Longitudinal study of cone photoreceptors during retinal degeneration and in response to ciliary neurotrophic factor treatment

Katherine E. Talcott, Kavitha Ratnam, Sanna M. Sundquist, Anna S. Lucero, Brandon J. Lujan, Weng Tao, Travis C. Porco, Austin Roorda, Jacque L. Duncan

Research output: Contribution to journalArticlepeer-review

225 Scopus citations

Abstract

PURPOSE. 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/degree2 more per year in sham-treated than in CNTFtreated 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.

Original languageEnglish (US)
Pages (from-to)2219-2226
Number of pages8
JournalInvestigative Ophthalmology and Visual Science
Volume52
Issue number5
DOIs
StatePublished - Apr 2011
Externally publishedYes

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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