The Dry Eye Zone

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Study: Peripheral vs central neuropathic corneal pain

Adding to the important body of literature on neuropathic corneal pain, this study focused on people with longstanding ocular surface pain who did not have significant dry eye and who did not respond to normal dry eye treatments. Amongst these, there were significant differences, as some had pain relief with anaesthetic eye drop while others did not.

Clinical and in vivo confocal microscopic features of neuropathic corneal pain. Ross et al, Br J Ophthalmol. 2019 Sep 18.



To describe clinical and in vivo confocal microscopy (IVCM) features of neuropathic corneal pain (NCP) without clinically visible signs.


Prospective, observational study of 27 eyes of 14 patients who had continuous severe ocular pain for one or more years, with minimal or no ocular surface signs and were non-responsive to topical lubricants, steroids and/or ciclosporin. All patients were evaluated using Ocular Surface Disease Index, Oxford grading scale, Schirmer test 1, Cochet Bonnet esthesiometry and response to topical anaesthesia. Central and paracentral regions of the cornea of patients and seven healthy controls were studied by IVCM. Corneal epithelial thickness and sub-basal nerve density were measured in patients and controls.


Four patients responded to topical anaesthesia (responsive group (RG)), indicating peripheral NCP while 10 patients did not show any improvement (non-responsive group (NRG)), indicating central NCP. Schirmer-1 test was within normal limits in the RG but significantly greater in the NRG (p<0.001). None of the other clinical parameters nor corneal epithelial thickness were statistically significantly different. The sub-basal nerve density was significantly reduced (p<0.008) in patients compared with controls. Stroma of all patients demonstrated activated keratocytes and spindle, lateral and stump microneuromas. There was a statistically significant greater number of microneuromas (p<0.0001) and activated keratocytes in RG compared with NRG.


NCP without visible clinical signs does not represent typical dry eye disease. Distinct signs demonstrated on IVCM suggest that peripheral NCP, which responds to topical anaesthesia, and central NCP, which does not, are separate entities.