Anatomic biomarkers as potential endpoints in diabetic macular edema: A systematic literature review with identification of macular volume as a key surrogate for visual acuity.

Optimization of diabetic macular edema (DME) treatment pathways can aid in the efficient introduction of new therapies that provide value to patients and healthcare systems. We performed a systematic literature review and multicorrelation analysis to identify and evaluate anatomic biomarkers as potential surrogate endpoints (SEs) for visual acuity (VA) in patients with DME. We performed EMBASE and MEDLINE searches to identify studies reporting on 4 priority biomarkers previously identified by clinical experts: hyperreflective foci, intraretinal cyst, macular volume (MV), and subretinal fluid. Endpoint and treatment effect correlation analyses were performed to establish correlation coefficients between MV and VA using Pearson's correlation. A total of 105 studies reported change from baseline data for VA, and at least 1 biomarker, with MV investigated most often (n = 70 studies). Data extracted from 55 studies focusing on the 6-mm zone for MV were used in statistical analyses. A moderate correlation was observed between MV and VA at the endpoint level (r = 0.58; p < 0.01); however, a corresponding treatment effect was not found (r = 0.32; p = 0.19). Our findings suggest MV's potential as an SE for VA in future clinical practice; however, the lack of a significant treatment effect warrants that these findings be interpreted cautiously. Further evidence and improvements in reporting the methods for collecting biomarker data are needed. Analysis of outliers and subanalyses by other optical coherence tomography measures could establish the most meaningful MV values correlating with VA.