to continuing to leverage our platform in the development of additional innovative ophthalmic compounds. For more information, visit In other news... In October, Belgium-based istar Medical announced that it has completed enrollment in its first-in-human trial for the MINIject, a micro-invasive glaucoma surgery device. The prospective, open, international, multicenter trial will be conducted on 25 patients with mild to moderate open-angle glaucoma uncontrolled by topical hypotensive medications and will assess the safety and performance of the MINIject, as measured by IOP reduction under medication from baseline to 6 months. Subsequent safety and performance measures will be taken at 12 and 24 months, according to istar. Nicox and Re-Vana Therapeutics will team up to explore a drug delivery platform to lower IOP. The non-exclusive collaboration will focus on developing Re-Vana s EyeLief drug delivery platform for sustained release of new standalone nitric oxide-donors developed by Nicox. EyeLief is a novel sustained-release, photo-crosslinked, preformed, biodegradable eye implant intended to release therapeutics over an extended period of time Novartis 9/17 US-CYP-17-E-2272 DECEMBER 2017 GLAUCOMA PHYSICIAN 3

5 Table of Contents GLAUCOMA PHYSICIAN DECEMBER 2017 GUEST MEDICAL EDITOR Robert D. Fechtner, MD EXECUTIVE VICE PRESIDENT & PUBLISHER, OPHTHALMOLOGY Douglas A. Parry EDITORIAL Senior Managing Editor Jennifer Ford SPECIAL PROJECTS Director Angela Jackson Manager Alicia Hoglund Editorial Assistant Angela Bickel DESIGN & PRODUCTION Production Director Sandra Kaden Production Manager William Hallman Art Director Rachael Weissman E-MEDIA GROUP Executive Vice President, E-media Rob Verna ; Fax: PENTAVISION LIVE! Director Abigail Markward MARKETING SERVICES GROUP National Account Manager Rob Verna E-media Production Manager Megan Nonemacher Web Services Manager Amanda Higgins Creative Services Manager Mindy Crawford Marketing Services Manager Adam Black Digital Marketing Coordinator Charlotte Higgins BUSINESS STAFF Marketing Manager Amy Wauhop Circulation Manager Carrie Eisenhandler Subscription inquiries/address changes CONFERENCE GROUP Conference Director Maureen Trusky, CMP Customer Service & Events Associate Julia McNamee EDITORIAL AND PRODUCTION OFFICES 321 Norristown Road, Suite 150 Ambler, PA SALES OFFICES President & Manager Thomas J. Wilson Business Manager Dianna Schell Director of Business Development, Western Region Abigail Markward ; Fax: Eastern Region Account Manager Cheryl Brown Business Development Manager Skyler Goldstein Sales Associate / Classified, List Rentals & Reprint Sales Ryan Langton ryan.langton@pentavisionmedia.com Sales Associate Jason Conaway jason.conaway@pentavisionmedia.com Glaucoma Physician is published by PentaVision LLC. Copyright 2017, PentaVision LLC. All Rights Reserved. The opinions expressed herein are those of the authors and do not necessarily reflect the opinions of Ophthalmology Management or Glaucoma Physician nor should they be taken as an endorsement by Ophthalmology Management or Glaucoma Physician. 4 GLAUCOMA PHYSICIAN DECEMBER 2017 Features Ocular Surface Disease and Glaucoma Improved detection and treatment of OSD may lead to better outcomes for glaucoma patients Tele-glaucoma: The Next Frontier How this technology can help improve care for many patients Widefield OCT Improves Glaucoma Management Ganglion cell complex analysis provides a more comprehensive picture of disease status Moving to the Front of the Line How glaucoma fellowships transformed from last pick to first pick Glaucoma in Africa A strategic approach to preventing blindness ECP in Refractory Glaucoma Patients How this existing therapy is creating new treatment opportunities for a wider range of patients The Significance of ECP in Today s Glaucoma Management A pressure-lowering workhorse emerges as potent pairing with MIGS Keeping a Closer Watch on IOP New technologies for frequent self-measurement open a new era in glaucoma care Departments Coding 36 Samples and Free Products 8

6 NEW FROM BAUSCH + LOMB VYZULTA DELIVERS A DUAL MECHANISM OF ACTION FOR THE REDUCTION OF IOP IN GLAUCOMA PATIENTS 1 ONE MOLECULE. TWO OUTFLOW PATHWAYS. PROVEN IOP REDUCTION 1-3* * In studies up to 12 months duration, the IOP-lowering effect was up to 7.5 to 9.1 mmhg, in patients with an average baseline IOP of 26.7 mmhg INDICATION VYZULTA (latanoprostene bunod ophthalmic solution), 0.024% is indicated for the reduction of intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension. IMPORTANT SAFETY INFORMATION Increased pigmentation of the iris and periorbital tissue (eyelid) can occur. Iris pigmentation is likely to be permanent Gradual changes to eyelashes, including increased length, increased thickness, and number of eyelashes, may occur. These changes are usually reversible upon treatment discontinuation Use with caution in patients with a history of intraocular inflammation (iritis/uveitis). VYZULTA should generally not be used in patients with active intraocular inflammation Macular edema, including cystoid macular edema, has been reported during treatment with prostaglandin analogs. Use with caution in aphakic patients, in pseudophakic patients with a torn posterior lens capsule, or in patients with known risk factors for macular edema IMPORTANT SAFETY INFORMATION (CONTINUED) There have been reports of bacterial keratitis associated with the use of multiple-dose containers of topical ophthalmic products that were inadvertently contaminated by patients Contact lenses should be removed prior to the administration of VYZULTA and may be reinserted 15 minutes after administration Most common ocular adverse reactions with incidence 2% are conjunctival hyperemia (6%), eye irritation (4%), eye pain (3%), and instillation site pain (2%) For more information, please see Brief Summary of Prescribing Information on next page. References: 1. VYZULTA Prescribing Information. Bausch & Lomb Incorporated Weinreb RN, Sforzolini BS, Vittitow J, Liebmann J. Latanoprostene bunod 0.024% versus timolol maleate 0.5% in subjects with open-angle glaucoma or ocular hypertension: the APOLLO study. Ophthalmology. 2016;123(5): Medeiros FA, Martin KR, Peace J, Sforzolini BS, Vittitow JL, Weinreb RN. Comparison of latanoprostene bunod 0.024% and timolol maleate 0.5% in open-angle glaucoma or ocular hypertension: the LUNAR study. Am J Ophthalmol. 2016;168: For more information about VYZULTA and how it works, visit vyzultanow.com VYZULTA and the V design are trademarks of Bausch & Lomb Incorporated or its affiliates Bausch & Lomb Incorporated. All rights reserved. VYZ.0019.USA.16

7 BRIEF SUMMARY OF PRESCRIBING INFORMATION This Brief Summary does not include all the information needed to use VYZULTA safely and effectively. See full Prescribing Information for VYZULTA. VYZULTA (latanoprostene bunod ophthalmic solution), 0.024%, for topical ophthalmic use. Initial U.S. Approval: INDICATIONS AND USAGE VYZULTA (latanoprostene bunod ophthalmic solution) 0.024% is indicated for the reduction of intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension. 4 CONTRAINDICATIONS None 5 WARNINGS AND PRECAUTIONS 5.1 Pigmentation VYZULTA (latanoprostene bunod ophthalmic solution), 0.024% may cause changes to pigmented tissues. The most frequently reported changes with prostaglandin analogs have been increased pigmentation of the iris and periorbital tissue (eyelid). Pigmentation is expected to increase as long as latanoprostene bunod ophthalmic solution is administered. The pigmentation change is due to increased melanin content in the melanocytes rather than to an increase in the number of melanocytes. After discontinuation of VYZULTA, pigmentation of the iris is likely to be permanent, while pigmentation of the periorbital tissue and eyelash changes are likely to be reversible in most patients. Patients who receive prostaglandin analogs, including VYZULTA, should be informed of the possibility of increased pigmentation, including permanent changes. The long-term effects of increased pigmentation are not known. Iris color change may not be noticeable for several months to years. Typically, the brown pigmentation around the pupil spreads concentrically towards the periphery of the iris and the entire iris or parts of the iris become more brownish. Neither nevi nor freckles of the iris appear to be affected by treatment. While treatment with VYZULTA (latanoprostene bunod ophthalmic solution), 0.024% can be continued in patients who develop noticeably increased iris pigmentation, these patients should be examined regularly [see Patient Counseling Information (17) in full Prescribing Information]. 5.2 Eyelash Changes VYZULTA may gradually change eyelashes and vellus hair in the treated eye. These changes include increased length, thickness, and the number of lashes or hairs. Eyelash changes are usually reversible upon discontinuation of treatment. 5.3 Intraocular Inflammation VYZULTA should be used with caution in patients with a history of intraocular inflammation (iritis/uveitis) and should generally not be used in patients with active intraocular inflammation as it may exacerbate this condition. 5.4 Macular Edema Macular edema, including cystoid macular edema, has been reported during treatment with prostaglandin analogs. VYZULTA should be used with caution in aphakic patients, in pseudophakic patients with a torn posterior lens capsule, or in patients with known risk factors for macular edema. 5.5 Bacterial Keratitis There have been reports of bacterial keratitis associated with the use of multiple-dose containers of topical ophthalmic products. These containers had been inadvertently contaminated by patients who, in most cases, had a concurrent corneal disease or a disruption of the ocular epithelial surface. 5.6 Use with Contact Lens Contact lenses should be removed prior to the administration of VYZULTA because this product contains benzalkonium chloride. Lenses may be reinserted 15 minutes after administration. 6 ADVERSE REACTIONS The following adverse reactions are described in the Warnings and Precautions section: pigmentation (5.1), eyelash changes (5.2), intraocular inflammation (5.3), macular edema (5.4), bacterial keratitis (5.5), use with contact lens (5.6). 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in 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. VYZULTA was evaluated in 811 patients in 2 controlled clinical trials of up to 12 months duration. The most common ocular adverse reactions observed in patients treated with latanoprostene bunod were: conjunctival hyperemia (6%), eye irritation (4%), eye pain (3%), and instillation site pain (2%). Approximately 0.6% of patients discontinued therapy due to ocular adverse reactions including ocular hyperemia, conjunctival irritation, eye irritation, eye pain, conjunctival edema, vision blurred, punctate keratitis and foreign body sensation. 8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary There are no available human data for the use of VYZULTA during pregnancy to inform any drug associated risks. Latanoprostene bunod has caused miscarriages, abortion, and fetal harm in rabbits. Latanoprostene bunod was shown to be abortifacient and teratogenic when administered intravenously (IV) to pregnant rabbits at exposures 0.28 times the clinical dose. Doses 20 μg/kg/day (23 times the clinical dose) produced 100% embryofetal lethality. Structural abnormalities observed in rabbit fetuses included anomalies of the great vessels and aortic arch vessels, domed head, sternebral and vertebral skeletal anomalies, limb hyperextension and malrotation, abdominal distension and edema. Latanoprostene bunod was not teratogenic in the rat when administered IV at 150 mcg/kg/day (87 times the clinical dose) [see Data]. The background risk of major birth defects and miscarriage for the indicated population is unknown. However, the background risk in the U.S. general population of major birth defects is 2 to 4%, and of miscarriage is 15 to 20%, of clinically recognized pregnancies. Data Animal Data Embryofetal studies were conducted in pregnant rabbits administered latanoprostene bunod daily by intravenous injection on gestation days 7 through 19, to target the period of organogenesis. The doses administered ranged from 0.24 to 80 mcg/kg/day. Abortion occurred at doses 0.24 mcg/kg/day latanoprostene bunod (0.28 times the clinical dose, on a body surface area basis, assuming 100% absorption). Embryofetal lethality (resorption) was increased in latanoprostene bunod treatment groups, as evidenced by increases in early resorptions at doses 0.24 mcg/kg/day and late resorptions at doses 6 mcg/kg/day (approximately 7 times the clinical dose). No fetuses survived in any rabbit pregnancy at doses of 20 mcg/kg/day (23 times the clinical dose) or greater. Latanoprostene bunod produced structural abnormalities at doses 0.24 mcg/kg/day (0.28 times the clinical dose). Malformations included anomalies of sternum, coarctation of the aorta with pulmonary trunk dilation, retroesophageal subclavian artery with absent brachiocephalic artery, domed head, forepaw hyperextension and hindlimb malrotation, abdominal distention/edema, and missing/fused caudal vertebrae. An embryofetal study was conducted in pregnant rats administered latanoprostene bunod daily by intravenous injection on gestation days 7 through 17, to target the period of organogenesis. The doses administered ranged from 150 to 1500 mcg/kg/day. Maternal toxicity was produced at 1500 mcg/kg/day (870 times the clinical dose, on a body surface area basis, assuming 100% absorption), as evidenced by reduced maternal weight gain. Embryofetal lethality (resorption and fetal death) and structural anomalies were produced at doses 300 mcg/kg/day (174 times the clinical dose). Malformations included anomalies of the sternum, domed head, forepaw hyperextension and hindlimb malrotation, vertebral anomalies and delayed ossification of distal limb bones. A no observed adverse effect level (NOAEL) was established at 150 mcg/kg/day (87 times the clinical dose) in this study. 8.2 Lactation Risk Summary There are no data on the presence of VYZULTA in human milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered, along with the mother s clinical need for VYZULTA, and any potential adverse effects on the breastfed infant from VYZULTA. 8.4 Pediatric Use Use in pediatric patients aged 16 years and younger is not recommended because of potential safety concerns related to increased pigmentation following long-term chronic use. 8.5 Geriatric Use No overall clinical differences in safety or effectiveness have been observed between elderly and other adult patients. 13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Latanoprostene bunod was not mutagenic in bacteria and did not induce micronuclei formation in the in vivo rat bone marrow micronucleus assay. Chromosomal aberrations were observed in vitro with human lymphocytes in the absence of metabolic activation. Latanoprostene bunod has not been tested for carcinogenic activity in long-term animal studies. Latanoprost acid is a main metabolite of latanoprostene bunod. Exposure of rats and mice to latanoprost acid, resulting from oral dosing with latanoprost in lifetime rodent bioassays, was not carcinogenic. Fertility studies have not been conducted with latanoprostene bunod. The potential to impact fertility can be partially characterized by exposure to latanoprost acid, a common metabolite of both latanoprostene bunod and latanoprost. Latanoprost acid has not been found to have any effect on male or female fertility in animal studies Animal Toxicology and/or Pharmacology A 9-month toxicology study administered topical ocular doses of latanoprostene bunod to one eye of cynomolgus monkeys: control (vehicle only), one drop of 0.024% bid, one drop of 0.04% bid and two drops of 0.04% per dose, bid. The systemic exposures are equivalent to 4.2-fold, 7.9-fold, and 13.5-fold the clinical dose, respectively, on a body surface area basis (assuming 100% absorption). Microscopic evaluation of the lungs after 9 months observed pleural/subpleural chronic fibrosis/inflammation in the 0.04% dose male groups, with increasing incidence and severity compared to controls. Lung toxicity was not observed at the 0.024% dose. Distributed by: Bausch + Lomb, a division of Valeant Pharmaceuticals North America LLC Bridgewater, NJ USA U.S. Patent Numbers: 6,211,233; 7,273,946; 7,629,345; 7,910,767; 8,058,467. VYZULTA is a trademark of Bausch & Lomb Incorporated or its affiliates. Bausch & Lomb Incorporated Based on /2017 VYZ.0055.USA.16 Issued: 11/2017

