Aging&Vision A publication for Practitioners, Researchers and Educators Volume 16 Number 2 Fall 2004 Age-Related Vision Impairment: Covering Vision Rehabilitation and Clinical Advances by Cynthia Stuen, DSW The last issue of Aging & Vision, covering highlights from the Schupf North American Scientific Symposium on Age-Related Vision Impairment held October 16-17, 2003, focused on clinical aspects of macular degeneration, glaucoma and diabetic retinopathy. In tandem with publicizing cutting-edge developments in clinical trials on eye disease, Lighthouse International's mission extends to helping people who have already been diagnosed with eye disease and experience vision impairment. Since the Symposium also covered presentations on vision rehabilitation, this issue of Aging & Vision features two of these whose subject matter constitutes some of today's hottest topics in the aging and vision fields - technology and driving. Dr. Michael Fischer, Director of Low Vision Services at Lighthouse International, explores who can benefit from assistive technology, which can dramatically alter and improve the way some people with vision impairment adapt to life with vision loss. And Valerie Ward, Director of Independent Living Services at Lighthouse International, shares her vast experience in "breaking the news" to older adults when driving is no longer an option due to visual impairment - a sometimes extremely delicate subject to broach. Because of the wealth of significant new medical findings presented at the Symposium, two articles providing clinical information were saved for this issue. Drs. Tricia Lennox and Jeffrey Liebmann offer a glaucoma overview with particular emphasis on a patient's risk factor assessment. And Dr. Emily Chew returns in this issue with an article on the nutritional aspects of age-related macular degeneration prevention and treatment. Also related to AMD, Lighthouse International, in conjunction with Novartis Opthalmics, has recently published "Seeing the Whole Picture: Visual Function and Age-Related Macular Degeneration," a brochure on macular degeneration for professionals. To receive a free copy, contact Lighthouse International's Information & Resource Service at 1-800-829-0500 or info@lighthouse.org. The Lighthouse is also currently producing a companion macular degeneration brochure for the consumer audience. Cynthia Stuen, DSW, Senior Vice President for Education, Lighthouse International In This Issue - Who Can Benefit from Assistive Technology? - When Driving Is Not an Option Due to Visual Impairment - Breaking the News - Glaucoma Overview: Risk Factor Assessment in the Glaucoma Patient - Micronutrients and Age-Related Macular Degeneration Presentations from the 2003 Schupf Symposium by Michael Fischer, OD; Jeffrey Liebmann, MD; Emily Chew, MD; and Valerie Ward, CSW can be viewed on video by logging on to http://www.visionconnection.org/SchupfVideos. Who Can Benefit from Assistive Technology? by Michael Fischer, OD, FAAO What Are Assistive Technologies? Assistive technologies are tools that help people who are partially sighted or blind be more independent at work, in school and at home. These tools, which can be sophisticated or surprisingly simple, are designed to make it easier to access printed material, to use computers, to travel and to perform activities of daily living. Assistive technology incorporates high tech methods. Some examples of assistive technology include: - Video magnification systems like closed circuit televisions (CCTVs) and portable video magnification devices, - Computer hardware and software that provides screen magnification, synthesized speech, tactile display, or combinations of these, - Other assistive devices for daily living, like talking scales, talking glucometers, color identifiers, talking compasses, and a variety of other devices. Low vision devices, such as microscopic spectacles, magnifiers and telescopes, utilize optical magnification to help visually impaired users achieve their goals. These optical low vision devices are still the staple of low vision care and have certain advantages in comparison to assistive technology. They are often more portable and more affordable than assistive technology devices and can be used in a variety of situations. For some patients, optical devices may just be easier to use. These devices can also have certain limitations, however, especially in higher powers, including a reduction in field of view, working distance, light and contrast. These limiting factors can sometimes significantly impact a person's successful use of optical low vision devices. When optical devices are difficult to use, assistive technology may allow the person to function more effectively. Evaluating Who Can Benefit For the person with partial sight, the first step is to have a low vision evaluation. During this visit, the low vision doctor will take a detailed history and ask questions about the individual's functional problems. The doctor will also investigate any physical limitations the person may have, which might interfere with the use of certain types of devices. Then, the low vision clinician will administer a series of tests to evaluate the patient's visual function, including visual acuity, visual fields (central and peripheral), contrast sensitivity and color vision. The information the doctor obtains from this testing will provide clues about whether assistive technology may be beneficial and, if so, what types of technology to prescribe. Visual Function and Its Impact on What a Doctor Prescribes Visual Acuity Loss: For the person with very reduced acuity, assistive technology may be easier to work with than