• Cornea/External Disease

    Review of: Pathogenic mechanism of dry eye–induced chronic ocular pain and a mechanism-based therapeutic approach

    Tei Y, Mikami Y, Ito M, et al. Investigative Ophthalmology & Visual Science, January 2022

    The mechanism by which chronic neuropathic pain develops in dry eye syndrome remains undetermined. This study attempts to shed light on the pathophysiology by inducing aqueous deficiency dry eye, and then assessing downstream effects in the cornea and the trigeminal ganglion. Additionally, the therapeutic effect of pregabalin on pain was evaluated.

    Study design

    A dry eye rat model was used, with unilateral lacrimal gland excision. The frequency of blinking was monitored as a measure of corneal hypersensitivity, as was eye wiping behavior. Markers of corneal epitheliopathy were evaluated as well. Finally, indicators of neuronal activity in the trigeminal nucleus were assessed. Eight weeks after surgery, when chronic dry eye induced pain was established, treatment commenced with hyaluronic acid artificial tears 4 times a day in both eyes, as well as lubricating ointment at bedtime. Systemic pregabalin was delivered in the treatment group but not in the control group, by continuous subcutaneous administration using an implantable micropump.


    As expected, lacrimal gland excision reduced tear fluid volume, increased corneal epitheliopathy as measured by Fluorescein score, and increased blinking and eye wiping. Markers of neuronal activity in the trigeminal ganglion were increased in the group that underwent lacrimal gland excision. After initial treatment with artificial tears and lubricating ointment, the addition of pregabalin for 2 weeks reduced blink rate, eye wiping activity, and neuronal activity in the trigeminal nucleus.


    This study did not utilize all contemporary treatments available to clinicians. The model included induction of severe dry eye due to lacrimal gland excision, which does not apply to most dry eye cases seen in clinic. In addition, the experiments were performed for a limited period of time and in rats, so they do not fully mimic the chronicity of dry eye diseases in humans. Finally, unrelated to this basic science study, other clinical trials in more common types of dry eye (for instance, LASIK induced) did not demonstrate any benefit in pregabalin treatment on dry eye symptoms or severity.

    Clinical significance

    This study raises the possibility that pregabalin may have a role in treating the neuropathic element in chronic, aqueous deficiency dry eye disease, but more clinical correlations are necessary to identify the groups who would benefit the most from this treatment.