Wet AMD. dept headline headline. headline headline. From Start to Finish

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1 Wet AMD dept headline headline From Start to Finish headline headline Deck Anti-VEGF therapy for patients with wet AMD is a standard of care that saves sight for thousands of people each year. dept byline But how do you treat this disease over the long haul? New Retina MD invited five retina experts to comment on the spectrum of wet AMD management, beginning with initial observations and treatment, and ending with a frank discussion about weighing treatment burden against potential benefits. 24 NEW RETINA MD. 2015/ISSUE 3

2 Treatment of Patients With Newly Diagnosed Wet AMD By Frank F. Tsai, MD; and Eric Nudleman, MD, PhD The development of anti-vegf agents has dramatically changed the conversation about treatment for wet age-related macular degeneration (AMD). Current treatments are so effective that disciform scarring and severe central vision loss are now uncommon in patients with wet AMD. Although retina specialists are armed with these excellent drugs, there are still active debates regarding choice of drug, treatment protocols, and long-term effects of chronic anti-vegf suppression. In this article, we discuss some of the current perspectives on the management of patients with newly diagnosed wet AMD. WHEN TO BEGIN THERAPY In patients who are symptomatic or show measurable change in vision, there is little debate about the benefit of initiating anti-vegf therapy. The landmark ANCHOR and MARINA trials demonstrated that approximately 90% of patients treated with monthly ranibizumab (Lucentis, Genentech) for wet AMD lost fewer than 15 letters over 2 years. 1,2 Similar outcomes were seen in patients treated with aflibercept (Eylea, Regeneron) in the VIEW 1 and VIEW 2 studies. 3 However, in patients who are minimally symptomatic or have excellent visual acuity, no strong consensus on treatment protocol exists in the retina community. Some retina specialists feel monitoring is appropriate for patients with little disease activity or those who are asymptomatic. Natural history data show that a subset of patients with choroidal neovascularization (CNV) may have vision that remains stable over time with observation alone. 4 Conversely, other retina specialists believe it is prudent to treat these cases promptly before significant vision loss or central involvement occurs and before disease progression results in irreversible vision loss due to occurrences such as large hemorrhage. Fellow eye status may also influence the defining of a threshold for treatment initiation. One may be more likely to initiate treatment in a monocular patient in whom the fellow eye was lost to a disciform scar (Figure 1). These factors should be discussed in detail with the patient and his or her family members to arrive at an informed decision. When the decision to begin treatment is made, it should be initiated as soon as possible. In addition to optical coherence tomography (OCT) imaging, baseline fluorescein angiography (FA) and fundus autofluorescence photos can be helpful in ensuring accurate diagnosis and following disease progression. Practically speaking, it may not be feasible to complete the examination and imaging and initiate treatment on the same visit. If insurance issues, patients schedules, or photography preclude completing the necessary studies in a single visit, it is reasonable to follow the protocol guidelines of the CATT trial, and initiate treatment within 1 week of the first visit. 5 SELECTING A TREATMENT AGENT The main factors when choosing an anti-vegf agent for the treatment of a patient with wet AMD are efficacy, dosing, safety, and cost. In terms of efficacy, the results from the CATT and IVAN studies compared ranibizumab with bevacizumab (Avastin, Genentech) for treatment of wet AMD and demonstrated equivalent visual outcomes 2015/ISSUE 3. NEW RETINA MD 25

