Differentiation of Clinical Phenotypes of Inflammatory and Neuropathic Ocular Pain Conditions with Morphologic Measures and Functional Brain Imaging

Chronic ocular pain is a highly distressing symptom as its occurrence results in high morbidity without effective treatment. Patients with dry eye (DE) commonly have painful ocular symptoms, yet the neural mechanisms underlying this type of pain may include inflammatory (as in Sjogren's syndrome) and/or neuropathic contributors (as in neuropathic ocular pain [NOP]). The cornea is innervated by the trigeminal nerve, which conveys peripheral input to the central nervous system. Using neuroimaging to evaluate peripheral nerves to supraspinal structures, we propose to define the structural and functional differences in the trigeminal circuit that differentiate inflammatory and neuropathic pain. In aim 1, we will determine trigeminal nerve pathology in persons with Sjogren's vs. NOP vs. controls using quantitative sensory testing (QST), in vivo corneal nerve microscopy (IVCM), and diffusion tensor imaging (DTI). In aim 2, we will define differences between Sjogren's vs. NOP in the central nervous system by comparing functional responses to light-induced pathways associated with photophobia using fMRI, and structure using MRI and DTI. This study is likely to yield (1) structural and functional diagnostic markers to differentiate inflammatory and neuropathic ocular pain with neuroimaging, and (2) evince a neurological source of pain symptoms with neuropathic ocular pain. Data generated from this investigation may be used to improve the diagnosis and monitoring of patients suffering from chronic ocular pain, and provide an objective marker to base clinical decision making.