Validating a Confirmatory Structure-Function Model Prognostic of Progression of Intermediate AMD: MACUSTAR Study Primary Endpoint Analysis

Abstract

Purpose : To evaluate the prognostic performance of prospectively defined structural and functional risk factors of progression from intermediate age-related macular degeneration (iAMD) to late-stage AMD. This constitutes the pre-specified primary endpoint analysis of the longitudinal part of the European multi-center cohort study MACUSTAR.

Methods : Patients with iAMD were recruited at 20 clinical sites across seven European countries and underwent 6-monthly visits for up to 4 years. A battery of functional, structural, and patient-reported assessments was conducted. Beckman AMD stage and further structural AMD biomarkers were determined by a central reading center. A three-variable time-discrete subdistribution hazard model was pre-specified as the main analysis in the MACUSTAR statistical analysis plan. Based on data from the Laser Intervention in early stages of AMD (LEAD) study, the following baseline variables were selected: (i) functional: pointwise standard deviation in mesopic microperimetry (mesPSD), (ii) structural: presence of reticular pseudodrusen (RPD) in the study eye, (iii) age at baseline. The primary endpoint was progression to late AMD (geographic atrophy, GA or exudative macular neovascularization, MNV). Death or eye-related confounding events were considered competing events.

Results : A total of 585 participants with iAMD (mean age 72±6, 66% female, 27% with RPD, mean mesPSD 2.8±1.5 dB) with a median follow-up of 3 years were enrolled. Seven percent had late AMD in the fellow eye. Eighty-four eyes (14%) progressed to late AMD (GA: 38, MNV: 46), nine (2%) had an eye-related confounding event and 8 (1%) died during the study. Presence of RPD (hazard ratio, HR=3.44, p<0.001) and higher mesPSD (HR=1.24, p<0.001) were associated with AMD progression, while age at baseline was not (HR=1.03, p=0.082).

Conclusions : The primary endpoint analysis of the MACUSTAR study confirms the independent prognostic relevance of structural and functional risk factors for iAMD progression in a multi-center setting, in particular presence of RPD and mesPSD at baseline. Our results further support the use of structural and functional baseline variables as criteria for enrichment of trial populations for individuals with high risk of progression to late stage AMD.

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