To Ensure That All Patients Have Access to Early Intervention, Regular Proactive Treatment, and Integrated Care, and That Research is Ongoing for Improved Treatment Options

Introduction

The only international organization focused exclusively on macular disease, AMD Alliance International (AMDAI) dedicates itself to bringing knowledge, hope, and help to persons around the globe whose lives are affected by age-related macular degeneration (AMD). Together with 70 member organizations in 26 countries, AMDAI works to generate awareness and understanding of age-related macular degeneration; to promote the importance of education and early detection and knowledge of treatment and rehabilitation options; and to preserve vision and improve the quality of life of individuals affected by AMD.

In the fall of 2010, AMDAI conducted a wet AMD patient survey and sponsored a series of wet AMD patient focus groups in England, France, Italy, and the U.S. to learn more about perceptions and understanding of wet AMD and patient experiences with diagnosis, treatment, and care. Patient and caregiver comments underscored the challenges patients face in being appropriately diagnosed and receiving timely and regular treatment for wet AMD. Survey and focus group findings also highlighted the significant impact that wet AMD has on quality of life.

The survey and focus groups, combined with AMDAI and other research, catalyze this call for action to:

• Increase understanding globally that wet AMD is a chronic disease
• Ensure early intervention and regular treatment for persons at risk for or living with wet AMD
• Provide an integrated model of care for persons living with wet AMD
• Encourage vigorous research efforts to close the gap on unmet patient needs

Wet AMD overview

Age-related macular degeneration is a leading cause of blindness in the developed world, with twice the prevalence of Alzheimer‟s Disease.¹ There is a strong genetic pre-disposition, but the greatest risk factor is age. While people in middle age have about a two percent risk of getting AMD, the risk increases to nearly 30 percent in those over age 75.2 Worldwide, approximately 30 million people live with AMD.

AMD is a progressive disease that gradually diminishes the central vision that is necessary to see objects clearly and to perform common daily tasks such as reading and driving. The disease can progress rapidly and lead to loss of vision in both eyes. AMD occurs in two forms: dry and wet. Wet AMD is an advanced stage of the disease and the leading cause of blindness in people over the age of 55 in the U.S. and Europe. Wet AMD is almost always preceded by the dry version.

The risk of developing AMD may be reduced by not smoking, regular exercise and a diet rich in colored vegetables and fruits. There is also some evidence that reducing exposure to strong UV light by wearing good sunglasses and/or hats that shade the eyes may also reduce risk. These preventative measures correlate strongly with risk reduction for cardiovascular disease, some cancers, and other chronic diseases.

There are currently no approved treatments for dry AMD, although a specific high-dose oral formulation of antioxidants and zinc – known as the AREDS (Age-Related Eye Disease Study) formulation³ – significantly reduces the risk of advanced AMD and its associated vision loss.

In wet AMD, abnormal blood vessels develop beneath the macular retina and leak blood and fluid that lead to scarring and visual impairment. Wet AMD usually progresses more rapidly than the dry version, and generally leads to more serious vision loss. Severe sight loss can occur in as little as three months. There is no cure, but several approved therapies are on the market, including laser surgery, photodynamic therapy, and, most recently, anti-VEGF therapy that is administered by a drug injection into the eye. This latter treatment can arrest and, in some cases, restore vision loss. Other anti-VEGF compounds are in development and have shown promise but are not yet licensed for use in wet AMD.

Wet AMD impacts quality of life

Wet AMD imposes not only sight loss on those who live with the disease, but also loss of independence, social isolation, lowered self-esteem, reduced quality of life, and depression and other psychological illness. Visual impairment and blindness inhibit a person's ability to live healthier longer, and to live with dignity in the home. Low vision and blindness rob a person of independence by impeding the ability to perform common daily tasks or to work at a paying job. One third of wet AMD patients report that they are unable or struggle to dress or wash themselves, compared with 24% of people who have suffered stroke or brain injury.⁴

Long-standing chronic medical conditions such as wet AMD are often associated with anxiety and depression, increased risk for suicide, and greater utilization of medical resources.5 In one study, 60 percent of persons living with AMD reported anxiety and depression, which is more than that reported by people with cancer (50%)6 and comparable to that experienced by stroke patients (61%)⁷ and by those with severe mental illness (54%). ⁸

Compared to people who are sighted, persons with vision loss experience:

• Reduced quality of life
• Greater difficulty with daily living and social dependence
• Higher rates of clinical depression
• Twice the risk of premature death
• Increased risk of falls and related hip fractures
• Premature admission to nursing homes

Wet AMD impacts all areas of life, from paid work outside the home to household management to socializing with friends (See Table 1 for some of the activities cited by focus group participants as being more difficult or impossible because of visual impairment). It is no wonder that the impact of sight loss on overall quality of life is similar to the impact on quality of life of stroke, severe cardiovascular disease, coronary artery disease, and cancer.⁹


