First-in-Human Application of Decellularized Human Amniotic Membrane Hydrogel as an Injectable Intraocular Scaffold for Large Idiopathic Full- Thickness Macular Hole Closure: Four-Month Clinical Outcomes

Background: Large idiopathic full-thickness macular holes (FTMH) with minimum diameter >400 μm carry surgical success rates of approximately 56% with standard vitrectomy and gas tamponade. Novel biologic scaffolds have improved closure rates but are limited by intraoperative handling challenges. We report the first clinical application of thermosensitive injectable decellularized human amniotic membrane (dAM) hydrogel as an intraocular scaffold for large FTMH, with four-month anatomical, functional, and electrophysiological outcomes. Methods: A 62-year-old man with a Gass stage 4 idiopathic FTMH (minimum diameter 572 μm) and preoperative BCVA of 20/200 underwent combined phacoemulsification and 25-gauge pars plana vitrectomy (PPV) with ILM peeling. Following fluid-air exchange, dAM hydrogel (10 mg/mL, thermosensitive, prepared by detergent decellularization and pepsin solubilization) was injected via a 25-gauge soft-tip cannula, followed by SF6 gas tamponade. Pre-clinical biocompatibility was confirmed by CCK-8 assay and transwell invasion assay prior to clinical use. Results: At one month, SD-OCT confirmed complete Type 1 anatomical closure and BCVA improved to 20/80. At four months (day 121), BCVA further improved to 20/40+1 (logMAR 0.30), with no metamorphopsia, IOP 12.7 mmHg, and sustained Type 1 closure with progressive ellipsoid zone (EZ) reconstitution on OCT. Multifocal ERG (103 segments) confirmed measurable foveal P1 responses (Ring 1: 34.19 nV/deg²) with normal central N1 implicit time (40.2 ms; normal range 36.8–46.4 ms). No intraocular adverse events occurred at any time point. Conclusions: Injectable dAM hydrogel achieves stable Type 1 FTMH closure with progressive visual and electrophysiological recovery over four months. mfERG evidence of preserved foveal photoreceptor function supports this approach as a feasible and safe biologic scaffold for large FTMH repair. Prospective comparative evaluation is ongoing (ClinicalTrials.gov: NCT06433284).