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Long-Chain Omega-3s and High-Dose Vitamin A Slow Visual Loss in Retinitis Pigmentosa

Retinitis pigmentosa is an eye disease of genetic origin that slowly damages the retina and impairs vision. It is usually first noticed by poor night vision, which progresses gradually to impaired peripheral vision (tunnel vision), then loss of central vision. The hallmark of the condition is black spicule-shaped deposits in the retina (Figure). The condition mainly affects the rod cells responsible for night vision, but may affect the cone cells as well. Retinitis pigmentosa affects about 1 in 4,000 people in the U.S.

The authors of this report have conducted 3 clinical trials on the effect of high-dose vitamin A supplementation with or without DHA on the decline in visual function in patients with retinitis pigmentosa. Trials lasted 4 to 6 years. Providing 15,000 IU of vitamin A per day (4,500 retinol equivalents) was associated with a slower decline in retinal function at doses up to 25,000 IU per day, without adversely affecting the liver. Supplemental lutein, a different carotenoid that concentrates in the macula of the retina, was also associated with a slower loss of midperipheral visual field over 4 years in patients taking 15,000 IU of vitamin A per day. The addition of DHA to vitamin A supplementation in patients not previously taking vitamin A slowed the course of the disease for 2 years, but not over 4 years. Patients already taking vitamin A who consumed an omega-3-rich diet also exhibited a slower decline in visual field sensitivity.

To better define the effects of higher intakes of DHA or long-chain omega-3 PUFAs (n-3 LC-PUFAs) on visual function in these patients, the investigators combined the data from the 3 previous trials to achieve greater statistical power. Data from nearly all participants were included except for 7 outliers, 9 patients who participated in 2 of the trials and 1 who was in all 3 trials. The 357 patients ranged from 18 to 60 years of age (average 35 years) and all had consumed 15,000 IU of vitamin A per day for at least 4 years. Baseline screening included a best-corrected Snellen distance visual acuity test of 20/100 or better in at least one eye. Dietary intakes were assessed at baseline and at each annual screening, using a food frequency questionnaire from which n-3 LC-PUFA intakes were estimated. Visual acuity was assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) chart.

Participant data were divided into two categories according to the median intake of n-3 LC-PUFAs of 200 mg/day observed in the second trial. Of all participants, 215 (58%) were at or above the median intake. Rates of loss in distance acuity (Snellen scores) and retinal acuity (ETDRS scores) were analyzed by longitudinal regression according to n-3 LC-PUFA intake, corrected for age, length of follow-up, intraclass correlations of visual acuity between fellow eye of individual patients at a single visit and between the same eye over time. Patients who underwent an intraocular lens implantation for cataract or reached an ETDRS score of zero had data subsequent to the event removed from the analysis.

Participants who consumed 200 mg or more of n-3 LC-PUFA per day experienced a significantly slower loss of distance acuity per year compared with those consuming less than 200 mg/day (-0.59 vs -1.00 letter per year, P = 0.001). Similarly, the higher n-3 LC-PUFA intake group experienced a significantly slower change in retinal acuity per year (1.5% vs 2.8% units, P = 0.03). Separate analysis indicated that age had no significant effect on these rates. The frequency of cataract increased by 11% among the high n-3 LC-PUFA group and 10% in the low intake participants over 4 to 6 years. There were no effects on full-field cone electroretinograms.

The key observation of this combined data analysis is that patients with retinitis pigmentosa who consume at least 200 mg per day of n-3 LC-PUFAs in addition to taking 15,000 IU of vitamin A daily have significantly slower rates of distance and retinal acuity loss compared with those who consume less than 200 mg n-3 LC-PUFAs per day. The difference was at least a 40% slower annual rate of loss for each type of visual acuity. The authors estimated that if a 35-year-old patient with an ETDRS acuity of 50 letters (Snellen score of 20/30) increased his/her consumption of n-3 LC-PUFAs to at least 200 mg per day and continued vitamin A supplementation, the patient would gain an additional 18 years of visual acuity before reaching an ETDRS score of 24 letters (Snellen score of 20/100).

The investigators commented that the combined intervention was likely attributable to the preservation of central retinal function. The lack of change in the full-field cone electroretinograms, which are generated by mid- and far-peripheral cones, supports this interpretation. This notion is bolstered by a previous report from the Berson group in which a combination of vitamin A and the consumption of at least 200 mg n-3 LC-PUFA per day improved the retention of central visual field sensitivity. These data strengthen the optimism of the authors that a combination of 15,000 IU vitamin A and at least 200 mg n-3 LC-PUFAs consumed daily would “make it possible for many patients with typical retinitis pigmentosa to retain both visual acuity and central visual field for most of their lives.” That’s foresight!

Berson EL, Rosner B, Sandberg MA, Weigel-Difranco C, Willett WC. ω-3 intake and visual acuity in patients with retinitis pigmentosa receiving vitamin A. Arch Ophthalmol 2012; Mar 12. [Epub ahead of print] PubMed

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