Brianne N. Hobbs, OD
January 06, 2014
Treatment With 9-cis Beta-Carotene-Rich Powder in Patients With Retinitis Pigmentosa: A Randomized Crossover Trial
Rotenstreich Y, Belkin M, Sadetzki S, et al.
JAMA Ophthalmol. 2013;131:985-992.
Study Summary
Retinitis pigmentosa is a devastating diagnosis. This condition can leave optometrists and ophthalmologists scrambling as they attempt to explain possible treatment options, none of which are very effective. There is no curative treatment for retinitis pigmentosa, and management strategies historically have focused on maximizing function of the limited vision that remains.
A defect in the retinoid cycle metabolic pathway is involved in the pathophysiology of retinitis pigmentosa in some patients, and it is speculated that dietary supplementation may be of benefit in restoring the integrity of this cycle. Previously omega-3 fatty acids and vitamin A have been used in the treatment of retinitis pigmentosa, with limited success. Recently supplementation with 9-cis beta-carotene, a precursor to retinol, has showed some promise in restoring retinal function in patients with retinitis pigmentosa.
Rotenstreich and colleagues conducted a trial in which they investigated the effects of 9-cis beta-carotene supplementation on the retinal function of 34 patients with retinitis pigmentosa. This was a randomized, double-masked, crossover trial. To be included in the study, patients had to be 18 years of age or older and have a diagnosis of retinitis pigmentosa confirmed by electroretinography (ERG).
Patients assigned to the treatment group received 300 mg capsules of 9-cis beta-carotene-rich algaDunaliella bardawil containing approximately 20 mg of beta-carotene for 90 days, then engaged in a washout period of 90 days. The crossover design allowed both groups to receive the treatment and allowed intrapatient comparison of the effects of placebo and beta-carotene.
The primary endpoint was the amplitude of the dark-adapted b-wave, which served as a sensitive measure of retinal function. Secondary endpoints included the light-adapted maximal b-wave amplitude, best corrected visual acuity, and dark- and light-adapted visual field. The study lasted for 270 days, consisting of 3 distinct 90-day periods: treatment, washout, and placebo (or in reverse order). The primary and secondary endpoints were measured 4 times throughout the study: at the beginning of the study and then every 90 days.
Of the original 34 eligible participants, 29 completed the study. There was a statistically significant difference in the dark-adapted b-wave amplitude between the beta-carotene group and the placebo group (+8.9 µV OD, +7.8 µV OS vs -7.9 µV OD, -3.9 µV OS). Is this outcome clinically significant as well?
Viewpoint
Several considerations should be mentioned in the interpretation of these results. The normal amplitude of the dark-adapted b-wave is several hundred µV, so an average increase of +8.4 µV binocularly does not necessarily have any substantial clinical implications. The ERG responses also vary according to testing conditions, so low-level fluctuations may not represent true changes in retinal function. Furthermore, the study found no statistically significant differences in the clinically relevant secondary outcome measures of visual acuity and visual field.
Despite these modest findings, it is likely that some benefit was derived from the treatment evaluated in this study in a certain subgroup of patients with retinitis pigmentosa. The patients in this study did not undergo genetic analysis, so it is difficult to extrapolate the findings (showing that about one third of patients derived some benefit) to the general population of patients with retinitis pigmentosa. Larger trials are needed to confirm the potential benefit, and genotyping would certainly be advantageous to identify the patients with the type of retinitis pigmentosa most likely to benefit from treatment with beta-carotene. The amplitude of the b-wave is not always directly indicative of visual function because a normal b-wave does not ensure that the signal is actually propagated within the optic nerve and reaches the visual cortex.
However, despite the limitations of a small sample size and brief study length, this trial was well designed and provided enough evidence to demonstrate the need for additional studies. Even if beta-carotene cannot help all patients with this condition, the results of this trial represent a step forward in the management of patients with retinitis pigmentosa.