Genetic and clinical factors associated with progression of geographic atrophy in age-related macular degeneration

Abstract

 

Purpose

 

Worldwide, age-related macular degeneration (AMD) is a serious threat to vision loss in individuals over 50 years of age with a pooled prevalence of approximately 9%. The late stage form manifests as geographic atrophy (GA) and neovascular complications. GA due to AMD is the result of gradual degeneration and disappearance of the retinal pigment epithelium (RPE) and photoreceptors. Continuous enlargement of atrophic lesions shows a high interindividual variability. Herein, we investigated clinical, demographic, and genetic factors for GA progression.

 

Methods

 

The present analysis included data of 388 patients with GA secondary to AMD. Patients were recruited in the prospective natural history FAM study (Fundus Autofluorescence in AMD, NCT00393692) and the Age-Related Eye Disease Study (AREDS), respectively. Fundus autofluorescence or color fundus photographs were used to assess GA size at different time points over a mean follow-up time of 4.5 (Standard deviation (SD) 2.85) years. We investigated the influence of previously published AMD risk variants as well as clinical covariates on GA progression using multivariate linear regression.

 

Results

 

Analyzing the currently largest dataset on GA lesion enlargement including 388 patients, we found an average growth rate of 1.54 (SD 1.51) mm² per year and an average square root growth rate of 0.30 (SD 0.25) mm per year. Neither gender, mean follow-up time nor the interval between examinations had a significant effect on GA progession (P > 0.05). In contrast, we found that presence of GA in both eyes significantly increased GA lesion growth (P = 0.00023, P(corrected) = 0.0037). In addition, we identified several genetic factors independently and significantly contributing to GA lesion growth (P < 0.001, P(corrected) < 0.02). These correlations jointly explain up to 7.2% of the observed inter-individual variance in GA lesion progression.

 

Conclusions

 

We demonstrate the impact of genetic and clinical factors on GA lesion growth over time. These findings not only add to our understanding of the underlying pathophysiology but may also be helpful in the design of future interventional clinical trials aimed at evaluating novel treatments to prevent visual loss from AMD due to GA.