Comprehensive ophthalmologists will have meaningful role in treating geographic atrophy
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Age-related macular degeneration is one of the leading causes of blindness in the United States. It is an age-related degeneration, so it primarily affects our senior population.
At age 60 to 70 years, only 0.7% of the U.S. population manifests AMD, but by age 80 to 90 years, it is present in 12% of Americans. This means less than one per 1,000 patients in their 60s will have AMD compared with more than one in 10 in their 80s.
The natural history is slow progression, usually over 20 years or more. Fine drusen and retinal pigment epithelium (RPE) disruption with areas of depigmentation and pigment clumping are the earliest funduscopic signs. If there is no visual loss, these can be considered precursor findings, and not all patients with these precursor fundus findings will develop visually significant AMD.
An important question is, how do we manage these patients? We all support evidence-based medicine, but there is also an art to medical therapy. I will share a few personal thoughts.
When I observe fine drusen and/or RPE dispersion, I share these findings with patients but tell them they do not yet have AMD, which is a frightening diagnosis. I tell them that they are at higher risk to develop AMD and will need a follow-up visit for any vision loss and at a minimum an annual visit. The key risk factors for developing visually significant AMD are genetics, behavior and associated diagnosis. I ask about family history of AMD but currently do not recommend genetic testing. I encourage a diet rich in green leafy vegetables, but few comply. While there is no evidence that treatment with AREDS-type vitamins affects the progression of early AMD, I discuss this option with patients. Most chose to adopt vitamin therapy using a standard daily vitamin plus an AREDS vitamin. Those who smoke are encouraged to stop. Smoking cessation may require referral to an expert. Patients with hypertension and/or hyperlipidemia are encouraged to seek good control with their primary care physician.
Once there are drusen, RPE changes and vision loss, the patient has early AMD. This group represents about 60% to 65% of AMD patients. Again, there is no level 1 evidence that AREDS vitamins help early AMD patients, but most of my patients choose to use them. As the drusen enlarge, RPE changes increase and visual loss progresses, we enter the stage of intermediate AMD, which represents about 20% to 25% of patients. Level 1 evidence supports as fact that these patients can delay the progression of their disease by using a daily vitamin and an AREDS vitamin. Some retina specialists also recommend omega-3 supplements. These vitamins are available in combined formulations from several companies.
Of the 20 million U.S. patients who have AMD, only 10% to 15%, or about 2 million to 3 million, develop late AMD. Late AMD can manifest as wet/exudative AMD with subretinal neovascularization and retinal or subretinal fluid, geographic atrophy (GA) with progressive zones of complete loss of RPE and photoreceptor death, or a combination of the two. About 45% of late AMD cases have wet AMD, 45% GA and 10% manifest both in combination.
Treatment of wet AMD with anti-VEGF intravitreal injections is a modern-day miracle and the most common procedure performed in ophthalmology today. Two to four monthly anti-VEGF injections followed by a treat-and-extend protocol result in significant vision improvement for most wet AMD patients, and they can easily appreciate the benefit. There is financial, personal and family pain but significant and appreciable gain.
The treatments for dry AMD and GA are quite different. AREDS vitamin supplementation for intermediate AMD and monthly intravitreal injections for GA only retard the progression of visual loss, with no expected improvement in current visual acuity or function. Vitamin therapy is easy to adopt, but monthly intravitreal injections are a challenge even in wet AMD, where the benefit is clear to the patient and family. While there are an equal number of wet AMD and GA patients in the U.S., I expect fewer GA patients will opt for intravitreal injection therapy.
We now have two FDA-approved intravitreal injection products that can delay the progression of GA. Treated patients can expect to retard the progression of their disease and retain reading and driving vision for more years of their remaining life than untreated patients. The decision to adopt intravitreal injection therapy for GA patients needs to be personalized and may require significant counseling. Smoking cessation is especially critical for the GA patient. Patients who have family members or close friends who have suffered significant visual and functional disability from GA are more likely to choose to be treated. In addition, GA patients who have bilateral disease with severe visual loss in the more advanced eye are likely to be motivated to treat their better eye.
I believe the comprehensive ophthalmologist will need to play a meaningful role in managing and counseling these patients. The natural history of AMD evolves over 20 years or more. We will need to differentiate between the stages of AMD and diagnose wet AMD and GA with accuracy. Fortunately, this can be done reliably with careful fundus examination, OCT and, if available, fundus photography and autofluorescence. All of us will need OCT, and many of us will want to acquire a fundus camera, ideally with autofluorescence and widefield capability. We must work with our retina colleagues and learn whom and when to refer. There is no need to refer an early or intermediate AMD patient to our already overburdened retina specialists. We can follow and treat these patients. The patients who develop wet or combined AMD deserve referral for intravitreal injection.
Those patients with GA who after counseling choose not to proceed with intravitreal injection therapy can be managed without referral until they wish to seek therapy. I expect many patients with GA will initially fall into this category. As their disease progresses, some patients will change their minds and request treatment, but not every GA patient will immediately opt for monthly intravitreal injections. All patients with significant visual loss deserve an evaluation for appropriate low vision aids.
We have much to learn, and many more advances can be anticipated as the innovation cycle fertilized by significant human and financial capital works its magic. As the population ages, nearly every ophthalmologist will play a role in counseling and managing patients with AMD. It is important for each of us to be prepared for this important task.
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