Local OCT Structural Correlates of Deep Visual Sensitivity Defects in Early Atrophic Age-Related Macular Degeneration

To determine local OCT structural correlates of deep visual sensitivity defects (threshold of ≤10 decibels on microperimetry) in early atrophic age-related macular degeneration (AMD). Prospective observational study. Forty eyes from 40 participants, with at least incomplete retinal pigment epithelium (RPE) and outer retinal atrophy (iRORA), or more advanced atrophic lesion(s). Participants underwent at least two targeted, high-density microperimetry tests of atrophic lesions of interest in one eye, and high-density 3×3 mm volume scans of that region on a swept-source OCT angiography device, all at a single visit. Seven OCT-defined features of atrophy were manually annotated: hypertransmission, RPE attenuation/disruption, complete RPE loss, ellipsoid zone (EZ) disruption, external limiting membrane (ELM) disruption, subsidence of the outer plexiform layer (OPL) and inner nuclear layer (INL), and/or hyporeflective wedge-shaped band, and outer nuclear layer (ONL) thickness. Association between OCT-defined features of atrophy and presence of a deep visual sensitivity defect at a local, pointwise level. All OCT-defined features of atrophy were individually associated with the presence of a deep visual sensitivity defect at a pointwise level in univariable mixed-effects logistic regression analyses (P < 0.001 for all). However, only hypertransmission, complete RPE loss, ELM disruption, and ONL thickness remained significantly and independently associated with deep visual sensitivity defects in a multivariable analysis (P ≤ 0.011). A prediction model incorporating these four OCT features (partial area under the curve [pAUC] at ≥90% specificity = 0.80) outperformed models using any single feature alone in predicting the presence of deep visual sensitivity defects (pAUC = 0.65 to 0.78 respectively; P ≥ 0.040). The study identified hypertransmission, complete RPE loss, ELM disruption, and ONL thickness as key OCT-defined features of atrophy independently associated with deep visual sensitivity defects. These findings are important when considering anatomical outcome measures for evaluating interventions for early atrophic AMD that are most likely to capture beneficial treatment effects that will be accompanied by evidence of functional preservation if measured directly.