New Findings Lead to Revised Therapeutic Regimen to Slow RP
By Alan Laties, M.D. Chairman of the FFB Scientific Advisory Board
The Berman-Gund Laboratory for the Study of Retinal Degenerations, at Harvard Medical School, has just completed the second in an ongoing series of clinical trials testing nutritional or other supplements as potential therapies for retinitis pigmentosa (RP). The first clinical trial completed in 1993 demonstrated a beneficial effect on visual function of Vitamin A and a deleterious effect of Vitamin E. As a result, the Foundation Fighting Blindness and the National Eye Institute jointly recommended for most adults the daily administration of 15,000 units of Vitamin A palmitate. Not fully understood, either then or now, the beneficial effect of Vitamin A was slow to take effect, becoming evident in the original clinical trial only after several years of administration.
Just completed, a second study was designed to test whether a lipid of special relevance to vision, DHA, taken as a dietary supplement would enhance the already recognized sight-saving benefit of Vitamin A. The results of the second trial are published in two reports in the September 2004 issue of the American Medical Association's Archives of Ophthalmology. The lead author of the report, Eliot L. Berson, M.D., is a member of the Scientific Advisory Board of the Foundation Fighting Blindness.
The results are complex and are best understood when it is kept in mind that the benefit to vision observed in the original trial took several years to become evident. In fact, some wondered at the announcement of the results of the first clinical trial if treatment effects so delayed were indeed valid.
The second trial sheds new light as it demonstrates an interaction between Vitamin A and DHA such that DHA apparently foreshortens the time for Vitamin A to become effective. This became evident when it was recognized that two groups of participants took part in the second clinical trial: subjects already taking Vitamin A and subjects not taking Vitamin A. Among many other considerations, this distinction was not recognized in the original study design and, hence, no notice of it was taken in the original randomization. However, early in the course of the just reported clinical trial an interaction was recognized. Thereafter, the clinical course of the two categories of participants was followed annually. At the conclusion of the clinical trial, subgroup analyses clearly documented that DHA accelerated the onset of visual benefit for those who were newly started on Vitamin A. But in participants who had already taken Vitamin A for a period of time long enough to achieve its full benefit, DHA did not add to that benefit.
The second clinical trial included a careful survey of dietary practices of all participants. When these were analyzed, it was discovered that intake once or twice a week of fish with a high fat content (such as tuna, mackerel, sardines, salmon or herring) conferred an additional visual benefit.
The study from the Berman-Gund Laboratory also showed that patients with higher red blood cell levels of DHA experienced a substantially slower loss of vision field sensitivity than did patients with lower levels. These results are consistent with findings from a previous FFB-sponsored trial by Dr. Dennis Hoffman of the University of Texas Southwestern Medical Center and colleagues in subjects with X-linked RP showing that increased DHA levels in the blood were associated with a decreased rate of decline in visual function.
Based on the findings of these clinical trials, Dr. Berson and his colleagues have issued an advisory letter. The letter follows and is also available on the Foundation Fighting Blindness web site (blindness.org). It contains specific recommendations and cautions. These include obtaining blood tests periodically as well as information on sources of appropriate Vitamin A and DHA supplements.
The research was supported by grants from the Foundation Fighting Blindness and the National Eye Institute.