Vitamin A and fish oils for retinitis pigmentosa

Cochrane Database Syst Rev. 2013 Dec 19;2013(12):CD008428. doi: 10.1002/14651858.CD008428.pub2.


Background: Retinitis pigmentosa (RP) comprises a group of hereditary eye diseases characterized by progressive degeneration of retinal photoreceptors. It results in severe visual loss that may lead to legal blindness. Symptoms may become manifest during childhood or adulthood, and include poor night vision (nyctalopia) and constriction of peripheral vision (visual field loss). This field loss is progressive and usually does not reduce central vision until late in the disease course.The worldwide prevalence of RP is one in 4000, with 100,000 patients affected in the USA. At this time, there is no proven therapy for RP.

Objectives: The objective of this review was to synthesize the best available evidence regarding the effectiveness and safety of vitamin A and fish oils (docosahexaenoic acid (DHA)) in preventing the progression of RP.

Search methods: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2013, Issue 7), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to August 2013), EMBASE (January 1980 to August 2013), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to August 2013), the metaRegister of Controlled Trials (mRCT) (, ( and the WHO International Clinical Trials Registry Platform (ICTRP) ( We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 20 August 2013.

Selection criteria: We included randomized controlled trials (RCTs) evaluating the effectiveness of vitamin A, fish oils (DHA) or both, as a treatment for RP. We excluded cluster-randomized trials and cross-over trials.

Data collection and analysis: We pre-specified the following outcomes: mean change from baseline visual field, mean change from baseline electroretinogram (ERG) amplitudes, and anatomic changes as measured by optical coherence tomography (OCT), at one year; as well as mean change in visual acuity at five-year follow-up. Two authors independently evaluated risk of bias for all included trials and extracted data from the publications. We also contacted study investigators for further information on trials with publications that did not report outcomes on all randomized patients.

Main results: We reviewed 394 titles and abstracts and nine records and included three RCTs that met our eligibility criteria. The three trials included a total of 866 participants aged four to 55 years with RP of all forms of genetic predisposition. One trial evaluated the effect of vitamin A alone, one trial evaluated DHA alone, and a third trial evaluated DHA and vitamin A versus vitamin A alone. None of the RCTs had protocols available, so selective reporting bias was unclear for all. In addition, one trial did not specify the method for random sequence generation, so there was an unclear risk of bias. All three trials were graded as low risk of bias for all other domains. We did not perform meta-analysis due to clinical heterogeneity of participants and interventions across the included trials.The primary outcome, mean change of visual field from baseline at one year, was not reported in any of the studies. No toxicity or adverse events were reported in these three trials. No trial reported a statistically significant benefit of vitamin supplementation on the progression of visual field loss or visual acuity loss. Two of the three trials reported statistically significant differences in ERG amplitudes among some subgroups of participants, but these results have not been replicated or substantiated by findings in any of the other trials.

Authors' conclusions: Based on the results of three RCTs, there is no clear evidence for benefit of treatment with vitamin A and/or DHA for people with RP, in terms of the mean change in visual field and ERG amplitudes at one year and the mean change in visual acuity at five years follow-up. In future RCTs, since some of the studies in this review included unplanned subgroup analysis that suggested differential effects based on previous vitamin A exposure, investigators should consider examining this issue. Future trials should take into account the changes observed in ERG amplitudes and other outcome measures from trials included in this review, in addition to previous cohort studies, when calculating sample sizes to assure adequate power to detect clinically and statistically meaningful difference between treatment arms.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review
  • Systematic Review

MeSH terms

  • Docosahexaenoic Acids / therapeutic use*
  • Electroretinography
  • Fish Oils / therapeutic use
  • Humans
  • Randomized Controlled Trials as Topic
  • Retinitis Pigmentosa / therapy*
  • Visual Acuity
  • Vitamin A / therapeutic use*
  • Vitamins / therapeutic use*


  • Fish Oils
  • Vitamins
  • Vitamin A
  • Docosahexaenoic Acids