8 FROM THE EDITOR A Slow Game Glaucoma physicians must be dedicated to a lifetime of caring about our patients Robert D. Fechtner, MD Guest Editor, Glaucoma Physician Because it is a busy time for glaucoma specialists, all comprehensive ophthalmologists must recognize their role in the treatment of glaucoma. The US population is aging, the prevalence of glaucoma is increasing, and our options for diagnosis and treatment are advancing. It is easy to get caught up in the excitement of new surgical techniques and devices. One cannot open a journal or attend a glaucoma meeting without attention being paid to MIGS. We now have devices to bypass Schlemm s canal, access the suprachoroidal space, or divert aqueous to the subconjunctival space all without the complexities of trabeculectomy. If that s not enough, there are two novel medications on the horizon one in an entirely new class. Glaucoma innovation is in fast forward mode. But I don t want to talk about any of that! Of course, we need these innovations to provide better care for our patients. In this issue of Glaucoma Physician, we highlight some things we already know or can do but could know or do better. Glaucoma is a chronic disease and, according to the World Health Organization, it is the second leading cause of blindness worldwide. There aren t enough providers around the world to diagnose or treat all glaucoma cases. The understanding and innovation that will originate with work in the developed countries can be translated into opportunities in the developing world. We have the ability and the resources to make a difference. The first step will be identifying the disease. But that alone doesn t have value unless there are accessible and affordable interventions. Some of these challenges and opportunities are discussed in this issue. I often remind myself that I m not in the business of lowering eye pressure, but rather, I am dedicated to preserving suffcient vision for patients so they can live independent lives with quality and dignity. We have long been teaching that early glaucoma has no symptoms. Any symptoms are actually the result of topical treatments prescribed to reduce IOP. With the publication of the latest DEWS II report this summer, it is a good time to reflect upon how we can minimize at least some of the symptoms associated with topical therapy. Glaucoma is a slow game. It is not characterized by dramatic wins or quick fixes. Glaucoma specialists must be dedicated to a lifetime of caring about our patients. While one could think of a chronic progressive blinding disease as a losing game, I prefer to think that the art of glaucoma management demands that we slow down the game so it ends before there s a final score. Because I believe that life with vision, dignity, and independence is a win. GP Dr. Fechtner is professor and chair of Ophthalmology at SUNY Upstate Medical University in Syracuse, NY. Cover image courtesy of Inder Paul Singh, MD, The Eye Centers of Racine and Kenosha, WI. DECEMBER 2017 GLAUCOMA PHYSICIAN 7

9 FEATURE OSD in Glaucoma Patients Ocular Surface Disease and Glaucoma Improved detection and treatment of OSD may lead to better clinical outcomes for glaucoma patients By Robert D. Fechtner, MD Dr. Fechtner is professor and chair of ophthalmology at SUNY Upstate Medical University in Syracuse, NY. The recent DEWS II report published in July has updated and refined our understanding of dry eye disease. This report serves as a timely reminder that we must continue to advance our understanding of the pathophysiology and clinical approaches to dry eye. As the population ages, the number of people with glaucoma increases. The likelihood of ocular surface disease (OSD) also increases with age. And, as OSD may be an under-recognized co-morbid condition in patients with glaucoma, improved detection and treatment may lead to better clinical outcomes. Understanding Dry Eye There are multiple contributing causes for an abnormal tear film and ocular surface disease, including aging, environment, hormonal changes, meibomian gland disorders, and medication use. The complex interactions between the inciting events and the pathophysiologic responses are often referred to as a vicious cycle. As our appreciation of OSD evolves to better understanding the factors interfering with homeostasis of the tear film, we can take a more targeted approach to improving the ocular health and comfort of our glaucoma patients, as well as our other patients who suffer with OSD or dry eye. OSD in Glaucoma Patients How prevalent is OSD in glaucoma patients? This question can best be interpreted by comparing studies in glaucoma patients to what we know about the general population. In the Women s Health Study, 2 nearly 40,000 female health professionals were asked about the symptoms of dry eye. Nearly 10% of women aged 75 or older reported symptomatic dry eye. In the Physicians Health Study, more than 25,000 men were surveyed about dry eye disease. 3 The prevalence among men 80 years and older was reported as nearly 8%. A crosssectional community study of more than 2,500 men and women aged 65 or older reported nearly 15% with one or more dry eye symptoms often or all the time. 4 These studies serve as benchmarks, allowing us to expect to see dry eye in about 8% to 15% of our glaucoma patients. However, the reality is far different. Several studies have evaluated the prevalence of OSD in treated glaucoma patients using the Ocular Surface Disease Index (OSDI). 5 The OSDI consists of 12 questions that assess the functional impact of the symptoms of dry eye disease. Leung and colleagues 6 surveyed 101 glaucoma or ocular hypertension subjects and found mild, moderate, or severe symptoms in 59% in a single-center study. Fechtner and colleagues 7 surveyed 630 treated subjects at 10 study sites and found similar results. In this study, 48.4% had mild, moderate, or severe symptoms. Slightly more than 27% of treated glaucoma patients had moderate to severe OSD symptoms. 7 This prevalence is much greater than we would have predicted from population studies, 8 GLAUCOMA PHYSICIAN DECEMBER 2017

10 but we now know that topical glaucoma treatments can negatively impact the health of the ocular surface. OSD Detection In the past, in many practices, detecting ocular surface disease wasn t a high priority because there were few effective interventions. A patient who complained of ocular irritation might have been given a sample of lubricating drops and sent on her way. Now that there are more ways to address these complaints, it is well worth eliciting them. A detailed history and careful clinical examination can help detect signs and symptoms of OSD. That said, it is important to note that the signs of OSD don t always match the symptoms. For example, a patient may be miserable but have a relatively healthy-appearing ocular surface. Conversely, a terrible-looking ocular surface can be accompanied by drynessinduced nerve damage, which can decrease actual symptoms. Multiple approaches have become available to evaluate the various contributing factors. It is important for clinicians to keep in mind that any new testing modality should be subjected to a meaningful validation process. Due to the complexity of OSD, no one test is best. Patient questionnaires have been validated and accepted as a means of assessing symptoms of OSD. The OSDI was developed to study the impact of medical intervention for OSD, and has since been adapted more broadly to survey for OSD. It is worth noting that, while this is a validated tool, it has not been validated specifically for the glaucoma population. Other shorter surveys are also available. We don t need to overly complicate the detection or treatment of OSD. A few simple questions, such as Are your eyes uncomfortable much of the time? or Do you find your vision gets worse late in the day? can help to identify potential cases of OSD. A look at the medical history for diseases associated with dry eye, such as autoimmune disease or thyroid disease, may also identify patients at risk. Diagnostic Testing A slit lamp biomicroscopic examination provides many opportunities to detect the signs of OSD. Simple diagnostic maneuvers, such as examination of the meibomian glands or measuring tear breakup time using fluorescein stain, can easily be added to a routine examination. Tear meniscus height is an indicator of tear volume and can be assessed during slit lamp examination. As the population ages, the number of people with glaucoma increases. The likelihood of ocular surface disease (OSD) also increases with age. And, as OSD may be an under-recognized co-morbid condition in patients with glaucoma, improved detection and treatment may lead to better clinical outcomes. For symptomatic patients, aim to distinguish between a lipid deficiency leading to evaporative disease and an aqueous production deficiency. Schirmer s testing can be useful in detecting aqueous production deficiency. This test does add to the examination time and the results can be variable, but it can be helpful in some cases. Tear film osmolarity can be an indicator of tear health. Increased tear osmolarity suggests that the tears are not stable in composition. It may be the result of lipid layer dysfunction allowing for evaporation. Inflammation can also be a biomarker for OSD. A combination of history, physical examination, and supplemental testing remains are considered best practices for assessing OSD. A Practical Approach to OSD A rational approach to OSD in glaucoma patients will address underlying medical and environmental conditions, as well as interventions to improve tear film quality and overall ocular health. Treatment of dry eye is being shaped by new medical therapies and devices. Restore tear film homeostasis The concept of restoring tear film homeostasis seems rather straightforward, but in actual practice, it is often anything but that. There is DECEMBER 2017 GLAUCOMA PHYSICIAN 9

11 FEATURE OSD in Glaucoma Patients OSD IN GLAUCOMA PATIENTS: A STEPWISE APPROACH TO TREATMENT We must start by recognizing that at least half of our treated glaucoma patients are symptomatic from ocular surface disease if we take the time and effort to look for it. The following is a stepwise approach to identifying OSD as well as treatment options for these patients. 1. Identify underlying factors for OSD in glaucoma patients. 2. Consider including questions about ocular surface symptoms when taking a history at each visit. 3. Examine the eye at the slit lamp, paying particular attention to meibomian glands, tear meniscus, and tear breakup time. 4. Obtain a current medication list. A patient using artificial tears is doing so for a reason. Are systemic medications contributing to dry eye symptoms? Can you reduce the number of drops or the preservative burden? 5. Review environmental factors. Is air-conditioning or forced-air heating contributing to dry eye? Recommend a humidifier. 6. Treat meibomian gland disease in a stepwise fashion. Start with hot compresses, expressing meibomian glands. Suggest dietary omega-3 fatty acid supplementation. Advance to other modalities. Consider off-label antibiotics, if needed. 7. Break the inflammation cycle. Consider using prescription medication for a limited time to allow the ocular surface to heal. 8. Be aware of emerging technologies. Critically evaluate the strength of evidence to support the use of these technologies in glaucoma patients with ocular surface disease. 10 GLAUCOMA PHYSICIAN DECEMBER 2017

12 a vicious cycle of changes in OSD. Interventions are available to influence the cycle at many points. However, it is not always clear what the fundamental process is that initiated this vicious cycle. There is no single diagnostic test, and there is no single treatment that will provide all patients relief from their dry eye symptoms. Paradoxically, we can often achieve symptomatic relief without resolving the underlying cause. An example might be the patient who has mild meibomian gland disease and achieves relief from occasional ocular lubricants, such as drops. The symptoms might be addressed but the underlying cause is not. Restoring tear film homeostasis should remain the goal for longterm ocular health. Improve meibomian gland function OSD caused by meibomian gland dysfunction is likely far more prevalent than that caused by aqueous deficiency. It takes little more than a brief, careful look at the eyelid margin to identify gland plugging or scarring (Figure 1). As mentioned above, deficiencies in the lipid layer lead to evaporative dry eye and can trigger a series of inflammatory responses. Restoring a healthy lipid layer should be one of the early considerations for patients with dry eye disease. Perhaps the most important environmental factor for the treated glaucoma patient is topical medication. It has been shown that the more eye drops a patient is administering, the greater the symptoms of OSD. A simple regimen of hot compresses and meibomian gland expression may help to restore tear film homeostasis. Various lid scrub preparations are available to help clear secretions and may have other benefits. Supplementation of dietary omega-3 fatty acids found in fish oil, ground flaxseed, and proprietary preparations help some patients. Off-label use of oral antibiotics, such as doxycycline or a topical antibiotic (e.g., azithromycin), can be considered for recalcitrant meibomian gland disease. It is rational to take a stepwise approach to manage this complicated and uncomfortable condition. Utilize eye drops Drops have long been the mainstay of dry eye treatment and remain a valuable tool. Often, occasional drop use may be all that is needed for mild dry eye disease. There are numerous formulations, including preservative-free options. It is often diffcult to predict in advance which formulation will be most comfortable for a specific patient. Reduce environmental irritants The first fundamental principle for addressing environmental irritants is to remove the environmental factors, if possible. Most articles about OSD provide a long list of possible environmental factors. A few of them are of particular interest for our glaucoma patients. In addition to ambient temperature and humidity, perhaps the most important environmental factor for the treated glaucoma patient is topical medication. It has been shown that Figure 1. Meibomian glad dysfunction is a prevalent cause of OSD. A careful look at the eyelid margin can help to identify gland plugging or scarring. DECEMBER 2017 GLAUCOMA PHYSICIAN 11

