Machine Learning OCT Predictors of Progression from Intermediate Age-Related Macular Degeneration to Geographic Atrophy and Vision Loss

PURPOSE: To describe spectral-domain OCT (SD-OCT) features, age, gender, and systemic variables that may be used in machine/deep learning studies to identify high-risk patient subpopulations with high risk of progression to geographic atrophy (GA) and visual acuity (VA) loss in the short term. DESIGN: Prospective, longitudinal study. PARTICIPANTS: We analyzed imaging data from patients with intermediate age-related macular degeneration (iAMD) (N = 316) enrolled in the Age-Related Eye Disease Study 2 (AREDS2) Ancillary SD-OCT with adequate SD-OCT imaging for repeated measures. METHODS: Qualitative and quantitative multimodal variables from the database were derived at each yearly visit over 5 years. Based on statistical analyses developed in the field of cardiology, an algorithm was developed and used to select person-years without GA on color fundus photography or SD-OCT at baseline. The analysis used machine learning approaches to generate classification trees. Eyes were stratified as low, average, above average, and high risk in 1 or 2 years, based on OCT and demographic features by the risk of GA development or decreased VA by 5+ and 10+ letters. MAIN OUTCOME MEASURES: New onset of SD-OCT–determined GA and VA loss. RESULTS: We identified multiple retinal and subretinal SD-OCT and demographic features from the baseline visit, each of which independently conveyed low to high risk of new-onset GA or VA loss on each of the follow-up visits at 1 or 2 years. CONCLUSIONS: We propose a risk-stratified classification of iAMD based on the combination of OCT-derived retinal features, age, gender, and systemic variables for progression to OCT-determined GA or VA loss. After external validation, the composite early end points may be used as exclusion or inclusion criteria for future clinical studies of iAMD focused on prevention of GA progression or VA loss.