Toward a Clinical Protocol for Assessing Rod, Cone, and Melanopsin Contributions to the Human Pupil Response

Abstract

PURPOSE. To better understand the relative contributions of rod, cone, and melanopsin to the human pupillary light reflex (PLR) and to determine the optimal conditions for assessing the health of the rod, cone, and melanopsin pathways with a relatively brief clinical protocol. METHODS. PLR was measured with an eye tracker, and stimuli were controlled with a Ganzfeld system. In experiment 1, 2.5 log cd/m(2) red (640 ± 10 nm) and blue (467 ± 17 nm) stimuli of various durations were presented after dark adaptation. In experiments 2 and 3, 1-second red and blue stimuli were presented at different intensity levels in the dark (experiment 2) or on a 0.78 log cd/m(2) blue background (experiment 3). Based on the results of experiments 1 to 3, a clinical protocol was designed and tested on healthy control subjects and patients with retinitis pigmentosa and Leber's congenital amaurosis. RESULTS. The duration for producing the optimal melanopsin-driven sustained pupil response after termination of an intense blue stimulus was 1 second. PLR rod- and melanopsin-driven components are best studied with low- and high-intensity flashes, respectively, presented in the dark (experiment 2). A blue background suppressed rod and melanopsin responses, making it easy to assess the cone contribution with a red flash (experiment 3). With the clinical protocol, robust melanopsin responses could be seen in patients with few or no contributions from the rods and cones. CONCLUSIONS. It is possible to assess the rod, cone, and melanopsin contributions to the PLR with blue flashes at two or three intensity levels in the dark and one red flash on a blue background.

The genetics of New World monkey visual pigments.

“…Melanopsins are related to circadian rhythms (Altimus et al, 2010;Berson, Dunn, & Takao, 2002;Hattar et al, 2002;Ruby et al, 2002) and the pupillary light reflex (Gooley, Lu, Chou, Scammell, & Saper, 2001;Güler et al, 2008;Park, Moura, Raza, Rhee, Kardon, & Hood, 2011;Xue et al, 2011), among other functions.…”

Pupillary light reflex and circadian synchronization in the elderly

“…Thus, the SCN, our inner master clock that controls the day-night cycle, fails to receive adequate information from ipRGCs for synchronization. Initial attempts to monitor the function of ipRGCs using chromatic pupillometry showed that specific light stimuli can help distinguish between cone functions with and without ipRGC input by looking at the post-illumination pupillary light reflex (PIPLR), since ipRGCs are related to the PIPLR (Chen, Badea, & Hattar, 2011;Park et al, 2011).To evaluate whether one cause of bad sleep behavior in obviously demented elderly might be a dysfunction in ipRGCs, preclinical testing was performed at two homes for the elderly near Vienna, Austria, first to test its acceptance and feasibility with this population, and then to evaluate individual PIPLRs and optimize the screening method. A total of 31 participants aged 60-99 years (M = 84.2, SD = 8.8) were tested, consisting of 23 females (60-99 years, M = 85.0, SD = 8.4) and eight males (65-95 years, M = 81.9, SD = 9.4).…”

Image and Non-Image Forming Melanopsin Function in Age-Related Macular Degeneration

“…To control for individual differences in resting pupil diameter, all data are reported as a percentage of the resting baseline pupil diameter (average pupil diameter during 5 s pre-stimulus period). The PIPR was quantified at six seconds after light stimulus offset (Park et al 2011). The PSQI questionnaire was scored and analysed using the global sleep score, sleep quality factor and sleep efficiency factor Chapter 4 has been published in the following study:…”

“…The participant was instructed to look straight ahead in the dark as if fixating a distant object and fixation was monitored with the IR camera. The consensual pupil reflex was measured in response to short wavelength light (464nm) with high melanopsin excitation Gamlin et al 2007;Kardon et al 2009;Park et al 2011) and to long wavelength light (638 nm) that biased activation to the outer retina (Park et al 2011) and provided a control. The corneal irradiance of the long and short wavelength stimuli was 15.1 log quanta.cm -2 .s -1 .…”

“…The Pupil Light Reflex (PLR) provides a rapid, objective, non-invasive measure of both inner (ipRGC) and outer (rod and cone) retinal function (Adhikari et al 2015b;Herbst, Sander, Milea, Lund-Andersen & Kawasaki 2011;Kankipati et al 2010;Kardon et al 2009;Markwell et al 2010;McDougal & Gamlin 2010;Park et al 2011). Following onset of an incremental light pulse, the initial PLR is mediated by the outer retina (Güler et al 2008;McDougal & Gamlin 2010) with increasing melanopsin input with longer stimulus durations (McDougal & Gamlin 2010), while ipRGCs control the Post-Illumination Pupil Response (PIPR), the sustained pupil constriction after light offset (Adhikari et al 2015b;Gamlin et al 2007).…”