13 FEATURE OSD in Glaucoma Patients DEWS II emphasizes the continuing need for us to better understand the multifactorial nature of OSD and create individualized plans to restore tear homeostasis. A systematic approach to evaluation and treatment should result in more comfortable and happier glaucoma patients. the more eye drops a patient is administering, the greater the symptoms of OSD. In one study, 8 subjects taking 0 or 1 drop medication had similar prevalence of OSD symptoms. Subjects taking more than one drop medication had a substantial increase in symptoms. Most patients appeared able to tolerate their first medication. Much attention has been paid to the preservative systems within drops. In particular, benzalkonium chloride is a common preservative that has been used for decades, but is implicated in OSD. 1 Now that alternative preservative systems and preservative-free medications have become available, these should be considered for glaucoma patients who are experiencing dry eye symptoms. Additionally, fixed combination medications can be used to simplify drug regimens and reduce the preservative burden. These environmental factors are well within the physician s control, although these potential benefits are not uniformly recognized by the decision-makers who control formulary access for patients. Treat inflammation Regardless of the inciting influence, inflammation can become a reinforcing factor in both aqueous deficient and evaporative dry eye disease. It may be necessary to break the inflammation cycle to restore ocular surface homeostasis. A mild steroid, such as lotoprednol, either alone or in combination with another medication, may help break the cycle. 9 Topical cyclosporine ophthalmic emulsion (Restasis, Allergan) was the first FDA-approved medication for dry eye disease. Cyclosporine is an immunomodulatory drug with anti-inflammatory properties and has demonstrated benefit for dry eye disease; however, it usually requires prolonged therapy. The most recently approved medication for dry eye is lifitegrast ophthalmic solution 5% (Xiidra, Shire). This medication aims to reduce inflammation by blocking the interaction between integrin lymphocyte function association antigen one (LFA-1) and intracellular adhesion molecule one (ICAM-1). This blocks T-cell migration and reduces cytokine release. Although it has been demonstrated to improve the signs and symptoms of dry eye disease, the role of this medication in improving OSD in treated glaucoma patients remains to be studied. A Better Understanding DEWS II emphasizes the continuing need for us to better understand the multifactorial nature of OSD and create individualized plans to restore tear homeostasis. A systematic approach to evaluation and treatment should result in more comfortable and happier glaucoma patients. GP References 1. Willcox MDP, Arueso P, Georgiev GA, et al. TFOS DEWS II tear film report. Ocul Surf. 2017;15(3): Schaumberg DA, Sullivan DA, Buring JE, Dana MR. Prevalence of dry eye syndrome among US women. Am J Ophthalmol. 2003;136(2): Schaumberg DA, Dana R, Buring JE, Sullivan DA. Prevalence of dry eye disease among US men: estimates from the Physicians Health Studies. Arch Ophthalmol. 2009;127(6): Schein OD, Muñoz B, Tielsch JM, Bandeen-Roche K, West S. Prevalence of dry eye among the elderly. Am J Ophthalmol. 1997;124(6): Schiffman RM, Christianson MD, Jacobsen G, Hirsch JD, Reis BL. Reliability and validity of the Ocular Surface Disease Index. Arch Ophthalmol. 2000;118(5): Leung EW, Medeiros FA, Weinreb RN. Prevalence of ocular surface disease in glaucoma patients. J Glaucoma. 2008;17(5): Fechtner RD, Godfrey DG, Budenz D, Stewart JA, Stewart WC, Jasek MC. Prevalence of ocular surface complaints in patients with glaucoma using topical intraocular pressure-lowering medications. Cornea. 2010;29(6): Rossi GC, Tinelli C, Pasinetti GM, Milano G, Bianchi PE. Dry eye syndromerelated quality of life in glaucoma patients. Eur J Ophthalmol. 2009;19(4): Sheppard JD, Donnenfeld ED, Holland EJ, Slonim CB, Solomon R, Solomon KD, et al. Effect of loteprednol etabonate 0.5% on initiation of dry eye treatment with topical cyclosporine 0.05%. Eye Contact Lens. 2014;40(5): GLAUCOMA PHYSICIAN DECEMBER 2017

14 PRESERVATIVE-FREE GLAUCOMA DROPS TM One Simple Drop. One Simple Regimen. Preservative-free treatment regimen for your patients Convenience of multiple medications into one combination drop May increase patient compliance by reducing the number of drops needed May reduce overall costs to your patients LAT TIM-LAT BRIM-DOR TIM-DOR-LAT TIM-BRIM-DOR TIM-BRIM-DOR-LAT Simple Drops Compounded Formulations * (Latanoprost) 0.005% (Timolol/Latanoprost) 0.5/0.005% (Brimonidine/Dorzolamide) 0.15/2% (Timolol/Dorzolamide/Latanoprost) 0.5/2/0.005% (Timolol/Brimonidine/Dorzolamide) 0.5/0.15/2% (Timolol/Brimonidine/Dorzolamide/Latanoprost) 0.5/0.15/2/0.005% info@imprimisrx.com 2017 Imprimis Pharmaceuticals, Inc. All Rights Reserved. IMPO /17 *For professional use only. ImprimisRx specializes in customizing medications to meet unique patient and practitioner needs. All formulationsare sold in accordance with state and federal regulations, which may vary. ImprimisRx dispenses these formulations only to individually identified patients with valid prescriptions. No compounded medication is reviewed by the FDA for safety or effcacy. ImprimisRx does not compound copies of commercially available products. References available upon request.

15 FEATURE Distance Care Tele-glaucoma: The Next Frontier How this technology can help improve care for many patients By Albert S. Khouri, MD Dr. Khouri is an associate professor of ophthalmology, director of the glaucoma division, and medical director of ophthalmology telemedicine at Rutgers New Jersey Medical School. He can be reached at Albert. Web-based communication, data analysis filters, wearable technology, and artificial intelligence are all being applied in telemedicine. Tele-glaucoma is an integral part of tele-ophthalmology and, perhaps, one of its most challenging fields, because glaucoma may not lend itself as well as other eye diseases, such as cataract and diabetic retinopathy, to telemedicine. Glaucoma is often slow and elusive, requiring both structural and functional testing. We know that IOP, which is widely investigated and used for screening, is not optimal for screening or detection. Although telemedicine has evolved in various disciplines over the past two decades, the advances in tele-glaucoma have not been as clearly visible. As a comparator, the American Telemedicine Association has a landmark publication delineating standards for telemedicine for diabetic retinopathy. 1 The VA healthcare system also applies tele-ophthalmology to screening and referring diabetic patients. Due to the complexities of detecting glaucoma, tele-glaucoma doesn t have similar current standards, such as those in place for diabetic eye disease. Establishing standards for tele-glaucoma are necessary for the field to evolve and improve. Validating and Comparing Tele-glaucoma to Standard of Care Perhaps the first step toward establishing standards is to validate tele-glaucoma models. In a systematic review, 2 tele-glaucoma was found to accurately discriminate between screening test results with greater odds for positive cases. In that review, tele-glaucoma detected more cases of glaucoma than an inperson examination. The advantages included early detection, reduction in wait and travel time for patients, improved specialist referral rates, and possible cost savings, specifically for remote and underserved communities. 2 The Philadelphia Telemedicine Glaucoma Detection and Follow-up Study 3 examined a protocol for detection of vision-threatening diseases, including glaucoma.the NJ Health Foundation Tele-Glaucoma Study is an ongoing trial that compares tele-glaucoma to standard of care clinical evaluation. 4 It includes more than 100 subjects with confirmed glaucoma who were evaluated through a tele-glaucoma protocol and then underwent a comprehensive clinical glaucoma evaluation. The outcomes were highly correlated for several clinical measures, including IOP and optic nerve examination, as well as for diagnostic accuracy and treatment recommendations. It was evident from the NJ tele-glaucoma study that OCT was an essential diagnostic tool. The versatility of OCT was apparent in the ability to acquire useful data, even when media opacity precluded quality imaging and limited the clinical exam (Figure 1). Another lesson learned from the study was the power of combining multiple imaging tools to improve the diagnostic capabilities of tele-glaucoma. It is known that splinter hemorrhages are less likely to be missed on an optic nerve image than on clinical exam. This was noted with the NJ tele-glaucoma study, in 14 GLAUCOMA PHYSICIAN DECEMBER 2017

16 which imaging picked up subtle hemorrhages, wedge retinal nerve fiber layer defects, and posterior segment pathology that were sometimes missed during clinical evaluation. Of course, clinical evaluation remains the standard of care and was superior in confirming or precluding pathology that was detected during tele-glaucoma (higher false positive rates on optic nerve and angle assessment with OCT). Media opacity also significantly affects tele-glaucoma fundus imaging through smaller pupils and in patients with cataracts, whereas slit lamp biomicroscopy is less hindered by those barriers. With tele-presence, patients can have their ocular data and images analyzed remotely by a trained ophthalmologist. This can be vital for diseases, such as glaucoma, where up to half of the population with the visionthreatening disease may not be aware of their condition. Tele-presence and Tele-glaucoma It is also known that patients would often fail to return for an eye evaluation after being identified during screening. This perhaps remains one of the most significant shortcomings of community screening for glaucoma and other diseases. Tele-presence allows subjects to be screened while a remotely placed physician has access to the individual s data through a secure web connection or other cloud-based solution. Tele-presence has the potential to be performed through an effcient captureand-forward technology, or more effectively through live, real-time streaming. This reduces the need for the subject to come in for an appointment. Tele-presence can be applied to glaucoma and other vision-threatening diseases and may rectify the issue of individuals having limited access to eye care. With tele-presence, patients can have their ocular data and images analyzed remotely by a trained ophthalmologist. This can be vital for diseases, such as glaucoma, where up to half of the population with the vision-threatening disease may not be aware of their condition. Software Solutions and Artificial Intelligence Digital images can be separated into components to enhance the appearance of pathology and improve detection. For example, red, green, blue separation is a well-recognized technique that has the ability to enhance the appearance of the retinal layer. Particularly, the blue and green wavelength channels can enhance pathology in the retina and nerve fiber layer, which can prove invaluable for detection of retinal nerve fiber layer (RNFL) defects. Splinter hemorrhages tend to appear with enhanced clarity on green channels, even when very subtle on a color image. Red channels are optimal for deeper pathology, such as AMD. Embossing techniques highlight pixel coordinates and can be applied to digital images to enhance RNFL defects (and the elevations/depressions in the retina that are seen in diabetic retinopathy and macular degeneration). Figure 1. Using teleglaucoma, OCT can acquire data even when digital imaging is hindered by media opacity. DECEMBER 2017 GLAUCOMA PHYSICIAN 15

