Short-term levodopa treatments ameliorate early stage electroretinogram (ERG) delays in diabetic patients

Abstract

Purpose : We previously showed that dim flash ERG stimuli reveal delayed oscillatory potentials (OPs) during early stage diabetic retinopathy (DR) in rodents and humans, prior to clinically-recognized vascular defects. Furthermore, we demonstrated that decreased dopamine levels contribute to this early dysfunction in rodents, and restoring dopamine levels preserved retinal and visual function. Here we evaluated whether levodopa treatments could alter OP delays in early stage diabetic participants using a handheld ERG device.

Methods : Male and female control participants (n=15; 30-70 yo) were tested for retinal function at baseline, 2 weeks, and 4 weeks. Diabetic participants (30-70 yo) without fundus signs of retinopathy were tested at baseline and then received either low (25 mg carbidopa/100 mg levodopa; n = 8) or high (50 mg carbidopa/200 mg levodopa; n = 7-10) dose Sinemet twice a day for two weeks. ERG testing (RETeval, LKC Inc) was performed at 2 days and 2 weeks following initiation of Sinemet treatment and 2 weeks after the end of treatment. ERGs were recorded from each eye without dilation using a cheek electrode after 10 min dark adaptation in response to dim (1.13 Tds) and bright (85 Tds) stimuli, and 10 min light adaptation (~1600 lux) with dim (32 Tds) and bright (85 Tds) flicker (28.3 Hz) stimuli. Amplitude and implicit times (ITs) of ERG waves were analyzed offline using custom MATLAB software.

Results : OP delays in diabetic subjects were detected at baseline using the dim (1.13 Tds), dark-adapted flash (Fig. 1; p<0.001). Low dose Sinemet restored OP ITs to control values at 2 and 4 weeks post-treatment initiation (Fig. 1) and high dose Sinemet restored changes by 2 days post-treatment, returned closer to baseline at 2 weeks, but then improved again at 4 weeks (Fig. 1) so that all groups were not stastically different from each other. ERG amplitudes did not show significant differences.

Conclusions : These data show that early retinal dysfunction in diabetic patients can be detected prior to fundus signs of retinopathy using a hand-held ERG device without dilation. Furthermore, low dose Sinemet improves OP timing with only 2 weeks of treatment. Future studies are needed to evaluate the utility of the RETeval as a screening tool for early stage DR and to determine long-term effects of dopamine treatments on DR.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.