Abstract Body:

Purpose: A key perceptual symptom in several neuro-ophthalmic disorders is photophobia - a phenomenon broadly defined by light-driven painful sensations, and subsequent tearing and squinting. Currently however, photophobia is mostly descriptive, with poorly understood mechanisms and no available objective assessment. Recently, studies have suggested that photophobia is likely mediated by the melanopsin-containing intrinsically photosensitive retinal ganglion cell (ipRCG) pathway. ipRGCs are a subset of retinal photoreceptors with a peak spectral sensitivity of ~480 nm (blue light) and a unique sustained firing response that is dependent on the ambient illumination levels and the retinal area stimulated. We aimed to: (1) design a novel psychophysical assessment that considers the spectral properties of melanopsin and (2) establish a normative dataset for previously tested photophobia characteristics that play a role in the degree of discomfort experienced: wavelength and viewing condition. We hypothesized that visually normal participants would experience greatest light discomfort under blue light stimuli and binocular viewing conditions.

Study Design: Prospective study

Methods: Eleven participants underwent pharmacological mydriasis (2.5% phenylephrine) prior to the experiment. A Ganzfeld system presented 7 randomized light intensities (1 s each) of either red (1.5, 19.1, 38.2, 57.3, 76.3, 152.7, 305.3 cd/m2) or blue (1.4, 7.1, 14.3, 28.6, 42.9, 57.1, 71.4 cd/m2) light, 20 times per intensity, in four 70 trial blocks (using the method of constant stimuli). White-light stimuli (3 cd/m2, 4 s duration) were interleaved with the chromatic trials. Participants rated each stimulus as either “uncomfortably bright” or “not uncomfortably bright”. The experiment was done binocularly and monocularly in separate sessions, and the color/viewing condition order was randomized across participants. The proportions of “uncomfortable” responses per testing session were used to generate psychometric functions from which 50% discomfort thresholds were calculated individually.

Results: Light-induced discomfort was higher under blue light stimulation compared to red light stimulation, both during binocular (t(10)= 3.58, p < 0.01) and monocular viewing (t(10)= 3.15, p=0.01). There was also a significant difference in discomfort between viewing conditions, with binocular viewing inducing more discomfort for blue light (p < 0.001), but not for red light stimulation.

Conclusions: Photophobia characteristics are consistent with the features of the melanopsin system. This is the first visual discomfort assessment designed around the melanopsin spectral properties which can be customized to assess photophobia in different clinical populations. In visually-normal  participants, the results support the hypothesis that photophobia is predominantly an ipRGC-mediated phenomenon.