Innovative Approaches in Delivery of Eye Care: Age-Related Macular Degeneration

  • Ryo KawasakiEmail author
  • Yumiko Kawasaki
Part of the Essentials in Ophthalmology book series (ESSENTIALS)


Age-related macular degeneration (AMD) is one of the leading causes of severe central vision loss and blindness in an elderly population. With aging of the global population, the projected number of people with AMD in 2020 is estimated to be 196 million, increasing to 288 million in 2040. The early stage of AMD is asymptomatic but can cause severe central vision impairment in later stages. Advancement in the treatment for neovascular AMD with anti-vascular endothelial growth factor (VEGF) injections has changed the treatment of AMD. Before anti-VEGF treatment was available, photodynamic therapy with photosensitizer and thermal direct macular photocoagulation were the only treatment modalities. With anti-VEGF available in the current management of neovascular AMD, it is not just stabilizing the vision, but we can expect improvement in the visual acuity. It is still challenging to improve vision in patients with geographic atrophy; however multiple trials are underway. Both genetic and environmental factors have been identified as playing major roles in the etiology of AMD. Smoking and nutritional factors have been considered to be the main target of lifestyle modification. Advanced imaging has provided a new insight into the etiology and classification into detailed subtypes which is expected to lead to better management of the disease.


Age-related macular degeneration Drusen Pigmentary abnormalities Choroidal neovascularization Geographic atrophy Smoking Nutrition Genetic polymorphisms 


  1. 1.
    Wong WL, Su X, Li X, et al. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. Lancet Glob Health. 2014;2(2):e106–16.CrossRefGoogle Scholar
  2. 2.
    Wong TY, Chakravarthy U, Klein R, et al. The natural history and prognosis of neovascular age-related macular degeneration: a systematic review of the literature and meta-analysis. Ophthalmology. 2008;115(1):116–26.CrossRefGoogle Scholar
  3. 3.
    Cruess A, Zlateva G, Xu X, Rochon S. Burden of illness of neovascular age-related macular degeneration in Canada. Can J Ophthalmol J Can Ophtalmol. 2007;42(6):836–43.CrossRefGoogle Scholar
  4. 4.
    Soubrane G, Cruess A, Lotery A, et al. Burden and health care resource utilization in neovascular age-related macular degeneration: findings of a multicountry study. Arch Ophthalmol (Chicago, Ill: 1960). 2007;125(9):1249–54.CrossRefGoogle Scholar
  5. 5.
    Lotery A, Xu X, Zlatava G, Loftus J. Burden of illness, visual impairment and health resource utilisation of patients with neovascular age-related macular degeneration: results from the UK cohort of a five-country cross-sectional study. Br J Ophthalmol. 2007;91(10):1303–7.CrossRefGoogle Scholar
  6. 6.
    Friedman DS, O’Colmain BJ, Muñoz B, Tomany SC, McCarty C, de Jong PT, Nemesure B, Mitchell P, Kempen J, Eye Diseases Prevalence Research Group. Prevalence of age-related macular degeneration in the United States. Arch Ophthalmol. 2004;122(4):564–72. Erratum in: Arch Ophthalmol. 2011 Sep;129(9):1188. PubMed PMID: 15078675.CrossRefGoogle Scholar
  7. 7.
    Rudnicka AR, Kapetanakis VV, Jarrar Z, Wathern AK, Wormald R, Fletcher AE, Cook DG, Owen CG. Incidence of late-stage age-related macular degeneration in American whites: systematic review and meta-analysis. Am J Ophthalmol. 2015;160(1):85–93.e3. Epub 2015 Apr 6. Review. PubMed PMID: 25857680.7.CrossRefPubMedGoogle Scholar
  8. 8.
    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;308(5720):385–9. Epub 2005 Mar 10. PubMed PMID: 15761122; PubMed Central PMCID: PMC1512523.CrossRefGoogle Scholar
  9. 9.
    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;308(5720):419–21. Epub 2005 Mar 10. PubMed PMID: 15761120.CrossRefGoogle Scholar
  10. 10.
    Edwards AO, Ritter R 3rd, Abel KJ, Manning A, Panhuysen C, Farrer LA. Complement factor H polymorphism and age-related macular degeneration. Science. 2005;308(5720):421–4. Epub 2005 Mar 10. PubMed PMID: 15761121.CrossRefGoogle Scholar
  11. 11.
