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Photophobia: shared pathophysiology underlying dry eye disease, migraine and traumatic brain injury leading to central neuroplasticity of the trigeminothalamic pathway
  1. Ryan J Diel1,
  2. Divy Mehra2,3,
  3. Randy Kardon1,4,
  4. Dawn C Buse5,
  5. Eric Moulton6,
  6. Anat Galor2,3
  1. 1 Department of Ophthalmology and Visual Sciences, University of Iowa Hospitals & Clinics, Iowa City, Iowa, USA
  2. 2 Ophthalmology, VA Medical Center Miami, Miami, Florida, USA
  3. 3 Ophthalmology, University of Miami Bascom Palmer Eye Institute, Miami, Florida, USA
  4. 4 Center for the Prevention and Treatment of Visual Loss, Iowa City VA Health Care System, Iowa City, IA, USA
  5. 5 Albert Einstein College of Medicine Department of Neurology, Bronx, New York, USA
  6. 6 Department of Anesthesiology, Center for Pain and the Brain; Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA
  1. Correspondence to Anat Galor, Ophthalmology, VA Medical Center Miami, Miami, FL, USA; agalor{at}


Background Photophobia is a potentially debilitating symptom often found in dry eye disease (DE), migraine and traumatic brain injury (TBI).

Methods We conducted a review of the literature via a PubMed search of English language articles with a focus on how photophobia may relate to a shared pathophysiology across DE, migraine and TBI.

Results DE, migraine and TBI are common conditions in the general population, are often comorbid, and share photophobia as a symptom. Across the three conditions, neural dysregulation of peripheral and central nervous system components is implicated in photophobia in various animal models and in humans. Enhanced activity of the neuropeptide calcitonin gene-related peptide (CGRP) is closely linked to photophobia. Current therapies for photophobia include glasses which shield the eyes from specific wavelengths, botulinum toxin, and inhibition of CGRP and its receptor. Many individuals have persistent photophobia despite the use of these therapies, and thus, development of new therapies is needed.

Conclusions The presence of photophobia in DE, migraine and TBI suggests shared trigeminothalamic pathophysiologic mechanisms, as explained by central neuroplasticity and hypersensitivity mediated by neuropeptide CGRP. Treatment strategies which target neural pathways (ie, oral neuromodulators, transcutaneous nerve stimulation) should be considered in patients with persistent photophobia, specifically in individuals with DE whose symptoms are not controlled with traditional therapies.

  • Ocular surface
  • Visual pathway
  • Cornea

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  • Contributors All authors contributed to this manuscript: design and conduct of the study (RD, DM, RK, DCB, EM and AG), management (RJD, DM, RK, DCB, EAM and AG), analysis (RJD, DM, RK, DCB, EAM and AG), interpretation of data (RJD, DM, RK, DCB, EAM and AG), preparation and review or approval of the manuscript (RJD, DM, RK, DCB, EAM and AG).

  • Funding Supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Clinical Sciences Research I01 CX002015 (Dr Galor), Biomedical Laboratory R&D (BLRD) Service I01 BX004893 (Dr Galor), Department of Defense GW190010 (Dr Galor), R01EY026174 (Dr Galor), NIH Center Core Grant P30EY014801 and Research to Prevent Blindness Unrestricted Grant, and discretionary funds from the Department of Anesthesiology, Boston Children’s Hospital (Dr Moulton). RR&D Iowa City Center for the Prevention and Treatment of Visual Loss C9251-C (RX003002) (Dr. Kardon), C2978-R (Dr. Kardon), 2 I01 RX000889-05A2 (Dr. Kardon), Department of Defense/VA/Chronic Effects of Neurotrauma Consortium W81XWH-13-2-0095, I01 CX001135 (Dr. Kardon), NIH (NEI) 1R01EY031544-01 FAIN: R01EY031544 (Dr. Kardon).

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data collected are being presented in this review.