macular degeneration
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Introduction
Age-related macular degeneration (AMD) is the leading cause of irreversible blindness among persons older than 65 years of age.
Classification
Etiology
- unknown
- risk factors[3][5]
- age
- atherosclerosis
- dyslipidemias
- hypertension (weak association)
- diabetes mellitus
- smoking: smoking cessation reduces risk[2]
- ultraviolet light exposure
- diet low in antioxidants
- obesity[13]
- aspirin increases risk of neovascular type late macular degeneration (RR = 1.7)[21][22]
Epidemiology
- prevalence increases with age
- 0.1% of population 43-54 years of age
- 30% of patients > 75 years of age have evidence of macular degeneration
- 18.34 million individuals in the US >= 40 years (11.6%) were living with early-stage macular degeneration and 1.49 million (0.94%) were living with late-stage macular degeneration in 2019[42]
- leading cause of irreversible blindness among persons > 65 years of age
- more common in caucasian females
- rare in blacks[7]
- baby boomers less likely than previous generation to develop macular degeneration[33]
- decrease coincides with a reduction in cardiovascular disease & dementia (both allegedly involve vascular & inflammatory factors)[33]
Pathology
- retinal degeneration especially of the macula
- three forms
- dry type, atrophic changes
- wet type
- subretinal neovascular membrane (choroidal neovascularization)
- fragile new vessels may leak fluid or hemorrhage, then scar
- a chorioretinal artery* may be protective against choroidal neovascularization[34]
- retinal edema[44]
- retinal pigment epithelium detachment with drusen
* present in ~20% of the population[34]
Genetics
- apolipoprotein E2 is a risk factor
- polymorphism in region of complement factor H gene that binds heparin & C-reactive protein confers 7-fold increased risk[12]
- defects in HMCN1 gene associated with ARMD1
- defects in ABCA4 gene associated with ARMD2
- defects in fibulin-5 gene associated with ARMD3
- genetic variation in ERCC6 is associated ARMD5
- defects in RAXL1 gene associated with ARMD6
- polymorphism in HTRA1 gene associated with ARMD7
- defects in ARMS2 gene associated with ARMD8
- polymorphism in TLR4 gene associated with ARMD10
- defects in RPGR associated with macular degeneration X-linked atrophic
- polymorphism in complement C2, variant Asp-318 is associated with reduced risk of macular degeneration
- risk alleles on chromosome 1 (CFH-CFHR5) & chromosome 10 (ARMS2/HTRA1)[41]
Clinical manifestations
- dry type (most common {90%}) with gradual changes
- painless; may be asymptomatic
- metamorphopsia
- micropsia
- scotomas, central scotoma
- loss of fine central vision, color vision
- relative preservation of peripheral vision
- drusen seen on funduscopic examination
- wet type with more acute changes*
- acute loss of central vision, may be severe
- distorted vision (Amsler grid)
- blurry vision
- conversion of dry type to wet type in 15% of cases
* refer to ophthalmologist within 24 hours
Laboratory
- fluorescein or indocyanine green angiography to identify neovascularization
- see ARUP consult[18]
Complications
- increased risk of stroke, absolute risk increase 2%[14]
- conversion of dry type to wet type with rapid visual loss
- prevalence of depression is 30%[7]
- loss of central vision impairs ability of older drivers to see pedestrians[20]
- glaucoma, cataracts, & age-related macular degeneration may increase risk of falls in the elderly[45]
Management
- ophthalmologic referral (within 24 hours if acute changes)
- within 1 week if within 24 hours not an option[7]
- vascular endothelial growth factor inhibitor (VEGF inhibitor) intravitreal injection in conjunction with laser photocoagulation for exudative or wet form
