March 2012
Volume 53, Issue 14
ARVO Annual Meeting Abstract  |   March 2012
The NAT-2 Study: genetic analysis
Author Affiliations & Notes
  • Eric H. Souied
    Retina Creteil, University Paris Est Creteil, Creteil, France
  • Cécile Delcourt
    Epidemiologie-Biostatistique, ISPED, INSERM U897, Bordeaux, France
  • Nathalie Puche
    Retina Creteil, University Paris Est Creteil, Creteil, France
  • Giuseppe Querques
    Retina Creteil, University Paris Est Creteil, Creteil, France
  • Alain Zourdani
    Retina Creteil, University Paris Est Creteil, Creteil, France
  • Pascale Benlian
    Biochemistry and Molecular Biology, Université Lille 2, Lille, France
  • NAT2 study group
    Retina Creteil, University Paris Est Creteil, Creteil, France
  • Footnotes
    Commercial Relationships  Eric H. Souied, Bauch&Lomb (C, R); Cécile Delcourt, Bausch&Lomb (C, R); Nathalie Puche, None; Giuseppe Querques, None; Alain Zourdani, Bausch&Lomb (C); Pascale Benlian, Bausch&Lomb (C, R)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 2934. doi:
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      Eric H. Souied, Cécile Delcourt, Nathalie Puche, Giuseppe Querques, Alain Zourdani, Pascale Benlian, NAT2 study group; The NAT-2 Study: genetic analysis. Invest. Ophthalmol. Vis. Sci. 2012;53(14):2934.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: : The NAT-2 (Nutritional AMD treatment-2) study was a randomized, placebo-controlled, double-blind, parallel, comparative study. The purpose of NAT-2 was to evaluate the efficacy of oral docosahexaenoic acid (DHA) supplementation for preventing exudative age-related macular degeneration (AMD). The purpose of this ancillary study was to correlate the effects of DHA supplementation with genetic background.

Methods: : 263 patients (Full Analysis Set) aged ≥55 and <85 years with early lesions of age-related maculopathy and visual acuity ≥+0.4 LogMAR units in the study eye and neovascular AMD in the fellow-eye. Patients were randomly assigned to receive either 840 mg/day DHA from fish oil capsules or the placebo (olive oil capsules) for 3 years. The primary outcome measure was time to occurrence of choroidal neovascularization (CNV) in the study eye. Secondary outcome measures in the study eye were: percentage of patients developing CNV and changes in visual acuity, occurrence and progression of drusen, and EPA+DHA concentration changes in red blood cell membrane (RBCM). The rs1061170 polymorphism of CFH gene and the rs10490924 polymorphism of the ARMS2 gene were analyzed.

Results: : Time to occurrence and incidence of CNV in the study eye were not significantly different between the DHA (19.5 ± 10.9 months, 28.4%, respectively) and placebo groups (18.7 ± 10.6 months, 25.6%, respectively). EPA+DHA concentration significantly increased in RBCM in the DHA group (+70%; p<0.001), suggesting a good ability of DHA to penetrate cells, but unexpectedly in the placebo group also (+9%; p=0.007). In the DHA treated group, high DHA responders (third tertile for EPA+DHA concentrations in RBCM) had a significantly lower risk (-70%; p=0.047) for developing CNV over 3 years. A significant effect of DHA was observed in patients without CFH at-risk allele. In this population without CFH at-risk allele, CNV occurred in 4/24 (16.7%) patients in the DHA group versus 13/34 (38.2%) in the placebo group (OR= 0.2, 95 % confidence interval [0.1-0.9]; p=0.034). No differences were found with the ARMS2 polymorphism.

Conclusions: : Oral DHA had the same effect on 3-year CNV incidence as placebo. However, CNV incidence appeared markedly reduced in DHA supplemented patients with the highest EPA+DHA index. A significant effect of DHA was observed in patients without CFH at risk allele.

Clinical Trial: : ISRCTN98246501

Keywords: age-related macular degeneration • genetics • lipids 

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