Supplementary Material for: Intravitreal triamcinolone acetonide for diabetic macular edema and macular edema secondary to retinal vein occlusion: a meta-analysis

Background: The comparative safety and efficacy of different doses of intravitreal triamcinolone acetonide (IVTA) for diabetic macular edema (DME) and macular edema (ME) secondary to retinal vein occlusion (RVO) is unclear. Objectives: This meta-analysis aimed to compare the safety and efficacy of different doses of IVTA in this setting. Methods: A systematic literature search for randomized clinical trials (RCTs) was conducted on Cochrane Library, Ovid MEDLINE and EMBASE from January 2005 to May 2022. Studies reporting on patients with DME or ME secondary to RVO that received treatment with different doses of IVTA. A random effects meta-analysis was performed. Cochrane’s risk of bias tool 2 was used to assess the risk of bias and grading of recommendations, assessment, development and evaluation (GRADE) guidelines were used to assess certainty of evidence. Results: Five RCTs reporting on 1,041 eyes at baseline were included in this meta-analysis. In eyes with ME secondary to RVO, high dose (4 mg) IVTA achieved a significantly better change in best-corrected visual acuity (WMD=-4.75 ETDRS letters, 95%CI=[-7.73, -1.78], p=.002) and reduction in retinal thickness (WMD=-93.02 µm, 95%CI=[-153.23, -32.82], p=.002) at months 4-6 compared to low dose (1-2 mg) IVTA. However, high dose IVTA had a higher risk of intraocular pressure (IOP)-related adverse events (RR=2.99, 95%CI=[1.05, 8.50], p=.04) and cataract surgery (RR=5.67, 95%CI=[3.09, 10.41], p<.00001) than low dose IVTA in eyes with ME secondary to RVO. These efficacy and safety differences in high dose and low dose IVTA were not observed in DME eyes. Conclusions: The RCT evidence in this setting is limited. High dose IVTA achieved greater improvements in visual acuity and reductions in retinal thickness than low dose IVTA at months 4-6. However, high dose IVTA had a less favourable safety profile than low dose IVTA. The significance of these outcomes was based on patients with ME secondary to RVO, but not DME.

背景：不同剂量玻璃体内注射曲安奈德（intravitreal triamcinolone acetonide, IVTA）用于糖尿病性黄斑水肿（diabetic macular edema, DME）及视网膜静脉阻塞（retinal vein occlusion, RVO）继发黄斑水肿（macular edema, ME）的比较安全性与有效性尚未明确。
目的：本荟萃分析旨在对比不同剂量IVTA在上述适应证中的安全性与有效性。
方法：本研究于2005年1月至2022年5月，在Cochrane图书馆、Ovid MEDLINE及EMBASE数据库中系统检索随机对照试验（randomized clinical trials, RCTs）。纳入接受不同剂量IVTA治疗的DME患者或RVO继发ME患者。采用随机效应模型开展荟萃分析，使用Cochrane偏倚风险评估工具2评价偏倚风险，并采用推荐分级、评估、制定与评价（grading of recommendations, assessment, development and evaluation, GRADE）指南评估证据确定性。
结果：本荟萃分析共纳入5项随机对照试验，涉及基线时1041只患眼。在RVO继发ME患眼中，与低剂量（1~2 mg）IVTA相比，高剂量（4 mg）IVTA在4~6个月随访时的最佳矫正视力（best-corrected visual acuity）提升更显著（加权均数差（weighted mean difference, WMD）=-4.75 ETDRS字母数，95%置信区间（confidence interval, CI）=[-7.73, -1.78]，p=0.002），视网膜厚度降低更明显（WMD=-93.02 μm，95%CI=[-153.23, -32.82]，p=0.002）。但在RVO继发ME患眼中，高剂量IVTA的眼压（intraocular pressure, IOP）相关不良事件发生风险更高（相对风险（relative risk, RR）=2.99，95%CI=[1.05, 8.50]，p=0.04），且白内障手术率更高（RR=5.67，95%CI=[3.09, 10.41]，p<0.00001）。上述高低剂量IVTA的有效性与安全性差异在DME患眼中未被观察到。
结论：本研究纳入的随机对照试验证据较为有限。在4~6个月随访时，高剂量IVTA较低剂量IVTA可更显著地改善最佳矫正视力并降低视网膜厚度，但安全性表现劣于低剂量IVTA。上述疗效与安全性差异仅在RVO继发ME患者中具有统计学意义，在DME患者中未观察到类似结果。