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

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posted on 2021-10-01, 14:27 authored by MG Thomas, GDE Maconachie, HJ Kuht, WM Chan, V Sheth, M Hisaund, RJ McLean, B Barry, B Al-Diri, FA Proudlock, Z Tu, EC Engle, I Gottlob
Congenital fibrosis of the extraocular muscles (CFEOM) is a congenital cranial dysinner-vation 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 character-izing 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 peripapil-lary 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.

Funding

This study was supported by the Ulverscroft Foundation, Fight for Sight (grant ref: 5009/5010) and the Medical Research Council (MRC), London, UK (grant number: MR/J004189/1, MRC/N004566/1 and MC_PC_17171). MGT is supported by the NIHR (CL-2017-11-003). This study was also supported by the Boston Children’s Hospital Intellectual and Developmental Disabilities Research Center (NICHD 1U54HD090255).

History

Citation

Int. J. Mol. Sci. 2021, 22(5), 2575

Author affiliation

Department of Neuroscience, Psychology and Behaviour

Version

  • VoR (Version of Record)

Published in

International Journal of Molecular Sciences

Volume

22

Issue

5

Pagination

2575

Publisher

MDPI

issn

1422-0067

eissn

1422-0067

Acceptance date

2021-02-26

Copyright date

2021

Available date

2021-03-04

Language

English

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