Novel Detection and Restorative Levodopa Treatment for Preclinical Diabetic Retinopathy

• Published in: Diabetes (New York, N.Y.) Vol. 69; no. 7; pp. 1518 - 1527
• Main Authors: Motz, Cara T, Chesler, Kyle C, Allen, Rachael S, Bales, Katie L, Mees, Lukas M, Feola, Andrew J, Maa, April Y, Olson, Darin E, Thule, Peter M, Iuvone, P Michael, Hendrick, Andrew M, Pardue, Machelle T
• Format: Journal Article
• Language: English
• Published: United States American Diabetes Association 01-07-2020
• Subjects: Adult; Aged; Carbidopa - therapeutic use; Complications; Diabetes; Diabetes mellitus; Diabetic retinopathy; Diabetic Retinopathy - diagnosis; Diabetic Retinopathy - drug therapy; Diabetic Retinopathy - physiopathology; Dopamine; Drug Combinations; Electroretinograms; Electroretinography - methods; Female; Humans; Levodopa; Levodopa - therapeutic use; Male; Middle Aged; Retina; Retinopathy; Timing
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/db19-0869

Diabetic retinopathy (DR) is diagnosed clinically by directly viewing retinal vascular changes during ophthalmoscopy or through fundus photographs. However, electroretinography (ERG) studies in humans and rodents have revealed that retinal dysfunction is demonstrable prior to the development of visible vascular defects. Specifically, delays in dark-adapted ERG oscillatory potential (OP) implicit times in response to dim-flash stimuli (<-1.8 log cd · s/m
) occur prior to clinically recognized DR. Animal studies suggest that retinal dopamine deficiency underlies these early functional deficits. In this study, we randomized individuals with diabetes, without clinically detectable retinopathy, to treatment with either low- or high-dose Sinemet (levodopa plus carbidopa) for 2 weeks and compared their ERG findings with those of control subjects (no diabetes). We assessed dim-flash-stimulated OP delays using a novel handheld ERG system (RETeval) at baseline and 2 and 4 weeks. RETeval recordings identified significant OP implicit time delays in individuals with diabetes without retinopathy compared with age-matched control subjects (
< 0.001). After 2 weeks of Sinemet treatment, OP implicit times were restored to control values, and these improvements persisted even after a 2-week washout. We conclude that detection of dim-flash OP delays could provide early detection of DR and that Sinemet treatment may reverse retinal dysfunction.