CNGB3-achromatopsia clinical trial with CNTF: Diminished rod pathway responses with no evidence of improvement in cone function

Wadih M. Zein, Brett G. Jeffrey, Henry E. Wiley, Amy E. Turriff, Santa J. Tumminia, Weng Tao, Ronald A. Bush, Dario Marangoni, Rong Wen, Lisa L. Wei, Paul A. Sieving

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


PURPOSE: Ciliary neurotrophic factor (CNTF) protects rod photoreceptors from retinal degenerative disease in multiple nonhuman models. Thus far, CNTF has failed to demonstrate rod protection in trials for human retinitis pigmentosa. Recently, CNTF was found to improve cone photoreceptor function in a canine CNGB3 achromatopsia model. This study explores whether this finding translates to humans with CNGB3 achromatopsia.

METHODS: A five-subject, open-label Phase I/II study was initiated by implanting intraocular microcapsules releasing CNTF (nominally 20 ng/d) into one eye each of CNGB3 achromat participants. Fellow eyes served as untreated controls. Subjects were followed for 1 year.

RESULTS: Pupil constriction in treated eyes gave evidence of intraocular CNTF release. Additionally, scotopic ERG responses were reduced, and dark-adapted psychophysical absolute thresholds were increased, attributable to diminished rod or rod pathway activity. Optical coherence tomography revealed that the cone-rich fovea underwent structural changes as the foveal hyporeflective zone (HRZ) became diminished in CNTF-treated eyes. No objectively measurable enhancement of cone function was found by assessments of visual acuity, mesopic increment sensitivity threshold, or the photopic ERG. Careful measurements of color hue discrimination showed no change. Nonetheless, subjects reported beneficial changes of visual function in the treated eyes, including reduced light sensitivity and aversion to bright light, which may trace to decreased effective ambient light from the pupillary constriction; further they noted slowed adaptation to darkness, consistent with CNTF action on rod photoreceptors.

CONCLUSIONS: Ciliary neurotrophic factor did not measurably enhance cone function, which reveals a species difference between human and canine CNGB3 cones in response to CNTF. ( number, NCT01648452.).

Original languageEnglish (US)
Pages (from-to)6301-6308
Number of pages8
JournalInvestigative Ophthalmology and Visual Science
Issue number10
StatePublished - 2014
Externally publishedYes


  • Achromatopsia
  • CNGB3
  • CNTF
  • CNTF-releasing implant
  • Cone photoreceptor
  • ECT implant
  • Human clinical trial
  • Rod photoreceptor

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience


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