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BackgroundWhile the development of targeted molecular therapy to inhibit vascular endothelial growth factor (VEGF) has revolutionized the treatment and visual prognosis of highly prevalent retinal diseases such as diabetic retinopathy and age-related macular degeneration, each intravitreal injection of these agents carries a small risk of endophthalmitis which can be visually devastating. In the absence of specific guidelines, current management of post-injection endophthalmitis is typically extrapolated from data regarding endophthalmitis occurring after cataract surgery despite potential differences in pathogenic organisms and clinical course. Here, we assess the contribution of intravitreal injections of anti-VEGF agents to all cases of endophthalmitis at our tertiary care referral center and characterize the clinical outcomes and microbial pathogens associated with post-injection endophthalmitis in order to inform management of this serious iatrogenic condition.ResultsDuring the 7-year study period analyzed, 199 cases of endophthalmitis were identified using billing records. Of these, the most common etiology was post-surgical, accounting for 62 cases (31.2 %), with bleb-associated, endogenous, and corneal ulcer-related infections representing the next most frequent causes, comprising 15.6 % (31/199), 13.1 % (26/199), and 13.6 % (27/199) of all cases, respectively. Intravitreal injections of anti-VEGF agents represented 8.5 % of endophthalmitis (17/199 cases). Intraocular cultures yielded positive results in 75 % of post-injection cases, with the majority associated with coagulase-negative Staphylococcus. Consistent with prior literature, a case of Strep viridans displayed more rapid onset and progression. We also report the first association of Enterobacter cloacae and Lactococcus garvieae with post-injection endophthalmitis. While all but one patient were treated with initial vitreous tap and intravitreal injection of antibiotics, both patients with these rare organisms exhibited persistent vitritis requiring subsequent vitrectomy. Long-term outcomes of post-injection endophthalmitis indicated visual recovery to baseline levels, even with resumption of anti-VEGF agents following resolution of the acute infection.ConclusionsAcute endophthalmitis following intravitreal injections of anti-VEGF agents is an uncommon but potentially devastating complication which may be managed effectively with vitreous tap and injection of intravitreal antibiotics. However, persistent vitritis requiring subsequent vitrectomy should raise suspicion for unusual pathogens.

BackgroundThe purpose of this study is to evaluate the ocular tolerability and efficacy of sirolimus administered as subconjunctival or intravitreal injections in patients with non-infectious uveitis. Sirolimus as a Therapeutic Approach for Uveitis (SAVE) is a prospective, randomized, open-label, interventional study. Thirty patients were enrolled and randomized in 1:1 ratio to receive either intravitreal injections of 352 μg sirolimus or subconjunctival injections of 1,320 μg at days 0, 60, and 120, with primary endpoint at month 6.ResultsAt month 6, all subjects with active uveitis at baseline showed reduction in vitreous haze of one or more steps. Forty percent of subjects showed reduction of two steps or more of vitreous haze (four in each group), and 60% showed a reduction of one-step vitreous haze (seven in group 1 and five in group 2). Changes in the inflammatory indices were statistically significant (p < 0.05) in both study groups. Thirty percent of patients gained one or more lines of visual acuity, 20% lost one or more lines, and 50% maintained the same visual acuity. There were no statistically significant differences between the two study groups at month 6. No serious adverse events were found to be related to the study drug.ConclusionLocal administration of sirolimus, either intravitreally or subconjunctivally, appears to be safe and tolerable. No drug-related systemic adverse events or serious adverse events were noted. Sirolimus delivered as either an intravitreal or subconjunctival injection has demonstrated bioactivity as an immunomodulatory and corticosteroid-sparing agent in reducing vitreous haze and cells, improving visual acuity, and in decreasing the need for systemic corticosteroids.

BackgroundThe purpose of this study is to describe and quantify the benefit of ultra-wide-field imaging and fluorescein angiography (FA) in the management of non-infectious retinal vasculitis. In this prospective observational cohort series, patients with non-infectious retinal vasculitis were evaluated and enrolled by four investigators from the Divisions of Retina and Ocular Immunology at the Wilmer Eye Institute. In each patient, disease activity and the need for management changes were assessed, based on clinical examination with or without standard (60°) imaging and then with the addition of ultra-wide-field pseudo-color scanning laser ophthalmoscope (SLO) images and FA using the Optos ultra-wide-field SLO (Optos Panoramic 200MA™, Optos PLC, Dunfermline, Scotland, UK). A standardized questionnaire was completed by each investigator at the time of the clinical evaluation.The primary outcome was the percentage of patients whose management was changed by clinical examination and standard FA, compared with clinical examination plus ultra-wide-field imaging. The secondary outcome was the percentage of patients whose disease was determined to be active based on each modality.ResultsSeventy-one visits from 23 patients were reviewed and analyzed. Based on examination plus ultra-wide-field imaging and ultra-wide-field angiography, disease activity was detected in 48/71 (68%) compared with 32/71 (45%) based on examination and standard FA (P = 0.0095). Based on the clinical examination alone, the decision to alter management was made in 4 of 71 visits (6%), and an additional 3 of 71 (4%) based on simulated standard FA. The addition of ultra-wide-field SLO pseudo-color images altered management in an additional 10/71 visits (14%), and 36/71 (51%) with the addition of ultra-wide-field FA.ConclusionsUltra-wide-field fluorescein imaging and angiography can provide additional information that may be important and relevant in the management of retinal vasculitis.

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These data suggest that decreases in plasma free-VEGF levels are greater after treatment with aflibercept or bevacizumab compared with ranibizumab at 4 weeks. At 52 and 104 weeks, a greater decrease was observed in bevacizumab versus ranibizumab. Results from 2 subgroups of participants who did not receive injections within at least 1 month and 2 months before collection suggest similar changes in VEGF levels after stopping injections. It is unknown whether VEGF levels return to normal as the drug is cleared from the system or whether the presence of the drug affects the assay's ability to accurately measure free VEGF. No significant associations between VEGF concentration and systemic factors were noted.

Approximately half of the treated eyes had resolution of intraocular inflammation at 3 months after corticosteroid injection.