Optic Nerve Head and Retinal Abnormalities Associated with Congenital Fibrosis of the Extraocular Muscles

Thomas, Mervyn, Maconachie, Gail D. E., Kuht, Helen J. , Chan, Wai-Man, Sheth, Viral, Hisaund, Michael, McLean, Rebecca J., Barry, Brenda, Al-Diri, Bashir, Proudlock, Frank A., Tu, Zhanhan, Engle, Elizabeth C. and Gottlob, Irene (2021) Optic Nerve Head and Retinal Abnormalities Associated with Congenital Fibrosis of the Extraocular Muscles. International Journal of Molecular Sciences, 22 (5). p. 2575. ISSN 1422-0067

Full content URL: https://doi.org/10.3390/ijms22052575

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Optic Nerve Head and Retinal Abnormalities Associated with Congenital Fibrosis of the Extraocular Muscles
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Abstract

Congenital fibrosis of the extraocular muscles (CFEOM) is a congenital cranial dysinnervation disorder caused by developmental abnormalities affecting cranial nerves/nuclei innervating the extraocular muscles. Autosomal dominant CFEOM arises from heterozygous missense mutations of KIF21A or TUBB3. Although spatiotemporal expression studies have shown KIF21A and TUBB3 expression in developing retinal ganglion cells, it is unclear whether dysinnervation extends beyond the oculomotor system. We aimed to investigate whether dysinnervation extends to the visual system by performing high-resolution optical coherence tomography (OCT) scans characterizing retinal ganglion cells within the optic nerve head and retina. Sixteen patients with CFEOM were screened for mutations in KIF21A, TUBB3, and TUBB2B. Six patients had apparent optic nerve hypoplasia. OCT showed neuro-retinal rim loss. Disc diameter, rim width, rim area, and peripapillary nerve fiber layer thickness were significantly reduced in CFEOM patients compared to controls (p < 0.005). Situs inversus of retinal vessels was seen in five patients. Our study provides evidence of structural optic nerve and retinal changes in CFEOM. We show for the first time that there are widespread retinal changes beyond the retinal ganglion cells in patients with CFEOM. This study shows that the phenotype in CFEOM extends beyond the motor nerves.

Keywords:congenital fibrosis of extraocular muscles, optic nerve hypoplasia, optical coherence tomography, retinal ganglion cells, congenital cranial dysinnervation disorders
Subjects:G Mathematical and Computer Sciences > G760 Machine Learning
A Medicine and Dentistry > A300 Clinical Medicine
G Mathematical and Computer Sciences > G740 Computer Vision
Divisions:College of Science > School of Computer Science
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ID Code:46681
Deposited On:05 Oct 2021 10:58

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