Endophthalmitis rates after intravitreal injections can decrease with the implementation of a few relatively easy changes.
This article was reviewed by Sunir J. Garg, MD, FACS
In recent years, various factors have been associated with lower rates of endophthalmitis, some of which are intuitive and others not so much so.
Interestingly, the outcomes of endophthalmitis after intravitreal injections often are worse compared with other intraocular and endophthalmitis mostly because of the roughly three times higher incidence of oral flora, e.g., Streptococcus viridans, Sunir J. Garg, MD, FACS, explained. In cases, with infection from this pathogen, the vision often decreases to hand motions.
Dr. Garg is professor of ophthalmology and co-director of retina research, at MidAtlantic Retina, The Retina Service of Wills Eye Hospital, Philadelphia.
“We know that the oral flora is from bacterial dispersion from the oropharynx,” he said. “A significant reduction in bacterial dispersion and endophthalmitis resulted from the use of masks and/or implementation of a no talking policy during the procedure by all individuals in the room.”
They published their findings in Ophthalmic Surg Lasers Imaging Retina (2015;46:1028-34).
Presentation is everything
Preparation is always important. Ranibizumab (Lucentis, Genentech Inc.) previously was administered in a vial but became available in the United States in a prefilled syringe in 2016. Dr. Garg and colleagues conducted a retrospective study of this change at 10 centers to determine the effect.
The team compared the treatments administered conventionally with those administered via a prefilled syringe. Researchers found that the suspected endophthalmitis rate was reduced with use of the prefilled syringe, although the difference did not reach significance.
The study (Am J Ophthalmol https://doi.org/10.1016/j.ajo.2018.11.023) included 165,347 conventional injections and 78,407 prefilled syringe injections that were associated, respectively, with 43 and 12 cases of suspected endophthalmitis. These numbers translated to respective incidence rates of 1/3,845 and 1/6,534, Dr. Garg reported.
However, he pointed out, what was more impressive were the culture-positive results, which did reach significance. The respective culture-positive cases were 22 and 2, with incidence rates of 1/7,516 in the conventional group and only 1/39,205 in the prefilled syringe group (p = 0.025).
Another finding was that 27.3% of the conventional cases developed endophthalmitis from oral flora, which was not the case in the prefilled syringe group. This result was directly related to the visual outcomes; the conventional cases lost an average of 4.5 lines of vision compared with 0.38 line of vision in the prefilled syringe group (p = 0.0062). The average respective visual acuities were 20/250 and 20/50 (p = 0.00039), and more than 25% of conventional patients had counting fingers vision or lower.
Aflibercept (Eylea, Regeneron Pharmaceuticals) also will become available in a prefilled syringe in the United States in early 2020.
To drop or not to drop
The use of topical antibiotics are unnecessary when administering intravitreal injections as confirmed by two studies. The DRCR.net prospective study (Arch Ophthalmol 2012;130:809-10; doi: 10.1001/archophthalmol.2012.227) found 6/4,697 with an antibiotic and 1/3,333 without.
Dr. Garg and colleagues conducted a retrospective study (Ophthalmology 2014;121:283-9) of 117,000 injections and reported that the routine use of antibiotics increased the incidence of both the suspected and culture-positive cases, the visual outcomes did not improve, and the drugs bred resistance (Ophthalmology 2012;119:1420-4. doi: 10.1016/j.ophtha.2012.01.016. Epub 2012 Mar 13).
Povidone iodine 5%, an inexpensive and widely used agent, and is the only agent that has been shown to prevent endophthalmitis. Up to 25% of eyes have preoperative positive cultures right after instillation.
A drawback to its use are that some patients dislike how they feel after instillation. An alternative antiseptic used for other surgical preparation is chlorhexidine gluconate, a broad-spectrum antibiotic, but this should not be used for the ocular surface; however aqueous chlorhexidine can be used for the ocular antiseptic procedure before injections.
A retrospective study of aqueous chlorhexidine (Ophthalmology 2016;123:2588-94) reported that only three cases of endophthalmitis developed in 40,535 cases of intravitreal injections, for a rate of 0.0074%.
A prospective study (Retina 2018;38:2064-6) of 40 consecutive patients, 20 each received either povidone iodine or chlorhexidine, reported that pain scores associated with use of povidone iodine were higher than with aqueous chlorhexidine (7/10 versus 2/10, P < 0.001). Culture-positive rates were the same.
In an unpublished study, Dr. Garg and colleagues compared culture rates, corneal epithelium, and patient comfort using the two agents in a prospective study of 100 patients undergoing same-day bilateral intravitreal injections. One eye was randomly administered povidone iodine and the other to aqueous chlorhexidine.
The study showed that pain was greater with povidone iodine immediately after instillation (p < 0.001) but not on day 1 (p = 0.06). Most had no pain with either agent. If they did have pain, it was worse with povidone iodine at both time points.
The Ocular Surface Score, which measures epitheliopathy, was significantly (p < 0.001) better with aqueous chlorhexidine. The culture-positive rates were similar between the two groups.
Some patients may tolerate aqueous chlorhexidine better than povidone iodine, and both agents showed similar antimicrobial efficacy. No random controlled trials have compared the two. Aqueous chlorhexidine is not a standard of care in the United States, is more expensive, and must be obtained from a compounding pharmacy, he noted.
“Masks, no talking, and the use of prefilled syringes are associated with less endophthalmitis,” Dr. Garg concluded. “Routine use of topical antibiotics is useless and potentially harmful, Aqueous chlorhexidine may be a useful alternative to povidone iodine in some eyes.”
Sunir J. Garg, MD, FACS
This article is adapted from Dr. Garg's presentation at the American Academy of Ophthalmology 2019 annual meeting. Dr. Garg has no financial interest in the subject matter of this report.