Risk of post-injection endophthalmitis peaks within the first three injections of anti-vascular endothelial growth factor therapy: A nationwide registry-based study.

PURPOSE: To report the incidence of post-injection endophthalmitis (PIE) and the cumulative risk associated with repeated injections of intravitreal anti-vascular endothelial growth factor (anti-VEGF). METHODS: We employed nationwide registries in Denmark to include all individuals aged ≥40 years who received at least one intravitreal anti-VEGF injection in 2007-2022. Our primary endpoint PIE was identified using specific diagnostic codes for endophthalmitis and procedure codes for vitreous biopsy within 10 days prior to and 120 days post-injection. Patients were stratified according to the underlying diagnoses for which they received the treatment. The relative risk (RR) for PIE was calculated between groups based on the number of injections received by the patients. RESULTS: We identified 60 825 patients who received intravitreal anti-VEGF treatment during study time, with a median age of 77.2 years and females constituting 58.1%. We identified 232 cases of PIE after 1 051 549 injections during follow-up, resulting in an incidence of 0.022% [95% CI 0.019%-0.025%]. Despite a linear growth in annual anti-VEGF use, the incidence remained stable at 0.020% [95% CI 0.017%-0.023%] from 2013 to 2022. Compared to patients receiving 1-3 injections, RR for patients receiving 4-20, 21-40, and >40 injections were 0.46 [95% CI 0.34-0.63], 0.32 [95% CI 0.21-0.50], and 0.54 [95% CI 0.36-0.81], respectively. Findings were similar across the different diagnoses. CONCLUSIONS: Based on 16 years of nationwide registry data, this study identified a low and stable incidence of PIE. Notably, the highest risk of endophthalmitis was within the first three anti-VEGF injections.

Legal obligation in the general population: face mask influence on endophthalmitis after intravitreal injection.

PURPOSE: To investigate whether compulsory face masking in public life changes the incidence or pattern of post-injection endophthalmitis (PIE). PATIENTS AND METHODS: All injections of bevacizumab, ranibizumab, aflibercept, dexamethasone or triamcinolone between 01/01/2015 and 12/31/2021 at the University Eye Clinic of Tuebingen were included in this retrospective analysis. The injection procedure itself was unchanged since 2015 and included the use of a sterile drape covering the head up to the shoulders which prevents airflow toward the eye. Furthermore, all staff wore a face mask and gloves at all times. The two study periods were defined by the introduction of a compulsory face masking rule in public life (01/01/2015 until 04/27/2020 vs. 04/28/2020 until 12/31/2021). RESULTS: A total of 83,543 injections were performed in the tertiary eye clinic, associated with a total of 20 PIE (0.024%, 1/4177 injections). Of these, thirteen PIE were documented during the pre-pandemic period (0.021%, 1/4773 injections) and seven PIE during the pandemic period (0.033%, 1/3071 injections). No significant difference in PIE risk was observed (p = 0.49), and there was no case of oral flora associated PIE. CONCLUSION: Although some potential confounders (wearing time, skin flora) could not be considered, there was no clear signal that the introduction of compulsory face masking in public life did alter the risk for PIE in our patient population. Three and six months after PIE, no difference in visual acuity was detectable between the two study periods.

Does Pharmaceutical Compounding of Vascular Endothelial Growth Factor Inhibitors for Intravitreal Use Alter the Risk of Post-injection Endophthalmitis?

PURPOSE: To investigate the safety of pharmaceutically compounded syringes for intravitreal administration of anti-vascular endothelial growth factor (anti-VEGF) drugs. METHODS: Single center, retrospective chart review. From 2015 to 2019, Oslo University Hospital, Norway gradually implemented pharmaceutical compounding and splitting of bevacizumab, ranibizumab, and aflibercept vials into multiple prefilled syringes for intravitreal use. Medical records of all post-injection endophthalmitis (PIE) cases in this 5-year period were reviewed. The incidences of PIE associated with compounded and clinician-withdrawn syringes were compared. RESULTS: In 5 years, the total number of anti-VEGF injections was 112,926; 68,150 procedures (60%) utilized compounded syringes, and 44,776 procedures (40%) utilized clinician-withdrawn syringes. A total of 11 PIE cases were identified (incidence 0.10 per 1000; 95% CI 0.05-0.17). Five PIE cases were associated with compounded syringes (incidence 0.07 per 1000; 95% CI 0.03-0.17); 3 of these were culture positive. Six PIE cases were associated with clinician-withdrawn syringes (incidence 0.13 per 1000; 95% CI 0.06-0.29); 2 of these were culture positive. The relative risk of PIE following procedures utilizing compounded versus clinician-withdrawn syringes was 0.55 (95% CI 0.17-1.79; p = 0.32). CONCLUSION: Use of compounded anti-VEGF drugs in a large clinical setting was not associated with an altered risk of PIE. The finding adds to the evidence that splitting of vials into prefilled syringes for intravitreal injections is safe, provided that an appropriate pharmaceutical compounding procedure is strictly followed.

