Abstract
PurposeThe diagnosis of neuropathic corneal pain (NCP) is challenging, as it is often difficult to differentiate it from conventional dry eye disease (DED). In addition to eye pain, NCP can present with similar signs and symptoms of DED. The purpose of this study is to find an objective diagnostic sign to identify patients with NCP, using in vivo confocal microscopy (IVCM). MethodsThis was a comparative, retrospective, case-control study. Patients with clinical diagnosis of NCP (n = 25), DED (n = 30), and age- and sex-matched healthy controls (n = 16), who underwent corneal imaging with IVCM (HRT3/RCM) were included. Central corneal IVCM scans were analyzed by 2 masked observers for nerve density and number, presence of microneuromas (terminal enlargements of subbasal corneal nerve) and/or nerve beading (bead-like formation along the nerves), and dendritiform cell (DC) density. ResultsThere was a decrease in total nerve density in both NCP (14.14 ± 1.03 mm/mm2) and DED patients (12.86 ± 1.04 mm/mm2), as compared to normal controls (23.90 ± 0.92 mm/mm2; p < 0.001). However, total nerve density was not statistically different between NCP and DED patients (p = 0.63). Presence of nerve beading was not significantly different between patients and normal controls (p = 0.15). Interestingly, microneuromas were observed in all patients with NCP, while they were not present in any of the patients with conventional DED (sensitivity and specificity of 100%). DC density was significantly increased in both NCP (71.89 ± 16.91 cells/mm2) and DED patients (111.5 ± 23.86 cells/mm2), as compared to normal controls (24.81 ± 4.48 cells/mm2 (p < 0.05). However, there was no significant difference in DC density between DED and NCP patients (p = 0.31). ConclusionIVCM may be used as an adjunct diagnostic tool for the diagnosis of NCP in the presence of neuropathic symptoms. Microneuromas may serve as a sensitive and specific biomarker for the diagnosis of NCP.
Highlights
Neuropathic pain is defined by the International Association for the Study of Pain as ‘pain caused by a lesion or disease of the somatosensory system’.1 The prevalence of neuropathic pain is estimated to be around 7-10%.2 Neuropathic pain can occur in the cornea, and has been called “neuropathic corneal pain” (NCP), 3–5 “corneal neuralgia”,6 or “ocular neuropathic pain”[3]
There was no significant difference in dendritiform cell (DC) density between dry eye disease (DED) and NCP patients (p=0.31)
Using in vivo confocal microscopy (IVCM), we have previously demonstrated a decrease in nerve density, presence of microneuromas and an increase in beading in NCP patients.[13,14,15]
Summary
Neuropathic pain is defined by the International Association for the Study of Pain as ‘pain caused by a lesion or disease of the somatosensory system’.1 The prevalence of neuropathic pain is estimated to be around 7-10%.2 Neuropathic pain can occur in the cornea, and has been called “neuropathic corneal pain” (NCP), 3–5 “corneal neuralgia”,6 or “ocular neuropathic pain”[3]. The prevalence and etiology of NCP are currently not known; dry eye disease (DED), infectious keratitis, and refractive surgeries are among the most commonly associated causes.[5]. Accurate diagnosis of NCP is paramount as most patients with NCP do not respond well to conventional DED therapies and the disease causes a significant decrease in patients’ quality of life.[5,6] Currently, the diagnosis of NCP is based on detailed history, lack of ocular surface signs on ophthalmic slit-lamp examination, validated pain questionnaires, and evidence of nerve injury.[5,7,8] corneal esthesiometry and functional corneal nerve testing have been proposed tools to aid in diagnosis,[5,7] but are not applicable yet
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