Posterior Segment Age-related Macular Degeneration


It can be seen that a growing body of evidence suggests an inverse association between the dietary intake of ω-3 fatty acids and AMD risk. Although more evidence is needed to support the routine recommendation of ω-3 fatty acid intake for prevention of AMD,67,68


all


studies to date have suggested a protective role of DHA for AMD, particularly for exudative AMD, despite differences in methodology and populations. There is a need for further research involving prospective cohort studies and randomised clinical trials.


Prospective Studies Evaluating Nutritional Supplements Containing Omega-3 Fatty Acids for the Treatment of Age-related Macular Degeneration


Few clinical trials have investigated the role of oral supplementation with ω-3 for the prevention of AMD. The Nutritional AMD treatment phase I (NAT-1) study evaluated the feasibility of a prospective study of oral supplementation with DHA and EPA for six months compared with placebo. Serum and red blood cell membrane levels of EPA and DHA were elevated in the treated group. No change was observed in the control group despite diet recommendations. Although no therapeutic benefit of the ω-3 fatty acid supplementation was observed over this short time period, no side effects were reported and a further study was considered feasible.69


The further benefits of DHA supplementation are currently being evaluated in the NAT-2 study.69


NAT-2 is a single-centre prospective interventional randomised double-masked trial currently being conducted in France. Among its objectives is an investigation of the benefits of ω-3 supplementation for AMD. In addition, the benefits of oral supplementation with ω-3 PUFAs on the progression of AMD is being evaluated in the AREDS2 study, a multi-centre randomised placebo-controlled trial.70


Current European Recommendations for Omega-3 Fatty Acid Intake


Several organisations have made recommendations on dietary intake of fatty acids and, although levels vary, all agree that intake of ω-6 fatty acids should be reduced and ω-3 fatty acids increased. The European Food Safety Authority (EFSA) currently states that there is insufficient evidence to derive an average requirement, lower threshold intake, population reference intake or tolerable upper intake level for α-linolenic acid.75


represent 0.5 % of the total energy derived from fat.75


It is recommended that α-linolenic Based on


cardiovascular considerations, an adequate intake of 250 mg/day of combined EPA + DHA is recommended in healthy adults, with an additional 100–200 mg daily for pregnant or lactating individuals to compensate for the loss of DHA to the foetus/infant.75


In clinical studies, DHA supplementation has been found to contribute to optimal visual development in infants.76–78


The EFSA states that


“DHA contributes to the visual development of infants” and recommends an adequate intake of 100 mg/day in this age group.75 Dietary advice for children aged 2–18 years is similar to adults, i.e. an adequate intake of ~250 mg/day combined EPA + DHA.75 French Food Safety Agency79


In 2010, the published its recommended intakes for


fatty acids in AMD prevention: 250 mg/day of both EPA and DHA (i.e. a total of EPA + DHA 500 mg/day).79


The study


began in 2008, has enrolled around 4,000 participants and will run for 5–6 years. Results from AREDS2 are expected in 2013.


An Italian study investigated the benefit of supplementation with a mixture containing acetyl-L-carnitine (ALC), PUFAs, coenzyme Q10 (CoQ10) and vitamin E in patients with early AMD (n=106) over a period of 12 months. An equal number of age- and sex-matched patients were treated with vitamin E only. A slight improvement in visual function was observed in the treated group and the divergence between treated and control groups became more marked with time but was not statistically significant.71


The Taurine, omega-3 fatty acids, zinc, antioxidant, lutein (TOZAL) study treated 37 patients with dry AMD with a nutritional supplement containing EPA and DHA for six months. Of the patients receiving the nutritional supplement, 76.7 % showed an improvement or stabilisation in best corrected visual acuity. There was a statistically significant improvement in visual acuity compared with a placebo cohort constructed from the literature (p=0.045).72


Increased median


serum levels of ω-3 long chain fatty acids were also observed after six months following combined supplementation of EPA and DHA with lutein and zeaxanthin.73


Data from a study to determine the effects of lutein, a component of macular pigment, and DHA on their serum concentrations and macular pigment optical density (MPOD) suggested that DHA facilitated accumulation of lutein in the blood and macula, especially in the most central part of the fovea, suggesting a different and maybe synergistic effect of DHA + lutein on the spatial pattern of increase in MPOD.74


46


Conclusions and Future Developments The majority of evidence supporting a retinoprotective role of ω-3 fatty acids is observational. These studies show that a higher level of ω-3 fatty acid intake or the regular consumption of oily fish is associated with a 30–50 % risk reduction in the occurrence or progression of AMD. The body of evidence in support of ω-3 supplementation is growing. Recently, a high intake of ω-3 fatty acids has been shown to negate the risk of AMD posed by genetic factors.80


The benefits of ω-3 fatty acids


for the therapeutic treatment of AMD have not been demonstrated in randomised controlled trials. However, some agencies have already stated recommendations to support dietary supplementation with ω-3 fatty acids in prevention of AMD. Moreover, the on-going prospective randomised placebo-controlled trials AREDS2 and NAT-2 should address some of these concerns.


Compared with 100 years ago, current Western diets contain higher levels of saturated fats, trans fatty acids and ω-6 fatty acids, and reduced ω-3 fatty acids.81


for general health, not just retinal health and visual function.48,82


Redressing this imbalance may be important In terms


of visual function, increasing the intake of DHA is likely to be more important than that of EPA because of the high levels and turnover of DHA in the retina.36


However, both have antiangiogenic and


anti-inflammatory properties, and EPA is a precursor to DHA, so an equal balance of both might be the best option. In the on-going AREDS2 study, the supplement is richer in EPA than DHA. Depending on the outcome of the AREDS2, this should be addressed in the design of future trials. Despite the fact that clinical trials of nutritional supplements are difficult to conduct and need large patient numbers, it is vital that studies are continued aimed at clarifying the benefits of ω-3 fatty acids. The EFSA has recommended an adequate intake of DHA and EPA. Equally important is that sustainable sources of ω-3 fatty acids continue to be developed and evaluated as alternatives to fish oils.35,83 Recently, it has been shown that combinations of nutrients from food including vitamins, antioxidants and ω-3 are more strongly associated with a lower risk of AMD than single nutrients.84


n EUROPEAN OPHTHALMIC REVIEW


Page 1  |  Page 2  |  Page 3  |  Page 4  |  Page 5  |  Page 6  |  Page 7  |  Page 8  |  Page 9  |  Page 10  |  Page 11  |  Page 12  |  Page 13  |  Page 14  |  Page 15  |  Page 16  |  Page 17  |  Page 18  |  Page 19  |  Page 20  |  Page 21  |  Page 22  |  Page 23  |  Page 24  |  Page 25  |  Page 26  |  Page 27  |  Page 28  |  Page 29  |  Page 30  |  Page 31  |  Page 32  |  Page 33  |  Page 34  |  Page 35  |  Page 36  |  Page 37  |  Page 38  |  Page 39  |  Page 40  |  Page 41  |  Page 42  |  Page 43  |  Page 44  |  Page 45  |  Page 46  |  Page 47  |  Page 48  |  Page 49  |  Page 50  |  Page 51  |  Page 52  |  Page 53  |  Page 54  |  Page 55  |  Page 56  |  Page 57  |  Page 58  |  Page 59  |  Page 60  |  Page 61  |  Page 62  |  Page 63  |  Page 64  |  Page 65  |  Page 66  |  Page 67  |  Page 68