3 Feature Story A B F G C D E H Figure 1. Presentation and management of new-onset exudative AMD. The patient is a 93-year-old woman who presented with new-onset decreased vision in the left eye for 3 weeks. She has had poor vision in the right eye for several years. Color fundus photograph of the right eye with a large disciform scar (A), and left eye showing drusen, retinal pigment epithelium atrophy, and thin subretinal hemorrhage surrounding a CNV membrane (B). FA of the left eye at presentation, showing early (C), mid (D), and late (E) frames, and demonstrating leakage from the CNV. OCT through the CNV at presentation, showing adjacent subretinal fluid, intraretinal fluid, and subretinal hyperreflective material (F). OCT scan 1 month following treatment with intravitreal bevacizumab, resulting in regression of the CNV and improvement in exudation, as well as visual acuity (G). OCT following 3 monthly injections of bevacizumab. The patient has been maintained on monthly injections. The macula has remained dry, with stable subretinal hyperreflective material and visual acuity for 6 months (H). in patients treated with either agent.5,6 Similarly, the VIEW 1 and VIEW 2 studies compared ranibizumab and aflibercept, and found aflibercept to be noninferior to ranibizumab for treatment of wet AMD.3 The VIEW 1 and VIEW 2 studies also evaluated four treatment regimens: 0.5 mg ranibizumab monthly, 0.5 mg aflibercept monthly, 2.0 mg aflibercept monthly, and 2.0 mg aflibercept every 2 months after three monthly loading doses of 2.0 mg aflibercept. The study concluded that outcomes with aflibercept dosed every 2 months were clinically equivalent to the other dosing regimens.3 Based on these results, some providers either initiate treatment with aflibercept or attempt to switch agents in an effort to extend treatment intervals. Often, the primary factor in selecting an anti-vegf agent is insurance coverage. Some providers require that physicians initiate treatment with bevacizumab and demonstrate failure prior to using other anti-vegf therapies.7 26 NEW RETINA MD. 2015/ISSUE 3 However, changes in compounding pharmacy regulations have restricted access to bevacizumab in many states. Resolving this dilemma and ensuring safe and reliable availability of all drugs has been an ongoing effort for our leadership in the major retina societies. COUNSELING PATIENTS WITH WET AMD When discussing wet AMD treatment options with patients, it is important to convey to them that although effective therapies are available, there is no cure for their disease. It is also important to emphasize from the beginning that both eyes must be closely followed. Monitoring the fellow eye is crucial, particularly if it has good vision and has not yet been affected by wet AMD. Finally, it is important to educate patients on the modifiable risk factors of AMD such as smoking, AREDS2 supplementation, and healthy diet, as well as the need for frequent monocular self-testing and routine follow-up.8

4 INJECTION PROTOCOLS Injection protocols must be tailored to individual patients. Typically, retina specialists will start by treating a patient monthly until the macula is dry. After this is achieved, it is important to have a discussion regarding monthly, treat-and-extend (TAE), or as-needed (PRN) treatment regimens. These discussions should include several key points. Clinical trial data have demonstrated that visual acuity tends to be slightly better with monthly treatment versus PRN treatment. 5 CATT data showed the difference in mean visual acuity improvement for patients treated by a PRN regimen compared with a monthly regimen was a loss of 2.4 letters. 5 However, the cost and time required for monthly injections can result in a significant burden for the patient and the physician. Perhaps not surprisingly, a TAE protocol has become the most utilized treatment strategy in the United States, 9 although level 1 evidence for how it compares with monthly and PRN treatments is not yet available. 10 TAE, as described by the LUCAS TAE protocol, involves treating the patient monthly until inactive disease is achieved, then gradually extending treatment intervals by 2 weeks per visit, up to a maximum of 12 weeks. If recurrent disease appears, the treatment interval is decreased by 2 weeks at a time. 11 It should be noted that the term treat-and-extend is often used loosely, and many employ a model closer to PRN-and-extend. AMD MANAGEMENT WITH LASER Although one could make the argument for laser photocoagulation of small CNV away from the perifoveal region or for patients unwilling or unable to receive anti-vegf or photodynamic therapy, these cases are rare. Nevertheless, in such cases, it would be particularly important to obtain FA in order to properly characterize the lesion and ensure adequate treatment, as previous studies have shown laser to be most effective for well-defined lesions not involving the fovea. 