Optic Nerve Head Abnormalities Associated with Congenital Fibrosis of Extraocular Muscles

Abstract

Purpose : To investigate optic nerve (ON) head morphology in patients with congenital fibrosis of extraocular muscles (CFEOM) using handheld spectral domain optical coherence tomography (SD-OCT).

Methods : Sixteen patients from eight families with CFEOM (8 male and 8 female; mean age ± SD: 20 ± 16.80 years) and sixteen age, gender and ethnicity matched healthy controls were recruited to this prospective, cross-sectional, observational study. Targeted next generation sequencing was performed to determine patient genotype. Handheld SD-OCT (Envisu C2300, Leica Microsystems, 2.4μm resolution) was used to acquire horizontal scans through the center of the optic disc in patients and controls. ON measurements included: horizontal disc diameter (DD), cup diameter (CD), cup depth, cup area, horizontal rim width (RW), rim area (RA) and nerve fiber layer (NFL) thickness.

Results : Mutations of KIF21A (n=4; from 2 families) or TUBB3 (n=7; from 2 families) were identified in 11/16 cases. OCT showed that loss of neuroretinal rim was much more pronounced than apparent on fundus examination leading to pseudo-normal appearance of the ON head. DD was significantly reduced in CFEOM patients compared to controls (p<0.005), with TUBB3 mutations most severely affected. RW and RA were significantly reduced in CFEOM (p<0.0001). KIF21A mutations were associated with a 66% reduction in RW while TUBB3 mutations were associated with a 57% reduction in RW. Cup diameter, depth and area were significantly increased in CFEOM (p<0.02). Cup-disc ratio was significantly larger in CFEOM (p<0.0001). Peripapillary NFL thickness was significantly reduced in CFEOM (p<0.005). Situs inversus of retinal vessels was seen in five patients, of which four patients had the KIF21A (p.R954W) mutation. There was no correlation of visual acuity (VA) with ON characteristics (DD, RA or NFL thickness).

Conclusions : Our study provides evidence of structural ON changes in patients with CFEOM. Consistent with previous MRI studies we find the ON is smaller in size in CFEOM patients. Both KIF21A and TUBB3 mutations had smaller optic nerves with reduced RW and NFL thickness. They have a pseudo-normal disc due to the relatively normal appearance on fundoscopy. Reduced VA could be partly due to the ON changes described. This study expands the phenotypic spectrum associated with CFEOM and shows that it extends beyond the motor nerves.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.