optical magnification. Devices like CCTVs can offer not only higher but also variable magnification. They can also allow the person to function more comfortably by providing increased working distance from the task at hand. Other types of assistive technology feature speech support, which may better suit an individual with very reduced acuity. If the person cannot see the word, the device can read it out loud. Some patients may also function better binocularly. Yet, if a person's visual acuity is worse than 20/200, binocularity becomes difficult with an optical device. Maintaining binocularity is possible at high levels of magnification through assistive technology. Central Field Loss: Patients with central scotomas often have to use eccentric viewing to function more effectively. When a person has a large scotoma, being able to effectively use an eccentric point can be more difficult with optical magnification. Eccentric viewing may be easier with an assistive technology device. Additionally, as fixation moves further from the fovea, the impact of crowding increases. Using different types of text presentation can lessen the effects of visual crowding. For example, studies have reported that using text stretching to increase the spacing between letters and words can reduce crowding and may be beneficial for the person trying to read with a central scotoma. Presenting text in a scrolled fashion (like the marquees at the bottom of the screen on television news programs), or presenting words one at a time consecutively in the same place in the person's field, may also make reading with an eccentric point easier. This type of text manipulation is possible via assistive technology. Peripheral Field Loss: Patients with severely constricted fields may not respond well to optical magnification since the print or object being magnified may stretch into their field loss. These same patients may also have difficulty with optical devices because they may have problems controlling the position of their usable field at near distance, which can be especially true when using high plus spectacles. Since visual field is an angular measure, a person's linear field of view increases further from the eye. Therefore, if you can present higher magnification at a greater distance, it may help someone with a severely constricted field see more. Assistive technology can accomplish this. Contrast Loss: Optical devices themselves can reduce light and contrast, so a patient with reduced contrast sensitivity may have greater difficulty using a magnifier or other low vision optical device compared to someone who doesn't experience reduced contrast sensitivity. Additionally, patients with reduced contrast may require higher magnification than would be indicated by their acuity alone, but stronger-power optical magnifiers and microscopic spectacles are more difficult to use. A patient with severe contrast sensitivity loss may function better using reverse contrast, which can only be achieved with electronic magnification assistive technology. Color Vision Loss: Many eye diseases, including macular degeneration, diabetic retinopathy, glaucoma and optic atrophy, can lead to reduced color perception. When color perception is impacted, a person may have difficulty with color contrasts, which may make text or objects on a colored background more difficult to see. Using electronic magnification, colors can be converted to black and white, and if necessary, contrast can also be enhanced. In addition, if a person has problems with color identification, assistive technology can offer solutions. Other Considerations: A patient's needs and goals are a primary consideration in determining whether assistive technology will be beneficial and in deciding which kind of technology would be most appropriate. For certain tasks, such as reading prices at the store, for example, it makes more sense for most patients to use a simple magnifier in a strength and design appropriate to their capabilities rather than turning to assistive technology. What about a person's age? While there is no question that visual needs are age dependent, age alone should not be a factor when considering if assistive technology is appropriate. People of all ages can benefit from assistive technology. However, a patient's abilities can become a factor. As with any activity, a physical disability or an impaired ability to learn to use a device may prohibit using assistive technology. Types of Assistive Technology In every facet of our lives, technology is advancing at a very rapid pace. This is equally true in the area of vision rehabilitation. What follows is a brief overview of available assistive technologies. Current video magnification systems include: - Desktop CCTVs (see photo 1) with enhanced features (auto focus, speech commands, flat screens, text manipulation), - Handheld cameras (see photo 2) that interface with a standard TV set or other portable devices, such as head borne video displays or miniature flat panel displays, - Head mounted systems (see photo 3), where the camera and LCD displays are combined in a single unit, - Self contained portable units (see photo 4), where the camera and screen are in single unit (these now include miniature LCD magnifiers (see photo 5) that are very small and lightweight). Computer based systems, which allow users to access information using screen magnification, speech output, or both, are also popular. Computers can be used in conjunction with scanners to allow users to import typewritten material, which they can then access using speech or screen enlargement. For those people who are not computer users, standalone systems