Two interventions have been shown to be effective for preventing post-cataract surgery endophthalmitis: prepping the eye with povidone iodine and injecting intracameral antibiotics at the end of the case.

It’s long been known that povidone iodine can prevent post-cataract surgery endophthalmitis. A 1991 nonrandomized parallel trial showed that eyes prepped with povidone iodine 5% had significantly less culture-positive endophthalmitis than eyes prepped with silver protein solution.¹ More recent studies from intravitreal injections not only confirmed the importance of povidone in preventing endophthalmitis but also showed the lack of benefit of topical antibiotic drops.^2,3 Fortunately, povidone use does not result in bacterial resistance.⁴

It is possible to have low endophthalmitis rates using povidone without intracameral antibiotics,⁵ but absolute endophthalmitis rate comparisons between studies are not valid due to variations in techniques, pre- and postoperative regimens, flora, complication rates and so on. Although the safety profile of cataract surgery with pre-operative povidone-iodine preparation is fantastic, the evidence is clear that it can still improve with the use of intracamerals.^6,7

At the same time, there are no commercially available drugs for intracameral injection in the United States. Surgeons who are currently using intracamerals are either using compounded drugs or moxifloxacin taken out of the Vigamox (Alcon) bottle, whose label specifically states that it is not for intracameral use even though it is preservative-free.

LAYING OUT THE EVIDENCE

Studies with multiple antibiotics in varied settings have demonstrated the benefit of intracamerals. The European Society of Cataract and Refractive Surgery performed a multinational study of 16,600 patients prospectively randomized to intracameral cefuroxime and topical levofloxacin. Cefuroxime reduced endophthalmitis risk five-fold, and patients received no benefit from levofloxacin eyedrops.⁸ A 16,000-patient study in California showed a 22-fold reduction in endophthalmitis using a combination of cefuroxime (84%), moxifloxacin (15%), and vancomycin (1%).⁹ Studies in Spain and Sweden also strongly support cefuroxime.^10-12

Moxifloxacin provides broader coverage against bacteria than cefuroxime, and studies have also demonstrated its effectiveness. Aravind Eye Hospital introduced intracameral moxifloxacin after manual small incision cataract surgery in its charity patients. The rate in the 38,000 patients postmoxifloxacin (0.02%) was significantly less than the rate in the 38,000 patients premoxifloxacin (0.08%, p<0.0001).¹³ This four-fold reduction occurred despite a significantly higher complication rate, a known risk factor for endophthalmitis, in the moxifloxacin group. The 0.02% rate was also lower than a group of private patients who did not receive intracameral antibiotics even though 79% of the private pay group had phacoemulsification (0.07%, p<0.0001). Similar reductions have been found after phacoemulsification in Japan (0.05% to 0.016%).¹⁴

Intracameral cefazolin reduced the endophthalmitis rate from 0.42% to 0.047% in Spain.¹⁵ Vancomycin decreased the rate from 0.097% to 0% (P=0.0015) at an ASC in Texas, and it also reduced endophthalmitis cases at a hospital in Australia (0.43% to 0.049%, P<0.0001).^16,17

On the other hand, postoperative topical antibiotics, used by 97% of ophthalmologists, have not been proven to prevent endophthalmitis.^18,6

THE OBJECTIONS TO INTRACAMERALS

In the 2014 ASCRS survey, 30% of U.S. participants injected intracamerals after surgery. Non-users cited lack of evidence (65%), compounding risk (49%) and cost (19%). By 2016, 40% used intracamerals, and 32% planned to within the next 12 months, presumably because of the strong evidence in favor of intracameral antibiotics.

Some argue that their endophthalmitis rates are so low that intracamerals are unnecessary, but even sites with low rates have improved with intracamerals. Resistance is not a major issue because such a high concentration of antibiotic is being delivered into the anterior chamber.⁷ In fact, transitioning from eyedrops to intracamerals could help antibiotics retain their effectiveness longer.

However, because commercially produced cefuroxime is unavailable in the United States, there are legitimate safety concerns. Vancomycin is associated with hemorrhagic occlusive retinal vasculitis (HORV), a complication that can be visually devastating, just like endophthalmitis.^19,20 Similar concerns have not arisen so far for the cephalosporins or moxifloxacin. Our understanding of HORV continues to evolve, including risk factors and incidence, which is fortunately extremely low. Given the effectiveness of intracameral vancomycin, I believe that surgeons are still justified in continuing to use the antibiotic. The American Society of Cataract and Refractive Surgery and American Society of Retinal Specialists jointly issued recommendations that continue to allow intracameral vancomycin use. They recommend that surgeons may want to consider a different antibiotic if the eyes are to be operated on in close succession, or may want to perform a dilated exam before the second eye surgery, if using vancomycin.²¹

At my surgery center, we use compounded moxifloxacin rather than product from a Vigamox bottle, which has been used intracamerally in studies.^22,23 Although any mixed or compounded medication has risk, compounded bevacizumab (Avastin, Genentech), for instance, is injected directly into the vitreous millions of times annually with a very low contamination rate.

CONCLUSION

I understand surgeons who still choose not to use intracamerals because of concerns over compounding. In an ideal world, a commercially available antibiotic should be available, but I do not see that happening any time soon. For me, the evidence of the effectiveness of intracameral antibiotic injection at the end of cataract surgery has made the small compounding-associated risk acceptable. OM

REFERENCES

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About the Author

Bryan S. Lee, MD, JD, is a cornea, cataract and refractive specialist in private practice at Altos Eye Physicians in Los Altos, Calif. He serves on the AAO Council and Online Education committee as well as the ASCRS Young Eye Surgeons committee and Phaco Fundamentals Classroom Editorial board.