17 FEATURE Distance Care Figure 2. Digital filters during tele-glaucoma enhance retinal nerve fiber layer defect that is detected on OCT (A: Color image, B: Blue channel, C: Emboss filter, D: OCT RNFL defect, E: OCT posterior pole ganglion cell loss). All of these software enhancements can make pathology more readily visible and correlate well with OCT findings (Figure 2). Although, as glaucoma physicians, we may be more focused on glaucoma detection, any tele-medicine protocol will have to optimize detection of various vision-threatening diseases (e.g., macular degeneration and diabetic retinopathy). Most recently, artificial intelligence (AI) has had various novel applications in medicine. Computers can gather information and analyze it to emulate the decision-making processes of human cognition. The integration and analysis of a large database can be used to enhance and streamline patterns of detection. There are AI applications that assist in analyzing optic nerve appearance as well as retinal pathology. Such technology will undoubtedly continue to evolve in the coming years. The application of AI and big data in tele-glaucoma is promising, and research in this area will shed light on its role, as well as its limitations. Current Applications in Community Outreach and Education Tele-glaucoma can be applied to allow patients access to care that would otherwise not be available. For example, tele-glaucoma programs that provide remote specialized care already exist in Canada and Australia. 5 The community outreach program at New Jersey Medical School employs teleglaucoma to provide access to specialized ophthalmology to subjects in homeless shelters, soup kitchens, and community centers in New Jersey. This program also provides medical students with an excellent opportunity to serve the community while gaining exposure to technology. Translational research opportunities for students, residents, and faculty help bridge the gap in the literature on existing tele-glaucoma standards for protocols and practice. Tele-glaucoma for consultation also can be applied across healthcare networks, particularly in the emergency room setting where the need surely exists. Other applications in education and training can be used to provide feedback to physicians in training. The impact on quality of training and patient care can be significant. Evolving Technology Tele-glaucoma as a field lends itself very well to the advances in hardware, software, and digital tele-communication. The applications of tele-glaucoma within healthcare, research, and education will undoubtedly continue to evolve. A collaborative effort by various societies will help set the standards that are needed for tele-glaucoma. GP References 1. Cavallerano J, Lawrence MG, Zimmer-Galler I, et al. Telehealth practice recommendations for diabetic retinopathy. Telemed J E Health. 2004;10(4): Thomas SM, Jeyaraman MM, Hodge WG, Hutnik C, Costella J, Malvankar- Mehta MS. The effectiveness of teleglaucoma versus in-patient examination for glaucoma screening: A systematic review and meta-analysis. PLoS One. 2014;9(12):e Hark LA, Katz LJ, Myers JS, et al. Philadelphia telemedicine glaucoma detection and follow-up study: Methods and screening results. Am J Ophthalmol. 2017;181: Mendez N, Kommana S, Szirth B, Khouri A. Glaucoma telemedicine versus conventional care: New Jersey Health Foundation prospective clinical trial. Paper presented during the AAO Annual Meeting; Oct , 2016; Chicago, IL. 5. Kassam F, Yogesan K, Sogbesan E, Pasquale LR, Damji KF. Teleglaucoma: improving access and efficiency for glaucoma care. Middle East Afr J Ophthalmol. 2013;20(2): GLAUCOMA PHYSICIAN DECEMBER 2017

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19 FEATURE Widefield OCT Widefield OCT Improves Glaucoma Management Ganglion cell complex analysis provides a more comprehensive picture of disease status By Robert Rothstein, MD Dr. Rothstein is the founder of Eyenamics NY in Forest Hills, NY, where he provides comprehensive eye care and specializes in neuro-ophthalmology and all stages of glaucoma. It is well known that glaucoma is a multifactorial, progressive optic neuropathy characterized by the loss of retinal ganglion cells. 1-2 For decades, glaucoma was diagnosed and monitored via clinical exam and serial optic disc photography to document optic nerve cupping and automated perimetry to detect functional vision loss. With the realization that damage caused by glaucoma can precede detection by perimetry 2 and the development of OCT and laser polarimetry in the 1990s, measurement of the ganglion cell axons in the circumpapillary retinal nerve fiber layer (cprnfl) was added to the glaucoma diagnostic regimen. The more recent development of spectral-domain OCT (SD-OCT), which features faster speeds and higher resolution, has enabled segmentation of the ganglion cell complex (GCC) from the full thickness of the retina. This capability may allow for earlier diagnosis of glaucoma and more precise monitoring of disease progression because the GCC contains not only the RNFL, but also the ganglion cell layer, which consists of the ganglion cell bodies, and the inner-plexiform layer (IPL), which consists of the ganglion cell dendrites. All three layers are affected by glaucoma. 3 Measuring Ganglion Cell Complex Thickness in the Macula Zeimer and colleagues were the first to correctly hypothesize that the macula is an area of interest in glaucoma and to report an association between glaucoma and decreased macular thickness. 4 The macula contains a substantial proportion of the retinal ganglion cells and is the only area of the retina where the ganglion cell layer is more than one cell layer thick. The central 20 degrees of the macula can contain up to 50% of the retinal ganglion cells. Furthermore, the anatomy of the optic nerve head varies across subjects more than the macular anatomy. For these reasons, glaucomatous changes may be more easily detected in the macula. Rao and colleagues 5 compared SD-OCT macular measurements of ganglion cell/ipl thickness with visual sensitivity measurements from standard automated perimetry and microperimetry and found that the former performed better in the diagnosis of glaucoma. Lee and colleagues 6 also investigated the relationship between central visual field sensitivity and macular ganglion cell/ipl thickness in glaucoma. They reported a correlation between inferotemporal ganglion cell/ipl thickness and corresponding visual field sensitivity in early to moderate glaucoma, and a correlation between superotemporal ganglion cell/ipl thickness and corresponding visual field sensitivity in advanced glaucoma. 6 Interestingly, a study by Bowd and colleagues 7 indicated the lack of a floor effect for SD-OCT measurement of ganglion cell/ IPL thickness. The study showed that a significant amount of ganglion cell/ipl tissue is spared in advanced glaucoma compared with other structural measurements, suggesting this may be a valuable parameter for detecting glaucoma progression 7 (See Case 2, page 22) and supporting a role for SD-OCT in advanced glaucoma. 18 GLAUCOMA PHYSICIAN DECEMBER 2017

20 The Avanti Widefield OCT system (Optovue) performs GCC thickness measurements and offers trend analysis that tracks change in both GCC and RNFL thickness and provides an estimate of the rate of future progression. Additional metrics are designed to increase the sensitivity and specificity of the analysis. Focal loss volume (FLV) measures the average amount of focal, or isolated, loss over the entire GCC map, while global loss volume measures the average amount of GCC loss over the entire GCC map. Trend analysis with widefield OCT requires only three OCT scans to generate an evaluation of progressive changes. In comparison, trend analysis with other OCT systems typically requires at least five separate scans. The parameters tracked by different systems differ as well. One system, for example, monitors optic nerve cupping and RNFL loss over time to create a trend analysis. A recent study demonstrated a non-linear relationship between neuroretinal rim loss and RNFL loss in glaucoma, leading the investigators to hypothesize that structural changes in peripapillary connective tissue and axons followed by retinal ganglion cell axon loss may account for this non-linear relationship. 8 It follows that trend analysis based on optic nerve cup-to-disc ratio and RNFL thickness is likely redundant. Hollo and Zhou 9 were the first to investigate progression rates of RNFL thickness and GCC in healthy eyes, eyes with ocular hypertension, and eyes with glaucoma using widefield OCT. They concluded that an average RNFL thickness progression rate faster than -1.5 µm/year and an average GCC progression rate faster than -1.3 µm/year are suggestive of glaucoma progression. 9 Similarly, Hollo and Naghizadeh 10 evaluated the latest version (6.12) of the RTVue OCT (Optovue) software with regard to its detection of macular GCC and RNFL changes by imaging healthy eyes, eyes with ocular hypertension, and eyes with glaucoma at 6-month intervals for an average of 5 years. Comparing the new software with a previous version (6.3), they concluded that the new software reduces long-term measurement variability across the spectrum of glaucoma severity and provides steeper GCC progression slopes and more cases of significant GCC progression slopes in glaucoma, which may serve to improve detection of glaucomatous progression in clinical practice. 10 [SD-OCT] may allow earlier diagnosis of glaucoma and more precise monitoring of disease progression because the GCC contains not only the RNFL, but also the ganglion cell layer, which consists of the ganglion cell bodies, and the inner-plexiform layer, which consists of the ganglion cell dendrites. All three layers are affected by glaucoma. 3 Zhang and colleagues with the Advanced Imaging for Glaucoma Study Group, evaluated RTVue measurements of the optic disc, cprnfl thickness, and macular GCC thickness and prediction of the development and progression of visual field loss. 11,12 They found that GCC-FLV was the most powerful single predictor of conversion to perimetric glaucoma. Eighty-two percent of visual field conversion was preceded by an abnormal OCT variable. A lag of 23 +/- 17 months existed between visual field conversion and an OCT abnormality. A borderline GCC-FLV carried a 3.8-fold conversion risk, while an abnormal GCC-FLV carried a 5-fold conversion risk. Based on Kaplan-Meier survival curves, eyes with a borderline or abnormal GCC-FLV at baseline had a nearly 4 times greater risk of visual field conversion after 6 years compared with eyes with normal GCC-FLV. The strongest risk factor for visual field progression was GCC-FLV, with NFL-FLV a close second. Eyes with a borderline or abnormal GCC- FLV at baseline had a significantly rapid visual field index (VFI) decline; the slope of VFI deterioration was twice as steep in eyes with abnormal GCC-FLV at baseline compared with eyes with borderline GCC-FLV. Another interesting finding was that eyes with decreased inferior GCC thickness were DECEMBER 2017 GLAUCOMA PHYSICIAN 19

21 FEATURE Widefield OCT Figure 1. Case 1: trend analysis OD showed an RNFL rate of change of µm/yr and a GCC rate of change of µm/yr. more likely to progress compared with eyes with decreased inferior NFL thickness. GCC Analysis in My Practice I routinely use the widefield OCT to assist me as I manage my glaucoma and glaucomasuspect patients. The addition of GCC analysis with FLV and GLV metrics provides me with an even more comprehensive view of each patient s disease status, as the following cases illustrate. Case 1 A 73-year-old woman with asymmetric optic disc cupping and mild sensitivity depression on perimetry had IOP in the mid to high teens that had occasionally risen to more than 20 mmhg. Her total, superior, and inferior GCC thickness averages were initially normal OD, but deteriorated to abnormal or borderline at the most recent visit (Figure 1). Total, superior, and inferior GCC thickness averages OS, initially borderline, progressed to abnormal (Figure 2). Also over time, GLV had progressed to abnormal while FLV remained normal, which indicates a more diffuse glaucomatous damage pattern. The initial scans showed borderline superior RNFL thickness that deteriorated to abnormal OU by the time of the most recent scans. Average RNFL thickness followed a similar course. At the most recent visit, overall, superior, and inferior RNFL averages were all decreased. At the same time, no significant change occurred in cup/disc ratios or neuroretinal rim areas. Trend analysis OD showed an RNFL rate of change of µm/yr and a GCC rate of change of µm/yr. Trend analysis OS showed an RNFL rate of change of µm/ yr and a GCC rate of change of µm/yr. Visual field trend analysis showed no significant progression in either eye. Based on disease progression documented with OCT, selective laser trabeculoplasty (SLT) was performed OU to achieve tighter control of IOP. 20 GLAUCOMA PHYSICIAN DECEMBER 2017

22 RETHINK GLAUCOMA RISK A more objective predictor of glaucoma progression. Corneal Hysteresis, only with Ocular Response Analyzer G3. Her sight depends on your confidence and only Ocular Response Analyzer G3 measures Corneal Hysteresis, which is more associated with visual field progression than CCT or IOP. 1-3 Learn more at reichert.com/glaucomaconfidence Corneal Hysteresis: CPT Code Advancing Eye Care. American Innovation AMETEK, Inc. & Reichert, Inc. ( ) Made in USA References: 1. Medeiros FA, Meira-Freitas D, Lisboa R, Kuang TM, Zangwill LM, Weinreb RN. Corneal hysteresis as a risk factor for glaucoma progression: a prospective longitudinal study. Ophthalmology Aug;120(8): De Moraes CV, Hill V, Tello C, Liebmann JM, Ritch R. Lower corneal hysteresis is associated with more rapid glaucomatous visual fi eld progression. J Glaucoma Apr- May;21(4): Aashish Anand, MD, Carlos Gustavo De Moraes, MD, Christopher C Teng, MD, Celso Tello, MD, Jeffrey M Liebmann, MD Robert Ritch, MD. Lower Corneal Hysteresis Predicts Laterality in Asymmetric Open Angle Glaucoma, IOVS Papers in Press. Published on June 23, 2010 as Manuscript iovs CPT is registered trademark of the American Medical Association.

