AGE-RELATED CATARACT: MANAGEMENT AND PREVENTION
2. UNDERSTANDING CATARACT
Cataract (word derived from Greek language, meaning waterfall (Johns et al.,2002;
Floyd, 2000)) is the name given to any opacity in the lens, not necessarily with any effect on vision. This definition may be extended to include opacity of the lens capsule and the deposition of material of non-lenticular origin (viz. True exfoliation in glass blowers, pseudoexfoliation, chalcosis of lens in Wilson’s disease, siderosis, argyrosis, gold deposits, mercury salts, etc) (Brown,1999).
AGE-RELATED CATARACT: MANAGEMENT AND PREVENTION 161 Understanding the normal physiology and biochemistry of the lens and the changes that induce cataract formation continues to be an area of active research today. Though some possible risk factors for cataract development have been suggested, there is no confirmed method to prevent cataract formation so far.
Cataracts can be caused by a variety of problems, including developmental abnor- malities, trauma, metabolic and drug induced changes (Brown,1999). The main cause of visually significant cataracts is aging, i.e., age-related (senile) cataracts is the focus of this chapter.
Until recently, there has been little need to accurately classify cataract type or severity. Traditionally, clinicians have used anatomical (cortical, nuclear, and posterior subcapsular (PSC)) or etiological (radiation, steroid, and so forth) terms to describe the type of cataract. Descriptors of cataract severity have been base on coarse, subjective scales and have included terms such as immature, advanced immature, and mature. As basic scientists developed means of identifying and quantitating mechanisms of human cataract formation, it became necessary to more accurately and consistently describe or classify cataracts. Also, as pharmaceutical companies encountered drugs with cataractogenic toxicity, and as epidemiologists began to study the risk factors of human cataract formation, better systems of cataract classification were needed. Several have been developed and they include the Lens Opacities Classification System, Versions I to III (LOCS I to III), the Oxford Cataract Classification System, the Wilmer System, and the Wisconsin System.
A number of epidemiological studies have linked UV exposure with the formation of cortical cataract, for the wavelengths UVB (280–315 nm) and UVA (315–400 nm). The preponderance of cortical cataract in the inferonasal quadrant, where levels of solar radiation are said to be highest, has also been offered as indirect evidence of an association between exposure to sunlight and cortical cataract (Schein et al.,1994;Graziosi et al.,1996).
Few studies have consistently demonstrated exposure to UVB light as a risk factor for cortical and perhaps PSC cataract (Bochow et al., 1989; West et al., 1998; Munoz et al., 1993). Calculations of attributable risk based on such work suggest that ocular UVB exposure may explain approximately 10% of the cortical cataract in some populations (VanNewkirk et al.,2002). These calculations and the relatively mild impact of cortical opacity on visual function, suggest that the effect of strategies involving reduced exposure to sunlight, even if practical, might be limited.
The hypothesis that antioxidants nutrients in the serum, lens and aqueous might be protective against lens opacity has attracted much attention. This is, in part, because of the appeal of supplementation as a practical anti-cataract surgery, an approach that has been highly successful in other disorders, as with fluoridated water (Van der Haar, 1997), iodized salt (Krause et al., 1998) and vitamin A (Christen,1999). However, epidemiological evidence for the antioxidant hypothesis among human subject has been conflicting (Taylor et al.,1995;Bunce et al.,1990;
Congdon and West Jr,1999; Sperduto et al., 1993). Until recently, the majority
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of studies of antioxidants and lens opacity have been observational, cross–sectional and uncontrolled in design, making it difficult to establish a clear role for any particular agent, and impossible to account for important confounders such as socio-economic status.
Recent controlled trials have largely obviated such concerns, and have cast significant doubt on the role of antioxidants in protecting against lens opacity in nutritionally replete populations. The Linxian Cataract Trial identified a limited protective role against nuclear cataracts among older persons receiving riboflavin and niacin. However, retinal, zinc, ascorbic acid, molybdenum, selenium, a-tocopherol and B-carotene were not protective, and this rural Chinese population appears to have been nutritionally deficient in many ways (Robman et al.,1999).
