Written by RI Research & Innovation Manager, Dr Nabin Paudel, BOptom, PhD
What is age-related macular degeneration?
Age-related macular degeneration (AMD) is a disease that damages the macular region of the retina, leading to gradual and progressive loss of central vision.
The retina is a thin layer of tissue at the back of the eye and the macula is the part of the retina which is responsible for central sharp vision and color vision. Photoreceptor cells – cells that are sensitive to light (particularly the cone) are densely packed in the macular region. The outermost layer of the retina is the retinal pigmented epithelium (RPE), a single layer of cells that plays a key role in maintaining the health of photoreceptors by regulating nutrients and waste products to and from the retina. The RPE also absorbs excessive light energy and protects the outer retina. In AMD, the RPE cells in the macular region begin to degenerate followed by damage to the photoreceptors, causing distorted vision and dark spots in a person’s central vision.
Macular degeneration is the third leading cause of irreversible vision loss in people over 60 years of age. Globally, the number of people with AMD was approximately 200 million in 2020 and is expected to increase to approximately 300 million by the year 2040. The economic burden of AMD is immense. In a recent study conducted by Retina International, it was found that the per annum estimated cost incurred due to advanced AMD in Bulgaria, Germany and the USA ranged from 449 million EUR (Bulgaria) to 43 billion EUR (USA).
Symptoms of AMD:
In the early stages of the disease, there are no noticeable symptoms. As the disease progresses, patients may notice slight blurring or distortion of central vision and difficulty while reading in low luminance. Late AMD significantly affects the central vision, therefore symptoms are more noticeable as dark or grey spots (scotoma) start appearing in the central vision. Late-stage AMD affects daily living activities including recognizing faces. See this video from National Institute of Health, USA on how people with late AMD perceive the world.
Types of Late Age-related Macular Degeneration:
There are two types of late age-related macular degeneration: Neovascular type (also known as wet AMD or neovascular AMD) and Atrophic Type (also known as dry AMD or geographic atrophy.)
The rate at which early/intermediate AMD progresses to late-stage AMD is not clear, it can be rapid or slow. People can develop one or both forms of AMD. The disease can be uniocular (in one eye) or binocular (both eyes).
Neovascular AMD or wet AMD:
Neovascular AMD is characterized by the formation of abnormal new blood vessels under the retina (called as choroidal neovascularization). These new blood vessels are weak and can leak blood and fluid in the spaces between the retina and choroid causing damage to the RPE and photoreceptor cells. Vision loss in this condition is rapid and sometimes people can develop profound vision loss in a matter of days or weeks.
Geographic Atrophy or advanced Dry AMD:
Geographic Atrophy is characterized by the formation of atrophic lesions that occur due to the loss of outer retinal tissues and surrounding blood vessels. The process is thought to be due in part to inflammatory and degenerative insults. The term geographic atrophy comes from the appearance of the regions of atrophy that look like a map to the doctor who is examining the retina. Vision loss in geographic atrophy is slow but progressive.
Efforts to prevent and delay the progression of AMD:
The only effective treatment to delay the progression of AMD to the advanced form is the dietary supplement of high doses of zinc and antioxidants. The supplement includes high doses of Zinc, Vitamin C, Vitamin E, Lutein, Zeaxanthin and Copper. The Age-related Eye Disease Study (AREDS) that used this treatment in a longitudinal multicenter clinical trial found that the supplement reduced the risk of progression to advanced AMD by 25% after an average follow up duration of 6.3 years. There have been some studies that have showed a protective role of fish and omega-3 fatty acids consumption, but the results are mixed.
Treatment of AMD:
Anti-Vascular Endothelial Growth factor (Anti – VEGF) injection into the vitreous cavity is the current gold standard treatment for neovascular AMD. Anti VEGF injections inhibit the angiogenic protein VEGF that is produced in the retina and induced by the lack of oxygen and other insults. VEGF promotes formation of new blood vessels that are weak and fragile. Widely used anti-VEGF drugs include Ranibizumab, Bevacizumab and Aflibercept. The injections can be done quickly and seamlessly in an outpatient setting with little to no recovery time required for the patients and minimal side effects. However, compliance of these injections among the patients has been a challenge as they require frequent visits to the clinician.
There is no FDA approved treatment available for the atrophic form of AMD (GA). Several clinical trials are underway and have demonstrated some encouraging findings in phase 3/4 trials. To find ongoing and completed clinical trials for GA treatment please follow the link: Clinical Trials in GA.
Future research:
AMD is a complex disease and practical therapeutic strategies may require a combination of multiple factors such as diet, lifestyle modification and improved personalised treatments. Several therapeutic areas that are currently being explored – either to slow down the progression to advanced AMD or to prevent AMD onset are: gene therapy, bioelectronic implants and stem cell therapies. Furthermore, to reduce the burden of frequent injections of existing anti-VEGF injections, research is being conducted to develop improved interventions that aim to considerably reduce the injection frequency. For all clinical trials that have been completed or are happening in the age-related macular degeneration space please visit the clinicaltrials.gov website.
Resources for support:
Retina International works hard to develop resources to aid the retina patient community. For more information on AMD, please visit our AMD toolkit: https://amd.retinaint.org/.
We’ve also partnered with Roche to create the Visionaries hub, a support resource developed by patients for patients. It includes questions and answers about AMD, plus inspiring true stories from people living with the condition as well as their caregivers.
We also encourage you to visit Living Well With Low Vision, an online resource developed by Prevent Blindness to educate those with loss of vision on how to maintain their independence and quality of life.
Last but not least, for more information on the economic burden of AMD, join us for the launch of our AMD Impact Study during our World Sight Day webinar this Thursday, October 13th.
References:
- The socio-economic impact of age-related macular degeneration (AMD) in Bulgaria, Germany and the USA: A disease burden assessment of GA and nAMD. Retina International, 2022
- Wong WL, Su X, Li X, Cheung CM, Klein R, Cheng CY, Wong TY. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. The Lancet Global Health. 2014 Feb 1;2(2):e106-16.
- Mitchell P, Liew G, Gopinath B, Wong TY. Age-related macular degeneration. The Lancet. 2018 Sep 29;392(10153):1147-59.
- Thomas CJ, Mirza RG, Gill MK. Age-Related Macular Degeneration. Medical Clinics. 2021 May 1;105(3):473-91.
- 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. 8. Arch Ophthalmol 2001; 119: 1417–36
- clinicaltrials.gov