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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.

BACKGROUND Diabetic retinopathy causes vascular dilatation caused by hypoxia, whereas oxygen tension improvement leads to retinal vessels narrowing. Given that laser photocoagulation aims to increase the oxygen tension in the retina, we hypothesized that the narrowing of vessel caliber after the treatment could be possibly demonstrated. This study aimed to assess the changes in the caliber of retinal vessels before and after laser photocoagulation in diabetic retinopathy. METHODS This research was a prospective cohort study on the treatment of diabetic retinopathy by laser photocoagulation, and it was conducted at Universitas Hasanuddin Hospital, Makassar, Indonesia between November 2017–April 2018. Retinal vascular caliber changes were analyzed before and 6–8 weeks after photocoagulation in 30 diabetic eyes. Central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE) were measured using the vessel assessment and measurement platform software for images of the retina (VAMPIRE) manual annotation tool. RESULTS A significant decrease of CRVE was observed after laser photocoagulation (p

Objectives Improved identification of individuals with type 2 diabetes at high cardiovascular risk could help in selection of newer cardiovascular risk-reducing therapies. The aim of this study was to determine whether retinal vascular parameters, derived from retinal screening photographs, alone and in combination with a genome-wide polygenic risk score for coronary heart disease (CHD PRS) would have independent prognostic value over traditional CV risk assessment in patients without prior cardiovascular disease. Research Design and Methods Patients in the GoDARTS study were linked to retinal photographs, prescriptions, and outcomes. Retinal photographs were analysed using VAMPIRE software, a semi-automated AI platform, to compute arterial and venous fractal dimension, tortuosity and diameter. CHD PRS was derived from previously published data. Multivariable Cox regression was used to evaluate the association between retinal vascular parameters and major adverse cardiovascular events (MACE) at 10 years compared to the pooled cohort equations (PCE) risk score. Results 5,152 individuals were included. 1,017 individuals suffered a MACE. Reduced arterial fractal dimension and diameter and increased venous tortuosity each independently predicted MACE. A risk score combining these parameters significantly predicted MACE after adjustment for age, sex, PCE and the CHD PRS (HR 1.11 per SD increase; 95% CI 1.04-1.18, p=0.002) with similar accuracy to PCE (AUC 0.663 vs. 0.658, p=0.33). A model incorporating retinal parameters and PRS improved MACE prediction compared to PCE (AUC 0.686 vs. 0.658, p Conclusions Retinal parameters alone and in combination with genome-wide CHD PRS have independent and incremental prognostic value compared to traditional CV risk assessment in type 2 diabetes.

Purpose To describe and compare associations with macular retinal nerve fiber layer (mRNFL), ganglion cell complex (GCC), and ganglion cell–inner plexiform layer (GCIPL) thicknesses in a large cohort. Design Cross-sectional study. Participants We included 42 044 participants in the UK Biobank. The mean age was 56 years. Methods Spectral-domain OCT macular images were segmented and analyzed. Corneal-compensated intraocular pressure (IOPcc) was measured with the Ocular Response Analyzer (Reichert, Corp., Buffalo, NY). Multivariable linear regression was used to examine associations with mean mRNFL, GCC, and GCIPL thicknesses. Factors examined were age, sex, ethnicity, height, body mass index (BMI), smoking status, alcohol intake, Townsend deprivation index, education level, diabetes status, spherical equivalent, and IOPcc. Main Outcome Measures Thicknesses of mRNFL, GCC, and GCIPL. Results We identified several novel independent associations with thinner inner retinal thickness. Thinner inner retina was associated with alcohol intake (most significant for GCIPL: –0.46 μm for daily or almost daily intake compared with special occasion only or never [95% confidence interval (CI), 0.61–0.30]; P = 1.1×10–8), greater social deprivation (most significant for GCIPL: –0.28 μm for most deprived quartile compared with least deprived quartile [95% CI, –0.42 to –0.14]; P = 6.6×10–5), lower educational attainment (most significant for mRNFL: –0.36 μm for less than O level compared with degree level [95% CI, –0.45 to 0.26]; P = 2.3×10–14), and nonwhite ethnicity (most significant for mRNFL comparing blacks with whites: –1.65 μm [95% CI, –1.86 to –1.43]; P = 2.4×10–50). Corneal-compensated intraocular pressure was associated most significantly with GCIPL (–0.04 μm/mmHg [95% CI, –0.05 to –0.03]; P = 4.0×10–10) and was not associated significantly with mRNFL (0.00 μm/mmHg [95% CI, –0.01 to 0.01]; P = 0.77). The variables examined explained a greater proportion of the variance of GCIPL (11%) than GCC (6%) or mRNFL (7%). Conclusions The novel associations we identified may be important to consider when using inner retinal parameters as a diagnostic tool. Associations generally were strongest with GCIPL, particularly for IOP. This suggests that GCIPL may be the superior inner retinal biomarker for macular pathophysiologic processes and especially for glaucoma.