The Vitamin E, Cataract and Age–related Maculopathy study in Australia (AREDS, 2001) and Age–Related Eye Disease Study (Manson et al.,1995) in the US have recently failed to demonstrate any beneficial effect on the progression of lens opacity of giving well nourished persons vitamin E alone, or in a combination of A, C and E (with or without zinc), respectively. Additional prospective studies, which may be expected to offer insight into this question, include the Women’s Antioxidant Cardiovascular study (Leske et al., 1999), the Women’s Health Study (McCarty et al., 1999) and the Physicians’ Health Study II. (Christen, 1999). However, at present, nutritional supplementation is not indicated as an anti-cataract strategy for well nourished populations in the developed world, although a possible role in undernourished populations in the developing world cannot be ruled out.
A set of potentially interrelated personal factors-diabetes, hypertension and body mass index (BMI) –has been implicated as representing an increasing risk for various forms of lens opacity. Diabetes has consistently been associated with increased risk for cortical cataract (Leske et al., 1999; McCarty et al., 1999; Klein et al., 1995), and variably for PSC (Leske et al.,1999; Klein et al.,1995) and nuclear opacities (McCarty et al.,1999). Body mass Index (BMI) has been identified as an independent risk factor for PSC and nuclear cataract (Caulfield et al., 1999;
Glynn et al.,1995), and also cortical opacity (Hiller et al.,1998), when controlling for diabetes, age and smoking. Hypertension has also been associated with cortical cataract (Leske et al.,1999). While all of these factors are potentially remediable, suggesting possible avenues for cataract prevention, the effectiveness of such strategies remains to be proven. Although there is some evidence that better diabetic control (demonstrated by lower hemoglobin AI c levels) may reduce the risk of lens opacity (Klein et al.,1998), no controlled, prospective data yet exist to demonstrate that improved treatment of diabetes or hypertension will in fact prevent or delay lens opacity. An added difficulty of intervening on BMI to prevent cataract is that the directionality of the association (e.g. whether elevated or reduced BMI, or both, contributes to lens opacity) has not been definitively established.
Female gender has generally been associated with an increased age-adjusted risk of both nuclear cataract (AREDS,2001) and cortical cataract (Mitchell et al.,1997) among all races studied, including persons of African (Congdon et al.,2001;Leske et al.,2000), Asian (Cheng et al., 2000) and European (Cumming and Mitchell,
AGE-RELATED CATARACT: MANAGEMENT AND PREVENTION 163 1997) descent. Although gender as a risk factor is clearly not subject to alteration, some studies suggests that post-menopausal use of estrogen may be associated with reduced risk of nuclear cataract (Cumming and Mitchell,1997). However, other studies have been unable to confirm this finding (McCarty et al.,1999).
Risk factors of importance in certain subpopulations include ocular conditions, such as uveitis and retinitis pigmentosa, both thought to be associated with PSC opacities, perhaps because of breakdown of the blood-ocular barrier and subsequent entry of cataractogenic factors into the eye. Ocular surgery is also an important risk factor, especially trabeculectomy (Klein et al., 1995; Collaborative Normal- Tension Glaucoma Study Group,1998) and retinal surgery (Wong et al.,2002). It has been suggested that surgically created alternative pathways for the drainage of aqueous from the eye may deprive the lens of aqueous-borne nutrients necessary to preserve normal clarity. A dose dependent association (measured both in terms of concentration and length application) between age-related cataract and mitomycin C, an anti-metabolite used regularly in glaucoma surgery, has also been established in a trial setting (Ramkrishnan et al.,1993). Ocular trauma can clearly be associated with lens opacity in certain individuals, although studies suggest that the impact on the prevalence in the population of lens opacity is probably minimal (Wong et al., 2002). Finally, periocular irradiation with gamma rays (Chen et al., 2001) and proton beams (Brovkina and Zarubei, 1986) can be associated with various forms of lens opacity. These smaller, well-defined subpopulations with a relatively high risk of rapid-onset cataract could ultimately serve as ideal subjects for trials of anti-cataract medications, although the relevance of the findings of such studies to age-related cataract would be unknown.
Finally, there are number of other risk factors for lens opacity which are either poorly understood, or, although they may be of importance for certain groups, do not represent a significant risk for the population as a whole. Several studies (Wong et al.,2001;Lim et al.,1999) have suggested that refractive errors, typically myopia, are associated with age-related cataract, particularly nuclear cataract and PSC (Lim et al.,1999; Wu et al.,1999;Vasavada et al., 2004). It is well known that increased refractive index of the lens in advanced nuclear cataract may cause a secondary myopia; pre-existing myopia may also serve as an independent risk factor (Lim et al.,1999). The mechanism for such as association, if indeed it exists, is not understood.
3. OXIDATION OF LENS MATERIAL AND CATARACT