12 Although laser may treat small CNV and obviate the need for frequent intravitreal injections, it does not prevent the development of new CNV. EARLY STEPS Regardless of how a retina specialist decides to treat a patient with newly diagnosed wet AMD, having a conversation to educate patients on how to best monitor and mitigate their disease may yield high dividends. Deciding on the treatment regimen should occur after macular dryness is achieved, but making the patient aware of the coming treatment burden will prepare them for the reality of their situation: that wet AMD management is a long-term process; that successful disease control depends (to a degree) on patient compliance; and that although no cure for wet AMD exists, retina specialists and patients have a number of pharmacologic options to reduce the likelihood of future visual loss and, in some cases, help patients regain vision. WHAT S NEXT? Unfortunately for our patients, these early visits are often the first in a series of year-round examinations. In the next part of this feature, Carl Regillo, MD, discusses how retina specialists can calculate the best treatment models for their patients. Eric Nudleman, MD, PhD, is an assistant clinical professor of ophthalmology at the Shiley Eye Institute and Jacobs Retina Center, University of California, San Diego, in La Jolla, Calif. He has no relevant financial disclosures. Dr. Nudleman may be reached at or enudleman@ucsd.edu. Frank F. Tsai, MD, is a second-year fellow at the Shiley Eye Institute and Jacobs Retina Center, University of California, San Diego, in La Jolla, Calif. He has no relevant financial disclosures. Dr. Tsai may be reached at fftsai@ucsd.edu. 1. Brown DM, Michels M, Kaiser PK, et al; ANCHOR Study Group. Ranibizumab versus verteporfin photodynamic therapy for neovascular age-related macular degeneration: two-year results of the ANCHOR study. Ophthalmology. 2009;116(1):57-65.e Rosenfeld PJ, Brown DM, Heier JS, et al; MARINA Study Group. Ranibizumab for neovascular age-related macular degeneration. N Engl J Med. 2006;355(14): Schmidt-Erfurth U, Kaiser PK, Korobelnik JF, et al. Intravitreal aflibercept injection for neovascular age-related macular degeneration: ninety-six-week results of the VIEW studies. Ophthalmology. 2014;121(1): Blinder KJ, Bradley S, Bressler NM, et al. Effect of lesion size, visual acuity, and lesion composition on visual acuity change with and without verteporfin therapy for choroidal neovascularization secondary to age-related macular degeneration: TAP and VIP report no. 1. Am J Ophthalmol. 2003;136(3): Martin DF, Maguire MG, Fine SL, et al; CATT Research Group. Ranibizumab and bevacizumab for treatment of neovascular age-related macular degeneration: two-year results. Ophthalmology. 2012;119(7): Chakravarthy U, Harding SP, Rogers CA, et al; IVAN Study Investigators. Ranibizumab versus bevacizumab to treat neovascular age-related macular degeneration: one-year findings from the IVAN randomized trial. Ophthalmology. 2012;119(7): American Society of Retina Specialists. Buyer Beware: Humana s Step Therapy Policy Blocks Patient Access to FDA-Approved Drugs American Academy of Ophthalmology Retina/Vitreous Panel. Preferred Practice Pattern Guidelines. Age-Related Macular Degeneration. San Francisco, CA: American Academy of Ophthalmology American Society of Retina Specialists. Global Trends in Retina Survey. Chicago, IL Wykoff CC. Treat & extend treatment with 0.5 mg ranibizumab vs monthly treatment with 0.5 mg ranibizumab (T-REX). ClinicalTrials.gov. clinicaltrials.gov/ct2/show/nct Berg K, Pedersen TR, Sandvik L, Bragadottir R. Comparison of ranibizumab and bevacizumab for neovascular age-related macular degeneration according to LUCAS treat-and-extend protocol. Ophthalmology. 2015;122(1): Argon laser photocoagulation for neovascular maculopathy. Five-year results from randomized clinical trials. Macular Photocoagulation Study Group. Arch Ophthalmol. 1991;109(8): /ISSUE 3. NEW RETINA MD 27