    Joachim N, Mitchell P, Burlutsky G, Kifley A, Wang JJ. The incidence and progression of age-related macular degeneration over 15 years: the Blue Mountains Eye Study. Ophthalmology. 2015;122(12):2482–9.CrossRefGoogle Scholar
  12. 12.
    Velilla S, García-Medina JJ, García-Layana A, et al. Smoking and age-related macular degeneration: review and update. J Ophthalmol. 2013;2013:895147. Scholar
  13. 13.
    Thornton J, Edwards R, Mitchell P, Harrison RA, Buchan I, Kelly SP. Smoking and age-related macular degeneration: a review of association. Eye (Lond). 2005;19(9):935–44.CrossRefGoogle Scholar
  14. 14.
    Schleicher M, Weikel K, Garber C, Taylor A. Diminishing risk for age-related macular degeneration with nutrition: a current view. Nutrients. 2013;5(7):2405–56.CrossRefGoogle Scholar
  15. 15.
    Zampatti S, Ricci F, Cusumano A, Marsella LT, Novelli G, Giardina E. Review of nutrient actions on age-related macular degeneration. Nutr Res (New York, NY). 2014;34(2):95–105.CrossRefGoogle Scholar
  16. 16.
    Chong EW, Wong TY, Kreis AJ, Simpson JA, Guymer RH. Dietary antioxidants and primary prevention of age related macular degeneration: systematic review and meta-analysis. BMJ (Clin Res Ed). 2007;335(7623):755.CrossRefGoogle Scholar
  17. 17.
    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;309(19):2005–15.Google Scholar
  18. 18.
    Wang JJ, Buitendijk GH, Rochtchina E, et al. Genetic susceptibility, dietary antioxidants, and long-term incidence of age-related macular degeneration in two populations. Ophthalmology. 2014;121(3):667–75.CrossRefGoogle Scholar
  19. 19.
    Ho L, van Leeuwen R, Witteman JC, et al. Reducing the genetic risk of age-related macular degeneration with dietary antioxidants, zinc, and omega-3 fatty acids: the Rotterdam study. Arch Ophthalmol (Chicago, Ill: 1960). 2011;129(6):758–66.CrossRefGoogle Scholar
  20. 20.
    Ratnapriya R, Chew EY. Age-related macular degeneration-clinical review and genetics update. Clin Genet. 2013;84(2):160–6.CrossRefGoogle Scholar
  21. 21.
    Sui GY, Liu GC, Liu GY, et al. Is sunlight exposure a risk factor for age-related macular degeneration? A systematic review and meta-analysis. Br J Ophthalmol. 2013;97(4):389–94.CrossRefGoogle Scholar
  22. 22.
    Chakravarthy U, Wong TY, Fletcher A, et al. Clinical risk factors for age-related macular degeneration: a systematic review and meta-analysis. BMC Ophthalmol. 2010;10:31.CrossRefGoogle Scholar
  23. 23.
    Ghaem Maralani H, Tai BC, Wong TY, et al. Metabolic syndrome and risk of age-related macular degeneration. Retina (Philadelphia, Pa). 2015;35(3):459–66.CrossRefGoogle Scholar
  24. 24.
    Mullins RF, Russel SR, Anderson DH, Hageman GS. Drusen associated with aging and age-related macular degeneration contain proteins common to extracellular deposits associated with atherosclerosis, elastosis, amyloidosis, and dense deposit disease. FASEB J. 2000;14:835–46.CrossRefGoogle Scholar
  25. 25.
    Sivaprasad S, Bailey TA, Chong VNH. Bruch's membrane and the vascular intima: is there a common basis for age-related changes and disease? Clin Exp Ophthalmol. 2005;33:518–23.CrossRefGoogle Scholar
  26. 26.
    Ishida O, Oku H, Ikeda T, Nishimura M, Kawagoe K, Nakamura K. Is Chlamydia pneumoniae infection a risk factor for age related macular degeneration? Br J Ophthalmol. 2003;87(5):523–4.CrossRefGoogle Scholar
  27. 27.
    Kalayoglu MV, Bula D, Arroyo J, Gragoudas ES, D'Amico D, Miller JW. Identification of Chlamydia pneumoniae within human choroidal neovascular membranes secondary to age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol Albrecht von Graefes Arch Klin Exp Ophthalmol. 2005;243(11):1080–90.CrossRefGoogle Scholar
  28. 28.
    Kessler W, Jantos CA, Dreier J, Pavlovic S. Chlamydia pneumoniae is not detectable in subretinal neovascular membranes in the exudative stage of age-related macular degeneration. Acta Ophthalmol Scand. 2006;84(3):333–7.CrossRefGoogle Scholar
  29. 29.
