AGE-RELATED MACULAR DEGENERATION
ANTERIOR ISCHEMIC OPTIC NEUROPATHY
Visual impairment, defined as visual acuity less than 20/40, increases exponentially with age such that 20% to 30% of the population aged 75 years or older is so affected. Blindness, visual acuity of 20/200 or worse, affects 2% of the population aged 75 years and older. Those aged 65 and over make up 12% of the total U.S. population, but 50% of the blind population. Refractive error, cataract, age-related macular degeneration, diabetic retinopathy, and glaucoma are the most common causes of blindness. The respective order of importance varies according to the region and race surveyed. As the baby boomers age, the elderly population will increase by 75% by the year 2030, and the prevalence of these conditions will surge.
Visual impairment has considerable impact on the medical system and the older population. Chronic eye conditions represent one of the most common reasons for office-based visits to the physician among the population aged 65 and over. Of all office visits by older persons, 14% are to ophthalmologists, one of the highest rates of all specialty visits. Falls and car crashes, each associated with impaired vision in elderly persons, consume considerable medical resources. Moreover, impaired vision has been linked to a significant deterioration in the quality of life and the activities of daily living of older persons.
The American Academy of Ophthalmology recommends a comprehensive eye examination every 1 to 2 years for persons aged 65 and over. The U.S. Preventive Services Task Force recommends annual vision testing. Prophylactic and therapeutic ocular management can effectively alter the course of various conditions causing visual impairment. About one third of all new cases of blindness can be avoided with effective use of available ophthalmological services.
The leading cause of visual impairment worldwide is refractive error and cataract, for which eyeglasses and surgical cataract extraction, respectively, are mainstays of treatment. Despite the considerable successes of these therapeutic options, many populations do not receive adequate treatment for these problems.
Refractive error may be categorized as emmetropia (neutral refraction), ametropia, or presbyopia. Three forms of ametropia exist: myopia (nearsightedness), hyperopia (farsightedness), and astigmatism. Typically, older patients demonstrate increasing hyperopia, unless a cataract is present, which can induce a myopic shift. Although contact lens wear and laser refractive surgery are available for myopic and hyperopic refractive errors, these alternative forms of treatment traditionally have been used more by younger persons. After the age of approximately 40, emmetropes begin to develop progressive presbyopia, impaired ability to focus at near objects, caused by gradual hardening of the lens and decreased muscular effectiveness of the ciliary body. Reading glasses or bifocal eyeglasses may be prescribed.
Approximately 20% of persons aged 65 years and over and 50% aged 75 years and over have a cataract, a vision-reducing lens opacity. Cataracts may be associated with increased glare, decreased contrast sensitivity, and decreased visual acuity. Several risk factors have been reported: decreased vitamin intake, light (ultraviolet B) exposure, smoking, alcohol use, long-term corticosteroid use, and diabetes mellitus. The most important risk factor is increased age.
Cataract extraction is one the most successful surgeries in medicine (90% of patients achieve vision of 20/40 or better). Approximately 1.5 million cataract procedures are performed each year in the United States alone. In inner cities and underdeveloped countries such as India, the demand for surgery has surpassed available resources.
Cataract extraction is a technically demanding operation requiring superior fine motor skills and extensive surgical experience. In the hands of a seasoned surgeon, however, the procedure is very safe and can be completed in less than 15 minutes under local or topical anesthesia. The surgery involves the sonographic breakdown and aspiration of the lens (phacoemulsification). An artificial implant (intraocular lens) is placed in the capsular bag that is the only remnant of the native lens retained. A secondary laser procedure (capsulotomy) may be necessary to ablate subsequent capsular opacification that may develop in 15% or more of patients.
Age-related macular degeneration (ARMD) is the most common cause of blindness in older persons throughout the developed world. Increased age is the most important risk factor, although a genetic predisposition also contributes. Other risk factors include smoking and hypertension. Fair-skinned persons are at greater risk of developing this disease than those who are black, in whom pigment may serve as a protective element.
An international committee of retinologists have developed standards for the definition of ARMD or age-related maculopathy (ARM). These criteria are important in differentiating those with ARM who are at risk of visual loss from those with typical aging changes in the macula who are not at risk for visual loss. The committee proposed that early ARM be defined as the presence of drusen of significant size or confluence. Geographic atrophy or choroidal neovascularization (Figure 26.1) characterize late ARM. Only 10% of ARM patients have the late variety. By contrast, almost 100% of ARM patients with severe visual loss have late ARM.
