title: Dark-adaptation functions in molecularly confirmed achromatopsia and the implications for assessment in retinal therapy trials.
abstract: OBJECTIVE
  To describe the dark-adaptation (DA) functions in subjects with molecularly proven achromatopsia (ACHM) using refined testing conditions with a view to guiding assessment in forthcoming gene therapy trials.
  
  
  METHODS
  The DA functions of nine subjects with ACHM were measured and compared with those of normal observers. The size and retinal location of the stimuli used to measure DA sensitivities were varied in four distinct testing condition sets, and the effect of altering these parameters assessed.
  
  
  RESULTS
  In three of the four testing condition sets, achromats had significantly higher mean final thresholds than normal observers, whereas in the fourth condition set they did not. A larger, more central stimulus revealed the greatest difference between the final DA thresholds of achromat and normal subjects, and also demonstrated the slowest rate of recovery among the achromat group.
  
  
  CONCLUSIONS
  In this, the largest study of DA functions in molecularly proven ACHM to date, we have identified optimal testing conditions that accentuate the relative difference between achromats and normal observers. These findings can help optimize DA testing in future trials, as well as help resolve the dichotomy in the literature regarding the normality or otherwise of DA functions in ACHM. Furthermore, the shorter testing time and less intense adaptation light used in these experiments may prove advantageous for more readily and reliably probing scotopic function in retinal disease, and be particularly valuable in the frequent post therapeutic assessments required in the context of the marked photophobia in ACHM.
authors.affiliation: UCL Institute of Ophthalmology, University College London, London, United Kingdom Moorfields Eye Hospital, London, United Kingdom.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Aboshiha
authors.affiliation: UCL Institute of Ophthalmology, University College London, London, United Kingdom.
authors.forename: Vy
authors.initials: V
authors.lastname: Luong
authors.affiliation: UCL Institute of Ophthalmology, University College London, London, United Kingdom.
authors.forename: Jill
authors.initials: J
authors.lastname: Cowing
authors.affiliation: UCL Institute of Ophthalmology, University College London, London, United Kingdom Moorfields Eye Hospital, London, United Kingdom.
authors.forename: Adam M
authors.initials: AM
authors.lastname: Dubis
authors.affiliation: UCL Institute of Ophthalmology, University College London, London, United Kingdom Moorfields Eye Hospital, London, United Kingdom.
authors.forename: James W
authors.initials: JW
authors.lastname: Bainbridge
authors.affiliation: UCL Institute of Ophthalmology, University College London, London, United Kingdom.
authors.forename: Robin R
authors.initials: RR
authors.lastname: Ali
authors.affiliation: UCL Institute of Ophthalmology, University College London, London, United Kingdom Moorfields Eye Hospital, London, United Kingdom.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Webster
authors.affiliation: UCL Institute of Ophthalmology, University College London, London, United Kingdom Moorfields Eye Hospital, London, United Kingdom.
authors.forename: Anthony T
authors.initials: AT
authors.lastname: Moore
authors.affiliation: UCL Institute of Ophthalmology, University College London, London, United Kingdom.
authors.forename: Frederick W
authors.initials: FW
authors.lastname: Fitzke
authors.affiliation: UCL Institute of Ophthalmology, University College London, London, United Kingdom Moorfields Eye Hospital, London, United Kingdom.
authors.forename: Michel
authors.initials: M
authors.lastname: Michaelides
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000378:metabolism*; D003117:Color Vision Defects / Q000175:diagnosis* / Q000378:metabolism / Q000628:therapy; D003623:Dark Adaptation; D004596:Electroretinography; D005260:Female; D005819:Genetic Markers; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques / Q000379:methods*; D011379:Prognosis; D012160:Retina / Q000503:physiopathology*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D005819:Genetic Markers
keywords: achromatopsia; dark adaptation; gene therapy; rod monochromatism; rod vision