Short-term outcomes of trabeculectomy with or without anti-VEGF in patients with neovascular glaucoma: a systematic review and meta-analysis

Author: Zhou X, Chen J, Luo W, Du Y.

Geographical coverage: Not reported

Sector: Treatment

Sub–sector: Safety and efficacy

Equity focus: Not explicitly stated

Study population: Patients with glaucoma

Review type: Effectiveness review

Quantitative synthesis method: Meta-analysis

Qualitative synthesis method: Not applicable

Background

Neovascular glaucoma (NVG) is a severe secondary glaucoma characterised by abnormal blood‑vessel growth in the eye, leading to high intraocular pressure (IOP) and poor vision. It accounts for 9 %–17.4 % of secondary glaucoma cases, mainly arising from proliferative diabetic retinopathy (PDR) and central retinal vein occlusion (CRVO). Vascular endothelial growth factor (VEGF) plays a key role in NVG, prompting the use of anti‑vascular endothelial growth factor agents—bevacizumab, aflibercept and ranibizumab—to reduce neovascularisation and improve surgical outcomes. Although trabeculectomy is the standard procedure for NVG, its success is often hindered by complications. Studies suggest that combining anti‑VEGF therapy with surgery enhances success and reduces adverse events.

Objectives

To compare the safety and efficacy of trabeculectomy alone with trabeculectomy combined with intravitreal injections of anti‑vascular endothelial growth factor agents in the treatment of NVG.

Main findings

The review included seven studies (525 patients; 353 eyes): six retrospective comparative studies and one randomised controlled trial (RCT), published between 2010 and 2020, with follow‑up ranging from 6 to 12 months.

• IOP reduction: Trabeculectomy plus anti‑VEGF achieved a greater reduction in IOP from the first postoperative week (standardised mean difference [SMD] = −1.36; 95 % confidence interval [CI] −2.76 to 0.04; p = 0.06) to six months (SMD = −0.79; 95 % CI −1.50 to −0.07; p = 0.03). The advantage was not sustained at 12 months (SMD = −0.30; 95 % CI −1.61 to 1.02; p = 0.66).
• Complications: The overall risk of complications was lower with anti‑VEGF augmentation (relative risk [RR] = 0.60; 95 % CI 0.41 to 0.89; p = 0.01), notably a reduced incidence of anterior‑chamber haemorrhage (RR = 0.48; 95 % CI 0.24 to 0.98; p = 0.04). Rates of bleb leakage, shallow anterior chamber and choroidal detachment did not differ significantly.
• Surgical success: The success rate was higher in the anti‑VEGF group (RR = 1.19; 95 % CI 1.02 to 1.40; p = 0.03), indicating short‑term benefit.

Overall, anti‑VEGF agents enhance trabeculectomy outcomes up to six months post‑operation, but the benefit diminishes thereafter.

Methodology

The authors searched PubMed, the Cochrane Library, Embase and Web of Science up to 1 January 2023. Eligible studies enrolled at least 10 participants with NVG, compared trabeculectomy with and without intravitreal anti‑VEGF, and reported IOP, success rate or complications. Data extraction and quality assessment (Newcastle‑Ottawa Scale) were performed independently by two reviewers, with disagreements resolved by discussion or a third reviewer. Random‑effects meta‑analysis was used; continuous outcomes employed SMD and 95 % CIs, while dichotomous outcomes used RR and 95 % CIs. Heterogeneity was assessed with the I² statistic; publication bias with funnel plots and Egger’s test; sensitivity via leave‑one‑out analysis.

Applicability / external validity

The review focused on postoperative IOP, surgical success and complications—outcomes consistently reported across studies. Primary diseases ranged from PDR to ocular ischaemic syndrome, limiting generalisability. Only established anti‑VEGF agents and published studies were included; emerging therapies were excluded. These factors warrant caution when applying findings to other clinical contexts and underscore the need for further research to improve external validity.

Geographic focus

The geographic location of the included studies was not reported.

Summary of quality assessment

Confidence in the conclusions is low owing to methodological limitations: unclear screening methods, no report of contacting study authors or experts, and no list of excluded studies.