Trabeculectomy with antimetabolite agents for normal tension glaucoma: A systematic review and meta-analysis

Author: Lai C, Shao SC, Chen YH, Kuo YK, Lai CC, Chuang LH.

Geographical coverage: Japan and United States

Sector: Glaucoma treatment

Sub-sector: Visual field progression rate, intraocular pressure control, and antiglaucoma medication

Equity focus: Not reported

Study population: Patients with glaucoma

Review type: Effectiveness review

Quantitative synthesis method: Meta-analysis

Qualitative synthesis method: Not applicable

Background:

Glaucoma, a leading cause of blindness worldwide in adults over 50, is marked by retinal ganglion cell loss. Primary open-angle glaucoma (POAG) is the most common subtype, and normal-tension glaucoma (NTG), a form of POAG with intraocular pressure (IOP) below 21 mmHg, accounts for up to 92% of POAG cases in Asia and 31% in the United States. Standard treatment involves reducing IOP through medication or surgical interventions, such as trabeculectomy, which is commonly used for refractory NTG. However, evidence on its effectiveness in slowing visual field (VF) progression is mixed, partly due to small study sample sizes.

Objectives

To systematically assess the visual field (VF) progression rate, intraocular pressure (IOP) control, and use of antiglaucoma medication after trabeculectomy with antimetabolites in patients with progressing NTG.

Main findings

Overall, trabeculectomy with antimetabolites was found to be beneficial for progressing NTG.

From 548 articles identified, seven retrospective studies were included in the meta-analysis, with a total of 166 subjects (151 eyes from six studies in Japan and 15 eyes from one study in the United States).

Preoperative VF mean deviation (MD) slopes ranged from –0.52 to –1.05 dB/year. Meta-analysis showed a significant improvement after surgery, with a pooled mean difference of 0.54 dB/year (95% CI: 0.40 to 0.67), indicating slower VF progression. Subgroup analyses by mean age, baseline MD, and baseline IOP supported the main results.

Postoperative mean IOP significantly decreased by –5.54 mmHg (95% CI: –6.02 to –5.06), and the number of antiglaucoma medications dropped by –1.75 (95% CI: –2.97 to –0.53). The most commonly reported early complications included hypotony (2–48%), hyphema (1–20%), and shallow anterior chamber (1–16%).

Methodology

Searches were conducted in PubMed, Embase, and the Cochrane Central Register of Controlled Trials to identify relevant English-language studies published from inception to 21 March 2022. Included were RCTs and observational studies assessing NTG patients treated with trabeculectomy using antimetabolites (e.g., Mitomycin C or 5-Fluorouracil), reporting pre- and postoperative MD slope data.

Two reviewers independently conducted study selection, data extraction, and risk-of-bias assessments. Disagreements were resolved by a third reviewer. The National Institutes of Health’s Quality Assessment Tool for Before-After (Pre–Post) Studies with No Control Group was used.

Findings were synthesised using a random-effects model meta-analysis. Heterogeneity was evaluated using I² statistics. Subgroup analyses explored variables such as age, baseline disease severity, and preoperative IOP. Complications were summarised descriptively.

Applicability / External validity

The review included seven observational studies, six from Japan and one from the USA, potentially limiting generalisability. The authors recommended further prospective studies to validate these findings.

Geographic focus

The included studies were conducted in Japan and the United States.

Summary of quality assessment

There is medium confidence in the study’s conclusions. The authors conducted a thorough database search, minimising language bias. However, they did not review the reference lists of included studies, which limits comprehensiveness.