The pupil light reflex (PLR) is a fundamental diagnostic tool for objective and noninvasive measurement of retinal and optic nerve function in neuro-ophthalmic disorders.
1 The pupil control pathway receives retinal input from intrinsically photosensitive retinal ganglion cells (ipRGCs), which also project to the suprachiasmatic nucleus (SCN) for photoentrainment,
2–7 and there is circadian modulation of the post-illumination pupil response (PIPR).
8,9 Given that outer retinal extrinsic rod, cone, and inner retinal intrinsic melanopsin photoresponses influence the human PLR,
2,3,8,10–16 there has been interest in developing PLR protocols that quantify outer and inner retinal input.
14,15,17–25 An established marker of direct, intrinsic melanopsin activity is the PIPR, the sustained pupilloconstriction after light offset.
11,26 With ipRGCs affected in optic nerve and retinal disease such as glaucoma,
21,24,27 retinitis pigmentosa,
14,17,20 diabetes,
22 age-related macular degeneration,
28 Leber's congenital amaurosis,
17 as well as in circadian disorders,
10 the PLR techniques may complement other clinical measures of retinal function in the healthy and diseased eye, such as the electroretinography (ERG) and perimetry. Depending on the measurement paradigms, ERGs measure the summed and local photoreceptor, bipolar, and ganglion cell responses. Visual field testing with standard automated perimetry (SAP) and other modes, including frequency-doubling technology (FDT), short-wavelength automated perimetry (SWAP), and flicker perimetry, measure the integrity of visual pathways. In contrast, the PLR can be used to simultaneously differentiate inner retinal function (mediated via ipRGCs) and outer retinal function (mediated via rods and cones) to provide a clinical tool for diagnosis and monitoring progression of ocular disorders, with the PIPR being a specific measure of ipRGCs. The PIPR has been reported in response to a range of stimulus durations, irradiances, and wavelengths
8,12,14,18,21–24,29 and quantified using five metrics, namely the plateau PIPR,
12,14 redilation velocity,
8,21 6-second PIPR,
17 area under curve (AUC) early and late recovery
18 (metrics are defined in the Methods).