Association of Acute Endophthalmitis With Intravitreal Injections of Corticosteroids or Anti–Vascular Growth Factor Agents in a Nationwide Study in France

Abstract

The number of patients affected by retinal diseases treated with intravitreal injections (IVTs) has resulted in a rapidly growing number of procedures. One of the worst complications after these injections is endophthalmitis.OBJECTIVE To evaluate the incidence of acute endophthalmitis after IVTs of corticosteroids or anti-vascular endothelial growth factor (anti-VEGF) agents. DESIGN, SETTING, AND PARTICIPANTS This population-based cohort study included patients undergoing IVTs from January 1, 2012, through December 31, 2015, in France. Data were acquired from the French medical-administrative database (Système National d'Information Inter-Régime de l'Assurance Maladie), which collects hospitalization discharge abstracts and out-of-hospital care information for the whole country. Data were analyzed from March through July 2017. EXPOSURES Intravitreal injections of corticosteroid or anti-VEGF agents. MAIN OUTCOMES AND MEASURES Incidence of acute endophthalmitis within 6 weeks after IVT by means of billing codes from a national database. RESULTS During the study period, 1 811 977 IVTs of corticosteroids or anti-VEGF agents performed on 254 927 patients (60.4% female; median age, 79 years [interquartile range, 70-85 years]) were analyzed. A total of 444 acute endophthalmitis cases (crude incidence, 0.0245%) were recorded. In multivariable analysis, which did not include adjustment for when the endophthalmitis occurred during the study period, the risk of endophthalmitis was lower in male patients (incidence rate ratio [IRR], 0.78; 95% CI, 0.63-0.96; P = .02), higher for corticosteroids than for anti-VEGF agents (IRR, 3.21; 95% CI, 2.33-4.44; P < .001), and higher for nonprefilled syringes of anti-VEGF medications than prefilled syringes for ranibizumab (IRR, 1.63; 95% CI, 1.15-2.30) and aflibercept (IRR, 1.82; 95% CI, 1.25-2.66; P < .001). CONCLUSIONS AND RELEVANCEThe findings from this study of a nationwide database appear to have confirmed the low incidence rate of acute endophthalmitis after IVTs of corticosteroids or anti-VEGF agents. Although an association may not necessarily indicate a cause and effect, the risk for acute endophthalmitis after IVTs appeared to be higher for corticosteroids compared with anti-VEGF agents, while a lower risk of endophthalmitis appeared to be found with prefilled syringes of anti-VEGF medications.

<p>Issues with Intravitreal Administration of Anti-VEGF Drugs</p>

“…Two large population-based studies have been published in recent years analyzing the endophthalmitis rate after intravitreal injection. 41,42 Baudin et al evaluated the incidence of acute endophthalmitis after intravitreal injection of corticosteroids or anti-VEGF agents in a nationwide study in France. Taking only the anti-VEGF injections into account, 1.67 million injections were evaluated from the French medical-administrative database.…”

“…The prefilled ranibizumab syringe therefore had decreased the rate of endophthalmitis by 40% compared with ranibizumab in a vial and by 46% for aflibercept in a vial. 41 Storey et al analysed 243 754 injections of ranibizumab in 10 centers in the USA (2016 to 2017) and Japan (2009 to 2017). 42 The suspected rate of endophthalmitis with an injection of ranibizumab in a vial was 0.026%, the rate of culture-positive endophthalmitis was 0.013%.…”

“…Both studies suggest that the endophthalmitis rate can be significantly reduced by prefilled syringes. 41,42 The main reason for decreased risk of endophthalmitis while using prefilled syringes is due to lack of need for transfer of drug into another syringe, thus reducing the manipulations. This results in improved safety.…”

The Argument for Sterile Loading of All Intravitreal Injections and the Benefit of Replicated Results

“…2 Baudin et al and our studies also found a 29% and 30% increased risk of endophthalmitis in women, repsectively. 1,2 These represent the first reports linking gender to endophthalmitis rates. Interestingly, despite age, gender and race almost uniformly being controlled for in other ophthalmic assessments (even when no demonstrable link exists to do so), gender has often been over-looked with regards to endophthalmitis after intravitreal injections.…”

“…Two recent studies have provided several new interesting findings that further our understanding of the risk factors associated with post-injection endophthalmitis. 1,2 While these findings are novel to many of us, it is possible Genentech suspected this issue would arise as they have already received FDA approval and distributed pre-packaged syringes for both their 0.5mg(October 2016) and 0.3mg(March, 2108) doses of ranibizumab. Together, these studies offer compelling evidence that a policy mandating the sterile packaging of all intravitreal injections needs to be strongly considered.…”