In Vivo Confocal Microscopy Demonstrates the Presence of Microneuromas and may Allow Differentiation of Patients with Corneal Neuropathic Pain from Dry Eye Disease

Abstract

Purpose : The diagnosis of corneal neuropathic pain (CNP) is challenging and most often difficult to differentiate from dry eye disease (DED). In addition to pain, CNP can present with similar signs and symptoms of DED. Thus, objective diagnostic tools to identify patients with CNP are needed. The purpose of this study is to compare subbasal corneal nerve and immune dendritiform cell alterations between patients with DED and CNP.

Methods : This cross-sectional, single center study included patients with DED (n=14), CNP (n=15), and age and sex-matched normal controls (n=16), who underwent central corneal laser in vivo confocal microscopy (IVCM, HRT3/RCM). Subbasal corneal nerve density and morphology (nerve beading, bead-like formation along the nerves), presence of microneuromas (enlarged nerve terminal sprouts), and dendritiform cell density (DCD) were assessed and compared between the groups by 2 masked observers.

Results : Total nerve density was decreased in both CNP patients (11.64±1.90 mm/mm²) and DED (13.63±1.56 mm/mm²) as compared to normal controls (23.90±0.92 mm/mm²; p <0.001). While total nerve density was lower in patients with CNP as compared with DED, it was not statistically significant (p=0.42). Nerve beading was present in all DED and CNP patients and in 14/16 of control group (P>0.05). Interestingly, microneuromas were observed in all patients with CNP, while they were not detected in any of the patients with DED (sensitivity and specificity of 100%). DCD was increased in both CNP (73.12±29.91 cells/mm2) and DED (82.29±18.28 cells/mm²) as compared to normal controls (24.81±4.48 cells/mm²; p=0.10). However, there was no significant difference in DCD between DED and CNP patients (p=0.79).

Conclusions : IVCM may be used as an adjunct diagnostic tool to differentiate CNP from DED. Micro-neuromas might serve as a sensitive and specific criterion in differentiating patients with CNP from DED.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.