Drop-Free Approaches for Cataract Surgery

Neal H. Shorstein; William G. Myers

Disclosures

Curr Opin Ophthalmol. 2020;31(1):67-73. 

In This Article

Endophthalmitis Prophylaxis

The choice of antibiotic agent for intracameral injection must consider both effectiveness of infection prevention and safety to the corneal endothelium and retina.

Effectiveness

The primary advantage of intracameral antibiotic injection is the delivery of a very high concentration of drug directly into the operative, anatomical space at most risk of initial infection. The first large study showing benefit of an injected antibiotic at the time of surgery, was by Montan and associates in Sweden, using cefuroxime.[34] Within 5 years, Barry et al.[35] and the European Society of Cataract and Refractive Surgeons completed a randomized controlled trial showing the benefit of intracameral cefuroxime injection in reducing the incidence of endophthalmitis. The study produced the first, large prospective evidence showing the prophylactic benefit of any topical or injected antibiotic. There was some criticism of the study in the years following its publication, citing a higher than expected background infection rate, potential bias from stopping the study prior to full enrollment[36] (because the safety committee found a clear benefit to the injection) and a potentially better prophylactic antibiotic in the form of moxifloxacin.[37]

Subsequent observational studies supported the effectiveness of both cefuroxime and moxifloxacin injection in reducing postop endophthalmitis.[13,38,39] Rates of endophthalmitis in Sweden, India, and the United States, in centers where antibiotic injection is widely adopted, now typically number one infection in 5000 cases or fewer,[38–40] a remarkable improvement from the peak rates of 0.25% (1 in 400) in the early aughts, when clear cornea incisions were first adopted.[41] These very low rates of infection following conversion to intracameral injection were achieved in centers with an already low baseline infection rate, which speaks to the potential broad benefit of this modality irrespective of preadoption endophthalmitis rate.

Choice of Drug

For surgeons and surgery centers in Europe, where an approved cefuroxime product is available, and in India, where moxifloxacin is commercially available, the conversion to intracameral antibiotic injection is straightforward. In the United States, where no FDA-approved, commercial product is available, antibiotic must be compounded. The most reliable sources for these agents are large compounding pharmacies, termed by the government as outsourcing facilities, that follow section 503B of the Federal Food, Drug and Cosmetic Act of 2013. These pharmacies are inspected by the FDA and must provide a strict sterile environment and perform validating testing following current good manufacturing practices.[42]

The choice of antibiotic should follow an analysis of the types of endophthalmitis-causing organisms prevalent in the region where the surgery center is located and where the patient lives. European cataract centers have had substantial and successful experience with cefuroxime. The overall endophthalmitis rate has significantly dropped, albeit with a slight proportional uptick in (cefuroxime resistant) Enterococcus-associated cases.[43] In India, where Gram-negative organisms cause a proportionally higher number of postoperative infections, cefuroxime does not appear to be as effective as moxifloxacin.[39,44]

In the United States, moxifloxacin is the most popular antibiotic injection choice.[5] This may relate to the theoretic advantage of Gram-negative coverage, though the preponderance of endophthalmitis organisms in the United States are Gram positive.[45,46] Moxifloxacin is also notable for the simplicity of injecting an aliquot of full-strength brand name topical solution.[47] A caveat to this approach, however, is the current labeling of the product as 'not for intraocular use'. Herrinton et al.[13] could not detect a statistical difference between infection rates in eyes injected with 1 mg cefuroxime and those injected with 0.1 ml of 0.1% moxifloxacin. Recent evidence indicates, however, that a higher dose of drug might be more effective.[48]

Vancomycin, which has exquisite action against Gram-positive organisms, has generally fallen out of favor among surgeons because of hemorrhagic occlusive retinal vasculitis which has been associated with injections of this agent.[49] The US FDA and the American Society of Cataract and Refractive Surgery have issued advisories against routine intracameral injection of vancomycin.

Safety

Regarding the two commonly injected intracameral agents, cefuroxime is relatively safe for the cornea endothelium at a dosage of 1 mg.[50] A 9-mg dose was reported to cause temporary macular edema,[51] whereas injections exceeding 50 mg have resulted in permanent corneal and retinal damage.[52] Injections of the correct dosage of cefuroxime have also been reported to result in macular changes on optical coherence tomography (OCT);[53,54] however, the agents used do not appear to be approved, manufactured products and may have been contaminated or incorrectly compounded.

There is no established dose or injection method for moxifloxacin at this time. Injection volumes between 0.03 ml (166 μg)[55] and 0.1 ml (500 μg)[47] of 'full strength' moxifloxacin (0.5%) have been reported. This is compared with the standard dose of 1000 μg of cefuroxime. 'Undiluted' or 'full strength' moxifloxacin refers to a concentration of 0.5%, corresponding to the topical brand Vigamox (Alcon, Irvine, CA, USA) which was used as a source of moxifloxacin in earlier studies. Moxifloxacin may have a narrower therapeutic index than cefuroxime because of reports of toxicity to the cornea endothelium in the lab in concentrations as low as 500 μg/ml.[50,56] To address this, larger volume injections of at least 0.4 ml have been recently proposed of 0.1% or 0.15% solution.[57,58] Larger injection volumes may have the advantage of producing a more consistent final concentration of drug in the anterior chamber irrespective of a patient's pseudophakic volume.[59]

Elimination of Topical Antibiotic

Following the report of initial success of injected cefuroxime in Sweden, subsequent studies were notable in that a low rate of endophthalmitis was achieved with antibiotic injection alone, without prescribing perioperative antibiotic drops.[60,61] In addition, two large studies showed no statistical difference in infection rates in eyes treated with intracameral antibiotics and topical drops versus eyes receiving injection alone.[13,38]

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