5 Optimizing Wet AMD Treatment Over the Long Haul By Carl Regillo, MD Wet age-related macular degeneration (AMD) treatment starts with frequent (ie, monthly) regular intravitreal injections of anti-vegf agents with the goal of drying the macula. Dryness is usually determined by optical coherence tomography (OCT) imaging and fundus examination. For most patients, drying the macula will translate into some degree of visual improvement, the degree of which may be limited by a number of variables, such as preexisting dry degenerative maculopathy or potential permanent damage to the retinal pigment epithelium (RPE) and neurosensory retina by the invading choroidal neovascularization (CNV). Frequently, retina specialists can create an exudation-free macula (determined by OCT scans) with several injections of an anti-vegf agent during the induction phase of therapy. INDUCTION PHASE All three pan-vegf-a blockers available in practice bevacizumab (Avastin, Genentech), ranibizumab (Lucentis, Genentech), and aflibercept (Eylea, Regeneron) work well at drying the macula, although some efficacy differences may be seen in patients with particular exudative scenarios such as pigment epithelial detachment. If a retina specialist does not see a completely dry macula or observes no continued improvement in exudative signs after three to four monthly treatments, he or she should consider switching to another anti-vegf agent. Although complete resolution of exudation is ideal, it may not be possible in all cases. Residual exudative signs, such as the presence of subretinal fluid or sub-rpe fluid, may or may not be well tolerated by the patient. After vision improvement plateaus during the induction phase, the retina specialist s priority shifts from improving vision to maintaining visual gains. This is achieved by keeping the macula as dry as possible while minimizing CNV growth. MAINTENANCE PHASE During the maintenance phase of therapy, retina specialists face the challenge of optimizing visual outcomes. It is important to keep in mind that anti-vegf therapy does not cure wet AMD; thus, therapy will be needed indefinitely. The ideal maintenance treatment regimen is unknown, and the ideal anti-vegf injection regimen may differ for each patient. As with many treatments in medicine, the best course of therapy for a given patient is function of safety, efficacy, and burden. Retina specialists may choose one of several treatment regimens for patients with wet AMD. A continuous, fixedinterval approach could be continued by injecting a patient every 1 to 2 months, but this is rarely practiced. Such a routine regimen amounts to potential overtreatment in many patients, resulting in increased treatment burden as well as ocular and systemic risks. Ocular risks include an increased cumulative endophthalmitis rate; sustained, elevated intraocular pressure directly correlated with the number of intravitreal injections; and possible promotion of geographic atrophy (GA). (Note that promotion of GA is not a proven side effect of anti-vegf therapy.) Systemic risks include transient VEGF suppression following intravitreal injections, which could theoretically put a patient at increased risk of hemorrhage or thromboembolic events. To date, such events have not been shown to occur to a statistically significant degree in clinical trials, but it remains a possible side effect, particularly for patients at high risk for stroke. 28 NEW RETINA MD. 2015/ISSUE 3

6 In addition to being a cost-effective option, individualized therapy minimizes side effects and maximizes safety. Individualized therapy with an anti-vegf agent during the maintenance phase of therapy employs either an as-needed or pro re nata (PRN) approach or a treat-and-extend (TAE) approach. PRN Treatment During PRN treatment, the eye is monitored closely after the macula is confirmed to be dry, and treatment occurs only when there are signs of recurrent exudation. Although this approach minimizes overtreatment, it requires frequent monitoring, thus sustaining the burden of frequent office visits. Furthermore, PRN therapy may not provide the highest likelihood of sustaining visual gains achieved during the induction phase. Even with close monitoring, the best available imaging techniques, and a zero tolerance for any signs of recurrent exudation, large-scale comparative clinical trials such as CATT and IVAN indicate that, on average, this approach did not control the disease as well over time compared with monthly injection regimens. 