A systematic review synthesizing functional neuroimaging studies in adults with chronic ocular surface pain (COSP) or photophobia, covering study designs, methodologies, and cumulative findings across an initial pool of 643 unique studies.
Only 5 eligible studies were identified (n=107 total: 83 cases, 24 controls); all used fMRI exclusively. Light consistently activated trigeminocortical nociceptive networks (spinal trigeminal/brainstem, S1, insula, anterior midcingulate), with partial attenuation following topical anesthesia, botulinum toxin, or FL-41 tinted lenses.
- Very small evidence base (5 studies, 107 participants) limits generalizability. - All studies used fMRI only; no other functional neuroimaging modalities (e.g., EEG, MEG) were represented, leaving neural oscillations and neuromodulatory targets unexplored. - Sex imbalance in cases vs. controls (37.3% vs. 29.2% female) and narrow study design homogeneity restrict diversity and broader applicability.
Clinicians should be aware that COSP and photophobia have measurable central (brain-level) signatures, suggesting brain-based biomarkers may complement surface metrics in assessment and treatment planning. Interventions like topical anesthesia, botulinum toxin, and FL-41 lenses show partial central pain attenuation, but the evidence base remains very limited.
