Figure 1.

Photophobia is a manifestation of dry eye, migraine and traumatic brain injury. Melanopsin-containing intrinsically photosensitive retinal ganglion cells (ipRGCs) transmit light-evoked signals (green pathway) to the olivary pretectal nucleus (OPN) and posterior thalamus. A parasympathetic-mediated vasodilatory response (gold pathway) is transmitted via the superior salivatory nucleus (SSN) and sphenopalatine ganglia (SPG) to ocular blood vessels. Nociceptive signals from ocular blood vessels, corneal surface and dural meninges are all transmitted via the ophthalmic branch (V1) of the trigeminal nerve (orange pathway) before converging at the trigeminal ganglia (TG), trigeminal nucleus caudalis (TNC) and posterior thalamus. Dry eye, migraine and traumatic brain injury all represent inputs which may act to sensitise the aforementioned underlying neuronal networks via calcitonin gene-related peptide (purple molecules). The TG, TNC and posterior thalamus are potential areas of neuroplasticity/sensitisation governing the sensations finally culminating as dryness, migraine pain, allodynia and photophobia (blue pathway). Direct activation of trigeminal afferents by an independent melanopsinmediated pathway originating from the iris and/or cornea is not shown. Light-sensing pathways mediating systemic hypothalamic-sympathetic and hypothalamic-parasympathetic pathways are also not shown. Illustration by Ryan J. Diel, MD.