- pegaptanib (Macugen) FDA-approved in 2004
- ranibizumab (Lucentis) FDA-approved in 2006
- bevacizumab (Avastin) off-label use (VAMC) as effective & less expensive than ranibizumab ($50 vs $2000 monthly)[17]
- aflibercept (Eylea) FDA-approved 2011
- laser photocoagulation for selected patients with exudative or wet form[2]
- used in connection with fluorescein angiography
- target choroidal neovascularization outside the foveal avascular zone
- injection of photoactive dye followed by laser
- verteporfin (Visudyne) IV may used in conjunction with photocoagulation
- verteporfin as sensitizer selectively binds to LDL receptor sites in choroidal neovascularization
- red laser of wavelength 689 nm activates drug & releases free radicals resulting in damage to & closure of the abnormal blood vessels
- neither VEGF inhibitor or laser photocoagulation of benefit for dry form[2]
- daily self Amsler grid evaluation
- prophylaxis
- dietary*
- management of dyslipidemia
- wear sunglasses
- antioxidants & zinc reduce risk/slow progression[2][13]
- folic acid, vit B6 & vit B12 supplements in combination may reduce risk[15]
- do not smoke
- smoking cessation reduces risk/slows progression[2]
- vitamin D & omega-3 fatty acids of no benefit
- metformin for diabetes mellitus type-2 may reduce risk of age-related macular degeneration; later study found no association[37]
- antioxidants plus zinc may have modest benefit on progression of disease[4] (Ocuvite PreserVision, AREDS)
- zinc (Zn+2) 80 mg
- vitamin C 500 mg
- vitamin E# 400 IU
- beta-carotene 15 mg
- lutein & zeaxanthin may be of benefit[9][11][26]
- addition of lutein + zeaxanthin, DHA + EPA, or both to AREDS formulation does not further reduce risk of progression[28]
- retinal implants: semiconductor chips implanted into the retina to interface directly with the central visual pathways
- referral to vision rehabilitation specialist for visual impairment & blindness[7]
- use peripheral vision as much as possible to maintain function[7]
- investigational
- human embryonic stem cell-derived retinal pigment epithelium improved visual acuity in some patients[27]
* dietary prophylaxis
- a Mediterranean diet may reduce risk of macular degeneration[32]
- lutein, zeaxanthin & nitrates in green leafy vegetable may play a role[43]
- one study[1] found that a higher dietary intake of carotenoids, specifically lutein & zeaxanthin, which are enriched in dark green leafy vegetables (noted are spinach & collard greens) is associated with a lower risk of age-related macular degeneration [as much as 43% lower].
# NOT helpful alone[6]
Comparative biology
- high-glycemic index diets worsen macular deneration in mice
- low glycemic index diets arrest progession of macular deneration in mice
- changes dependent on changes in the gut microbiome[31]
- oligomeric Abeta1-42 injected into the eyes of wild-type mice induces age-related macular degeneration like pathology within 2 weeks[39]
More general terms
More specific terms
- age-related macular degeneration/ABCR mutation associated
- bull's eye maculopathy (concentric annular macular dystrophy)
- Stargardt disease
- vitelliform macular dystrophy; Best macular dystrophy
Additional terms
- Amsler grid (AG)
- drusen
- macula retinae, macula lutea, macula, area centralis or punctum luteum
- metamorphopsia
- micropsia
- Ocuvite PreserVision; AREDS formulation
- scotoma
References
- ↑ 1.0 1.1 Seddon JM et al Dietary carotenoids, vitamins A, C, and E, and advanced age-related macular degeneration. Eye Disease Case-Control Study Group. JAMA 272:1413 1994 PMID: https://www.ncbi.nlm.nih.gov/pubmed/7933422
- ↑ 2.0 2.1 2.2 2.3 2.4 2.5 Medical Knowledge Self Assessment Program (MKSAP) 11, 15, 16, 17, 18. American College of Physicians, Philadelphia 1998, 2009, 2012, 2015, 2018.
Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022 - ↑ 3.0 3.1 3.2 Journal Watch 21(19):157, 2001 Hall NF et al Risk of macular degeneration in users of statins: cross sectional study. BMJ. 2001 Aug 18;323(7309):375-6. No abstract available. PMID: https://www.ncbi.nlm.nih.gov/pubmed/11509429
- ↑ 4.0 4.1 Journal Watch 21(22):174, 2001 Jampol LM Antioxidants, zinc, and age-related macular degeneration: results and recommendations. Arch Ophthalmol 119:1533, 2001 PMID: https://www.ncbi.nlm.nih.gov/pubmed/11594957
- ↑ 5.0 5.1 Mangione C. In: Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 12-15, 2001
- ↑ 6.0 6.1 Journal Watch 22(17):135, 2002 Taylor HR et al Vitamin E supplementation and macular degeneration: randomised controlled trial. BMJ 325:11, 2002 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/12098721 (<Internet> http://bmj.com/cgi/content/full/325/7354/11)
- ↑ 7.0 7.1 7.2 7.3 7.4 7.5 Geriatrics Review Syllabus, American Geriatrics Society, 5th edition, 2002-2004
Geriatric Review Syllabus, 7th edition Parada JT et al (eds) American Geriatrics Society, 2010
Geriatric Review Syllabus, 8th edition (GRS8) Durso SC and Sullivan GN (eds) American Geriatrics Society, 2013
Geriatric Review Syllabus, 11th edition (GRS11) Harper GM, Lyons WL, Potter JF (eds) American Geriatrics Society, 2022 - ↑ AREDS report #8, Arch Ophthal 119:1417, 2001
- ↑ 9.0 9.1 Huang J, West Los Angeles VAMC, March 18, 2003
- ↑ K. Small, UCLA 8th Annual Research Conference on Aging, June 25, 2003
- ↑ 11.0 11.1 Prescriber's Letter 11(5):28 2004 Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=200510&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 12.0 12.1 Edwards AO, Ritter R 3rd, Abel KJ, Manning A, Panhuysen C, Farrer LA. Complement factor H polymorphism and age-related macular degeneration. Science. 2005 Apr 15;308(5720):421-4. Epub 2005 Mar 10. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15761121
Haines JL, Hauser MA, Schmidt S, Scott WK, Olson LM, Gallins P, Spencer KL, Kwan SY, Noureddine M, Gilbert JR, Schnetz-Boutaud N, Agarwal A, Postel EA, Pericak-Vance MA. Complement factor H variant increases the risk of age- related macular degeneration. Science. 2005 Apr 15;308(5720):419-21. Epub 2005 Mar 10. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15761120
Klein RJ, Zeiss C, Chew EY, Tsai JY, Sackler RS, Haynes C, Henning AK, Sangiovanni JP, Mane SM, Mayne ST, Bracken MB, Ferris FL, Ott J, Barnstable C, Hoh J. Complement factor H polymorphism in age-related macular degeneration. Science. 2005 Apr 15;308(5720):385-9. Epub 2005 Mar 10. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15761122 - ↑ 13.0 13.1 13.2 van Leeuwen R et al, Dietary intake of antioxidants and risk of age-related macular degeneration. JAMA 2005 Dec 28; 294:3101-7. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16380590
- ↑ 14.0 14.1 Wong TY, Klein R, Sun C, Mitchell P, Couper DJ, Lai H, Hubbard LD, Sharrett AR; Atherosclerosis Risk in Communities Study. Age-related macular degeneration and risk for stroke. Ann Intern Med. 2006 Jul 18;145(2):98-106. Summary for patients in: Ann Intern Med. 2006 Jul 18;145(2):I37. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16847292
- ↑ 15.0 15.1 Christen WG et al Folic acid, pyridoxine, and cyanocobalamin combination treatment and age-related macular degeneration in women: The Women's Antioxidant and Folic Acid Cardiovascular Study. Arch Intern Med 2009 Feb 23; 169:335. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19237716
- ↑ Prescriber's Letter 16(7): 2009 COMMENTARY: Age-Related Macular Degeneration: An Update CONTINUING EDUCATION: Natural Medicines in the Clinical Management of Eye Disorders Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=250719&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 17.0 17.1 The CATT Research Group. Martin DE et al Ranibizumab and bevacizumab for neovascular age-related macular degeneration. N Engl J Med 2011 May 19; 364:1897 PMID: https://www.ncbi.nlm.nih.gov/pubmed/21526923
- ↑ 18.0 18.1 ARUP Consult: Macular Degeneration, Age-Related - AMD deprecated reference
- ↑ Jager RD, Mieler WF, Miller JW. Age-related macular degeneration. N Engl J Med. 2008 Jun 12;358(24):2606-17 PMID: https://www.ncbi.nlm.nih.gov/pubmed/18550876
