title: Development of a Chromatic Pupillography Protocol for the First Gene Therapy Trial in Patients With CNGA3-Linked Achromatopsia.
abstract: To establish a feasible and sensitive pupillographic protocol to assess outer and inner retinal function for the first gene therapy trial in achromatopsia patients (ACHM) with mutations in CNGA3.
  
  
  
  Twenty-seven CNGA3-ACHM patients and 22 age-matched control subjects were tested using chromatic pupillography. Three different protocols were established to assess the pupillary light reflex parameters and to create the final protocol. In the individual protocols, various stimulus parameters (i.e., intensity, duration, wavelength, adaptation states) were applied to evaluate the impact of these stimuli on the pupillary response in untreated ACHM patients.
  
  
  
  In the light-adapted conditions, CNGA3-ACHM patients showed significantly reduced maximal amplitudes compared with the control group when using a 1-second high intensity (28-lux corneal illumination) blue or red stimulus (P < 0.005). In the dark-adapted conditions, CNGA3-ACHM patients unexpectedly revealed significantly increased maximal amplitudes when stimulating with red (1 second) or blue (4 ms and 1 second) stimuli of low intensity (0.01-lux corneal illumination; P < 0.05). Pupil responses of CNGA3-ACHM patients after high intensity (28 lux) red and blue 1-second stimuli were within the normal range.
  
  
  
  Chromatic pupillography demonstrated significant reduced pupil responses to stimuli addressing primarily cone function, an increased sensitivity to rod-favoring stimuli and evidence for disinhibition of intrinsically photosensitive retinal ganglion cells in CNGA3-ACHM patients. A final protocol was established based on these findings. These conclusions may be useful for the objective assessment of efficacy gained by gene therapy or other innovative interventions in this hereditary retinal disorder.
authors.affiliation: Pupil Research Group at the Centre for Ophthalmology, University of Tübingen, Tübingen, Germany 2Medical University of Bialystok, Bialystok, Poland.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Lisowska
authors.affiliation: Pupil Research Group at the Centre for Ophthalmology, University of Tübingen, Tübingen, Germany 2Medical University of Bialystok, Bialystok, Poland.
authors.forename: Lukasz
authors.initials: L
authors.lastname: Lisowski
authors.affiliation: Pupil Research Group at the Centre for Ophthalmology, University of Tübingen, Tübingen, Germany.
authors.forename: Carina
authors.initials: C
authors.lastname: Kelbsch
authors.affiliation: Pupil Research Group at the Centre for Ophthalmology, University of Tübingen, Tübingen, Germany 3Department of Orthoptics and Visual Sciences, Faculty of Medical Technology, Niigata University of Health and Welfare, Niigata, Japan.
authors.forename: Fumiatsu
authors.initials: F
authors.lastname: Maeda
authors.affiliation: Pupil Research Group at the Centre for Ophthalmology, University of Tübingen, Tübingen, Germany.
authors.forename: Paul
authors.initials: P
authors.lastname: Richter
authors.affiliation: Centre for Ophthalmology, University of Tübingen, Tübingen, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Kohl
authors.affiliation: Centre for Ophthalmology, University of Tübingen, Tübingen, Germany.
authors.forename: Ditta
authors.initials: D
authors.lastname: Zobor
authors.affiliation: Pupil Research Group at the Centre for Ophthalmology, University of Tübingen, Tübingen, Germany.
authors.forename: Torsten
authors.initials: T
authors.lastname: Strasser
authors.affiliation: Pupil Research Group at the Centre for Ophthalmology, University of Tübingen, Tübingen, Germany.
authors.forename: Krunoslav
authors.initials: K
authors.lastname: Stingl
authors.affiliation: Centre for Ophthalmology, University of Tübingen, Tübingen, Germany 5Werner-Reichardt-Centre for Integrative Neuroscience (CIN), Tübingen, Germany.
authors.forename: Eberhart
authors.initials: E
authors.lastname: Zrenner
authors.affiliation: Pupil Research Group at the Centre for Ophthalmology, University of Tübingen, Tübingen, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Peters
authors.affiliation: Pupil Research Group at the Centre for Ophthalmology, University of Tübingen, Tübingen, Germany.
authors.forename: Helmut
authors.initials: H
authors.lastname: Wilhelm
authors.affiliation: Centre for Ophthalmology, University of Tübingen, Tübingen, Germany.
authors.forename: M Dominik
authors.initials: MD
authors.lastname: Fischer
authors.affiliation: Pupil Research Group at the Centre for Ophthalmology, University of Tübingen, Tübingen, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Wilhelm
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002985:Clinical Protocols; D003117:Color Vision Defects / Q000503:physiopathology / Q000628:therapy*; D003623:Dark Adaptation / Q000502:physiology; D003941:Diagnostic Techniques, Ophthalmological; D005260:Female; D015316:Genetic Therapy; D006801:Humans; D008027:Light; D008297:Male; D008875:Middle Aged; D010775:Photic Stimulation / Q000379:methods; D012025:Reflex, Pupillary / Q000502:physiology*; D055815:Young Adult