1,2 Also, the data from these studies indicate that continuous treatment, compared with PRN treatment, resulted in greater retention of visual acuity improvements achieved during the induction phase. The issue with a PRN regimen in this setting is that it allows for recurrences of exudation before retreatment. Multiple recurrences will likely lead to significant disease progression (ie, CNV growth) with corresponding vision loss. TAE Treatment Many retina specialists believe that the TAE regimen combines the advantages of PRN and monthly regimens, allowing for a high level of disease control and a reduced treatment burden. Approximately 75% of US retina specialists treating wet AMD routinely use TAE regimens. 3 TAE therapy can be considered both continuous and individualized therapy because treatment is performed at every patient encounter, and follow-up and treatment intervals are adjusted for each patient. These adjustments aim to maintain a dry macula and minimize recurrences, thereby maximizing the visual gains achieved during the induction phase. Although there are no available clinical trial data that directly compare TAE with the monthly and PRN approaches, all published studies to date, both retrospective and prospective, show consistent, positive visual outcomes from TAE regimens. These data also show a reduction in the number of intravitreal injections and office visits compared with the other approaches. Additionally, visual results for patients undergoing TAE regimens appear to be similar to those seen in trials examining patients undergoing monthly regimens. Recently published studies indicate that visual acuity gains that occur during the induction phase are wellsustained through 3 years of follow-up, something studies with patients assigned to PRN regimens have yet to show. 4,5 PULLING IT ALL TOGETHER Retina specialists should keep in mind that treatment regimens used in the maintenance phase are not mutually exclusive and that a combination of approaches may be necessary to safely and cost-effectively achieve the best results for a particular patient. Regardless of the specific treatment regimen used, the goals and objectives are the same: Use just enough anti-vegf agent to keep the macula as dry as possible and prevent vision loss secondary to CNV. Unfortunately, vision losses may still occur in patients undergoing long-term treatment despite good control of CNV, as progression of dry AMD a disease for which retina specialists have no effective treatment could erode visual gains achieved during the induction phase. BUT HOW LONG CAN IT LAST? Let s face it: Our patients with AMD are elderly, and the likelihood that they face nonophthalmic health problems grows as they age, further intensifying treatment burden. In the next article in this series, Rishi P. Singh, MD, offers tips on managing patients with AMD who have been treated for several years. Also, David Boyer, MD, reviews a surgical option and a pipeline drug that may give patients with GA hope of maintaining a nondependent lifestyle. Carl Regillo, MD, is director of the retina service at Wills Eye Hospital and is a professor of ophthalmology at Thomas Jefferson University, both in Philadelphia. He receives consulting and research grant support from Genentech, Regeneron, Allergan, and Novartis. Dr. Regillo may be reached at cregillo@midatlanticretina.com. 1. Martin DF, Maguire MG, Ying GS, et al; The CATT Research Group. Ranibizumab and bevacizumab for neovascular age-related macular degeneration. N Engl J Med. 2011;364(20): Chakravarthy U, Harding SP, Rogers CA, et al; IVAN Study Investigators. Ranibizumab versus bevacizumab to treat neovascular age-related macular degeneration: one-year findings from the IVAN randomized trial. Ophthalmology. 2012;119(7): American Society of Retina Specialists preferences and trends survey. Presented at: The American Society of Retina Specialists annual meeting; August 24-28, 2013; Ontario, Canada. 4. Rayess N, Houston SK 3rd, Gupta OP, et al. Treatment outcomes after 3 years in neovascular age-related macular degeneration using a treat-and-extend regimen. Am J Ophthalmol. 2015;159(1):3-8.e1. 5. Arnold JJ, Campain A, Barthelmes D, et al. Two-year outcomes of treat and extend intravitreal therapy for neovascular age-related macular degeneration. Ophthalmology. 2015;122(6): /ISSUE 3. NEW RETINA MD 29