- ↑ 20.0 20.1 Bronstad PM et al. Driving with central field loss I: Effect of central scotomas on responses to hazards. JAMA Ophthalmol 2013 Jan 17 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23329309 <Internet> http://archopht.jamanetwork.com/article.aspx?articleid=1557937
- ↑ 21.0 21.1 Klein BEK et al Long-term Use of Aspirin and Age-Related Macular Degeneration JAMA. 2012;308(23):2469-2478 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23288416 <Internet> http://jama.jamanetwork.com/article.aspx?articleid=1486830
Prescriber's Letter 20(3): 2013 Does Aspirin Increase the Risk of Macular Degeneration? Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=290306&pb=PRL (subscription needed) http://www.prescribersletter.com - ↑ 22.0 22.1 22.2 Liew G et al. The association of aspirin use with age-related macular degeneration. JAMA Intern Med 2013 Feb 25; 173:258. PMID: https://www.ncbi.nlm.nih.gov/pubmed/23337937
Kaul S and Diamond GA. Relationship of aspirin use with age-related macular degeneration: Association or causation? JAMA Intern Med 2013 Feb 25; 173:264 PMID: https://www.ncbi.nlm.nih.gov/pubmed/23338290 - ↑ Arroyo JG. A 76-year-old man with macular degeneration. JAMA. 2006 May 24;295(20):2394-406. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16720825
- ↑ Pumariega NM, Smith RT, Sohrab MA, Letien V, Souied EH. A prospective study of reticular macular disease. Ophthalmology. 2011 Aug;118(8):1619-25. PMID: https://www.ncbi.nlm.nih.gov/pubmed/21550118
- ↑ Silva R, Cachulo ML, Fonseca P et al Age-related macular degeneration and risk factors for the development of choroidal neovascularisation in the fellow eye: a 3-year follow-up study. Ophthalmologica. 2011;226(3):110-8. PMID: https://www.ncbi.nlm.nih.gov/pubmed/21822000
- ↑ 26.0 26.1 Yuan A, Kaiser PK. Emerging therapies for the treatment of neovascular age related macular degeneration. Semin Ophthalmol. 2011 May;26(3):149-55. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/21609228
- ↑ 27.0 27.1 Schwartz SD et al. Human embryonic stem cell-derived retinal pigment epithelium in patients with age-related macular degeneration and Stargardt's macular dystrophy: Follow-up of two open-label phase 1/2 studies. Lancet 2014 Oct 15 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25458728 <Internet> http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2814%2961376-3/fulltext
- ↑ 28.0 28.1 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):2005-15. PMID: https://www.ncbi.nlm.nih.gov/pubmed/23644932
- ↑ Lanzetta P, Mitchell P, Wolf S, Veritti D. Different antivascular endothelial growth factor treatments and regimens and their outcomes in neovascular age-related macular degeneration: a literature review. Br J Ophthalmol. 2013 Dec;97(12):1497-507. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/23929309
- ↑ Smith AG, Kaiser PK. Emerging treatments for wet age-related macular degeneration. Expert Opin Emerg Drugs. 2014 Mar;19(1):157-64. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/24555421
- ↑ 31.0 31.1 Rowan S, Jiang S, Korem T et al. Involvement of a gut-retina axis in protection against dietary glycemia-induced age-related macular degeneration. Proc Natl Acad Sci U S A 2017 May 15; http://www.pnas.org/content/early/2017/05/09/1702302114
- ↑ 32.0 32.1 Garcia J Mediterranean Diet May Protect Against Macular Degeneration. Medscape - Nov 10, 2016. http://www.medscape.com/viewarticle/871752
Frellick M Mediterranean Diet May Cut AMD Risk by More Than a Third Medscape - Oct 19, 2016. http://www.medscape.com/viewarticle/870519
Janeczko LL Mediterranean Diet Linked With Lower Incidence of Advanced AMD. Medscape - Jun 01, 2018. https://www.medscape.com/viewarticle/897504 - ↑ 33.0 33.1 33.2 Cruickshanks KJ, Nondahl DM, Johnson LJ et al Generational Differences in the 5-Year Incidence of Age-Related Macular Degeneration. JAMA Ophthalmol. Published online November 16, 2017. PMID: https://www.ncbi.nlm.nih.gov/pubmed/29145549 https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2663390
Goldacre RR, Keenan TDL Age-Related Maculopathy - Degeneration by Generation. JAMA Ophthalmol. Published online November 16, 2017. PMID: https://www.ncbi.nlm.nih.gov/pubmed/29145551 https://jamanetwork.com/journals/jamaophthalmology/article-abstract/2663383 - ↑ 34.0 34.1 34.2 Snyder K, Yazdanyar A, Mahajan A et al Association Between the Cilioretinal Artery and Choroidal Neovascularization in Age-Related Macular Degeneration. A Secondary Analysis From the Age-Related Eye Disease Study. JAMA Ophthalmol. Published online July 5, 2018. PMID: https://www.ncbi.nlm.nih.gov/pubmed/29978186 https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2686391 Chew EY. The Cilioretinal Artery - A Friend to Age-Related Macular Degeneration? JAMA Ophthalmol. Published online July 5, 2018. PMID: https://www.ncbi.nlm.nih.gov/pubmed/29978193 https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2686387