Purpose The pathophysiology of nonarteritic anterior ischemic optic neuropathy (NAION) is not completely understood. Studies of the retinal vasculature phenotype in patients with NAION could help us to understand vascular abnormalities associated with the disease. Design Retrospective case series with matched control subjects. Methods Study population: 57 patients with NAION and 57 control subjects matched to NAION patients for sex, age, systemic hypertension, diabetes, and obstructive sleep apnea syndrome between September 2007 and July 2017. Main Outcome Measures All patients and control subjects underwent a complete ocular examination and 45° funduscopic color photographs. The widths of the 6 largest arteries in zone B (between 0.5 and 1 optic disc diameter from the optic disc), summarized by the central retinal artery equivalent (CRAE), the widths of the 6 largest veins in zone B, summarized by the central retinal vein equivalent (CRVE), the arteriole to venule ratio, tortuosity, and fractal dimension were measured on the 2 groups using Vessel Assessment and Measurement Platform for Images of the Retina, a software tool for efficient semiautomatic quantification of the retinal vasculature morphology in fundus camera images. The Wilcoxon signed-rank test and MacNemar χ2 test for paired sample and generalized estimating equations for modeling the Vessel Assessment and Measurement Platform for Images of the Retina parameters as dependent variables were used. Results CRVE and fractal dimension (D0a) were significantly higher in the NAION group when compared with the control group, whereas the arteriole to venule ratio and vascular tortuosity were significantly lower. Compared with control subjects, acute NAION yielded an increased CRAE value (174 ± 33 vs 160 ± 13 μm) while resolution NAION yielded a decreased CRAE value (152 ± 12 vs 156 ± 33 μm). Acute NAION yielded an increased CRVE value (244 ± 35 vs 210 ± 21 μm) while resolution NAION yielded an unchanged CRVE value. We found no difference between groups for age, refraction, optic disc diameter, CRAE, or fractal dimension. Conclusions Retinal vascular parameters were different in our sample between NAION and control patients, especially at the acute stage of the disease. Our results suggest a normalization of the same parameters at the resolution stage.

Microvascular haemodynamic alterations are associated with coronary artery disease (CAD). The conjunctival microcirculation can easily be assessed non-invasively. However, the microcirculation of the conjunctiva has not been previously explored in clinical algorithms aimed at identifying patients with CAD. This case-control study involved 66 patients with post-myocardial infarction and 66 gender-matched healthy controls. Haemodynamic properties of the conjunctival microcirculation were assessed with a validated iPhone and slit lamp-based imaging tool. Haemodynamic properties were extracted with semi-automated software and compared between groups. Biomarkers implicated in the development of CAD were assessed in combination with conjunctival microcirculatory parameters. The conjunctival blood vessel parameters and biomarkers were used to derive an algorithm to aid in the screening of patients for CAD. Conjunctival blood velocity measured in combination with the blood biomarkers (N-terminal pro-brain natriuretic peptide and adiponectin) had an area under receiver operator characteristic curve (AUROC) of 0.967, sensitivity 93.0%, specificity 91.5% for CAD. This study demonstrated that the novel algorithm which included a combination of conjunctival blood vessel haemodynamic properties, and blood-based biomarkers could be used as a potential screening tool for CAD and should be validated for potential utility in asymptomatic individuals.