Intrinsically photosensitive retinal ganglion cells (ipRGCs) absorb short wavelength light via the photopigment melanopsin [1]. ipRGCs are critical for photo-entrainment, circadian rhythms, pupillary responses, alertness, and cognition, which persist in blindness or the absence of visual perception [2]. Moreover, Dacey et al. showed that “giant” ipRGSs send signals to the LGN and visual cortex substantiating their role in visual perception [3]. These giant ipRGCs show a unique opponent S-cone off response wherein S cones inhibit ipRGC firing rate while L and M cones enhance it [3]. High contrast stimuli and silent substitution revealed long-latency ERGs from ipRGCs which can be decreased in glaucoma [4]. However, high contrasts can inadvertently stimulate other photoreceptors lessening selectivity of pathway activation. We used selective chromatic adaptation, similar to SWAP perimetry, wherein a blue stimulus, effective for S cones and ipRGCs, was presented on an amber rod and LM cone saturating background to isolate S cone and putative responses from ipRGCs over a 4 log unit luminance range.

Fourteen healthy adults (mean 24.2 ± 1.6 years, 11 females, 3 males) participated in our IRB approved protocol after providing informed consent. A calibrated Ganzfeld (Diagnosys, LLC) was used to fully illuminate the retina with a 200 ms blue flash (448 nm) presented on a constant bright amber background (590 nm, 560 cd/m2). Simultaneous flash ERGs (DTL fiber electrode at lower limbus of right eye referenced to right earlobe) and VEPs (active electrode 1 cm above inion, referenced to forehead, common ground: left temple) were recorded after 30 s of adaptation to the amber background. Signals from the right eye (left eye occluded) were band-pass filtered (0.612–10 Hz) to isolate low frequency ipRGC responses [4] and recorded in 1000 ms epochs as the average response to 30 artifact free blue flashes (1 flash/2 s). Separate recordings were obtained at four blue intensities spanning 4 log units (16.7–0.0167 cd/m2). Digital values from all subjects (µV vs. ms) were averaged to compute mean ERG and VEP waveforms. The absence of rod and LM cone ERGs in waveforms and non-recordable ERGs to the ISCEV scotopic flash (0.01 cd/m2/s) on the amber background confirmed S cone and putative ipRGC response isolation.

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