Purpose: To assess the safety and efficacy of mesenchymal stem cells (MSCs) and MSC-derived exosomes (MSC-Exos) for promoting healing of large and refractory macular holes (MHs).

Hypothesis: MSC and MSC-Exo therapy may promote functional and anatomic recovery from MH. MSC-Exo therapy may be a useful and safe method for improving visual outcomes of surgery for refractory MHs.

Based on the purpose and hypothesis,the participants with large and longstanding idiopathic MHs underwent vitrectomy, internal limiting membrane peeling, MSC or MSC-Exo intravitreal injection, and heavy silicon oil, air, 20% SF6, or 14% C3F8 tamponade. MSCs were isolated from human umbilical cord, and MSC-Exos were isolated from supernatants of MSCs via sequential ultracentrifugation. At the time of study enrollment, as well as physical examinations, best-corrected visual acuity (BCVA) and intraocular pressure will be measured and fundoscopy be performed. All diagnoses of MH are going to confirmed via spectral-domain optical coherence tomography (OCT), and the minimum linear diameter (MLD) of each MH will be measured parallel to the retinal pigment epithelium.The participants are going to be followed up for at least 6 months via BCVA measurement, fundoscopy, OCT, and physical examinations.

Inclusion Criteria:

1.Clinical diagnosis of idiopathic macular hole whose diameter is greater than 400 microns

Exclusion Criteria:

1. Only one functional eye
2. In other clinical trials.
3. Other diseases which can affect visual acuity, such as cataract, diabetic retinopathy, glaucoma, corneal diseases, etc.
4. Eye had undergone vitrectomy or scleral buckling, cataract surgery, Nd:YAG laser less than one month ago.
5. Contralateral eye has poor prognosis than the study eye.
6. Idiopathic or autoimmune uveitis history.
7. Aphakic eye
8. Physical condition is poor that can not keep prone position.
9. Secondary macular lesions
10. The equivalent spherical diopter of the study eye before any refractive correction or cataract surgery, which is greater than 6.0d or above 26mm of the ocular axis of the study eye.
11. Intraocular pressure is higher than 25mmHg
12. Within ocular inflammation, such as eye blepharitis, scleritis, keratitis and conjunctivitis.
13. Systemic condition is poor, such as the poor control of diabetes and hypertension, myocardial infarction, cerebrovascular accident, renal failure and so on,and the researchers assessed those who are unable to complete the trail.