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Graefe's Archive for Clinical and Experimental Ophthalmology

Open Access 25-04-2024 | Artificial Intelligence | Genetics

Clinical and genetic studies for a cohort of patients with Leber congenital amaurosis

Authors: Yunyu Zhou, Lijuan Huang, Yan Xie, Wen Liu, Shasha Zhang, Lili Liu, Ping Lin, Ningdong Li

Published in: Graefe's Archive for Clinical and Experimental Ophthalmology

Abstract

Purpose

Leber congenital amaurosis (LCA) is a group of early-onset retinal degenerative disorders, resulting in blindness in children. This study aimed to describe the clinical and genetic characteristics of a cohort of patients with LCA and to investigate the retinal vascular characteristics in LCA patients.

Methods

Fifty-two children with LCA were included in the study. All patients underwent detailed ocular examinations. Electroretinography (ERG) was used to evaluate the retinal function. Optical coherence tomography (OCT) was used to assess the structure change of the retina for those patients who were able to cooperate very well. Panel-based next-generation sequencing was performed to identify pathogenic variants in genes associated with LCA. Diameters of the retinal vessels were measured using the EVision AI screening system with an artificial intelligence (AI) technique. An ultrasound Doppler was used to evaluate hemodynamic parameters, including peak systolic velocity (PSV), resistive index (RI), and pulsatility index (PI), in the ophthalmic, central retinal, posterior ciliary, carotid, and internal carotid as well as external carotid arteries in 12 patients aged from 3 to 14 years.

Results

We detected 75 pathogenic variants from ten genes of RPGRIP1, CEP290, GUCY2D, LCA5, AIPL1, CRB1, RPE65, CRX, RDH12, and TULP1, including 29 novel and 36 previously reported variants in 52 affected children with LCA, with the highest detective rate in RPGRIP1 (26.9%). Fundus appearance is diverse in patients with LCA, ranging from normal to severe peripheral or central retinopathy. Retinal vasculature was evaluated in 12 patients with different gene variants, showing narrowed arteries with an average diameter of 43.6 ± 3.8 μm compared to that of 51.7 ± 2.6 μm in the normal controls (P < 0.001, n = 12). Meanwhile, their hemodynamic parameters were changed as well in the ophthalmic artery (OA), with a decreased PSV (P = 0.0132, n = 12) and slightly increased PI (P = 0.0488, n = 12) compared to the normal controls. However, the hemodynamic parameters did not change significantly in the other vessels.

Conclusions

Blood supply to the eyeball is predicted to be reduced in patients with LCA, presumably due to photoreceptor cell degeneration. The novel identified variants will expand the spectrum of variants in LCA-related genes and be useful for studying the molecular mechanisms of LCA.

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Title: Clinical and genetic studies for a cohort of patients with Leber congenital amaurosis
Authors: Yunyu Zhou
Lijuan Huang
Yan Xie
Wen Liu
Shasha Zhang
Lili Liu
Ping Lin
Ningdong Li
Publication date: 25-04-2024
Publisher: Springer Berlin Heidelberg
Keyword: Artificial Intelligence
Published in: Graefe's Archive for Clinical and Experimental Ophthalmology
Print ISSN: 0721-832X
Electronic ISSN: 1435-702X
DOI: https://doi.org/10.1007/s00417-024-06450-9

At a glance: The STEP trials

Springer Medicine

Clinical and genetic studies for a cohort of patients with Leber congenital amaurosis

Abstract

Purpose

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

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