Endophthalmitis risk low after Intravitreal Injections, finds JAMA study

Endophthalmitis (EO) is a severe form of eye inflammation that may result in irreversible blindness if the intraocular infection is not properly treated. Anti-VEGF injections require repeated injections on a regular basis. Despite that subsequent injections did not increase the risk of EO compared with the first one, awareness of the risk remains clinically relevant as the number of injections increases.

Given the high volume of IVIs performed annually with limited availability of Operating Rooms (ORs), these injections were typically administered in an office setting in the US. Iatrogenic infection remains a primary concern for office based IVI, yet evidence from primary research remains controversial. These findings suggest a need for systemic evidence on EO rates and other safety outcomes following anti-VEGF IVIs in the 2 settings. Tong Li and team conducted a meta-analysis evaluating the safety of anti-VEGF IVI in the office and OR settings and discuss the implications for future practice.

This study was performed based on the Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guideline. PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov were searched from database inception to July 2020. The study focused on patients who received IVI with anti-VEGF drugs alone or combined with panretinal photocoagulation, laser, or photodynamic therapy. Two reviewers (T.L. and J.S.) independently screened the titles and abstracts to assess the initial eligibility of a study. A meta-analysis was conducted to determine the rates of endophthalmitis (EO) and culture-positive EO. Rates of EO and culture-positive EO following anti-VEGF IVIs in the OR and office-based setting were determined.

Thirty-one studies with a total of 12,75,815 injections were included. Comparative analysis suggested no difference between rates of EO after IVIs performed in the office and OR settings (P = .57) were identified, yet a higher rate of culture-positive EO was found in the office setting (P = .006).

The pooled rates of EO following anti-VEGF IVIs were 0.03% (95% CI, 0.03-0.04) and 0.02% (95% CI, 0.01-0.04) in office and OR settings, respectively, and the pooled rates of culture-positive EO were 0.01% (95% CI, 0.01-0.02) and 0.01% (95% CI, 0-0.02). The pooled rates of other ocular and systemic adverse events were low.

IVIs of anti-VEGF agents are conducted in the OR because of the perception that the negative pressure environment of the OR can effectively reduce the risk of intraocular infections. However, a growing number of practitioners in high-income countries, began to perform office-based IVIs as it is a more cost-effective, convenient, and efficient approach without compromising safety.

This comparative analysis, however, observed that culture-positive EO rates were significantly elevated in the office setting, yet this finding may be overestimated, as socioeconomic status was a potential confounder of the injection setting. Coagulase Negative Staphylococci (CoNS) has accounted for most culture-positive EO cases in both settings. As a normal flora typically found on the skin and conjunctiva, the spread of CoNS during the injection procedure (that is, from a patient's conjunctiva and lacrimal apparatus to the vitreous body) is a notable cause of infectious EO. Almost all studies included in this analysis reported povidone-iodine use prior to administering an IVI. Application of topical povidone-iodine for at least 30 seconds before each IVI can effectively reduce conjunctival bacteria counts and has become the standard of care for prophylaxis of intraocular infection.

S viridans was predominantly isolated in the office settings; a decreased rate of Streptococcus-induced EO was reported after IVIs in the OR. S viridans is a normal bacterial flora typically found in the oral cavity, upper respiratory tract, and gastrointestinal tract. It is postulated that talking or coughing during the IVI procedure, especially in the office setting where a face mask is not a standard of care, increases the chance of needle or conjunctiva contamination. Young age and female sex have been identified as risk factors associated with EO after IVIs of anti-VEGF medications.

Overall and culture-positive EO rates for ranibizumab appear higher in the office setting, while rates for bevacizumab seem higher in the OR, yet none of these results were statistically meaningful. The findings give the implication that not only a clean environment with strict aseptic rules during the injection procedure but also the degree to which sterile techniques were used for syringe preparation may also affect post injection EO.

Through simplifying the process of drawing up medication from vials, use of prefilled syringe was shown to effectively reduce the risk of contamination and subsequent post injection EO regardless of the anti-VEGF medication inside. The relatively higher EO rates after bevacizumab administration in the OR may be a result of suboptimal aseptic rules followed during drug preparation in a setting other than the standard compounding pharmacy.

"In conclusion, the rate of clinically suspected or culture positive EO following anti-VEGF IVIs was low whether the procedure was performed in the office or OR. Bacterial spectrum can differ between the 2 settings. In resource-limited regions, we were unable to identify evidence that in-office procedures would lead to more EO than injections in the OR. Using antisepsis from drug packaging and loading the syringes to the completion of IVIs in a well-controlled, clean environment may contribute to prophylaxis of post injection EO."

Source: JAMA Ophthalmol. doi:10.1001/jamaophthalmol.2021.3096