can convert typewritten text to speech and read documents aloud in a synthesized voice. An ever-increasing number of "simple" technologic devices that provide greater accessibility for those with vision impairments have been appearing on the market, such as personal digital assistants (PDAs) using speech recognition to cell phones with talking alerts. Technology continues to improve, and in many cases, has also become less expensive. Ultimately, all of our patients will benefit from assistive technology in the future. Michael Fischer, OD, FAAO, Director of Low Vision Services, Lighthouse International (Callout - page 3) "... The information the doctor obtains from testing to evaluate the patient's visual function will provide clues about whether assistive technology may be beneficial and, if so, what types of technology to prescribe ..." (photo caption page 3) 1. A standard (desktop) CCTV: Assist Vision Royal (Times Corp.) (photo captions, page 4) 2. A handheld camera plugged into a standard TV: Primer (Innoventions) 3. A head mounted video magnification system: Jordy (Enhanced Vision) (Callout - page 4) "... A patient's needs and goals are a primary consideration in determining whether assistive technology will be beneficial ..." (photo captions, page 5) 4. A portable video magnification unit (camera and screen): Traveller (Tieman/Optelec) 5. A miniature LCD magnifier: PocketViewer (PulseData) (Callout - page 5) Note: The photos in this article depict one example of an assistive technology device in each category: desktop CCTVs, handheld cameras, head mounted systems, self contained portable units and miniature LCD magnifiers. Units manufactured by alternative companies can also be found. (Callout - page 6) "People of all ages can benefit from assistive technology. However ... As with any activity, a physical disability or an impaired ability to learn to use a device may prohibit using assistive technology." When Driving Is Not an Option Due to Visual Impairment - Breaking the News by Valerie Ward, MSW, CSW In today's modern, mobile society, the automobile is the preferred mode of transportation for millions of people. Driving allows us to be independent and gives us a level freedom that is difficult to give up even when our driving becomes hazardous to ourselves and others on the road. If you drive, you can go where you want, when you want and you don't have to be dependent on others for assistance. As Mr. W., age 75, stated, "Driving allows me to be in control of my own destiny." Our society has relied heavily on the automobile, maybe too much, because those now living in suburban homes made accessible by the automobile are now struggling to find alternate means of transportation when driving is no longer an option for them. In these communities, driving is not considered a luxury but rather a necessity of life and replacing the automobile with a suitable alternative presents a considerable challenge. While many older adults with severe vision impairments will acknowledge that they no longer have the ability to drive safely and thus refrain from doing so, others continue to drive even when they are at risk. Losing the ability to drive can be a major life event, sometimes signifying yet another loss in the life of an older adult. Mrs. C's Experience Mrs. C., an 85-year-old woman who was legally blind due to glaucoma, was a proud woman who lived alone in a small city apartment where she had resided for 50 years. Despite her advanced age and medical problems, Mrs. C. had been able to care for herself with minimal assistance from others until her recent onset of vision loss. After a low vision examination, Mrs. C. was referred to me for short-term psychotherapy to reduce her depression associated with her deteriorating vision and ability to drive safely. Her family had reported to the low vision staff that Mrs. C. had recently experienced several near-accidents while driving but adamantly refused to surrender the keys to her car. Mrs. C. also vehemently denied that she was an unsafe driver or had had any near-accidents despite the presence of her frightened relatives during some of these incidents. She refused to realistically discuss the situation with her concerned relatives only resulting in increased family tensions. During our sessions, Mrs. C. made the following statements which highlighted the significant impact that the loss of her ability to drive would have on her life. "This is the beginning of the end for me! What more can be taken away from me? I don't have much time left in my life and I have already lost so much, my youth, my husband, my health! Why do I have to give up driving also? I have been driving since I was 15 years old and I have never had an accident." "My family just wants to make all my decisions for me. I might as well be dead or in a nursing home." In psychotherapy, Mrs. C. was eventually able to overcome her anger at her family in addition to her denial about her problems when driving and she reluctantly agreed to find another method of transportation. Her initial reactions to the loss were traumatic, however, and exacerbated her depression and anxiety about her future ability to care for herself independently. Leaving the wheel represented the end of her individual freedom and she desperately fought to avoid it. Assessing the Risk of Older Drivers As social workers, counselors, rehabilitation professionals, practitioners and family members, we should first conduct a detailed assessment of a person's ability to drive safely before we advise the individual to stop driving. Encourage the person to obtain the proper testing by qualified officials. Many older persons