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

Kazutaka Hirabayashi, Hannah J. Yu, Yu Wakatsuki, Kenneth M. Marion, Charles C. Wykoff, Srinivas R. Sadda

Research output: Contribution to journalArticlepeer-review

27 Scopus citations


PURPOSE: To determine the frequency of multiple OCT biomarkers of intermediate age-related macular degeneration (iAMD) and their relationship with the development of complete retinal pigment epithelium and outer retinal atrophy (cRORA) after 2 years.

DESIGN: Retrospective cohort study.

PARTICIPANTS: This retrospective analysis included 330 eyes of 330 consecutive patients with iAMD in ≥ 1 eye who had 24 months of follow-up data.

METHODS: Spectralis OCT volume scans (49 B-scans over 6 × 6 mm, automatic real time = 6, fovea-centered) at baseline were evaluated for the previously described iAMD biomarkers, including a high-central drusen volume (DV; ≥ 0.03 mm 3), intraretinal hyper-reflective foci (IHRF), subretinal drusenoid deposits (SDDs), hypo-reflective drusen cores (hDCs), and a thin or thick (multilayered) double-layer sign (DLS). The age-related macular degeneration (AMD) status in the fellow eye was also assessed and classified as normal or early AMD, iAMD, exudative macular neovascularization, or cRORA.

MAIN OUTCOME MEASURES: Incidence of cRORA, odds ratio for demographics, and OCT features.

RESULTS: At month 24, 16.36% (54/330) of the iAMD eyes developed cRORA. Several baseline features, including high-central DV, IHRF, SDD, hDC, thin DLS, and cRORA in the fellow eye, were associated with a significantly greater risk for development of cRORA at 2 years. The odds ratio, 95% confidence interval, P value, and baseline frequencies of these biomarkers were DV (6.510, 2.467-17.176, P < 0.001, 49.1%), IHRF (12.763, 4.763-34.202, P < 0.001, 38.8%), SDD (2.307, 1.003-5.304, P = 0.049, 34.2%), hDC (3.012, 1.152-7.873, P = 0.024, 13.0%), thin DLS (4.517, 1.555-13.126, P = 0.006, 11.8%), and cRORA in the fellow eye (7.184, 1.938-26.623, P = 0.003, 8.2%).

CONCLUSIONS: In addition to the 4 previously reported factors that are present in a significant proportion of iAMD (DV, IHRF, hDC, and SDD), a thin DLS and cRORA in the fellow eye were associated with an increased risk of progression to cRORA over 2 years. These biomarkers may aid in prognostication, risk stratification, and selection of patients for clinical trials.

FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Original languageEnglish (US)
Pages (from-to)253-260
Number of pages8
JournalOphthalmology Retina
Issue number3
StatePublished - Mar 2023


  • Age-related macular degeneration
  • Double-layer sign
  • Hypo-reflective drusen cores
  • Intraretinal hyper-reflective foci
  • Subretinal drusenoid deposit
  • Tomography, Optical Coherence
  • Humans
  • Risk Factors
  • Child, Preschool
  • Disease Progression
  • Atrophy
  • Macular Degeneration/diagnosis
  • Retrospective Studies

ASJC Scopus subject areas

  • Ophthalmology


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