Efficacy and safety of preservative-free triamcinolone acetonide (OphTA) for vitreous visualization during vitrectomy: a phase III multicenter trial in China (the VIVID trial)

To evaluate the efficacy and safety of OphTA, a preservative- and excipient-free formulation of triamcinolone acetonide for ophthalmic injection, in enhancing posterior vitreous cortex visualization during pars plana vitrectomy (PPV) among Chinese patients. This prospective, multicenter, open-label, single-arm Phase III trial utilized a pre-post treatment comparison design with masked independent central image review for the primary endpoint. Adults scheduled for PPV were enrolled. During surgery, OphTA (10 mg/mL) was injected intravitreally (0.5–4 mg total dose) after core vitrectomy until adequate visualization was achieved. Visualization grades (0 = none to 4 = excellent) were assessed pre- and post-instillation by both masked independent reviewers and operating surgeons. The primary endpoint was the change in grade assessed by independent reviewers, analyzed against a pre-defined clinically meaningful margin of 2 points using a one-sided Wilcoxon signed-rank test (α = 0.025). Safety assessments included adverse events (AEs) monitoring up to Day 7 ± 1 postoperatively. A total of 120 subjects were enrolled; 115 received OphTA (Safety Set SS and Full Analysis Set FAS), and 103 constituted the Per-Protocol Set (PPS). For the primary endpoint, the mean (SD) visualization grade in the FAS significantly improved from 1.6 (1.24) pre-instillation to 3.6 (0.71) post-instillation (mean increase: 2.0 points; P = 0.0244), the PPS analysis yielded consistent results (P = 0.0183), meeting the pre-specified criterion. Surgeon assessments (FAS, n = 115) corroborated these findings, showing a significant grade improvement from 0.6 (0.69) to 3.5 (0.54) (P < 0.0001), also meeting the pre-specified criterion. Post-hoc analysis showed a shift from 90.4% low-grade (0–1) to 97.4% high-grade (3–4) after instillation. No serious AEs or study discontinuations due to AEs occurred. Adverse reactions deemed at least possibly related to OphTA were reported in 32 subjects (27.8%), with increased intraocular pressure being the most common (25.2%). Residual OphTA particles cleared rapidly, absent in all examined eyes by Day 7. OphTA resulted in a statistically significant improvement in posterior vitreous cortex visualization during PPV, meeting the pre-specified criterion. It demonstrated a favorable safety profile characterized by expected perioperative events and rapid particle clearance. OphTA is an effective and well-tolerated adjunct for enhancing visualization in vitrectomy.