    Robman L, Mahdi O, McCarty C, et al. Exposure to Chlamydia pneumoniae infection and progression of age-related macular degeneration. Am J Epidemiol. 2005;161(11):1013–9.CrossRefGoogle Scholar
  30. 30.
    Robman L, Mahdi OS, Wang JJ, et al. Exposure to Chlamydia pneumoniae infection and age-related macular degeneration: the Blue Mountains Eye Study. Invest Ophthalmol Vis Sci. 2007;48(9):4007–11.CrossRefGoogle Scholar
  31. 31.
    Miller DM, Espinosa-Heidmann DG, Legra J, et al. The association of prior cytomegalovirus infection with neovascular age-related macular degeneration. Am J Ophthalmol. 2004;138(3):323–8.CrossRefGoogle Scholar
  32. 32.
    Kawasaki R, Yasuda M, Song SJ, et al. The prevalence of age-related macular degeneration in Asians: a systematic review and meta-analysis. Ophthalmology. 2010;117(5):921–7.CrossRefGoogle Scholar
  33. 33.
    Yasuda M, Kiyohara Y, Hata Y, et al. Nine-year incidence and risk factors for age-related macular degeneration in a defined Japanese population the Hisayama study. Ophthalmology. 2009;116(11):2135–40.CrossRefGoogle Scholar
  34. 34.
    Chong EW, Kreis AJ, Wong TY, Simpson JA, Guymer RH. Alcohol consumption and the risk of age-related macular degeneration: a systematic review and meta-analysis. Am J Ophthalmol. 2008;145(4):707–15.CrossRefGoogle Scholar
  35. 35.
    Seddon JM, Reynolds R, Yu Y, Rosner B. Validation of a prediction algorithm for progression to advanced macular degeneration subtypes. JAMA Ophthalmol. 2013;131(4):448–55.CrossRefGoogle Scholar
  36. 36.
    Buitendijk GH, Rochtchina E, Myers C, et al. Prediction of age-related macular degeneration in the general population: the Three Continent AMD Consortium. Ophthalmology. 2013;120(12):2644–55.CrossRefGoogle Scholar
  37. 37.
    Chiu CJ, Mitchell P, Klein R, et al. A risk score for the prediction of advanced age-related macular degeneration: development and validation in 2 prospective cohorts. Ophthalmology. 2014;121(7):1421–7.CrossRefGoogle Scholar
  38. 38.
    Interactive A. Macular degeneration test. 2015. Accessed 1 Apr 2016.
  39. 39.
    Sivaprasad S, Bird A, Nitiahpapand R, Nicholson L, Hykin P, Chatziralli I, Moorfields UCL AMD Consortium. Perspectives on reticular pseudodrusen in age-related macular degeneration. Surv Ophthalmol. 2016;61(5):521–37.CrossRefGoogle Scholar
  40. 40.
    Salti HI, Antonios RS, Haddad SS, Hamam RN, Bashshur ZF, Ghazi NG. Combined nonmydriatic spectral-domain optical coherence tomography and nonmydriatic fundus photography for the detection of age-related macular degeneration changes. Ophthalmic Surg Lasers Imaging Retina. 2015;46(5):531–7. PubMed PMID: 26057756.CrossRefPubMedGoogle Scholar
  41. 41.
    Bird AC, Bressler NM, Bressler SB, et al. An international classification and grading system for age-related maculopathy and age-related macular degeneration. The International ARM Epidemiological Study Group. Surv Ophthalmol. 1995;39(5):367–74.CrossRefGoogle Scholar
  42. 42.
    Ferris FL 3rd, Wilkinson CP, Bird A, et al. Clinical classification of age-related macular degeneration. Ophthalmology. 2013;120(4):844–51.CrossRefGoogle Scholar
  43. 43.
    Joachim N, Mitchell P, Rochtchina E, Tan AG, Wang JJ. Incidence and progression of reticular drusen in age-related macular degeneration: findings from an older Australian cohort. Ophthalmology. 2014;121(4):917–25.CrossRefGoogle Scholar
  44. 44.
    Yoneyama S, Sakurada Y, Mabuchi F, et al. Genetic and clinical factors associated with reticular pseudodrusen in exudative age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol Albrecht von Graefes Arch Klin Exp Ophthalmol. 2014;252(9):1435–41.CrossRefGoogle Scholar
  45. 45.