Numerous genetic conditions resulting in premature macular degeneration exist for which the mutated sequence has been cloned and the protein product isolated. Mutations in ABC-R (ATP-binding cassette protein of the retina), a photoreceptor protein involved in molecular transport and exchange, leads to the development of Stargardt’s disease, in which patients classically develop macular flecks and atrophy associated with central visual loss by the second or third decade of life. Stargardt’s macular dystrophy has been found to have perhaps some association with ARM. Certain populations of ARM patients have been found to have an increased incidence of the heterozygous form of this mutation; other data has been conflicting. Sorsby’s fundus dystrophy is associated with many of the features of ARM. Visual loss however, typically develops before the age of 50. The affected gene has been sequenced and codes for a protein involved in extracellular remodeling, TIMP-3 (tissue-inhibitor of metalloprotease). Genetic studies have failed to uncover an association of this mutation with ARM.
Vitamin and antioxidant supplementation to prevent ARM is controversial. Although associations have been made between dietary intake and serum levels of vitamins and antioxidants with the presence of ARM, no reliable cause-and-effect data exist. The results of a nationally sponsored, prospective study of the effects of antioxidant supplementation such as oral zinc on the course of ARMD are still pending. Prophylactic laser therapy for those patients with drusen who are at high risk of developing neovascularization does not prevent visual loss. Laser therapy for choroidal neovascular membranes has been beneficial but only under very special circumstances, when membranes are well defined (ie, the margins of the lesion are clearly delineated) and extra- or juxtafoveal. Photodynamic therapy using porphyrin-derived dyes has been shown to be useful in those patients with subfoveal choroidal neovascular membranes in whom conventional laser therapy will destroy the fovea. According to the Treatment of Age-related Macular Degeneration with Photodynamic Therapy (TAP) Study Group, 43% of patients receiving photodynamic therapy sustained moderate visual loss (> 15 letters from baseline) after 1 year follow-up versus 57% of patients not receiving the photoactivated dye laser treatment. Moreover, 16% of those receiving photoactivated dye laser sustained an improvement in visual acuity, but only 7% in the placebo group showed improvement. Although the benefits are not overwhelming, photodynamic therapy is a relatively safe alternative that is the most effective procedure available for delaying visual loss in patients with ARM-related subfoveal choroidal neovascularization.
Duration of disease and control of blood sugar represent the most important variables in the development and progression of diabetic retinopathy. After 10 years, 70% of those with type 2 diabetes demonstrate some form of retinopathy, and nearly 10% show proliferative disease. Diet control, exercise, and proper glucose management with frequent daily glucose testing and the use of oral hypoglycemics or insulin, or both, are crucial in maintaining glycosylated hemoglobin levels lower than 7%. The Diabetic Control and Complications Trial demonstrated that tight blood-sugar control in those with type 1 diabetes resulted in a decreased rate of development and progression of diabetic retinopathy. The United Kingdom Prospective Diabetic Study validated these results in the older population with type 2 diabetes. Tight blood-pressure control (≤ 140/80) with either β-blockers or angiotensin-converting enzyme (ACE) inhibitors was also found to be an important factor in decreasing microvascular (and macrovascular) complications, such as the need for retinal laser therapy.
Background diabetic retinopathy or nonproliferative diabetic retinopathy, the earliest stage of retinopathy, may first be manifested by retinal microaneurysms, best appreciated with fluorescein angiography. Intraretinal hemorrhages and exudates, with or without associated edema, may ensue. Progressive ischemia characterized by increasing hemorrhages, venous caliber changes, intraretinal microvascular abnormalities, and capillary nonperfusion characterize the preproliferative stage of diabetic retinopathy. About 40% of patients with preproliferative retinopathy develop proliferative diabetic retinopathy (PDR) within 1 to 2 years, characterized by neovascularization, or new blood vessel growth of the retina or disc, or both.
Visual loss in the setting of diabetic retinopathy may occur as a result of macular nonperfusion or macular edema. The Early Treatment Diabetic Retinopathy Study demonstrated the benefit of focal or grid laser photocoagulation in stabilizing and improving vision in diabetics with clinically significant macular edema (Figure 26.2). Neovascularization (Figure 26.3) may cause severe visual loss in the setting of PDR as a result of vitreous hemorrhage or tractional retinal detachment. PDR is amenable to treatment by panretinal laser photocoagulation to inhibit the growth stimulus for neovascularization. The Diabetic Retinopathy Study demonstrated an 11% incidence of severe visual loss in patients treated with panretinal photocoagulation but a 26% incidence in those who did not receive laser during a 2-year follow-up. Nonclearing vitreous hemorrhage or tractional macular detachment may be addressed surgically by pars plana vitrectomy, membrane peeling, and endolaser.
