A novel method of inducing endogenous pupil oscillations to detect patients with unilateral optic neuritis

Abstract

PurposeTo use and test a new method of inducing endogenously generated pupillary oscillations (POs) in patients with unilateral optic neuritis (ON), to describe a signal analysis approach quantifying pupil activity and to evaluate the extent to which POs permit to discriminate patients from control participants.MethodPupil size was recorded with an eye-tracker and converted in real time to modulate the luminance of a stimulus (a 20° disk) presented in front of participants. With this biofeedback setting, an increasing pupil size transforms into a high luminance, entraining a pupil constriction that in turn decreases the stimulus luminance, and so on, resulting in endogenously generated POs. POs were recorded for 30 seconds in the affected eye, in the fellow eye and in binocular conditions with 22 patients having a history of unilateral ON within a period of 5 years, and with 22 control participants. Different signal analysis methods were used to quantify the power and frequency of POs.ResultsOn average, pupil size oscillated at around 1 Hz. The amplitude of POs appears not to be a reliable marker of ON. In contrast, the frequency of POs was significantly lower, and was more variable over time, in the patients’ affected eye, as compared to their fellow eye and to the binocular condition. No such differences were found in control participants. Receiver operating characteristic analyses based on the frequency and the variability of POs to classify patients and control participants gave an area under the curve of 0.82, a sensitivity of 82% (95%CI: 60%-95%) and a specificity of 77% (95%CI: 55%-92%).ConclusionsThe new method used to induce POs allowed characterizing the visual afferent pathway defect in ON patients with encouraging accuracy. The method was fast, easy to use, only requiring that participants look ahead, and allows testing many stimulus parameters (e.g. color, stimulus location, size, etc).

Computerized biofeedback to characterize Pupil Cycle Time (PCT) in neuropathies and retinopathies

“…We also considered the possibility that in both neuropathies and retinopathies, the integration time of visual stimulation could be lengthened, which could be reflected in the lengthening of the PCT. In this study, we employed different spatial layouts (Large field stimulation, central disk and peripheral ring) with different colors (Grey, Red, Green, Blue), and applied the method of Lamirel et al (2018) with patients suffering from Retinitis Pigmentosa (RP), Stargardt disease (SD), Leber Hereditary Optic Neuropathy (LHON), and with healthy individuals (see supplementary Table 1). Retinitis Pigmentosa (RP) is a rare genetic disease characterized by a progressive loss of peripheral vision that can lead to a "tunnel vision" and evolves toward blindness at a late stage; RP is secondary to the death of photoreceptors.…”

“…In current practice, periodic cycles of pupillary dilation and constriction are induced by illuminating the pupil margin using a thin beam of a slit-lamp, placed in such a way that pupil size “controls” the amount of light entering the eye: the beam of light first causes a pupil constriction, such that the beam light falls on the iris, outside the pupil, not stimulating the retina; the so induced decreased retinal illumination in turn elicits a pupil dilation, such that the beam light enters the eye again, eliciting a constriction, and so on (Figure 1). With this method, measuring the peak-to-peak time between oscillations revealed that the PCT is significantly longer for patients with Optic Neuritis or Glaucoma 27,28 .…”

Method to Quickly Map Multifocal Pupillary Response Fields (mPRF) Using Frequency Tagging

“…The timing of pupillary response may bring additional information on the existence and effects of a clinical condition on vision, as was found in ROC analyses. For instance, damages to the optic nerve, such as the demyelination observed in optic neuritis, alter the temporal dynamics of pupillary responses [ 19 ].…”

“…Importantly, ipRGCs share many structural and anatomical features with RGCs, including their sensitivity to similar harms [ 16 ]. Finally, damage to the optic nerve may also perturb pupillary dynamics [ 18 , 19 ].…”