title: Blue cone monochromacy: visual function and efficacy outcome measures for clinical trials.
abstract: BACKGROUND
  Blue Cone Monochromacy (BCM) is an X-linked retinopathy caused by mutations in the OPN1LW / OPN1MW gene cluster, encoding long (L)- and middle (M)-wavelength sensitive cone opsins. Recent evidence shows sufficient structural integrity of cone photoreceptors in BCM to warrant consideration of a gene therapy approach to the disease. In the present study, the vision in BCM is examined, specifically seeking clinically-feasible outcomes for a future clinical trial.
  
  
  METHODS
  BCM patients (n = 25, ages 5-72) were studied with kinetic and static chromatic perimetry, full-field sensitivity testing, and eye movement recordings. Vision at the fovea and parafovea was probed with chromatic microperimetry.
  
  
  RESULTS
  Kinetic fields with a Goldmann size V target were generally full. Short-wavelength (S-) sensitive cone function was normal or near normal in most patients. Light-adapted perimetry results on conventional background lights were abnormally reduced; 600-nm stimuli were seen by rods whereas white stimuli were seen by both rods and S-cones. Under dark-adapted conditions, 500-nm stimuli were seen by rods in both BCM and normals. Spectral sensitivity functions in the superior retina showed retained rod and S-cone functions in BCM under dark-adapted and light-adapted conditions. In the fovea, normal subjects showed L/M-cone mediation using a 650-nm stimulus under dark-adapted conditions, whereas BCM patients had reduced sensitivity driven by rod vision. Full-field red stimuli on bright blue backgrounds were seen by L/M-cones in normal subjects whereas BCM patients had abnormally reduced and rod-mediated sensitivities. Fixation location could vary from fovea to parafovea. Chromatic microperimetry demonstrated a large loss of sensitivity to red stimuli presented on a cyan adapting background at the anatomical fovea and surrounding parafovea.
  
  
  CONCLUSIONS
  BCM rods continue to signal vision under conditions normally associated with daylight vision. Localized and retina-wide outcome measures were examined to evaluate possible improvement of L/M-cone-based vision in a clinical trial.
authors.affiliation: Scheie Eye Institute, Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Xunda
authors.initials: X
authors.lastname: Luo
authors.affiliation: Scheie Eye Institute, Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Artur V
authors.initials: AV
authors.lastname: Cideciyan
authors.affiliation: Hamilton Eye Institute, Department of Ophthalmology, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Iannaccone
authors.affiliation: Scheie Eye Institute, Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Alejandro J
authors.initials: AJ
authors.lastname: Roman
authors.affiliation: Hamilton Eye Institute, Department of Ophthalmology, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America.
authors.forename: Lauren C
authors.initials: LC
authors.lastname: Ditta
authors.affiliation: Hamilton Eye Institute, Department of Ophthalmology, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America.
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Jennings
authors.affiliation: Pittsburgh Cytogenetics Laboratory, Center for Medical Genetics and Genomics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Svetlana A
authors.initials: SA
authors.lastname: Yatsenko
authors.affiliation: Scheie Eye Institute, Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Sheplock
authors.affiliation: Scheie Eye Institute, Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Alexander
authors.initials: A
authors.lastname: Sumaroka
authors.affiliation: Scheie Eye Institute, Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Swider
authors.affiliation: Scheie Eye Institute, Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Sharon B
authors.initials: SB
authors.lastname: Schwartz
authors.affiliation: Molecular Genetics Laboratory, Institute for Ophthalmic Research, Centre for Ophthalmology, University of Tuebingen, Tuebingen, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Wissinger
authors.affiliation: Molecular Genetics Laboratory, Institute for Ophthalmic Research, Centre for Ophthalmology, University of Tuebingen, Tuebingen, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Kohl
authors.affiliation: Scheie Eye Institute, Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Samuel G
authors.initials: SG
authors.lastname: Jacobson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D002986:Clinical Trials as Topic; D003117:Color Vision Defects / Q000378:metabolism / Q000503:physiopathology*; D055358:Cone Opsins / Q000378:metabolism; D003623:Dark Adaptation / Q000502:physiology; D005133:Eye Movements / Q000502:physiology; D005584:Fovea Centralis / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D008027:Light; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D010775:Photic Stimulation / Q000379:methods; D017949:Retinal Cone Photoreceptor Cells / Q000378:metabolism*; D012164:Retinal Diseases / Q000378:metabolism / Q000503:physiopathology; D014785:Vision, Ocular / Q000502:physiology*; D058609:Visual Field Tests / Q000379:methods; D055815:Young Adult
chemical_list: D055358:Cone Opsins