23 FEATURE Widefield OCT Figure 2. Trend analysis OS showed an RNFL rate of change of µm/yr and a GCC rate of change of µm/yr. Case 2 This case involves a 49-year-old man with initial average IOPs of 16 mmhg OD and 32 mmhg OS, thin central cornea OU, mild superior arcuate visual field defects OD, and dense superior and inferior arcuate visual field defects OS. Both FLV and GLV were reduced bilaterally and were worse in the left eye. RNFL and GCC thickness continued to decrease in both eyes as FLV and GLV also worsened (Figure 3). For tighter control of IOP, the patient received SLT OD and trabeculectomy OS. FLV/GLV continued to worsen, but the damage was likely non-pressure-dependent and may have been a result of continued apoptosis and cell death even after IOP was well controlled. In this case, OCT demonstrates the absence of a floor effect for GCC measurements as opposed to the floor effect observed for RNFL measurements. Progression is noted in both the RNFL and GCC measurements OD. In contrast, RNFL progression levels off OS, while GCC progression continues because in late glaucoma, RNFL progression is slower than GCC progression; this demonstrates the lack of a GCC floor effect in late glaucoma and the need for GCC trend analysis in such cases. Case 3 An 81-year-old man with secondary openangle glaucoma following laser iridotomy OU had also been diagnosed with pseudoexfoliative glaucoma. Despite therapy with three IOP-lowering drops OU and IOPs in the midteens, OCT detected progression of GCC and RNFL thickness loss. The rate of GCC loss was greater than the rate of RNFL loss OD, and the rate of RNFL loss was greater than the rate of GCC loss OS, demonstrating that progression in these two parameters is not necessarily synchronous and GCC loss can outpace RNFL loss. Initially, FLV and GLV values were normal OD and 22 GLAUCOMA PHYSICIAN DECEMBER 2017

24 Figure 3. Case 2: OCT demonstrates the absence of a floor effect for GCC measurements as opposed to the floor effect observed for RNFL measurements. abnormal OS. Progression, significant OD and mild OS, occurred in both parameters. Based on the OCT trend analysis, in an effort to stop disease progression, SLT was performed OU. Benefits for Patients and Physicians OCT technology continues to improve our ability to accurately diagnose and monitor glaucoma. The addition of a more direct way to measure the macular GCC in combination with the cprnfl and optic disc analysis improves risk prediction as well. This comprehensive analysis further enables individualized treatment protocols for the best possible patient care. GP References 1. Quigley HA, Dunkelberger GR, Green WR. Retinal ganglion cell atrophy correlated with automated perimetry in human eyes with glaucoma. Am J Ophthalmol. 1989;107(5): Quigley HA. Ganglion cell death in glaucoma: pathology recapitulates ontogeny. Aust N Z J Ophthalmol. 1995;23(2): Tan O, Chopra V, Lu AT-H, et al. Detection of macular ganglion cell loss in glaucoma by Fourier-domain optical coherence tomography. Ophthalmology. 2009;116(12): Zeimer R, Asrani S, Zou S, Quigley H, Jampel H. Quantitative detection of glaucomatous damage at the posterior pole by retinal thickness mapping: a pilot study. Ophthalmology. 1998;105(2): Rao HL, Hussain RS, Januwada M, et al. Structural and functional assessment of macula to diagnose glaucoma. Eye (Lond). 2017;31(4): Lee JW, Morales E, Sharifipour F, et al. The relationship between central visual field sensitivity and macular ganglion cell/inner plexiform layer thickness in glaucoma. Br J Ophthalmol. Epub ahead of print Jan. 11, Bowd C, Zangwill LM, Weinreb RN, Medeiros FA, Belghith A. Estimating optical coherence tomography structural measurement floors to improve detection of progression in advanced glaucoma. Am J Ophthalmol. 2017;175: Patel NB, Sullivan-Mee M, Harwerth RS. The relationship between retinal nerve fiber layer thickness and optic nerve head neuroretinal tim tissue in glaucoma. Invest Ophthalmol Vis Sci. 2014;55(10): Holló G, Zhou Q. Evaluation of retinal nerve fiber layer thickness and ganglion cell complex progression rates in healthy, ocular hypertensive, and glaucoma eyes with the Avanti RTVue-XR optical coherence tomograph based on 5-year follow-up. J Glaucoma. 2016;25(10):e905-e Holló G, Naghizadeh F. Influence of a new software version of the RTVue-100 optical coherence tomograph on the detection of glaucomatous structural progression. Eur J Ophthalmol. 2015;25(5): Zhang X, Loewen N, Tan O, et al., for the Advanced Imaging for Glaucoma Study Group. Predicting development of glaucomatous visual field conversion using baseline Fourier-domain optical coherence tomography. Am J Ophthalmol. 2016;163: Zhang X, Dastiridou A, Francis BA, et al. Baseline Fourier-domain optical coherence tomography structural risk factors for visual field progression in the Advanced Imaging for Glaucoma Study. Am J Ophthalmol. 2016;172: DECEMBER 2017 GLAUCOMA PHYSICIAN 23

25 FEATURE Fellowships Moving to the Front of the Line How glaucoma fellowships transformed from last pick to first pick By Alena Reznik, MD Dr. Reznik is an assistant professor of clinical ophthalmology and the codirector of the Glaucoma Fellowship Program at the University of Southern California, Roski Eye Institute in Los Angeles. Her research focuses on the development of novel surgical techniques and new approaches for patients with early glaucoma. She can be reached via at Alittle more than a decade ago, glaucoma was defined as a disease of pressure in the eye higher than the statistical norm and treatment consisted of burdensome ocular drops or complicated surgeries, including trabeculectomy and tube shunts. Patients and physicians were dissatisfied. As a result, glaucoma fellowships were left unfilled as ophthalmology residents raced toward higher-paying, more exciting cataract and retina subspecialties. But baby boomers kept aging, creating an ever-increasing number of glaucoma patients, which led to innovation in the market. We now know that glaucoma is probably similar to other degenerative nerve diseases, such as Alzheimer s or Parkinson s Disease. The American Academy of Ophthalmology (AAO) has modified the definition of glaucoma to a disease that damages your eye s optic nerve. While the only modifiable risk factor remains IOP, the ophthalmic industry has invested heavily in improved options for treating patients safely and more effciently. When I was surveying specialties 7 years ago, I noted all of the devices and products in development for glaucoma, and the anticipated progress enticed me to apply for a glaucoma fellowship. I wasn t the only person; glaucoma is now rumored be the most-enrolled specialty in ophthalmology. Why Glaucoma? There are many reasons that glaucoma has become a very attractive specialty. First, diagnostic advances have changed outcome potential. Previously, glaucoma specialists were treating patients with such severe disease that irreparable vision loss was often inevitable. Now that OCT is used for diagnosis, detection of disease happens earlier, so risky surgeries are less likely and vision loss often can be prevented. It s a much more satisfying experience for a physician when he or she has the ability to make a significant impact on a patient s quality of life. The development of the istent Trabecular Micro-Bypass (Glaukos) marked the birth of micro-invasive glaucoma surgery. Since then, other minimally invasive glaucoma (MIGS) treatments have emerged. MIGS is recognized as minimally invasive treatments that restore the eye s natural outflow system, thereby reducing IOP and protecting the optic nerve. Collectively, these new treatments and procedures led to a tremendous change glaucoma care shifted from pharmaceutical management to surgical management. Furthermore, these new procedures are very elegant and offer lower pressures with few side effects or adverse events. A straightforward procedure with fewer side effects also means that surgeons can perform them more frequently. Although reimbursement for glaucoma procedures has not increased, this is offset by our ability to perform more surgeries in less time. The improved safety profile means that follow-up visits are minimal as well. This is combined with an ever-growing patient population. The result is that new glaucoma specialists can set up shop just about anywhere in the U.S. and have enough patients to fill their schedule within a couple of months. The physicians can also combine glaucoma with general ophthalmology or cataract services, developing a wide spectrum of patients and cases. 24 GLAUCOMA PHYSICIAN DECEMBER 2017

26 I was looking for a surgical field that involved complex surgery under the microscope, but I also wanted to have the opportunity to develop relationships with my patients. For me, glaucoma fits the bill. I have a large variety of disease management options, and I see patients on an ongoing basis, so I get to know them much as a primary care doctor would. MIGS Training I completed my residency training at the University of California-Davis, an institution known for being on the brink of innovation. There, the focus is on early diagnosis and early adoption of MIGS procedures. I was very fortunate to be able to perform istent, endocyclophotocoagulation, Kahook Dual Blade, and other procedures during my residency. I completed my fellowship at the Stein Eye Institute at the University of California-Los Angeles. There, I gained experience working in private practice as well as in public service with an underserved population. Experiencing the whole range of disease and patients was excellent training for establishing how I wanted to approach treatment in my practice. Now that I work with the University of Southern California (USC), I see both underserved as well as private insurance patients in the same clinic. This is rewarding because, in most cases, I believe that the earlier we can intervene surgically for glaucoma, the better. Surgical solutions remove the risk of patients being noncompliant with topical medication regimens, which could lead to vision loss. Not all ophthalmology students have the option to practice MIGS surgery during their residency or fellowship, and some ophthalmologists completed their training prior to the emergence of the MIGS devices. Luckily, there are other ways to get exposure and training. Companies, such as Alcon (maker of the CyPass Micro-Stent) and Glaukos provide excellent training programs for new physicians. The Glaukos training includes a wet lab, for which they supply artificial eyes and all tools needed to complete formal training. Training also includes online modules and an expert who is present in the OR to guide trainees through several cases. The expert is also present for the first post-op visit and to assist throughout follow up. Glaukos has also taken the progressive step of creating a training course specifically for residents and fellows. It begins at their headquarters, with a deep dive on MIGS, an overview covering existing and emerging devices, and hands-on training and video reviews. It continues with highly experienced speakers who share their knowledge in a very interactive way. I send all of my residents and fellows who are interested in glaucoma to that course. In addition to company-specific training courses, ophthalmology conferences are an excellent opportunity to gain information and experience. The American Glaucoma Society s annual meeting is devoted to glaucoma, but the American Society of Cataract and Refractive Surgery and the AAO also have good subspecialty days in which talented young surgeons present on all of the latest treatments, including videos of techniques and complications. In my third year of medical school, I attended multiple meetings and saw how the leaders in the field were managing glaucoma. It was infectious to hear them talk about the future, and was an important factor in my decision to focus on glaucoma for my fellowship. I was looking for a surgical field that involved complex surgery under the microscope, but I also wanted to have the opportunity to develop relationships with my patients. For me, glaucoma fits the bill. Individual glaucoma surgeons in your local community are another excellent resource. Find someone who is willing to take you into the OR several times over a few weeks so you can see the full spectrum of techniques available. The Future of Glaucoma Management Working in a training institution, we have a responsibility to the continued growth of the field. At USC, we participate in a wide variety of continued on page 29 DECEMBER 2017 GLAUCOMA PHYSICIAN 25

27 FEATURE Preventing Blindness Worldwide Glaucoma in Africa A strategic approach to preventing blindness By Tony Realini, MD, MPH, and Adeyinka Ashaye, MD, MSc Dr. Realini is professor of ophthalmology at the West Virginia University Eye Institute. His clinical practice and research efforts are focused on improving the lives of and preventing blindness in patients with glaucoma. Dr. Ashaye is head of the department of ophthalmology in the College of Medicine at the University of Ibadan. She is the principal investigator for Eyes of Africa: The genetics of blindness, an H3Africa project funded by the NIH and Wellcome Trust. The burden of glaucoma in Africa represents a perfect storm of high prevalence and limited resources. There are an estimated 8 million people with openangle glaucoma in Africa, and this number will double by Vision loss and blindness from glaucoma occur in Africa at twice the average global rate. 2 The sub-saharan region of Africa (SSA) lacks the economic and human resources to address this burden SSA is home to the world s 10 poorest nations and has the fewest number of doctors per capita of any other global region, according to the World Health Organization. There are many barriers to preventing glaucoma-related vision loss and blindness. Often, patients present with late-stage disease because of a pervasive low level of awareness and lack of knowledge about glaucoma and its most serious implications, including the risk of vision loss and blindness. More than 90% of persons with glaucoma don t know they have it, 3 and screening for glaucoma has been largely unfruitful, owing, in part, to significant overlap in the appearance of healthy and glaucomatous optic nerves, particularly in black patients who have larger optic nerves and cups than their Caucasian counterparts. 4,5 Suboptimal Treatment Options Once diagnosed, treatment is often suboptimal for a variety of reasons. Adult literacy is low throughout Africa (62%), 6 and nearly half (47%) of the population lives on less than $1.90 USD a day. 7 The cost of glaucoma care becomes a burden to the family, perpetuating the cycle of poverty. Access to care is also a problem. Most eyecare workers are concentrated in the large cities. There are very few working in resourcedeprived facilities, and these typically lack a clear public health control strategy and highquality integrated glaucoma care. The majority of the population living in rural areas have no access to health facilities at all or must depend on inadequately equipped facilities. Long-distance trips prevent many from receiving care, complying with treatments, and returning for follow up. Among those who do have access to providers, additional barriers prevent effective glaucoma management. The cost of medical treatment is high and often not sustainable by a majority of patients. Surgery is not widely accepted, partly because of high initial cost and/or a fear of going blind from the surgery. Also, the volume of glaucoma surgery varies widely among ophthalmologists in Africa, and so do surgical outcomes. The Role of SLT Solving Africa s glaucoma problem will not be easy. Medical therapy the mainstay of treatment in developed regions is impractical in most poor African countries, where the cost of medications may exceed the average annual per capita income. Likewise, surgical interventions are limited by cost, a paucity of surgeons trained to perform glaucoma procedures, and high refusal rates by patients. Recently, attention has turned to the role of laser therapy specifically selective laser trabeculoplasty (SLT) as part of the solution to Africa s glaucoma burden. A preliminary prospective study of SLT in an Afro- Caribbean population in St. Lucia demonstrated mean IOP reductions on the order of 30% to 40% with no adjunctive medical ther- 26 GLAUCOMA PHYSICIAN DECEMBER 2017

28 Cyclo G6 Glaucoma Laser System With continuous wave and MicroPulse Technology One laser, three probes to treat all stages of glaucoma; from early to mid to refractory stage: G-Probe for traditional transscleral cyclophotocoagulation (TSCPC) MicroPulse P3 for CPC with MicroPulse Technology G-Probe Illuminate for TSCPC with built-in transillumination IRIDEX-patented MicroPulse Technology allows highly effective, non-incisional, non-destructive, and repeatable glaucoma treatment that significantly improves patient safety and downtime. Visit our website to see physician testimonials, download clinical articles, learn about available specials and trade-in opportunities, and to watch seminars from ESCRS 2017 and AAO 2017 to learn how the Cyclo G6 Glaucoma Laser is revolutionizing glaucoma treatment around the world iridex.com/cyclog IRIDEX. All rights reserved. IRIDEX, the IRIDEX logo, Cyclo G6, MicroPulse P3, G-Probe, G-Probe Illuminate, and MicroPulse are trademarks or registered trademarks of IRIDEX. AD

