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

Mitra Tavakoli, Andrew Marshall, Lorraine Thompson, Margaret Kenny, Stephen Waldek, Nathan Efron, Rayaz Malik

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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 onERT (P<0.01). However, corneal sensation assessed withNCCAwas 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 QSTand 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.

Original languageEnglish
Pages (from-to)976-984
Number of pages9
JournalMuscle and Nerve
Issue number6
Publication statusPublished - Dec 2009
Externally publishedYes



  • Corneal confocal microscopy
  • Corneal nerves
  • Fabry disease
  • Neurodegeneration
  • Neuropathy small fibers

ASJC Scopus subject areas

  • Physiology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Physiology (medical)

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