Analysis of the Retinal and Choroidal Vasculature Using Ultrawidefield Fundus Imaging in Mild Cognitive Impairment and Normal Cognition

Purpose: To utilize ultrawidefield (UWF) imaging to evaluate retinal and choroidal vasculature and structure in individuals with mild cognitive impairment (MCI) compared with that of controls with normal cognition. Design: Prospective cross sectional study. Participants: One hundred thirty-one eyes of 82 MCI patients and 230 eyes of 133 cognitively normal participants from the Eye Multimodal Imaging in Neurodegenerative Disease Study. Methods: A scanning laser ophthalmoscope (California, Optos Inc) was used to obtain UWF fundus color images. Images were analyzed with the Vasculature Assessment Platform for Images of the Retina UWF (VAMPIRE-UWF 2.0, Universities of Edinburgh and Dundee) software. Main outcome measures: Imaging parameters included vessel width gradient, vessel width intercept, large vessel choroidal vascular density, vessel tortuosity, and vessel fractal dimension. Results: Both retinal artery and vein width gradients were less negative in MCI patients compared with controls, demonstrating decreased rates of vessel thinning at the periphery (P &lt; 0.001; P = 0.027). Retinal artery and vein width intercepts, a metric that extrapolates the width of the vessel at the center of the optic disc, were smaller in MCI patients compared with that of controls (P &lt; 0.001; P = 0.017). The large vessel choroidal vascular density, which quantifies the vascular area versus the total choroidal area, was greater in MCI patients compared with controls (P = 0.025). Conclusions: When compared with controls with normal cognition, MCI patients had thinner retinal vasculature manifested in both the retinal arteries and the veins. In MCI, these thinner arteries and veins attenuated at a lower rate when traveling toward the periphery. MCI patients also had increased choroidal vascular density. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.</p

Ultra-Widefield Imaging of the Retinal Macrovasculature in Parkinson Disease Versus Controls With Normal Cognition Using Alpha-Shapes Analysis

Purpose: To investigate retinal vascular characteristics using ultra-widefield (UWF) scanning laser ophthalmoscopy in Parkinson disease (PD).Methods: Individuals with an expert-confirmed clinical diagnosis of PD and controls with normal cognition without PD underwent UWF imaging (California, Optos). Patients with diabetes, uncontrolled hypertension, glaucoma, dementia, other movement disorders, or known retinal or optic nerve pathology were excluded. Images were analyzed using Vasculature Assessment and Measurement Platform for Images of the Retina (VAMPIRE-UWF; Universities of Edinburgh and Dundee, UK) software which described retinal vessel width gradient and tortuosity, vascular network fractal dimension, as well as alpha-shape analysis to further characterize vascular morphology [complexity (Opαmin) and spread (OpA)].Results: In the PD cohort, 53 eyes of 38 subjects, and in the control cohort, 51 eyes of 33 subjects were assessed. Eyes with PD had more tortuous retinal arteries in the superotemporal quadrant (p = 0.043). In eyes with PD, alpha-shape analysis revealed decreased OpA, indicating less retinal vasculature spread compared to controls (p = 0.032). Opαmin was decreased in PD (p = 0.044), suggesting increased vascular network complexity. No differences were observed in fractal dimension in any ROI.Conclusions: This pilot study suggests that retinal vasculature assessment on UWF images using alpha-shape analysis reveals differences in retinal vascular network spread and complexity in PD and may be a more sensitive metric compared to fractal dimension.Translational Relevance: Retinal vasculature assessment using these novel methods may be useful in understanding ocular manifestations of PD and the development of retinal biomarkers

Ultra-Widefield Imaging of the Retinal Macrovasculature in Parkinson Disease Versus Controls With Normal Cognition Using Alpha-Shapes Analysis

PURPOSE: To investigate retinal vascular characteristics using ultra-widefield (UWF) scanning laser ophthalmoscopy in Parkinson disease (PD).METHODS: Individuals with an expert-confirmed clinical diagnosis of PD and controls with normal cognition without PD underwent Optos California UWF imaging. Patients with diabetes, uncontrolled hypertension, glaucoma, dementia, other movement disorders, or known retinal or optic nerve pathology were excluded. Images were analyzed using Vasculature Assessment and Measurement Platform for Images of the Retina (VAMPIRE-UWF) software, which describes retinal vessel width gradient and tortuosity, provides vascular network fractal dimensions, and conducts alpha-shape analysis to further characterize vascular morphology (complexity, Opαmin; spread, OpA).RESULTS: In the PD cohort, 53 eyes of 38 subjects were assessed; in the control cohort, 51 eyes of 33 subjects were assessed. Eyes with PD had more tortuous retinal arteries in the superotemporal quadrant (P = 0.043). In eyes with PD, alpha-shape analysis revealed decreased OpA, indicating less retinal vasculature spread compared to controls (P = 0.032). Opαmin was decreased in PD (P = 0.044), suggesting increased vascular network complexity. No differences were observed in fractal dimension in any region of interest.CONCLUSIONS: This pilot study suggests that retinal vasculature assessment on UWF images using alpha-shape analysis reveals differences in retinal vascular network spread and complexity in PD and may be a more sensitive metric compared to fractal dimension.TRANSLATIONAL RELEVANCE: Retinal vasculature assessment using these novel methods may be useful in understanding ocular manifestations of PD and the development of retinal biomarkers.</p