29 FEATURE Preventing Blindness Worldwide apy at 12 months. 8 A more robust prospective study evaluated SLT in glaucoma patients from both St. Lucia and Dominica and found mean IOP reductions at 12 months of ~30% with success rates of ~80% (IOP reduced at least 20% from untreated baseline on no medications) at 12 months after a single treatment session. 9 Additionally, a retrospective study of SLT in black Africans demonstrated mean IOP reductions on the order of 40% with ~90% response rate at 12 months. 10 More than 90% of persons with glaucoma don t know they have it, 3 and screening for glaucoma has been largely unfruitful, owing, in part, to significant overlap in the appearance of healthy and glaucomatous optic nerves, particularly in black patients who have larger optic nerves and cups than their Caucasian counterparts. 4,5 Taken together, these studies suggest that SLT lowers IOP 30% to 40% in people of African descent, with initial response rates in the range of 80% to 90%. Importantly, SLT is very safe no serious vision-threatening complications were reported in any of these studies, and complications following SLT are rare throughout the world. 11 In this population with a high disease burden, SLT offers effcacy consistent with incisional surgery and safety rivaling medical therapy. In addition, SLT has many attributes that favor its use in Africa. It is noninvasive, easy to learn and perform, requires no postoperative anti-inflammatory 12,13 or anti-microbial therapy, is portable, and is cost-effective relative to medical therapy. 14,15 Once the equipment and expertise are on site, the incremental cost of each SLT treatment is limited to the costs of electricity, lens coupling gel, and equipment maintenance. Equally important, SLT can be safely repeated and provides comparable effcacy to initial SLT Helping Hands The enormous task of reducing glaucoma blindness in Africa will require a coordinated effort by many people with a multitude of skills. To this end, the African Glaucoma Consortium was founded in 2017 specifically for this purpose. The Consortium is a collective of African ophthalmologists, clinical scientists, and program builders working together to identify and develop the necessary resources for a successful continent-wide glaucoma care program. The group s long-term goal is to develop an integrated network of glaucoma centers of excellence throughout Africa. These centers will provide tertiary glaucoma care including both laser and incisional surgery in partnership with local and regional primary and secondary care partners, offer training to young surgeons to expand capacity, and conduct impactful research to clarify optimal care processes for glaucoma in this region. Also ongoing is the Human Heredity and Health in Africa (H3Africa) initiative. Funded by the NIH in partnership with Wellcome Trust and with guidance from the African Society of Human Genetics, this program is designed to provide African scientists with new opportunities to lead research into the genetics and environmental contributors to health and disease issues of importance to Africa. In this study, the researchers will address multiple aspects of African glaucoma from improving diagnosis to novel treatment strategies all of which are integrated with state of the art gene discovery. Working Together In summary, novel research and collaborative initiatives are inspiring innovative solutions to Africa s glaucoma burden. Efforts are under way to address issues ranging from population screening to optimizing care processes to exploring the genetic basis of glaucoma. Some goals include helping to improve the skill sets of the existing healthcare providers and the recruitment and training of new providers to expand regional capacity for care delivery. Working together to understand the barriers to care and develop strategies to surmount 28 GLAUCOMA PHYSICIAN DECEMBER 2017

30 these obstacles, we will build a glaucoma care program capable of providing high-level, evidence-based clinical care to the millions of Africans with glaucoma. GP References 1. Tham YC, Li X, Wong TY, Quigley HA, Aung T, Cheng CY. Global prevalence of glaucoma and projections of glaucoma burden through 2040: a systematic review and meta-analysis. Ophthalmology. 2014;121(11): Flaxman SR, Bourne RRA, Resnikoff S, Ackland P, Braithwaite T, Cicinelli MV, et al. Global causes of blindness and distance vision impairment : a systematic review and meta-analysis. Lancet Glob Health. Published October Available at Last accessed Nov. 3, King A, Azuara-Blanco A, Tuulonen A. Glaucoma. BMJ. 2013;346:f Lee RY, Kao AA, Kasuga T, Vo BN, Cui QN, Chiu CS, et al. Ethnic variation in optic disc size by fundus photography. Curr Eye Res. 2013;38(11): Varma R, Tielsch JM, Quigley HA, Hilton SC, Katz J, Spaeth GL, et al. Race-, age-, gender-, and refractive error-related differences in the normal optic disc. Arch Ophthalmol. 1994;112(8): Literacy and non-formal education. UNESCO. Available at new/en/dakar/education/literacy/. Last accessed Nov. 4, Africa Hunger Facts. World Hunger Education Service. Available at worldhunger.org/africa-hunger-poverty-facts/. Last accessed Nov. 4, Realini T. Selective laser trabeculoplasty for the management of open-angle glaucoma in St. Lucia. JAMA Ophthalmol. 2013;131(3): Realini T, Shillingford-Ricketts H, Burt D, Balasubramani GK. West Indies Glaucoma Laser Study (WIGLS): Month Efficacy of Selective Laser Trabeculoplasty in Afro- Caribbeans with Glaucoma. Am J Ophthalmol. Sep pii: S (17) Goosen E, Coleman K, Visser L, Sponsel WE. Racial Differences in Selective Laser Trabeculoplasty Efficacy. J Curr Glaucoma Pract. 2017;11(1): Song J. Complications of selective laser trabeculoplasty: a review. Clinical Ophthalmology. 2016;10: De Keyser M, De Belder M, De Groot V. Randomized Prospective Study of the Use of Anti-Inflammatory Drops After Selective Laser Trabeculoplasty. J Glaucoma. 2017;26(2):e22-e Realini T, Charlton J, Hettlinger M. The impact of anti-inflammatory therapy on intraocular pressure reduction following selective laser trabeculoplasty. Ophthalmic Surg Lasers Imaging. 2010;41(1): Stein JD, Kim DD, Peck WW, Giannetti SM, Hutton DW. Cost-effectiveness of medications compared with laser trabeculoplasty in patients with newly diagnosed open-angle glaucoma. Arch Ophthalmol. 2012;130(4): Wittenborn JS, Rein DB. Cost-effectiveness of glaucoma interventions in Barbados and Ghana. Optom Vis Sci. 2011;88(1): Francis BA, Loewen N, Hong B, et al. Repeatability of selective laser trabeculoplasty for open-angle glaucoma. BMC Ophthalmol. 2016;16: Polat J, Grantham L, Mitchell K, Realini T. Repeatability of selective laser trabeculoplasty. Br J Ophthalmol. 2016;100(10): Khouri AS, Lari HB, Berezina TL, Maltzman B, Fechtner RD. Long term efficacy of repeat selective laser trabeculoplasty. J Ophthalmic Vis Res. 2014;9(4): Avery N, Ang GS, Nicholas S, Wells A. Repeatability of primary selective laser trabeculoplasty in patients with primary open-angle glaucoma. Int Ophthalmol. 2013;33(5): Hong BK, Winer JC, Martone JF, Wand M, Altman B, Shields B. Repeat selective laser trabeculoplasty. J Glaucoma. 2009;18(3): Ayala M. Intraocular pressure reduction after initial failure of selective laser trabeculoplasty (SLT). Graefes Arch Clin Exp Ophthalmol. 2014;252(2): Durr GM, Harasymowycz P. The effect of repeat 360-degree selective laser trabeculoplasty on intraocular pressure control in open-angle glaucoma. J Fr Ophtalmol. 2016;39(3): continued from Fellowships, page 25 clinical trials and hold CME courses that are open to everyone. Our approach to education is to be very open to investigating new technologies. I recently performed my initial implants of the Xen Gel Stent (Allergan) and invited several surgeons to be present in the OR to see how we managed. Large universities are the first to participate in studies, publish the outcomes, and work out side effects and techniques. Thus, I believe they should share those experiences with private community physicians. Our responsibility is to spread knowledge for the benefit of our patients. I look forward to innovations still in the pipeline for glaucoma. We know that IOP is an inconsistent diagnostic, so there are attempts to diagnose the mechanics of the optic nerve head. Here at USC, we are participating in a study evaluating blood flow and the mechanics of the lamina fibrosa, as well as diurnal fluctuations in IOP to see how we can predict glaucoma progression. It s a race to diagnose early, then provide effective treatments without side effects to prevent the loss of vision. We are also working on strategies to validate the mechanics of the optic nerve rather than just the structure, so we can be sure to treat the patients who are most likely to progress. Soon, we will have devices that slowly release medications inside of the eyes, relieving patients of the burden of topical drops. Farther into the future, it would be great to have a stent that can gauge pressure and automatically dilate to maintain pressure where it needs to be. In Demand The demand for glaucoma treatment is large and growing. It will take both glaucoma specialists and comprehensive ophthalmologists to treat this vast number of patients. Training all residents, regardless of future specialty, in the management of glaucoma is essential in my view, as almost all ophthalmologists will be performing some kind of glaucoma surgery in the future. GP DECEMBER 2017 GLAUCOMA PHYSICIAN 29

31 FEATURE ECP Therapy ECP in Refractory Glaucoma Patients How this existing therapy is creating new treatment opportunities for a wider range of patients By Juan Carlos Izquierdo, MD Dr. Izquierdo is the director of glaucoma services for Oftalmo Salud in Lima, Peru. He can be reached at juancarlosizq@gmail.com. We are well aware that the rapidly increasing population of glaucoma patients has generated a surge in the development of new treatments, both pharmaceutical and surgical. This market demand has also incited renewed interest in existing therapies, including endocyclophotocoagulation (ECP). In ECP, we have an excellent treatment modality, and by slightly modifying the treatment technique, the safety profile improves, so it can be used in a wider variety of patients than previously thought. Endoscopic Precision The most unique feature of ECP is the Endo Optiks laser endoscope (Beaver Visitec International), which enables the surgeon to view the ciliary body from the anterior or posterior segment, and apply a precise, visualized laser application. The procedure is highly localized, with little effect outside of the ciliary processes and no damage to the ocular surface. It is gentle, titratable, and repeatable. Refractory Patient Outcomes In a soon-to-be-published study, I evaluated 50 eyes in 39 patients with uncontrolled pressure on maximum medical therapy. Most of the patients were using timolol, dorzolamide, brimonidine, and travoprost. I performed ECP on all 50 eyes, and ECP plus phacoemulsification in eyes in which a cataract was also present. I placed intracameral anesthesia in each eye, followed by viscoelastic in the sulcus, and then performed ECP for a full 360 degrees. At the conclusion of the procedure, I used an intracameral injection of 0.1% triamcinolone to prevent inflammation. I also gave the patients atropine to relax the ciliary muscle and reduce pain. One year following the ECP procedure, patients demonstrated a mean drop in IOP of roughly 35%. Two years following ECP, the mean pressure decrease was more than 40%. Most complications can be avoided with good technique and are transitory if they do occur. In this group, 82% of eyes had no complications, 12% had pupillary membrane, and one eye had a choroidal detachment. These patients were all refractory glaucoma patients on maximum medical therapy and still unable to reach their target IOPs. Following ECP, most patients were able to maintain target IOP with one or two medications. A review of major ECP studies shows that, in primary open angle glaucoma, ECP yields a mean IOP decrease of 7 mmhg, or 31%. In studies of advanced secondary glaucomatous eyes, ECP yields a mean IOP decrease of 18 mmhg, or 50%. 1 I am also conducting a study of 40 eyes with angle closure glaucoma (ACG) who have previously undergone iridotomy with a YAG laser. All 40 eyes received ECP in combination with phacoemulsification and are showing excellent IOP results. We also examined these patients with 30 GLAUCOMA PHYSICIAN DECEMBER 2017

