A Conversation with Harvard’s Dr. William Christen, Noted Eye Disease Researcher

William G. Christen Jr, ScD, PhD, OD, is Associate Professor (Medicine) in the Division of Preventive Medicine, Brigham and Women’s Hospital, Harvard Medical School, in Boston. Dr. Christen has studied the epidemiology of eye disease in randomized trials and large cohort studies for over 25 years. Here he talks with ScienceBased Health about his research. This is an edited, condensed version of the full interview, available at sciencebasedhealth.com

ScienceBased Health (SBH): Dr. Christen, you and your collaborators conducted a large intervention trial of B-vitamins in women free of AMD at the outset. Can you briefly describe this trial and its findings?

William Christen (WC): In the Women’s Antioxidant and Folic Acid Cardiovascular Study (WAFACS), comprised of women at high risk for CVD, we found that among the more than 5,000 women who had no reported AMD at study entry, those randomly assigned to a daily combination of folic acid (2.5 mg), vitamin B6 (50 mg), and vitamin B12 (1 mg), compared to those given placebo, had a 35% to 40% lower risk of AMD after 7.3 years of treatment and follow-up.

SBH: You’ve also investigated the relationship between low dose aspirin use and AMD in women, finding no harm or benefit over 10 years. Some recent studies have reported a link between aspirin use and AMD risk. Can you comment?

WC: Several recent observational studies have reported that long-term users of aspirin have an increased risk of AMD, specifically neovascular AMD. As you might expect, these reports have raised concern in the vision community and beyond, particularly given the widespread use of aspirin for cardioprotection. But before concluding causality, we need to consider the inherent limitations of observation studies, most notably uncontrolled confounding.

In all three studies, persons who reported being regular aspirin users differed from non-regular users in a number of ways including being much more likely to report a personal history of CVD. Aspirin therapy is commonly recommended for persons with CVD, so this isn’t surprising. But AMD and CVD are thought to share similar underlying mechanisms and risk factors, so the potential for confounding, particularly confounding by indication, is great in these studies.

SBH: Your group recently reported results for the multivitamin component of the large-scale Physician Health Study II.  What did you find?

WC: We examined whether a daily multivitamin taken for an average of 11 years affected the incidence of
cataract or AMD in a large cohort of male physicians. Our results showed that men in the multivitamin group, compared to those in the placebo group, had a statistically significant 9% lower risk of cataract over the course of treatment.

Although the risk reduction is modest, cataract is so common that if the findings are real, even a modest reduction in risk would have a large public health impact. There was no significant benefit or harm of multivitamin supplementation on visually significant AMD (i.e. AMD of sufficient severity to reduce best-corrected visual acuity to 20/30 or worse).

SBH: Several studies have associated low vitamin D status with increased risk of AMD or higher serum levels with protection against early AMD in women. Do you think it’s time for an intervention trial?

WC: It’s interesting you should ask. In fact, we are collecting data for AMD in the ongoing VITamin D and OmegA-3 TriaL (VITAL). VITAL is a large 2×2 factorial trial designed to test whether vitamin D (cholecalciferol, 2000 IU/day) and marine omega-3 fatty acid (EPA +DHA, 1 g/day) can prevent cancer and CVD. The trial is enrolling a multi-ethnic population of more than 25,000 US men aged ≥50 and women aged ≥55.

AMD is one of several secondary endpoints, in addition to the primary endpoints of cancer and CVD that will be examined in VITAL ancillary studies. Current plans are for an average treatment and follow-up of about 5 years. So we anticipate that in the near future, we should be able to provide reliable data to evaluate whether vitamin D (and EPA + DHA) can prevent AMD.

SBH: What projects are you currently working on?

CW: In addition to examining AMD occurrence in the VITAL trial, we are also collecting data to examine the effects of the VITAL interventions on dry eye. We’re also trying to better understand the apparent beneficial effect of B vitamin supplements on AMD that we observed in WAFACS; is it due to homocysteine-lowering or some other mechanism?  Finally, we’re collaborating with other groups to examine the genetic epidemiology of glaucoma.