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*Department of Ophthalmology, PGIMER, Chandigarh; **Department of Ophthalmology, Government Medical College, Chandigarh.
ARMD is one of the important causes of severe visual loss in the elderly population. This review article discusses the numerous risk factors associated with ARMD and stresses the need for a population based multicentric study to estimate the true prevalence and risk factors of ARMD in India.

Age related macular degeneration (ARMD) is one of the leading causes of visual impairment in individuals more than 50 years of age in developed countries[1,2]. It is the major challenge in the new millennium in the developing countries also, as the size of elderly population continues to rise due to betterment of medical facilities and increased life expectancy.[3] ARMD was found to be second only to cataract as the cause of severe visual loss even in Asian countries.[4] ARMD is associated with depressive disorder in addition to visual disability. In a recent series, 32.5% of ARMD patients were found to suffer from depressive disorders in addition to visual disability.[5] To prevent the age related macular changes and to enhance functioning of this segment of population, the knowledge of epidemiology and risk factors for ARMD is important.

There is no universally accepted definition of ARMD. Age-related Eye Disease Study categorized ARMD into 5 groups (Table 1).[6]

Classification of ARMD (age-related eye disease study
Category Clinical features
Category 1 No drusen or non-extensive small drusen only in both eyes
Category 2 Extensive small drusen, non-extensive intermediate drusen, or pigment abnormalities in atleast one eye
Category 3 Large drusens, extensive intermediate drusens, or noncentral geographical atrophy in atleast one eye
Category 4 Geographical atrophy in atleast one eye
Category 5 (Neovascular) evidence suggesting CNVM or RPE detachment, (serous/haemorrhagic) in one eye

However, some investigators reserve the diagnosis of ARMD only to those eyes in which the clinical picture of drusens, geographical atrophy or choroidal neovascularisation are associated with some degree of visual loss in individuals over 50 years of age.[7] In Asian population, ARMD usually presents as occult choroidal neovascularisation (CNV) in 19%, serous pigment epithelial detachment (PED) in 31%, PED with CNV in 19%, drusens in 19%.[8]

The prevalence of ARMD varies from 1.2% to 29.3%.[9,10] Three population based studies-the Beaver Dam Eye Study,[11] Blue Mountain Eye Study[12] and the Rotterdam Study[13] report the prevalence rates to be 1.7% in US, 1.4% in Australia and 1.2% in Netherland respectively. Earlier studies reported ARMD to be unusual in coloured races, but now it is well established that it is not so infrequent in these races and the prevalence varies from 1.1% in South India[14] to 17.4% in Africa.[15] Another study from North India reports the prevalence rate to be 4.7%.[16] In China the incidence in a observational series was 5.88% and that for per for persons more than 65 years was 16.83%.[17]

The Health and Nutrition Survey (HANES) reported equal incidence of ARMD in whites and blacks.[18] However in some series the prevalence of exudative form is significantly higher in whites than blacks. Light iris is also associated with a higher incidence.[19] Melanin is thought to be protective against ARMD as it absorbs light.

The prevalence of ARMD is strongly age related. The prevalence increases from 1.6% in 52-64 years to 11% in 65-74 years and 27.9% in more than 74 years.[2] The findings are applicable to all races and geographical areas and are confirmed in a recent study of pooled in data from 3 continents. The prevalence varied from 0.2% of the combined population aged 55-64 years, rising to 13% in the population older than 85 years.[20] The prevalence of neovascular ARMD increased from 0.17% amongst subjects aged 55-64 years to 5.8% for those older than 85 years.[20] The median age for the disease in Asians is 73 years.[8]

Apart from age the other non-modifiable personal risk factors for ARMD include short height, vital capacity, hyperopia, body mass index (BMI).[6,21,23]

Hyperopia was the most significant risk factor for ARMD in a study from North India.[14] In addition, they also reported higher incidence of ARMD in individuals with peripheral cataracts than central cataracts. Central cataracts could have a protective influence on ARMD by cutting the solar rays reaching the macula.

