Ophthalmological findings in facioscapulohumeral dystrophy

Abstract

Ophthalmological abnormalities in facioscapulohumeral dystrophy may lead to treatable vision loss, facilitate diagnostics, could help unravelling the pathophysiology and serve as biomarkers. In this study, we provide a detailed description of the ophthalmological findings in a well-defined cohort of patients with facioscapulohumeral dystrophy using state of the art retina imaging techniques. Thirty-three genetically confirmed patients (aged 7-80 years) and 24 unrelated healthy controls (aged 6-68 years) underwent clinical ophthalmological examination, fundus photography, optical coherence tomography/angiography, genotyping and neurological examination. All patients had normal corrected visual acuity and normal intraocular pressure. In 27 of the 33 patients, weakness of the orbicularis oculi was observed. Central retinal pathology, only seen in patients and not in healthy controls, included twisting (tortuosity) of the retinal arteries in 25 of the 33 patients and retinal pigment epithelium defects in 4 of the 33 patients. Asymmetrical foveal hypoplasia was present in three patients, and exudative abnormalities were observed in one patient. There was a correlation between the severity of retinal tortuosity and the D4Z4 repeat array size (R ² = 0.44, P < 0.005). Follow-up examination in a subgroup of six patients did not show any changes after 2 years. To conclude, retinal abnormalities were frequent but almost always subclinical in patients with facioscapulohumeral dystrophy and consisted primarily of arterial tortuosity and foveal abnormalities. Retinal tortuosity was seen in the retinal arterioles and correlated with the D4Z4 repeat array size, thereby providing clinical evidence for an underlying genetic linkage between the retina and facioscapulohumeral dystrophy.

Keywords: facioscapulohumeral; muscular dystrophy; neuromuscular diseases; retinal telangiectasis.

Graphical Abstract

Figure 1

Tortuosity of the retinal arteries. Sample patients with (A) absent, (B) mild and (C) severe tortuosity of the retinal arteries.

Figure 2

Tortuosity index compared with controls. Tortuosity index of patients versus controls showing an increased arterial tortuosity in patients with FSHD.

Figure 3

Tortuosity correlates with genetic severity. Regression analysis of tortuosity and (A) genetic severity as measured by the repeat size, (B) disease severity as measured by the FSHD clinical score and (C) age at examination.

Figure 4

Retinal abnormalities on OCT scans. Types of retinal abnormalities detected on OCT scans of patients with FSHD. (A) Focal retinal pigment epithelium defect (44-year-old male; arrow), (B) foveal hypoplasia (17-year-old female) and (C) exudative abnormalities (72-year-old female, arrow).

Figure 5

Retinal abnormalities on OCTA scans. Sample OCTA images of a patient with FSHD: (A) inner vessel layer; (B) intermediate vessel layer; and (C) outer vessel layer. Note the tortuosity of the largest retinal vessels in the inner layer.

Figure 6

Macular vessel density and tortuosity compared to controls. Comparison of the macular vessel density (A) and vessel tortuosity (B) between patients with FSHD and healthy controls. None of the layers showed a significantly different density or tortuosity (unpaired t-tests: 1.21 versus 1.20, P = 0.25, for inner vessel layer; 1.26 versus 1.26, P = 0.87, for intermediate vessel layer; 1.43 versus 1.42, P = 0.68, for outer vessel layer). The variation of vessel tortuosity was broader in patients with FSHD in the DCP layer. DCP = deep capillary plexus; SCP = superficial capillary plexus.

Figure 7

Follow-up of arterial tortuosity. A male patient at A baseline (age 11 years) and B after 2-year follow-up (age 13 years). Arterial tortuosity is seen, which is unchanged after the follow-up period.