gms | German Medical Science

Advanced dry age-related macular degeneration (AMD), or ‘geographic atrophy’ (GA), is a frequent cause for severe visual loss with increasing incidence and prevalence. Areas of geographic atrophy are associated with RPE cell death and loss of overlying photoreceptors with corresponding absolute scotoma. These areas enlarge continuously over time resulting in foveal involvement and progressive visual impairment. Natural history studies have recently identified prognostic markers. Using autofluorescence (AF) imaging in the context of the FAM-Study it has been shown that an increased AF-signal may precede the enlargement of GA and the development of new atrophic patches. Specific patterns of abnormal AF allow distinction between slow and fast progressors. So far known genetic risk variants including genes of the complement pathway appear not to influence porgession once this GA has occurred. This is also the case for other risk factors associated with AMD including smoking or BMI.

Recently, various therapeutic approaches have been brought forward which aim at slowing enlargement of GA. Along with experimental evidence indicating toxic effects of excessive lipofuscin accumulation and its molecular constituents such as A2-E there is a rationale to reduce accumulation of such by products of the visual cycle in order to slow or prevent the development of atrophy. Other approaches include antiapoptotic and antioxidative agents as well as the slow-release of ciliary neurotrophic factor (CNTF) to rescue photoreceptors and protecting them from degeneration.

A meaningful anatomical clinical endpoint for interventional studies in patients with geographic atrophy is the size of the atrophic patches as these correspond to functional loss. These areas can be readily identified and quantified by AF-imaging.

After therapeutic breakthrough in neovascular AMD, tackling dry AMD represents the next major challenge in the therapeutic armentarium for AMD. The understanding of the pathogenesis of atrophic forms of AMD is, however, still incomplete. Importantly, development of atrophy is also a relevant cause for visual impairment despite anti-VEGF-therapy in neovascular AMD. Various therapeutic targets have already been identified which appear promising for interference with the occurence and spread of geographic atrophy, and, thus, for the prevention of severe visual loss from atrophic age-related macular disease.