VEGFA-targeting Gene Therapy to Treat Retinal and Choroidal Neovascularization Diseases

Inclusion Criteria:

1. Patients with nAMD at the age ≥50; Or patients with diabetic macular edema (DME) atthe age ≥18; Or patients with macular edema following retinal vein occlusion (RVO-ME) at the age ≥18.

2. Early Treatment Diabetic Retinopathy Study (ETDRS) best corrected visual acuity ≤63and letter score ≥19 Corresponding Snellen vision ≤20/63 and ≥20/400).

3. OCT confirms the presence of intraretinal fluid or subretinal fluid in the fovea.

4. Have received anti-VEGF therapy in the past and have responded to anti-VEGF therapy.

5. With refractory conditions: repeated anti-VEGF treatments are required due to thedisease condition. When the treatment is interrupted, the disease condition recurs (OCT examination indicates increased subretinal/inner effusion in the macula)

6. For patients with both eyes suffered, enroll the one with more severe condition.

7. Routine blood test, liver and kidney function, coagulation index of patients isnormal：AST/ALT < 2.5 × ULN; TB < 1.5 × ULN; PT < 1.5 × ULN; Hb > 10 g/dL (male) and > 9 g/dL (female); PLT > 100 × 10^3/µL; eGFR > 30 mL/min/1.73 m^2.

Subjects voluntarily join the study, sign an informed consent form, have good compliance, and cooperate with follow-up.

Exclusion Criteria:

1. Choroidal neovascularization or macular edema induced by other diseases.

2. Any other factors that affect vision improvement in the study eye, such as fibrosis,atrophy, or RPE tear in the fovea of the macula.

3. The study eye already has severe proliferative retinopathy, such as retinalneovascularization, traction retinal detachment, etc. (only for DME and RVO-MEpatients) .

4. Retinal detachment or advanced glaucoma in the study eye.

5. Implants in the study eye (except intraocular lenses).

6. Received internal eye surgery within 3 months prior to enrollment.

7. Vitrectomy surgery on the study eye.

8. Received intravitreal glucocorticoid or other clinical research drugs (exceptanti-VEGF therapy) within 6 months prior to enrollment.

9. Myocardial infarction, cerebrovascular accident or transient ischemic attackoccurred within 6 months prior to enrollment.

10. Poorly controlled hypertension under maximum medication (systolic blood pressure>180mmHg, diastolic blood pressure>100 mmHg).

11. Poor blood glucose control under medication (fasting blood glucose is greater thanor equal to 10.0 umol/L).

12. Women who are willing to give birth; pregnant/breastfeeding women Have received genetherapy in the past.