successfully drive safely into their 70s, 80s and 90s, so being 85 doesn't necessarily make a person an unsafe driver. As vision care professionals, we are concerned about those older persons with vision impairments who are unsafe and at risk drivers. In addition to your review of their eye and low vision assessments and functioning, here are some questions to consider for your discussion: - Have they been involved in a car accident or multiple accidents? - Are they able to see cars clearly when driving, use rear view mirrors, etc? - Have they been ticketed for moving violations? - When driving, are they getting lost more than usual? Is the 15-minute drive to the supermarket now taking an hour or more? - Are they driving through stop signs, traffic lights, missing exits, not yielding the right of way? - Are they driving too slowly, causing other drivers to honk their horns at them often? - Do they get confused, overwhelmed, and fearful when driving? - Are they able to drive safely at all times - days, nights, in sunny or cloudy weather, for example? If the person shares difficulties in one or more areas mentioned above, you should consider it of immediate concern and proceed to break the news that driving may no longer be an option. Breaking the News Breaking the news to a person who has become a risk when driving is not an easy task for professionals nor for family. Some individuals may accept their inability to drive and adjust to it accordingly, even considering the decision to no longer drive a relief. Hearing the news from a "professional" often eliminates the individual's burden of having to deny difficulties to those close to them and enables the person to retain his or her dignity. For many others though, the news is devastating and our ability to effectively communicate the message that driving is no longer an option and to provide the necessary assistance is crucial to their adjustment. Tips for How to Break the News 1. Involve the doctors. If the driver's eye care doctor or other physician has issued recommendations against driving, get it in writing and have it available for your discussion. 2. Be truthful with the older persons with whom you discuss this. Talk about the nature of their eye condition and the consequences of their vision impairment. People have a right to know the truth and be respected no matter how difficult it may be for you to tell them. 3. Be compassionate, non-judgmental and acknowledge the individual's loss. Do not try to minimize it. Allow the person to express feelings and emotions, which may range among denial, anger, shame, resentment or depression. 4. Develop a list of your safety concerns and those of significant others and discuss the implications of continued driving. If the driver has loved ones, discuss how an accident would negatively impact friends and family. 5. Involve the family or significant others in the discussion if possible. Individuals will need the support and assistance of others if driving is no longer an option. 6. Offer your assistance in helping the person find alternate methods of transportation (via your local area agency on aging, for example) now that he or she will no longer be driving. Help the individual find other ways to travel to friends and continue activities for which the car had been necessary. 7. Don't ignore signs of ongoing emotional distress. Recognize the need for ongoing psychotherapy and discuss it. If such service is unavailable in your agency, refer the person to an appropriate organization. 8. Be patient and persistent. If the individual agrees to stop driving, commend this difficult decision. If you do not succeed the first time, try, try, again. Valerie Ward, MSW, CSW, Director of Independent Living Services, Lighthouse International (callout, page 7) "... we should first conduct a detailed assessment of a person's ability to drive safely before we advise the individual to stop driving." (callout, page 9) "Breaking the news to a person who has become a risk when driving is not an easy task ... Some individuals may accept their inability to drive ... for many others though, the news is devastating and our ability to effectively communicate the message ... is crucial to their adjustment." Glaucoma Overview: Risk Factor Assessment in the Glaucoma Patient by Tricia L. Lennox, MD, and Jeffrey M. Liebmann, MD Definition of Glaucoma Glaucoma is an optic neuropathy causing visual field damage characterized by progressive injury to retinal ganglion cells and their axons. Currently, in the diagnosis or treatment of glaucoma, we evaluate a patient's history, the presence or absence of risk factors, intraocular pressure (IOP), gonioscopy, optic nerve examination and visual field testing. Risk Assessment Two major categories exist when measuring a glaucoma patient's risk: first, assessment of the risk of developing glaucoma and, secondly, assessment of the risk of vision loss. Several recent controlled clinical trials including the Ocular Hypertension Treatment Study (OHTS), the Early Manifest Glaucoma Trial (EMGT), the Collaborative Normal Tension Glaucoma Study (CNTGS), the Advanced Glaucoma Intervention Study (AGIS) and the Collaborative Initial Glaucoma Treatment Study (CIGTS) have provided us with information regarding the risk factors for developing glaucoma, the risk factors for progressing to disabling vision loss and the potential reduction of this progression with lower intraocular pressure. Risk for Developing Glaucoma Elevated intraocular pressure is a known risk factor for developing glaucoma. The OHTS showed that patients with ocular hypertension who were treated were less likely to develop glaucoma at five