March 2019

RESIDENTS

EyeWorld journal club
Review of “Safety and efficacy of intracameral moxifloxacin for prevention of post-cataract endophthalmitis: randomized controlled clinical trial”


by the residents of the University of Illinois at Chicago and William Mieler, MD


William Mieler, MD, director of
residency and vitreoretinal fellowship training, Department of Ophthalmology & Visual Sciences, University of Illinois at Chicago


University of Illinois at Chicago residents; top row, from left: third-year residents Lindsay Machen, MD, Wyatt Messenger, MD, Alisa Thavikulwat, MD, Grace Dunbar, MD; middle row, from left: second-year residents Levi Kanu, MD, Judy Chen, MD, Priyanka Chhadva, MD, Kelley Bohm, MD, Talisa de Carlo, MD, Daniel Oh, MD; bottom row, from left: first-year residents Nita Valikodath, MD, Emily Cole, MD, Lawrence Geyman, MD, Samuel Burke, MD, Rajvi Mehta, MD
Source: University of Illinois at Chicago

Critics of intraocular antibiotic prophylaxis often point to the lack of enough randomized clinical evidence. I asked the University of Illinois at Chicago residents to review this relatively small randomized trial looking at intracameral moxifloxacin prophylaxis that is published in this month’s JCRS.

—David F. Chang, MD,
EyeWorld journal club editor


Postoperative endophthalmitis (POE) is a rare but serious potential complication of cataract surgery with often devastating visual outcomes. In an effort to reduce the incidence of POE, cataract surgeons have increasingly utilized prophylactic intracameral (IC) antibiotics, the most common of which include vancomycin, moxifloxacin, and cefuroxime. The utility of IC antibiotics has been recognized in the Preferred Practice Pattern guidelines from the American Academy of Ophthalmology.1 Despite the significant reduction in infection rates with IC antibiotics, widespread adoption remains stagnant, limited both by antibiotic availability and concern regarding dilution errors and contamination.2,3
The strongest data supporting the use of IC antibiotics are from the European Society of Cataract & Refractive Surgeons, which in 2007, published the results of the first large prospective, randomized, multicenter study that demonstrated IC cefuroxime to be associated with a 4.92-fold decrease (95% confidence interval 1.97–12.9) in the risk of POE.2 Since then, the use of prophylactic IC cefuroxime has been adopted in Europe where IC cefuroxime is commercially available (Aprokam, Thea Pharmaceuticals, Clermont-Ferrand, France). This formulation is not currently available in the U.S. or in much of the rest of the world.
In Australia, Au et al. performed a retrospective cohort study on 14,805 cataract surgeries before and after the introduction of IC vancomycin. They found a nine-fold reduction in the incidence of POE (P<0.0001).4 However, a recent report published by a joint American Society of Cataract and Refractive Surgery/American Society of Retina Surgeons task force found 36 cases of hemorrhagic occlusive retinal vasculitis associated with prophylactic IC vancomycin use after uncomplicated cataract surgery.5 Because of this potentially catastrophic complication, use of IC vancomycin fell out of favor with some cataract surgeons.
Finally, preservative-free isotonic IC moxifloxacin 0.5% was found in a large retrospective study including 600,000 cases by Haripriya et al. to reduce the rate of POE after phacoemulsification by nearly six-fold.6 Thus, for American cataract surgeons interested in the use of IC antibiotics to prevent POE, moxifloxacin is an appealing and available option. However, no randomized control trials had been performed until the article of interest we present here.
“Safety and efficacy of intracameral moxifloxacin for prevention of post-cataract endophthalmitis: a randomized controlled clinical trial” was the first prospective, randomized, controlled clinical trial to evaluate the safety and efficacy of IC moxifloxacin to prevent POE following cataract surgery. It was a single-site, prospective, randomized Phase 3 trial with partial masking. This contrasts with prior studies, which were predominantly retrospective, non-randomized, and observational in nature.
Melega and colleagues compared the outcomes of 3,640 eyes from 3,640 patients who were randomized 1:1 to receive either IC moxifloxacin or no IC injection at the conclusion of phacoemulsification cataract surgery. Both groups received the standard postoperative drop regimen including topical moxifloxacin. Fewer than 1% of patients were lost to follow up in each group. The authors reported similar preoperative demographics between groups, as there were no significant differences in gender, age, or preoperative best corrected visual acuity (BCVA). However, some relevant preoperative factors were not reported. The incidence of blepharitis, presence of ocular surface disease, prior intraocular surgery, presence of glaucoma drainage devices, and hospital location of surgery were not reported for inclusion in the evaluation.
The primary outcome of the study was the rate of POE by postop week 6. The intervention included a standard formulation of moxifloxacin drawn up into a 0.5 mL syringe with 0.03 mL injected via the sideport incision. The antibiotic was considered inherently safe due to the absence of preservatives, near-neutral pH, and isotonicity. The data show a statistically significant reduction in the rate of POE from 0.38% in the control group vs. 0.05% in the intervention group (p=0.035) without any notable effect on additional ocular parameters including BCVA, endothelial cell count, intraocular pressure, and central corneal thickness by postoperative week 6. This result is consistent with previous randomized trials and large retrospective analyses, which have demonstrated reduced rates of POE following injection of IC antibiotics.2–6
In total, there were eight cases of POE reported in this study. Only one case of POE occurred in the group treated with IC moxifloxacin, in which cultures grew methicillin- resistant Staphylococcus aureus sensitive only to vancomycin. Two of the remaining cases of POE, in the control group, were culture-positive for fluoroquinolone-sensitive organisms, suggesting that IC moxifloxacin provides additional prophylaxis against POE beyond the standard postop fluoroquinolone drop regimen. While most cases of POE present within the first few weeks of treatment, further follow up beyond 6 weeks would have provided rates of subacute or chronic POE, which have clinically significant implications.
Although intraoperative complications, especially posterior capsule rupture, are known to be significant risk factors for POE, in only one case of POE in this study was there an intraoperative complication. Despite the high rate of posterior capsule rupture in this study (approximately 8% in both groups), intraoperative complications did not appear to influence the development of POE. Accordingly, some reporting from the authors about postop factors or complications that could have affected the POE rate would have been beneficial. Although the rates of posterior capsule rupture may not reflect those in every practice setting, they make this study particularly relevant to residency training programs, which have higher rates than private practice settings.7,8 Future studies could analyze data from combined private practice and academic centers, as well as control for surgeon experience and baseline levels of intraoperative complications.
Since moxifloxacin has wider commercial availability than some of the other IC preparations that have been studied, the lack of toxicity noted in this study could facilitate the implementation of IC moxifloxacin. IC moxifloxacin has been shown to have a broad spectrum of coverage with long-term stability and ease of preparation.9 These factors may motivate clinicians to reconsider the importance of IC antibiotics at the conclusion of phacoemulsification, especially in the academic setting with resident surgeons.
Limitations of the study include partial blinding, lack of a sham injection, use of resident surgeons alone, and the low incidence (37.5%) of culture-proven POE, raising the possibility of confounding cases of sterile vitritis or toxic anterior segment syndrome rather than infectious POE. Unfortunately, polymerase chain reaction (PCR) was unavailable for the detection and identification of bacterial contaminants. Additionally, surgeons and residents were not masked to the treatment, which may have introduced bias in postoperative assessments. However, the retina surgeons consulted to evaluate and treat the potential cases of POE were masked to the use of IC moxifloxacin. Surgery for all patients in this study was performed by ophthalmology residents, and the authors noted a slightly increased baseline incidence of POE in their population. Thus, there may be limited applicability to other practice settings in which resident surgeons are not employed. Finally, a sham injection would have improved the study by providing blinding of the surgeon and by being more comparable to the treatment group as any additional instrument introduced into the eye adds a potential risk for infection.
Overall, this rigorous study proves significant benefit to use of IC moxifloxacin in reducing the incidence of POE. In the future, assessment of specific infectious agents responsible for presumed POE will further clarify antibiotic effectivity. With its safety, widespread availability, and clear reduction in infection risk, IC moxifloxacin may be regarded as the next step in the evolution of cataract surgery.

