%0 Journal Article
%A Krishnan, Arun kumar
%A Charng, Jason
%A Jacobson, Samuel G
%A Roman, Alejandro J
%A Garafalo, Alexandra
%A Sumaroka, Alexander
%A Swider, Malgorzata
%A Semenov, Evelyn
%A Sheplock, Rebecca
%A Heon, Elise
%A Cideciyan, Artur V
%T Transient pupillary light reflexes driven by foveal cones in CEP290- or in NPHP5-associated LCA-ciliopathies
%B Investigative Ophthalmology & Visual Science
%D 2019
%J Investigative Ophthalmology & Visual Science
%V 60
%N 9
%P 1833-1833
%@ 1552-5783
%X    To identify photoreceptors driving the transient pupillary light reflex (TPLR) in ciliopathy patients selected for similarity in phenotype.    Patients with severe blindness due to CEP290 (n=3) or NPHP5 (n=3) mutations were evaluated. Full-field stimulus test (FST; Diagnosys) thresholds and TPLR (Roland Consult) were recorded from 11 eyes sequentially with red (R) and blue (B) stimuli under dark-adapted conditions. Stimuli were 0.2 or 1 s long for FST and TPLR, respectively. TPLR response amplitude and latency were quantified as a function of luminance and compared to FST thresholds.    CEP290 patients had Leber congenital amaurosis (LCA); NPHP5 patients had LCA and nephronophthisis. FST thresholds were -1.2 (SE= ±0.06, R) or -1.3 (±0.04, B) log cd.m-2. Perimetry showed small cone-mediated islands centered at the fovea; there was no peripheral vision. TPLR intensity response functions had a threshold of -1.31 (±0.19, R) or -1.28 (±0.11, B) log cd.m-2 to reach a criterion amplitude of 0.3 mm when measured at the fixed time of 0.9 s after stimulus onset; the maximum response amplitudes were 1.5 (±0.18, R) or 1.9 (± 0.16, B) mm (Fig panels A-C). B minus R differences for TPLR amplitude fluctuated near zero for all luminances except for the highest (2.7 log cd.m-2) stimulus where B responses were larger. There was evidence of increasingly greater B-R differences at times later than 0.9 s. TPLR latency to reach criterion amplitude of 0.3 mm was 0.81 (±0.03, R) or 0.83 (±0.05, B) s at -1.3 log cd.m-2 (panels A, C, D); there was progressive acceleration with intensity such that latency reached 0.46 (±0.02, R) or 0.44 (±0.02, B) s with maximal stimuli. Normal thresholds, amplitudes, B-R differences and latencies (panels B, D, dashed lines) were substantially different than patients.    Luminances corresponding to perceptual (FST) or criterion (TPLR) thresholds were nearly identical and photopically matched suggesting foveal cone mediation for both tests in patients. Normal FST and TPLRs at threshold were likely mediated by rods. Beyond threshold, TPLR responses of patients could be quantified for an additional 4 log units of range. TPLR latency was likely driven by foveal cones at threshold and beyond. TPLR amplitude at 0.9 s was driven by cones for the first 3 log units with evidence of melanopic signaling at 4 log above threshold.  This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.        
%[ 1/25/2021