years compared to similar patients who were left untreated (4.4% versus 9.5%). In addition, the OHTS suggested that persons with untreated ocular hypertensive eyes develop glaucoma at a rate of 2% per year. The OHTS also found additional risk factors for developing glaucoma including a large cup/disc ratio, older age and a visual field with greater pattern standard deviation. In addition, thin central corneas were found to be a strong predictor of future damage. Patients with a corneal thickness of 555 microns or less had a three-fold greater risk of developing primary open angle glaucoma (POAG) than did individuals with a corneal thickness of more than 588 microns. Corneal thickness seems to influence intraocular pressure measurements: the measured IOP is less than the actual IOP for eyes with thin corneas while the measured IOP is greater than the actual IOP for thick corneas. African Americans have a higher prevalence and incidence of open angle glaucoma than do other ethnic groups. Compared to whites, African Americans in Baltimore, MD have a four to five times' higher rate of glaucoma. In addition, they have a greater degree of visual loss occurring over a shorter period of time. Up to 10% of African Americans who are aged 70-years-old have glaucoma. The OHTS data suggests that this racial effect may be due to thinner central corneas and larger cup/disc ratios. Additional risk factors for the development of glaucoma include family history and exfoliation syndrome. The genetic basis of glaucoma is still being investigated; however, it is felt that POAG is likely a multifactorial or polygenetic disorder. Risk Factors for Vision Loss Elevated intraocular pressure is predictive of vision loss. In addition, recent studies show that lowering intraocular pressure slows the progression of glaucoma. In the EMGT, a 10% decrease in the risk of glaucoma progression accompanied every additional 1 mmHg decrease in intraocular pressure. The EMGT study also identified additional risk factors for progression. These risk factors included higher IOP, glaucoma in both eyes, worsening visual field, negative or neutral response to treatment and the presence of disc hemorrhages. The Collaborative Normal Tension Glaucoma Study randomized patients with normal tension glaucoma to treatment or observation. This study also showed that lowering the intraocular pressure provided a benefit to slowing progression. Risk factors for progression of visual field defects in the CNTGS were found to be migraines, female gender, vasospasm, disk hemorrhage and racial heritage. An analysis of the Advanced Glaucoma Intervention Study revealed that patients whose intraocular pressures remained below target (18 mmHg) had better visual field preservation than those individuals whose intraocular pressure was above target. A small hemorrhage in the neural rim of the optic disc is a distinct risk factor for visual field deterioration. Disc hemorrhages may be a sign of active disease and an indicator of individuals who are more likely to progress. Treatment The current treatment goal for glaucoma is to intervene to prevent or delay optic nerve damage and visual field loss so that a patient can maintain functional vision over the lifetime. Presently, the only risk factor that is modifiable is intraocular pressure. Patients identified as at risk can be treated earlier. However, the question remains: who should be treated and how aggressively? Should all patients with ocular hypertension be treated? How aggressive should patients with glaucoma be treated? Which treatment is best? Patients need to be evaluated as individuals. They should have their own target intraocular pressure set based on the severity of the disease, the rate and extent of glaucoma progression, their intraocular pressure and their life expectancy. Target intraocular pressure represents a range of acceptable IOP levels, within which the progression of glaucomatous neuropathy will be delayed or halted. Target IOP range should be dynamic and adjusted over the course of treatment. The benefits and risks of therapy should be weighed in all treatment decisions. The lower the IOP is, the lower the risk of visual field deterioration. The American Academy of Ophthalmology practice guidelines recommend an initial target pressure 20 to 40% lower than the baseline pressure. Screening and early treatment gives us the best outcome for our patients. In addition, new technologies allow for improved structural and functional assessment. Technologies to detect earlier structural change in the optic nerve and nerve fiber layer include HRT, GDx, OCT and RTA1. Technologies to detect early functional changes prior to defects seen on an achromatic visual field include SWAP, FDT and mfVEP2. Conclusions Risk factor assessment is critically important in identifying persons and populations at risk for developing glaucoma or glaucomatous progression. Prospective clinical trials and population studies will help us to understand these risk factors and to better care for our patients. By combining risk factor assessment with technologies for early detection and progression, we will be able to intervene earlier in the life-cycle of this chronic disease to assist our patients in maintaining functional vision over their lifetimes. Notes 1. HRT (Heidelberg Retina Tomograph), GDx Nerve Fiber Analyzer, OCT (Optical Coherence Tomography), RTA (Retinal Thickness Analyzer) 2. SWAP (Short-Wavelength Automated Perimetry), FDT (Frequency Doubling Technology), mfVEP (Multi-Focal Visual Evoked Potentials) References 1. Heijl, A., Leske, M.C., Bengtsson, B., Hyman, L., Hussein, M. Reduction of intraocular pressure and glaucoma progression: Results of the Early Manifest Glaucoma Trial. Arch Ophthalmol. 