References

1. Olson RJ, et al. Cataract in the Adult Eye Preferred Practice Pattern. Ophthalmology.
2017;124:P1–P119.
2. ESCRS Endophthalmitis Study Group. Prophylaxis of postoperative endophthalmitis
following cataract surgery: results of the ESCRS multicenter study and identification of risk factors. J Cataract Refract Surg. 2007;33:978–88.
3. Barry P. Adoption of intracameral antibiotic prophylaxis of endophthalmitis following cataract surgery: update on the ESCRS Endophthalmitis Study. J Cataract Refract Surg. 2014;40:138–42.
4. Au CP, et al. Efficacy and cost-effectiveness of intracameral vancomycin in reducing
postoperative endophthalmitis incidence in Australia. Clin Exp Ophthalmol. 2016;44:803–811.
5. Witkin AJ, et al. Vancomycin-associated hemorrhagic occlusive retinal vasculitis:
clinical characteristics of 36 eyes. Ophthalmology. 2017;124:583–595.
6. Haripriya A, et al. Endophthalmitis reduction with intracameral moxifloxacin prophylaxis: analysis of 600,000 surgeries. Ophthalmology. 2017;124:768–775.
7. Nguyen ET, Shorstein NH. Preparation of intracameral antibiotics for injection. J Cataract Refract Surg. 2013;39:1778–9.
8. Pingree MF, et al. Cataract surgery complications in 1 year at an academic institution. J Cataract Refract Surg.1999;25:705–8.
9. Hollander DA, et al. Bacterial endophthalmitis after resident-performed cataract surgery. Am J Ophthalmol. 2006;141:949–51.

Contact information

Mieler: wmieler@uic.edu

Review of “Safety and efficacy of intracameral moxifloxacin for prevention of post-cataract endophthalmitis: randomized controlled clinical trial” Review of “Safety and efficacy of intracameral moxifloxacin for prevention of post-cataract
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