Establishing associations between structure, function, and clinical outcomes in intermediate age-related macular degeneration (iAMD) remains an unmet need. This study aims to (1) cross-sectionally investigate the relationships between optical coherence tomography (OCT) biomarkers and quantitative contrast sensitivity function (qCSF)-measured contrast sensitivity (CS), and (2) longitudinally assess their relationship with progression from iAMD to late stages of the disease.

Cross-sectional and cohort study.

Our study was conducted at Massachusetts Eye and Ear (Boston, MA, USA) and included eyes with (1) baseline diagnosis of iAMD, (2) same-day OCT and qCSF test, (3) visual acuity ≥20/200 Snellen, and (4) 24+ months of follow-up. qCSF metrics included the area under the logCSF curve, contrast acuity, and CS thresholds at 1- to 18-cycle-per-degree (cpd). Two independent graders reviewed macular OCT scans for various biomarkers, and outer nuclear layer (ONL) thickness and retinal pigment epithelium (RPE) volume were measured. Progression to wet AMD or geographic atrophy (GA) was confirmed using imaging studies. Generalized linear mixed-effects models assessed associations between qCSF and OCT biomarkers, while Cox regression models evaluated their association with progression to late AMD.

We included 205 iAMD eyes from 134 patients (age: 73 [69-78] years; 63% female). Higher RPE volume in the central subfield and a greater number of intraretinal hyperreflective foci were associated with reduced area under the logCSF curve, contrast acuity, and CS at 6 to 12 cpd ( P < .05). ONL thinning in the inner ring and a greater number of intraretinal hyperreflective foci were associated with reduced CS at 1 and 3 cpd ( P < .05). During follow-up, 35 eyes developed wet AMD (17%) and 53 progressed to GA (26%). subretinal drusenoid deposit, ONL thinning in the inner ring, and reduced CS at 1.5 cpd were associated with wet AMD ( P < .05). Higher RPE volume in the inner ring, hyporeflective drusen cores, subretinal drusenoid deposit, higher HRF count, and reduced CS at 1 cpd were associated with GA ( P < .05).

Our study reveals significant structure-function relationships between OCT biomarkers and qCSF-measured CS in iAMD. These findings highlight the impact of AMD alterations on CS function and offer valuable insights for patient stratification and prognostication in research and clinical settings.