Characterization of vitreoretinal interface disorders using OCT in the interventional phase 3 trials of ocriplasmin.

PURPOSE: We determined the reproducibility of a novel optical coherence tomography (OCT) protocol designed to evaluate formally vitreoretinal interface abnormalities on scans obtained during two phase 3 studies of intravitreal ocriplasmin to treat symptomatic vitreomacular adhesion with or without macular hole. METHODS: Certified technicians obtained time-domain OCT scans that included a macular thickness map (MTM), Fast MTM, and three high resolution linear scans: one 10 mm horizontal and one 10 mm vertical through the optic nerve head (ONH), and one 10 mm 5-degree-offset through the ONH and fovea. Reading Center teams graded all 3695 scans from 652 study eyes for pre-established quantitative and morphologic features. Grading reproducibility at baseline and follow-up visits was tested for presence of vitreomacular adhesion (VMA), width of vitreous adhesion (focal <1500 μm versus broad >1500 μm), presence and minimum width of full thickness macular hole (FTMH), and presence of epiretinal membrane (ERM). RESULTS: Team grading reproducibility for VMA (kappa 0.91, 95% confidence interval [CI] 0.81-1.00), broad versus focal width of vitreous adhesion (kappa 0.87, 95% CI 0.78-0.95), FTMH (kappa 0.87, 95% CI 0.78-0.95), and ERM (kappa 0.87, 95% CI 0.78-0.95) was high. Percent agreement was 97%, 92%, 95%, and 82% for VMA, vitreous adhesion width, FTMH, and ERM, respectively. For repeated measurements of FTMH width, the intraclass correlation was 0.89 (95% CI 0.85-0.93), and the mean paired difference between grading team measurements was 34.4 μm (95% limits of agreement -149.5-218.2 μm). CONCLUSIONS: Quantitative and morphologic vitreoretinal interface features were assessed reproducibly using a newly developed OCT scan acquisition and grading protocol. This protocol will be useful to evaluate OCT endpoints in future clinical trials, and can facilitate identification of vitreoretinal interface pathology during care of individual patients. (ClinicalTrials.gov number, NCT00781859 and NCT00798317.).

Duke Scholars

Author Cynthia Ann Toth Ophthalmology, Vitreoretinal Diseases & Surgery

Author Sandra Sue Stinnett Biostatistics & Bioinformatics, Division of Biostatistics

Author Glenn Jay Jaffe Ophthalmology, Vitreoretinal Diseases & Surgery