Behavior of hyperreflective spots noted on optical coherence tomography following intravitreal therapy in diabetic macular edema: A systematic review and meta-analysis

PURPOSE: Hyperreflective spots (HRS) are considered as spectral domain optical coherence tomography biomarkers in predicting response to intravitreal therapy (IVT) in diabetic macular edema (DME). We aimed to determine if there was a quantitative reduction in HRS following IVT in DME, if the response to antivascular endothelial growth factor (anti-VEGF) drugs was different from steroids, and if HRS-response was associated with improvement in visual acuity (VA) or reduction in central macular thickness (CMT). METHODS: PubMed/MEDLINE, Scopus, ProQuest, CINAHL, Wiley online, and Web of Science were searched (between January 1, 2011 and July 1, 2020). Publication bias and heterogeneity were assessed. Meta-analysis was done using the random-effects model. RESULTS: Totally, 1168 eyes from 19 studies were eligible for inclusion. IVT was associated with a reduction in quantitative HRS (z = -6.3, P < 0.0001). Studies, however, showed heterogeneity (I(2) = 93.2%). There was no difference between anti-VEGF and steroid therapies (P = 0.23). The evidence on predicting VA and CMT outcomes were limited by the number of analyzable studies, owing to the wide variation in individual study designs, and lack of randomized controlled trials. CONCLUSION: We could conclude that there is a definite reduction in quantitative HRS following either form of IVT. We highlight the lacunae in the existing literature on HRS in DME and propose goals for future studies to harness the advantage of this promising biomarker.