Macular Thickness in Intermediate Age-Related Macular Degeneration Is Influenced by Disease Severity and Subretinal Drusenoid Deposit Presence

PURPOSE. To investigate how macular thickness varies with intermediate age-related macular degeneration (iAMD) severity and the presence of subretinal drusenoid deposits (SDDs). METHODS. A longitudinal prospective study of 143 participants >50 years of age with no to intermediate AMD who were followed with multimodal imaging and functional testing. Participants were stratified by iAMD severity according to imaging features. Macular thicknesses measurements over the central circles with 1-mm, 3-mm, and 6-mm diameters obtained from ocular coherence tomography imaging were compared across severity categories using cross-sectional (143 eyes) and longitudinal (subset of 77 eyes followed for 4 years) multivariate analyses. RESULTS. Compared with control eyes without large drusen or SDDs (Group 0), central maculas of lower risk eyes with unilateral large drusen (Group 1) were thicker (P = 0.014), whereas higher risk eyes with SDDs (Group SDD) were thinner (P = 0.02) in cross-sectional multivariate analyses. In longitudinal analyses, maculas with SDDs thinned more rapidly over 4 years relative to control eyes (P = 0.0058), which did not show significant thinning. More rapid central macular thinning was associated with worse baseline best-corrected visual acuity (BCVA) (P = 0.016) and more rapid BCVA decline (P = 0.0059). CONCLUSIONS. Macular thickness in iAMD varies with disease severity, showing small increases in eyes with large drusen and decreases in eyes with SDDs. Active processes possibly related to neuroinflammation and neurodegeneration may be contributory. Longitudinal central macular thickness evaluation is an accessible outcome measure relevant to functional measures and is potentially useful for iAMD interventional studies.