Not all neovascular age-related macular degeneration (nAMD) follows the same long-term course. New data from Japan suggest that classifying disease according to drusen and pachychoroid characteristics may help to provide more prognostic information than conventional categories such as typical nAMD, polypoidal choroidal vasculopathy (PCV), and retinal angiomatous proliferation (RAP).
In a retrospective cohort study published in BMC Ophthalmology, researchers from Keio University School of Medicine in Tokyo analyzed 120 treatment-naïve eyes with nAMD that were followed for at least six years. All patients received three loading doses of anti-VEGF therapy followed by a pro re nata regimen. Eyes were categorized using both the conventional classification and a newer system (based on a novel classification proposed by Yanagi et al. in 2020) that separated cases into drusen, pachychoroid, mixed, and other phenotypes.
Overall, 71% of eyes maintained best-corrected visual acuity (BCVA), defined as losing fewer than 15 ETDRS letters. Under the conventional classification, visual retention did not differ significantly between typical nAMD, PCV, and RAP. By contrast, the novel classification revealed a clear divergence: 82% of pachychoroid-type eyes maintained vision compared with just 38% of drusen-type eyes, with mixed and other phenotypes falling between the two.
The investigators also examined retinal pigment epithelial and outer retinal atrophy (RORA) and complete RORA (cRORA), both of which were associated with significant deterioration in BCVA when they emerged. Mean logMAR BCVA worsened from 0.10 to 0.35 at RORA onset and from 0.36 to 0.82 at cRORA onset.
Again, the novel classification appeared more discriminating. At six years, RORA/cRORA prevalence reached 76.9%/61.5% in the drusen group, compared with 47.0%/27.2% in the pachychoroid group, 50.0%/14.3% in the mixed group, and 40.7%/29.6% in the other group. The difference in final cRORA prevalence was statistically significant, with the drusen phenotype carrying the greatest burden. Conventional classification, meanwhile, showed no significant differences in RORA or cRORA prevalence between subtypes.
The study authors suggest that underlying biology may explain the contrast. Drusen-driven disease is associated with inflammatory and complement-mediated RPE damage, oxidative stress, and impaired photoreceptor support, whereas pachychoroid-associated neovascularization may involve less of this atrophic pathway.
The findings are exploratory. As previously mentioned, the study was retrospective and conducted at a single Japanese center, and several of the subgroups – particularly RAP – were small. Different anti-VEGF agents were also used over the study period. Because the study was retrospective, the authors caution that prospective studies are now needed in order to establish causality.
Still, their results suggest that phenotyping nAMD according to drusen and pachychoroid features could help clinicians to identify patients at greater risk of long-term atrophy and vision loss, and potentially support a more individualized monitoring and management approach to nAMD.
