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.

中文翻译：

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高反射点在预测玻璃体内治疗糖尿病性黄斑水肿中的作用：系统评价和荟萃分析

目的：预测DME对玻璃体内治疗的反应已成为一项艰巨的任务。个别研究表明，HRS可能是可靠的生物标志物。这项系统性综述旨在确定玻璃体内治疗后糖尿病性黄斑水肿（DME）中高反射点（HRS）的数量是否减少，玻璃体内治疗的类型（抗VEGF与类固醇）是否对定量HRS变化产生不同的影响，以及最后，如果在治疗开始时HRS与视力改善（VA）或中央黄斑厚度减少（CMT）有关。我们还旨在找出DME中有关HRS的现有文献中的空白，并提出未来研究的目标。方法：PubMed / MEDLINE，Scopus，ProQuest，CINAHL，根据MOOSE指南（针对2011年1月1日至2020年7月1日之间HRS作为DME中的生物标志物进行评估）基于WiOSE在线和Web of Science进行了搜索。使用Begg和Mazumdar秩相关检验和漏斗图分析了出版偏倚。使用I2统计量评估异质性。使用随机效应模型进行荟萃分析。结果：来自19个研究的1168只眼睛合资格入选。汇总的标准化均值差异表明玻璃体内治疗与定量HRS降低有关（z = -6.3，CI95％=-1.09至-0.55，p <0.0001）。观察到极端的研究间异质性（I2 = 93.2％），且发表偏倚显着。抗VEGF和类固醇疗法之间的预后没有差异（p = 0.23）。关于HRS在确定最终VA和CMT方面的预测价值，无法得出明确的结论。结论：本综述可以得出结论，无论哪种玻璃体内治疗形式，定量HRS都会显着降低。由于研究设计，方法和报告的差异很大，我们关于HRS在预测视觉结果和CMT变化中的作用的结论受到可分析研究的数量的限制。