Baseline Optical Coherence Tomography Biomarkers Associated with Visual Acuity in Diabetic Macular Edema: A Systematic Review and Meta-Analysis

Determine effect estimates and certainty of evidence for the associations between baseline optical coherence tomography (OCT) biomarkers and (1) patients' visual acuity (VA) and (2) changes in VA from baseline to 6, 12, and 24 months after initiation of anti-vascular endothelial growth factor, steroid, or laser treatment for diabetic macular edema. Understanding the prognostic value conferred by biomarkers can help predict disease activity and inform treatment decisions. This review was registered in PROSPERO (CRD42023487798). Ovid MEDLINE, EMBASE, and CENTRAL databases were searched. The QUIPS tool informed risk of bias assessments and GRADE guidelines informed certainty of evidence. Twenty-eight reports from 27 studies evaluating 75 biomarkers were included. No biomarker with at least a 'Moderate' certainty was associated with improved VA or change in VA. Are reported in Early Treatment Diabetic Retinopathy Study (ETDRS) letters. Five biomarkers were associated with reduced VA at two or more time points with 'Moderate' certainty: (i) hyper-reflective retinal foci (HRF) (6 months: -6.5; 95% CI: -10.4 to -2.6; 1 study (196 eyes); 12 months: -7.3; 95% CI: -11.6 to -3.0; 1 study (196 eyes)), (ii) hyper-reflective choroidal foci (HCF) (6 months:-7.3; 95% CI: -13.3 to -1.3; 1 study (196 eyes); 12 months:-7.5; 95%CI: -11.9 to -3.0; 1 study (196 eyes)) (iii) disorganization of retinal inner layers (DRIL) (6months: -6.0; 95% CI:-11.7 to -0.3;1 study (196 eyes); 12months:-7.3; 95%CI:-12.8 to -1.7;1 study (196 eyes)), (iv) disrupted ellipsoid zone (EZ) or external limiting membrane (ELM) (6months:-9.7; 95%CI: -15.4 to -3.9; 1 study (196 eyes); 12months:-7.5; 95%CI:-11.9 to -3.0; 1 study (196 eyes); 12 months isolated EZ disruption:-5.4; 95%CI:-9.2 to -1.6; 2 studies (263 eyes); I2: 0%; 24months: -9.0; 95%CI:-14.3 to -3.6; 1 study (196 eyes)), and (v) disrupted cone outer segment termination (COST) line (12months:-8.5; 95%CI:-13.5 to -3.5; 1 study (196 eyes); 24 months: -8.8; 95%CI: -14.0 to -3.6; 1 study (196 eyes)). Baseline HRF, HCF, DRIL, disrupted EZ or ELM, and disrupted COST lines were associated with worse VA at two or more time points with "Moderate" certainty. Greater standardization in biomarker classification and better control of confounding variables are needed.