Multimodal imaging determinants of contrast sensitivity loss in geographic atrophy

Aims To investigate associations between imaging biomarkers and quantitative contrast sensitivity (CS) function (qCSF) metrics in geographic atrophy (GA). Methods Cross-sectional study including 97 eyes from 70 patients (>55 years) with GA within 1500 µm of the fovea and visual acuity (VA)>20/320. Participants underwent VA and qCSF testing (area under the log CS function (AULCSF), contrast acuity (CA), and CS at 1–18 cycles per degree (cpd)) and multimodal imaging with blue autofluorescence (BAF), optical coherence tomography (OCT), and, in 55 eyes, swept-source OCT angiography (SS-OCTA). Imaging biomarkers included GA size, prior growth rate, configuration, BAF pattern, circularity, percentage of foveal involvement (%FI), foveal distance and macular inner choroid flow deficit percentage (mICFD%). Generalised linear mixed-effects and random forest (GRF) models evaluated structure–function relationships. Results Participants (age 78.8±5.6 years; 70% female) had a median GA size of 4.0 mm², with 64% showing subfoveal involvement. Larger GA size and higher %FI were significantly associated with worse VA, AULCSF, CA and CS at 1–12 cpd (all p<0.01). Unifocal lesions correlated with lower VA and CS at 6 cpd, while diffuse/banded BAF patterns and greater mICFD% were linked to reduced CS at 1–1.5 cpd. GRF analysis identified GA size and %FI as primary predictors of CS loss, with best performance for AULCSF and CS at 3 cpd (R²=0.319, 0.314). Conclusions GA size and %FI are key determinants of CS loss in GA. qCSF outperformed VA in predictive accuracy, supporting its use as a sensitive functional endpoint in GA trials.