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Subgroup Analyses

Eliot L. Berson, MD; Bernard Rosner, PhD; Michael A. Sandberg, PhD; Carol Weigel-DiFranco, MA; Ann Moser, BA; Robert J. Brockhurst, MD; K. C. Hayes, DVM, PhD; Chris A. Johnson, PhD; Ellen J. Anderson, RD; Alexander R. Gaudio, MD; Walter C. Willett, MD; Ernst J. Schaefer, MD

Arch Ophthalmol. 2004;122:1306-1314.

Objective  To determine whether docosahexaenoic acid will slow the course of retinal degeneration in subgroups of patients with retinitis pigmentosa who are receiving vitamin A.

Design  A cohort of 208 patients with retinitis pigmentosa, aged 18 to 55 years, were randomly assigned to 1200 mg of docosahexaenoic acid plus 15 000 IU/d of vitamin A given as retinyl palmitate (DHA + A group) or control fatty acid plus 15 000 IU/d of vitamin A (control + A group) and followed up over 4 years. Seventy percent of the patients in each group were taking vitamin A, 15 000 IU/d, prior to entry. We compared rates of decline in ocular function in the DHA + A vs control + A groups among the subgroups defined by use or nonuse of vitamin A prior to entry. We also determined whether decline in ocular function was related to red blood cell phosphatidylethanolamine docosahexaenoic acid level, dietary -3 fatty acid intake, or duration of vitamin A use. Main outcome measures were Humphrey Field Analyzer visual field sensitivity, 30-Hz electroretinogram amplitude, and visual acuity.

Results  Among patients not taking vitamin A prior to entry, those in the DHA + A group had a slower decline in field sensitivity and electroretinogram amplitude than those in the control + A group over the first 2 years (P = .01 and P = .03, respectively); these differences were not observed in years 3 and 4 of follow-up or among patients taking vitamin A prior to entry. In the entire cohort, red blood cell phosphatidylethanolamine docosahexaenoic acid level was inversely related to rate of decline in total field sensitivity over 4 years (test for trend, P = .05). This was particularly evident over the first 2 years among those not on vitamin A prior to entry (test for trend, P = .003). In the entire control + A group, dietary -3 fatty acid intake was inversely related to loss of total field sensitivity over 4 years (intake, <0.20 vs 0.20 g/d; P = .02). The duration of vitamin A supplementation prior to entry was inversely related to rate of decline in electroretinogram amplitude (P = .008).

Conclusions  For patients with retinitis pigmentosa beginning vitamin A therapy, addition of docosahexaenoic acid, 1200 mg/d, slowed the course of disease for 2 years. Among patients on vitamin A for at least 2 years, a diet rich in -3 fatty acids (0.20 g/d) slowed the decline in visual field sensitivity.

From the Berman-Gund Laboratory for the Study of Retinal Degenerations, Harvard Medical School, Massachusetts Eye and Ear Infirmary (Drs Berson, Rosner, Sandberg, Brockhurst, and Gaudio and Mss Weigel-DiFranco and Anderson), the Department of Nutrition, Harvard School of Public Health (Dr Willett), and the Lipid Metabolism Laboratory, Jean Mayer US Department of Agriculture Human Nutrition Research, Center on Aging at Tufts University (Dr Schaefer), Boston, Mass; the Kennedy Krieger Institute, Peroxisomal Diseases Laboratory, Baltimore, Md (Ms Moser); the Foster Biomedical Research Laboratory, Brandeis University, Waltham, Mass (Dr Hayes); and the Devers Eye Institute, Portland, Ore (Dr Johnson). The authors have no relevant financial interest in this article.

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Clinical Trial of Docosahexaenoic Acid in Patients With Retinitis Pigmentosa Receiving Vitamin A Treatment
Eliot L. Berson, Bernard Rosner, Michael A. Sandberg, Carol Weigel-DiFranco, Ann Moser, Robert J. Brockhurst, K. C. Hayes, Chris A. Johnson, Ellen J. Anderson, Alexander R. Gaudio, Walter C. Willett, and Ernst J. Schaefer
Arch Ophthalmol. 2004;122(9):1297-1305.
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