POE is a rare but severe complication of cataract surgery, usually caused by the invasion of pathogens into the eyeball via the incision wound.2,3 Early-onset endophthalmitis occurs within 2 weeks after surgery; however, it is mostly seen within 1 week after surgery. A patient with this condition may experience eye pain and sudden loss of vision. Since the majority of patients are at home after surgery, diagnosis may be delayed. Once diagnosed, hospitalization and appropriate antibacterial therapy are required for a patient. A wound of 2–3 mm is made during cataract surgery and bacteria can enter the eye through this wound. Although lens replacement surgery is performed to improve visual acuity, endophthalmitis may greatly deteriorate vision and quality of life. Appropriate precautions should be taken to prevent POE.2,3 We conducted the first network meta-analysis of antimicrobial agents administered for the prevention of POE in a population of 6.5 million eyes. Among a wide variety of techniques, intracameral administration is currently the most reliable prophylaxis procedure with accumulated evidence (Fig. 3A, 3B). Intracameral vancomycin and cefazoline injections led to the best OR and P-scores in the main model (Fig. 3A, Supplementary Table 5). Cefuroxime and moxifloxacin via intracameral injection with the next best OR were supported by more robust evidence from numerous studies including one RCT for each drug (Table 1, Fig. 3A). These findings were validated by sensitivity analysis (Fig. 3C). To date, intracameral cefuroxime and moxifloxacin have been frequently evaluated on this topic; however, vancomycin and cefazoline may work as superior preventive medications. None of the combination regimen was a reasonable option.
We detected only two RCTs on this topic during our search. The European Society of Cataract and Refractive Surgeons multicenter study published in 2007 applied a 2 by 2 factorial design for 16,603 patients.8 The use of intracameral cefuroxime injection soon after surgery lowered the risk of POE, whereas topical perioperative levofloxacin did not.8 In 2019, Melega et al. reported another RCT that recruited 3,640 patients. Intracameral moxifloxacin injection reduced the occurrence of post-cataract endophthalmitis. Two ultra-large-scale retrospective cohort studies also confirmed the effectiveness of prophylactic intracameral antibiotic administration. Daien et al. investigated data from more than 2 million subjects and concluded that intracameral cefuroxime injection reduced the frequency of POE.9 According to a recent Indian observational study with 2 million post-surgical eyes, intracameral moxifloxacin lowered the incidence.10 Based on these RCTs and large cohort studies, intracameral cefuroxime and moxifloxacin were used as first-choice prophylaxis for POE after cataract surgery.
On the other hand, according to our network meta-analysis, vancomycin and cefazoline inoculated into the anterior chamber might be a better choice. We would like to discuss the merit of vancomycin and cefazoline in terms of antibacterial spectrum. Lalwani et al. reported that coagulase-negative Staphylococcus accounted for 50 of 73 (68.4%) eyes as causative microbe of endophthalmitis after cataract surgery.11 Fisch et al. described that POE was most frequently caused by Staphylococcus epidermidis and that gram-negative organisms were rarely isolated from this population.12 Cataracts are an age-related condition, and elderly patients with a history of hospitalization or previous antimicrobial therapy are likely to carry methicillin-resistant S. aureus or methicillin‐resistant S. epidermidis. From the perspective of antimicrobial spectrum, it is easy to explain why vancomycin, which is effective for methicillin-resistant microbes, was highly effective in preventing endophthalmitis. Cefazoline is a narrow-spectrum first-generation cephalosporin That is especially effective against gram-positive bacteria, and it may be an optimal agent to cover POE-causing microbes. Cefazoline is widely used to prevent wound infection in various surgeries involving skin incisions.13 Moxifloxacin is a broad-spectrum antibiotic that covers gram-positive, gram-negative, and anaerobic bacteria.14 However, moxifloxacin is usually not prescribed for the treatment of gram-positive coccus infections because more potent antibiotics with narrower coverage are preferred.15 Regarding the results of the network meta-analysis and the antimicrobial spectrum, vancomycin and cefazolin provided into the anterior chamber are attractive options. Nevertheless, we hesitate to recommend only vancomycin and cefazoline as first-choice prophylactic agents because they have been evaluated in a small number of observational studies and in far fewer patients than cefuroxime and moxifloxacin (Table 1, Table 2). Rather, we would like to equally recommend single-agent intracameral injection of the four drugs for now, and we hope to accumulate data on vancomycin and cefazolin in the future.
A limitation of this study is that a majority of the articles used for quantitative synthesis were observational studies without confounding factor adjustment (Table 1). The frequency of POE of 0.066% makes it very difficult to conduct high-quality RCTs and prospective studies. In addition to the prophylactic administration of antimicrobial agents, the development of postoperative endophthalmitis is also associated with underlying diseases, therapeutic agents, incision type, disinfection, and intraoperative complications. However, these factors were not considered in this study.
Despite this limitation, our research integrated the currently available data using a solid methodology. Our data would help clinicians and researchers select prophylactic antimicrobial administration after cataract surgery.
In conclusion, we performed the first network meta-analyses using data of more than 6.5 million eyes to identify efficacious antibiotic regimens to prevent POE. Multiple analyses confirmed the advantages of single-agent intracameral antibiotic administration. Cumulative evidence suggests that intracameral injection of cefuroxime and moxifloxacin decreased endophthalmitis. Vancomycin and cefazoline injected into the anterior chamber may be a better option. We would like to recommend single-agent intracameral injection of either vancomycin, cefazoline, cefuroxime, or moxifloxacin for the prevention of POE, and we hope that in future, more research will evaluate intracameral vancomycin and cefazoline in detail.