7 Strategies for Managing Late-Stage Wet AMD By Rishi P. Singh, MD The US Food and Drug Administration (FDA) approved ranibizumab (Lucentis, Genentech) for the treatment of wet age-related macular degeneration (AMD) in Assuming some of the patients enrolled in phase 3 ANCHOR and MARINA trials have continuously received treatment with ranibizumab, a segment of the population has received anti-vegf therapy for wet AMD for more than a decade. LONG-TERM RESULTS APPEAR GREAT I have been impressed with the durability of treatment in some patients with wet AMD. Many of the patients I started injecting in 2006 followed me from fellowship to practice and have maintained good vision. Those who have lost vision in one eye during the course of anti-vegf therapy have decided on a mandated treatment approach in the fellow eye, but fortunately, only a few of my patients have lost vision to this degree. Those willing to undergo years of intravitreal injections understand the importance of constant treatment and monitoring. It is important for retina specialists to consider both anatomy and function during treatment. Frequently, subretinal fluid volume fluctuates from visit to visit, despite no change in visual acuity. Although retina doctors generally treat toward functional vision, it is important to remember that anatomic changes could have long-term consequences if not addressed during therapy. UNTIL THEY DON T Some patients who have undergone years of anti-vegf therapy for wet AMD will begin to tire of the constant need for injections, the vision fluctuations, or the inability to improve despite multiple injections. With patients, I emphasize the importance of monitoring and maintenance, and advise that they continue Amsler grid evaluations at home. Before these patients leave my office, I offer them a piece of hope by explaining that emerging therapies such as sustained delivery or drugs with different mechanisms of action grow closer to clinical availability each day, and that they may benefit from some of these upon FDA approval. Although these options are unlikely to see the market for 3 to 5 years, I explain that the potentials for therapy are on the horizon. There has been speculation of a causal relationship between duration of anti-vegf exposure and geographic atrophy (GA) development. To test this hypothesis, you would have to find an untreated wet AMD cohort and follow them over time. Unfortunately, no untreated cohort of patients exists to lend definitive data to the claim that exposure to anti-vegf leads to GA progression, and it seems likely that GA naturally occurs during the aging process. Remember: The choroid thins with age, and retinal pigment epithelium cells and the outer retina are dependent on choroidal circulation for nutrients, and that alone may be the reason for this finding. Until we have a definitive study to link the two, or an alterative to anti-vegf treatment, it is a moot point whether exposure to anti-vegf agents induces GA. As responsible physicians, retina doctors want to know if they are potentially harming patients by treating them for wet AMD. That said, no retina doctor would forgo the only FDA-approved pathway to treating wet AMD out of fear of a heightened risk for GA progression. At this moment, the benefits of anti-vegf therapy greatly outweigh the risk of possibly promoting GA. IT TAKES A TEAM OF SPECIALISTS Some of my patients with late-stage AMD benefit from consultation with other vision experts. I generally refer such patients to the Cleveland Sight Center, which arranges for patients with low vision to meet with optometrists who offer refractive options such as glasses or custom hand magnifiers to improve visual acuity. Patients may also meet with low vision specialists at this location. Although my patients are frustrated that they have reached a point where they have to seek help 30 NEW RETINA MD. 2015/ISSUE 3

8 THE CUTTING EDGE OF END-STAGE AMD TREATMENT By David S. Boyer, MD Our options for treating patients with end-stage dry age-related macular degeneration (AMD) are limited. Thanks to advances in both anterior and posterior segment technology, retina specialists have a surgical option to recommend, and yet another surgical option may be on its way. Plus, a pharmacologic option is currently undergoing evaluation in phase 3 clinical trials. Based on results from two studies (IMT-002-LTM and IMT-002- LTME) that followed patients with end-stage AMD who received the Implantable Miniature Telescope (IMT; VisionCare), the US Food and Drug Administration (FDA) recently expanded approval for the device. The IMT s label is now indicated for patients 65 and older; the former label indicated the device for patients 75 and older. Results of a study that followed patients with the IMT for 60 months found that patients younger than 75 years fared better than those over 75 years. 