age-related macular degeneration
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Age-related macular degeneration is a progressive and chronic disease of the eye that is the leading cause of central vision loss in patients living in developed countries.1The disease damages the central part of the retina, which is involved in allowing us to see objects ahead of us. Age-related macular degeneration does not lead to complete loss of vision since only the central vision is affected. Patients with macular degeneration usually retain their peripheral vision.3

Although many factors may contribute to the development of the disease, age is the most important risk factor. Patients over the age of 50 are more likely to develop this irreversible disease.3 With an ageing population around the world, age-related macular degeneration is the third most common cause of blindness.4

This disease is more prevalent in developed countries because patient lifespan is longer due to more favourable living conditions and access to care. In addition, there seems to be a difference in the rates of age-related macular degeneration among different races.

One analysis showed a prevalence of 5.4% among white patients, 4.6% among Chinese patients, 4.2% in Hispanics, and 2.4% in African-Americans. The prevalence of age-related macular degeneration is more important in the western countries; however, due to the westernization of diet and lifestyle, other countries are reporting increases in the rates of the disease. Considering the overwhelming statistics and the incurable nature of the disease, strong efforts are aimed at preventing age-related macular degeneration.5

Pathophysiology

The retina is a very important structure of the eye since it is where the light-sensitive cells are located. This structure is found at the back of the eye. The macula is the spot in the centre of the retina with the highest concentration of light-sensitive cells, called rods and cones, which produce the sharpest images. These cells also allow for colour vision.  The retinal pigment epithelium contains cells that are located immediately behind the rods and cones to keep them healthy and functioning normally. In age-related macular degeneration, the macula progressively deteriorates.3

Dry vs. Wet Macular Degeneration

There are two different forms of age-related macular degeneration: dry and wet. All cases of age-related macular degeneration start as the dry form and may progress to the wet form.7

Dry age-related macular degeneration is characterized by the deterioration of the retinal pigment epithelium which causes the slow destruction of the cells in the macula.

Wet age-related macular degeneration occurs in about 15% of patients. This form of age-related macular degeneration is more severe than the dry form. It results from the development of abnormal new blood cells under the retina. This increased blood flow around the retina causes swelling of the macula. If blood pools into this small area the macula can become raised in the retina and may detach from the retinal pigment epithelium. Scarring may then appear under the retina. 2

The prevalence of the wet form of age-related macular degeneration is lower than the dry form; however, between 80% and 90% of vision loss occurring in age-related macular degeneration is a result of the wet form of the condition. 2

Age is the most critical risk factor for age-related macular degeneration. Other risk factors include:

  • Ethnicity 3
  • Family history 7
  • Genetic abnormalities 3
  • History of Smoking 3
  • Obesity 3
  • High intake of saturated fats and low intake of omega-3 fatty acids 3
  • Cardiovascular disease 7
  • High blood pressure 7
  • Sun exposure7
  • Low dietary intake of vitamins A, C, and E and zinc 1

Symptoms

The symptoms of age-related macular degeneration depend on the form of the disease.

Dry age-related macular degeneration symptoms include:

  • slow and painless loss of central vision in both eyes,
  • difficulty noticing fine details and reading,
  • a washed out appearance of objects in central vision,
  • and development of blind spots in their vision.

Patients with wet age-related macular degeneration will experience a faster progression of the disease. The progression of the disease may be days or weeks. If one of the abnormal blood vessels bleeds the progression may be even quicker. As with the dry form, peripheral vision is usually not affected. Unlike the dry form, in wet age-related macular degeneration, one eye will be affected at a time and patients will experience difficulties watching television and reading.7

Diagnosis

An eye doctor can examine the eye for signs of age-related macular degeneration. By shining a light into the back of the eye through an ophthalmoscope, eye specialists can detect signs of age-related macular degeneration before any damage causes permanent symptoms. For the wet form of age-related macular degeneration, the doctor will take colour photographs of the eye or will take a closer look at the blood vessels around the retina through another diagnostic test called fluorescein angiography.7

Stages of Disease

There are four stages of age-related macular degeneration: early, intermediate, advanced dry, and advanced wet or neovascular age-related macular degeneration.

In the early stages, doctors may detect drusen in the eye. Drusen are deposits of lipids under the retina. These deposits do not cause age-related macular degeneration but they increase a patient’s likelihood of developing the disease. As the disease progresses from early, to intermediate, and finally to the advanced stage, the number and size of the deposits increases.

In the early stages, mild abnormalities will be seen in the retinal pigment epithelium. As the disease progresses the amount of damage to the retina will expand. In the very advanced stage of wet age-related macular degeneration, swelling of the eye and bleeding may occur. 3

Treatments

The damage caused by age-related macular degeneration is irreversible and non-treatable. 3 Throughout the progression of the disease, patients will require low-vision aids to adapt to the loss of central vision. These include magnifiers and high-power reading glasses. 7

In wet age-related macular degeneration, vascular endothelial growth factor inhibitors can be effective in decreasing the loss of vision. 10 Photodynamic therapy and laser photocoagulation are non-medicinal techniques previously used in the treatment of age-related macular degeneration; however, are no longer considered the first line of treatment.1

Laser Photocoagulation

Laser photocoagulation was introduced in the 1980s and showed promising results in about 20% of wet age-related macular degeneration cases where the abnormal blood vessels were formed in specific areas of the macula. Due to its limited success and high rates of the disease recurring it is no longer in widespread use for the treatment of wet age-related macular degeneration. 1

