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EPIDEMIOLOGY OF AGE-RELATED MACULOPATHY
PRAVEEN K NIRMALAN, R KIM, V NARENDRAN, P NAMPERUMALSAMY
Aravind Eye Care System, Madurai 625020, Tamil Nadu, India
INTRODUCTION
Epidemiological studies looking at age related maculopathy (ARM) have mostly been in industrialized nations and among Caucasian populations.[1-8] ARM is a leading cause of blindness in developed nations;[1-8] however, there have not been many studies looking at the epidemiology of this disease in India. Age-related macular degeneration may emerge a public health problem in India as life expectancies increase. This article will review current epidemiological knowledge on the prevalence and risk factors for ARM.
DEFINITION
The International ARM Epidemiological Study group[9] has developed a classification system for ARM. This system basically classifies ARM as early and late ARM (AMD).
Early ARM
-Drusen: Drusen are defined as discrete whitish yellowish spots external to the neuroretina or the retinal pigment epithelium (RPE). They may be soft and confluent, with indistinct borders. Soft distinct drusen have uniform density with sharp edges, soft indistinct drusen have decreasing density from centre outwards with fuzzy edges. Isolated hard drusen in the absence of any other features outlined above do not characterize ARM.
-Areas of increased pigmentation or hyperpigmentation in the outer retina or choroid associated with drusen.
-Areas of depigmentation or hypopigmentation of the RPE, most often more sharply demarcated than drusen, without any visibility of choroidal vessels associated with drusen.
Late ARM or AMD
This includes both "dry" and "wet" AMD.
Dry AMD : Otherwise known as geographic atrophy, is characterized by-Any sharply delineated roughly round or oval area of hyperpigmentation or depigmentation or apparent absence of the RPE in which choroidal vessels are more visible than in surrounding areas that must be at least 175 mm in diameter.
Wet AMD : Otherwise known as neovascular AMD or exudative AMD is characterized by one of the following
-RPE detachments that may be associated with neurosensory retinal detachment, associated with other forms of ARM.
-Sub retinal or Sub RPE neovascular membranes.
-Epiretinal, intraretinal, sub retinal, or sub pigment epithelial scar/glial tissue or fibrin-like deposits.
-Sub retinal haemorrhages that may be nerly black, bright red, or whitish-yellow and that are not related to other retinal vascular disease.
-Hard exudates (lipids) within the macular area related to any of the above, and not related to any other retinal vascular disease.
MAGNITUDE
Epidemiological data on the prevalence of ARM is largely confined to Caucasian populations. There is not much population-based data on the prevalence of ARM from India. We found the population-based age-adjusted (adjusted to the US population of 2000) prevalence of ARM to be 3.8% (95% CI: 3.28, 4.32) in a rural southern Indian population aged 50 years (unpublished data).
The prevalence of ARM detected by grading of retinal photographs with the definition of the disease being independent of visual acuity ranges from 0-10% at age 50 to almost 100% at age 90. The Blue Mountains study in Australia[10] found significantly lower age-adjusted rates of soft drusen and retinal pigment abnormalities compared with Beaver Dam study;[4] the rates of AMD was also lower, though not statistically significant. The prevalence decreased if a visual acuity cutoff was included in the definition of the disease; the prevalence ranged from < 10% among those aged 50-59 years to between 20-50% among those aged 85 years. Severe ARM (AMD) is less common than early ARM, approximately 10% of those aged > 75 years may have severe ARM.
There are regional differences in the prevalence reported from different countries - these differences may be due to differences in the application of the grading scheme between centres, or may be even a true difference. Photographic grading in the presence of lenticular or corneal opacities is not easy and may influence the classification of ARM. The difficulty in grading is illustrated by the results reported from a 5 year follow-up of the cohort studied in the Chesapeake bay Study.[11] Nearly 30% of the cases identified as early ARM at baseline had recovered. Almost half of these ‘recovered’ cases were among those who were considered borderline ARM at baseline. Observer variation studies for the grading systems have reported kappa values of between 0.45 and 0.85 for the different lesions, suggesting considerable misclassification is possible, especially among the early lesions.
RISK FACTORS
Gender : Evidence linking gender, as a risk factor for ARM is inconclusive. Although the Rotterdam study[12] found no evidence of increased risk among either gender, the Blue Mountains Eye Study[10] in Australia found an increased prevalence among women-this difference, however, was not statistically significant. NHANES-III reported a significant increase of risk for ARM among females (age-race adjusted odds ratio 1.4; 95% CI:1.1, 1.8). The Beaver Dam study[4] reported an increased risk of exudative disease among females (6.7% compared to 2.6% for males). The Barbados Study[7] reported females having significantly small drusen, but no other sign of ARM.
