Brain Anomalies Exist in Patients With Dry Eye and Photophobia

Stronger than normal visual cortex activation in patients with DED-related photophobia may require neurally-based treatment.

Brain anomalies found in patients with dry eye disease (DED) and photophobia  conditions are similar to those found in patients with tinnitus, hyperacusis, and neuropathic pain, according to a report published in Revue Neurologique. Researchers say these findings support “novel neurally oriented methods for the care of patients with photophobia.”

The prospective analysis examined 11 adults older than 18 years of age with disabling photophobia and 8 healthy age-, sex-, and eye-color-matched control individuals who underwent imaging at an academic hospital in France, from March 2018 to March 2019. The researchers used functional magnetic resonance imaging (fMRI) to detect brain anomalies. Scanning included 27-second periods of screen-diffused LED white-light stimulation alternated with light-off rest. Investigators distinguished seed as a 6 mm-radius sphere positioned at the occipital activation peak nearest the full group’s peak.

During the light-on phase, patients exhibited stimulation more broadly, reaching into the right subcortical regions. In a comparison with the healthy group, patients had stronger activation in the occipital cortex (MNI -8 -80 40, Z=5.29) and cerebellum (MNI 26 -48 -20, Z=3.99). The DED cohort also showed less deactivation of the superior temporal cortex than in healthy individuals. 

Further, regarding psychophysiological interaction connectivity, patients had significantly less disconnection of occipital cortex seeds with parts of salience and visual networks: the left insula, left ventral and posterior occipital cortex, as well as left thalamus and lenticular nucleus.

Disclosing the existence of demonstrable brain dysfunction to patients and to caregivers may by itself lead to improved care, through a better understanding of the pathophysiology underlying DED patients’ disability.

Ample stimulation of the visual cortex should trigger deactivation of the auditory region, thus, patients’ lack of normal response indicates an abnormal pattern. Patients had an unusually decreased uncoupling between the visual network and salient network — with salience typically responsible for pinpointing more important external stimuli.

“In patients, the aberrant persistence of coupling between the processing of irrelevant stimulation in early occipital cortex and the visual cortex as a whole may contribute to photophobia,” the study authors explain, adding that in tinnitus, prior research shows hyperactive connectivity of the auditory resting state network and left superior temporal cortex. “Disclosing the existence of demonstrable brain dysfunction to patients and to caregivers may by itself lead to improved care, through a better understanding of the pathophysiology underlying DED patients’ disability.”

Previous studies have not found meaningful associations between corneal damage and photophobia; but theories propose microstructural shifts in the cornea and slight tear film instability may contribute to light intolerance. Research such as that presented by the Tear Film and Ocular Surface Society (TFOS) suggest close ties of photophobia with the pain process. Accordingly, brain anomalies have been integrated into the group’s latest definition of DED.

Patients of the current study reported DED symptoms in assessments including the Ocular Surface Disease Index (OSDI) and displayed at least 1 objective sign such as in Schirmer 1 testing, but no optic neuropathy, corneal or neurological disease. Of participants with DED, 37.5% were not employed because they could not drive, use a screen, or experienced depression. Three patients were excluded due to technical issues or closed eyes during fMRI.

A limitation of this analysis is a small sample, and a strength of the masking of fMRI technicians. The investigation suggests that proof of maladaptive brain function, when revealed to patients and caregivers may create improved understanding of photophobia.

This article originally appeared on Ophthalmology Advisor


Tazi S, Boulanouar AK, Cassagne M, et al. Abnormal brain function in photophobic patients with dry eye disease: an fMRI study. Revue Neurologique. Published online February 28, 2023. doi:10.1016/j.neurol.2022.11.014