Comparative analysis of the safety and efficacy of intracameral cefuroxime, moxifloxacin and vancomycin at the end of cataract surgery: a meta-analysis

Methodological quality of the review:  High confidence

Author: Bowen RC, Zhou AX, Bondalapati S, Lawyer TW, Snow KB, Evans PR, Bardsley T, McFarland M, Kliethermes M, Shi D, Mamalis CA, Greene T, Rudnisky CJ, Ambati BK

Region: Canada, USA, India, Japan, Australia and Colombia

Sector: Cataract surgery

Sub-sector: Antibiotics, safety and efficacy

Type of cataract: Age-related cataract

Equity focus: None specified

Quantitative synthesis method: Narrative synthesis and meta-analysis

Qualitative synthesis method: Not applicable

Background:

Current practice methods are unclear as to the most safe and effective prophylactic pharmacotherapy and method of delivery to reduce postoperative endophthalmitis (POE) occurrence.

Research objectives:

The aim of this study was to evaluate the safety and efficacy of intracameral cefuroxime (ICC) intracameral moxifloxacin (ICM) and intracameral vancomycin (ICV) as prophylactic pharmacotherapy for prevention of POE.

Main findings:

Authors included a total of 17 studies in the review, of which one was a randomized controlled trial (RCT) and 16 were observational studies (15 retrospective cohort studies and 1 case-control study). Within the 16 observational studies, 9 compared ICC 1 mg/0.1 mL (4 ICC only and 5 ICC with topical antibiotics), 6 compared ICM 100–500 mcg/0.1 mL (with 1 study ranging from 5 to 50 mcg/0.1 mL)19 (2 ICM only and 4 ICM with topical antibiotics),7 11 19 20 24 25 and 5 compared ICV 1 mg/0.1 mL (1 ICV only and 4 ICV with topical antibiotics) against their corresponding controls. One study did not define the antibiotic doses administered. Of the 17 studies, eight were based in Europe (including the RCT), two were based in Canada, two in the USA, two in India, and one each was based in Japan, Australia and Colombia.

The 17 included studies had mild to moderate risk of bias. The overall quality of evidence for the included observational studies was moderate, and the RCT was attributed high quality and low risk of bias.

Based on the meta-analysis conducted by the authors, they noted that pooled data favoured the use of IC antibiotics at the end of phacoemulsification cataract surgery (odds ratio (OR), 0.20; 95% confidence interval (CI) 0.13 to 0.32; P<0.00001). Within ICC groups, a lower incidence of endophthalmitis in the treatment group was observed (OR, 0.26; 95% CI 0.15 to 0.45; P<0.00001). Authors reported these findings to be similar to the included RCT (OR, 0.21; 95% CI 0.08 to 0.54; P=0.001). Authors also note that a lower incidence of endophthalmitis in treatment groups was also observed for ICM and ICV.

In the secondary analyses, authors reported no statistically significant difference in POE rates between patients treated with IC antibiotics plus topical antibiotics and patients treated with IC antibiotics alone within the cefuroxime, vancomycin, and moxifloxacin groups.

Authors noted that the safety analysis showed minimal toxicity for moxifloxacin. Dosing errors led to the majority of toxicities with cefuroxime. Although rare, authors found that vancomycin was associated with toxic retinal events.

Based on analysis conducted, authors concluded that intracameral cefuroxime and moxifloxacin reduced endophthalmitis rates compared with controls with minimal or no toxicity events at standard doses. Additionally, intracameral antibiotics alone may be as effective as intracameral plus topical antibiotics.

Methodology:

Authors considered randomized controlled trials and observational studies that evaluated patients undergoing phacoemulsification cataract surgery with a minimum sample size of 500 eyes. Interventions included IC antibiotics at the end of cataract surgery. Comparisons included non-IC antibiotics at the end of cataract surgery. The primary outcome was the incidence of post-cataract surgery endophthalmitis. Secondary analyses examined the effects of geographic location, and the addition of topical antibiotics on POE incidence. Studies were excluded if they included extracapsular cataract extraction (ECCE) surgeries that could not be separated from phacoemulsification surgery data.

Authors also reviewed studies within their literature search that reported safety or toxicity data with ICC, ICM and ICV. Eligible studies included animal models or postoperative humans who underwent phacoemulsification cataract surgery. Toxicity to the cornea, anterior chamber (AC), or retina, or a change in intraocular pressure (IOP) or visual acuity (VA) were analysed.

Authors conducted a search on the several databases including BIOSIS Previews (ISI Web of Knowledge), CINAHL (EBSCOhost), ClinicalTrials. gov, Cochrane Library (Wiley Interscience), Dissertations & Theses Global (ProQuest), EMBASE (Embase.com), PubMed (National Library of Medicine), ScienceDirect (Elsevier) and Scopus (Elsevier) from inception to January 2017. There were no language restrictions. References in full-text articles were screened for relevance and added if they met inclusion criteria. Reviewers also contacted authors as needed for additional study details to assist in the data analysis.

Study selection was conducted by two reviewers independently. Two risk of bias tools were used to appraise included studies: one for the efficacy analysis, and one for the safety analysis. In addition, authors used the GRADEprofiler to assess the quality of evidence.

Review authors conducted a statistical analysis where included studies were stratified by the antibiotic used post-surgery. OR estimates were combined using the random effects Mantel-Haenszel method. Summary of OR estimates was given for each stratum and collection of studies. ORs compared IC versus non-IC antibiotics.

Heterogeneity was assessed by the Q and I2 statistics and results were displayed using forest plots. Funnel plots enabled evaluation of publication bias. Secondary analyses examined the effect of geographic location (Europe vs non-Europe) on the risk of POE while stratifying by antibiotic type. Similarly, the effect on POE of topical antibiotics in conjunction with the primary IC antibiotic was examined and stratified by antibiotic type. The number and percent of microorganisms identified in POE cases as well as the safety analysis were tabulated as descriptive statistics.

Applicability/external validity:

Authors note that geographic forest plot analysis showed statistical significance in favour of IC antibiotics regardless of location.

Geographic focus:

The review does not focus specifically on low- and middle-income countries. However, authors reported findings based on geographical location (European vs non-European), on the risk of POE of topical antibiotics in conjunction with the primary IC antibiotic. Authors noted that geographic forest plot analysis showed statistical significance in favor of IC antibiotics regardless of location. The average weighted POE incidence of ICC in Europe was 0.0366% compared with 0.0303% in non-European countries.

Quality assessment:

Overall, there is high confidence in the conclusions about the effects of this review. Authors conducted thorough searches of the literature to ensure all relevant studies were included in the review. Reviewers also used appropriate methods to select studies for inclusion, extract and assess risk of bias of included studies. Authors ensured included studies were similar enough to combine them in the meta-analysis, and appropriately reported heterogeneity and statistical significance of results.