2002; 120:1268-1279. 2. The Advanced Glaucoma Intervention Study (AGIS): 7. The Relationship Between Control of Intraocular Pressure and Visual Field Deterioration. The AGIS Investigators. Am J. Ophthalmol. 2000; 130:429-440. 3. Comparison of glaucomatous progression between untreated patients with normal-tension glaucoma and patients with therapeutically reduced intraocular pressures. Collaborative Normal-Tension Glaucoma Study Group. Am J. Ophthalmol. 1998; 126:487-497. 4. Kass, M.A., Heuer, D.K., Higginbotham, E.J., et al. for the Ocular Hypertension Study Group. The Ocular Hypertension Treatment Study: a randomized trial determines that topical ocular hypotension medication delays or prevents the onset of primary open-angle glaucoma. Arch Ophthalmol. 2002; 120:701-13. 5. Brandt, J.D., Beiser, J.A., Kass, M.A., Gordon, M.O. Central corneal thickness in the Ocular Hypertension Treatment Study (OHTS). Ophthalmology. 2001;108:1779-88. 6. Lichter, P.R., Musch, D.C., Gillespie, B.W., et al. Interim clinical outcomes in the Collaborative Initial Glaucoma Treatment Study comparing initial treatment randomized to medications or surgery. Ophthalmology. 2001; 108:1943-1953. 7. Tielsch, J.M., Sommer, A., Katz, J., Royall, R.M., Quigley, H.A., Javitt, J. Racial variations in the prevalence of primary open-angle glaucoma: the Baltimore Eye Survey. JAMA 1991; 266:369-74. 8. Ishida, K., Yamamoto, T., Sugiyama, K., and Kitazawa, Y. Disc hemorrhage is a significantly negative prognostic factor in normal-tension Glaucoma. Am. J. Ophthalmology. 2000; 129:707-714. 9. Drance, S., Anderson, D.R., and Schulzer, M. Risk Factors for Progression of Visual Field Abnormalities in Normal-tension Glaucoma. Am. J. Ophthalmology. 2001; 131:699-708. Tricia L. Lennox, MD, New York Eye and Ear Infirmary, New York, NY, and in private practice at Matossian Eye Associates, Ewing, NJ Jeffrey M. Liebmann, MD, Clinical Professor of Ophthalmology, New York University School of Medicine, and Director, Glaucoma Services, Manhattan Eye, Ear, & Throat Hospital and New York University Medical Center, New York, NY (Callout, page 10) "... The Ocular Hypertension Treatment Study showed that patients with ocular hypertension who were treated were less likely to develop glaucoma at five years compared to similar patients who were left untreated" Micronutrients and Age-Related Macular Degeneration by Emily Y. Chew, MD Age-related macular degeneration (AMD) is the most common cause of visual impairment in the US.1 The disease is projected to increase at an alarming rate as the longevity of the American population increases.2 The treatment of AMD is currently limited with the use of laser photocoagulation,3,4 photodynamic therapy,5,6 and surgical procedures. Although the pathogenesis of AMD is unknown, there is growing evidence that oxidative stress may play a role.7,8 The results of the Age-Related Eye Disease Study (AREDS) showed that oral supplements of high dose antioxidant vitamins C, E, and beta-carotene and zinc (with copper) reduced the risk of progression to advanced AMD.9 Smoking is also a known risk factor associated with the risk of AMD and smoking is known to deplete the body's antioxdative potential.10 These data further support the possible role of oxidative stress in AMD. Carotenoids: Lutein/Zeaxanthin The role of micronutrients in the pathogenesis of AMD was explored in 1988.11 Investigators reviewed the dietary intake of patients with and without AMD in the first NHANES (National Health and Nutritional Examination Healthy Survey) and found that participants with the highest consumption of fruits and vegetables rich in vitamins A and C reduced their risk of AMD by as much as 41% when compared to participants who did not eat such foods. The Eye Disease Case Control Study, conducted by the National Eye Institute, compared blood levels of carotenoids and other vitamins in patients who had neovascular AMD with those without AMD.12 The study found that patients with the highest blood levels of carotenoids, compared with those with the lowest levels, had the lowest risk of macular degeneration, with reductions as high as 70 percent. Patients with moderate blood levels of carotenoids had a 50 percent risk reduction. In addition, patients with a high dietary intake of the carotenoids lutein and zeaxanthin, found in green leafy vegetables such as spinach and collard greens, had a 43 percent or more risk reduction for AMD compared with those with low or minimal intake.13 The higher consumption of these foods was associated with a lower risk of AMD, appearing to show a dose response. The lowest risk of AMD was found in participants eating spinach six times a week when compared to those who never eat the vegetable. This association of dietary lutetin/zeaxanthin with AMD was also found in the third NHANES study.14 Lutein and zeaxanthin are the major components of the yellow pigment found in the center part of the mammalian eye. Like other vitamins, lutein and zeaxanthin are not manufactured by the body, so they must be consumed in the diet. They act as the major filter for ultraviolet radiation, and as such, might help prevent oxidative stress. In plants, lutein acts like a sunscreen; plants that are deficient in the vitamin become scorched. Lutein is often touted as a treatment for macular degeneration. However, this is based upon observational, case-controlled studies and such information is inconclusive due to unknown, confounding factors that may influence findings. For example, a person's decision to take vitamin supplements may be associated with their