OCT Risk Factors Linked to cRORA Development in Eyes with Intermediate AMD


OCT features including a thin double-layer sign and cRORA in the fellow eye were associated with an increased risk of progression to cRORA over 2 years in eyes with iAMD.

Srinivas R. Sadda, MD │ Doheny Eye Institute

Srinivas R. Sadda, MD

Courtesy of Doheny Eye Institute

In eyes with intermediate age-related macular degeneration (iAMD), a thin double-layer sign and complete retinal pigment epithelium and outer retinal atrophy (cRORA) in the fellow eye were associated with an increased risk of progression to cRORA over 2 years.1

The results from a retrospective study noted these identified biomarkers are in addition to the 4 previously reported factors present in a significant proportion of eyes with iAMD, including high-central drusen volume, intraretinal hyper-reflective foci, hypo-reflective drusen cores, and subretinal drusenoid deposits.

“These biomarkers may aid in prognostication, risk stratification, and selection of patients for clinical trials,” wrote the investigative team, led by Srinivas R. Sadda, MD, Director, Artificial Intelligence and Imaging Research, Doheny Eye Institute and Professor of Ophthalmology at the University of California – Los Angeles.

Sadda and colleagues performed the retrospective analysis to determine the frequency of multiple OCT biomarkers on iAMD and their association with the development of complete retinal pigment epithelium and outer retinal atrophy after 2 years. It included 330 eyes of 330 consecutive patients with iAMD in ≥1 eye with 24 months of follow-up data.

At baseline, Sadda and colleagues evaluated Spectralis OCT volume scans (49 B-scans over 6 × 6 mm, automatic real time = 6, fovea-centered) for iAMD biomarkers. The biomarkers included a high-central drusen volume (≥0.03 mm3), intraretinal hyper-reflective foci, subretinal drusenoid deposits, hyporeflective drusen cores, and a thin or thick double-layer sign.

The team additionally assessed the AMD status in the fellow eye and classified as normal or early AMD, iAMD, exudative macular neovascularization, or cRORA. The main outcome measures were the incidence of cRORA, odds ratios for demographics, and OCT features.

Upon analysis at month 24, data showed 16.36% (54 of 330) of the iAMD eyes developed cRORA. Investigators noted several baseline features were linked to a significantly greater risk for development of cRORA at 2 years.

These included high-central drusen volume (odds ratio [OR], 6.510; 95% confidence interval [CI], 2.467 – 17.176; P <.001; baseline frequency, 49.1%) intraretinal hyper-reflective foci (OR, 12.763; 95% CI, 4.763 – 34.202; P <.001; baseline frequency, 38.8%), and subretinal drusenoid deposits (OR, 2.307; 95% CI, 1.003 – 5.304; P = .049; baseline frequency, 34.2%).

In addition, hyporeflective drusen cores (OR, 3.012; 95% CI, 1.152 – 7.873; P = .024; baseline frequency, 13.0%), thin double-layer sign (OR, 4.517; 95% CI, 1.555 – 13.126; P = .006; baseline frequency, 11.8%), and cRORA in the fellow eye (OR, 7.184; 95% CI, 1.938 – 26.623; P = .003; baseline frequency, 8.2%) were each associated with a greater risk for cRORA development at 2 years.


  1. Hirabayashi, K., Yu, H. J., Wakatsuki, Y., Marion, K. M., Wykoff, C. C., &amp; Sadda, S. R. (2023). OCT risk factors for development of atrophy in eyes with intermediate age-related macular degeneration. Ophthalmology Retina, 7(3), 253–260. https://doi.org/10.1016/j.oret.2022.09.007
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