Patients who meet all of the following criteria are eligible for participation in the study:
Ophthalmic inclusion criteria:
1. Patient with at least one eye with extensive loss of vision from hand motion to no light perception.
2. Phakic or pseudophakic with a stable intraocular lens in the blind eye.
3. Normal cornea with good visualization of the anterior segment.
4. Normal anterior segment anatomy including the iris bed.
General and metabolic inclusion criteria:
1. Male and female subjects ages 18 to 75 years of age and no history of non-compliance.
2. Clinical history compatible with T1D or T2D with or without insulin-dependence at the time of enrollment.
3. Stable renal function of native or transplanted kidney if applicable.
4. Ability to provide written informed consent.
5. Mentally stable and able to comply with the procedures of the study protocol.
Exclusion Criteria: Patients who meet any of these criteria are not eligible for participation in the study:
Ophthalmic exclusion criteria (only in surgical eye):
1. Poor visualization of the anterior chamber (corneal opacity, corneal edema, Herpes Keratitis).
2. Aphakic status (no lens).
3. Narrow angle of iris anatomy: Spade Scale IV.
4. History of uncontrolled glaucoma or glaucoma that had required surgical intervention (e.g., trabeculectomy or shunting devices).
5. Active uncontrolled uveitis.
6. Presence of silicone in the anterior segment after complex diabetic retinopathy surgery.
7. History of allergy to topical steroids and immune-modulatory drugs including CSA and Tacrolimus.
General and metabolic exclusion criteria:
1. HbA1c \>10%.
2. Blood Pressure: SBP \>160 mmHg or DBP \>100 mmHg.
3. Calculated GFR of ≤40 mL/min/1.73 m2 for patients with kidney transplant or \<80 mL/min/1.73 m2 for those without kidney transplant, using the subject's measured serum creatinine and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation1.
4. Strict vegetarians (vegans) will be excluded only if their estimated GFR is ≤35 mL/min/1.73 m2 for patients with kidney transplant or \<70 mL/min/1.73 m2 for those without kidney transplant.
5. Proteinuria (albumin/creatinine ratio or ACr \>300mg/dl) of new onset or since kidney transplantation if applicable.
6. Calculated panel-reactive anti-HLA antibodies \>20%.
7. Positive crossmatch.
8. Antibodies (i.e., presumed de-novo) to the kidney transplant donor, if applicable.
9. For female subjects: Positive pregnancy test, presently breast-feeding, or unwillingness to use effective contraceptive measures for the duration of the study and 4 months after discontinuation. For male subjects: intent to procreate during the duration of the study (24 months) or within 4 months after discontinuation, or unwillingness to use effective measures of contraception. Oral contraceptives, Norplant®, Depo-Provera®, and barrier devices with spermicide are acceptable contraceptive methods; condoms used alone are not acceptable.
10. Presence or history of active infection including hepatitis B, hepatitis C, HIV, or tuberculosis (TB). Subjects with laboratory evidence of active infection are excluded even in the absence of clinical evidence of active infection.
11. Negative screen for Epstein-Barr Virus (EBV) by IgG determination.
12. Invasive aspergillus, histoplasmosis, and coccidioidomycosis infection within one year prior to study enrollment.
13. Active malignancy (cancer) except if successfully treated and declared cancer-free and/or in-remission by the oncologist.
14. Known active alcohol or substance abuse.
15. Baseline Hb below the lower limits of normal at the local laboratory; lymphopenia (\<1,000/µL), neutropenia (\<1,500/µL), or thrombocytopenia (platelets \<100,000/µL). Participants with lymphopenia are allowed if the investigator determines there is no additional risk with additional clearance from a hematologist.
16. Severe co-existing cardiac disease, characterized by any one of these conditions:
1. Recent myocardial infarction (within past 6 months).
2. Evidence of ischemia on functional cardiac exam within the last year.
3. Left ventricular ejection fraction \<30%.
17. Hyperlipidemia despite medical therapy (fasting low-density lipoprotein \[LDL\] cholesterol \>130 mg/dL, treated or untreated; and/or fasting triglycerides \>200 mg/dL) for patients with kidney transplant.
18. Receiving treatment for a medical condition requiring chronic use of systemic steroids, except for the use of ≤5 mg prednisone daily, or an equivalent dose of hydrocortisone, for physiological replacement only.
19. Use of any investigational agents within 4 weeks of enrollment.
20. Administration of live attenuated vaccine(s) within 2 months of enrollment.
21. Any medical condition that, in the opinion of the investigator, will interfere with the safe participation in the trial.