32 anterior segment OCT before and after surgery, and we have seen significant opening of the angles. I hypothesize that our final results will show that this combination of reduced aqueous inflow and increased aqueous outflow will provide very good outcomes in these patients. What Is Proper Technique? Traditional cyclophotocoagulation (CPC) was known to cause destruction of the epithelium, pigment clumping, coagulative necrosis, and destruction of the deeper ciliary stroma. By using a laser and endoscopic system, the ciliary body can be visualized. This eliminates any guesswork related to the location of the anatomy. Initially, it takes time to get used to the endoscopic view. Rather than looking directly at the anatomy via a microscope, you are looking at a monitor. This may make it diffcult to judge distances. I place my endoscope so that I can see a total of six ciliary processes on the monitor. This means that the probe is about 2 mm to 3 mm away from the ciliary processes, a good distance from which to treat. Previously, CPC was performed by treating the ciliary processes until they popped or exploded. However, we have since discovered that this isn t necessary to effectively lower IOP and only complicates recovery by generating excessive inflammation. Maintaining the proper distance and applying 200 to 300 mw of laser energy, you can treat the ciliary processes until they shrink and blanch, stopping prior to the pop. Combining Procedures As shown in many previous studies, including my ongoing study of refractive ACG patients mentioned above, ECP combined with phacoemulsification works very well. 2,3 Not only is it effective at lowering IOP without significantly impacting visual acuity or postoperative complications 3, ECP doesn t noticeably change the refractive outcomes of cataract surgery, either with regard to effective lens position 4 or induced astigmatism. 5 In refractory patients, I find it safe and effective to combine ECP with other minimally invasive glaucoma (MIGS) procedures, such as the Kahook Dual Blade (New World Medical). ECP lowers the production of aqueous, while the dual blade or other MIGS procedures increase aqueous outflow. In ECP, we have an excellent treatment modality, and by slightly modifying the treatment technique, the safety profile improves, so it can be used in a wider variety of patients than previously thought. These glaucoma procedures can be done with or without phacoemulsification, depending on the patient s needs. I find combining a series of less invasive procedures preferable to putting a drainage device in the eye or combining phacoemulsification with trabeculectomy. Patients are much more comfortable with far fewer complications. An Excellent Option With so many new and shiny options in the surgical treatment of glaucoma, it can be easy to skip past those procedures that have been around for a while. ECP should not be pushed to the back of the shelf. It is an extremely flexible approach, and it is safe and effective, so it remains an excellent option to treat many of our glaucoma patients. GP References 1. Kaplowitz K, Kuei A, Klenofsky B, Abazari A, Honkanen R. The use of endoscopic cyclophotocoagulation for moderate to advanced glaucoma. Acta Ophthalmologica. 2015;93(5): Lindfield D, Ritchie RW, Griffiths MF. Phaco-ECP : combined endoscopic cyclophotocoagulation and cataract surgery to augment medical control of glaucoma. BMJ Open. 2012;2:e Francis BA, Berke SJ, Dustin L, Noecker R. Endoscopic cyclophotocoagulation combined with phacoemulsification versus phacoemulsification alone in medically controlled glaucoma. J Cataract Refract Surg. 2014;40(8): Kang S, Luk S, Han H, et al. Refractive outcome of combined phacoemulsification and endoscopic cyclophotocoagulation. Int Ophthalmol. 2017;37(6): Noecker RJ. Combining ECP with laser cataract surgery. Cataract & Refractive Surgery Today; October Available at: articles/2015-oct/combining-ecp-with-laser-cataract-surgery/; last accessed Nov. 7, DECEMBER 2017 GLAUCOMA PHYSICIAN 31

33 FEATURE ECP & MIGS The Significance of ECP in Today s Glaucoma Management A pressure-lowering workhorse emerges as potent pairing with MIGS By Erin Murphy, Contributing Editor In the era of minimally invasive glaucoma surgeries (MIGS), it is important to remember that some would say endocyclophotocoagulation (ECP) was one of the first MIGS procedures. Predating the implants and other approaches used today, it has long been a powerful workhorse for patients with early mild to moderate glaucoma and concomitant cataracts. MIGS procedures have replaced ECP in many of these cases, but ECP still benefits many patients most recently, when used in combination with MIGS. ECP + MIGS Steven R. Sarkisian, Jr., MD, is clinical professor and glaucoma fellowship director at Dean McGee Eye Institute at the University of Oklahoma in Oklahoma City. There, ECP is used for cataract patients who have a history of chronic angle closure, and, as such, newer MIGS offerings would not be the best choice. He also uses ECP for pseudophakic patients who require extra IOP lowering, as well as in some cases in which a tube shunt or trabeculectomy has failed. However, Dr. Sarkisian explains, the sweet spot for ECP in his armamentarium has shifted. Today, I primarily use ECP in combination with MIGS devices and procedures. The combination allows us to improve outflow pathways and reduce aqueous production by delivering laser energy to the ciliary processes. The cumulative effect is much like putting a patient on a beta blocker or a carbonic anhydrase inhibitor as well as a prostaglandin, he says. Dr. Sarkisian performs a variety of combination procedures, each chosen based on the severity of the patient s glaucoma, the type of cataract surgery, and the number of medications the patient is taking preoperatively. For example, if a patient whose pressure is well controlled on one medication has visually significant cataracts, Dr. Sarkisian typically performs cataract surgery with istent (Glaukos); but, if a patient with cataracts has pressures that are uncontrolled on two or three medications, he considers a more aggressive approach that combines cataract, MIGS, and ECP with the Endo Optiks laser endoscope (Beaver Visitec International) even adding Trab 360 (Sight Sciences) as a fourth procedure in some cases. Dr. Sarkisian always performs 360 degrees of ECP to achieve the maximum IOP reduction. He notes that he does not perform ECP in patients who are receiving a premium lens as part of their cataract surgery. My colleagues and I have a large case series on the combination of ECP with cataract surgery and istent, and we have presented this data at national and international meetings, he says. The addition of ECP has improved outcomes in our patients by several millimeters of mercury. I also have been combining ECP with the CyPass Micro-Stent (Alcon) with good results, but I have not yet analyzed my data. 32 GLAUCOMA PHYSICIAN DECEMBER 2017

34 Combining three or four procedures may seem aggressive, Dr. Sarkisian says, but this approach is still less destructive than trabeculectomy, and his results have been very good. We can get patients with advanced glaucoma on three medications, with pressures in the twenties or thirties, down to the low or mid teens with fewer meds and no bleb, he explains. He adds that because the Xen Gel Stent (Allergan) has become available, I m even more comfortable with this approach, because if we still need to decrease pressures, we have a safe way to perform subconjunctival filtration. Clinical Pearls Each element of a combination glaucoma procedure chips away at the IOP. The surgeon must decide how many of those elements are required to reach target pressures. Doctors evaluate their own data and gauge how much they can reduce IOP with cataract surgery, with the addition of a MIGS procedure, and then with the addition of ECP and/or other measures. It is diffcult to say, This combination will lower IOP 6 mmhg, because the higher the pressure is at the start, the bigger drop we might get from any particular procedure, explains Mark Welch, DO, vice chief of ophthalmology and chief of glaucoma at San Antonio Military Center. A patient with pressures in the 20s who has cataract surgery with istent will likely get to the mid to high teens, possibly lower. If my target pressure is in the mid to low teens, then I perform ECP as well as an outflow treatment. I make the same choice for patients who are intolerant of their medications, where adding a second or third procedure will allow them to reduce their medication burden. Dr. Welch points out another reason it is attractive to perform combination cataract- MIGS-ECP procedures: they aren t significantly more traumatic than cataract surgery alone, nor is the duration of surgery too long. In addition, the preoperative and postoperative management of MIGS and ECP are similar to cataract surgery alone, according to Dr. Welch. Patients have a topical antibiotic, topical steroid, and topical NSAID. For ECP, he recommends that surgeons consider adding oral acetazolamide for 1 to 2 days post-op to mitigate any pressure spikes. Additionally, because ECP can cause inflammation up to a week later, he notes that physicians must be fairly aggressive about controlling the inflammatory process. At a minimum, I inject subconjunctival dexamethasone at the end of the case, and, in most cases, I also give intraocular dexamethasone (4 mg/cc with a dose of 0.1 cc to 0.2 cc). For an extensive treatment, perioperative, systemic dexamethasone (2 mg to 8 mg IV) should also be given, along with a post-operative oral steroid burst for 5 to 7 days. According to Dr. Welch, one of the added reasons to control inflammation is that cataract patients expect to emerge from surgery with better vision and a quiet eye. I usually treat 270 degrees of the ciliary processes, painting the whole process anteriorly and posteriorly, Dr. Welch explains. I set the power to 0.1 watts to 0.2 watts and start with the probe about 2 mm from the ciliary processes, so I can see about six processes at once. You want to avoid pops of the tissue by adjusting the power of the treatment or distance of the probe from the target tissue. Careful technique and judicious use of steroids typically lowers IOP without hypotony and also minimizes inflammation. A Winning Combination Drs. Welch and Sarkisian agree that the overall goal behind combining MIGS and ECP is to reach target pressures while maintaining a very high safety profile. With an ever-growing list of alternatives that are much less invasive than trabeculectomy, the potential for combination surgeries is exciting. In this changing MIGS landscape, ECP has emerged as a beneficial way to combine inflow and outflow treatments for complementary outcomes and a cumulative impact on IOP. GP Steven R. Sarkisian, Jr., MD, is clinical professor and glaucoma fellowship director at Dean McGee Eye Institute at the University of Oklahoma, Oklahoma City. He is a paid consultant to BVI Endo Optiks. Mark Welch, DO, is vice chief of ophthalmology and chief of glaucoma at San Antonio Military Center. The views expressed in this article are Dr. Welch s, not those of the U.S. government. DECEMBER 2017 GLAUCOMA PHYSICIAN 33

35 FEATURE Self-monitoring Keeping a Closer Watch on IOP New technologies for frequent self-measurement open a new era in glaucoma care By Desireé Ifft, Contributing Editor Devising a way for IOP to be frequently measured outside of a clinic or lab without the help of a medical professional has long been an objective in the field of glaucoma. And, with a few new options, this concept is now a reality. One device for personal monitoring of IOP is already in clinical use, and a second is FDA-approved but undergoing further evaluation. A third device is approved in Europe and headed for a U.S. pilot study. Personal, a.k.a. self or home, IOP monitoring promises to provide answers to many questions about glaucoma, and is already making a difference in patient care. Questions in Need of Answers Inder Paul Singh, MD, The Eye Centers of Racine and Kenosha in Wisconsin, explains why personal IOP monitoring is important. Right now, patients typically have their IOP measured only one time out of a 24- hour day, one day out of a few months, a few months out of a year, he says. We re missing a true understanding of the actual dynamics of the pressure of the eye and the aqueous outflow system. When a device can record IOP automatically or enable patients to check their own, measurements can be taken frequently throughout the day or night, providing a far more accurate picture of what s going on. Fluctuations in IOP, which are known to occur within a 24-hour period and in different patterns over time, are thought to be associated with progression of the disease and are of the most interest. Knowing a patient s true IOP levels, especially if and when pressure spikes occur, can reveal the need for tighter IOP control through different or more aggressive treatment. In the longer-term, once large amounts of IOP data can be studied, answers to other questions may emerge. For example, Dr. Singh says, This should help explain why some patients glaucoma gets worse despite what seem to be controlled pressures in the offce. We may learn whether everyday activities such as wearing a necktie or doing yoga might raise episcleral venous pressure, which is a factor in the regulation of IOP, and whether some patients are more susceptible to that. Furthermore, as Sanjay G. Asrani, MD, of Duke University Eye Center, North Carolina, points out, While there is consensus that fluctuation in IOP leads to glaucoma progression, we don t know which aspect of the fluctuation is really causing the damage. Is it the peak, the delta, the difference between the trough and the peak, the number of times the peak occurs? Having multiple readings over time will help figure that out. In Practice and in the Pipeline Glaucoma specialists will be hearing more about the following three devices for personal IOP monitoring. Icare HOME tonometer (Icare USA) Patients use the Icare HOME tonometer, cleared by the FDA in March, to take their own IOP measurements, which are stored in the device and retrieved by the doctor via Icare LINK software. No anesthesia is required. Rather than an 34 GLAUCOMA PHYSICIAN DECEMBER 2017

36 Right now, patients typically have their IOP measured only one time out of a 24-hour day, one day out of a few months, a few months out of a year. We re missing a true understanding of the actual dynamics of the pressure of the eye and the aqueous outflow system. Inder Paul Singh, MD, The Eye Centers of Racine and Kenosha in Wisconsin air puff, the tonometer utilizes rebound technology, which has been shown to correlate with Goldmann applanation tonometry (GAT). 1,2 Dr. Asrani sends the device home with patients whose OCT or visual field tests suggest disease progression despite what appear to be on-target IOP measurements in the clinic. (He doesn t use the device for patients with corneas thicker than 590 microns or those with corneal edema or transplants, all of which could interfere with accurate readings.) He asks patients to record their IOP a minimum of three times each day, five times if possible, for 3 weeks. We have found that indeed the pressures are not really controlled, and that s why they re progressing, he says. Using the Icare HOME recently convinced a previously reluctant patient, a working-age, monocular male, to undergo tube surgery. Over several years, his in-clinic IOP measurements had been 11 to 12 mmhg, but visual field testing was showing gradual possible progression. Multiple readings on multiple days with the home tonometer captured pressures reaching into the high teens and low 20s and as high as 23 mmhg in the late evening. Triggerfish (Sensimed) The Triggerfish system consists of a silicone contact lens embedded with a micro-sensor that captures spontaneous circumferential changes at the corneoscleral area. The information transmits wirelessly to an adhesive antenna that is placed around the eye and then through a thin cable to a portable recorder worn by the patient. At the end of a 24-hour recording period, the information is transferred via Bluetooth from the recorder to software on the physician s computer. Although not a direct measure of IOP, the ocular dimensional changes assessed by Triggerfish have been shown to be closely related to IOP curves and associated with the rate of visual field progression in treated glaucomatous eyes. 3 The Triggerfish received FDA approval in 2016, but, rather than launching the product right away, Sensimed is executing a study to confirm its utility in predicting the course of glaucoma progression and to further establish ocular volume change patterns as a standalone biomarker for use in the management and treatment of glaucoma patients. EYEMATE (Implandata Ophthalmic Products GmbH) The EYEMATE is a ring-shaped, implantable, telemetrically powered IOP-sensing microchip that is read by the patient with a handheld mesograph. The measurements, which have shown similar profiles to those of GAT, 4 are transferred wirelessly to a cloud database accessible by the doctor. A version of the EYEMATE that is implanted in the sulcus during cataract surgery received approval in Europe earlier this year. A U.S. pilot study is expected to begin in the second half of The study, which will involve approximately 12 patients and either that implant or a suprachoroidal version that could be implanted without cataract surgery, 5 will evaluate safety and the sensor s correlation with GAT. According to Implandata s Max Ostermeier, The final decision is not made yet, but most probably we would enter the FDA process with the suprachoroidal sensor implant and wait with the intraocular design until we have integrated the sensor into an intraocular lens. continued on page 38 DECEMBER 2017 GLAUCOMA PHYSICIAN 35

