Safety of multiple intravitreal injections of ocriplasmin in subjects with non–proliferative diabetic retinopathy (NPDR): Results of the CIRCLE study.

Abstract

Purpose : The CIRCLE study was conducted to assess the efficacy and the safety of up to 3 intravitreal (IVT) injections of ocriplasmin to induce total posterior vitreous detachment (PVD), in order to reduce the risk of disease progression to proliferative diabetic retinopathy (PDR). A single intravitreal injection of ocriplasmin 0.125mg is approved for the treatment of symptomatic vitreomacular adhesion (VMA)/vitreomacular traction (VMT).

Methods : The CIRCLE study was a multicenter, sham-controlled, double-masked study. Subjects were randomized 2:2:1 to receive up to 3 IVT injections of ocriplasmin 0.0625mg, ocriplasmin 0.125mg, or a sham procedure, 1 month apart. They were followed for 24 months.

Results : Recruitment in the study was stopped early due to a slow recruitment rate. As a result, the study was not powered for its primary endpoint (total PVD by Month 3) and the main goal became the assessment of the safety of up to 3 IVT injections of ocriplasmin. Forty-eight (48) subjects were randomized: 20 to ocriplasmin 0.0625mg, 19 to ocriplasmin 0.125mg and 9 to sham. The subjects were mostly white and male. The mean age at Baseline was 56.2 years. The mean time since the diagnosis of diabetes was 16.9 years. There were no relevant imbalances between treatment arms. The most frequently reported treatment–related adverse events (AEs) in the study eye were Conjunctival Haemorrhage in the ocriplasmin 0.0625mg arm (3 events in 3/20 [15.0%] subjects) and Vitreous Floaters in the ocriplasmin 0.125mg arm (5 events in 3/19 [15.8%] subjects). This is similar to the most frequently observed treatment–related AEs following a single injection of ocriplasmin 0.125mg in patients with symptomatic VMA/VMT. No new type of AE was identified. The majority of AEs were mild or moderate in intensity, started within the first week after injection and resolved within a few days. The frequency or intensity of AEs did not increase following the second or third injection with ocriplasmin.

Conclusions : Up to three (3) IVT injections with ocriplasmin were considered safe, given that no new type of AE unknown to ocriplasmin was identified, as compared to a single injection of ocriplasmin 0.125mg in patients with symptomatic VMA/VMT. Neither the frequency nor the intensity of the AEs increased following the second or third injection with ocriplasmin.

This is a 2021 ARVO Annual Meeting abstract.