Fiber medicine

Pain intensity in diabetic neuropathy correlates with loss of corneal nerve fibers

According to the results of the study published in the European Journal of Neurology.

Patients (n=118) with diabetes and healthy control participants (n=38) underwent assessment of clinical, neurological, and ophthalmic characteristics. The study population was stratified by severity of neuropathic pain and clinical differences were compared.

Participants in the control group, patients with no pain (n = 43), with mild pain (n = 34) and with moderate to severe pain (n = 41) had a median age of 57, 68, 68 and 61 years. ; 18, 11, 12 and 21 were female; and glycated hemoglobin was 5.6%, 7.2%, 7.4% and 8.1%, respectively.

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Compared to control individuals, neuropathy-related disability was higher in all pain groups (all P <.0001 between the pain cohorts no significant difference in neuropathic disability was observed. a similar trend observed for vibration perception threshold>P <.0001 sural sensory nerve conduction>P <.0001 and sural nerve action potential>P <.0001>

The cold perception threshold differed between the control and patient cohorts (all P 0.004) and was different for patients with moderate to severe pain compared to patients with no or mild pain (both P .009). A similar trend was observed for the heat perception threshold (all P .01).

Corneal sensitivity was significantly higher in the most severe pain cohort compared to all other groups (all P .02).

Participants in the control group differed significantly from all pain groups for corneal nerve fiber density (all P <.0001 and between patients with moderate to severe pain versus no or mild>P .01). A similar trend was observed for corneal nerve fiber length (all P .004).

Corneal nerve branch density differed between controls and pain cohorts (all P <.0001 and between the most severe least pain groups>P =.02).

The visual analog scale was correlated with corneal nerve fiber length (r, -0.4; P P = 0.0002) and branch density (r, -0.3; P =.001), warm perception test (r, 0.3; P =.0004) and cold perception test (r, -0.35; P =.0001).

A diagnosis of PDN could be determined with a threshold corneal nerve fiber density of 23.69 no/mm2 (area under the characteristic curve of the receiving operator [AUC ROC], 0.78; sensitivity, 0.73; specificity, 0.72), corneal nerve branch density threshold of 51.04 no/mm2 (AUC ROC, 0.75; sensitivity, 0.66; specificity, 0.66) and corneal fiber length of 21.48 no/mm2 (AUC ROC, 0.74; sensitivity, 0.66; specificity, 0.65).

The study was limited by the use of the visual analogue scale, which is a subjective tool and may have biased results.

The data indicated that PDN could be detected by ophthalmologic examination and showed that progression of PDN increases corneal nerve fiber loss.

“…[I]t is shown that [corneal confocal microscopy] has good diagnostic accuracy for PDN and detects progressively greater loss of small nerve fibers in patients with increasing severity of PDN,” the study authors wrote. “[Corneal confocal microscopy] may have clinical utility as a rapid and objective test for the assessment of NDS.


Kalteniece A, Ferdousi M, Azmi S, et al. Corneal nerve loss is linked to severity of painful diabetic neuropathy. Eur J Neurol. 2022;29(1):286-294. doi:10.1111/ene.15129