Macular Degeneration

Original Editor - Lucinda hampton

Top Contributors - Angeliki Chorti and Lucinda hampton  

Introduction[edit | edit source]

A medical illustration depicting macular degeneration

Macular degenerative changes involve the central part of the retina that is the fovea. The retina is a light sensitive neural tissue at the back of the eye that serves as a film, on which the image is projected. Central vision is affected, resulting in difficulty in reading, driving, recognising faces, distinguishing colour contrasts and distance/depth. Macular Degeneration (MD) accounts for 8.7% of all types of blindness worldwide.[1]

Age-Related Macular Degeneration (ARMD) is one form of macular degeneration and it is the most common cause of blindness prevalent in developed countries, particularly in people older than 60 years. The number of people living with macular degeneration is expected to reach 196 million worldwide by 2020 and increase to 288 million by 2040.[2]

Types[edit | edit source]

Depiction of a woman suffering from ARMD. A normal macula has been in shown in comparison with the two types of macular degeneration - dry and wet.

There are two basic types of Macular Degeneration: “dry” and “wet.” [2][3]

  1. The dry form of macular degeneration, also known as geographic atrophy (GA), in which the light sensitive cells of the macula slowly break down by lipid-containing deposits causing pigment disturbance with loss of photoreceptors and choroidal capillaries.. These deposits are known as drusden and subretinal drusenoid deposits (SDDs) and refer to different disease processes.[4] Dry MD is the most common type, accounting for 90 percent of diagnosed cases.
  2. Wet (exudative) macular degeneration, or neovascular accounts for approximately 10 percent of cases, but results in 90 percent of legal blindness. It is considered advanced macular degeneration (there is no early or intermediate stage of wet macular degeneration). Wet macular degeneration is always preceded by the dry form of the disease.

Causes[edit | edit source]

The specific factors that cause macular degeneration are not conclusively known, and research into this little understood disease is limited by insufficient funding. At this point, what is known about ARMD is that the causes are complex and multifactorial, including both heredity (e.g. family history of ARMD) and environment. Several risk factors have been identified and associated with this disease:

  • Aging involves a process of progressive and accumulated low oxidative damage and adaptive parainflammatory responses consistently increasing the risk of ARMD in related studies. [5]
  • Inflammation seems to play an integral role in the pathogenesis of ARMD. [6]
  • Smoking is the second most important modifiable risk factor for macular degeneration. Studies suggest that the risk is not only far greater than non-smokers, it promotes the development of ARMD earlier in life. [7]
  • A mild to moderate association between elevated blood pressure and ARMD has also been described. [8]
  • Atherosclerotic lesions increase the risk of late ARMD. No consistent relationship between cholesterol level and ARMD has been documented. [1]
  • Previous cataract surgery has shown strong and consistent associations with late ARMD. [8]

Scientists are working to understand what causes the cells of the macula to deteriorate, seeking a macular degeneration treatment breakthrough.[9]

Symptoms[edit | edit source]

Dry macular degeneration sometimes doesn't cause any symptoms. When symptoms do occur, they may include:

  • increasingly blurred vision
  • faded colors
  • difficulty recognizing faces
  • gradual increase in the haziness of central vision
  • straight lines appear wavy or crooked
  • blurred or blind spot in the center of your field of vision
Scenes as they might be viewed by a person with age-related macular degeneration.

Symptoms of wet macular degeneration begin abruptly and worsen rapidly. They include:

  • distorted vision; straight lines may appear wavy or crooked
  • decreased central vision
  • decreased intensity or brightness of colors
  • blurry or blind spot in your field of vision

Macular degeneration generally does not affect side vision, even in advanced cases. [10]

Diagnosis[edit | edit source]

  • History taking. Patients with AMD may report changes and vision loss, especially when light is low. The patient should also be asked about distorted vision (metamorphopsia), an early sign of AMD. [3]
  • AMSLER Grid. This grid tests for early signs of distorted vision. The lines should look straight and the boxes should appear the same size, with each intersection forming a 90 degree angle. [11]
  • Ophthalmological Examination. This may include visual acuity (best corrected) examination and funduscopic evaluation with dilated pupils. [3]
  • Optical Coherence Tomography (OCT) and OCT angiography are non-invasive imaging that has a key role in diagnostic confirmation of ARMD. [3]
  • Fluorescein angiography usually takes place when there is suspicion of neovascularisation (wet ARMD) and is considered the gold standard for its diagnosis. [3]

