Risk factors for disease progression in eyes with geographic atrophy (GA)

• Applicant: Professorin Dr. Monika Fleckenstein
• Subject Area: Ophthalmology
• Term: from 2013 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 235219383

Various risk factors for geographic atrophy (GA) progression in age-related macular degeneration (AMD) have been identified by natural history studies. These include morphological characteristics visualized by high-resolution in vivo imaging and genetic variants. However, the heterogeneity of these studies does not allow for direct comparison of these factors with respect to their precise prognostic value on disease progression. With the FAM- (NCT00393692, DFG SPP 1088) and the ongoing DSGA- (Directional spread of GA in AMD, NCT02051998, DFG FL 658/4-1) study, a unique longitudinal data collection is available that allow for systematic analysis of these previously described risk factors. In work package 1 (WP1), we aim to determine the most relevant prognostic variables for GA progression based on the combined FAM- and DSGA-datasets. The information is of importance both for a patient's individual outcome as well as for the design of future interventional clinical trials. Accurate knowledge of the most relevant prognostic factors would facilitate to identify patients at high risk for fast disease progression. Accordingly, the design for interventional studies could be adapted in order to reduce the observation period, sample size, and costs. Choroidal architecture and degeneration processes with subsequent perfusion deficit have been hypothesized to represent a contributing factor for multifactorial GA development and expansion. However, due to the lack of appropriate imaging techniques, the hypothesized sequence of impaired choriocapillaris (CC) perfusion preceding the development and expansion of GA has not yet been proven. By applying optical coherence tomography angiography (OCT-A), a novel imaging technology that allows for three dimensional visualization of the vascular structures and perfusion of the choroid, we aim to investigate alterations in CC perfusion and their impact on directional spread of GA in the ongoing DSGA-study (WP2). In the early stages of GA, patients typically show no or only minimal impairment in central visual acuity. However, patients often report marked symptoms including impaired reading performance. Decrease in reading speed has been shown to be highly dependent on the location and extent of GA. However, the exact dependency of reading speed on directional GA progression has not yet been investigated. In the ongoing DSGA-study we will test the hypothesis that the decline in reading speed over time correlates with GA size and progression in distinct retinal sectors (WP3). The analysis aims to validate changes in reading speed as a potential functional outcome measure for GA progression. Moreover, this data will help to identify patients at high risk to lose reading capability. If therapies successfully slow GA progression, this information is of importance for treating physicians, regulatory authorities, and payers.

• DFG Programme: Research Grants
• Co-Investigators: Professor Dr. Matthias Schmid; Dr. Marc Steffen Schmitz-Valckenberg