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In the news: Vitamin D Levels in AMD, Omega-3s & Anti-VEGF in AMD

Vitamin D Levels in ‘Wet’ vs. ‘Dry’ AMD

Over the past several years, a number of studies have found an association between serum vitamin D levels and both early and late stage AMD. Researchers from the Department of Ophthalmology, Duke University Medical Center now report results of the largest study to compare vitamin D levels in patients with different clinical forms of AMD (1).

The researchers found that mean serum vitamin D [25(OH)D] levels were significantly lower in 146 patients with neovascular AMD compared to 216 patients with the non-neovascular form and to 100 controls without AMD.

The prevalence of vitamin D insufficiency (< 30 ng/mL), deficiency (< 20 ng/mL), and severe deficiency (< 10 ng/mL) were highest in the neo-vascular group.

The highest 20% or quintile of serum vitamin D levels (> 40 ng/mL) was associated with 65% lower odds for neovascular AMD versus the lowest quintile, adjusted for age and BMI.

As a retrospective review, this study has limitations. The results are compelling, though, because of the biologic plausibility of the association. In addition to its anti-inflammatory properties, active vitamin D has demonstrated anti-neovascular activity in rodent models of diabetic retinopathy, for example, and to interrupt key signaling pathways in angiogenesis.

The authors call for further study to examine whether improving vitamin D status may lower the risk for developing ‘wet’ AMD.

Currently, the recommended daily intake of vitamin D set by the Institute of Medicine is 600 IU daily for adults and 800 IU per day for those 70 and older, based largely on the impact of vitamin D on skeletal outcomes. In contrast, the US Endocrine Society indicates that 1500–2000 IU per day may be needed for adults and those over 70 to raise serum [25(OH)D] consistently above 30 ng/mL which is considered to be the optimal level by the guideline Task Force.

Omega-3 Fats and Anti-VEGF in Wet AMD

Inhibitors of vascular endothelial growth factor (VEGF) have proven to be effective treatments against wet AMD. However, as with any medication, anti-VEGF may have some associated risks such as a higher incidence of geographic atrophy in patients receiving more frequent anti-VEGF injections. This prompted researchers from the University of Montreal, Canada to explore an adjunct therapy in anti-VEGF treatment.

The study, an open label pilot trial, included 3 cohorts with wet AMD and a control group with epiretinal membrane or macular hole (2). Wet AMD patients already being treated with anti-VEGF (bevacizumab) were randomly assigned to daily supplements of antioxidants, zinc, and carotenoids with (Group 1, n=10) or without (Group 2, n=10) omega-3 fatty acids (200 mg of DHA and 400 mg of EPA). A third group (n=10) consisted of wet AMD patients who were just beginning anti-VEGF treatment. Group 4 was the control group (n=10). Groups 3 and 4 were not supplemented.

Patients receiving omega-3s (Group 1) had significantly lower levels of vitreal VEGF-A compared to Group 2 and Group 3, but similar levels to the control group. All groups showed similar values for plasma VEGF-A and measurements of central foveal thickness.

This pilot trial reports a significant decrease of VEGF-A in the vitreous of wet AMD patients on anti-VEGF therapy taking EPA and DHA – omega-3s thought to influence processes implicated in retinal angiogenesis. The results suggest that omega-3s selectively lower pathological levels of VEGF-A in the retina, but not in the general circulation where the normal function of VEGF is to create new blood vessels after injury, muscle following exercise, and new vessels to bypass blocked vessels. Long-term studies will be required to determine whether the omega-3s plus anti-VEGF therapy translates into slower progression of new vessel formation in the choroid.

References

1. Itty S, et al. Vitamin D deficiency in neovascular versus non-neovascular age-related macular degeneration. Retina 0:1–8, Jun 18, 2014. [Epub ahead of print].
2. Rezende FA, et al. Omega-3 supplementation combined with anti-VEGF lowers vitreal levels of VEGF in wet age-related macular degeneration. Am J Ophthalmol Aug 1, 2014. [Epub ahead of print]