Berni Alessandro, Coletto Andrea, Li Jianqing, Shen Mengxi, Bandello Francesco, Reibaldi Michele, Borrelli Enrico
Department of Ophthalmology, IRCCS San Raffaele Scientific Institute, Milan, Italy; School of Medicine, Vita-Salute San Raffaele University, Milan, Italy.
Department of Surgical Sciences, University of Turin, Turin, Italy; Department of Ophthalmology, "City of Health and Science" Hospital, Turin, Italy.
Ophthalmol Retina. 2025 Jul;9(7):625-644. doi: 10.1016/j.oret.2025.01.011. Epub 2025 Jan 20.
Macular atrophy incidence in neovascular age-related macular degeneration (AMD) patients undergoing anti-VEGF treatment.
Macular atrophy is a significant event that may occur in eyes with neovascular AMD treated with anti-VEGF therapy.
We conducted a systematic review and meta-analysis following PRISMA guidelines (PROSPERO, CRD42024474924). A comprehensive literature search of MEDLINE, EMBASE, and Web of Science was performed up to November 1, 2023. Randomized and nonrandomized studies of treatment-naive neovascular AMD patients reporting macular atrophy incidence at 24 ± 3 months after anti-VEGF therapy were eligible. Two independent reviewers conducted screening, data extraction, and quality assessment. For randomized controlled trials, the Cochrane Risk of Bias 2 tool was employed, whereas nonrandomized studies were evaluated using the Risk Of Bias In Nonrandomized Studies of Interventions tool. Random-effects meta-analysis models accounted for study variability. Heterogeneity was assessed with the I statistic, and publication bias by funnel plots and Egger test. The primary outcome was the incidence of new macular atrophy at 24 months post-treatment, with secondary outcomes at 12 months. Atrophy was diagnosed using color fundus photograph, fluorescein angiography, fundus autofluorescence, OCT, or multimodal imaging.
Twenty-three studies met the inclusion criteria for qualitative analysis, with 11 included in the meta-analysis (N = 3013 eyes). The pooled 24-month incidence of macular atrophy was 29% (95% confidence interval [CI]: 20%-38%, I = 93%). Subgroup analysis revealed incidence rates of 26% (95% CI: 15%-37%, I = 88%) for 814 eyes with type 1/2 macular neovascularization (MNV), 49% (95% CI: 18%-80%, I = 92%) for type 3 MNV (N = 230 eyes), and 29% (95% CI: 18%-40%, I = 96%) for all MNV types (N = 2131 eyes). The pooled 12-month incidence among 2214 eyes was 11% (95% CI: 4%-18%, I = 93%). The certainty of evidence, as assessed by Grading of Recommendations, Assessment, Development and Evaluation, was low.
Although this meta-analysis has limitations, including a moderate risk of bias in nonrandomized studies, inconsistencies in the results indicated by high heterogeneity, and imprecision due to the different imaging modalities used to diagnose macular atrophy, our results suggest that macular atrophy could be a common complication in patients with neovascular AMD receiving anti-VEGF therapy.
FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
接受抗血管内皮生长因子(VEGF)治疗的新生血管性年龄相关性黄斑变性(AMD)患者的黄斑萎缩发生率
黄斑萎缩是在用抗VEGF疗法治疗的新生血管性AMD眼中可能发生的重大事件。
我们按照系统评价和Meta分析的首选报告项目(PRISMA)指南(国际前瞻性系统评价注册平台,CRD42024474924)进行了系统评价和Meta分析。截至2023年11月1日,对MEDLINE、EMBASE和科学网进行了全面的文献检索。符合条件的是对未经治疗的新生血管性AMD患者进行的随机和非随机研究,这些研究报告了抗VEGF治疗后24±3个月时的黄斑萎缩发生率。两名独立的审阅者进行筛选、数据提取和质量评估。对于随机对照试验,采用Cochrane偏倚风险2工具,而对于非随机研究,则使用干预性非随机研究中的偏倚风险工具进行评估。随机效应Meta分析模型考虑了研究的变异性。用I统计量评估异质性,用漏斗图和Egger检验评估发表偏倚。主要结局是治疗后24个月时新发生黄斑萎缩的发生率,次要结局是12个月时的发生率。使用彩色眼底照片、荧光素血管造影、眼底自发荧光、光学相干断层扫描(OCT)或多模态成像诊断萎缩。
23项研究符合定性分析的纳入标准,其中11项纳入Meta分析(N = 3013只眼)。黄斑萎缩的24个月合并发生率为29%(95%置信区间[CI]:20%-38%,I² = 93%)。亚组分析显示,1/2型黄斑新生血管(MNV)的814只眼中发生率为26%(95%CI:15%-37%,I² = 88%),3型MNV(N = 230只眼)中发生率为49%(95%CI:18%-80%,I² = 92%),所有MNV类型(N = 2131只眼)中发生率为29%(95%CI:18%-40%,I² = 96%)。2214只眼中的12个月合并发生率为11%(95%CI:4%-18%,I² = 93%)。根据推荐意见分级、评估、制定与评价(GRADE)评估的证据确定性较低。
尽管这项Meta分析存在局限性,包括非随机研究中存在中度偏倚风险、高异质性表明结果不一致以及用于诊断黄斑萎缩的成像方式不同导致的不精确性,但我们的结果表明,黄斑萎缩可能是接受抗VEGF治疗的新生血管性AMD患者的常见并发症。
在本文末尾的脚注和披露中可能会发现专有或商业披露信息。