Characterization of pupil responses to blue and red light stimuli in autosomal dominant retinitis pigmentosa due to NR2E3 mutation.
OBJECTIVE
We characterized the pupil responses that reflect rod, cone, and melanopsin function in a genetically homogeneous cohort of patients with autosomal dominant retinitis pigmentosa (adRP).


METHODS
Nine patients with Gly56Arg mutation of the NR2E3 gene and 12 control subjects were studied. Pupil and subjective visual responses to red and blue light flashes over a 7 log-unit range of intensities were recorded under dark and light adaptation. The pupil responses were plotted against stimulus intensity to obtain red-light and blue-light response curves.


RESULTS
In the dark-adapted blue-light stimulus condition, patients showed significantly higher threshold intensities for visual perception and for a pupil response compared to controls (P = 0.02 and P = 0.006, respectively). The rod-dependent, blue-light pupil responses decreased with disease progression. In contrast, the cone-dependent pupil responses (light-adapted red-light stimulus condition) did not differ between patients and controls. The difference in the retinal sensitivity to blue and red stimuli was the most sensitive parameter to detect photoreceptor dysfunction. Unexpectedly, the melanopsin-mediated pupil response was decreased in patients (P = 0.02).


CONCLUSIONS
Pupil responses of patients with NR2E3-associated adRP demonstrated reduced retinal sensitivity to dim blue light under dark adaptation, presumably reflecting decreased rod function. Rod-dependent pupil responses were quantifiable in all patients, including those with non-recordable scotopic electroretinogram, and correlated with the extent of clinical disease. Thus, the chromatic pupil light reflex can be used to monitor photoreceptor degeneration over a larger range of disease progression compared to standard electrophysiology.
Neuro-Ophthalmology Unit, Hôpital Ophtalmique Jules Gonin, University of Lausanne, Lausanne, Switzerland. aki.kawasaki@fa2.ch
Aki
A
Kawasaki
Sylvain V
SV
Crippa
Randy
R
Kardon
Lorette
L
Leon
Christian
C
Hamel
D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002648:Child; D005260:Female; D006801:Humans; D008027:Light; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics*; D057093:Orphan Nuclear Receptors / Q000235:genetics*; D010641:Phenotype; D010775:Photic Stimulation; D011680:Pupil; D012025:Reflex, Pupillary; D012174:Retinitis Pigmentosa / Q000235:genetics*; D012684:Sensory Thresholds / Q000502:physiology; D055815:Young Adult
C403073:NR2E3 protein, human; D057093:Orphan Nuclear Receptors