PURPOSE: This study evaluated outcomes and foveal morphological changes following human amniotic membrane transplantation (hAMT) in complex macular holes. METHODS: A multicenter, retrospective analysis was conducted on 30 eyes that underwent vitrectomy with hAMT for indications including failed prior macular hole closure, macular hole-associated retinal detachment in high myopia (axial length >
28mm), giant macular holes (>
1000µm), and large macular holes (≥400µm) unsuitable for internal limiting membrane flaps (ILM). Postoperative assessments included closure rates, visual outcomes, and foveal structural changes on optical coherence tomography (OCT) at 1, 3, and 6 months. RESULTS: Macular hole closure with retinal tissue reconstitution was observed in 73.3% of eyes at 1 month, whereas 23.3% showed foveolar dehiscence with exposed hAM in the subretinal space. Visual acuity improved from logMAR 1.22 (20/320) to 0.99 (20/200) at 1 month (P= 0.026), 0.98 at 3 months (P=0.013), and 0.97 at 6 months (P=0.013). The bare hAM area decreased over time in eyes with foveolar dehiscence (P=0.016), and retinal tissue reconstitution was observed in three of these cases. A larger preoperative minimal linear diameter was significantly associated with this pattern (P=0.033). CONCLUSION: hAMT demonstrated favorable outcomes in complex macular holes, supporting its potential role in the anatomical restoration.