1 Because the IMT is a surgical solution to end-stage AMD, patient selection is key. Patients must be motivated to work with low vision rehabilitation specialists to learn how to live with their new vision. Clinically, patients must have retinal findings of geographic atrophy (GA) or disciform scarring with foveal involvement and must be phakic in at least one eye. Another surgical option may soon be available for end-stage dry AMD patients. The Argus II retinal prosthesis (Second Sight Medical Products) was recently implanted in a patient with dry AMD. The device was activated 2 weeks after implantation, and preliminary reports indicate that the patient has demonstrated some useful vision. A study enrolling five patients with late-stage dry AMD will assess the device s safety and efficacy. 2 The Argus II is approved in the United States for use in patients with retinitis pigmentosa and in the European Union for patients with outer retinal degeneration. It is not, however, indicated for dry AMD in either location. Following positive results from the phase 2 MAHALO study, researchers have begun investigating lampalizumab (Genentech/ Roche) in patients with GA. Researchers are enrolling patients in the Chroma and Spectri trials, a pair of parallel phase 3 studies designed to evaluate safety and efficacy of lampalizumab in patients with GA. At 18 months in MAHALO, patients with GA showed a 20% reduction in GA lesion progression after monthly lampalizumab treatments compared with sham. 3 Patients with the complement factor I (CFI) genetic biomarker fared better than patients without the biomarker in MAHALO, showing a 44% reduction in GA lesion size. The Chroma and Spectri studies will investigate whether patients with the CFI biomarker respond better to treatment than patients without the biomarker. n David S. Boyer, MD, is a clinical professor of ophthalmology at the University of Southern California Keck School of Medicine in Los Angeles. He is a consultant to Genentech, Roche, VisionCare, and Ophthotec. Dr. Boyer may be reached at or vitdoc@aol.com. 1. Boyer D, Freund KB, Regillo C, et al. Long-term (60-month) results for the implantable miniature telescope: efficacy and safety outcomes stratified by age in patients with end-stage age-related macular degeneration. Clin Ophthalmol. 2015;9: Second Sight announces first age-related macular degeneration patient receives the Argus II retinal prosthesis system as part of groundbreaking study [press release]. Sylmar, CA: Second Sight; July 22, Regillo CD. Lampalizumab (anti-factor D) in patients with geography atrophy: the MAHALO phase 2 results. Paper presented at: American Academy of Ophthalmology 2013 Annual Meeting; November 16-19, 2013; New Orleans, LA. outside of my office, they are satisfied with the quality-of-life gains that follow consultations with other vision specialists. DISCONTINUING THERAPY As if failing vision weren t enough, treatment burden frequently contributes to the encumbrance associated with wet AMD progression. Patients on the better side of the end-stage AMD visual acuity spectrum (ie, those with visual acuities between 20/100 and 20/200) should be advised that keeping the macula dry leaves open the possibility of improvement or relief via yet-to-be-approved therapeutic options. For those on the worse end of the end-stage AMD visual acuity spectrum (ie, those with visual acuities of counting fingers or worse), I tend to have a conversation about discontinuing treatment if they find that the burden of anti-vegf therapy outweighs the potential benefits. Some of these patients wish to continue therapy; others feel that the inconvenience at their particular stage in life is too great. Discontinuing therapy is not an easy decision to make, but sometimes, given quality-of-life considerations, a retina specialist understands a patient s desire to eliminate the burden of routine intravitreal injection therapy. n Rishi P. Singh, MD, is a staff physician at Cole Eye Institute, Cleveland Clinic, medical director of the clinical systems office in Cleveland Clinic, and an assistant professor of ophthalmology at Case Western Reserve University, all in Cleveland. He is a consultant for Genentech, Regeneron, Alcon, and Shire. Dr. Singh may be reached at drrishisingh@gmail.com. 2015/ISSUE 3. NEW RETINA MD 31