Prophylactic Antibiotics for Postcataract Surgery Endophthalmitis: A Systematic Review and Network Meta-Analysis of 6.8 Million Eyes

Authors: Kato A, Horita N, Namkoong H, Nomura E, Masuhara N, Kaneko T, Mizuki N, Takeuchi M.

Geographical coverage: USA, UK, Singapore, Turkey, Canada, Colombia, Ireland, Norway, Israel, Argentina, Australia, Nepal, France, Spain, India, Brazil, China, and Sweden

Sector: Cataract surgery

Sub-sector: Antibiotics

Equity focus: Not reported

Study population: Patients with cataract

Review type: Effectiveness review

Quantitative synthesis method: Meta-analysis

Qualitative synthesis method: Not applicable

Background:

Cataract surgery is one of the most commonly performed ophthalmic procedures in developed countries, with its frequency rising due to ageing populations and advances in surgical technology. A major postoperative concern is endophthalmitis, a serious vision-threatening intraocular infection typically caused by bacteria from the patient’s own eyelid flora. To mitigate this risk, perioperative antibiotic prophylaxis is widely practised via various routes of administration. However, because endophthalmitis is very rare (occurring in <0.1% of cases), conducting high-quality randomised controlled trials is challenging. As a result, clinical guidelines often rely on observational data. Previous meta-analyses suggest that antibiotics such as cefuroxime, moxifloxacin, and vancomycin can reduce infection risk, though robust comparative evidence remains limited. Therefore, the optimal antibiotic and route of administration for preventing endophthalmitis after cataract surgery is still uncertain.

Objective:

To identify the optimal prophylactic antibiotic regimen for preventing postoperative endophthalmitis (POE) following cataract surgery.

Main findings:

The review included 51 studies (43 retrospective observational, 6 prospective observational, and 2 RCTs). Most studies were conducted in the United States (n=10), followed by Spain (n=7), India (n=6), Brazil (n=3), China (n=3), and Sweden (n=3). Forty-five studies provided data allowing direct head-to-head comparisons, and six studies included three or more treatment arms. Notably, 38 studies (75%) included a treatment arm with no prophylactic antibiotics. The most commonly evaluated prophylactic regimens were single-drug intracameral cefuroxime (15 studies) and single-drug intracameral moxifloxacin (12 studies). Network analysis indicated that comparisons between no antibiotic prophylaxis and these two regimens were the most frequently assessed.

An intracameral injection of vancomycin had the greatest protective effect against endophthalmitis (odds ratio [OR] ~0.03, 99.6% confidence interval [CI]: 0.00–0.53; corrected P = 0.006; P-score = 0.945), followed by intracameral cefazolin (OR ~0.09, 99.6% CI: 0.02–0.42; corrected P < 0.001; P-score = 0.821), cefuroxime (OR ~0.18, 99.6% CI: 0.09–0.35; corrected P < 0.001; P-score = 0.660), and moxifloxacin (OR ~0.36, 99.6% CI: 0.16–0.79; corrected P = 0.003; P-score = 0.455). While one RCT supported the efficacy of intracameral cefuroxime and another supported moxifloxacin, no RCTs evaluated vancomycin or cefazolin. A sensitivity analysis by route of administration showed that intracameral injection (pooled OR ~0.19, 99.4% CI: 0.12–0.30; corrected P < 0.001; P-score = 0.726) was the only route that significantly decreased the risk of POE.

Methodology:

Searches were conducted in PubMed, Web of Science Core Collection, the Cochrane Library, and Embase (initial search on 28 May 2021) without date restrictions. An updated PubMed search was done on 22 July 2022. Reference lists of relevant review articles were also scanned for additional studies. Both RCTs and observational studies were included if they were published in English, involved patients undergoing cataract surgery, and reported on the use of perioperative antibiotics via any route.

Two reviewers independently screened all titles and abstracts, reviewed full texts, and extracted data. Discrepancies were resolved through discussion or consultation with a third reviewer. The quality of observational studies was assessed using the Newcastle–Ottawa Scale, and RCTs were evaluated with the Cochrane Risk of Bias Tool. Data were synthesised using a random-effects network meta-analysis. Heterogeneity was assessed using the I² statistic, and sensitivity analyses were performed focusing on antibiotic type and single-arm incidence of endophthalmitis.

Applicability/External Validity:

The review did not explicitly discuss the external validity of its findings. However, it noted that most included studies were observational and often lacked adjustment for confounders. There was also considerable variability in clinical practices (e.g. surgical techniques and disinfection protocols) across studies. The evidence for vancomycin and cefazolin in particular was based on relatively few studies. These factors may limit the generalisability of the results. The authors highlighted the need for further research, ideally through well-designed trials or large registries, to confirm that the findings are applicable across different healthcare settings.

Geographical focus:

No geographical limits were applied. The included studies were conducted across a broad range of countries, including the USA, UK, Singapore, Turkey, Canada, Colombia, Ireland, Norway, Israel, Argentina, Australia, Nepal, France, Spain, India, Brazil, China, and Sweden. This diversity suggests wide relevance, although the restriction to English-language publications means some regions’ data might not be represented.

Summary of quality assessment:

Overall, there is medium confidence in the review’s conclusions. The literature search was comprehensive. Inclusion and exclusion criteria were clearly defined. Two reviewers independently performed study selection and data extraction, resolving disagreements by discussion or with a third reviewer. Study quality was appraised using established tools, and the characteristics of included studies were well documented. The network meta-analyses were appropriately performed and heterogeneity was addressed. However, the search was limited to English-language articles, and the review did not provide a list of excluded studies. Furthermore, the findings were not stratified by the risk-of-bias status of the studies. These limitations mean the results should be interpreted with some caution.