Outer Retinal Structure and Function Deficits Contribute to Circadian Disruption in Patients With Type 2 Diabetes

Light transmitted by retinal photoreceptors provides the input for circadian photoentrainment. In diabetes, there is a high prevalence of circadian and sleep disruption but the underlying causes are not well understood. Patients with diabetes can exhibit dysfunctional photoreceptors but their role in circadian health is not known. Here we quantify photoreceptor function and contributions to circadian health and sleep in patients with diabetes without diabetic retinopathy and healthy controls.

Rod, cone, and melanopsin function was derived using chromatic pupillometry in 47 participants including 23 patients with type 2 diabetes and 24 age-matched healthy controls after an ophthalmic examination including retinal thickness assessment using optical coherence tomography. Circadian health was determined using dim light melatonin onset (DLMO) and sleep questionnaires; light exposure was measured using actigraphy.

Compared with the control group, the patients with diabetes had a significantly earlier DLMO (1 hour) (P = 0.008), higher subjective sleep scores (P < 0.05), a reduction in pupil constriction amplitude for red stimuli (P = 0.039) and for the early postillumination pupil response (PIPR) for blue (P = 0.024) stimuli. There were no between-group differences in the light exposure pattern, activity levels, and intrinsic melanopsin-mediated PIPR amplitude (P > 0.05). A significant correlation was evident between outer retinal thickness and DLMO (r = -0.65, P = 0.03) and the pupil constriction amplitude (r = 0.63, P = 0.03); patients with thinner retina had earlier DLMO and lower pupil amplitudes.

We infer that the observed changes in circadian function in patients with no diabetic retinopathy are due to structural and functional outer retinal rod photoreceptor deficits at early stage of diabetic eye disease.