Management[edit | edit source]

Low Vision Center Store Sign.jpeg

There is no cure for wet or dry macular degeneration. Some treatments can help slow or stop the disease from getting worse. The earlier treatment is started, the more vision is likely to be saved.[10] Follow-up visits are conducted to document the progression of the disease and to be able to intervene appropriately. Applications that aim to detect exudative recurrences of macular oedema have been developed as a home vision monitoring digital health tool between visits, [12] but these can be used only in addition to medical follow-ups. [13]

Management strategies include:

  • For early ARMD, pursuing lifestyle changes like a proper diet, exercise, avoiding smoking, and protecting your eyes from ultraviolet light. [9]
  • The Age-Related Eye Disease Study (AREDS) documented that antioxidant and zinc supplementation decreases the risk of ARMD progression and vision loss in intermediate stages of the condition. [14][15]
  • Photodynamic therapy: Treatment that can help control the abnormal blood vessel growth and bleeding in the macula for those with wet macular degeneration.
  • Hormone replacement therapy or estrogen therapy in women after menopause has been found to have a potential protective effect in some studies but there is still no consensus. [16][17][18]
  • Physicians have also used anti-VEGF bevacizumab injections in the forms of Avastin™ (an “off-label” treatment for wet macular degeneration), Lucentis, and Eyelea. This approach may prevent the development of abnormal blood vessels leaking into the macula, and thus, the progression of wet ARMD, but it may require repeated injections of the medication. [19]A new therapy using the biological drug Vabysmo (faricimab-svoa) has also been lately approved in Europe for the same condition. [20]
  • Vision rehabilitation and low vision aids: Help improve the quality of life for those who are visually impaired [2]

Future directions in management of MD[edit | edit source]

  • New methods have been developed to promote the delivery of medications. Genentech's Susvimo, FDA approved in October 2021, is a port delivery refillable (every six months) system that is implanted into the eye.
  • A new local epigenetic target (FTO protein) has been identified that prevents the development of abnormal blood vessel overgrowth in the retina and possibly tackles the issue of drug resistance with conventional therapy. [21]
  • Gene therapy: CRISPR/ Cas9 or siRNAs may be used to target cytokines leading to inflammation. [6]
  • Stem cell therapy: Development of safe and efficient stem cell therapies are under way to help some patients with ARMD [22]

Physiotherapy[edit | edit source]

Balance-board-benefits.jpg

Older people with ARMD have impaired balance, slow visual reaction times, and poor vision, which in combination result in a significantly greater risk of falls than population norms.

Strategies to enhance balance may be particularly beneficial to prevent falls in this group[23]. See Balance training, Otago Exercise Program.

See also Eyesight in the Elderly

References[edit | edit source]

