The Clinical and Functional Effects of Common Eye Conditions

This paper analyzes the clinical and functional effects of age-related macular degeneration, more commonly known as ARMD and cataracts.

Age-related Macular Degeneration

More than a quarter of Americans aged 75 or above have some signs of ARMD, and 6%-8% are in the advanced stages associated with severe vision loss, although no one goes completely blind from macular degeneration. Early warning signs include difficulty reading and driving; an increased reliance on very bright light; and, most distinctively, a blurry spot in the middle of the field of vision, which may gradually expand. One sign of a more serious form of the disease is that straight lines like door edges become distorted and look wavy.(Delcourt, 12-17)

Women get macular degeneration more often than men, and whites are more vulnerable than African and Mexican Americans. The disease runs in families, and at least six genes related to it have been identified. But so far, no single gene seems to be primarily responsible. It's not clear whether high blood pressure is a risk factor, but it may increase the risk of developing symptoms in the second eye if one is already affected. Eye color may be important: an Australian study found that people with blue eyes had a 70% greater risk for some forms of macular degeneration. The theory is that blue eyes, and perhaps light-colored eyes in general, have less of the pigment melanin, which protects retinal tissue against the damage caused by light. But other studies haven't found a connection to eye color, so there's still doubt about how important it is.(Anshel, 22-28)

Unfortunately, there aren’t many foolproof prevention tips, but the only certain precautionary measure is to not smoke. Smoking is a proven risk factor that predisposes one to macular degeneration and which can be controlled by people. The results of the many diet and vitamin studies have stirred up more questions than answers.(Delcourt, 12-17)

Doctors don't have a definitive treatment for macular degeneration, and there's no cure that restores vision. Macular degeneration is one of the great unsolved problems of ophthalmology, and both private companies and the federal government are pouring money into research.

Supplementing the body with vitamins and minerals might help in the condition being slowed down. One should also talk to his doctor about whether it's okay to take a standard multivitamin in addition to other supplements as the synchronistic effect may not be as imagined.

Drusen are small yellowish deposits that collect under the macula. Experts disagree about whether they make macular degeneration worse or are an innocuous by-product. For a while, many ophthalmologists were using lasers to remove drusen, but the practice has fallen out of favor because the clinical trial results have been mixed. Some studies even suggested that the treatments were doing more harm than good. A National Eye Institute-sponsored trial of one kind of prophylactic laser surgery is in its fourth year now -- a clue that the results are neither overwhelmingly positive nor negative. (Anshel, 22-28)

Laser therapy is the corecure for wet macular degeneration, the gravest form of the infection, which is resulted by unusual blood vessels at the back the eye. But traditional laser therapy is only moderately effective and may harm other tissue. This collateral damage leaves some patients with a dark, blind spot in the middle of their vision. Photodynamic therapy, which has been billed as a major improvement, involves the injection of photosensitive dye and a special "cool laser" that activates the dye so it shrinks and plugs leaky blood vessels. The advantage of this technique is that it homes in on the blood vessels and doesn't harm other tissues. But it requires repeat treatments, is expensive, and may not be covered by Medicare, depending on the type of macular degeneration. It seems to be most effective in the minority of wet macular degeneration patients who have well-defined, so-called "classic" lesions instead of the more common "occult" variety. (Gormley, 78-89)

Anti-angiogenic drugs may be the next major development in the treatment of wet macular degeneration. Angiogenesis is the growth of blood vessels; anti-angiogenic drugs cripple the molecules that stimulate that growth. Researchers are testing half a dozen different anti-angiogenic compounds for wet macular degeneration. Two are in the final trials necessary for FDA approval: Macugen, made by EyeTech Pharmaceuticals, and rhuFab V2, made by Genentech. The results of the Macugen trial may be announced later this year.

Many of the new treatments for wet macular degeneration are designed to prune back these overgrown blood vessels and keep them from leaking. (Richer, 12-49)

Cataracts

Much plausible aetiology for cataract have been suggested by epidemiological and laboratory studies. Aetiological classification of cataract is the most useful system to understand the effect of various cataractogenic stressors on the lens and the identification of target molecules in the lens for which potential treatment strategies can be developed. Cataract can be broadly separated into categories such as: age-related, malnutrition with reduced dietary intake of antioxidant, radiation (ultraviolet-B [UV-B]) exposure, diabetes, severe dehydration and side-effect of therapeutic drugs such as steroids. This is by no means an exhaustive list and many causes of cataract remain unknown. Public health strategies to prevent cataract may be possible in developing countries where it is found to be associated with severe dehydration resulting from cholera-related diarrhea or poor nutrition. (Vitale, 195-203)

The scope for further prevention in developed countries, however, is limited because most of the risk factors are intractable, with the exception of reducing radiation exposure and possibly the stopping of smoking. Anti-cataract drugs are therefore an alternative option in prevention of cataract.

Due to age related cataract, the lens crystalline have little biochemical turnover and are vulnerable to chemical modification from a number of insults. These post-translational modifications, which cause the crystalline to unfold and expose reactive groups such as thiols, have been found to be induced by the Maillard reaction. (Gormley, 78-89)

Maillard reactions are nonenzymatic modification of amino acids by reaction with sugars, cyanate and steroids. The unfolded crystalline are susceptible to oxidative damage characterized by the linkage of polypeptide chains through disulphide bonds and formation of high molecular weight, water-insoluble aggregates. The latter accounts for the increased scattering of light resulting in opacity and a cataractous lens. Absorption of UV radiation and subsequent chemical reactions give rise to oxidizing agents such as superoxide, hydroxyl radicals, hydrogen peroxide and singlet oxygen from photo-ionization of crystalline or bound chromophore groups. In addition to oxidizing crystalline in the nucleus of the lens these oxidants also destroy membrane integrity leading to osmotic imbalance and formation of cortical cataract. The role of oxidizing agents is supported by experimental findings. (Richer, 12-49)

The lens is, however, highly adapted to withstand oxidative stress with natural antioxidants that act as scavenger molecules in mopping up oxidizing agents. Glutathione is synthesized in the lens.

In its reduced state, glutathione protects the thiol groups on lens crystalline thereby preventing the formation of protein aggregates through disulphide bonding.

Lens membrane contains vitamin E that protects against lipid peroxidation (LPO). Vitamin C, a powerful reducing agent, is accumulated in the lens by an active transport system. It together with glutathione scavenges carboncentred radicals. The lens also has detoxification enzymes such as catalase and glutathione peroxidase as well as superoxide dismutase that protect against damaging effects of hydrogen peroxide and superoxide radicals, respectively.

Finally, lens crystalline itself has been shown to form functional aggregates that act as a chaperon like protein to maintain transparency by sequestering unfolded lens proteins and inhibiting their subsequent aggregation. (Gormley, 78-89) There is little doubt age-related cataract represents the cumulative effect of a variety of cataractogenic stressors that accelerate natural protein degradation coupled with a reduced efficiency of the lens’ protective mechanisms. The concentration of glutathione reduces with age but more markedly in eyes with cataract. (Richer, 12-49)

The activity of the enzymatic antioxidant systems is also reduced. Therefore replacing the natural antioxidants in the lens may at least in theory increase the ability of the lens to withstand oxidative stress thereby preventing the onset of cataract.