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Age-related macular degeneration (AMD) is a chronic, progressive, degenerative eye disease that leads to central vision loss and primarily affects people older than age 60 [1,2]. End-stage AMD is the leading cause of blindness in high-income countries. Approximately 1.75 million Americans are living with the advanced stages of the disease, and that number is projected to increase to nearly 3 million by 2020 [3,4]. With an overall global prevalence of 8.69%, about 228 million people will be diagnosed with AMD in 2040 [5].

Patients with early- and intermediate-stage AMD can have mild to moderate visual acuity loss; however, patients with advanced-stage AMD typically develop severe vision loss (Figure 1) and can have a number of symptoms depending on the type of AMD they develop: neovascular or non-exudative (wet and dry, respectively). Wet AMD symptoms include spots in a patient’s central vision or complaints that straight lines appear wavy and distorted, greatly inhibiting the patient’s ability to read. Dry AMD symptoms include washed-out colors and difficulty seeing fine details. Objects in the patient’s central vision may appear distorted and faded. Approximately 80% of the people diagnosed with AMD will have the dry or atrophic subtypes, which accounts for about 20% of legal blindness (defined as 20/200 or worse in the better-seeing eye, best corrected with standard glasses or contacts) [3,6-9].

Figure 1: Simulated Comparison of Normal vs. End-Stage AMD Vision.

There is no known cure for AMD, but pharmacologic and laser treatments may help slow disease progression and temporarily restore some of the vision lost [10-15]. Visual gains from these interventions are difficult to maintain, however, and, anatomically, there remain patients who will progress to severe vision loss [16]. Pharmacologic treatments can be costly, entail ongoing vitreous cavity injections, may not be effective in all patients, and may result in a slow regression over the long-term [16]. Learning to live with low vision through rehabilitation and use of external devices and tools is often the only choice that remains for patients with advanced AMD.

The disease impacts quality of life (QoL), as patients often incur falls and injuries, depression, suicidal thoughts, stress, and feelings of social isolation [17]. There is a significant need for a treatment for advanced AMD that enhances patient QoL through improved everyday function. In 2010, the U.S. Food and Drug Administration approved the first prosthesis for severely visually impaired patients with bilateral endstage AMD, the implantable miniature telescope (IMT; VisionCare Ophthalmic Technologies, Saratoga, CA) [18,19]. The device was designed to allow patients to regain everyday functional abilities (e.g., reading, writing, and watching TV) and greater independence [20]. The IMT is currently the only treatment approved for patients with end-stage AMD in the United States. This paper discusses the QoL implications for patients with advanced AMD, as well as the current treatment and management options.

Quality of life

Advanced AMD is severely debilitating to patients, leading to reduced independence and significant emotional distress [21]. Patients with moderate vision loss from advanced AMD have a 32% decrease in QoL, which is similar to what patients experience after breaking a hip [22]. As the disease progresses, patients report a 60% decrease in QoL, which equates to the experience of someone with end-stage cancer who requires around-the-clock care. Despite this evidence, physicians often understate the impact end-stage AMD has on patients. Brown et al. for example, found that AMD patients have a reduced QoL ranging from 96% to 750% greater than what their eye care provider estimates [22].

Depression

It is well known that depression diminishes QoL [23-26]. It is the fourth major cause of disability worldwide [27] and a common side effect in people with vision loss [28-33]. Multiple studies have found close to a 30% prevalence rate of depression among elderly patients with advanced AMD, [27,34] and these patients are at an increased risk of suicide [35].

Patients with AMD struggle to read, eat, watch TV, recognize faces, and participate in hobbies and activities that they used to enjoy, often resulting in a feeling of hopelessness and clinical depression [17]. Many patients with AMD are legally blind and therefore cannot drive, which adds to social isolation and dependence on caregivers. Vision loss robs people of the joy of living, prevents them from pursuing pleasurable activities and engaging in their surroundings, and diminishes their self-esteem, autonomy, and perceived value to society [36,37].