Urgent Vitrectomy with Vancomycin Infusion, Silicone Oil Endotamponade, and General Antibiotic Treatment in Multiple Cases of Endophthalmitis from a Single Day of Intravitreal Injections-Case Series.

The aim of this study was to report on the anatomical and functional results of surgical management of seven cases of endophthalmitis related to a single day of intravitreal aflibercept injections. Patients with signs of endophthalmitis who underwent aflibercept injections (seven eyes) performed on the same day were retrospectively evaluated. The data of visual acuity and optical coherence tomography (OCT) within nine months of the follow-up and the treatment and results of microbiological cultures are reported. Four of the total seven cases had a positive bacterial culture outcome (Streptococcus mitis). All patients underwent vitrectomy combined with phacoemulsification when the eyes were not pseudophakic, vancomycin infusion, and silicone oil tamponade within 24 h; additionally, systemic antibiotics were administered intravenously. The final best-corrected visual acuity (BCVA) after the treatment was finger counting or light perception in all cases, and all eyes were saved with disruption of the inner retinal layers and stabilization of the retina in regard to changes related to the wet age-related macular degeneration (AMD). Although the retinal anatomy was mostly preserved, most of the patients affected by Streptococcus mitis-induced endophthalmitis did not regain baseline vision after the therapy.

Effectiveness of immediate vitrectomy and intravitreal antibiotics for post-injection endophthalmitis.

PURPOSE: To show that an immediate vitrectomy with an intravitreal injection of antibiotics can be an effective approach for the treatment of acute endophthalmitis following intravitreal injections. METHODS: We reviewed all cases of clinical endophthalmitis caused by an intravitreal injection that were treated in our department between March 2012 and November 2019. Only patients that underwent a vitrectomy within 6 h after presentation to the clinic and with a documented visual acuity shortly before the causative event were included. Baseline best-corrected visual acuity (BCVA) before the causative event was compared to BCVA measured within a follow-up period of 8 months (up to 14 months). RESULTS: In total, 30 eyes of 30 patients were included. The BCVA before the intraocular infection was a mean value of 0.55 logMAR, and the BCVA on the day of the endophthalmitis decreased significantly to 1.66 logMAR. Within 2 months following the pars plana vitrectomy (PPV), the mean BCVA improved to 0.83 logMAR. Eight months following PPV (mean value, 8.20 months; SD, 3.59 months), the mean BCVA was 0.63 logMAR. In the last follow-up interval most of the eyes recovered, and the BCVA did not differ significantly from baseline. Two eyes underwent further pars plana surgery during the follow-up period. No enucleation was required. CONCLUSION: In this study, we have shown that an immediate vitrectomy with subsequent intravitreal injection of antibiotics is an effective option for treating post-injection endophthalmitis and frequently results in recovery of vision; thus, it should be performed as early as possible, where available.

Protocolo de injeções intravítreas do Hospital de Clínicas de Porto Alegre: uma revisão de condutas para uma assistência mais que qualificada / Hospital de Clínicas de Porto Alegre intravitreal injection protocol: a literature review to improve assistance

A injeção intravítrea é o procedimento oftalmológico mais realizado no mundo. Através dessa técnica é possível administrar medicamentos para o segmento posterior do olho, sendo a via de escolha para o tratamento da maioria das patologias coriorretinianas. O evento ocular adverso mais grave é a endoftalmite pós injeção. Diversas medidas foram sugeridas para diminuição do risco dessa complicação, com evidências variáveis. Tendo em vista o grande número de injeções realizado em nosso serviço de oftalmologia do Hospital de Clínicas de Porto Alegre (HCPA), realizamos uma revisão da literatura com o objetivo de definir as melhores práticas. Nós descrevemos a evidência disponível para os principais aspectos dos diferentes estágios do procedimento (pré injeção, peri injeção e pós injeção) e apresentamos nosso protocolo. A medida com maior evidência científica na profilaxia da endoftalmite é a aplicação de iodopovidona tópica pelo menos trinta segundos antes da injeção. (AU)

Intravitreal injection is the most widely performed ophthalmologic procedure in the world. This technique allows for delivering therapeutic substances to the posterior segment of the eye, being the route of choice for the treatment of most chorioretinal diseases. The most feared adverse event is post-injection endophthalmitis. Many measures have been described to lower the risk of this complication, with variable evidence. In view of the great number of injections performed at our ophthalmology practice at Hospital de Clínicas de Porto Alegre (HCPA), we searched the literature for available evidence on the best practice standards. We describe the available evidence for major aspects of the different stages of the procedure (pre-injection, peri-injection, and post-injection) and then introduce our protocol. The measure with most scientific evidence of efficacy in preventing endophthalmitis is topical povidone- iodine administration at least 30 seconds before the injection. (AU)