An important cause of visual impairment in the elderly, often leading to legal blindness within five years after onset, is senile macular degeneration or age-related macular degeneration (ARMD or AMD) (7-10,107,108). The disease accounts for nearly half of the registered (legal) cases of blindness in the United States and England. The incidence of ARMD increases with increasing age, from about 4% in the 66 to 74 years age group, to 17% in the 75 to 84 years age group, and 22% in the >84 years age group.
The macula lutea is an area of retina 6 mm in diameter that is located at the posterior end of the eye's visual axis (Fig. 2B). Through its high density of cones and involvement in day and color vision, the macula, and in particular its central zone, the fovea, provides the structural basis for high visual acuity. Hence, macular degeneration, more than any other eye disease, affects visual acuity and central vision. This disease occurs generally in both eyes and more often (50%) in women. It is believed to be a hereditary disorder, not caused by simple aging of the retinal nerve cells, but largely related to manifestation of inherited pathologies in the nonneural retinal elements such as the pigment epithelium. The patients also show an increased incidence of hyperopia (farsightedness). The disease may result from disturbances in the walls of subretinal capillaries or in the thickness of subretinal membrane or the RPE (7-12). For a recent review of the pathogenesis of ARMD, see Ref. 109.
BOX 1 Options Available for Visual Corrections After Removal of Cataractous Lens
1. Eyeglasses: These are thick and heavy, and increase object size by 25%; they induce optical distortions and interfere with peripheral vision; although they provide good central vision, they cannot be used after surgery, if the other eye is normal.
2. Contact lenses: Hard or soft extended-wear contact lenses have been used; they are more difficult to use, and eyeglasses are required for reading; however, they correct central and peripheral vision, increase image size by only 6%, and can be used after surgery on one or both eyes.
3. Intraocular implant lens: This is surgically placed in front of or behind the iris at the time of cataract surgery; it requires the use of bifocal eyeglasses and has a higher incidence of surgical and postsurgical complications; however, it increases image size by only 1%, corrects central and peripheral vision, and can be used on one or both eyes; lens implants are made of silicone, acrylic, or hydrogel materials; the lens implants are placed either in front of the iris (intracapsular) or behind the iris (extracapsular).
4. Refractive keratoplasty. In this method, the cornea is cut and reshaped by making surgical or laser incisions; this method has become effective and popular in recent years in correcting forfar-and near-sightedness and astigmatism, but its applications for correcting for presbyopia or cataract are still in the experimental stage. Recently, newer methods have been developed, namely penetrating keratoplasty (PK) and deep lamellar keratoplasty (DLK). DLK is a better surgical choice because it involves less endothelial cell rejection and offers better-corrected visual acuity (BCVA); it is also safer in the short term and long term (90,91).
Recent Biochemical and Pathological Findings in ARMD
Tissue inhibitors of metalloproteinases (TIMP-3) have been implicated in aging and in ARMD. TIMP-3 levels in Bruch's membrane in macula increase with age, and these levels are higher in ARMD subjects compared to normal age-matched individuals (110). Gelatinase-A (MMP-2) levels are highest in the interphotoreceptor matrix and vitreous gel and do not increase with age; however, levels are twice higher in the matrix of RPE-associated cases (111). A summary of the pathological hallmarks and possible sequence of events leading to ARMD is listed in Table 2.
A recent study by Bailey et al. (112) suggests that TIMP-3 expression does not alter significantly with age, so that TIMP-3 protein accumulation with age in the retina must occur by a mechanism other than increased expression. Bailey et al. (112) confirm that TIMP-3 protein levels may still prove to contribute significantly to events associated with macular aging, such as matrix remodeling in Bruch's membrane. Another study by An et al. (113) found that RPE cells secrete a variety of extracellular matrix proteins, complement factors, and protease inhibitors that have been reported to be major constituents of "drusen" (hallmark deposits in ARMD). Interestingly, RPE cells from ARMD donors secreted two- to threefold more galectin-3-binding protein, fibronectin, clusterin, matrix metalloprotei-nase-2, and pigment-epithelium-derived factor than RPE cells from age-matched healthy donors. Conversely, compared to healthy subjects, "secreted protein acidic and rich in cysteine" was reduced by twofold in RPE cells from ARMD donors. Overall, data strongly suggest that RPE cells are involved in the biogenesis of drusen and the pathology of ARMD.
Risk factors for and treatment of ARMD are less well known than those for cataract and glaucoma. They are summarized in Box 3. Information on visual dysfunctions in Alzheimer's disease (AD) is presented in Box 4.
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