The prognostic power of baseline visual function deficits in intermediate age-related macular degeneration (iAMD) for progression to late AMD - A MACUSTAR study report

Abstract

Purpose : Having detected heterogenous visual function deficits in 70% of those with iAMD in the MACUSTAR baseline cohort, we examined the prognostic value of visual function deficits for progression to late AMD.

Methods : Participants with iAMD performed a visual function test battery: best-corrected visual acuity (BCVA); low luminance visual acuity (LLVA); Moorfields acuity test (MAT); Pelli-Robson Contrast Sensitivity; International Reading Speed Test; mesopic and scotopic Average Threshold (mAT & sAT; Macular Integrity Assessment, iCare) and Rod Intercept Time (AdaptDx, Lumithera) followed by multimodal imaging at 6-month intervals for up to 4 years. Images were graded by a central reading centre (GRADE) for progression to late AMD. Baseline visual function results were dichotomized against pre-established normal reference limits to determine whether a visual function deficit was present. Multivariable time-discrete hazard models with complementary log-log link function were constructed for each visual function measure with progression to late AMD as the outcome. Models were adjusted for age, presence of reticular pseudodrusen and presence of deficit at baseline. The prognostic value of 2 baseline visual function deficits and the cumulative effect of each additional deficit were derived from similar models.

Results : 585 participants with iAMD (67% female, mean age 72±7 years) were followed for a median 3 years (IQR: 1.5, 3.5). 84 progressed to late AMD over a median 2.5 years (IQR: 1, 3). Baseline deficits, present in 21% for BCVA, 24% for LLVA, 23% for MAT, 21% for mAT and 18% for sAT, were each significantly associated with a higher risk of progression to late AMD (p≤0.01). Having deficits in at least 2 visual function tests, present in 43% of participants, significantly increased progression risk (p=0.01), as did each additional visual function deficit present (p=0.0006).

Conclusions : Demonstrating a link between visual function deficits in iAMD and higher progression risk supports the clinical relevance of visual dysfunction in iAMD. Furthermore, the utility of visual function tests as baseline enrichment factors to identify those with iAMD at high risk of progression for future investigational trials should be considered. Work to identify optimal combinations of visual function tests to enrich trial populations is ongoing.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.