Prognostic value of structural biomarkers for disease progression in intermediate age-related macular degeneration: a MACUSTAR study report

Abstract

Purpose : To analyze the impact of structural biomarkers of intermediate (i-) age-related macular degeneration (AMD) on disease progression towards geographic atrophy (GA) or macular neovascularization (MNV) based on the European multicenter natural history study MACUSTAR.

Methods : In 585 study eyes with iAMD (mean age 72±7 years), the presence of established structural biomarkers was assessed in a multimodal retinal imaging grading approach. The standardized grading protocol comprised the qualitative assessment on the presence of reticular pseudodrusen (RPD), hyperreflective foci (HRF), vitelliform material, pigmentary abnormalities (PA), refractile deposits as well as incomplete (i-) and complete (c-) retinal pigment epithelium and outer retinal atrophy (RORA). Development of late-stage AMD was determined at six-monthly visits during a period of up to 4 years. The association of baseline structural biomarkers with progression to late-stage AMD was analyzed by multivariable time-discrete subdistribution hazard models.

Results : Disease progression to late-stage AMD was detected in 14.4% (n=84) study eyes with GA development in 38 cases and MNV in 46 cases. Study eyes with HRF (hazard ratio, HR=4.88 [95%-confidence interval: 2.49-9.57]) and RPD (HR=2.44 [1.48-4.01]) at baseline were more likely to convert to late-stage AMD during the observational period (both: p<0.001). In contrast, the presence of refractile deposits (HR=1.94 [0.99-3.79], p=0.051), PA (HR=1.23 [0.69-2.21], p=0.474) or vitelliform material (HR=0.77 [0.30-1.99], p=0.604) did not show a significantly higher risk for disease progression in the multivariable model. Regarding early biomarkers for structural photoreceptor and outer retinal impairment, only eyes with cRORA lesions showed a higher risk for progression to late-stage AMD (HR=4.49 [2.47-8.17], p=0.001). In this period, presence of iRORA at baseline was not significantly associated with progression to late AMD (HR=1.24 [0.57-2.67], p=0.580).

Conclusions : Among established iAMD biomarkers, presence of HRF, cRORA and RPD were associated with a higher risk for progression towards late-stage AMD. Further analyses will address the topographical information of structural iAMD features as well as their prognostic value in a pathway-specific manner, i.e., with regards to the development of either exudative or non-exudative advanced AMD.

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