December 2015




Finding a cure for AMD the geographic atrophy way

by Matt Young and Gloria D. Gamat EyeWorld Contributing Writers


Late stage atrophic AMD from a 75-year-old patient of German descent Source: Claudia von Strachwitz, MD

Now that wet AMD is being addressed, geographic atrophy may be the next frontier

The usual suspects in perpetrating vision loss in patients with age-related macular degeneration (AMD) are choroidal neovascularizations (CNV). But thats not a complete lineup. More recent studies have shown severe vision loss in approximately 35% of late-stage AMD cases (and still within the dry spectrum of AMD) is attributable to another monster: geographic atrophy (GA).

Atrophy-AMD connection

GA is the hallmark of dry AMD. The progression of geographic atrophy causes the most vision loss in the dry form of the disease, said Andrew M. Schimel, MD, surgical and medical vitreoretinal specialist, Center for Excellence in Eye Care, Miami, and assistant professor of ophthalmology, Florida International University, Wertheim College of Medicine, Miami. Consequently, experts have started paying more attention to this pathway to fully understand AMD.

The treatment of geographic atrophy is the holy grail for macular degeneration at this point, as the majority of patients with macular degeneration have the dry type, Dr. Schimel said. Although clinical trials are underway to evaluate therapies for GA, there is no definite (or approved) treatment proven to halt or slow the progression of GA. Currently, potential therapeutic agents for GA such as lampalizumab (Roche, Basel, Switzerland) and GSK933776 (GlaxoSmithKline, London) are in phase 3 and phase 2 clinical trials, respectively. While such clinical trials are underway, theres a greater need for a procedure to monitor and predict the progression of GA that really works. Korean researchers have recently reported in the journal Eye that patients at high risk for GA progression can be identified using a modified fundus camera (mFC), a commonly available method capable of providing additional information that would help predict the progression of GA. FAF (fundus autofluorescence) imaging using mFC is a good noninvasive tool for visualizing variable FAF patterns in vivo, reported Sung Pyo Park, MD, Department of Ophthalmology, Kangdong Sacred Heart Hospital, Hallym University Medical Center, Seoul, Korea, and colleagues. The diffuse and banded FAF pattern on baseline FAF images indicates a high risk of GA progression compared with other patterns in patients with AMD. On the other hand, German researchers who evaluated the safety and efficacy of AL-8309B (tandospirone, Alcon, Fort Worth, Texas) in the management of patients with GA secondary to AMD hypothesized that combination therapy with agents that would target different aspects of the progression of GA may be more effective compared to single therapeutic agents directed at specific biochemical pathways.

Reporting in the American Journal of Ophthalmology this year, Frank G. Holz, MD, Department of Ophthalmology, University of Bonn, Germany, and colleagues stated that although different dosages of AL-8309B did not have an effect on the growth of GA lesions in eyes with AMD, the large natural history of the dataset obtained from their study provides valuable information for future study designs and comparisons of potential novel therapeutic agents.

Genetics in GA progression in AMD

Importantly, AMD lesions presenting as GA are highly variable in affected individuals. Also, there is not sufficient information about its prognostic factors. To circumvent these issues, another group of German researchers have examined GA in AMD in a more holistic way by elucidating how clinical, demographic and genetic factors contribute to the progression of GA.

Analyzing the currently largest dataset on GA lesion growth (n=388), our findings suggest a significant and independent contribution of three factors on GA lesion growth including at least two genetic factorsone in ARMS2 (rs10490924) and one in the C3 gene (rs2230199), as well as one clinical component [presence of GA in the fellow eye], reported Bernhard H.F. Weber, PhD, Institute of Human Genetics, University of Regensburg, Germany.

Published in the May 2015 issue of PLOS One, the research team thinks that such correlations jointly explain up to 7.2% of noticed inter- individual variance in GA lesion progression and should be noted when analyzing innovative treatment options for advanced GA due to AMD. These factors can greatly confound the outcome, particularly when GA growth rate is the main outcome parameter, they reported. However, they emphasized that further studies are necessary to fully assess the impact of genetic and clinical factors on visual perception. As the area and growth rate of GA lesions do not necessarily correlate with visual acuity due to the frequently observed phenomenon of foveal sparing over a long period of time, it is difficult to draw any conclusion from our data on how long the patients vision can be retained, they said. According to Dr. Schimel, the future treatments for GA lesions in AMD may be based on genetics. We are going to find various factors to determine who [among patients] is more likely to progress, he said. As GA is becoming very interesting, agents are going to be targeted at this. Injections for wet AMD may slightly lead to progression of GA; therefore, we can look forward to more interesting studies coming out on this in the next few years.


1. Grassmann F, et al. Clinical and genetic factors associated with progression of geographic atrophy lesions in age-related macular degeneration. PLOS One. 2015 May 11;10(5):e0126636.

2. Jaffe GJ, et al. Randomized trial to evaluate tandospirone in geographic atrophy secondary to age-related macular degeneration: The GATE Study. Am J Ophthalmol. 2015 Aug 24. pii: S0002-9394(15)00518-8.

3. Jeong YJ, et al. Predictors for the progression of geographic atrophy in patients with age-related macular degeneration: fundus autofluorescence study with modified fundus camera. Eye. 2014 Feb;28(2):20918.

Editors note: Drs. Park and Weber have no financial interests related to this article. Dr. Holz has financial interests with Alcon, Allergan (Dublin), Bayer (Leverkusen, Germany), Heidelberg Engineering (Heidelberg, Germany), Genentech (San Francisco), Novartis (Basel, Switzerland), and Roche. Dr. Schimel has financial interests with Regeneron (Tarrytown, N.Y.).

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