title: Longitudinal study of cone photoreceptors during retinal degeneration and in response to ciliary neurotrophic factor treatment.
abstract: OBJECTIVE
  To study cone photoreceptor structure and function in patients with inherited retinal degenerations treated with sustained-release ciliary neurotrophic factor (CNTF).
  
  
  METHODS
  Two patients with retinitis pigmentosa and one with Usher syndrome type 2 who participated in a phase 2 clinical trial received CNTF delivered by an encapsulated cell technology implant in one eye and sham surgery in the contralateral eye. Patients were followed longitudinally over 30 to 35 months. Adaptive optics scanning laser ophthalmoscopy (AOSLO) provided high-resolution images at baseline and at 3, 6, 12, 18, and 24 months. AOSLO measures of cone spacing and density and optical coherence tomography measures of retinal thickness were correlated with visual function, including visual acuity (VA), visual field sensitivity, and full-field electroretinography (ERG).
  
  
  RESULTS
  No significant changes in VA, visual field sensitivity, or ERG responses were observed in either eye of the three patients over 24 months. Outer retinal layers were significantly thicker in CNTF-treated eyes than in sham-treated eyes (P < 0.005). Cone spacing increased by 2.9% more per year in sham-treated eyes than in CNTF-treated eyes (P < 0.001, linear mixed model), and cone density decreased by 9.1%, or 223 cones/degree(2) more per year in sham-treated than in CNTF-treated eyes (P = 0.002, linear mixed model).
  
  
  CONCLUSIONS
  AOSLO images provided a sensitive measure of disease progression and treatment response in patients with inherited retinal degenerations. Larger studies of cone structure using high-resolution imaging techniques are urgently needed to evaluate the effect of CNTF treatment in patients with inherited retinal degenerations.
authors.affiliation: Department of Ophthalmology, Division of Preventive Medicine and Public Health, University of California at San Francisco, CA, USA.
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Talcott
authors.forename: Kavitha
authors.initials: K
authors.lastname: Ratnam
authors.forename: Sanna M
authors.initials: SM
authors.lastname: Sundquist
authors.forename: Anna S
authors.initials: AS
authors.lastname: Lucero
authors.forename: Brandon J
authors.initials: BJ
authors.lastname: Lujan
authors.forename: Weng
authors.initials: W
authors.lastname: Tao
authors.forename: Travis C
authors.initials: TC
authors.lastname: Porco
authors.forename: Austin
authors.initials: A
authors.lastname: Roorda
authors.forename: Jacque L
authors.initials: JL
authors.lastname: Duncan
mesh_terms: D000328:Adult; D020934:Ciliary Neurotrophic Factor / Q000008:administration & dosage*; D018450:Disease Progression; D004343:Drug Implants; D004596:Electroretinography; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D009887:Ophthalmoscopy; D011446:Prospective Studies; D017949:Retinal Cone Photoreceptor Cells / Q000473:pathology*; D012174:Retinitis Pigmentosa / Q000188:drug therapy* / Q000503:physiopathology; D041623:Tomography, Optical Coherence; D052245:Usher Syndromes / Q000188:drug therapy* / Q000503:physiopathology; D014792:Visual Acuity / Q000502:physiology; D014794:Visual Fields / Q000502:physiology
chemical_list: D020934:Ciliary Neurotrophic Factor; D004343:Drug Implants