Diet vitamins and lifestyle in AMD prevention

Diet vitamins and lifestyle in AMD prevention

Rachid Chigara

Age-related macular degeneration (AMD), is a degenerative disease that affects the central portion of the retina (macula). It is the most common cause of visual impairment and may lead to loss of central vision or blindness, affecting individuals older than 50 years. In the early stages of AMD, patients may be asymptomatic, however, in its advanced forms the disease may cause serious central vision dysfunction.


The burden of AMD

AMD is the leading cause of blindness in the developed world. The prevalence of AMD increases exponentially with age, affecting less than 1% of the Caucasian population in the sixth decade of life, 10% of subjects after the age of 80, more than 15% of the Population in the ninth decade. {1}
In Algeria, AMD is the 4th cause of blindness according to a survey conducted in 2009 across the national territory, ranked after cataract, glaucoma, and diabetic retinopathy respectively, with a prevalence of around 2.1% of the population aged over 50. {15}

Pathogenesis

The pathophysiology of age-related maculopathy is characterized by degenerative alterations involving the outer retina, pigment epithelium, and Bruch’s membrane. With advancing age, the pigment epithelium cells become less efficient, thus the retina can no longer receive adequate nutrients and waste accumulates, leading to deposits called amorphous drusen. Thus, the cells of the retinal pigment membrane slowly degenerate, resulting in central vision loss. This form of slowly progressive disease is called dry type AMD. Alternatively, if the integrity of the Bruch’s membrane is lost, choroidal neovascular complexes grow in the epithelial and subretinal spaces, in a process called choroidal neovascularization. The new blood vessels are fragile and incompetent, allowing for leakage and bleeding, and therefore leading to edema, which compromises the integrity of the retina, the macula, and the fovea, and progressively impairs visual function. The final result is a dense fibrovascular scar, which can involve the entire macular area. This form of the disease is called exudative or wet type AMD, accounting for 90% of cases of severe vision loss in the elderly.


Risk factors

AMD is a multifactorial and polygenic disease, combining environmental risk factors, lifestyle factors and genetic factors.

Age

Population-based studies have demonstrated that of the risk factors for AMD, age is the first and foremost, in resource-rich countries, showing that AMD affects 1% of the Caucasian population in the sixth decade of life, 10% of subjects after the age of 80, more than 15% of the Population in the ninth decade. {1} 

Smoking 

It is currently the most consensually accepted risk factor, with a dose effect often found in studies. In the EUREYE study, smokers have a risk of developing wet AMD 2.6 (95% CI, 1.4-4.8) and 4.8 (95% CI, 2.1-11.1) for the atrophic form. In the same study, the relative risk of 1.7 for former smokers {2}

Alcohol consumption

A meta-analysis published in 2008, analyzing the results of 5 prospective cohort studies and including 136,946 subjects, shows that alcohol consumption (more than 3 drinks per day) is associated with a relative risk of 1.47 (95% CI, 1.10-1.95) to develop age-related maculopathy. On the other hand some authors say that small doses of alcohol could have a protective role on the macula. It would be logical to think that alcohol can have a protective role in low dose and a toxic effect in high doses, but studies are needed to clarify the impact of alcohol on the disease.

Elevated plasma high density lipoprotein 

Evidence has been found showing that HDL-cholesterol is a causal risk factor for AMD, with an odds ratio estimate of 1.22 per 1 standard deviation increase in HDL-cholesterol. No causal effect of LDL-cholesterol or triglycerides was found. Variants in the Cholesteryl Ester Transfer Protein CETP gene region associated with increased circulating HDL-cholesterol also associate with increased AMD risk, although variants in the Hepatic lipase LIPC gene region that increase circulating HDL-cholesterol have the opposite direction of association with AMD risk. {3} 

Arterial hypertension 

In the Los Angeles Latino Eye Study, diastolic hypertension is associated with a risk of developing 3-fold exudative AMD after matching for age, gender and tobacco status. In addition, an increase in diastolic blood pressure of 10mmHg doubles the risk of exudative AMD. The study also found a significant association between diastolic blood pressure greater than or equal to 85mmHg and confluent serous drusen, with an odds ratio of 1.3. {4} 

Cardiovascular and cerebrovascular 

Accidents among patients with AMD, the cumulative 10-year incidence of coronary artery disease was 30.9% (4 cases / 15) versus 10% (918 cases / 11,399) for those without AMD. After adjusting for age, sex and ethnicity, AMD appears to be significantly associated with the risk of coronary heart disease, with a relative risk of 3. Nevertheless, the limited number of cases with AMD in this study does not allow for further multivariate analysis. In another study of 195 patients with AMD in at least one eye, 97 patients with AMD without neovascularization and 115 patients without serous drusen or pigmented epithelium abnormalities Between cardiovascular disease and AMD, with a relative risk of 7.53. AREDS report 13 also highlights cardiovascular excess mortality in patients with AMD. {5} 

