{ "abstract": "Objectives To develop a vessel quantification pipeline (VESPAR) for fundus autofluorescence (FAF) and infrared (IR) imaging in inherited retinal diseases (IRDs) to enable gene-phenotype association studies and explore vascular changes in these conditions.Methods Retrospective IRD patient data (55-degree blue-FAF and 30-degree IR from Heidelberg Spectralis, 2004–2019) were gathered from Moorfields Eye Hospital (MEH), the Royal Liverpool Hospital (RLH) and Oxford Eye Hospital (OEH). Manual segmentation of retinal blood vessels was undertaken in 127 FAF images from 69 patients representing 28 distinct genes by two expert graders, as well as 16 IR images from 16 patients representing 11 distinct genes by a third grader, from the RLH. A U-Mamba model trained on 72 FAF scans and tested on 23 FAF and 16 IR scans, segmented 42,268 FAF scans (3,616 patients, 179 genes) and 77,090 IR scans (4,307 patients, 198 genes) from MEH. Quantitative metrics were then derived using reti-py.Results Model-grader Dice was 0.68 on FAF (intergrader Dice 0.66) and 0.59 on IR. VESPAR’s fractal dimension strongly correlated with manual values, while fractal dimension and vessel density showed the best repeatability across intra- and inter-visit cohorts.Retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA) exhibited the lowest fractal dimensions at baseline (1.30 - 1.40), whereas optic atrophy (OPA1) and choroideremia had the highest (1.49 and 1.46). Dominant RP genes showed higher vessel density (11.8%) and fractal dimension (1.421) than X-linked (8.2% and 1.351) and recessive genes (9.1% and1.369); while tortuosity density (0.737) was significantly lower than in recessive RP (0.748). In PRPH2, the RP phenotype had lower vessel density (12.4%) than the macular dystrophy phenotype (15.6%). In ABCA4, the most severe phenotype and genotype groups had significantly lower vessel density than the least severe groups. Moreover, vessel metrics correlated with VA and age and, revealed distinct progression rates across different genes and phenotypes.Conclusions VESPAR paves the way for robust gene-phenotype associations by facilitating cross-sectional and longitudinal analyses of vascular changes in IRDs.", "authors": [ { "affiliations": [ "University College London Institute of Ophthalmology", "Moorfields Eye Hospital NHS Foundation Trust" ], "name": "Bernardo Souza Mendes" }, { "affiliations": [ "University College London Institute of Ophthalmology", "Moorfields Eye Hospital NHS Foundation Trust" ], "name": "William Woof" }, { "affiliations": [ "University College London Institute of Ophthalmology", "Moorfields Eye Hospital NHS Foundation Trust", "Department of Ophthalmology Faculdade São Leopoldo Mandic" ], "name": "Thales AC de Guimarães" }, { "affiliations": [ "Oxford Eye Hospital", "Nuffield Laboratory of Ophthalmology" ], "name": "Saoud Al-Khuzaei" }, { "affiliations": [ "St Paul’s Eye Unit" ], "name": "Paula Burke" }, { "affiliations": [ "St Paul’s Eye Unit" ], "name": "David Parry" }, { "affiliations": [ "University College London Institute of Ophthalmology", "Moorfields Eye Hospital NHS Foundation Trust" ], "name": "Malena Daich Varela" }, { "affiliations": [ "University College London Institute of Ophthalmology", "Moorfields Eye Hospital NHS Foundation Trust" ], "name": "Sagnik Sen" }, { "affiliations": [ "University College London Institute of Ophthalmology", "Moorfields Eye Hospital NHS Foundation Trust" ], "name": "Pallavi Bagga" }, { "affiliations": [ "University College London Institute of Ophthalmology", "Moorfields Eye Hospital NHS Foundation Trust" ], "name": "Gunjan Naik" }, { "affiliations": [ "University College London Institute of Ophthalmology", "Moorfields Eye Hospital NHS Foundation Trust", "Manchester Centre for Genomic Medicine and Department of Ophthalmology", "Division of Evolution, Infection and Genomics University of Manchester" ], "name": "Siying Lin" }, { "affiliations": [ "University College London Institute of Ophthalmology", "Moorfields Eye Hospital NHS Foundation Trust" ], "name": "Mital Shah" }, { "affiliations": [ "University College London Institute of Ophthalmology", "Moorfields Eye Hospital NHS Foundation Trust" ], "name": "Quang Nguyen" }, { "affiliations": [ "University College London Institute of Ophthalmology", "Moorfields Eye Hospital NHS Foundation Trust" ], "name": "Shafi Balal" }, { "affiliations": [ "Cancer Research UK and UCL Clinical Trials Centre" ], "name": "Memuna Rashid" }, { "affiliations": [ "University College London Institute of Ophthalmology", "Moorfields Eye Hospital NHS Foundation Trust" ], "name": "Biraja Ghoshal" }, { "affiliations": [ "Moorfields Eye Hospital NHS Foundation Trust" ], "name": "Yiu Wai Chan" }, { "affiliations": [ "University College London Translational Research Office (TRO)" ], "name": "Jennifer Furman" }, { "affiliations": [ "University College London Translational Research Office (TRO)" ], "name": "Jessica Walsh" }, { "affiliations": [ "University College London Institute of Ophthalmology", "Moorfields Eye Hospital NHS Foundation Trust" ], "name": "Dayyanah Sumodhee" }, { "affiliations": [ "University College London Institute of Ophthalmology", "Moorfields Eye Hospital NHS Foundation Trust" ], "name": "Dun Jack Fu" }, { "affiliations": [ "University College London Institute of Ophthalmology", "Moorfields Eye Hospital NHS Foundation Trust" ], "name": "Praveen Patel" }, { "affiliations": [ "University College London Institute of Ophthalmology", "Moorfields Eye Hospital NHS Foundation Trust" ], "name": "Ismail Moghul" }, { "affiliations": [ "University College London Institute of Ophthalmology", "Moorfields Eye Hospital NHS Foundation Trust" ], "name": "Michalis Georgiou" }, { "affiliations": [ "University College London Institute of Ophthalmology", "Moorfields Eye Hospital NHS Foundation Trust" ], "name": "Mariya Moosaje" }, { "affiliations": [ "University College London Institute of Ophthalmology", "Moorfields Eye Hospital NHS Foundation Trust" ], "name": "Andrew R Webster" }, { "affiliations": [ "University College London Institute of Ophthalmology", "Moorfields Eye Hospital NHS Foundation Trust" ], "name": "Omar A Mahroo" }, { "affiliations": [ "University College London Institute of Ophthalmology", "Moorfields Eye Hospital NHS Foundation Trust" ], "name": "Konstantinos Balaskas" }, { "affiliations": [ "Oxford Eye Hospital" ], "name": "Susan M Downes" }, { "affiliations": [ "St Paul’s Eye Unit" ], "name": "Savita Madhusuhan" }, { "affiliations": [ "University College London Institute of Ophthalmology", "Moorfields Eye Hospital NHS Foundation Trust" ], "name": "Michel Michaelides" }, { "affiliations": [ "University College London Institute of Ophthalmology", "Moorfields Eye Hospital NHS Foundation Trust" ], "name": "Nikolas Pontikos" } ], "title": "#ECR-Paper-03 VESPAR: quantitative analysis of the retinal vasculature using a novel segmentation algorithm to enable gene-phenotype association studies in a cohort of 3,944 patients with inherited retinal diseases", "uid": "6165995b-4322-5086-9c06-e72b70bd80ac" }