First Author: K.Liu SWITZERLAND
Co Author(s): J. Gilhotra A. Chang I. Ho
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Vitreomacular traction (VMT) is a sight-threatening disease, which may be associated with macular hole (MH) and other ocular complications, manifesting as metamorphopsia, visual distortion or loss. Ocriplasmin is a recombinant truncated form of human plasmin which exerts enzymatic activity on proteins responsible for VMT. Spectral domain-optical coherence tomography (SD-OCT) has provided greater insight into the tractional forces at the vitreoretinal interface and the resulting macular pathologies, allowing further investigation of ocriplasmin efficacy and safety. The purpose of OVIID-II was to provide additional safety and efficacy experience with ocriplasmin, especially in populations that were under-represented in studies of similar design.
This was a Phase 4, multicentre, prospective, single-arm, open-label study.
Subjects attended a screening visit to determine their eligibility to participate according to pre-determined inclusion and exclusion criteria. 52 subjects diagnosed with VMT with evidence of focal (≤1500 μm) VMA visible on SD-OCT without an epiretinal membrane over the central macula were included in this study. Eligible subjects received a single dose of ocriplasmin 0.125 mg in 0.1 ml administered by intravitreal injection at Visit 1, followed by 4 post-injection visits at Day 7, Day 28, Day 90, and Day 180. SD-OCT was performed at all visits, except on the day of injection (Visit 1/Day 0) and scans were sent to the central reading centre (CRC) for evaluation. The primary endpoint was the overall proportion of subjects with nonsurgical resolution of vitreomacular adhesion (VMA) at Day 28. Secondary endpoints included nonsurgical changes in best-corrected visual acuity (BCVA) at Days 7, 28, 90 and 180 compared to baseline, proportion of subjects with closure of MH at Days 7, 28, 90, and 180, and proportion of subjects with nonsurgical resolution of VMA at Day 7, 90, and 180. Adverse events were monitored, as were safety-related parameters, such as intraocular pressure, biomicroscopy/slit-lamp parameters, and dilated fundus parameters.
The overall proportion of subjects with nonsurgical resolution of VMA at Day 28 was 26.9%. Mean (SD) nonsurgical changes in BCVA (EDTRS letters) were 1.0 (7.67), 2.1 (8.07), and 3.3 (9.16) at Day 28, Day 90, and Day 180, respectively (of note, on Day 7 a mean decrease in BCVA of -1.8 (7.09) was observed). The proportion of nonsurgical closure of MH was 50.0% at Day 28 (2 of 4 subjects with MH present at baseline). The proportion of subjects with nonsurgical VMA resolution increased over time (38.5% at Day 90, and 40.4% at Day 180). No subject discontinued the study due to a treatment-related event and no new safety signals were identified for ocriplasmin.
Ocriplasmin injection resulted in anatomical improvements with nonsurgical resolution of VMA in 26.9% [95% (CI 15.6, 41.0)] of subjects at Day 28. Of note, this proportion was lower than that observed in the similarly-designed OVIID-I study where 47.4% of subjects achieved nonsurgical resolution of VMA. There were, however, some notable differences between the two study populations including an older mean age of subjects and fewer subjects with MH at baseline in the present study. The higher number of subjects with MH at baseline in OVIID-I versus OVIID-II is noteworthy as there was a greater rate of nonsurgical resolution of VMA in subjects with MH at baseline in OVIID-I. Functional improvements in BCVA were similar to that observed in OVIID-I with mean increase in BCVA in the present study of 3.3 letters at Day 180 (versus 3.5 letters at Day 180 in OVIID-I). In terms of safety, ocriplasmin administered as a single injection was well tolerated.