Obesity 

In a cohort of 261 patients over the age of 60 with age-related maculopathy during an average follow-up of 4.6 years, Seddon et al. Show that the risk of disease progression increases with body mass index {6} 

Refractive disorders 

Several studies have found a significant association between hyperopia and AMD. In the AREDS study, a significant association appears between hyperopia and exudative AMD, with an odds ratio of 2.31. In the EDCCS (Eye Disease Case-Control Study), an association between hyperopia and exudative AMD is also established, with an odds ratio of 1.5. The studies NHANES I, Beaver Dam, Framingham and Rotterdam, also establish an association between hyperopia and ARM or AMD.

Exposure to UV rays

In the AREDS study, sunlight appears initially as a risk factor for AMD, but the results are no longer significant using a multivariate analysis model. Similarly, in the POLA study, the relationship between exposure to UV and AMD could not be established. {7} 

Vitamin A 

Various studies conducted in AMD seem to exclude vitamin A as a factor of susceptibility or protective factor. In the Blue Mountains study, a comparison of 159 cases with 1,884 controls does not suggest a significant association. In the AREDS study, a comparison of vitamin A nutrient intakes in 4,519 participants aged 60-80 years, after adjusting for age, gender and energy intakes, does not lead to a significant difference. {8}, {9}

Carotenoids 

Lutein and zeaxanthin are the only carotenoids found in all ocular tissues, with the exception of the cornea, vitreous and sclera, concentrating mainly in the macular area, in Henle's fibre layer and the inner plexiform layer. In the AREDS study, the risk of developing AMD or ARM was inversely associated with dietary intake of lutein and zeaxanthin {10} 

Polyunsaturated fatty acids Omega-3 

A meta-analysis by Chong and al. summarizes the results of major studies published on this topic, including 3 prospective studies, 3 case-control studies and 3 cross-sectional studies . In 4 studies, omega-3 consumption is associated with a lower risk of severe AMD, with an odds ratio of 0.62. In 6 studies, fish consumption was associated with a lower risk of ARM and severe AMD, with an odds ratio of 0.76 and 0.67, respectively.
It should be emphasized that the results of these numerous studies are extremely concordant, demonstrating a protective effect of the consumption of fatty fish or of omega-3 fatty acids. {11} 

Monounsaturated fatty acids, saturated fatty acids and cholesterol 

In addition to the concluded protective effect of omega-3 in exudative AMD, the AREDS report No. 22 shows that high dietary intakes of monounsaturated fatty acids, saturated fatty acids and cholesterol are significantly associated with a risk of exudative AMD with respective odds ratios of 1.80, 1.56 and 1.16 respectively. {12} 

Antioxidants and zinc 

At the observational level, studies show a protective effect of vitamin E and zinc in AMD or a dissociative effect that can be protective for zinc and at risk for vitamin E. In a French study, a protective effect was also found on vitamin E. {13}, {14}


Clinical assessment

There are three stages of AMD defined in part by the size and number of drusen under the retina. It is possible to have AMD in one eye only, or to have one eye with a later stage of AMD than the other. Early AMD is diagnosed by the presence of medium-sized drusen, which are about the width of an average human hair. Patients with early AMD typically do not have vision loss. Patients with Intermediate AMD typically have large drusen, pigment changes in the retina, or both. Again, these changes can only be detected during an eye exam. Intermediate AMD may cause some vision loss, but most people will not experience any symptoms. Late AMD. In addition to drusen, people with late AMD have vision loss from damage to the macula. There are two types of late AMD: In geographic atrophy (also called dry AMD), there is a gradual breakdown of the light-sensitive cells in the macula that convey visual information to the brain, and of the supporting tissue beneath the macula. These changes cause vision loss. In neovascular AMD (also called wet AMD), abnormal blood vessels grow underneath the retina. These vessels can leak fluid and blood, which may lead to swelling and damage of the macula. The damage may be rapid and severe, unlike the more gradual course of geographic atrophy. It is possible to have both geographic atrophy and neovascular AMD in the same eye, and either condition can appear first.

