Photophobia in migraine: Electrophysiological analysis of chromatic opponent responses via electroretinogram and visual evoked potential

Background Migraine is characterized by recurrent headaches and sensory hypersensitivities, with photophobia affecting up to 90% of patients during attacks. The mechanisms underlying ictal photophobia remain unclear, potentially involving altered excitability of the visual cortex, trigeminovascular sensitization, or cone-driven retinal pathways. Prior interictal studies have shown preserved macular cone opponent mechanisms, but ictal investigations are lacking. Methods In this prospective study, we simultaneously recorded Ganzfeld blue-red (B-R) and blue-yellow (B-Y) focal flash (8 Hz) macular cone electroretinogram (ERG) and the subsequent visual evoked potential (VEP) in 11 patients with migraine without aura during acute attacks and in 20 healthy volunteers. First (1F) and second (2F) harmonic amplitudes and phases were analyzed using discrete Fourier transformation and T 2 circ statistics. Responses were correlated with clinical variables, including photophobia severity (0–10 scale) during attacks, using Spearman's coefficient. Results For B-Y stimuli, a selective reduction in ERG 1F amplitude was noted in patients (F = 4.19, p = 0.02), with preserved phases and no differences in other harmonics or VEP responses. A significant negative correlation was observed between the phase of the first harmonic of the VEP and the level of photophobia during the attack. No significant differences were observed in 1F or 2F ERG/VEP amplitudes or phases for B-R stimuli between patients with migraine and HVs. Conclusions Ictal macular cone-opponent pathways remain largely intact in migraine, with a specific S-cone amplitude attenuation suggesting an autonomic-mediated inference on blue-light hypersensitivity. The finding of a correlation of B-Y VEP phase with photophobia implies that this symptom may arise from subcortico-cortical integrations (e.g., thalamic-trigemino-cortical convergence) rather than focal retinal dysfunction.