Treatment for Retinitis Pigmentosa Reported

Most adults with blinding retinitis pigmentosa (RP) should take adaily, 15,000 IU vitamin A supplement, based on results from a large,randomized clinical trial published today in the Archives ofOphthalmology.

This recommendation is the first from a well-designed clinical trialindicating that people can be treated for this retinal disease. “Thisis exciting news,” said Carl Kupfer, M.D., director of theNational Eye Institute, which supported the six-year study. “Whilevitamin A supplementation certainly does not represent a cure, it doessignify a first step in managing these diseases.”

Eliot L. Berson, M.D., the study’s principal investigator andProfessor of Ophthalmology at Harvard Medical School, said that adultswho supplemented their diets with 15,000 IU of vitamin A daily had onaverage about a 20 percent slower annual decline of remaining retinalfunction than those not taking this dose.

Based on this finding, Dr. Berson and his colleagues estimated thatan average patient in the study who started taking a 15,000 IU vitaminA capsule at age 32 would retain some useful vision until age 70,whereas a patient not on this dose would lose useful vision at age 63.

The investigators also recommended that adults with RP should avoidtaking high-dose vitamin E supplements. In the study, the diseaseappeared to progress faster on average in patients on a daily, 400 IUvitamin E supplement than in those taking a trace amount of thevitamin. Dr. Berson said that the study showed no evidence that normaldietary or small supplemental amounts of vitamin E have an adverseeffect on the disease.

Retinitis pigmentosa is a group of inherited retinal diseases thataffects about 100,000 Americans and 1.5 million people worldwide. Itcauses the progressive deterioration of specialized, light-absorbingcells in the retina, the paper-thin tissue that lines the back of theeye like film in a camera.

As these cells slowly degenerate, people with RP develop nightblindness and a gradual loss of peripheral vision. By about age 40,most have tunnel vision, although many may retain good central vision.Between the ages of 50 and 80, however, they typically lose theirremaining sight. The extent of vision loss in people of the same agewith RP may be different.

Dr. Berson stressed that adults considering vitamin Asupplementation should first:

• Consult with their eye care professional about vitamin Asupplementation.
• Have their blood level of vitamin A measured before startingtreatment. If people have pre-existing liver disease or abnormallyhigh blood levels of vitamin A, they will need to adjust theirvitamin A intake.
• Take vitamin A palmitate, as this was the form of the vitaminstudied. Supplements of beta- carotene, a natural precursor ofvitamin A, are not a predictable source of the vitamin since eachperson breaks down beta-carotene differently.
• Make a point of eating a balanced diet, without selecting foodsthat are especially high in vitamin A.
• Avoid taking high-dose vitamin E supplements.

“One of my biggest concerns is that people will make themistake of thinking that vitamin A supplementation in excess of the15,000 IU recommended will provide even greater benefit,” saidDr. Berson. “We have evidence in fact that supplementation of aregular diet with greater than 15,000 IU of vitamin A does not providegreater benefit. Moreover, a daily vitamin A intake exceeding 25,000IU over the long term can be toxic in adults and may cause sideeffects such as liver disease.

“Our interpretation of the study results is that the course ofthe common forms of retinitis pigmentosa is slower on average amongadult patients on a regular diet who take a daily, 15,000 IU vitamin Asupplement in the palmitate form compared with the course of thosepatients not on this supplement,” he said.

Because the study involved adults between the ages of 18 and 49, noformal recommendations can be made for patients under the age of 18.

Dr. Berson warned that women with RP should not take 15,000 IUvitamin A supplements during pregnancy because high doses of vitamin Ahave been linked to birth defects.

A single capsule containing 15,000 IU of vitamin A in the palmitateform will soon be available commercially. For further information onits availability, Contact the RP Foundation Fighting Blindness*toll-free at 1-800-683-5555.

Background Information on the Study

This study was a prospective, double-masked clinical trial (neitherthe patient nor the clinician knew to which treatment group thepatient had been assigned). It was designed to assess theeffectiveness of vitamin A and/or E supplements in halting or slowingthe progression of RP.

An independent Data Safety and Monitoring Committee provided adviceto the investigators and monitored the accumulating data on a regularbasis for evidence of harm or benefit to study participants.

A total of 601 RP patients from across the United States and Canadawere enrolled in the study. All were in good general health, betweenthe ages of 18 and 49, and entered the study with different initiallevels of retinal function. Following an examination, participantswere assigned randomly to one of four treatment groups:

• 15,000 IU vitamin A + 3 IU vitamin E
• 75 IU vitamin A + 3 IU vitamin E
• 15,000 IU vitamin A + 400 IU vitamin E
• 75 IU vitamin A + 400 IU vitamin E

Thereafter, the researchers examined each patient annually, with amean follow-up time of 5.2 years. The electroretinogram (ERG) was usedas the study’s primary outcome measure. The ERG is a light-evokedelectrical response from the retina that can be accurately measuredusing a special Contact lens, much like an electrocardiogram measurescoronary function. An ERG provides an objective measure of a person’sretinal function. The scientists also used visual fields and visualacuity as additional measures of visual function.

This clinical trial was conducted at the Berman-Gund Laboratory forthe Study of Retinal Degenerations at the Massachusetts Eye and EarInfirmary in Boston, Massachusetts. It was supported by the NationalEye Institute and, in part, by the RP Foundation Fighting Blindness*in Baltimore, Maryland. The National Eye Institute, a part of theNational Institutes of Health, is the Federal government’s lead agencyfor the conduct and support of research on the human visual system inhealth and disease.

*RP Foundation Fighting Blindness is now called the FoundationFighting Blindness.

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Citations

• Berson EL, Rosner B, Sandberg MA, Hayes KC, Nicholson BW, Weigel-DiFranco C, Willett W. A Randomized Trial of Vitamin A and Vitamin E Supplementation for Retinitis Pigmentosa. Arch Ophthalmol. 1993 Jun. PubMed

June 1993