Corneal confocal microscopy: A novel noninvasive means to diagnose neuropathy in patients with fabry disease

Abstract

Neuropathy is a cause of significant disability in patients with Fabry disease, yet its diagnosis is difficult. In this study we compared the novel noninvasive techniques of corneal confocal microscopy (CCM) to quantify small-fiber pathology, and non-contact corneal aesthesiometry (NCCA) to quantify loss of corneal sensation, with established tests of neuropathy in patients with Fabry disease. Ten heterozygous females with Fabry disease not on enzyme replacement therapy (ERT), 6 heterozygous females, 6 hemizygous males on ERT, and 14 age-matched, healthy volunteers underwent detailed quantification of neuropathic symptoms, neurological deficits, neurophysiology, quantitative sensory testing (QST), NCCA, and CCM. All patients with Fabry disease had significant neuropathic symptoms and an elevated Mainz score. Peroneal nerve amplitude was reduced in all patients and vibration perception threshold was elevated in both male and female patients on ERT. Cold sensation (CS) threshold was significantly reduced in both male and female patients on ERT (P < 0.02), but warm sensation (WS) and heat-induced pain (HIP) were only significantly increased in males on ERT (P < 0.01). However, corneal sensation assessed with NCCA was significantly reduced in female (P < 0.02) and male (P < 0.04) patients on ERT compared with control subjects. According to CCM, corneal nerve fiber and branch density was significantly reduced in female (P < 0.03) and male (P < 0.02) patients on ERT compared with control subjects. Furthermore, the severity of neuropathic symptoms and the neurological component of the Mainz Severity Score Index correlated significantly with QST and CCM. This study shows that CCM and NCCA provide a novel means to detect early nerve fiber damage and dysfunction, respectively, in patients with Fabry disease.

Vascular tortuosities of the upper eyelid: A new clinical finding in Fabry patient screening

“…It is characterized by a deficiency of the lysosomal enzyme alpha-galactosidase A (GLA or -gal A) [11], secondary to protein misfolding and/or an inability to direct the enzyme towards the lysosomes. In Fabry, the enzyme deficiency leads to an accumulation of substrate within the cells, with a preference for organs that naturally accumulate the greatest amount (the heart and kidneys) [12]; it also favours the vascular endothelial cells, renal dorsal root ganglion cells, the cornea, and the skin [13]. This is why the observation of vascular changes on the palpebral area is quite likely.…”

Corneal confocal microscopy in chronic inflammatory demyelinating polyneuropathy

“…Corneal confocal microscopy (CCM), a rapid noninvasive ophthalmic imaging technique, has been demonstrated to quantify axonal loss in a variety of peripheral neuropathies including hereditary sensory and autonomic neuropathy,6 Charcot–Marie–Tooth disease type 1A,7 Fabry disease,8 and idiopathic small fiber neuropathy 9. It has also been widely used to evaluate diabetic neuropathy in multiple studies10 demonstrating that this technique is a viable surrogate endpoint for early diagnosis,11 stratification of neuropathy severity,12 and assessing the response to treatment 13.…”

Oküler Bulguların Fabry Hastalığı Tanısındaki Önemi

“…Fabry hastalarında bildirilmiş olan subepitelyal sinir sayısında azalmayı olgumuzda gözlemlemedik. 11 Stroma tutulumu daha ileri olgularda görüldüğünden dolayı olgumuzda kornea stroması normaldi. 9 Fabry hastalığında en sık görülen göz bulgusu olan vorteks keratopatinin tespit edilmesi tanıya giden süreçte yol gösterici olabilir.…”