Body mass index of men has also been related to incidence of visually significant ARMD. However the relationship between BMI and dry ARMD is J-shaped. The obese and the leanest individuals are at a higher risk of ARMD.[23] Obesity is related to high level of oxidative stress. Dietary deficiencies are speculated to be the cause of ARMD in lean men. In females however, waist to hip ratio as compared to BMI is more significantly associated with risk of developing ARMD.[24]

The present and past history of systemic diseases like cardiovascular disease, hypertension, arteriosclerosis and lung infection was also associated with higher degree of ARMD.[25,26]

The Beaver Dam Study showed trends of association of hyperglycaemia to exudative ARMD in men.[26] Recently POLA study demonstrated the risk of drusens is less in subjects with CVS disease and increases with the increase in high density lipoproteins (HDL) cholesterol.[25] Hypertension and also intake of angiotensin converting enzyme-inhibitors (ACE-inhibitors) is associated with higher risk of ARMD.[6,7] Other drugs linked to ARMD include thyroid hormones, antacids and hydrochlorothiazide.[6]

Interestingly the less education, the type of work and the lower socio economic status were independently associated with increased risk of early ARMD.[27] White-collar jobs are at a lower risk of developing ARMD. Education may be a marker for unknown life long exposures not as yet directly studied. In Asian population, highest incidence of ARMD is seen amongst miners (7.98%), followed by peasants (7.33%), factory workers (4.94%) and office cadres (2.78%).[17]

Amongst the environmental factors sunlight exposure is the single important risk factor for ARMD. More than 2 lac hours of sunlight exposure are found to be associated with increased risk of ARMD.[28] Short wavelengths are more damaging than the long ones as higher energy photons are more damaging to retina.[29] High energy visible and ultraviolet photons produce damage by photochemical mechanism. The lesion is exacerbated by oxygen, which initiates free-radical chain reaction. Melanin and cataractous lens have protective influence on retina.[14,29] However, latest report of Beaver Dam Study shows no association of ARMD with Ultra violet-B radiation though sunlight exposure may have bearing on ARMD.[30] Only borderline protection is achieved with sun-glasses and hats.

Amongst modifiable risk factors, diet and smoking are important risk factors. Smoking is one of the most consistently documented modifiable risk factor by majority of workers. Strong history of smoking was present in 26.8% of all ARMD cases in a recent study from New Zealand.[31] In pooled data from Europe, America, Australia history of smoking was present and it emerged as the most important preventable cause of ARMD.[20] The damage could be directly through oxidative stress, indirectly by promotion of atherosclerosis, or by decreasing macular pigment density. ARMD is found to be associated with the duration of smoking and not amount of smoking.[20] Alcohol intake is also an important potential risk factor and the mechanism of damage is oxidative damage.[20]

Dietary habits also have controversial role in ARMD. Diet high in omega 3 fatty acids and fish is found to be inversely associated with the risk of ARMD when the intake of linoleic acid is low.[32] Specific types of fats like vegetables, monounsaturated and polyunsaturated fats and linoleic acid may increase risk of ARMD. Large population based studies, have not shown any relationship of intake of coffee and caffeine and zinc to ARMD.[33,34]

Recently genetic makeup of man has been associated to the development of the disease. Beaver Dam Study found that family history was strongly positive in ARMD and was a definitive predictor of the disease.[35] Risk of the disease is 3 fold in D2177N carriers and 5 fold in 91961E carriers.[36] Many studies however show no association of allelic variation of ABCR and ARMD prevalence. ApoE gene polymorphism is significantly associated with risk of ARMD. The lower frequency of epsilon 4 allele in ARMD patients suggest that apoE gene plays protective role in ARMD. However some studies disapprove of it being the major risk factor.[37]

In summary, ARMD is one of the important causes of severe visual loss in elderly population even in coloured races. ARMD has been associated with numerous risk factors, several of which are modifiable. Severe visual loss can be prevented in some cases by public education and modification of the risk factors like dietary habits, environmental factors and cigarette smoking. The risk factors are essentially the same in Asia and Western countries. However, the prevalence of ARMD from a population based study is not known from India. Further prospective and multicentric study is needed to estimate the true prevalence and risk factors of ARMD in India.


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