 


Table 1: Wet AMD Impact on Daily Life

Daily Activities	Hobbies and Pastimes
Bill paying Check writing and bill paying Computer use Cooking and meal preparation Dressing and washing Driving Home maintenance and repairs House cleaning Reading Grocery shopping, errand running Writing Yard work Using ATM machines	Card playing and other games Fishing Gardening Golf and other outdoor sports Jewelry making Knitting and sewing Movie going Outdoor activities in the sun Painting Playing musical instruments Television watching Volunteer work Woodwork

Focus group participants also spoke about the emotional toll of having to get rid of their cars because they could no longer drive, and having to move into long-term care facilities earlier than planned because of visual impairment. They expressed frustration at being forced to rely on others, even as they are no longer able to help others (to look after grandchildren, for example, or to volunteer for charities). Focus group comments (found in Table 2) personalize the broad impact on daily life, social relationships, and overall quality of life.


 
 

 



 
 
 



 


Table 2: Comments from Persons Living with Wet AMD
Isolation and helplessness
[Wet AMD] has affected me a lot. It‟s very frustrating – I don't want to ask for help; I still want to be independent. I don‟t go out at night. I can‟t cross the road because of traffic. Once it starts getting dark, my life comes to an end. It is such a lonely experience watching day to day as my sight deteriorates. You wake up and just wait for your vision to deteriorate further. You end up quite neurotic.
Impact on daily activities
I am heartbroken – reading was my passion; I no longer go into stores; I always have to ask for help with everything from everyone. I can't accept living like this. It is hard to accept that I can no longer read or write. I used to love to write . . . I need help from others for anything I do outside the house.
Impact on work I had to give up my job. That had huge financial implications. I had to go to work part-time. I used the computer a lot, and the concentration that required took too much out of me. I used to be a dressmaker, but sewing is hard for me now.
Lifestyle changes
Do I have reduced life choices? Oh, yes, definitely. A curtain was pulled over my social life. My son came back to live with me. We have a good relationship, but I try very hard to not intrude on his life. I carry a cane when I go shopping, so that when I ask questions, people don‟t say “can‟t you read?”

Wet AMD is a chronic disease

Wet AMD has all the hallmarks of a chronic disease: it is a persistent, progressive, and incurable disease that must be assessed and treated on a regular, ongoing basis – sometimes as often as monthly – if treatment is to be effective and sight loss arrested or restored. Untreated or inappropriately treated, wet AMD leads to declining sight and complete loss of vision, which in turn dramatically increases the burden to society in direct health care costs, lost productivity, and the need for supportive services and care.

Those costs are high: the real financial cost of visual impairment worldwide due to AMD in 2010 is estimated at US$343 billion, or 12 percent of the total global cost of visual impairment (US$2,954 billion).10 It is also estimated that persons with visual impairment were deprived of the equivalent of 118 million years of healthy life due to disability and premature death in 2010; AMD was the cause of approximately six million of those years.¹¹ Because of these devastating consequences, society cannot afford to treat wet AMD as an acute disease, where treatment is provided once, for a short-term period, or on an ad hoc basis.

Unfortunately, in some countries, treatment for wet AMD is reimbursed as if for an acute disease, decreasing access, limiting patient outcomes, and potentially endangering sight. The recognition of wet AMD as a chronic disease will help improve access to appropriate care and ensure appropriate reimbursement for that care, thereby reducing needless sight loss and minimizing the economic burden placed on societies throughout the world by visual impairment.

Early intervention and regular treatment ensure optimal patient outcomes

Severe sight loss from wet AMD can lead to blindness in as little as three months, and without treatment, those diagnosed with wet AMD will become functionally blind within two years. It is therefore critically important that those at risk for developing wet AMD be seen regularly by an eye care specialist for regular monitoring, or that they self-monitor for vision changes that may be symptomatic of wet AMD and report to a physician as quickly as possible if such changes are detected, so that an appropriate diagnosis can be made and an appropriate regimen of therapy begun before significant vision loss occurs.

Persons living with wet AMD have best outcomes when they have regular assessments from their health care providers and are treated with regular, planned, proactive therapy. Better treatment outcomes translate into diminishment, arrest, or restoration of sight loss. For the person living with wet AMD, this means greater independence; enhanced ability to perform daily life tasks and engage in work, hobbies, and social activities; and improved physical and mental health. For society at large, it means that the high costs associated with medical, residential, and social service care are reduced. Treatment and reimbursement must therefore reflect the chronic nature of the disease and not be limited to a few doctor visits and/or a few injections (if treatment by injection is indicated).

