OCT Risk Factors for Development of Atrophy in Eyes with Intermediate Age-Related Macular Degeneration

November 2022

Written by:  Katherine E. Talcott, MD
Cole Eye Institute / Cleveland Clinic

Hirabayashi K, Yu HJ, Wakatsuki Y, Marion KM, Wykoff CC, Sadda SR. OCT risk factors for development of atrophy in eyes with intermediate age-related macular degeneration. Ophthalmol Retina. 2022;6;S2468-6530(22)00486-9. doi 10.1016/j.oret.2022.09.007. Online ahead of print.

While treatments for atrophic age-related macular degeneration (AMD) are on the horizon, it appears that many will slow the progression of atrophy rather than reverse vision loss that has already occurred. It may be more beneficial for patients to intervene earlier in the disease process. Given this, it will be important to identify patients in earlier stages of AMD who are at highest risk for progression to advanced or atrophic AMD. This study by Hirabayashi et al aimed to identify the importance and prevalence of various optical coherence tomography (OCT) biomarkers for predicting the progression from intermediate AMD (iAMD) to atrophy.

Hirabayashi et al is a retrospective analysis of 330 eyes of 330 patients from a single retina group with iAMD in one eye who had follow-up for 24 months. OCT scans were examined at baseline for known iAMD biomarkers, including high central drusen volume (DV), intraretinal hyperreflective foci (IHRF), subretinal drusenoid deposits (SDDs), hyporeflective drusen cores (hDCs), and a thin or thick (multilayered) double-layer sign (DLS). Fellow eye AMD status was noted as normal, early AMD, iAMD, exudative macular neovascularization, or atrophy as noted by presence of complete retinal pigment epithelium and outer retinal atrophy (cRORA). At 24 months, they examined these OCTs again for presence of cRORA to help determine the incidence of atrophy as their primary outcome.

Overall, they found that 16% of iAMD eyes had developed cRORA. The baseline frequency of the biomarkers were as follows: high central DV (49%), IHRF (39%), SDD (34%), hDC (13%), thin DLS (12%), and cRORA (8%) in the fellow eye. They found that these baseline features were also associated with a significantly increased risk for development of cRORA at 2 years. The odds ratio for these biomarkers were as follows: high central DV (6.5, P<.001), IHRF (12.8, P<.001), SDD (2.3, P=.049), hDC (3.0, P=.024), thin DLS (4.5, P=.006), and cRORA in the fellow eye (7.2, P=.003).

The authors conclude that in addition to previously identified OCT biomarkers for progression from iAMD to atrophic AMD, a thin DLS and cRORA in the fellow eye are also associated with an increased risk over 2 years. It is important to note that the authors chose 2 years as their follow-up time point and a representative clinic population, suggesting that these markers could potentially be used in a clinical trial. This is important for clinical trials in the future, as new therapeutic targets emerge, prior to the onset of atrophy. While the identification of these biomarkers may be ready for a clinical trial reading center, it is less clear how retinal specialists could reliably identify them in a busy clinical practice.


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