Neural mechanisms underlying photophobia and dry eye

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It is estimated that 19% of US veterans have dry eye (DE), of which painful ocular symptoms are a common manifestation. These can include sensations of dryness, burning, and extreme sensitivity to light (i.e., photophobia). The symptoms interfere with activities of daily living including driving and reading. Photophobia, in particular, is one of the most distressing symptoms as its occurrence results in high morbidity without effective treatment. Individuals most severely affected become prisoners in their own homes due to intolerance to even small amounts of light. Even in less severe cases, most individuals have significant functional limitations and often require sunglasses in and outdoors. A knowledge gap exists with regards to the mechanism that underlie these painful sensations, thus limiting the ability to target appropriate treatment strategies. Our overall hypothesis is that photophobia is an indicator of central pathologic plasticity of 1) trigeminal pathways, and 2) their interaction with melanopsin pathways. To test this hypothesis, in aim 1, we define peripheral and central neural responses to light in individuals with chronic ocular pain and photophobia as compared to controls. In aim 2, we examine the contribution of different pathways to photophobia by blocking corneal afferent drive (to assess trigeminal pathways) and intrinsically photosensitive retinal ganglion cell (ipRGC) drive (to assess melanopsin pathways). In Aim 3, we determine the effect of neural blockade with botulinum toxin injection on photophobia. This study is greatly needed, as a critical barrier to progress in the field is the lack of information on neural pathways that underlie disease. The data generated can be used to improve the rehabilitation of ocular pain and increase function and quality of life in veterans and non-veterans alike.