Investigation of oral fenretinide for treatment of geographic atrophy in age-related macular degeneration

Retina. 2013 Mar;33(3):498-507. doi: 10.1097/IAE.0b013e318265801d.


Background: Excessive accumulation of retinol-based toxins has been implicated in the pathogenesis of geographic atrophy (GA). Fenretinide, an orally available drug that reduces retinol delivery to the eye through antagonism of serum retinol-binding protein (RBP), was used in a 2-year trial to determine whether retinol reduction would be effective in the management of geographic atrophy.

Methods: The efficacy of fenretinide (100 and 300 mg daily, orally) to slow lesion growth in geographic atrophy patients was examined in a 2-year, placebo-controlled double-masked trial that enrolled 246 patients at 30 clinical sites in the United States.

Results: Fenretinide treatment produced dose-dependent reversible reductions in serum RBP-retinol that were associated with trends in reduced lesion growth rates. Patients in the 300 mg group who achieved serum retinol levels of ≤ 1 μM (≤ 2 mg/dL RBP) showed a mean reduction of 0.33 mm in the yearly lesion growth rate compared with subjects in the placebo group (1.70 mm/year vs. 2.03 mm/year, respectively, P = 0.1848). Retinol-binding protein reductions <2 mg/dL correlated with further reductions in lesion growth rates (r = 0.478). Fenretinide treatment also reduced the incidence of choroidal neovascularization (approximately 45% reduction in incidence rate in the combined fenretinide groups vs. placebo, P = 0.0606). This therapeutic effect was not dose dependent and is consistent with anti-angiogenic properties of fenretinide, which have been observed in other disease states.

Conclusion: The findings of this study and the established safety profile of fenretinide in chronic dosing regimens warrant further study of fenretinide in the treatment of geographic atrophy.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Contrast Sensitivity / physiology
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Fenretinide / adverse effects
  • Fenretinide / therapeutic use*
  • Geographic Atrophy / blood
  • Geographic Atrophy / drug therapy*
  • Geographic Atrophy / pathology
  • Humans
  • Male
  • Middle Aged
  • Retinol-Binding Proteins, Plasma / antagonists & inhibitors
  • Surveys and Questionnaires
  • Treatment Outcome
  • Visual Acuity / physiology
  • Vitamin A / blood


  • Antineoplastic Agents
  • Retinol-Binding Proteins, Plasma
  • Vitamin A
  • Fenretinide