OCRIPLASMIN FOR VITREOMACULAR TRACTION IN CLINICAL PRACTICE: The INJECT Study.

PURPOSE: Randomized clinical trials have demonstrated the safety and efficacy of ocriplasmin in patients with vitreomacular traction (VMT), including those with macular hole (MH). The INJECT study prospectively evaluated ocriplasmin in the setting of clinical practice. METHODS: INJECT was a Phase 4, multicenter, prospective observational study. Patients were followed up for 12 months. Assessments included nonsurgical VMT resolution, nonsurgical MH closure, best-corrected visual acuity, occurrence of vitrectomy, and adverse events. RESULTS: The efficacy population (N = 395) received an ocriplasmin injection and had optical coherence tomography-confirmed VMT at baseline. At Day 28, the rate of nonsurgical VMT resolution was 40.7% in the overall group, and the rate of nonsurgical MH closure was 36.0% in the VMT with MH group. At Month 12, the rate of ≥2-line best-corrected visual acuity gain (irrespective of vitrectomy) was 36.8% in the overall group and 59.6% in the VMT with MH group. The percentage of patients who underwent vitrectomy in the study eye was 29.1% in the overall group and 55.6% in the VMT with MH group. Photopsia (9.8%) and vitreous floaters (6.8%) were the most frequent adverse events. CONCLUSION: The INJECT study showed that ocriplasmin is effective in a clinical setting in patients with VMT, with or without MH. No new safety signals were identified from this large and surgeon-selected patient group, although the significant limitations of the study design without an image reading center and scheduled study visit timings should be noted.

Resolution of outer retinal abnormalities in eyes with vitreomacular traction without macular hole in the OASIS trial.

BACKGROUND/AIMS: To describe the clinical impact of external limiting membrane (ELM) disruption, ellipsoid zone (EZ) disruption and subretinal fluid (SRF) seen on optical coherence tomography (OCT) in eyes with vitreomacular traction (VMT) without macular hole (MH) in the Ocriplasmin for Treatment for Symptomatic Vitreomacular Adhesion Including Macular Hole study. METHODS: Phase 3b randomised double-blind sham-controlled multicentre study including 144 eyes with VMT without MH. Eyes were randomised to receive a single intravitreal injection of ocriplasmin or sham injection and were followed for 24 months. Eyes were analysed for presence, course and clinical impact of ELM disruption, EZ disruption and SRF on OCT. RESULTS: ELM disruption, EZ disruption and SRF were present in 32.6%, 52.2% and 45.8% of ocriplasmin-treated eyes and 39.6%, 42.6% and 37.5% of sham-treated eyes at baseline. VMT resolution was associated with resolution of ELM and EZ disruption and SRF. A small number of eyes had persistent ELM disruption, EZ disruption and/or SRF at the seventh visit or later (17 months or later) following medical or surgical VMT resolution. Resolution of ELM disruption, EZ disruption and/or SRF was associated with an improvement of visual acuity from baseline. Following VMT resolution, ELM recovery usually preceded EZ recovery and SRF resolution. CONCLUSIONS: ELM disruption, EZ disruption and/or SRF are present in a significant percentage of eyes with VMT without MH. Release of VMT is usually associated with outer retinal recovery and an associated improvement in visual acuity. ELM recovery typically precedes EZ recovery and SRF resolution following VMT release.

Phase 1 Dose-Escalation Study of Plasma Kallikrein Inhibitor THR-149 for the Treatment of Diabetic Macular Edema.

Purpose: The purpose of this study was to evaluate the safety and preliminary efficacy of a single intravitreal injection of 3 dose levels of THR-149 in adults with center-involved diabetic macular edema (DME). Methods: A phase 1, open-label, multicenter 3 + 3 dose-esclation study with 3-month follow-up. The primary endpoint was the incidence of dose-limiting toxicities (DLTs) up to and including the Day 14 visit. Additional key endpoints included the incidence of (serious) adverse events ([S]AEs), mean change from baseline in best-corrected visual acuity (BCVA) and central subfield thickness (CST), and additional imaging parameters on widefield fluorescein angiography and optical coherence tomography (OCT) angiography. Results: Twelve subjects were treated: 3 subjects received THR-149 0.005 mg, 3 received 0.022 mg and 6 received 0.13 mg. Baseline ocular characteristics were balanced between subjects at each dose level. There were no DLTs or ocular SAEs, and all subjects completed the study. Six subjects experienced a total of 10 AEs in the study eye; 1 case of mild anterior chamber inflammation was deemed related to THR-149 and/or the injection procedure. Mean change from Baseline in BCVA was +7.5 Early Treatment of Diabetic Retinopathy Study (ETDRS) letters on Day 14, and +6.4 ETDRS letters by Month 3. CST was variable, and mean CST change from baseline was +30.0 µm at Month 3. There were no clinically meaningful changes in imaging parameters. Conclusions: THR-149 was safe and well tolerated; preliminary efficacy in terms of BCVA improvement was observed. Translational Relevance: This work bridges the gap between basic research and clinical care by providing first in human safety and preliminary efficacy data, supporting the further investigation of THR-149 as a potential treatment for DME.