- ↑ Chakravarthy U, Peto T Current Perspective on Age-Related Macular Degeneration. JAMA. Published online August 6, 2020. PMID: https://www.ncbi.nlm.nih.gov/pubmed/32780786 https://jamanetwork.com/journals/jama/fullarticle/2769321
- ↑ Christen WG, Cook NR, Manson JE et al Effect of Vitamin D and w-3 Fatty Acid Supplementation on Risk of Age-Related Macular Degeneration. An Ancillary Study of the VITAL Randomized Clinical Trial. JAMA Ophthalmol. Published online October 29, 2020. PMID: https://www.ncbi.nlm.nih.gov/pubmed/33119047 https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2772366
Frank RN Of Age-Related Macular Degeneration and Vitamins. JAMA Ophthalmol. Published online October 29, 2020. PMID: https://www.ncbi.nlm.nih.gov/pubmed/33119041 https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2772363 - ↑ 37.0 37.1 Blitzer AL, Ham SA, Colby KA, Skondra D. Association of Metformin Use With Age-Related Macular Degeneration. A Case-Control Study. JAMA Ophthalmol. Published online January 21, 2021. PMID: https://www.ncbi.nlm.nih.gov/pubmed/33475696 https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2775160
Domalpally A, Whittier SA, Pan Q et al Association of Metformin With the Development of Age-Related Macular Degeneration. JAMA Ophthalmol. 2023;141(2):140-147. PMID: https://www.ncbi.nlm.nih.gov/pubmed/36547967 https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2799978 - ↑ National Eye Institite Age-Related Macular Degeneration. https://www.nei.nih.gov/learn-about-eye-health/eye-conditions-and-diseases/age-related-macular-degeneration
- ↑ 39.0 39.1 39.2 University of Southampton. New study links protein causing Alzheimer's disease with common sight loss. ScienceDaily, 10 March 2021. http://www.sciencedaily.com/releases/2021/03/210310122439.htm
Lynn SA, Johnston DA Scott et al Oligomeric Abeta1-42 Induces an AMD-Like Phenotype and Accumulates in Lysosomes to Impair RPE Function Cells. 2021 Feb 17;10(2):413 PMID: https://www.ncbi.nlm.nih.gov/pubmed/33671133 PMCID: PMC7922851 Free PMC article - ↑ Apte RS Age-Related Macular Degeneration. N Engl J Med 2021; 385:539-547. Aug 5 PMID: https://www.ncbi.nlm.nih.gov/pubmed/34347954 https://www.nejm.org/doi/full/10.1056/NEJMcp2102061
- ↑ 41.0 41.1 Schmitz-Valckenberg S, Fleckenstein M, Zouache MA et al Progression of Age-Related Macular Degeneration Among Individuals Homozygous for Risk Alleles on Chromosome 1 (CFH-CFHR5) or Chromosome 10 (ARMS2/HTRA1) or Both. JAMA Ophthalmol. Published online February 3, 2022. PMID: https://www.ncbi.nlm.nih.gov/pubmed/35113155 https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2788507
Scholl HPN Complement Inhibition in Age-Related Macular Degeneration - Treat Early! JAMA Ophthalmol. Published online February 3, 2022 PMID: https://www.ncbi.nlm.nih.gov/pubmed/35113132 https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2788510 - ↑ 42.0 42.1 Rein DB, Wittenborn JS, Burke-Conte Z et al Prevalence of Age-Related Macular Degeneration in the US in 2019. JAMA Ophthalmol. Published online November 3, 2022 PMID: https://www.ncbi.nlm.nih.gov/pubmed/36326752 https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2797921
- ↑ 43.0 43.1 Broadhead GK, Agron E, Peprah D et al Association of Dietary Nitrate and a Mediterranean Diet With Age-Related Macular Degeneration Among US Adults. The Age-Related Eye Disease Study (AREDS) and AREDS2. JAMA Ophthalmol. 2023;141(2):130-139. PMID: https://www.ncbi.nlm.nih.gov/pubmed/36547942 https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2799979
- ↑ 44.0 44.1 NEJM Knowledge+ Ophthalmology
- ↑ 45.0 45.1 Tsang JY et al. Risk of falls and fractures in individuals with cataract, age-related macular degeneration, or glaucoma. JAMA Ophthalmol 2023 Dec 28; [e-pub]. PMID: https://www.ncbi.nlm.nih.gov/pubmed/38153708 https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2813168
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