Novel linkage approach to join community-acquired and national data.

BACKGROUND: Community optometrists in Scotland have performed regular free-at-point-of-care eye examinations for all, for over 15 years. Eye examinations include retinal imaging but image storage is fragmented and they are not used for research. The Scottish Collaborative Optometry-Ophthalmology Network e-research project aimed to collect these images and create a repository linked to routinely collected healthcare data, supporting the development of pre-symptomatic diagnostic tools. METHODS: As the image record was usually separate from the patient record and contained minimal patient information, we developed an efficient matching algorithm using a combination of deterministic and probabilistic steps which minimised the risk of false positives, to facilitate national health record linkage. We visited two practices and assessed the data contained in their image device and Practice Management Systems. Practice activities were explored to understand the context of data collection processes. Iteratively, we tested a series of matching rules which captured a high proportion of true positive records compared to manual matches. The approach was validated by testing manual matching against automated steps in three further practices. RESULTS: A sequence of deterministic rules successfully matched 95% of records in the three test practices compared to manual matching. Adding two probabilistic rules to the algorithm successfully matched 99% of records. CONCLUSIONS: The potential value of community-acquired retinal images can be harnessed only if they are linked to centrally-held healthcare care data. Despite the lack of interoperability between systems within optometry practices and inconsistent use of unique identifiers, data linkage is possible using robust, almost entirely automated processes.

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.

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.

Microvasculopathy in spinal muscular atrophy is driven by a reversible autonomous endothelial cell defect.

Spinal muscular atrophy (SMA) is a neuromuscular disorder due to degeneration of spinal cord motor neurons caused by deficiency of the ubiquitously expressed SMN protein. Here, we present a retinal vascular defect in patients, recapitulated in SMA transgenic mice, driven by failure of angiogenesis and maturation of blood vessels. Importantly, the retinal vascular phenotype was rescued by early, systemic SMN restoration therapy in SMA mice. We also demonstrate in patients an unfavorable imbalance between endothelial injury and repair, as indicated by increased circulating endothelial cell counts and decreased endothelial progenitor cell counts in blood circulation. The cellular markers of endothelial injury were associated with disease severity and improved following SMN restoration treatment in cultured endothelial cells from patients. Finally, we demonstrated autonomous defects in angiogenesis and blood vessel formation, secondary to SMN deficiency in cultured human and mouse endothelial cells, as the underlying cellular mechanism of microvascular pathology. Our cellular and vascular biomarker findings indicate microvasculopathy as a fundamental feature of SMA. Our findings provide mechanistic insights into previously described SMA microvascular complications, and highlight the functional role of SMN in the periphery, including the vascular system, where deficiency of SMN can be addressed by systemic SMN-restoring treatment.

2D alpha-shapes to quantify retinal microvasculature morphology and their application to proliferative diabetic retinopathy characterisation in fundus photographs.

The use of 2D alpha-shapes (α-shapes) to quantify morphological features of the retinal microvasculature could lead to imaging biomarkers for proliferative diabetic retinopathy (PDR). We tested our approach using the MESSIDOR dataset that consists of colour fundus photographs from 547 healthy individuals, 149 with mild diabetic retinopathy (DR), 239 with moderate DR, 199 pre-PDR and 53 PDR. The skeleton (centrelines) of the automatically segmented retinal vasculature was represented as an α-shape and the proposed parameters, complexity ([Formula: see text]), spread (OpA), global shape (VS) and presence of abnormal angiogenesis (Gradα) were computed. In cross-sectional analysis, individuals with PDR had a lower [Formula: see text], OpA and Gradα indicating a vasculature that is more complex, less spread (i.e. dense) and the presence of numerous small vessels. The results show that α-shape parameters characterise vascular abnormalities predictive of PDR (AUC 0.73; 95% CI [0.73 0.74]) and have therefore potential to reveal changes in retinal microvascular morphology.

Automated detection of age-related macular degeneration in color fundus photography: a systematic review.

The rising prevalence of age-related eye diseases, particularly age-related macular degeneration, places an ever-increasing burden on health care providers. As new treatments emerge, it is necessary to develop methods for reliably assessing patients' disease status and stratifying risk of progression. The presence of drusen in the retina represents a key early feature in which size, number, and morphology are thought to correlate significantly with the risk of progression to sight-threatening age-related macular degeneration. Manual labeling of drusen on color fundus photographs by a human is labor intensive and is where automatic computerized detection would appreciably aid patient care. We review and evaluate current artificial intelligence methods and developments for the automated detection of drusen in the context of age-related macular degeneration.