Longitudinal evaluation of visual function in early and intermediate dry age-related macular degeneration over 24 months

Abstract

Purpose : To evaluate visual function changes in early and intermediate age-related macular degeneration (eAMD and iAMD respectively) over 24 months

Methods : 101 subjects (33 eAMD, 47 iAMD, and 21controls) were enrolled in a prospective, observational natural history study at Duke Eye Center. Visual function (VF) tests included: Best corrected visual acuity (BCVA), low luminance visual acuity (LLVA), microperimetry (MP), cone contrast tests (CCT), and dark adaptation (DA). Mixed-Effect Model Repeated Measure (MMRM) was used to model the longitudinal progression of these VF tests at 6, 12, 18 and 24 months, controlling for covariates (baseline value, age, coronary artery disease, dry eye and cataract status). In addition, 9 AMD-risk genetic variants were genotyped. The number of risk alleles in each variant and in all 9 variants together (genetic burden score) were tested as predictors of diagnosis and of VF performance.

Results : 70 subjects completed the 2-year visit (22 eAMD, 31 iAMD, and 17 controls), a 30% drop out rate from 101 patients at the baseline visit. MP average threshold, MP percent reduced threshold, and CCT red were the VF measures that most consistently distinguished iAMD and controls across study time points. While generally only subtle longitudinal changes were observed relative to baseline within groups, both MP measures and CCT red revealed significant longitudinal deterioration within the iAMD group (Cohen’s d=0.15-0.2, p<0.05) that started to become detectable at 18 and 24 months. No consistent significant differences between groups were noted for LLVA or low luminance deficit, CCT blue, CCT green, or dark adaptation when controlled for baseline value. Nonetheless, dark adaptation in the iAMD patients group was worse at all follow up visits compared with baseline and demonstrated functional decline over time (rank-based model without baseline correction p<0.01), while eAMD subjects showed a less prominent decline. The total genetic burden score was associated with diagnosis (Relative Risk for iAMD=1.64, p<0.01), and there were suggestive associations between some genetic variants and VF tests.

Conclusions : MP variables, CCT red, as well as DA revealed functional decline in iAMD subjects over 24 months and may represent possible functional endpoints for future proof of concept clinical trials.

This is a 2020 ARVO Annual Meeting abstract.