An Analysis of Biomarkers to Identify Disease Progression in AMD

A study sought to determine whether characteristic morphologic patterns can be identified on optical coherence tomography (OCT) in eyes with age-related macular degeneration (AMD) that progress to macular atrophy (MA) and macular neovascularization (MNV).

OCT volumes from patients with early or intermediate AMD in the fellow eye in the HARBOR (A Study of Ranibizumab Administered Monthly or on an As-needed Basis in Patients With Subfoveal Neovascular Age-Related Macular Degeneration) trial were included. For two years, patients underwent monthly imaging following a standardized protocol. The researchers determined the time of progression to MNV and MA and used validated artificial intelligence algorithms to automatically segment drusen and hyperreflective foci (HRF) volumes in three dimensions.

There were 1,097 patients enrolled in HARBOR, of whom early or intermediate AMD in the fellow eye at baseline was observed in 518 (mean age, 78.1 years; 59.7% were female). Over 24 months of follow-up, 135 eyes (26%) developed MNV, 50 (10%) developed MA, and 333 (64%) did not progress to advanced AMD. Distinct topographic patterns were observed in drusen and HRF.

Eyes progressing to MNV had a mean drusen thickness at the fovea of 29.6 μm (95% confidence interval [CI], 20.2-39.0); the mean in eyes progressing to MA was 17.2 μm (95% CI, 9.8-24.6), and for eyes without disease progression was 17.1 μm (95% CI, 12.5-21.7). Mean drusen thickness at 0.5 mm eccentricity was 25.8 μm (95% CI, 19.1-32.5) for eyes progressing to MNV, 21.7 μm (95% CI, 14.6-28.8) for eyes progressing to MA, and 14.4 μm (95% CI, 11.2-17.6) for eyes without disease progression. For eyes progressing to MNV, the mean HRF thickness at the foveal center was 0.072 μm (95% CI, 0.000-0.152). For eyes progressing to MA, the mean HRF thickness at the foveal center was 0.059 μm (95% CI, 0.000–0.126 μm), and for eyes without disease progression, the mean HRF thickness at the foveal center was 0.044 μm (95% CI, 0.007-0.081).

Eyes progressing to MA had the largest mean HRF thickness at 0.5 mm eccentricity (0.227 μm; 95% CI, 0.104-0.349) followed by eyes progressing to MNV (0.161 μm; 95% CI, 0.101-0.221) and eyes without disease progression (0.085 μm; 95% CI, 0.058-0.112).

“In this study, drusen and HRF represented imaging biomarkers of disease progression in AMD, demonstrating distinct topographic patterns over time that differed between eyes progressing to MNV, eyes progressing to MA, or eyes without disease progression. Automated localization and precise quantification of these factors may help to develop reliable methods of predicting future disease progression,” the researchers concluded.