Randomized, Controlled Study to Investigate the 12-month Efficacy and Safety of Resveratrol Vitamin Supplements in Patients With Non-proliferative Diabetic Retinopathy Without Center Involved Diabetic Macular Edema (REVOLUTION Study)

Diabetic retinopathy (DR) is a common microvascular complication of diabetes mellitus and a leading cause of visual impairment. Oxidative stress and inflammation play important roles in its pathogenesis. Resveratrol, a naturally occurring polyphenol with antioxidant and anti-inflammatory properties, has been proposed as a potential supplementary treatment for diabetic retinopathy.

The REVOLUTION study is a prospective, randomized, controlled clinical trial designed to investigate the efficacy and safety of resveratrol-containing vitamin supplements in patients with non-proliferative diabetic retinopathy (NPDR) without center-involved diabetic macular edema (DME).

Patients attending the Second Department of Ophthalmology will be enrolled and randomly assigned to either a resveratrol-containing vitamin supplementation group or a control group. Participants will be followed for 12 months to assess changes in diabetic retinopathy severity, potential disease progression, and the safety and tolerability of supplementation.

The study aims to determine whether resveratrol-containing vitamin supplements may provide additional clinical benefits in the management of NPDR and help prevent disease progression.

• Resveratrol-Containing Vitamin Supplement (Combination product): Patients with non-proliferative diabetic retinopathy (NPDR) without center-involved diabetic macular edema will receive an approved oral resveratrol-containing vitamin supplement for 12 months. The efficacy and safety of supplementation will be evaluated through ophthalmological examinations at baseline and at 3, 6, and 12 months.

Primary outcomes

• Patients with improvement in diabetic retinopathy severity [Baseline and 12 months]: The proportion of patients demonstrating improvement in diabetic retinopathy severity, assessed using the International Clinical Diabetic Retinopathy Disease Severity Scale (DRSS) at month 12 compared with baseline.

Secondary outcomes

• Change in retinal perfusion assessed by optical coherence tomography angiography (OCT-A) [Baseline and 12 months]: Changes in retinal microvascular perfusion and ischemia-related parameters assessed using OCT-A at month 12 compared with baseline.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

1. Patients diagnosed with type 2 diabetes mellitus (T2DM).
2. Presence of non-proliferative diabetic retinopathy (NPDR), classified according to the International Clinical Diabetic Retinopathy Disease Severity Scale (DRSS).
3. Absence of center-involved diabetic macular edema (DME).
4. Provision of written informed consent.

Exclusion Criteria:

1. Proliferative diabetic retinopathy (PDR).
2. Center-involved diabetic macular edema (DME).
3. Age-related macular degeneration (AMD).
4. Retinal vein occlusion.
5. Uncontrolled glaucoma (intraocular pressure >30 mmHg).
6. Uveitis.
7. Corneal or lens disorders that may interfere with ophthalmological examinations or imaging.
8. Other ocular diseases that may affect study outcomes.

• Soufi FG, Mohammad-Nejad D, Ahmadieh H. Resveratrol improves diabetic retinopathy possibly through oxidative stress - nuclear factor kappaB - apoptosis pathway. Pharmacol Rep. 2012;64(6):1505-14. doi: 10.1016/s1734-1140(12)70948-9. PMID 23406761