Education : In contrast to cataract, ARM has not been found to have an association with education.[4]
Race : The prevalence belief is that ARM is less common among pigmented populations. The Baltimore Eye Survey[8] reported that although the Black population had twice the age-adjusted rates of legal blindness, the rates of bilateral blindness due to AMD was much lower compared to whites (0:30%). The Barbados study[7] reported rates of early ARM similar to white populations elsewhere, although the rates of neovascular disease was much lower.
Blood Pressure : Recent large cross sectional[13] and case-control studies[14] have not found an association between blood pressure and ARM.
Atherosclerosis : The Rotterdam study[15] reported an increased risk for AMD among people with evidence of atherosclerosis. In subjects aged < 85 years, plaques in the carotid bifurcation was associated with a 4.7 times increased risk of AMD, and plaques in the common carotid artery wereassociated with a 2.5 times increased risk for AMD. The risk of AMD was 2.5 among those with lower extremity diseases. However, further studies in different populations are required to explore this association.
Blood Lipids : The Eye Disease Case Control Study[14] found an increased risk of neovascular AMD with increasing levels of total cholesterol, however, the Beaver Dam [13] study did not show an association between AMD and serum cholesterol levels. The POLA[16] study reported recently increased odds ratios with HDL-cholesterol (1.52, 95% CI: 1.14, 2.02).
Cardiovascular diseases : The evidence linking cardiovascular disease with ARM is again inconclusive. Although a study by Hyman et al reported a relative risk of 1.7 (95% CI:1.1, 2.7) of ARM associated with a history of one or more cardiovascular diseases, the Eye Disease Case Control Study[14] and the Beaver Dam Study[13] did not show any association between cardiovascular disease and ARM.
Solar Radiation : The evidence for an association between solar radiation and AMD is inconclusive - a case control study[14] reported no association, while the Beaver Dam Study[13] leisure time spent outdoors to be associated with increased retinal pigment and increased neovascular AMD.
Ocular pigmentation : There is no strong evidence linking the levels of ocular pigmentation to ARM, the Eye Disease Case Control study[14] did not find any association between iris colour and neovascular AMD.
Antioxidants : It has been proposed that antioxidants may have a role to play in preventing cellular damage to the retina by acting as singlet oxygen and free radical scavengers. A recent report from AREDS[17] suggested that a combination of anti-oxidants and Zinc might be beneficial in subjects with ARM. The Eye Disease Case Control Study[14] found high and medium levels of most serum carotenoids - namely lutein/zeaxanthin, æ and ß-carotene, cryptoxanthin - were associated with a reduced risk of neovascular AMD. This study, however, did not find lycopene to be protective. In contrast the Beaver Dam study[13] found lycopene to be protective, although other antioxidants were not.
Smoking : Smoking may have direct effects on the choroidal circulation supplying blood to the retina and can also have an effect on the blood plasma levels of antioxidant micronutrients. The Eye Disease Case Control Study[14] reported an odds ratio 1.5 of neovascular disease among former smokers and 2.2 among current smokers, compared to non-smokers. However, the Beaver Dam study[18] did not find an association between smoking and early ARM and geographic atrophy, although there was an association between smoking and neovascular AMD.
Oestrogens : The Eye Disease Case Control Study[14] reported a lower risk of neovascular AMD (odds ratio 0.3, 95% CI : 0.1, 0.8) with the use of post-menopausal exogenous oestrogens while the Rotterdam study[19] reported a two-fold risk of AMD in women who had their menopause before the age of 45 years. However, the Beaver Dam study[20] did not find any significant association between oestrogen replacement or hysterectomy and AMD.
Genetic factors : It has been reported that siblings of an affected person have nearly a 20 times higher risk of developing the disease compared to the general population.[21] Segregation analysis of the siblings in the Beaver Dam study found results consistent with a major gene effect accounting for 62% and 59% of the expression of ARM in the right and left eyes.[22]
A better understanding of the risk factors may help develop preventive strategies. However, there is not much conclusive evidence regarding risk factors for AMD. Besides aging, the greatest risk is associated with sharing genetic material with an affected sibling. However, the susceptibility loci are yet to be identified.
Modifiable risk factors based on current knowledge can include cessation of smoking, reducing exposure to intense light, increasing dietary and plasma levels of antioxidants, and exogenous oestrogens for post-menopausal women. Further Research
1. Prevalence and incidence studies are required, using standardized definitions as set out by the International ARM Epidemiological Study Group.
2. Case-Control Studies to identify the risk factors for ARM and AMD in India, as well as the progression of ARM to AMD.
3. Randomized controlled trials looking at the utility of antioxidant supplementation in the Indian subcontinent.
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