An integrated model of care is essential for persons living with wet AMD

An integrated model of care is necessary to ensure optimal outcomes for persons living with wet AMD and to lessen the overall burden of wet AMD on society. Integrated care should encompass:

• Primary prevention: Persons known to be at risk for AMD should take precautions that may help prevent development of AMD. They should have regular comprehensive dilated eye exams, not smoke, eat a healthy diet, exercise, maintain normal blood pressure and weight, and protect their eyes from the sun. Persons who have been diagnosed with dry AMD (which almost always precedes wet AMD) should have annual comprehensive dilated eye exams and take the AREDS formula if so advised by their physicians.
• Early detection and timely diagnosis: Early detection of wet AMD is key to saving vision. Persons living with dry AMD should be regularly monitored by a qualified health care provider to ensure that wet AMD, if it develops, is diagnosed as early as possible.
• Early treatment and ongoing monitoring: Wet AMD progresses rapidly. Persons who have been diagnosed with the disease should begin treatment as soon as possible after diagnosis to slow or arrest disease progression. Patients should also have access to and reimbursement for the full course of therapy prescribed by their physicians, which may be as often as monthly.
• Ongoing rehabilitation: Because there is currently no cure for wet AMD, many persons living with wet AMD will have need of rehabilitation services throughout life. They need access to information, to qualified physicians, and to low vision equipment and supportive services.

The consequences of not providing an integrated model of care are that the person living with wet AMD will be less productive in and outside the home; in far more need of costly in-home care, nursing homes, or assisted living facilities; and subject to psychological and physical comorbidities that have been demonstrated to diminish quality of life and add to health care expenditures.

Research must be ongoing to develop new and improved therapies

In an age of growing cost controls, developing innovative new therapies for wet AMD is increasingly challenging. Off-label use of less expensive drugs not indicated for the treatment of wet AMD has become common practice, with little or no data about the efficacy or side-effects of such unapproved treatments.¹², ¹³ As private and public payers determine optimal treatments for wet AMD, decisions must be based on what is optimal for patients.

Until a cure for wet AMD is found, translational research must be ongoing to:

• Reduced quality of life
• Reduce treatment/dosing frequency
• Identify combined drug therapies that improve treatment efficacy and burden
• Discover drugs that reverse the disease process
• Improve efficacy of intravitreal drugs
• Develop standardized treatment
• Identify preventative interventions

Key drivers for the success of any new therapies will be that they have proven clinical safety and long term efficacy, be made available to all who live with wet AMD, and ultimately arrest disease progression and restore sight.

¹ Tracy Hampton, PhD, “Genetic Research Provides Insights Into Age-Related Macular Degeneration,” Journal of the American Medical Association, October 13, 2010; 304(14):1541-1543.
² Facts About Age-Related Macular Degeneration, National Eye Institute, US National Institutes of Health, http://www.nei.nih.gov/health/maculardegen/armd_facts.asp
³Ibid.
⁴ M. Langelaan, M. R. de Boer, R. M. A. van Nispen, et al., “Impact of visual impairment on quality of life: A comparison with quality of life in the general population and with other chronic conditions” Ophthomalogic Epidemiology 2007;14:119-126.
⁵ Yemi Aina, MD and Jeffrey L. Susman, MD, “Understanding Comorbidity with Depression and Anxiety Disorders,” Journal of the American Osteopathic Association, May 2006, pp 9-14.
⁶ D. Wiersma and J. van Busschbach, “Are needs and satisfaction of care associated with quality of life? An epidemiological survey among the severely mentally ill in the Netherlands,” European Archives of Psychiatry and Clinical Neuroscience, 251(5):239–246.
⁷ P. J. Dorman, M. Dennis, P. Sandercock, “How do scores on the EuroQol relate to scores on the SF-36 after stroke?” Stroke, 30 (10), 2146-2151.
⁸ D. Wiersma and J. van Busschbach, “Are needs and satisfaction of care associated with quality of life?”
⁹ AMD Alliance International data on file, September 2007.
¹⁰ The Global Economic Cost of Visual Impairment, Access Economics, prepared for AMD Alliance International, March 2010 (costs reported in 2008 US dollars).
¹¹Ibid.
¹²Miriam Karmel, “AMD Therapies: Comparing Costs and Quality of Life,” EyeNet Magazine, American Academy of Ophthalmology, http://www.aao.org/publications/eyenet/200610/feature.cfm.
¹³ D. Wong and G. Kyle, “Some ethical considerations for the „off label‟ use of drugs such as bevacizumab,” Commentary by Ophthalmol 2006; 90:1218-1219.

This report was made possible by grants from Bayer Healthcare and Regeneron. The content of this report has been determined independently by AMD Alliance International