    Ueda-Arakawa N, Ooto S, Nakata I, et al. Prevalence and genomic association of reticular pseudodrusen in age-related macular degeneration. Am J Ophthalmol. 2013;155(2):260–269.e262.CrossRefGoogle Scholar
  46. 46.
    Gallego-Pinazo R, Dolz-Marco R, Gomez-Ulla F, Mrejen S, Freund KB. Pachychoroid diseases of the macula. Med Hypothesis Discov Innov Ophthalmol. 2014;3(4):111–5.PubMedPubMedCentralGoogle Scholar
  47. 47.
    Miyake M, Ooto S, Yamashiro K, et al. Pachychoroid neovasculopathy and age-related macular degeneration. Sci Rep. 2015;5:16204.CrossRefGoogle Scholar
  48. 48.
    Pang CE, Freund KB. Pachychoroid neovasculopathy. Retina (Philadelphia, Pa). 2015;35(1):1–9.CrossRefGoogle Scholar
  49. 49.
    Warrow DJ, Hoang QV, Freund KB. Pachychoroid pigment epitheliopathy. Retina (Philadelphia, Pa). 2013;33(8):1659–72.CrossRefGoogle Scholar
  50. 50.
    Freund KB, Mrejen S, Gallego-Pinazo R. An update on the pharmacotherapy of neovascular age-related macular degeneration. Expert Opin Pharmacother. 2013;14(8):1017–28. Epub 2013 Apr 8. Review. PubMed PMID: 23560774.CrossRefPubMedGoogle Scholar
  51. 51.
    Koizumi H, Yamagishi T, Yamazaki T, Kinoshita S. Relationship between clinical characteristics of polypoidal choroidal vasculopathy and choroidal vascular hyperpermeability. Am J Ophthalmol. 2013;155(2):305–313 e301.CrossRefGoogle Scholar
  52. 52.
    Toyama T, Ohtomo K, Noda Y, Ueta T. Polypoidal choroidal vasculopathy and history of central serous chorioretinopathy. Eye (Lond). 2014;28(8):992–7.CrossRefGoogle Scholar
  53. 53.
    Ueta T, Obata R, Inoue Y, et al. Background comparison of typical age-related macular degeneration and polypoidal choroidal vasculopathy in Japanese patients. Ophthalmology. 2009;116(12):2400–6.CrossRefGoogle Scholar
  54. 54.
    Sarwar S, Clearfield E, Soliman MK, et al. Aflibercept for neovascular age-related macular degeneration. Cochrane Database Syst Rev. 2016;2:CD011346.PubMedPubMedCentralGoogle Scholar
  55. 55.
    Solomon SD, Lindsley K, Vedula SS, Krzystolik MG, Hawkins BS. Anti-vascular endothelial growth factor for neovascular age-related macular degeneration. Cochrane Database Syst Rev. 2014;8:CD005139.PubMedCentralGoogle Scholar
  56. 56.
    Kent C. Maximizing the benefits of anti-VEGF. 2014. Accessed 1 Apr 2016.
  57. 57.
    Cimarolli VR, Casten RJ, Rovner BW, Heyl V, Sorensen S, Horowitz A. Anxiety and depression in patients with advanced macular degeneration: current perspectives. Clin Ophthalmol (Auckland, NZ). 2016;10:55–63.Google Scholar
  58. 58.
    Eramudugolla R, Wood J, Anstey KJ. Co-morbidity of depression and anxiety in common age-related eye diseases: a population-based study of 662 adults. Front Aging Neurosci. 2013;5:56.CrossRefGoogle Scholar
  59. 59.
    Jivraj J, Jivraj I, Tennant M, Rudnisky C. Prevalence and impact of depressive symptoms in patients with age-related macular degeneration. Can J Ophthalmol J Can Ophtalmol. 2013;48(4):269–73.CrossRefGoogle Scholar
  60. 60.
    Dawson SR, Mallen CD, Gouldstone MB, Yarham R, Mansell G. The prevalence of anxiety and depression in people with age-related macular degeneration: a systematic review of observational study data. BMC Ophthalmol. 2014;14:78.CrossRefGoogle Scholar
  61. 61.
    Rovner BW, Casten RJ, Hegel MT, et al. Low vision depression prevention trial in age-related macular degeneration: a randomized clinical trial. Ophthalmology. 2014;121(11):2204–11.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Public HealthYamagata University Graduate School of Medical ScienceYamagataJapan
  2. 2.Department of Vision InformaticsOsaka University Graduate School of MedicineSuitaJapan

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