Age-Related Macular Degeneration

February 13, 2017 By Dr Chang

Epidemiology

Age-related macular degeneration (AMD) is the number 1 cause of blindness in the Western world. It affects 8 million Americans, including more than 30% of American older than 75 years of age. Even though it is a disease that mostly affects the older population, as many as 6-7% of population of age 40 and over have clinical findings of AMD. Its prevalence is projected to increase by 50% by 2020.

Risk Factors

The most important risk factors to develop AMD include age, family history, cigarette smoking, obesity, and race (with Caucasian at highest risk, Hispanics and Asians moderate, and African-Americans lowest). Of these, smoking and obesity are the only modifiable factors, and thus smoking cessation and lifestyle modification are almost always recommended for AMD patients. Other less well-substantiated risk factors include blue light emitted from TV, laptop, smartphone, and LED/CFL light bulbs; sunlight exposure, hypertension, hyperlipidemia, hyperopia (farsightedness), light iris colors, and female gender. To date, more than 30 gene loci have been found to confer increased risk of AMD. While genetic testing is available, these services are not covered by insurance, and are not currently recommended by the American Academy of Ophthalmology except for research purpose.

Pathophysiology

Early on in the AMD process, lipids are deposited in Bruch’s membrane, which is a barrier between the retina and the underlying choroid. These lipids ultimately become apparent on clinical exams, and are called “drusen.” Drusen cause thickening and calcification of the Bruch’s membrane, causing fluid and nutrient flow from the choroid to the retina. Eventually, as the disease progresses, the Bruch’s membrane breaks down and blood vessels invade from the choroid into the subretinal space, causing what is referred to as “wet AMD” because the vessels can leak fluid or bleed into the retina. AMD does not need to be wet- in fact, 80-90% of all AMD are of the dry type. In dry AMD, photoreceptors simply degenerate as a result of poor nutrient flow from the choroid, but there are no abnormal choroidal vessels causing fluid or blood accumulation.

Diagnosis

 A careful, dilated fundus exam is crucial to the diagnosis of AMD. If drusen are detected on exam, your doctor may order fluorescein angiography to see whether there is leakage from abnormal blood vessels. In recent years, the advancement in the imaging technology called optical coherence tomography (OCT) has allowed ophthalmologists to see different layers of the retina and the choroid clearly, and thus angiography (which is invasive and more time-consuming) is not utilized as often. To monitor treatment progress, OCT is done on every clinical visit to assess the amount of fluid in and under the retina. Angiography is typically done at the initial assessment to decide whether AMD is dry (no leakage) or wet (abnormal leakage). Some physicians would repeat angiography after having treated patients for a while to assess for therapeutic response, or when treatment change is being considered.

Treatment

If AMD is dry (or “non-exudative”), routine monitoring and eye vitamins are recommended. The patient is typically examined by the doctor once a year, unless there is an acute deterioration in the vision. Amsler Grid has been in place for home monitoring since the 1940s, but there are now commercially available computer devices that generate alarm signal to the doctor’s office when there is a change in the patient’s self-testing. While patients with early dry AMD would not necessary benefit from nutritional supplementation, it has been shown that such supplementation can reduce the risk of disease progression over 5 years by as much as 25% in patients with intermediate stage of the disease. The supplementation is called AREDS 2 (AREDS refers to Age-Related Eye Disease Study, while the number 2 refers to the revised formula) and contains vitamin C, vitamin E, zinc, copper, lutein, and zeaxanthin. You should talk to your doctor before deciding if the AREDS 2 is right for you.

In addition to supplementation and a healthy lifestyle, smoking cessation is extremely important in smokers who are newly diagnosed with AMD. UV protection with sunglasses are also highly recommended to prevent disease progression. Despite all these, dry AMD can occasionally progress to the advanced stage called geographic atrophy, which can be devastating to the vision if the fovea is involved. There is currently no treatment for this stage of the disease, but clinical trials involving stem cells are underway.

In case of wet (exudative) AMD, eye injections are given to keep the abnormal vessels from the choroid from leaking. The injections are done with topical anesthetics in the office, typically every 1 to 2 months. Depending on the treatment response, the treating physician may elect to lengthen the interval between injections (“treat-and-extend”) or to treat only when there is change in patient’s vision or when new leakage is noted on imaging tests (“as needed”). Very few physicians nowadays employ monthly injections indefinitely, as it creates a huge burden to both the patient and physician alike. There are currently 3 medications available and they all target the vascular endothelial growth factor (VEGF): bevacizumab (Avastin®), ranibizumab (Lucentis®), and ablifercept (Eylea®). Which drug to employ depends on many factors, not least the cost. In cases of wet AMD that are resistant to injections, vitreoretinal specialists may employ photodynamic therapy (PDT) to augment the treatment efficacy or potentially lower the treatment burden from the continuous injections. PDT is available here at MERSI.

Surgery is not routinely done for AMD, except in the rare circumstance when wet AMD is complicated by a massive submacular hemorrhage. A combination of pars plana vitrectomy, tissue plasminogen activator, anti-VEGF, and intraocular gas can be utilized to help evacuate from the subretinal space the hemorrhage, which is toxic to the photoreceptors. Patients who have this AMD complication very often experience significant, irreversible vision loss.

In summary, AMD is becoming more prevalent as the life expectancy of our population increases. The key to proper management of AMD is early detection, vigilant avoidance of modifiable risk factors, prompt treatment, and proper longitudinal monitoring.

Dr. Chang is a vitreoretinal and uveitis specialist at MERSI. He is accepting new patients and has a strong interest in macular degeneration among other retinal diseases.

 

 

 

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