socioeconomic status or with patient compliance. In other words, patients who take vitamins may, in general, be of higher socioeconomic status, or may be more compliant in taking medicines for high blood pressure or other conditions. In general, people who take dietary supplements may otherwise take better care of themselves. Age-Related Eye Disease Study (AREDS) In 1992, the National Eye Institute mounted a controlled clinical trial called the Age-Related Eye Disease Study (AREDS) to evaluate the role of antioxidant vitamins and zinc in the treatment of age-related cataract and macular degeneration.15 Only rigorous testing in controlled clinical trials that account for known and unknown confounders can determine whether a treatment is effective for a given disease or condition. AREDS was designed to examine the natural history of macular degeneration and cataract, but an additional interest was the investigation of the nutritional aspects of these diseases through a randomized trial. Goals of the study included determining whether antioxidants or minerals could slow the progression of lens opacity in cataract, and whether these nutrients could prevent or slow the progression of AMD. The 4,757 patients in the study were randomly assigned to one of four treatment groups: placebo (a sham treatment); antioxidants; zinc; or antioxidants plus zinc. The antioxidants used in the study were vitamin C (500 mg/day), vitamin E (400 IU/day), and beta-carotene (15 mg/day or 2500 IU/day). When the AREDS was designed, lutein and zeaxanthin were not commercially available and thus not tested. Zinc (80 mg/day) was given together with copper (2 mg/day). Zinc was of interest because many patients were already taking this mineral based on the results of just a single small study done in the 1980s that showed benefit in reducing minor vision impairment.16 Because zinc at high doses can cause significant health problems, including copper deficient-anemia, in the AREDS study, copper was given to counter the harmful effects of zinc. As of 2001 when the major AREDS results were announced, the patients had been followed for an average of more than six years. Cataract After five years, cataracts developed in 29.8 percent of patients who took antioxidants and 30.4 percent who did not take antioxidants. Thus, the antioxidants were neither beneficial nor harmful in terms of cataract development, nor were they beneficial in preventing surgery for cataract. At five years, 10.5 percent who took antioxidants, and 11.3 percent who did not, underwent cataract surgery. Loss of visual acuity with cataract at five years was virtually the same in both groups - 4.7 percent in the antioxidant group and 4.8 percent in those not taking antioxidants. These antioxidant vitamins are not recommended for the prevention or treatment of cataracts. Age-Related Macular Degeneration Four groups of patients with varying risk of AMD were enrolled in AREDS. The risk of AMD was identified by an examination of the retina to evaluate the size and the area of drusen, or yellow spots. Although people with no risk for macular degeneration normally develop a few drusen over their lifetime, patients with AMD have more and larger drusen. The four AMD groups included: 1) people thought to have no risk for macular degeneration (few or no drusen); 2) people at risk for early AMD (intermediate drusen); 3) people with intermediate risk for AMD (extensive intermediate or large drusen); and 4) people who already have AMD in one eye and one unaffected eye. Patients at low risk for macular degeneration were not given zinc because of its potential harmful effects. The study of zinc was limited to those who had early AMD or worse. In all clinical trials, some of the most valuable data includes information on the natural history of the disease. In AMD, it was found that people with small to moderate drusen had a very low risk of developing advanced disease. At five years, only 1.3 percent developed the advanced form of AMD. People at intermediate risk, who had moderate to large drusen, had an 18 percent chance of developing advanced AMD in five years. People who already had macular degeneration in one eye had the highest risk - 43 percent - of developing advanced disease. The results of the randomized, controlled clinical trial showed that 28 percent of the patients taking placebo developed advanced AMD - either the neovascular or the atrophyic form - after five years. Of those taking the combination of antioxidants and zinc, only 20 percent developed advanced disease in 5 years. The combination treatment with zinc and antioxidants reduced the risk of advanced AMD by 25 percent while zinc alone reduced the risk by 21 percent, and antioxidants alone reduced the risk of advanced AMD by 17. The combination treatment was the best. Regarding vision loss, 29 percent of patients taking placebo developed moderate vision loss at the end of five years, whereas 23 percent of patients taking antioxidants and zinc actually had a reduction in terms of moderate vision loss. Given alone, the antioxidants and zinc were each effective to some extent in preventing macular degeneration and in preserving vision, but the combination therapy again resulted in the most beneficial effects. AREDS is the first vitamin study that has shown beneficial effects for a disease of considerable public health significance and is the first study in which a treatment has been shown to prevent the development of macular degeneration. Risks of Vitamin Therapy The risks associated with the treatment used in AREDS include: 1. Possible increased risk of lung cancer in people already at risk. As was shown in the NIH sponsored Alpha-Tocopherol Beta-Carotene Trial (ATBC trial)17 in Finland, heavy smokers who took beta carotene significantly increased their risk of developing lung cancer. In addition, the CARET Study18 (the beta-Carotene and Retinol Efficacy Trial), which followed the ATBC trial, replicated much of the findings of the former study in patients who were either heavy smokers or had exposure to asbestos. This study was also sponsored by the NIH. As in the ATBC trial, participants in CARET who took beta-carotene had an increased risk of developing lung cancer and an increased death rate. Thus, beta carotene therapy for AMD would not be recommended in smokers or others at risk for lung cancer. 