37 CODING Offsetting Costs Samples and Free Products What does CMS, FDA, and AMA have to say about them? By Kevin J. Corcoran, COE, CPC, CPMA, FNAO New aqueous drainage assist devices attract a great deal of interest from glaucoma surgeons because they offer alternatives to traditional filtration surgery, tube shunts, and other standard glaucoma procedures. Unfortunately, Medicare reimbursement is not universally available for many new procedures that are described as temporary, emerging technology including many minimally invasive glaucoma surgery (MIGS) devices and as such, have Category III CPT codes. 1 Likewise, other third party payers might not pay for products and services that are too new to be described as standard of care and are, therefore, considered to be experimental or investigational. Within CPT, permanent Category I codes are those that satisfy all of the following criteria. All devices and drugs necessary for performance of the procedure of service have received FDA clearance or approval when such is required for performance of the procedure or service. The procedure or service is performed by many physicians or other qualified healthcare professionals across the United States. The procedure or service is performed with frequency consistent with the intended clinical use (i.e., a service for a common condition should have high volume). The procedure or service is consistent with current medical practice. The clinical effcacy of the procedure or service is documented in literature that meets the requirements set forth in the CPT code-change application. It takes years to meet the threshold for a permanent CPT code and subsequently garner widespread coverage and payment by insurers. In the interim between Category III and Category I designation, beneficiaries are financially responsible for the professional and facility charges associated with noncovered Category III CPT codes. Understandably, there is strong resistance from patients to pay for noncovered items and services, even if the alternative is a procedure that might not be the best for their specific needs. Experience shows that only a small minority of patients will agree to pay thousands of dollars for their own eye care when their insurance refuses to cover it. Safe Handling All manufacturers are keenly aware of this dilemma, and have some sympathy for the patient s plight, as do physicians and healthcare systems. A number of healthcare programs exist to provide charity care for free or at a reduced cost to low-income patients who are uninsured or underinsured. These programs have the support of manufacturers who provide samples to offset the cost of health care. Yet despite all the good intentions, problems can arise when samples aren t handled properly. According to CMS, Many drug and biologic companies provide physicians with free samples physicians may give to patients free of charge. It is legal to give these samples to your patients for free, but it is illegal to sell them. The Federal Government prosecutes physicians for billing Medicare for free samples. If you choose to accept samples, you will need reliable systems in place to safely store the samples and ensure samples remain separate from your commercial stock. 2 In a similar vein, within the Food and Drug Administration, the Prescription Drug Marketing Act bans the sale, purchase, or trade (including the offer to sell, purchase, or trade) of prescription drug samples. 3 CMS also limits the Medicare payment to hospital outpatient departments for device-intensive procedures that include a full or partial credit for the device, which applies to many MIGS procedures. 4 In practice, this frequently occurs during clinical trials of new implants, but it also pertains to replacement devices as well as reduced cost initial implants. Within ambulatory surgery centers (ASCs), claims for reimbursement are usually submitted on a CMS-1500 claim form rather than a UB-04 claim form, so a separate line item for the aqueous drainage assist device with a revenue code is impossible. For 2018, the CMS Final Rule 5 requires the FB modifier along with 36 GLAUCOMA PHYSICIAN DECEMBER 2017

38 The Most Versatile Glaucoma Treatment in Ophthalmology Endoscopic CycloPhotocoagulation (ECP) Mild, moderate and advanced glaucomas Stand-alone or combined with Phaco and MIGS Plateau Iris and other novel uses ECP is an ideal way to address moderately controlled glaucoma and cataract in one procedure. Mr. Philip Bloom MBChB, FRCS(Ed), FRCOphth Western Eye Hospital Hillingdon Hospital London, UK ECP-Plus is an effective treatment for refractory and ultra refractory glaucoma. Our 2 year data shows outstanding sustained IOP lowering and medication reduction. * Brian Francis, MD, MS Doheny Eye Institute Los Angeles, CA USA Combining ECP with a variety of other MIGS procedures allows me to offer a balanced therapy that is tailored to each patient. Nathan Radcliffe, MD Coney Island Hospital NYU Langone Medical Center New York, NY USA beaver-visitec.com *Tan, J.C.H., Francis, B.A., Noecker, R., Uram, M., et. al. Endoscopic Cyclophotocoagulation and Pars Plana Ablation (ECP-Plus) to Treat Refractory Glaucoma. J. Glaucoma, May 14, doi: /ijg. 278

39 CODING Offsetting Costs the applicable Category III code for the procedure when the MIGS device is provided at no cost or full credit, and the FC modifier when the manufacturer provides a partial credit of 50% or more (but less than 100%). 6 CMS would reduce the amount of reimbursement for the ASC facility fee to reflect the no-cost or low-cost MIGS device. AMA Ethical Guidelines In addition to the legal and regulatory prohibitions cited above, the American Medical Association published ethical guidelines for physicians on the use of drugs and devices: 7 Opinion Prescribing and Dispensing Drugs and Devices (1) Physicians should prescribe drugs, devices, and other treatments based solely upon medical considerations and patient need and reasonable expectations of the effectiveness of the drug, device, or other treatment for the particular patient. (2) Physicians may not accept any kind of payment or compensation from a drug company or device manufacturer for prescribing its products. Furthermore, physicians should not be influenced in the prescribing of drugs, devices, or appliances by a direct or indirect financial interest in a firm or other supplier, regardless of whether the firm is a manufacturer, distributor, wholesaler, or repackager of the products involved. (3) A third party s offer to indemnify a physician for lawsuits arising from the physician s prescription or use of the third party s drug, device, or other product, introduces inappropriate incentives into medical decision making. Such offers, regardless of their limitations, therefore constitute unacceptable gifts. This does not address contractual assignments of liability between employers or in research arrangements, nor does it address government indemnification plans. A Winning Situation Samples of drugs and implantable devices are a useful part of charity care, especially for services not covered by insurance. Because they are free, there is no cost to reimburse. Providers are prohibited from obtaining payment for samples. Ethical considerations complement the legal and regulatory instructions. GP References 1. Corcoran KJ. Coding for Minimally Invasive Glaucoma Surgery. Glaucoma Physician; March Avoiding Medicare Fraud and Abuse: A Roadmap for Physicians. Centers for Medicare & Medicaid Services. Avilable online: Network-MLN/MLNProducts/Downloads/Avoiding_Medicare_ FandA_Physicians_FactSheet_ pdf. Last accessed Oct, 23, FDA Compliance Program Guidance Manual, Chapter 56, Drug Quality Assurance. Program Available online: GuidanceComplianceRegulatoryInformation/UCM pdf. Last accessed Oct. 23, CMS Manual System, Pub Medicare Claims Processing, Transmittal Available online: Regulations-and-Guidance/Guidance/Transmittals/Downloads/ R3181CP.pdf. Last accessed Oct. 23, Federal Register. Medicare Program: Hospital Outpatient Prospective Payment and Ambulatory Surgical Center Payment Systems and Quality Reporting Programs. Available online at last accessed Nov. 2, Government Publishing Office. Federal Register Vol 82 No 138, page July 20, Available online: gov/fdsys/pkg/fr /content-detail.html. Last accessed Oct. 23, American Medical Association. AMA Journal of Ethics. November Available online: org/2010/11/coet1-1011html. Last accessed Oct. 23, Kevin J. Corcoran, COE, CPC, CPMA, FNAO, is president and co-owner of Corcoran Consulting Group. continued from Self-monitoring page 35 A pivotal study for obtaining FDA approval would follow in Another Piece of the Puzzle Dr. Singh says doctors will be watching closely as technologies for personal monitoring of IOP mature, with particular interest in their accuracy and reliability. Education will be key, too, he says, because patients will need to understand that self-monitoring doesn t replace doctor visits. That said, he continues, the information to be obtained from such devices will give us another important piece of the glaucoma puzzle, a better understanding of disease progression and how best to treat each patient. Dr. Asrani agrees, adding that this group of technologies will open a completely new era in glaucoma management. GP References 1. Termühlen J, Mihailovic N, Alnawaiseh M, Dietlein TS, Rosentreter A. Accuracy of measurements with the icare HOME rebound tonometer. J Glaucoma. 2016;25(6): Asrani S, Chatterjee A, Wallace DK, Santiago-Turla C, Stinnett S. Evaluation of the ICare rebound tonometer as a home intraocular pressure monitoring device. J Glaucoma. 2011;20(2): De Moraes CG, Jasien JV, Simon-Zoula S, Liebmann JM, Ritch R. Visual field change and 24-hour IOP-related profile with a contact lens sensor in treated glaucoma patients. Ophthalmology. 2016;123(4): Koutsonas A, Walter P, Roessler G, Plange N. Implantation of a novel telemetric intraocular pressure sensor in patients with glaucoma (ARGOS study): 1-year results. Invest Ophthalmol Vis Sci Jan 22;56(2): Mariacher S, Ebner M, Januschowski K, Hurst J, Schnichels S, Szurman P. Investigation of a novel implantable suprachoroidal pressure transducer for telemetric intraocular pressure monitoring. Exp Eye Res Oct;151: GLAUCOMA PHYSICIAN DECEMBER 2017

40 Be open. Kahook Dual Blade Perform without limits. Performing minimally invasive procedures shouldn t be limited to cataract surgery. The Kahook Dual Blade s intuitive design enables safe and precise excision of trabecular meshwork to access multiple collector channels and maintain natural outflow, anytime it is needed. Learn how the Kahook Dual Blade lets you perform without limits. Visit KDBcert.com 2017 New World Medical, Inc. All rights reserved. New World Medical, Kahook, and Kahook Dual Blade are registered trademarks of New World Medical, Inc.

41 WELCOME TO GENERATION XEN A NEW ERA IN THE SURGICAL TREATMENT OF REFRACTORY GLAUCOMA - The first ab-interno approach to create a new pathway for aqueous flow from the anterior chamber to the subconjunctival space 1 - Minimally invasive a 6-mm gel stent designed to be implanted through a small corneal incision 1,2 - Established effectiveness and safety 1 Minimally Invasive. Powerfully Effective. 1,2 INDICATIONS The XEN Glaucoma Treatment System (XEN 45 Gel Stent preloaded into a XEN Injector) is indicated for the management of refractory glaucomas, including cases where previous surgical treatment has failed, cases of primary open-angle glaucoma, and pseudoexfoliative or pigmentary glaucoma with open angles that are unresponsive to maximum tolerated medical therapy. IMPORTANT SAFETY INFORMATION CONTRAINDICATIONS XEN Gel Stent is contraindicated in angle-closure glaucoma where angle has not been surgically opened, previous glaucoma shunt/valve or conjunctival scarring/pathologies in the target quadrant, active infl ammation, active iris neovascularization, anterior chamber intraocular lens, intraocular silicone oil, and vitreous in the anterior chamber. WARNINGS XEN Gel Stent complications may include choroidal effusion, hyphema, hypotony, implant migration, implant exposure, wound leak, need for secondary surgical intervention, and intraocular surgery complications. Safety and effectiveness in neovascular, congenital, and infantile glaucoma has not been established. Avoid digital pressure following implantation of the XEN Gel Stent to avoid the potential for implant damage. PRECAUTIONS Examine the XEN Gel Stent and XEN Injector in the operating room prior to use. Monitor intraocular pressure (IOP) postoperatively and if not adequately maintained, manage appropriately. Stop the procedure immediately if increased resistance is observed during implantation and use a new XEN system. Safety and effectiveness of more than a single implanted XEN Gel Stent has not been studied. ADVERSE EVENTS The most common postoperative adverse events included best-corrected visual acuity loss of 2 lines ( 30 days 15.4%; > 30 days 10.8%; 12 months 6.2%), hypotony IOP < 6 mm Hg at any time (24.6%; no clinically signifi cant consequences were associated, no cases of persistent hypotony, and no surgical intervention was required), IOP increase 10 mm Hg from baseline (21.5%), and needling procedure (32.3%). Caution: Federal law restricts this device to sale by or on the order of a licensed physician. For the full Directions for Use, please visit or call Please call to report an adverse event. 1. XEN Directions for Use. 2. Data on fi le, Allergan, Allergan. All rights reserved. XEN is a registered trademark of AqueSys, Inc., an Allergan affiliate. Allergan and its design are trademarks of Allergan, Inc. XenGelStent.com XEN103680_v2 06/