Elderly patients with depression and end-stage AMD report extreme dissatisfaction in a variety of social and functional activities as compared with patients with either disorder independently, suggesting that the combination has a particularly negative impact on QoL [38]. Depression has been reported to exacerbate AMD symptoms, [39] causing many AMD patients to believe that their vision is worse than it is [33]. Patients with vision loss and depression often report challenges such as difficulty traveling to the clinic for appointments, trouble communicating with staff once there, and difficulty retaining the information provided [38]. Combined, these challenges and negative outlook lead to noncompliance, loss to follow-up, and worse outcomes overall [33].

In elderly patients, visual impairment is associated with increased cognitive decline [40,41]. A South Korean study of 170 AMD patients and 190 non-AMD community-based controls showed that visuospatial function, verbal memory, visual memory, and frontal function were impaired in AMD patients vs. controls. Mild cognitive impairment was also higher in AMD patients than in controls (52.4% vs. 26.8%; P<0.001), with the greatest cognitive impairment in those patients with poor visual acuity (≤ 20/100) [40].

Because depression has such a profound impact on QoL and AMD treatment and outcomes, it is now suggested that healthcare providers screen for depression among their elderly and vision-impaired patients. Relatively easy screening tests can be performed in-office in about 5 minute [32]. Once depression has been identified, supportive care is needed. Problem-solving therapy may help restore self-esteem by concentrating on the positive, or what the patient can do rather than what they cannot [42]. A self-management program consisting of health education and problem-solving skills may improve mood and self-efficiency and reduce emotional distress [26]. Furthermore, integrated mental health and low-vision intervention has been shown alleviate depressive disorders in patients with AMD by as much as half compared with low-vision rehabilitation alone [43].

The treatment options for patients with advanced AMD are limited and often unsuccessful long term, [16] therefore addressing the patient’s depression may have the biggest impact on overall QoL. Healthcare providers that recognize and evaluate depression symptoms in their patients can provide supportive care, and encourage patients to seek professional psychological help in concurrence with low-vision rehabilitation when appropriate.

Falls

Falls are the leading cause of injury-related death in the elderly [44] and can cause debilitating, often life-threating complications such as fractures, joint dislocations, and head and internal organ injuries that may incur significant medical costs in both lengthy hospital stays and nursing home admission [45].

Vision impairment is a well-known risk factor for falls and hip fractures in the older population, [46-49] and the risk is higher in patients with AMD than without [50]. AMD causes visual function loss, reduced contrast sensitivity, and difficultly viewing straight lines, all of which increases the risk of slips, stumbles, loss of balance, and falls caused by the patient’s inability to identify environmental hazards [51-53]. The Beaver Dam Study showed a correlation between poor visual acuity (20/25 or worse) and an increased risk of falls. The odds ratios for two or more falls in the past year for patients with poor vision were 2.02 (95% CI, 1.13–3.63) for current binocular acuity and 1.85 (95% CI, 1.10–3.12) for visual sensitivity [52]. Wood et al. found that 74% of patients with AMD reported sustaining a fall or non-fallrelated injury (e.g., lacerations or collisions with an object), while 30% of patients reported more than one fall [54].

Fear of falling is also higher in patients with AMD than without, which leads to anxiety, decreased mobility (e.g., walking, getting up and sitting down), and increased frailty [52,53,55]. Patients with AMD who fear falling are less likely to leave the house, which compounds social isolation and depressive symptoms. West et al. found that for every line of visual acuity lost, the odds for mobility limitations increased by 10%. Similarly, every 10% change in visual field equated to a 20% increase in the chance for mobility limitations [56].

Because falls and fear of falling have such a negative impact on QoL in patients with AMD, it becomes imperative to recognize those patients at high risk. Reduced contrast sensitivity has been shown to be the strongest predictor of falls and other injuries in patients with AMD [54] Melillo et al. developed a classification tree to help ophthalmologists and optometrists identify patients at high-risk of falling within 1 year [57]. Once high-risk patients have been identified, healthcare professionals should refer patients to rehabilitation specialists for guidance on interventions and modifiable risk factors such as exercise [58,59], video game technology [59,60], appropriate footwear, floor coverings, and hip protectors [61] to reduce the incidence of falls and the risk of injury.

End-stage amd

End-stage AMD is defined as moderate (≤ 20/80) to profound (20/600 or worse) vision impairment [62]. It is the most advanced form of AMD and is the leading cause of blindness in people over age 60 in high-income countries [1,2]. Patients with end-stage AMD experience central vision loss of and blurry peripheral vision. Figure 2 depicts the retina of a patient with end-stage AMD. These patients are most affected by diminished QoL and have difficulty with even the most simplistic of daily activities that rely upon vision.

