April 2009
Volume 50, Issue 13
ARVO Annual Meeting Abstract  |   April 2009
Electroretinographic (ERG) and Psychophysical Testing of Normal Subjects Given a Single Dose of a Visual Cycle Modulator (All-Trans-N-Retinylacetamide)
Author Affiliations & Notes
  • K. G. Locke
    Retina Foundation of Southwest, Dallas, Texas
  • G. Caniano
    Retina Foundation of Southwest, Dallas, Texas
  • R. Tzekov
    Acucela Inc., Bothell, Washington
  • R. Kubota
    Acucela Inc., Bothell, Washington
  • D. G. Birch
    Retina Foundation of Southwest, Dallas, Texas
    Department of Ophthalmology, Univ. of TX Southwestern Medical Center, Dallas, Texas
  • Footnotes
    Commercial Relationships  K.G. Locke, None; G. Caniano, None; R. Tzekov, Acucela Inc., E; R. Kubota, Acucela Inc., E; D.G. Birch, Acucela Inc., C; Acucela Inc., R.
  • Footnotes
    Support  None.
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 967. doi:
  • Views
  • Share
  • Tools
    • Alerts
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      K. G. Locke, G. Caniano, R. Tzekov, R. Kubota, D. G. Birch; Electroretinographic (ERG) and Psychophysical Testing of Normal Subjects Given a Single Dose of a Visual Cycle Modulator (All-Trans-N-Retinylacetamide). Invest. Ophthalmol. Vis. Sci. 2009;50(13):967.

      Download citation file:

      © ARVO (1962-2015); The Authors (2016-present)

  • Supplements

Purpose: : Recent studies suggest modulation of visual cycle kinetics may decrease rod photoisomerization and reduce levels of the toxic retinal fluorophores which lead to accumulation of lipofuscin in the retinal pigment epithelium. All-trans-N-retinylacetamide (ACU-3223) is a retinoid which has been shown to modulate the visual cycle in rats and non-human primates. Here we assess the safety and efficacy of ACU-3223 in modulating normal human rod function.

Methods: : Normal, healthy subjects (n=6, age=55-75 yrs) were given a single oral dose of ACU-3223 at 3 mg/kg. Visual function measures included visual acuity, color vision and ISCEV standard ERGs. Additionally rod ERG and visual thresholds were measured concurrently following exposure to a bleaching light. Patients were tested prior to dosing, and at 6 hours, 1 day and 2 days following dosing. Subjects with abnormal test results on day 2 had weekly testing until resolved. Safety measures and adverse events (AE) were collected on each visit.

Results: : Following the bleach, ACU-3223 caused 30% reduction in amplitude at 10 to 20 minutes post-bleach compared to pre-dosing. Psychophysically, the cone-rod break was delayed 55% compared to pre-dosing. In 4 subjects, these changes had resolved by day 7; in 2 subjects by day 21. There was no effect on visual acuity, color vision or cone ERG. Minor AEs included complaints of difficulty adapting to changes in light levels and increased sensitivity to glare. Serum creatine phosphokinase activity, believed to be a retinoid-associated finding, was elevated markedly on day 2 and resolved by day 7. No subject reported serious AEs.

Conclusions: : ACU-3223 was well tolerated and effective in slowing the recovery of rod function following bleach with minimal effect on cone function. The slow metabolism of ACU-3223, causing persistent effects over several days, limits its clinical utility.

Keywords: age-related macular degeneration • receptors: pharmacology/physiology • electroretinography: clinical 

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.