OCT Prognostic Biomarkers for Progression to Late Age-related Macular Degeneration: A Systematic Review and Meta-analysis

Abstract

Topic: To evaluate which OCT prognostic biomarkers best predict the risk of progression from early/intermediate to late age-related macular degeneration (AMD).

Clinical relevance: Among > 100 OCT prognostic biomarkers for AMD, it is unclear which are the most relevant for clinicians and researchers to focus on. This review evaluated which OCT biomarkers confer the greatest magnitude of prediction for progression to late AMD.

Methods: Study protocol was registered on PROSPERO (CRD42023400166). PubMed and Embase were searched from inception to March 2, 2023, and eligible studies assessed following the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. The primary outcome was any quantified risk of progression from treatment-naive early/intermediate AMD to late AMD, including hazard ratios (HRs), odds ratios (ORs), and standardized mean differences (at baseline, between eyes with versus without progression), subgrouped by each OCT biomarker. Further meta-analyses were subgrouped by progression to geographic atrophy or neovascularization.

Results: A total of 114 quantified OCT prognostic biomarkers were identified. With high GRADE certainty of evidence, the greatest magnitudes of prediction to late AMD belonged to: external limiting membrane abnormality (OR, 15.42 [7.63, 31.17]), ellipsoid zone abnormality (OR, 10.8 [4.58, 25.46]), interdigitation zone abnormality (OR, 7.68 [2.57, 23]), concurrent large drusen and reticular pseudodrusen (HR, 6.73 [1.35, 33.65], hyporeflective drusen cores (HR, 2.48 [1.8, 3.4]; OR 1.85 [1.29, 2.66]), intraretinal hyperreflective foci (IHRF; HR, 2.16 [0.92, 5.07]; OR 5.08 [3.26, 7.92]), and large drusen (HR, 2.01 [1.35, 2.99]); OR, 1.98 [1.27, 3.08]). There was greater risk of geographic atrophy for IHRF and hyporeflective drusen cores (P < 0.05), and neovascularization for ellipsoid zone abnormality (P < 0.05). Other OCT biomarkers such as drusenoid pigment epithelium detachment, shallow irregular retinal pigment epithelium elevations, and nascent geographic atrophy exhibited large magnitudes of risk but required further studies for validation.

Conclusion: This review synthesizes the 6 most relevant OCT prognostic biomarkers for AMD with greater predictive ability than large drusen alone, for clinicians and researchers to focus on. Further study is required to validate other biomarkers with less than high certainty of evidence, and assess how the copresence of biomarkers may affect risks.

Financial disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Keywords: Age-related macular degeneration; Geographic atrophy; Neovascularization; OCT; Prognosis.