Endophthalmitis in Eyes Treated With the Port Delivery System With Ranibizumab: Summary of Cases During Clinical Trial Development.

ABSTRACT

PURPOSE: The Port Delivery System with ranibizumab (PDS) is approved in the United States for neovascular age-related macular degeneration. The US Prescribing Information has a Boxed Warning for endophthalmitis and reports the incidence rate in patients developing endophthalmitis after receiving the PDS compared to monthly intravitreal ranibizumab. Endophthalmitis cases noted in the Boxed Warning, treatment outcomes, potential contributing factors, and potential mitigations are summarized. DESIGN: Retrospective review of endophthalmitis cases in PDS-treated patients in the phase 2 Ladder (NCT02510794) and phase 3 Archway (NCT03677934) and Portal (NCT03683251) trials. PARTICIPANTS: Endophthalmitis cases in the pooled all-PDS safety population (N = 555) including PDS patients in Ladder, Archway, or Portal. METHODS: Ladder patients received PDS (10, 40, or 100 mg/mL) with pro re nata refill-exchanges. Archway patients received PDS 100 mg/mL with fixed refill-exchanges every 24 weeks (PDS Q24W). Portal patients received PDS Q24W from day 1. MAIN OUTCOME MEASURES: Clinical features, management, and visual outcomes were summarized. Cases were summarized by date of PDS implant and/or refill, other prior invasive procedures/refills, and preceding/concurrent conjunctival complications. RESULTS: Twelve endophthalmitis events were reported in 11 patients (11/555 [2.0%]) through March 12, 2021. All were cultured (3 were culture positive) and treated with intravitreal antibiotics. Two cases (2/555 [0.4%]) occurred in the immediate postoperative period (days 5 and 6). Nine cases occurred later (day range 57-853), including 4 before the first refill-exchange (day range 57-161). Five patients received between 1-11 refill-exchanges before the event (onset 6-168 days after last refill-exchange). Seven cases (7/11 [63.6%]) had preceding/concurrent conjunctival complications. At last follow-up, 7 patients recovered vision to study baseline levels or ≥ 20/40; 4 patients experienced vision loss of ≥ 15 ETDRS letters. CONCLUSIONS: Endophthalmitis is a serious complication that can endanger vision after any ocular procedure, including PDS implantation. This limited series of endophthalmitis cases notes most, but not all, cases were late onset, associated with conjunctival breach, and recovered vision with treatment. Meticulous attention to PDS surgical techniques with vigilant monitoring of conjunctiva during follow-up may minimize risk of endophthalmitis. Prompt treatment is critical for optimizing patient outcomes.