Chronic migraine is associated with reduced corneal nerve fiber density and symptoms of dry eye

Abstract

Background: We used in vivo corneal confocal microscopy to investigate structural differences in the sub-basal corneal nerve plexus in chronic migraine patients and a normal population. We used a validated questionnaire and tests of lacrimal function to determine the prevalence of dry eye in the same group of chronic migraine patients. Activation of the trigeminal system is involved in migraine. Corneal nociceptive sensation is mediated by trigeminal axons that synapse in the gasserian ganglion and the brainstem, and serve nociceptive, protective, and trophic functions. Noninvasive imaging of the corneal sub-basal nerve plexus is possible with in vivo corneal confocal microscopy.

Methods: For this case-control study, we recruited chronic migraine patients and compared them with a sex- and age-similar group of control subjects. Patients with peripheral neuropathy, a disease known to be associated with a peripheral neuropathy, or prior corneal or intraocular surgery were excluded. Participants underwent in vivo corneal confocal microscopy using a Heidelberg Retinal Tomography III confocal microscope with a Rostock Cornea Module. Nerve fiber length, nerve branch density, nerve fiber density, and tortuosity coefficient were measured using established methodologies. Migraine participants underwent testing of basal tear production with proparacaine, corneal sensitivity assessment with a cotton-tip applicator, measurement of tear break-up time, and completion of a validated dry eye questionnaire.

Results: A total of 19 chronic migraine patients and 30 control participants completed the study. There were no significant differences in age or sex. Nerve fiber density was significantly lower in migraine patients compared with controls (48.4 ± 23.5 vs. 71.0 ± 15.0 fibers/mm2 , P < .001). Nerve fiber length was decreased in the chronic migraine group compared with the control group, but this difference was not statistically significant (21.5 ± 11.8 vs. 26.8 ± 5.9 mm/mm2, P < .084). Nerve branch density was similar in the two groups (114.0 ± 92.4 vs. 118.1 ± 55.9 branches/mm2 , P < .864). Tortuosity coefficient and log tortuosity coefficient also were similar in the chronic migraine and control groups. All migraine subjects had symptoms consistent with a diagnosis of dry eye syndrome.

Conclusions: We found that in the sample used in this study, the presence of structural changes in nociceptive corneal axons lends further support to the hypothesis that the trigeminal system plays a critical role in the pathogenesis of migraine. In vivo corneal confocal microscopy holds promise as a biomarker for future migraine research as well as for studies examining alterations of corneal innervation. Dry eye symptoms appear to be extremely prevalent in this population. The interrelationships between migraine, corneal nerve architecture, and dry eye will be the subject of future investigations.

Keywords: corneal nerves; dry eye syndrome; in vivo corneal confocal microscopy; migraine.

Conflict of interest statement

Conflict of Interest: None.

© 2015 American Headache Society.

Figures

Figure

Representative in vivo corneal confocal microscopy (ICCM) images obtained with the Heidelberg Retinal Tomography III, Rostock Cornea Module with 670 nm diode laser, 300 × 300 μm images and aperture of 0.9. (a) Image of the sub-basal nerve plexus in a control subject. (b) Analysis of the same image of the same control subject. Red = main nerve fibers; blue = branches; green = branch points. (c) Image of the sub-basal corneal nerve plexus in a chronic migraine subject. (d) Analysis of the same image from the same migraine subject.