Choriocapillaris flow impairment under the fovea is associated with delayed rod-mediated dark adaptation in the perifovea of eyes with early and intermediate age-related macular degeneration: ALSTAR2 baseline

Abstract

Purpose : To probe regions of metabolic vulnerability in age-related macular degeneration (AMD) by evaluating topographic associations between choriocapillaris flow deficits (FD%), choroidal thickness, and rod-mediated dark adaptation (RMDA).

Methods : This cross-sectional analysis included participants aged ≥60 years from the Alabama Study on Early Age-Related Macular Degeneration 2 (ALSTAR2) baseline. AMD status was determined using AREDS 9-step. RMDA was tested (AdaptDx, LumiThera, Harrisburg PA) at eccentricities of 5° (1.4 mm, superior parafovea) where rods are sparse and 12° (3.5 mm, superior perifovea) where rods are numerous. Using two adjacent 4.4 x 4.4 mm Spectralis OCTA (Heidelberg Engineering), FD% was quantified within annular regions with outer radii in mm of 0.5 (assigned to 0° location), 1.5 (5.2°), 2.2 (7.7°), 4.0 (14.0°), and 5.0 (17.5°) mm superiorly. Choroidal thickness was manually quantified 0°, 5° and 12° superiorly using a custom ImageJ plugin. Age-adjusted Spearman correlations (R) examined structure-function associations between regional FD% and choroidal thicknesses with RMDA at 5° and 12°.

Results : In 366 eyes of 366 participants (aged 71.3 ± 5.5 years), foveal FD% was more strongly associated with delayed RMDA at 5° (R=0.52, P<0.0001) than at 12° (R=0.39, P<0.0001). FD% was significantly worse with increasing AMD severity in all regions (overall P<0.05). The worst FD% was observed under the fovea (P<0.0001), decreasing at larger eccentricities. In pairwise comparisons, FD% was worse with greater AMD severity (P<0.05) at eccentricities <2.2 mm. At greater eccentricities, eyes with intermediate, but not early AMD differed from older normal eyes. Compared to FD%, choroidal thicknesses were more weakly associated with delayed RMDA at 5° and 12° (R=0.10-0.20, P<0.05) and were not associated with AMD severity (all P>0.10).

Conclusions : Reduced transport across choriocapillaris-Bruch’s membrane-RPE complex which contributes to high-risk soft drusen formation under the macula, also may impair retinoid resupply to rods close to the fovea. Microvascular impairment may precede macrovascular choroidal thinning, positioning FD% as a potential early imaging signature in AMD emergence. Further evaluation of spatio-temporal relationships is ongoing in the 3-year follow-up of ALSTAR2.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.