Colour fundus photograph showing soft, confluent, large drusen in a patient with non neovascular (dry) (AMD). Corresponding spectral-domain optical coherence tomography (SD-OCT) image of the soft drusen. Auto fluorescence image of an eye with areas of confluent drusen

Colour fundus photographs of right and left eyes,
demonstrating advanced geographic atrophy

Corresponding auto fluorescent images of
GA in the e patient with atrophic AMD

Treatment and prevention

Early AMD Currently, no treatment exists for early AMD, which in many people shows no symptoms or loss of vision. A comprehensive dilated eye exam is recommended at least once a year. The exam will determine if AMD is advancing. As for prevention, AMD occurs less often in people who exercise, avoid smoking, and eat nutritious foods including green leafy vegetables and fish. Adopting some of these habits may help keep the patients vision longer. Intermediate and late AMD Researchers at the National Eye Institute tested whether taking nutritional supplements could protect against AMD in the Age-Related Eye Disease Studies (AREDS and AREDS2). They found that daily intake of certain high-dose vitamins and minerals can slow progression of the disease in people who have intermediate AMD, and those who have late AMD in one eye. The first AREDS trial showed that a combination of vitamin C, vitamin E, beta-carotene, zinc, and copper can reduce the risk of late AMD by 25 percent. The AREDS2 trial tested whether this formulation could be improved by adding lutein, zeaxanthin or omega-3 fatty acids. The AREDS2 trial found that adding lutein and zeaxanthin or omega-three fatty acids to the original AREDS formulation (with beta-carotene) had no overall effect on the risk of late AMD. However, the trial also found that replacing beta-carotene with a 5-to-1 mixture of lutein and zeaxanthin may help further reduce the risk of late AMD. Moreover, while beta-carotene has been linked to an increased risk of lung cancer in current and former smokers, lutein and zeaxanthin appear to be safe regardless of smoking status. Here are the ingredients based on AREDS and AREDS2 research: 

• 500 milligrams (mg) of vitamin C.
• 400 international units of vitamin E.
• 80 mg zinc as zinc oxide.
• 2 mg copper as cupric oxide.
• 10 mg lutein and 2 mg zeaxanthin.

In intermediate or late AMD, might benefit from taking supplements containing these ingredients. Many supplements have different ingredients, or different doses, from those tested in the AREDS trials. Therefore choosing the appropriate supplement is necessary. Some recent studies have claimed that, depending on genotype, some patients will benefit from AREDS supplements and others could be harmed. These claims are based on a portion of data from the AREDS research. The US NEI investigators have done comprehensive analyses of the complete AREDS data. Their findings to date indicate that AREDS supplements are beneficial for patients of all tested genotypes. Based on the overall data, the American Academy of Ophthalmology does not support the use of genetic testing to guide treatment for AMD. The AREDS formulation is not a cure. It does not help people with early AMD, and will not restore vision already lost from AMD. But it may delay the onset of late AMD. It also may help slow vision loss in people who already have late AMD. Advanced neovascular AMD Neovascular AMD typically results in severe vision loss. Different therapies such as intravitreal anti-VEGF injections, dynamic phototherapy and laser procedures are used to stop further vision loss, and in some cases visual acuity was improved in a significant number of cases.

Multiple recent studies, particularly AREDS, allowed better understanding of possible links between diet and lifestyle factors that potentially influence the onset of AMD, thus allowing better prevention. (An ounce of prevention is worth a pound of cure)-B.F.

References 

{1} (Lee P.P., Feldman Z.W., Ostermann J., Brown D.S., Sloan F.A. Longitudinal prevalence of major eye diseases Arch Ophthalmol 2003 ; 121 : 1303-1310).
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{3} (Mendelian Randomization Implicates High-Density Lipoprotein Cholesterol–Associated Mechanisms in etiology of Age-Related Macular Degeneration Stephen Burgess, George Davey Smith, MD, DSc Manuscript no. 2016-1021).
{4} (Klein R., Deng Y., Klein B.E., Hyman L., Seddon J., Frank R.N., and al. Cardiovascular disease, its risk factors and treatment, and age-related macular degeneration: Women’s Health Initiative Sight Exam ancillary study Am J Ophthalmol 2007 ; 143 : 473-483.
{5} (Clemons TE, Kurinij N, Sperduto RD; AREDS Research Group. Associations of mortality with ocular disorders and an intervention of high-dose antioxidants and zinc in the Age-Related Eye Disease Study: AREDS Report No. 13. Arch Ophthalmol 2004; 122:716–26).
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{12} (Age-Related Eye Disease Study Research Group, SanGiovanni JP, Chew EY, Clemons TE, Ferris FL 3rd, Gensler G, et al. The relationship of dietary carotenoid and vitamin A, E, and C intake with age-related macular degeneration in a case-control study: AREDS Report No. 22. Arch Ophthalmol 2007; 125:1225–32).

{13} (Van Leeuwen R., Boekhoorn S., Vingerling J.R., Witteman J.C., Klaver C.C., Hofman A., and al. Dietary intake of antioxidants and risk of age-related macular degeneration JAMA 2005 ; 294 : 3101-3107).
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{15} (AALC) ASSOCIATION ALGERIENNE DE LUTTE CONTRE LA CECITE.