Endophthalmitis following intravitreal injection of anti-VEGF agents: long-term outcomes and the identification of unusual micro-organisms

Abstract

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.

A prospective, randomised, placebo-controlled, double-masked, three-armed, multicentre phase II/III trial for the Study of a Topical Treatment of Ischaemic Central Retinal Vein Occlusion to Prevent Neovascular Glaucoma – the STRONG study: study protocol for a randomised controlled trial

“…In addition to the patients’ burden, several ocular drawbacks and side effects such as IOP elevation, endophthalmitis, retinal detachment or injury of the lens [20, 21], might be associated with the invasive and often multiple intravitreal injections. At present, PRP is the common method used for reducing retinal ischaemia or neovascularisation in patients with iCRVO, even though there are major drawbacks of PRP, such as persistent visual field defects.…”

Post-intravitreal injection endophthalmitis secondary to Turicella otitidis: a case report

“…Corynebacterium, a genus of gram positive bacilli or coccobacilli, is a rare cause of post-procedural endophthalmitis [5][6][7]. Corynebacterium was found in only about 1% of the Endophthalmitis Vitrectomy Study culture positive endophthalmitis cases [8] and has only rarely been reported after anti-VEGF injection [2]. This is the first report of Corynebacterium species Turicella otitidis endophthalmitis following an ocular procedure.…”

“…Intravitreal anti-vascular endothelial growth factor (VEGF) agents have transformed care for many vitreoretinal disorders, allowing visual improvement or stability in diseases with previously poor visual outcomes, such as age-related macular degeneration (AMD) with associated choroidal neovascularization (CNV). However, endophthalmitis remains a rare but potentially devastating complication of anti-VEGF intravitreal injection, with rates of post-injection endophthalmitis ranging from 1 case in 1000 to 1 in 6450 [1][2][3][4]. The majority of culture-positive endophthalmitis cases are coagulase-negative Staphylococcus species, which usually are associated with good outcomes.…”

Safety and Biocompatibility of Aflibercept-Loaded Microsphere Thermo-Responsive Hydrogel Drug Delivery System in a Nonhuman Primate Model

“…10 Repeated injections carry a risk of serious potential complications, including IVT hemorrhage, cataracts, endophthalmitis, and retinal detachment. 11,12 Furthermore, the human health care burden of these frequent injections is immense with approximately 6 million injections performed in the United States alone in 2016-a number that is expected to increase annually. 13,14 Therefore it is critical to find a therapy that is efficacious but requires less frequent administration to minimize the socioeconomic impact associated with recurrent injections and to lower the risk of associated potential complications.…”