Photodynamic Therapy

Photodynamic therapy involves an injection of a photosensitive dye that accumulates in the newly developed blood vessels and is activated by infrared light. The activated dye causes damage to the surrounding blood vessels and this strategy helps to control the development of the abnormal vessels that cause wet age-related macular degeneration. Today this treatment is rarely used.1

Vascular Endothelial Growth Factor Inhibitors

Vascular endothelial growth factor inhibitors are the standard of care for the treatment of wet age-related macular degeneration. These include ranibizumab, bevacizumab, aflibercept, and pegaptanib. Vascular endothelial growth factors block the development of blood vessels. They also help to reduce the swelling of the macula and restoring the normal structure of the eye. The administration of these agents is through injections into the eye. Local numbing agents are used to lessen the pain associated with the injection. Since the eye is very prone to infections, the doctor administering the treatment will also have the patient use antiseptic drops into the affected eye prior to receiving the needle. If the treatments are effective, patients will receive a dose every two to four weeks. 10

The most common side effects are pain and bacterial infections. Bacterial endophthalmitis is the most severe consequence of these injections and requires quick treatment to prevent a drastic loss of vision. 10

Prevention

Since age-related macular degeneration is not a treatable disease, prevention must be emphasized. In dry age-related macular degeneration, there is no way to reverse the damage. Certain supplements can help patients with extensive drusen, pigment changes in the macula or signs of atrophy or cell death of the macula reduce the likelihood of developing the advanced form of the disease by about 25 percent. 2

Oxidative stress is thought to play a role in the development and progression of age-related macular degeneration. Vitamins and minerals that act as antioxidants have been studied for their effects on slowing down and preventing age-related macular degeneration.

Vitamins and minerals

Two large studies on antioxidant formulations for preventing age-related macular degeneration were conducted in 2001 and 2013.11 In 2001, the age-related eye diseases (AREDS) formulation contained zinc oxide 80mg, copper 2mg, vitamin C 500mg, vitamin E 400 units, and beta-carotene. In 2006, the formulation was modified slightly (AREDS 2) to reduce the amount of zinc oxide to 25 mg and to substitute beta-carotene for zeaxanthin 2mg and lutein 10mg. Both formulations showed a decrease in the risk of vision loss and a decrease in the risk of progression to advanced age-related macular degeneration. Smokers are must avoid the use of the original AREDS formulations with beta-carotene since there is a risk of developing lung cancer in smokers taking beta-carotene supplements. 3

The only two formulations that were studied in depth are the PreserVision Eye Vitamin AREDS Formula and the PreserVision Eye Vitamin AREDS 2 Formula. It is recommended that patients use the exact products that were used in the study since other similar products have different combinations of ingredients and their effectiveness has not been extensively studied. 3

Controlling risk factors

Controlling risk factors for age-related macular degeneration is also important. Smoking cessation and maintaining a healthy body weight are major lifestyle changes that can help prevent or slow down the progression of the disease.

Age-related macular degeneration is a disease usually affecting people of advanced age. With a rising life expectancy in the western world, this disease is expected to be more and more discussed in routine check-ups. Since treatment options are lacking, a focus on quick diagnosis and detection of clinical signs of a progressing disease are necessary. Once a diagnosis is established, doctors and patients must discuss methods for slowing down the progression and preservation of the eyesight. Visual aids and counselling may help patients with advanced loss of vision cope and function with limited sight. Finally, current studies are investigating new treatment options and effective preventative measures, and visual prostheses. These advances will, one day, provide better outcomes for patients with age-related macular degeneration. 1

Written by Jessica Caporuscio, PharmD

Read about the latest research on age-related macular degeneration here. 


References:

  1. Lim LS, Mitchell P, Seddon JM, et al. Age-related macular degeneration. Lancet. 2012
  2. Mehta, S. Merck Manual Professional Version. Age-Related Macular Degeneration (AMD or ARMD). 2017 https://www.merckmanuals.com/en-ca/professional/eye-disorders/retinal-disorders/age-related-macular-degeneration-amd-or-armd
  3. Canadian Pharmacist’s Letter. Management of Eye Disorders: Age-related Macular Degeneration, Cataracts, and Glaucoma. Self-Study Course. 2017. canadianpharmacistsletter.therapeuticresearch.com
  4. Priority Eye Diseases: Age-Related Macular Degeneration. 2010. International Council of Ophthalmology. http://www.who.int/blindness/causes/priority/en/index7.html
  5. Current Knowledge and Trends in Age-Related Macular Degeneration. Genetics, Epidemiology, and Prevention. Retina. 2014.
  6. National Eye Institute. Facts About Age-Related Macular Degeneration. National Institutes of Health. 2015. https://nei.nih.gov/health/maculardegen/armd_facts
  7. Mehta, S. Merck Manual Consumer Version. Age-Related Macular Degeneration (AMD or ARMD). 2017. https://www.merckmanuals.com/en-ca/home/eye-disorders/retinal-disorders/age-related-macular-degeneration-amd-or-armd
  8. Sparrow JR, Hicks D, Hamel CP. The retinal pigment epithelium in health and disease. Curr Mol Med. 2010
  9. Porter, D. What Are Drusen? American Academy of Ophthalmology. 2018. https://www.aao.org/eye-health/diseases/what-are-drusen
  10. Potter, M. Age-Related Macular Degeneration. Canadian Pharmacist Association. RXTX. 2018. https://www.e-therapeutics.ca/
  11. National Eye Institute. Age-Related Eye Disease Study-Results AREDS. 2013. https://nei.nih.gov/amd
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