Abstract： Objective:To observe the efficacy of platelet-rich fibrin (PRF) membrane tamponade combined with air filling for giant macular hole (MH).Methods:A prospective case-control study. From January 2019 to February 2021, 56 patients (56 eyes) diagnosed with giant MH from Eye Center of Renmin Hospital of Wuhan University were enrolled. Among them, there were 17 males with 17 eyes and 39 females with 39 eyes. The average age of the patients was 64.23±9.30 years old. The average MH minimum diameter was 827.36±83.16 μm. The best corrected visual acuity (BCVA) and optical coherence tomography angiography (OCTA) examination were performed before surgery. The Chinese version of 25-item National Eye Institute visual functioning questionnaire (NEI VFQ-25) was used to investigate patient's visual-related quality of life. There were 28 eyes of 28 cases receiving PRF membrane covering, as PRF group, another 28 eyes of 28 cases receiving inverted internal limiting membrane (ILM) insertion into giant MH, as ILM group. The differences of the age ( t=-1.588), sex ratio ( χ2=0.760), BCVA ( Z=-0.400), macular hole minimum diameter ( t=-0.604), choriocapillary blood flow area (CBFA) ( t=1.331) and NEI VFQ-25 score ( t=0.921) were not statistically significant ( P>0.05). All eyes underwent 23G minimally invasive vitrectomy. In the PRF group, PRF membrane was used to fill the hole, and in the ILM group, the hole was filled with ILM inversion, and filled with sterile air after full gas-liquid exchange. The follow-up time after surgery was ≥6 months. The same equipment and methods as before surgery were used to conduct related examinations, and the changes of BCVA, the shape of hole closure, CBFA and the improvement of vision-related quality of life were compared between the two groups. For comparison between groups, independent samples t-test was used for data with normal distribution, and Mann-Whitney U test was used for data with non-normal distribution. For intra-group comparisons, paired-samples t-test was used for data with normal distribution, and Wilcoxon rank-sum test was used for non-normally distributed data. Results:Six months after surgery, in the eyes of PRF group and ILM group, the hole of 27 (96.4%, 27/28) and 26 (92.6%, 26/28) eyes were closed; the median BCVA was 0.70 and 0.70, respectively; CBFA were 1.99±0.20 and 1.91±0.18 mm 2; NEI VFQ-25 scores were 81.36±12.39 and 78.39±10.12, respectively. Compared with before surgery, the BCVA ( Z=-4.636,-4.550) and CBFA ( t=-27.115,-31.135) of the affected eyes in the PRF group and ILM group were significantly improved after surgery, and the NEI VFQ-25 scores ( t=-15.557, -10.675) was significantly increased, and the difference was statistically significant ( P<0.05). There was no significant difference in BCVA ( Z=-0.167), CBFA ( t=1.554), and NEI VFQ-25 scores ( t=0.980) between the two groups after interocular surgery ( P=0.726, 0.126, 0.331). Conclusion:PRF membrane insertion with air filling has the same efficacy as ILM insertion in the treatment of giant MH, which can improve the closure rate of MH, patients' vision and vision-related quality of life, and increase choroidal blood perfusion.