Intravitreal injection is associated with increased posterior capsule rupture risk during cataract surgery: A meta-analysis

Author: Zhong Z, He Z, Yu X, Zhang Y.

Geographical coverage: United Kingdom (UK), United States of America (USA), and Sweden

Sector: Cataract surgery

Sub-sector: Treatment complications

Equity focus: Not reported

Study population: Patients with cataract

Review type: Effectiveness review

Quantitative synthesis method: Meta-analysis

Qualitative synthesis method: Not applicable

Background:

Posterior capsule rupture (PCR) is a significant complication of cataract surgery, heightening the risk of adverse outcomes such as endophthalmitis, retinal detachment, and macular oedema. While relatively rare, PCR remains a critical modifiable factor influencing surgical success. Intravitreal injections (IVIs)—particularly anti-VEGF agents and corticosteroids—are now the most commonly performed intraocular procedures worldwide, used primarily to treat neovascular age-related macular degeneration (nAMD), diabetic macular oedema (DME), and retinal vein occlusions (RVO). Despite their widespread use, studies investigating the link between IVIs and PCR have yielded conflicting results. Some report increased PCR risk regardless of injection frequency, while others suggest a dose-response relationship. Understanding this association is increasingly important as more patients with IVI histories undergo cataract surgery.

Objectives:

To summarise current evidence on the association between prior intravitreal injection (IVI) and posterior capsule rupture (PCR) during cataract surgery.

Main findings:

Six retrospective cohort studies published between 2016 and 2021 were included in this meta-analysis. These studies were conducted in the UK (3 studies), the USA (2), and Sweden (1). All six studies, covering a total of 1,051,097 surgical eyes, examined the association between prior IVI and PCR. The studies were of good quality, with an average Newcastle-Ottawa Scale (NOS) score of 7.12 (range: 6 to 8).

Key findings:
– Prior IVI significantly increased the risk of PCR during cataract surgery (pooled odds ratio [OR]: 2.01; 95% confidence interval [CI]: 1.35 to 3.00).
– Subgroup analysis excluding crude estimates still showed a statistically significant association (OR: 1.44; 95% CI: 1.17 to 1.77).
– Four studies explored the number of prior IVIs and found a dose-response relationship: each additional IVI increased the odds of PCR by 3% (OR: 1.03; 95% CI: 1.01 to 1.06).
– Subgroup analysis with adjusted estimates confirmed a statistically significant, albeit attenuated, effect (OR: 1.02; 95% CI: 1.01 to 1.04).

Methodology:

The authors searched PubMed, Embase, and ClinicalTrials.gov for English-language case-control or cohort studies published before October 2021. These studies assessed the association between prior intravitreal injections (IVIs) and posterior capsule rupture (PCR). Reference lists of included articles were also screened for additional eligible studies.

Two reviewers independently screened titles and abstracts, followed by full-text assessment and data extraction. Disagreements were resolved through discussion or consultation with a third reviewer. Study quality was assessed using the Newcastle-Ottawa Scale (NOS). Data were synthesised using a random-effects meta-analysis model, with subgroup analyses based on whether estimates were adjusted. Heterogeneity was assessed using the Cochrane Q-test and I² statistics. Sensitivity analysis was performed using single-study exclusion, and publication bias was evaluated with Begg’s and Egger’s tests.

Applicability/external validity:

The review did not directly address applicability or generalisability. All included studies were from high-income countries, and the absence of discussion on surgical techniques, healthcare settings, or patient comorbidities introduces uncertainty about whether findings are transferable to other settings. Publication bias was evident in relation to the effect of prior IVIs on PCR risk.

Geographic focus: The six studies were conducted in the UK, USA, and Sweden. No geographic restrictions were applied during study selection.

Summary of quality assessment: Overall, there is medium confidence in the review’s conclusions. While the included studies were of good methodological quality, the restriction to English-language articles and presence of publication bias limit the overall strength of the evidence base.