Glaucoma is the second most common cause of blindness worldwide and, in the United States, the most common cause of blindness in black Americans. It affects more than 2.25 million Americans aged 40 years or over and results in more than 3 million office visits each year. The financial burden is considerable because of the prevalence and chronicity of this disease and the debilitation that results. Federal costs are reported to reach as high as $1 billion for glaucoma-related Medicare and Medicaid payments and disability.
The definition of glaucoma, now defined as characteristic optic nerve head damage and visual field loss, has undergone a considerable evolution. Elevated intraocular pressure (IOP) is no longer considered an absolute criterion, although it is a very important risk factor. There are many different types of glaucoma, of which primary open-angle glaucoma (POAG) is the most common.
POAG is a chronic disease most commonly affecting older patients. Aqueous may access the filtration site, but the network is “clogged,” resulting in impaired passage out of the angle. Slow aqueous drainage leads to chronically elevated IOPs. This is in contrast to acute angle-closure glaucoma, in which the entry site is suddenly blocked off, IOP rises precipitously, and the patient presents with considerable pain and discomfort. The IOP rise in POAG is slow and much less severe. Patients with POAG are asymptomatic and may suffer substantial field loss before consulting an ophthalmologist.
Development of POAG is most likely multifactorial and polygenic. Initial pedigrees were found to demonstrate linkage to the 1q locus. Subsequent investigations have more precisely defined the GLC1A gene that encodes for myocillin, the trabecular meshwork-induced glucocorticoid response protein. Several other chromosomal loci, including those mapped to chromosomes 2, 3, 7, and 10, have also been found to be associated with the development of glaucoma.
Management of POAG may be approached in a stepwise manner. A variety of IOP-lowering medications, both local and systemic, exist. Mechanisms of action include decreased aqueous production or increased aqueous outflow. Various eyedrop formulations are available; latanoprost, a prostaglandin analog which increases uveal-scleral outflow, and brimonidine, an α2-adrenergic agonist that decreases aqueous production, are two relatively new and effective drugs. In the face of visual field progression despite maximal medications or intolerance to medications, argon laser trabeculoplasty (application of laser energy to the trabecular meshwork) can be effective in lowering IOP in approximately 50% of patients for 3 to 5 years after treatment. Intraocular surgery involves the creation of a fistula or filtration site to allow an alternative route of aqueous egress (trabeculectomy). Adjunctive antimetabolite use with 5-fluorouracil or mitomycin-C has increased the success of this procedure in those patients at high risk of failure because of fibrosis and scarring of the filtration site. Alternative surgeries for glaucoma include drainage devices or aqueous shunts. Drainage devices, which are made of a foreign material such as plastic, shunt fluid from the anterior chamber to the subconjunctival space. Ciliary body destructive procedures with cryotherapy or laser (cyclocryoablation or cyclophotocoagulation) may be used in eyes with a poor visual prognosis.
Anterior ischemic optic neuropathy (Figure 26.4) may result in acute vision or field loss. Microvascular occlusion of the blood supply to the optic nerve may be attributed to atherosclerotic vascular disease or inflammation in the setting of giant cell (or temporal) arteritis. The former, the nonarteritic form, typically affects patients with vasculopathic risk factors such as diabetes mellitus and hypertension; the latter, the arteritic form, tends to occur in elderly patients with a history of myalgias, headaches, and weight loss. An elevated Westergren erythrocyte sedimentation rate and a positive temporal artery biopsy are diagnostic. Systemic corticosteroid treatment is crucial to avoid visual loss in the other eye.
Tears serve several important functions, including corneal lubrication, debris clearance, and immune protection. With age, tear production decreases, and older patients are prone to develop dry eye syndrome or keratitis sicca, characterized by redness, foreign body sensation, and reflex tearing. Management includes tear replacement with artificial tears during the day and an ointment at bedtime. Temporary and permanent punctal plugs may be employed to retard tear egress through the nasolacrimal drainage system in more severe cases. Keratitis sicca may be associated with autoimmune disease; conditions such as Sjögren’s syndrome should be excluded.
Lid abnormalities are a common problem for older persons. Because of the gradual loss of elasticity and tensile strength that develops with age, secondary degenerative changes may take place. Blepharochalasis (drooping of the brow) and blepharoptosis (drooping of the eyelid) may cause cosmetic deformity and, if severe, may impair vision. Lid ectropion or entropion, eversion and inversion of the lid margins, respectively, can disrupt the ocular surface and cause discomfort for the patient. Various surgical procedures are available to address these problems.
