*Purpose: mTOR inhibitors are known for their antiangiogenic effect. We compared the impact of everolimus (E) and mycophenolic acid (MPA) on the course of diabetic retinopathy (DR) in a prospective randomized trial in pancreas and kidney transplant recipients; EUDRACT No.2013-004934-14.

*Methods: Waitlisted Type-1 diabetic subjects were randomized to treatment with MPA or E together with tacrolimus, 6 weeks steroids and ATG induction. Eye examination including optical coherence tomography (OCT) was done at the baseline, 6, 12 and 24 months. The composite primary endpoint comprised new need for laser therapy, newly diagnosed proliferation, clinically significant macular edema (CSME), best corrected visual acuity (BCVA) worsening. For statistical evaluation we used t-test, Mann-Whitney test, Fisher’s test, Kaplan-Meier test and log-rank test. Endpoints were evaluated per patient and per eye.

*Results: Out of 64 enrolled patients, 55 (MPA 29, E 26) completed the follow-up. Most of these had proliferative DR (MPA 82.4% eyes, E 78.2% eyes) with previous laser treatment. 2-year patient and death-censored graft survival rates did not differ between the groups. 59% of the patients in the MPA group and 50% in E group met the primary endpoint (p=0.6), mostly due to new proliferation, need for laser treatment and BCVA worsening. When analyzed per eye, the need for laser therapy was more frequent in the MPA group, reaching statistical significance in the second year post-transplant (22.8% vs 5.8%, p=0.015), which corresponded with BCVA worsening (33.3% and 15.7%, p=0.045). Retinopathy-related BCVA worsening rate was significantly higher in the MPA than E group (22.8% vs 5.8%, p=0.015). Total occurrence of bleeding was 19.3% in MPA vs 3.9% in the E group (p=0.0154). There was no case of new blindness. Central retinal thickness increased in the 6^th month post-transplant in both groups with subsequent restoration at 12 months. CSME rate was almost identical in both groups (MPA 7%, E 7.8%, p=0.9). Patients treated with laser less than 12 months pre-transplant were more likely to suffer from further DR progression meeting the primary endpoint in 72.7% (MPA) and 66.7% (E).

*Conclusions: We demonstrated more favorable course of diabetic retinopathy in treated with everolimus subjects in a prospective randomized trial.

Supported by Czech Ministry of Education – grant LTAUSA19073 and by MH CZ – DRO Institute for Clinical and Experimental Medicine – IKEM, IN 00023001

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