Figure 2: The Retina of a Patient with End-Stage AMD.

Patients with end-stage AMD can maximize the impact of their remaining vision and learn how to use it to the best of their ability through low-vision training and vision rehabilitation. Low-vision specialists have shown some success in helping patients learn how to shift visual fields from central to peripheral vision. This specialized training has also led to a resurgence in the need for this subspecialty in the eye care field [63].

Current amd treatment and management landscape

The goal of AMD treatment is to preserve the patients’ remaining vision and prevent further visual decline. Pharmacologic treatment with intravitreal anti-vascular endothelial growth factor (VEGF) injections have become the mainstay of treatment for early- to intermediate-stage AMD; studies have found this treatment modality can reduce the odds of legal blindness from wet AMD by up to 70% over 2 years [36]. Unfortunately, the initial visual improvement is unlikely to be sustained over the long-term as the disease continues to progress, with a majority of patients losing those initial gains within 7 years (even with ongoing treatment adherence) [13]. Further, more than half of patients do not show signs of visual improvement with anti-VEGF therapy, and approximately 10% of patients do not respond at all to treatment [37]. There are currently no pharmacolgic treatments approved in the United States for end-stage AMD.

Laser treatments are used in some wet AMD cases, but their invasive nature may inadvertently destroy surrounding healthy tissue that exacerbates vision loss [64]. Laser treatments are predominantly used to slow the progression of the disorder rather than restore vision.

Low-vision rehabilitation

Low-vision specialists, along with a multidisciplinary team including other vision rehabilitation professionals, occupational therapists, and orientation and mobility specialists, are the primary caregivers for people with advanced vision loss. Low-vision rehabilitation can improve the QoL for patients with advanced AMD by teaching them skills such as how to use magnifying and adaptive devices like the IMT, how to navigate safely around their home and in public, and how to perform daily activities including getting dressed, cooking, and reading.

Patient compliance with low-vision rehabilitation services varies widely, as some people do not have access to reliable transportation services and/or must rely upon family members for help [65]. Yet there is ample evidence that low-vision rehabilitation has substantial utility and value [66]. Both the LOVIT and LOVIT II trials examined the impact of low-vision rehabilitation on veterans, concluding that patients who underwent rehabilitation showed significant improvement in reading, mobility, vision information processing, and visual motor skills compared to those who did not undergo rehabilitation [67-70].

Furthermore, the VITAL trial found that integrated low-vision and mental health intervention halved the frequency of depressive disorders in high-risk patients with AMD (12.6% vs. 23.4%), [43] thereby illustrating that low-vision rehabilitation can serve as a preventative measure to reduce the overall incidence of depression in the visually impaired.

Low-vision devices

Low-vision devices can improve daily function for patients with advanced AMD and help reduce depression. Large print books, highpowered lenses, desk, stand/handheld magnifiers, and electronic assistive technology can assist with reading, while telescopes and virtual reality devices can make watching TV and other distance activities more enjoyable. Large-button phones and keyboards with solid, contrasting numbers can help reduce social isolation, and talking and/or large-numbered clocks can help visually impaired patients easily keep track of their day. Other innovative, electronic vision enhancement systems (head-mounted, desktop, or handheld) can also assist patients with everyday activities such as applying makeup, getting dressed, and cooking.

Small telescopic devices, such as the Keplerian and Galilean telescopes, can be mounted on eyeglasses, and others are connected to computers so the person can see the object on a large computer screen. Adaptive computer software can also help improve visual performance [63].

Although these devices can enhance vision and improve QoL, many patents find them cumbersome to use and cosmetically unappealing. In addition, low-vision devices can be quite costly as most third-party insurance plans don’t pay for them [71]. With some prices reaching several thousands of dollars, this places many higher tech devices out of reach for many patients. Even when able to secure, training on use and optimal success may be hindered by previously mentioned barriers such as decreased cognition and motivation, depression, physical disabilities, and lack of transportation to ancillary providers for proper training.

