The post‐illumination pupil response of melanopsin‐expressing intrinsically photosensitive retinal ganglion cells in diabetes

Abstract

ABSTRACT.Purpose: This study investigates the clinical utility of the melanopsin-expressing intrinsically photosensitive retinal ganglion cell (ipRGC) controlled postillumination pupil response (PIPR) as a novel technique for documenting inner retinal function in patients with Type II diabetes without diabetic retinopathy. Methods: The PIPR was measured in seven patients with Type II diabetes, normal retinal nerve fibre thickness and no diabetic retinopathy compared to healthy age-similar controls. A 488-and 610-nm, 7.15-diameter stimulus was presented in Maxwellian view to the right eye and the left consensual pupil light reflex was recorded. Results: The group data for the blue PIPR (488 nm) identified a trend of reduced ipRGC function in patients with diabetes with no retinopathy. The transient pupil constriction was lower on average in the diabetic group. The relationship between duration of diabetes and the blue PIPR amplitude was linear, suggesting that ipRGC function decreases with increasing diabetes duration. Conclusion: This is the first report to show that the ipRGC-controlled PIPR may have clinical applications as a non-invasive technique for determining the progression of inner neuroretinal changes in patients with diabetes before they are ophthalmoscopically or anatomically evident. The lower transient pupil constriction amplitude indicates that outer retinal photoreceptor inputs to the pupil light reflex may also be affected in diabetes.

Auditory/Visual Integration Assessment and Treatment in Brain Injury Rehabilitation

“…It is also believed that the ipRGCs influence an intrinsic retinal circadian clock to regulate retinal melatonin levels by both exogenous light stimulation and endogenous circadian stimulation) [41]. The effects that the ipRGC have on degenerative processes are studied in diseases such as glaucoma and diabetes [42].…”

The retinal clock in mammals: role in health and disease

“…55,104 In patients with type 2 diabetes, ipRGC dysfunction has been proposed to be investigated for diagnostic purpose by using the postillumination pupil response (PIPR), a sustained constriction of the pupil after light offset. 105 The classic hallmark of glaucomatous optic neuropathies is the progressive loss of RGCs and their axons, with concomitant insidious defects in the visual field. As for RGCs, ipRGC abnormalities have been reported in rodent models of experimental glaucoma [106][107][108][109] and in glaucomatous patients.…”

Image and Non-Image Forming Melanopsin Function in Age-Related Macular Degeneration

“…While their involvement in AMD is currently not fully understood, pilot data indicate that they are dysfunctional in late stages of the condition . Whether they are affected in early AMD as has been shown for glaucoma (Adhikari, Zele, Thomas & Feigl 2016b) and in diabetes without retinopathy (Feigl et al 2012b) is yet to be determined. The choroid lies posterior to the retina and is separated from the retinal pigment epithelium (RPE) by Bruch's membrane (BM).…”

“…IpRGCs also signal to the olivary pretectal nucleus (OPN) for mediation of the pupil light reflex (PLR) (Gamlin et al 2007;Kawasaki & Kardon 2007) and in particular the post-illumination pupil response (PIPR) (Adhikari et al 2016a;Gamlin et al 2007;Kawasaki & Kardon 2007;Markwell et al 2010), which is an emerging method for the direct assessment of ipRGC function in healthy and diseased eyes and in persons with chronobiological disorders Feigl et al 2012b;Gamlin et al 2007;Gracitelli et al 2016;Gracitelli et al 2014;Gracitelli et al 2015;Kawasaki & Kardon 2007;Markwell et al 2010;Maynard et al 2015). Two recent studies observed that sleep duration was altered in advanced AMD patients; sleep duration decreased in wet AMD and increased in dry AMD (Khurana et al 2016;Pérez-Canales et al 2016) but the effect of aberrant ipRGC signalling in AMD Maynard et al 2015) as a contributing factor was not evaluated.…”

“…IpRGC function has been measured using the PIPR in diabetic patients without diabetic retinopathy (Feigl et al 2012b), glaucoma (Feigl et al 2011b;Gracitelli et al 2014;Kankipati et al 2011), retinitis pigmentosa Kawasaki, Crippa, Kardon, Leon & Hamel 2012;Markwell et al 2010), Leber's hereditary optic neuropathy (Kawasaki, Herbst, Sander & Milea 2010) and retinal dystrophy (Vugler, Semo, Joseph & Jeffery 2008). In AMD, the PLR has been used as a measure of outer retinal function (Asakawa, Ishikawa, Ichibe & Shimizu 2014;Brozou et al 2009;Nakayama, Nowak, Ishikawa, Asakawa & Ichibe 2014;Rosli et al 2012;Sabeti et al 2013;Sabeti et al 2011) and demonstrates a longer latency to constriction and reduction in maximum pupil constriction amplitude.…”