Skip to content Skip to navigation

Imaging, Genetic, and Demographic Factors Associated With Conversion to Neovascular Age-Related Macular Degeneration: Secondary Analysis of a Randomized Clinical Trial

Publication Type:

Journal Article


JAMA Ophthalmol, Volume 137, Number 7, p.738-744 (2019)


2168-6173 (Electronic)<br/>2168-6165 (Linking)

Accession Number:




*Choroidal Neovascularization/diagnostic imaging/drug, *Polymorphism, Single Nucleotide, *Retinal Drusen/diagnostic imaging/epidemiology/genetics, *Tomography, Optical Coherence, *Wet Macular Degeneration/diagnostic imaging/drug therapy/epidemiology/genetics, Acyl-CoA Dehydrogenase/*genetics, Aged, Aged, 80 and over, Angiogenesis Inhibitors/therapeutic use, Demography, Double-Blind Method, Female, Humans, Intravitreal Injections, Male, Proportional Hazards Models, Ranibizumab/therapeutic use, Retrospective Studies, Risk factors, Survival Analysis, therapy/epidemiology/genetics, Vascular Endothelial Growth Factor A/antagonists & inhibitors, Visual Acuity


Importance: Risk factors associated with the development of neovascular age-related macular degeneration (AMD) have been identified. However, population size and methods to integrate imaging, genetic, and demographic factors associated with conversion to neovascular AMD are limited, specifically when treatment is administered in 1 eye. Objective: To determine the imaging, genetic, and demographic factors associated with conversion from nonneovascular to neovascular AMD in fellow eyes. Design, Setting, and Participants: This post hoc secondary analysis of the 24-month phase 3 multicenter, double-masked, active treatment-controlled HARBOR trial included 686 fellow eyes with nonneovascular AMD at baseline. Imaging features describing the presence, number, extent, density, and relative reflectivity of drusen were automatically extracted from spectral-domain optical coherence tomography scans. Genetic analysis included 34 single-nucleotide polymorphisms. Least absolute shrinkage and selection operator regression was performed to narrow imaging features. Survival analysis and Cox proportional hazards regression were performed to determine the association of the selected imaging features and genetic and demographic factors with conversion to neovascular AMD. Data were collected from November 2016 through October 2017 and analyzed from October 2017 through October 2018. Exposure: Nonneovascular AMD in the fellow eye. Main Outcomes and Measures: Features associated with conversion to neovascular AMD. Hazard ratios (HRs) and their 95% CIs were calculated. Results: Among the 686 fellow eyes included in the analysis (406 [59.2%] women; mean [SD] age, 78.12 [8.28] years), 154 (22.4%) converted to neovascular AMD. Female sex was significantly associated with conversion to neovascular AMD (HR, 1.57; 95% CI, 1.11-2.20; P = .009). After controlling for demographic and treatment effects, drusen area within 3 mm of the fovea (HR, 1.45; 95% CI, 1.24-1.69; HR for 1-SD increase, 1.36 [95% CI, 1.20-1.54]) and mean drusen reflectivity (HR, 3.97; 95% CI, 1.11-14.18; HR for 1-SD increase, 1.32 [95% CI, 1.02-1.71]) were significantly associated with conversion to neovascular AMD. In addition, 1 genetic variant (rs61941274) was found to be associated with conversion to neovascular AMD. Conclusions and Relevance: Two imaging features (total en face area of drusen restricted to a circular area 3 mm from the fovea and mean drusen reflectivity) and 1 genetic variant (ACAD10 locus) were associated with conversion to neovascular AMD. Drusen characteristics may be associated with conversion to neovascular AMD despite treatment in 1 eye. Trial Registration: identifier: NCT00891735.