May 13, 2009 (Fort Lauderdale, Florida) — Although no statistically significant difference was seen in best corrected distance visual acuity (BC DVA) at 12 months, oral supplementation with lutein and zeaxanthin with coantioxidants may improve functional and morphologic outcomes at 36 months in patients at high risk for progression to late age-related macular degeneration (AMD). The findings were presented here at the Association for Research in Vision and Ophthalmology (ARVO) 2009 Annual Meeting.
In the Carotenoids and Co-Antioxidants in Age-Related Maculopathy (CARMA) study, investigators examined the effects of supplementation with serum lutein and zeaxanthin to coantioxidants (vitamins C and E and zinc), compared with placebo, on visual function and progression from early to late stages of AMD. Investigative team member Usha Chakravarthy, MD, PhD, from Queens University of Belfast in Northern Ireland, presented the results.
A total of 433 patients (with early AMD features in at least 1 eye, or any level of AMD in the study eye and late-stage AMD in the fellow eye) were enrolled in 2 centers in the United Kingdom (1 in Belfast and 1 in Waterford). The patients were randomized to receive either carotenoids plus coantioxidants (C+CA; n = 216) or placebo (n = 217).
The primary outcome was BC DVA as measured on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at 4 meters at 12 months. Secondary outcomes included improved or preserved interferometric acuity, contrast sensitivity, shape discrimination ability, Raman spectroscopy for macular pigment, and change in AMD severity as monitored by fundus photography by trained readers.
At every study visit (baseline and at 12, 18, 24, 30, and 36 months), fundus photographs were graded, and serum lutein, zeaxanthin, and the other antioxidants were measured. An analysis of covariance adjusted for baseline covariates was performed at 12 months.
Results at 36 Months Significant
Results from this study showed that although the mean change in BC DVA at 12 months favored the C+CA group (0.002 in the C+CA group vs 0.007 in the placebo group), the difference was not statistically significant (P = 0.5). Stronger differences were found in the study's later stages, especially at the 36-month mark.
However, as the trial went on, the number of participants in the C+CA and placebo groups dropped significantly because of self withdrawal: at 18 months, there were 122 and 126 participants, respectively; at 24 months, 92 and 95; at 30 months, 58 and 52; and at 36 months, 21 and 20.
"There was a steady increase in the differential change in best corrected visual acuity between treatment groups," explained Dr. Chakravarthy. "At the 36-month follow-up, BC DVA was better in the treated eyes, and statistically significant, although admittedly, there were very few numbers [of patients] by that stage."
In addition, a 10-fold increase in serum lutein was associated with a 4-letter improvement in DVA (B –0.77, t –2.42; P = .017), and a higher serum lutein was associated with a slower rate of AMD progression (P = .011).
"In conclusion, the CARMA study suggests that supplementation with lutein and zeaxanthin results in better macular function in patients with early AMD," said Dr. Chakravarthy. "And as the eyes of persons who had high serum [lutein] demonstrated a less severe early AMD change over time, supplementation may prove beneficial in preventing progression to late AMD. The Raman count did not decline in the active group, but fell over time in the placebo group. Therefore, we concluded that supplementation results in maintained levels of macular pigment."
Study Did Not Achieve Stated Objective
After the presentation, Dr. Chakravarthy told Medscape Ophthalmology that "overall, I am optimistic about the study findings. We did observe a trend to better visual acuity in the treatment group, with statistical difference reached in the later stage of the study in those who remained for 36 months. However, the results are based on outcomes that were specified as secondary outcomes, and therefore the study did not achieve its stated objective." Still, although the difference only became statistically significant at 3 years, "a trend of separation between the groups was seen after 2 years."
Session moderator Antonio Capone Jr, MD, from Associate Retinal Consultants and clinical associate professor of biomedical sciences at Oakland University in Auburn Hills, Michigan, said after the presentation: "I think we all have high hopes that nutritional supplementation of one agent or another will end up offering our patients an ability to alter their risk profile with regard to the likelihood of developing vision loss from age-related macular degeneration.
"On the one hand, I think this study is encouraging because there are data that suggest that there may be some protective effect with the carotenoid therapy," Dr. Capone said. On the other hand, "the disappointing component is that it appears that the study ended up being underpowered to make that sort of comment or recommendation as definitively as we would have liked."
He continued: "They didn't meet their primary outcome at 12 months, but did at later months. However, as a study cohort starts to diminish in size, attrition ends up having a significant impact on outcome and decreases the power of any study. So I'm encouraged and it sounds hopeful, but I'm looking for something that's a better hope to hang my hat on from a therapeutic perspective."
This study was funded and sponsored by Bausch and Lomb. Dr. Chakravarthy has received honoraria from Bausch and Lomb and an educational grant from Dr. Mann Pharma, a Berlin-based pharmaceutical and ophthalmic product manufacturer owned by Bausch and Lomb. Dr. Capone has disclosed no relevant financial relationships.
Association for Research in Vision and Ophthalmology (ARVO) 2009 Annual Meeting: Abstract 1257. Presented May 4, 2009.
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Cite this: ARVO 2009: Lutein, Zeaxanthin Supplements May Result in Better Macular Function in Early AMD - Medscape - May 13, 2009.