Inner Retinal Reflectivity Loss and Concurrent Thickening Predict Short-Term Conversion to Neovascular AMD

Purpose: To examine inner retinal changes preceding conversion from intermediate age-related macular degeneration (iAMD) to exudative neovascular AMD (nAMD), using topographic optical coherence tomography (OCT) reflectivity and thickness analysis. Methods: This retrospective case-control study included 60 individual eyes with iAMD (30 converters and 30 non-converters to nAMD within 1 year). Baseline macular OCT scans were segmented for the retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), and inner plexiform layer (IPL). Raw linear reflectivity (normalized against vitreous intensity) and thickness were extracted from 48 × 48 grids. Primary outcomes were differences in reflectivity (%) and thickness (µm) between converters and non-converters, adjusted for person-level factors. Secondary outcomes examined retinal macrovascular metrics and odds of conversion (odds ratios [ORs]), further adjusted for traditional AMD factors. Results: Converters showed global reductions in reflectivity across the RNFL (-6.24%), GCL (-2.01%), and IPL (-1.58%), with modest RNFL thickening (4.48 µm). Topographic analyses revealed nasal reflectivity loss in all layers and localized thickening in the nasal RNFL and paracentral GCL/IPL (P < 0.0001). Macrovascular metrics did not differ between groups. Global and topographic reflectivity loss strongly predicted conversion (univariable ORs up to 1.85 per 1% decrease; 95% confidence interval [CI], 1.38-2.72). RNFL thickening was also predictive (univariable ORs up to 1.64 per 1-µm increase; 95% CI, 1.25-2.32). Both metrics remained significant in multivariable models, whereas drusen volume, pigmentary abnormalities, and fellow-eye status did not. Conclusions: Inner retinal reflectivity loss with mild thickening is a strong predictor of short-term progression to nAMD. These OCT-derived biomarkers showed stronger associations with conversion than traditional risk factors and may improve short-term risk stratification and monitoring.