How to Diagnose Corneal Neuropathy?

The diagnosis of corneal neuropathy used to be a diagnosis of exclusion. Often doctors & surgeons would try various treatments. If none of them worked or the patient did not have pain relief with anesthetic drops, we noted it must be corneal neuropathy.

Then along came Confocal Microscopy which allowed researchers to see the corneal nerve axons. Still, though, there has not been a well published normative database. In other words, what is normal exaclut for a 25 year old female? 

Now a  relatively new blood test which can measure the serum IgM binding to the trisulfated disaccharide IdoA2S-GlcNS-6S (TS-HDS). Higher levels of serum IgM binding to TS-HDS is associated with neuropathy. I am looking for normative data to understand the cut off values. 




2019 Nov 26;19(12):103.

 doi: 10.1007/s11910-019-1020-1.

Current Diagnosis and Treatment of Painful Small Fiber Neuropathy



  • 1Department of Neurology at Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, WAC 835, Boston, MA, 02114, USA.
  • 2Wentworth Health Partners, 121 Corporate Drive, Portsmouth, NH, 03801, USA.


Purpose of review: Small fiber neuropathy (SFN) could cause significant morbidity due to neuropathic pain and autonomic dysfunction. SFN is underdiagnosed and the knowledge on the condition is limited among general public and health care professionals. This review is intended to enhance the understanding of SFN symptoms, causes, diagnostic tools, and therapeutic options.

Recent findings: There is evidence of SFN in up to 40% patients with fibromyalgia. The causes of SFN are glucose metabolism defect, dysimmune, gluten sensitivity and celiac disease, monoclonal gammopathy, vitamin deficiencies, toxic agents, cancer, and unknown etiology. Auto-antibodies targeting neuronal antigens trisulfated heparin disaccharide (TS-HDS) and fibroblast growth factor 3 (FGFR3) are found in up to 20% of patients with SFN. Treatment of SFN includes treating the etiology and managing symptoms. SFN should be considered in patients with wide-spread body pain. The search for known causes of SFN is a crucial step in disease management.

Keywords: Amyloidosis; Autonomic neuropathy; FGFR3; Fibromyalgia; Small fiber neuropathy; TS-HDS.

Comparative Study


2012 Jun;45(6):866-72.

 doi: 10.1002/mus.23256.

Clinical and laboratory features of neuropathies with serum IgM binding to TS-HDS



Introduction: In this investigation we studied clinical and laboratory features of polyneuropathies in patients with serum IgM binding to the trisulfated disaccharide IdoA2S-GlcNS-6S (TS-HDS).

Methods: We retrospectively compared 58 patients with selective IgM binding to TS-HDS to 41 consecutive patients with polyneuropathies without TS-HDS binding.

Results: Patients with IgM vs. TS-HDS commonly had distal, sensory, axonal neuropathies. Weakness was associated with IgM M-proteins. Hand pain and serum IgM M-proteins were more common than in control neuropathy patients. TS-HDS antibody binding was often selectively κ class. Biopsies showed capillary pathology with thickened basal lamina and C5b9 complement deposition. IgM in sera with TS-HDS antibodies often bound to capillaries.

Conclusions: Serum IgM binding to TS-HDS is associated with painful, sensory > motor, polyneuropathies with an increased frequency of persistent hand discomfort, serum IgM M-proteins, and capillary pathology. Serum IgM binding to TS-HDS suggests a possible immune etiology underlying some otherwise idiopathic sensory polyneuropathies.

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