Surgical options

Surgical options for the treatment of AMD are limited, regardless of disease stage. Cataract surgery may be helpful for patients with cataracts and early- to intermediate-stage AMD and result in improved QoL [72,73]. Specialized intraocular lenses (IOLs) and implantable telescopes (IMT) may help patients with late-stage AMD make the best of the vision they have left. IOLs for AMD are different from the monofocal IOLs used post-cataract surgery. These IOLs either improve vision through magnification or redirect images to the patient’s preferred retinal locus (PRL), thereby creating a prismatic effect. Implantable telescopes typically use a Galilean- or Cassegrain-style approach to magnify images in the patient’s central vision, allowing use of healthier areas of the patient’s retina and minimizing the effects of the central scotoma.

The IMT

The IMT is about the size of a pea (Figure 3), and is a fixed-focus, monocular prosthetic telescope using ultraprecise, quartz glass, wideangle micro-optics. It is implanted in the anterior chamber of only one eye using standard procedures similar to cataract surgery, and it uses the eye’s natural movements to enhance vision by creating a wider field of view. The fellow eye is used for peripheral vision, while the IMTimplanted eye is used for central vision and details.

Figure 3: The IMT Device.

The device is available in two magnification powers: 2.2X and 2.7X, with full field view of 24° and 20°, respectively [74,75]. The 2.7X device is almost exclusively used in the United States, because 5-year data revealed more visual gains over time as disease progressed than with the 2.2X device [76]. The 2.2X model does have its advantages, however, providing more light and a larger field of view for patients with less advanced disease and less demanding visual goals

The IMT has been proven to safely provide end-stage AMD patients with clinically meaningful improvements in NEI VFQ-25 scores longterm (mean scores more than 7 points above baseline) [18-20,76]. Patients have experienced improved QoL and general vision (near and distance) as well as improved psychosocial vision-targeted subscales such as social functioning, mental health, and dependency. On average, IMT patients experienced a 12.5% QoL gain [77]. Long-term study data 60 months post-implantation revealed that 47.4% of patients maintained a 3-line gain in vision, while 61.8% maintained a 2-line gain [76]. Adverse events did occur, but were well within expectations, and included iris transillumination defects, iritis, posterior synechiae, and guttata [18].

The IMT has alleviated many of the issues facing patients with advanced AMD. Not all patients are qualified candidates for the device, and part of that lies with the patient’s dedication to a low-vision rehabilitation program as well as ensuring that the patient’s goals align with what the technology can offer. Patients must commit to a minimum of 6 low-vision rehabilitation visits in order to use the device effectively and adjust to the presence of diplopia, image size differences, and field-of-view restriction [20]. Patients will also require ongoing care under a vision rehabilitation specialist to monitor visual and functional status. Patients who are unwilling to commit to this level of care or who do not have reliable transportation and caregiver support are not optimal candidates for the implant.

Careful selection in choosing the eye for IMT implantation is also critical. The implanted eye should become the better-seeing eye, which will help patients achieve maximum visual gains. Potential candidates must be thoroughly vetted through a simulation test using an external telescope system administered by a qualified low-vision specialist, patient questionnaires, and dominance testing [20].

Other technologies

There are currently no other technologies approved for the treatment of end-stage AMD in the United States. A few investigational devices are in development outside of the United States (e.g., the iol-AMD, the IOL-VIP System, and the Lipshitz macular implant), but these devices do not provide the magnification of the IMT, [78-83] and QoL improvements are not uniform or verified.

Age-related macular degeneration is a chronic, debilitating eye disease affecting older and elderly patients and has a profound, often underappreciated impact on patient QoL. Patients may frequently experience reduced cognition, depression, social isolation, reduced independence and mobility, and a greater chance of falls and injuries with potentially catastrophic results. Because there is no cure, improving patient QoL should be the goal for healthcare professionals across disciplines. It becomes imperative for those physicians and providers caring for the elderly to understand the ancillary effects of vision loss, especially from AMD, and to have a general understanding of treatment and management options to improve QoL in their patients. The IMT can be an option to enhance QoL in patients with end-stage AMD for which no other medical or surgical option exists. Many patients can regain independence with improved visual function for a variety of activities.

VisionCare Ophthalmic Technologies supported the publication of this article.