The role of retinal photoreceptors in the regulation of circadian rhythms and sleep in systemic disease

Retinal photoreceptors provide light signals to regulate the pupil light reflex, circadian photoentrainment and sleep. People with either diabetes or Parkinson's disease experience circadian disruption, but the pathophysiology is not well understood. This thesis demonstrates that in diabetes, dysfunctional outer retinal rod inputs to melanopsin ganglion cells contribute to the sleep disruption. In Parkinson's disease, the dysfunction is at the level of melanopsin ganglion cells, with additional non-selective reductions in retinal contrast gain. These findings identify new retinal pathways contributing to sleep and circadian disruption in people with systemic disease

Outer retinal structure and function deficits contribute to circadian disruption in patients with type 2 diabetes

PURPOSE 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. METHODS. 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. RESULTS 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 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. CONCLUSIONS. 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

Melanopsin Cell Dysfunction Is Involved in Sleep Disruption in Parkinson's Disease

Background: Melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) signal the environmental light to mediate circadian photoentrainment and sleep-wake cycles. There is high prevalence of circadian and sleep disruption in people with Parkinson's disease, however the underlying mechanisms of these symptoms are not clear. Objective: Based on recent evidence of anatomical and functional loss of melanopsin ganglion cells in Parkinson's disease, we evaluate the link between melanopsin function, circadian, and sleep behavior. Methods: The pupil light reflex and melanopsin-mediated post-illumination pupil response were measured using chromatic pupillometry in 30 optimally medicated people with Parkinson's disease and 29 age-matched healthy controls. Circadian health was determined using dim light melatonin onset, sleep questionnaires, and actigraphy. Ophthalmic examination quantified eye health and optical coherence tomography measured retinal thickness. Results: The melanopsin-mediated post-illumination pupil response amplitudes were significantly reduced in Parkinson's disease (p0.05). Conclusion: Our evidence-based data identify a mechanism through which inner retinal ipRGC dysfunction contributes to sleep disruption in Parkinson's disease in the presence of normal outer retinal (rod-cone photoreceptor) function. Our findings provide a rationale for designing new treatment approaches in Parkinson's disease through melanopsin photoreceptor-targeted light therapies for improving sleep-wake cycles. </p

Segmentation errors in macular ganglion cell analysis as determined by optical coherence tomography in eyes with macular pathology

Abstract Background To evaluate artifacts in macular ganglion cell inner plexiform layer (GCIPL) thickness measurement in eyes with retinal pathology using spectral-domain optical coherence tomography (SD OCT). Methods Retrospective analysis of color-coded maps, infrared images and 128 horizontal B-scans (acquired in the macular ganglion cell inner plexiform layer scans), using the Cirrus HD-OCT (Carl Zeiss Meditec, Dublin, CA). The study population included 105 eyes with various macular conditions compared to 30 eyes of 30 age-matched healthy volunteers. The overall frequency of image artifacts and the relative frequency of artifacts were stratified by macular disease. Results Scan errors and artifacts were found in 55.1% of the 13,440 B-scans in eyes with macular pathology and 26.8% of the 3840 scans in normal eyes. Segmentation errors were the most common scan error in both groups, with more common involvement of both segmentation borders in diseased eyes and anterior segmentation border in normal eyes. Conclusion Segmentation errors and artifacts in SD OCT GCA are common in conditions involving the macula. These findings should be considered when assessing macular GCIPL thickness and careful assessment of scans is suggested

Comparison of choroidal vessel thickness in children and adult eyes by enhanced-depth imaging optical coherence tomography imaging

AIM: To evaluate choroidal thickness, medium choroidal vessel thickness (MCVT) and large choroidal vessel thickness (LCVT) in normal children and adult subjects. METHODS: Manual measurements of subfoveal choroidal thickness (SFCT), MCVT and LCVT at subfoveal and 750 μm nasal and temporal to fovea locations were completed on enhanced-depth imaging optical coherence tomography (EDI-OCT) scans of normal children and adult subjects. RESULTS: Fifty adult and fifty-seven child subjects were included in the study (including 80 adult and 103 child eyes). Mean (±SD) SFCT of adult and children eyes in the study was 309.3±95.7 μm and 279.3±50.4 μm respectively. SFCT and subfoveal MCVT in adult eyes were significantly more than children (P=0.01 and P≤0.0001 respectively). CONCLUSION: There is choroidal thickening with associated thickening of medium choroidal vessels in adults, suggesting that there is alteration in choroidal vasculature with ageing

Prevalence and Distribution of Segmentation Errors in Macular Ganglion Cell Analysis of Healthy Eyes Using Cirrus HD-OCT - Fig 3

<p>Composite figure demonstrating various artifacts on ganglion cell-inner plexiform layer automated segmentation: (A) Both, Inner and outer layer misidentification, note the purple does not follow the contour of the inner ganglion cell layer and the yellow line does not follow the outer inner plexiform layer; (B) Blink artifact: missing retinal image due to blink; (C) Out of register artifact: shifting of the scan superiorly with loss of information of temporal area; (D) Absence of outer segmentation line; (E) and (F) Degraded image with misidentification of layers in temporal (F) and nasal (E) regions. Of note, all signal strengths of these scans are >6.</p

Example of macular ganglion cell inner plexiform layer (GCIPL) thickness measurement as determined automatically by optical coherence tomography: (Top maps) macular GCIPL thickness maps.

<p>Sectoral maps shows macular GCIPL thicknesses at superotemporal, superior, superonasal, inferonasal, inferior, and inferotemporal sectors. Sectoral thicknesses are measured in an elliptical annulus with a vertical outer radius of 2.0 mm and a horizontal radius of 2.4 mm. Deviation map shows the deviation of GCIPL measurements from age-matched healthy controls, shown as red (less 1% probability), yellow (1–5% probability), green (5–95% probability), and white (more than 95% probability). Cross-sectional scans at the level of fovea shows the segmentation of GCIPL. The outer border of the RNFL (retinal nerve fiber layer) is presented as a solid purple line and the outer border of the IPL is presented as a solid yellow line.</p

Evaluation of choroidal layer thickness in central serous chorioretinopathy

Purpose: To evaluate medium and large choroidal vessel layer thickness (MCVT and LCVT, respectively) in eyes with acute and chronic central serous chorioretinopathy (CSC) in comparison with age-matched controls. Methods: The study included 96 eyes of 96 patients with CSC, including 53 eyes with acute CSC, 43 eyes with chronic CSC, and 30 eyes of 30 age-matched normal subjects. Manual measurements of subfoveal choroidal thickness (SFCT), MCVT, and LCVT at subfoveal and 750 μm nasal and temporal to the fovea locations were made on enhanced depth imaging optical coherence tomography (EDI-OCT) of the macula in all subjects using ImageJ software (National Institutes of Health, Bethesda, MD, USA). Results: SFCT in acute CSC was significantly larger than that in healthy eyes (P = 0.0001). SFCT in acute CSC did not differ significantly from that in chronic CSC eyes. Subfoveal LCVT and MCVT in acute CSC eyes were greater than those in healthy eyes (P = 0.02 and P = 0.03, respectively). Mean SFCT and MCVT in chronic CSC eyes were significantly larger than those in control eyes (P = 0.01 and P = 0.04, respectively). No significant difference in LCVT was observed between chronic and control eyes. Conclusion: Choroidal vasculature is altered in both acute and chronic CSC. SFCT, MCVT, and LCVT are higher in eyes with acute CSC. The thickening of medium choroidal vessels is still detectable in chronic CSC compared to control eyes