The pupillary response to sparse multifocal stimuli : neural bases and applications in visual field assessment

Abstract

Multifocal pupillographic objective perimetry (mfPOP) is a diagnostic technique currently under development, which shows promise in the diagnosis and monitoring of glaucoma and other disorders. Glaucoma is a degenerative optic neuropathy which is increasing in prevalence due to aging populations. Early diagnosis is instrumental in its treatment, yet this is somewhat problematic. The mfPOP method utilizes the pupillary contractions elicited by the dichoptic presentation of sparse multifocal luminance stimuli, in order to determine the level of visual function in many locations across the visual field. This thesis focuses on the enhancement of mfPOP through the investigation of the neural systems subserving mfPOP responses, and the development of new stimuli and the subsequent assessment of their diagnostic utility in patients with glaucoma. The proportional distribution of visual signals in the midbrain pathways that mediate pupillary luminance responses was investigated through the topographic variation in the relationship between direct and consensual pupillary responses in normal subjects. Uniformly larger direct than consensual responses were obtained to stimulation in the temporal field; however, little significant difference was seen in the nasal field. A parsimonious model which explains inconsistent results on contraction anisocoria reported in the literature was proposed. Pupillary stimuli targeting the melanopsin response of intrinsically photosensitive retinal ganglion cells (ipRGCs) were assessed for their utility in glaucoma diagnosis. These ipRGCs mediate the sub-cortical pupillary luminance response, and at photopic levels are activated by input from all three cone-photoreceptor types as well by their intrinsic melanopsin response. A slow blue stimulus, which targeted this melanopsin response, was prone to confounding effects of aging and the disease process, and was unable to detect localized dysfunction, one of the determining characteristics of glaucoma. An investigation of the topography and characteristics of the pupillary response to stimuli eliciting both sub-cortical and cortically derived response components was undertaken on normal subjects. This was achieved using stimuli with varying contributions from color-and luminance-contrast. Response amplitudes were influenced primarily by the stimulus luminance, while latencies were more influenced by color changes. At high luminance-contrast the luminance signal dominated that of color. Two stimulus protocols, similar to those assessed in the previous series of experiments, were evaluated for their diagnostic accuracy in glaucoma. These stimuli, targeting both cortical and sub-cortical response components, more accurately separated glaucoma patients from normal subjects than stimuli targeting sub-cortical components alone. Both amplitudes and latencies of pupillary responses were highly diagnostic, producing accuracies of 100% in eyes with severe visual field damage. Accuracies of 89% and 84% were obtained for eyes with moderate and mild visual field damage, respectively. This research has led to the development of a promising new mfPOP stimulus protocol Information has also been gained regarding the distribution of pupillary signal in midbrain pathways, and the interaction between cortical and sub-cortically derived pupillary response components. In addition, an awareness has been gained of the problems inherent in using short-wavelength pupillometric stimuli in aging populations. Show more