Retinal vascular changes in Alzheimer’s dementia and mild cognitive impairment:a pilot study using ultra-widefield imaging

Purpose: Retinal microvascular abnormalities measured on retinal images are a potential source of prognostic biomarkers of vascular changes in the neurodegenerating brain. We assessed the presence of these abnormalities in Alzheimer’s dementia and mild cognitive impairment (MCI) using ultra-widefield (UWF) retinal imaging. Methods: UWF images from 103 participants (28 with Alzheimer’s dementia, 30 with MCI, and 45 with normal cognition) underwent analysis to quantify measures of retinal vascular branching complexity, width, and tortuosity. Results: Participants with Alzheimer’s dementia displayed increased vessel branching in the midperipheral retina and increased arteriolar thinning. Participants with MCI displayed increased rates of arteriolar and venular thinning and a trend for decreased vessel branching. Conclusions: Statistically significant differences in the retinal vasculature in peripheral regions of the retina were observed among the distinct cognitive stages. However, larger studies are required to establish the clinical importance of our findings. UWF imaging may be a promising modality to assess a larger view of the retinal vasculature to uncover retinal changes in Alzheimer’s disease. Translational Relevance: This pilot work reports an investigation into which retinal vasculature measurements may be useful surrogate measures of cognitive decline, as well as technical developments (e.g., measurement standardization), that are first required to establish their recommended use and translational potential

Longitudinal Analysis of Retinal Microvascular and Choroidal Imaging Parameters in Parkinson's Disease Compared with Controls

Purpose: To quantify rate of change of retinal microvascular and choroidal structural parameters in subjects with Parkinson's disease (PD) compared with controls using OCT and OCT angiography (OCTA). Design: Prospective longitudinal study. Participants: Seventy-four eyes of 40 participants with PD and 149 eyes of 78 control individuals from the Eye Multimodal Imaging in Neurodegenerative Disease database. Methods: Subjects underwent OCT and OCTA imaging at 2 time points approximately 12 months apart. Main Outcome Measures: Imaging parameters included central subfield thickness, ganglion cell-inner plexiform layer (GC-IPL) thickness, peripapillary retinal nerve fiber layer thickness, choroidal vascularity index, superficial capillary plexus perfusion density (PFD), vessel density (VD), and foveal avascular zone area. Results: Participants with PD had greater rate of yearly decrease in GC-IPL (PD = −0.403μm, control = + 0.128 μm; P = 0.01), greater yearly decline in PFD in the 3 × 3 mm ETDRS circle (PD = −0.016, control = + 0.002; P < 0.001) and ring (PD = −0.016, control = + 0.002; P < 0.001); 6 × 6 mm ETDRS circle (PD = −0.021, control = 0.00; P = 0.001), and outer ring (PD = −0.022, control = 0.00; P = 0.001). Participants with PD had greater rate of yearly decline in VD in 3 × 3 mm circle (PD = −0.939/mm, control = + 0.006/mm; P < 0.001) and ring (PD = −0.942/mm, control = + 0.013/mm; P < 0.001); 6 × 6 mm circle (PD = −0.72/mm, control = −0.054/mm; P = 0.006), and outer ring (PD = −0.746/mm, control = −0.054/mm; P = 0.005). When stratified by PD severity based on Hoehn and Yahr stage, faster rates of decline were seen in Hoehn and Yahr stages 3 to 4 in the 3 × 3 mm circle PFD and VD as well as 3 × 3 mm ring VD. Conclusions: Individuals with PD experience more rapid loss of retinal microvasculature quantified on OCTA and more rapid thinning of the GC-IPL than controls. There may be more rapid loss in patients with greater disease severity. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article

Intrasession Repeatability of OCT Angiography Parameters in Neurodegenerative Disease

Purpose: To assess the intrasession repeatability of macular OCT angiography (OCTA) parameters in Alzheimer's disease (AD), mild cognitive impairment (MCI), Parkinson's disease (PD), and normal cognition (NC). Design: Cross sectional study. Subjects: Patients with a clinical diagnosis of AD, PD, MCI, or NC were imaged. Images with poor quality and of those with diabetes mellitus, glaucoma, or vitreoretinal disease were excluded from analysis. Methods, Intervention or Testing: All participants were imaged using the Zeiss Cirrus HD-5000 with AngioPlex (Carl Zeiss Meditec, Software Version 11.0.0.29946) and repeat OCTA images were obtained for both eyes. Perfusion density (PFD), vessel density (VD), and Foveal avascular zone (FAZ) area were measured from 3 × 3 mm and 6 × 6 mm OCTA images centered on the fovea using an ETDRS grid overlay. Main Outcome Measures: Intraclass correlation coefficients were used to quantify repeatability of PFD, VD, and FAZ area measurements obtained from imaging. Results: 3 × 3 mm scans of 22 AD, 40 MCI, 21 PD, and 26 NC participants and 6 × 6 mm scans of 29 AD, 44 MCI, 29 PD, and 30 NC participants were analyzed. Repeatability values ranged from 0.64 (0.49–0.82) for 6 × 6 mm PFD in AD participants to 0.87 (0.67–0.92) for 3 × 3 mm PFD in AD participants. No significant differences were observed in repeatability between NC participants and those with neurodegenerative disease. Conclusions: Overall, similar OCTA repeatability was observed between NC participants and those with neurodegeneration. Regardless of diagnostic group, macular OCTA metrics demonstrated moderate to good repeatability. Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article