Role of hyper-reflective spots in predicting outcomes of intravitreal therapy in diabetic macular edema: A systematic review and meta-analysis

Abstract

Purpose: Predicting response to intravitreal therapy in DME has become a challenging task. Individual studies have shown that HRS could be a reliable biomarker. This systematic review aimed to determine if there was a quantitative reduction in hyperreflective spots (HRS) following intravitreal therapy in diabetic macular edema (DME), if the type of intravitreal therapy (anti-VEGF versus steroid) had differential effects on quantitative HRS change and finally, if HRS at the start of therapy was associated with improvement in visual acuity (VA) or reduction in central macular thickness (CMT). We also aimed at bringing out the lacunae in the existing literature on HRS in DME and propose goals for future studies. Methods: PubMed/MEDLINE, Scopus, ProQuest, CINAHL, Wiley online and Web of Science were searched based on MOOSE guidelines for non-randomized studies evaluating HRS as a biomarker in DME (between 1st January 2011 and 1st July 2020). Publication bias was analyzed using Begg and Mazumdar rank correlation test and funnel plots. Heterogeneity was assessed using the I2 statistic. Meta-analysis was done using a random-effects model. Results: A total of 1168 eyes from 19 studies were eligible for inclusion. Pooled standardized mean differences showed that intravitreal therapy was associated with a reduction in quantitative HRS (z=-6.3, CI95%=-1.09 to -0.55, p<0.0001). Extreme between-study heterogeneity was observed (I2=93.2%) with significant publication bias. There was no difference in outcomes between anti-VEGF and steroid therapies (p=0.23). No definite conclusions could be drawn regarding the predictive value of HRS in determining the final VA and CMT. Conclusion: This review could conclude that there is a definite reduction in quantitative HRS following either form of intravitreal therapy. Our conclusion about the role of HRS in predicting visual outcome and CMT change was limited by the number of analyzable studies owing to the wide variation in the study designs, methods and reporting.