Herpes zoster ophthalmicus, or shingles, is a painful reactivation of varicella zoster virus that not uncommonly affects older persons. Dermatomal distribution of weeping vesicles affecting the ophthalmic division of the trigeminal nerve is the classic presentation. Ocular involvement may be signaled by lesions on the tip of the nose (Hutchinson’s sign) and may include dendritic keratopathy or uveitis. Oral acyclovir may shorten the course of disease. Post-herpetic neuralgia may be quite debilitating; various local ointments (eg, capsaicin, lidocaine) or systemic medications (eg, corticosteroids, tricyclic antidepressants) may be helpful. (See also Dermatologic Diseases and Disorders.)
Despite considerable advancements in the medical treatment of ocular conditions, many patients, especially those with late ARM, may ultimately sustain permanent visual loss. Visual training and the provision of visual aids are indispensable services available to the patient with low vision (visual acuity < 20/60).
Patients with low vision may develop useful adaptive skills with proper instruction. Eccentric viewing uses the principle of off-center fixation in ARM patients with central macular pathology. The patient can benefit from formal training to find and use the most effective eccentric viewing points. Instruction in scanning and tracking and other skills may help the patient integrate his or her visual environment.
Various low-vision aids are available to improve one’s ability to see both near and far. The fine detail required for reading is the most common indication for visual aids. Improved lighting is a simple modification that can enhance visualization of print. Selection of reading material using bold, enlarged fonts and accentuated black-on-white contrast may also be helpful. Magnification also is commonly employed. Various devices such as high-plus spectacles, hand-held magnifiers, stand magnifiers, and closed-circuit television can also enhance reading. Distance magnification may be achieved with the use of telescopic devices that can be hand-held for spot viewing or spectacle mounted for continuous viewing. Talking devices, which are computers used to create voice synthesis such as those used at stoplights, or Braille may be especially helpful for those who have lost vision altogether.
■ Bird AC, Bressler NM, Bressler SB, et al. An international classification and grading system for age-related maculopathy and age-related macular degeneration: The International ARM Epidemiological Study Group. Survey Ophthalmol. 1995;39(5):367–374.
An international panel of expert retinologists convened to design standard criteria in the definition and grading of age-related maculopathy. Standard, accepted parameters may allow a clearer understanding of the disease and may promote more proficient research in this field.
■ Ferris FL 3rd, David MD, Aiello LM. Treatment of diabetic retinopathy. N Engl J Med. 1999;341(9):667–678.
This review article summarizes the epidemiology, diagnosis, and laser management of diabetic retinopathy. Studies supporting optimal systemic control of various parameters, such as glucose, blood pressure, cholesterol, and kidney function, are also well represented.
■ Treatment of Age-related Macular Degeneration With Photodynamic Therapy (TAP) Study Group. Photodynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfin: one-year results of 2 randomized clinical trials—TAP Report 1. Arch Ophthalmol. 1999; 117(10):1329–1345.
The treatment of choroidal neovascularization in the setting of age-related maculopathy may be complicated by various factors, including the subfoveal presence of the new blood vessels. Photodynamic therapy uses a dye-activated laser to ablate the subretinal vessel complex that preferentially absorbs the laser energy; the overlying fovea remains relatively free of damage. The TAP study prospectively demonstrated the benefit of this treatment in delaying visual loss in patients with late age-related maculopathy.
■ U.K. Prospective Diabetes Study Group. Efficacy of atenolol and captopril in reducing risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 39. BMJ. 1998;317(7160):713–720.
The UKPDS validated the importance of tight blood-pressure control, either with β-blockers or angiotensin-converting enzyme inhibitors, in decreasing the rate of both microvascular and macrovascular complications of diabetes. The two classes of hypotensive drug were found to be equally effective.
■ U.K. Prospective Diabetes Study Group. Intensive blood glucose control with sulfonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 1998; 352(9131):837–853.
Unlike the Diabetes Control and Complications Trial, which studied persons with type 1 diabetes, the UKPDS prospectively investigated those with type 2 diabetes but yielded similar conclusions. Tight blood-sugar control, aiming for a glycosylated hemoglobin level of less than 7%, decreases the rate of progression of microvascular complications, such as diabetic retinopathy.
David Sarraf, MD
Anne L. Coleman, MD, PhD
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