  1. 1.0 1.1 Ruia S, Kaufman EJ. Macular Degeneration. StatPearls [Internet]. 2021 Aug 9.Available: https://www.ncbi.nlm.nih.gov/books/NBK560778/ (accessed 12.9.2021)
  2. 2.0 2.1 2.2 Bright Focus Foundation Macular Degeneration Available: https://www.brightfocus.org/macular/article/age-related-macular-facts-figures (accessed 12.9.2021)
  3. 3.0 3.1 3.2 3.3 3.4 Stahl A. The diagnosis and treatment of age-related macular degeneration. Dtsch Arztebl Int 2020; 117(29-30):513-520.
  4. Wei W., Mazzola M., Otero-Marquez O., Tong Y., Souied E., Querques G., Freund K.B. Smith R.T. Two potentially distinct pathways to geographic atrophy in age-related macular degeneration characterized by quantitative fundus autofluorescence. Eye 2023 Jan 9.
  5. Chen M., Xu H. Parainflammation, chronic inflammation, and age-related macular degeneration. J Leukoc Biol. 2015 Nov;98(5):713-725.
  6. 6.0 6.1 Tan W., Zou J.,Yoshida S., Jiang B., Zhou y. The Role of Inflammation in Age-Related Macular Degeneration. Int J Biol Sci. 2020; 16(15): 2989–3001.
  7. Velilla S., García-Medina J., García-Layana A., Dolz-Marco R., Pons-Vázquez S., Pinazo-Durán M., Gómez-Ulla F., Arévalo F., Díaz-Llopis M., Gallego-Pinazo R. Smoking and Age-Related Macular Degeneration: Review and Update. J Ophthalmol. 2013; 2013: 895147.
  8. 8.0 8.1 Chakravarthy U., Wong T., Fletcher A., Piault E., Evans C., Zlateva G., Buggage R., Pleil A., Mitchell P. Clinical risk factors for age-related macular degeneration: a systematic review and meta-analysis. BMC Ophthalmology. 2010;10:31.
  9. 9.0 9.1 macular org. macular degeneration Available:https://www.macular.org/what-macular-degeneration (accessed 12.9.2021)
  10. 10.0 10.1 Harvard health Publishing Macular Degeneration Available:https://www.health.harvard.edu/macular-degeneration2 (accessed 12.11.2021)
  11. Faes L., Bodmer N., Bachmann L., Thiel M., Schmid M. Diagnostic accuracy of the Amsler grid and the preferential hyperacuity perimetry in the screening of patients with age-related macular degeneration: systematic review and meta-analysis. Eye (Lond). 2014 Jul;28(7):788-96.
  12. Brucker J., Bhatia V., Sahel J., Girmens J., Mohand-Saïd S. Odysight: A Mobile Medical Application Designed for Remote Monitoring-A Prospective Study Comparison with Standard Clinical Eye Tests. Ophthalmol Ther. 2019 Sep;8(3):461-476.
  13. Kielwasser G., Kodjikian L., Dot C., Burillon C., Denis P., Mathis T. Real-Life Value of the Odysight® Application in At-Home Screening for Exudative Recurrence of Macular Edema. J Clin Med. 2022 Aug 26;11(17):5010.
  14. 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 Oct;119(10):1417-36.
  15. Age-Related Eye Disease Study 2 Research Group. Lutein + zeaxanthin and omega-3 fatty acids for age-related macular degeneration: the Age-Related Eye Disease Study 2 (AREDS2) randomized clinical trial. JAMA. 2013 May 15;309(19):2005-2015.
  16. Freeman E., Muñoz B., Bressler S., West S. Hormone replacement therapy, reproductive factors, and age-related macular degeneration: The Salisbury Eye Evaluation Project. Ophthalmic Epidemiol. 2005 Feb;12(1):37–45.
  17. Tomany S., Wang ., Van Leeuwen R., Klein R., Mitchell P., Vingerling J., Klein B., Smith W., De Jong P. Risk factors for incident age-related macular degeneration: pooled findings from 3 continents. Ophthalmology. 2004 Jul;111(7):1280–1287.
  18. Haan M., Klein R., Klein B., Deng Y., Blythe L., Seddon J., Musch D., Kuller L., Hyman L., Wallace R. Hormone therapy and age-related macular degeneration: The Womens Health Initiative Sight Exam Study. Arch Ophthalmol. 2006 Jul;124(7):988–992.
  19. Editorial. Age-related macular degeneration: treatment at what cost? Lancet 2018;392(10153):1090
  20. Shirley M. Faricimab: First Approval. Drugs. 2022 May;82(7):825-830. doi: 10.1007/s40265-022-01713-3.
  21. Wang SB, Nagasaka Y, Argyle D, Nagasaka A, Yerramothu P, Gelfand BD, Ambati J. Targeting the m6A mRNA demethylase FTO suppresses vascular endothelial growth factor release and choroidal neovascularization. Signal Transduct Target Ther. 2023 Feb 20;8(1):72.
  22. Petrus-Reurer S., Lederer A., Baqué-Vidal L., Douagi I., Pannagel B., Khven I., et al. Molecular profiling of stem cell-derived retinal pigment epithelial cell differentiation established for clinical translation. Stem Cell Reports. 2022 Jun 14;17(6):1458-1475.
  23. Szabo SM, Janssen PA, Khan K, Potter MJ, Lord SR. Older women with age‐related macular degeneration have a greater risk of falls: a physiological profile assessment study. Journal of the American Geriatrics Society. 2008 May;56(5):800-7.Available:https://pubmed.ncbi.nlm.nih.gov/18363677/ (accessed 12.9.2021)