The Pupillary Light Reflex in Idiopathic Intracranial Hypertension.

Idiopathic intracranial hypertension (IIH) is a condition of elevated intracranial pressure (ICP) for which a cause cannot be determined. Loss of visual function is the primary morbidity for most IIH patients, with approximately 10% of patients progressing to bilateral blindness.1,2 As reviewed elsewhere,3 visual dysfunction in IIH appears to be due to a series of events initiated by increased ICP. Elevation in ICP likely produces increased pressure around the distal optic nerve, which, in turn, results in axoplasmic flow stasis.4–6 Reduced axoplasmic transport produces intra-axonal edema,7 which is likely followed by venule compression, ischemia, and loss of visual function. Because visual function within the central visual field is typically normal, or nearly normal, until the late stages of the disease8,9 vision loss in IIH is most commonly characterized by standard automated perimetry to measure peripheral visual field sensitivity.1,8–10 However, not all IIH patients have marked visual field abnormalities, and ganglion cell dysfunction may precede measurable reductions assessed by perimetry.11 Moreover, perimetry is an inherently subjective test and it is vulnerable to patient error. Objective assessments of visual pathway function in IIH may provide new insight into vision loss associated with the disease and could have the potential to provide additional data upon which clinical management decisions can be based. Objective measures of RGC function have been performed in patients with IIH using electrophysiological techniques. For example, previous work has shown that the amplitude of the pattern electroretinogram (pERG) can be reduced in patients with IIH.12 However, standard pERG measurements are limited in that they primarily assess function within the central visual field. More recently, it was shown that the photopic negative response (PhNR), a late negative component of the full-field photopic single-flash ERG that originates largely from RGCs,13,14 can also be abnormal in patients with IIH.11 Pupillometry is an additional objective technique that can assess inner retina, outer retina, and subcortical function, which may have application to patients with IIH. The response of the pupil to a flash of light (the pupillary light reflex; PLR) is a complex response with contributions from more than one photoreceptor type. However, by altering the adaptation conditions and stimulus characteristics, contributions of the rod pathway, cone pathway, and intrinsically photosensitive RGC (ipRGC) pathway, which contains the photopigment melanopsin,15,16 can be assessed.17–19 Thus, the PLR is a powerful tool because it provides insight into ipRGC function, as well as rod and cone inputs into the ipRGCs. The PLR has been useful for understanding diseases of the inner retina and optic nerve, such as in hereditary optic neuropathies,20–22 glaucoma,23–26 and ischemic optic neuropathy.27 To date, the PLR has not been reported in patients with IIH. Pupillometry is a promising approach for functional assessment in IIH because it shares many of the advantages of PhNR measurement, in that it is noninvasive, objective, performed quickly with minimal patient demands, does not require refraction or steady fixation, and can be measured using full-field stimuli. Additionally, pupillometry does not require pupil dilation and can provide measures of rod, cone, and melanopsin RGC function. The generators of the PLR likely differ from those of the PhNR, as pupillometry selectively targets ipRGCs. Although IIH is not typically associated with outer retina abnormalities, a recent report has shown cone receptor density loss in a patient with IIH28 and an earlier report showed light adapted flicker ERG deficits in patients with chronic papilledema.29 Thus, pupillometry may provide new insight into outer retina function in patients with IIH. The goal of the present study was to evaluate rod-, cone-, and melanopsin-mediated PLRs in patients with IIH. These pupil responses were assessed using a previously published paradigm,19 with slight modification, in patients with IIH and in visually-normal control subjects. The patients' PLRs were compared with other measures of visual function including Humphrey visual field mean deviation (HVF MD) scores and PhNR amplitude. The results of the present study are intended to determine the extent to which pupillometry can be used as a clinical tool to assess retinal dysfunction in patients with IIH.