Current understanding of photophobia, visual networks and headaches

Abstract

Objective: To review clinical and pre-clinical evidence supporting the role of visual pathways, from the eye to the cortex, in the development of photophobia in headache disorders.

Background: Photophobia is a poorly understood light-induced phenomenon that emerges in a variety of neurological and ophthalmological conditions. Over the years, multiple mechanisms have been proposed to explain its causes; however, scarce research and lack of systematic assessment of photophobia in patients has made the search for answers quite challenging. In the field of headaches, significant progress has been made recently on how specific visual networks contribute to photophobia features such as light-induced intensification of headache, increased perception of brightness and visual discomfort, which are frequently experienced by migraineurs. Such progress improved our understanding of the phenomenon and points to abnormal processing of light by both cone/rod-mediated image-forming and melanopsin-mediated non-image-forming visual pathways, and the consequential transfer of photic signals to multiple brain regions involved in sensory, autonomic and emotional regulation.

Conclusion: Photophobia phenotype is diverse, and the relative contribution of visual, trigeminal and autonomic systems may depend on the disease it emerges from. In migraine, photophobia could result from photic activation of retina-driven pathways involved in the regulation of homeostasis, making its association with headache more complex than previously thought.

Keywords: Migraine; autonomic; hypothalamus; photoreceptors; retina; thalamus.

Figure 1.

Schematic representation of the retino-thalamo-cortical pathways proposed to explain the most common light-induced sensory symptoms in migraine when patients are exposed to ambient light during attacks. LP: lateral posterior thalamic; Po: posterior nucleus of the thalamus; Pul: pulvinar; RGC: retinal ganglion cells; ipRGC: intrinsically sensitive retinal ganglion cells; SSN: superior salivatory nucleus; SPG: sphenopalatine ganglion; TG: trigeminal ganglion; Sp5: spinal trigeminal nucleus.

Figure 2.

Schematic representation of the retino-hypothalamo-parasympathetic (SSN) and sympathetic (IML) pathways proposed to explain a host of light-induced autonomic responses during migraine attacks, and to a lesser extent, between attacks. SCG: superior cervical ganglion; IML: intermediolateral nucleus.

Figure 3.

Schematic representation of the retino-midbrain-parasympathetic (SSN) pathway proposed to explain bright light-induced ocular pain. Pupillary light reflex circuit, which is abnormal in migraine, is also depicted. CG: ciliary ganglion; E-W: Edinger-Westphal nucleus.