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.

Abstract

Background: Large idiopathic full-thickness macular holes (FTMH) with minimum diameter > 400 μm carry surgical success rates of approximately 60% with standard vitrectomy and gas tamponade. Novel biologic scaffolds have improved closure rates but are limited by intraoperative handling challenges. We describe a surgical technique using thermosensitive injectable decellularized human amniotic membrane (dAM) hydrogel as an intraocular scaffold for large FTMH, and illustrate its feasibility and safety in a first-in-human application with four-month anatomical, functional, and electrophysiological outcomes.

Surgical technique: 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.

Outcomes: 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: This injectable dAM hydrogel scaffold technique is a feasible, instrument-sparing method for large FTMH repair, achieving stable Type 1 closure with progressive visual and electrophysiological recovery over four months. mfERG evidence of preserved foveal photoreceptor function supports its safety. Prospective comparative evaluation is ongoing (ClinicalTrials.gov: NCT06433284).

Clinical trial registration: ClinicalTrials.gov NCT06433284 (MACROHOLE trial). Registered April 2024.