Neuropathic pain felt on the periphery or in the center of the cornea may be two distinct issues that respond differently to topical anesthesia, specifically if the pain presents without clinically visible cues, a study in the British Journal of Ophthalmology reports.

The investigation included 27 eyes of 14 patients who had continuous severe ocular pain but with minimal or no ocular surface signs for at least one year. The patients were also non-responsive to topical lubricants, steroids or cyclosporine. 

The study looked at Ocular Surface Disease Index scores, Oxford grading scale, Schirmer 1, esthesiometry and responses to topical anesthesia. The investigators used in vivo confocal microscopy to examine the central and paracentral cornea in the patients with corneal pain and in seven healthy controls. The researchers also measured corneal epithelial thickness and sub-basal nerve density.

The study found four patients responded to topical anesthesia (the responsive group), indicating peripheral neuropathic corneal pain, while 10 patients showed no improvement (non-responsive group), which pointed to central neuropathic corneal pain.

The investigators also reported the Schirmer 1 was within normal limits in the responsive group but was significantly greater in the non-responsive group. None of the other clinical parameters or corneal epithelial thickness were markedly different.

Also of note: the sub-basal nerve density was significantly reduced in corneal pain patients compared with controls, and the stroma of all study participants showed activated keratocytes and spindle, lateral and stump microneuromas. Investigators observed a much greater amount of microneuromas and activated keratocytes in the responsive group compared with the non-responsive group.

Neuropathic corneal pain without visible clinical signs does not represent typical dry eye disease, the researchers added.