Researchers set out recently to determine the role that drusen subtypes and neovascular changes play in the likelihood of disease progression from intermediate age-related macular degeneration (AMD) to neovascular AMD (nAMD).

The retrospective study examined 632 eyes from 418 patients (older than 50 years) with intermediate AMD. For each patient, researchers used OCT to evaluate drusen subtypes, choroidal thickness and neovascular changes, which were also observed using fluorescein angiography and indocyanine green angiography (ICGA).

The five-year cumulative incidence of progression to nAMD from intermediate AMD was 17.8% in eyes with soft drusen and 17% in eyes with pachydrusen, showing no significant difference between the two subtypes. Though pachydrusen was not associated with typical nAMD, it was associated with progression to polypoidal choroidal vasculopathy (PCV).

“The proportion of progression to PCV differed between eyes with soft drusen and pachydrusen (0.4% vs. 11.5%, respectively),” the researchers wrote. “Thus, in reference to soft drusen, pacby­drusen might have a protective effect against progression to typical nAMD and increase the risk of progression to PCV.”

In coordinance with other studies, preexisting nAMD in one eye is a significant risk factor for the progression to late AMD in the other. Other risks observed for nAMD progression include older age and reticular pseudodrusen (RPD). Smoking was also found to be a risk factor, but it was only marginally significant.

Eyes with combined soft drusen and RPD had a much higher cumulative incidence rate compared with eyes that only had soft drusen (22.6% vs. 14.6%, respectively). The presence of RPD not only increased the risk for nAMD progression but also for retinal angiomatous proliferation (RAP). In fact, RAP occurs more frequently with RPD than without. Although eyes with RAP often have thinner choroids, this study found no correlation between choroid thinning and risk of progression of RAP, suggesting that the thinner choroid in patients with RAP is a result of the disease course.

“Older age contributes to the degenerative changes in retinal and choroidal tissue,” the researchers explained. “Moreover, there is a possibility that the pathogenesis related to the development and progression to PCV or RAP might differ from that of typical nAMD.”

Patients with nAMD in the fellow eye, RPD or those of older age have the highest risk of developing nAMD from intermediate AMD. Recommend the necessary treatment to these patients in order to help slow disease progression.

Kim KL, Joo K, Park SJ, et al. Progression from intermediate to neovascular age-related macular degeneration according to drusen subtypes: Bundang AMD Cohort Study Report 3. Acta Ophthalmol. August 12, 2021. [Epub ahead of print].