Baseline OCT Biomarkers Predicting Visual Outcomes in Neovascular Age-Related Macular Degeneration: A Meta-Analysis

Abstract

Topic: To determine the effect estimates and certainty of evidence for baseline OCT biomarkers predicting visual acuity (VA) and changes in VA from baseline at 6, 12, and 24 months after anti-vascular endothelial growth factor therapy for neovascular age-related macular degeneration.

Clinical relevance: Understanding the prognostic utility of biomarkers can improve treatment decisions.

Methods: Results were reported in ETDRS letters. Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) guidelines for prognostic studies informed certainty of evidence. Results were interpreted using a 5-letter minimally important difference.

Results: Twenty-nine reports (8863 eyes) evaluating 80 biomarkers were included. Two biomarkers predicted better VA at 12 months with a low-certainty: the presence of an intact external limiting membrane (+14.0; 95% confidence interval [CI], +3.1 to +24.8) and the presence of an intact ellipsoid zone (+6.8; 95% CI, +2.8 to +10.8). Three biomarkers predicted worse VA at 12 months with a low certainty; the presence of intraretinal fluid (IRF; -5.6; 95% CI, -9.7 to -1.5), the presence of IRF in the foveal center point (-7.4; 95% CI, -10.1 to -4.7), and the presence of subretinal hyperreflective material (-8.7; 95% CI, -19.0 to 1.6). No other biomarker predicted an effect size that crossed the minimally important difference. However, noteworthy results occurred when interpreting biomarkers with statistically significant findings relative to a threshold of 0 letters and moderate certainty: the presence of a pigment epithelial detachment, geographic atrophy (GA), and both IRF and subretinal fluid (SRF) predicted reduced vision at 12 months. The presence of SRF predicted a positive change in VA at 12 months. The absence of a posterior vitreous detachment predicted a negative change in VA at 12 months. Finally, the presence of IRF in the central 1 mm, retinal pigment epithelial elevation, and GA predicted negative changes in VA at 24 months.

Discussion: With low-certainty evidence, the baseline presence of an intact external limiting membrane and ellipsoid zone predicted better VA at 12 months, and the presence of IRF, IRF in the foveal center point, and subretinal hyperreflective material predicted worse VA at 12 months. Improved standardization in biomarker classification and control of confounding variables is needed.

Financial disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Keywords: Age-related macular degeneration; Biomarkers; Meta-analysis; OCT; Personalized treatment regimens.