Functional Outcomes Across High-Risk OCT-Based Phenotypes in Intermediate Age-Related Macular Degeneration-PINNACLE...

To evaluate the association between structural optical coherence tomography (OCT) biomarkers and functional outcomes in intermediate age-related macular degeneration (iAMD) and to investigate whether stratifying eyes by OCT-based biomarkers identifies phenotypes of iAMD with impaired visual function.

The baseline cohort of the PINNACLE trial underwent OCT imaging, microperimetry, best-corrected visual acuity (BCVA), and low-luminance visual acuity (LLVA) testing. OCT volumes were assessed for the presence of different morphologic features. Drusen volume and outer nuclear layer (ONL) and ellipsoid zone (EZ) thickness were quantified. Linear mixed-effect models evaluated associations between each feature and functional outcomes, including a stratification into phenotypes based on significant OCT morphology with each eye assigned to a single group.

This analysis included 247 eyes of 190 patients (mean age, 74.2 ± 7.4 years). The presence of subretinal drusenoid deposits (SDDs) and markers of retinal atrophy were significant contributors to lower mean retinal sensitivity (P < 0.05). Also, higher drusen volume and lower ONL and EZ thickness were associated with lower sensitivity. Significant changes in BCVA, LLVA, and low-luminance deficits (LLDs) were associated with increasing drusen volume and the presence of hyperreflective foci (HRF). Significant functional differences were found between individual phenotypic groups, especially highlighting functional deficit in eyes with signs of early atrophy.

Integrating comprehensive analyses of structural OCT biomarkers with functional assessments revealed distinct phenotypic subtypes of iAMD that are associated with significant functional deficits. Particularly, early atrophy markers should be considered for patient selection and risk assessment in clinical trials and routine practice.