2. Skin yellowing. Beta-carotene increased the yellowing of the skin. This discoloration has no health consequence. 3. Genital/urinary problems. Zinc use increased hospitalizations for genital and urinary problems. The most common problem was prostate enlargement in men. 4. Possible adverse effects on cholesterol levels. Although the AREDS study found no treatment effect on cholesterol, previous studies have reported that zinc may cause a decrease in HDL ("good") cholesterol or an increase in LDL ("bad") cholesterol. 5. Anemia from Zinc. The AREDS showed no increase in anemia in those patients taking zinc. Overall, the AREDS study showed that, at the 6-year follow-up, combination therapy with zinc and antioxidants proved beneficial for AMD with fairly few side effects. Patients enrolled will be followed for additional years to assess long-term effects. Who Should Take Vitamin Therapy for AMD? The American Academy of Ophthalmology recommends that people over age 65 have a yearly eye exam with pupil dilation to screen for cataract, glaucoma, and macular degeneration. People who are not at risk for AMD, and even those at the low risk end - those with few drusen - need not take vitamins since, in five years' time, only one percent of people in this group develop the disease. This risk is determined by the ophthalmologist following a dilated eye exam. Patients who have a family history of AMD may not necessarily be in the higher risk group for AMD and may not benefit from taking these supplements. It is estimated that about 55 million people over the age of 55 in the United States today may be at risk for macular degeneration. Of these, eight million are at high risk and are the people who are likely to benefit from combination zinc and antioxidant therapy. If all eight million people at high risk for AMD took supplement therapy, more than 300,000 of them could be saved from advanced AMD in the next five years. 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Arch Ophthalmol. 1999; 117:1329-45 6. Verteporfin therapy of subfoveal choroidal neovascularization in age-related macular degeneration: two-year results of a randomized clinical trial including lesions with occult with no classic choroidal neovascularization-verteporfin in photodynamic therapy report 2. Am J Ophthalmol. 2001; 131:541-60. 7. Young, R.W., 1988. Solar radiation and age-related macular degeneration. Surv. Ophthalmol. 1988;32; 252-269. 8. Beatty, S., Koh, H.-H., Henson, D., Boulton, M. The role of oxidative stress in the pathogenesis of age-related macular degeneration. Surv. Ophthalmol. 2000; 45: 115-134. 9. Age-related Eye Disease Study Research Group. A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no. 9. Arch Ophthalmol. 2001;119: 1439-52. 10. Age-Related Eye Disease Study Research Group. 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Am J Epidemiol. 2001;153(5):424-432. 15. The Age-Related Eye Disease Study Research Group. Design Paper, the Age-Related Eye Disease Study (AREDS): Design implication. AREDS Report no. 1. Control Clin Trials 1999;20:573-600. 16. Newsome DA, Swartz M, Leone NC, Elston RC, Miller E. Oral zinc in macular degeneration. Arch Ophthalmol. 1988;106:192-198. 17. The Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group. The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. N Engl J Med. 1994;330:1029-1035. 18. Omenn GS, Goodman GE, Thornquist MD, et al. Effects of a combination of betacarotene and vitamin A on lung cancer and cardiovascular disease. N Engl J Med.1996;334:1150-1155. Emily Y. Chew, MD, Division of Epidemiology and Clinical Research, National Eye Institute/National Institutes of Health, Bethesda, MD. Aging&Vision Cynthia Stuen, DSW Senior Vice President for Education, Director of Lighthouse Center for Education Sarah Lloyd Director of Educational Publications Aging & Vision Editorial Board Cynthia Stuen, DSW, Chair Aries Arditi, PhD Eleanor E. Faye, MD, FACS Michael Fischer, OD, FAAO Kent Higgins, PhD Amy Horowitz, DSW Bruce Rosenthal, OD, FAAO Carol Sussman-Skalka, CSW, MBA This newsletter is available in alternate formats and on our website: www.lighthouse.org. Lighthouse International Barbara Silverstone, DSW President and CEO Lighthouse International is a leading resource worldwide on vision impairment and vision rehabilitation. Through its pioneering work in vision rehabilitation services, education, research, prevention and advocacy, Lighthouse International enables people of all ages who are blind or partially sighted to lead independent and productive lives. Founded in 1905 and headquartered in New York, Lighthouse International is a not-for-profit organization, and depends on the support and generosity of individuals, foundations and corporations. Lighthouse International 111 East 59th Street New York, NY 10022-1202 Tel: (212) 821-9200 (800) 829-0500 Fax: (212) 821-9705 TTY: (212) 821-9713 E-mail: aging&vision@lighthouse.org www.lighthouse.org (c) 2004 Lighthouse International