Sensory Corneal Nerve Function Testing and Morphological Corneal Nerve Alterations Demonstrate Neurosensory Abnormalities and May Allow for Identification of Patients at Risk of Symptom Development

Abstract

Purpose : To investigate morphological and functional corneal nerve changes as potential predictors of patient symptoms.

Methods : This is a prospective, cross-sectional, controlled, single center study of 99 subjects that included asymptomatic, symptomatic, and intolerant contact lens wearers (ACLW, SCLW, and ICLW), normal controls, and neuropathic corneal pain (NCP) subjects. Baseline clinical tests were performed, and pain and discomfort information was derived from visual analogues scale (VAS, 0-10) for pain and ocular surface disease index (OSDI). Corneal nerve function was assessed by response to topical 5% hypertonic saline and cold preservative-free 0.9% normal saline (4°C), registered using the VAS. In vivo confocal microscopy (IVCM) analysis of corneal nerve density and morphology was performed in a masked fashion. Data are presented as mean±SD.

Results : OSDI score increased incrementally across groups compared to controls (p<0.001). Similarly, corneal neuro-imaging revealed an incremental loss of nerve density (p<0.01) as well as increased percentage of subjects with micro-neuromas across groups (controls: 7.7%, ACLW: 27.8%, SCLW: 68.4%, ICLW: 83.3%, and NCP: 94.4%, p<0.001). Topical application of cold saline resulted in minor change in all groups (p>0.05). Whilst hypertonic saline (HS) response in ACLW group (11.0%) did not significantly deviate from controls (6%, p>0.05), a significantly increased response was noted in SCLW (58.0%), ICLW (75.0%), and NCP (92.0%) groups (p<0.05). Morphological and functional changes significantly correlated with worsening of OSDI scores across groups (P<0.05), and HS response was a better indicator of abnormal neuronal function compared to cold saline response. Further, the frequency of micro-neuromas and HS response among symptomatic subjects were similar (81.0% and 72.0%, respectively).

Conclusions : Taken together, our data highlights the presence of morphological and functional alterations even in the ACLW group (i.e. preceding symptoms), although a larger number of subjects demonstrated the presence of micro-neuromas. Therefore, functional testing combined with morphological alterations of corneal nerves may allow for identification of patients with neurosensory abnormalities and at risk for development of symptoms of discomfort and pain.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.