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Bulgarian Review of Ophthalmology

Optical coherence tomography-angiography in the multimodal imaging of age-related macular degeneration - a review

Vladimir Stavrev, Nelly Sivkova, Desislava Koleva-Georgieva


Age-related macular degeneration is the leading cause of irreversible visual function loss in individuals from developed countries over the age of 65 years. The global prevalence of age-related macular degeneration is expected to increase by 50% in 2020 due to increased life expectancy and aging population worldwide. The central vision loss in the late stage of the disease - geographic atrophy and choroidal neovascularization is a serious social and economic problem. It requires regular screening, early diagnosis, and timely treatment. Оptical coherence tomography-angiography is a relatively new diagnostic method. Based on its noninvasiveness it is widely used in age-related macular degeneration.


аge-related macular degeneration; optical coherence tomography-angiography; multimodal imaging

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Freund KB, Yanuzzi LA, Sorenson JA. Age-related macular degeneration and choroidal neovascularization. Am J Ophthalmol. 1993;115(6):786-91.

Khandhadia S, Cherry J, Lotery AJ. Age-related macular degeneration. Adv Exp Med Biol. 2012;724:15-36. doi: 10.1007/978-1-4614-0653-2_2.

Cook HL, Patel PJ, Tufail A. Age-related macular degeneration: diagnosis and management. Br Med Bull. 2008;85:127-149. doi: 10.1093/bmb/ldn012.

Klein R, Peto T, Bird A, Vannewkirk MR. The epidemiology of age-related macular degeneration. Am J Ophthalmol. 2004; 137(3): 486-95. doi: 10.1016/j.ajo.2003.11.069.

Smith W, Assink J, Klein R, Mitchell P, Klaver CC, Klein BE, et al. Risk factors for age-related macular degeneration: pooled findings from three continents. Ophthalmology. 2001;108(4):697-704.

Chou R, Dana T, Bougatsos C, Grusing S, Blazina I. Screening for impaired visual acuity in older adults: updated evidence report and systematic review for the US Preventive Services Task Force. JAMA. 2016;315(9):915-33. doi: 10.1001/jama.2016.0783.

Wong WL, Su X, Li X, Cheung CM, Klein R, Cheng CY, et al. Global prevalence of age-related macu-lar degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. Lancet Glob Health. 2014;2(2):e106-e16. doi: 10.1016/S2214-109X(13)70145-1.

Day S, Acquah K, Lee PP, Mruthyunjaya P, Sloan FA. Medicare costs for neovascular age-related macular degeneration, 1994-2007. Am J Ophthalmol. 2011;152(6):1014-20. doi:10.1016/j.ajo.2011.05.008.

Holz FG, Sadda SR, Staurenghi G, Lindner M, Bird AC, Blodi BA, et al. Imaging protocols in clinical studies in advanced age-related macular degeneration. Ophthalmology. 2017;124(4):464-78. doi: 10.1016/j.ophtha.2016.12.002.

Grunwald JE, Daniel E, Ying GS, Pistilli M, Maguire MG, Alexander J, et al. Photographic assessment of baseline fundus morphologic features in the Comparison of Age-Related Macular Degeneration Treatments Trials. Ophthalmology. 2012;119(8):1634-41. doi: 10.1016/j.ophtha.2012.02.013.

Wu Z, Ayton LN, Luu CD, Baird PN, Guymer RH. Reticular pseudodrusen in intermediate age-related macular degeneration: prevalence, detection, clinical, environmental, and genetic associations. Invest Ophthalmol Vis Sci. 2016;57(3):1310-6. doi: 10.1167/iovs.15-18682.

De Bats F, Mathis T, Mauget-Faysse M, Joubert F, Denis P, Kodjikian L. Prevalence of reticular pseudodrusen in age-related macular degeneration using multimodal imaging. Retina. 2016;36(1):46-52. doi: 10.1097/IAE.0000000000000648.

Delori FC, Dorey CK, Staurenghi G, Arend O, Goger DG, Weiter JJ. In vivo fluorescence of the ocular fundus exhibits retinal pigment epithelium lipofuscin characteristics. Invest Ophthalmol Vis Sci. 1995;36(3):718-29.

Krebs I, Lois N, Forrester JV. Fundus autofluorescence. Graefes Arch Clin Exp Ophthalmol. 2011;249(2):309. doi: 10.1007/s00417-010-1330-0.

Holz FG, Pauleikhoff D, Spaide RF, Bird AC, eds. Agerelated Macular Degeneration. 2nd ed. Berlin, Heidelberg: Springer-Verlag Berlin Heidelberg; 2013.

Holz FG, Steinberg JS, Gobel A, Fleckenstein M, Schmitz-Valckenberg S. Fundus autofluorescence imaging in dry AMD: 2014 Jules Gonin lecture of the Retina Research Foundation. Graefes Arch Clin Exp Ophthalmol. 2015;253(1):7-16. doi: 10.1007/s00417-014-2858-1.

Bindewald A, Bird AC, Dandekar SS, Dolar-Szczasny J, Dreyhaupt J, Fitzke FW, et al. Classification of fundus autofluorescence patterns in early age-related macular disease. Invest Ophthalmol Vis Sci. 2005;46(9):3309-14. doi: 10.1167/iovs.04-0430.

Landa G, Rosen RB, Pilavas J, Garcia PM. Drusen characteristics revealed by spectral-domain optical coherence tomography and their corresponding fundus autofluorescence appearance in dry age-related macular degeneration. Ophthalmic Res. 2012;47(2):81-6. doi: 10.1159/000324988.

Mimoun G, Soubrane G, Coscas G. Macular drusen. J Fr Ophtalmol. 1990;13(10):511-30.

Smith RT, Sohrab MA, Busuioc M, Barile G. Reticular macular disease. Am J Ophthalmol. 2009;148(5):733-43.e2. doi: 10.1016/j.ajo.2009.06.028.

Pilotto E, Benetti E, Convento E, , Guidolin F, Longhin E, Parrozzani R, et al. Microperimetry, fundus autofluorescence, and retinal layer changes in progressing geographic atrophy. Can J Ophthalmol. 2013;48(5):386-93. doi: 10.1016/j.jcjo.2013.03.022.

Holz FG, Bindewald-Wittich A, Fleckenstein M, Dreyhaupt J, Scholl HP, Schmitz-Valckenberg S, et al. Progression of geographic atrophy and impact of fundus autofluorescence patterns in age-related macular degeneration. Am J Ophthalmol. 2007;143(3):463-72. doi: 10.1016/j.ajo.2006.11.041.

McBain VA, Townend J, Lois N. Fundus autofluorescence in exudative age-related macular degeneration. Br J Ophthalmol. 2007;91(4):491-6. doi: 10.1136/bjo.2006.095109.

Camacho N, Barteselli G, Nezgoda JT, El-Emam S, Cheng L, Bartsch DU, et al. Significance of the hyperautofluorescent ring associated with choroidal neovascularisation in eyes undergoing anti-VEGF therapy for wet age-related macular degeneration. Br J Ophthalmol. 2015;99(9):1277-83. doi: 10.1136/bjophthalmol-2014-306226.

Batioglu F, Demirel S, Ozmert E, Oguz YG, Ozyol P. Autofluorescence patterns as a predictive factor for neovascularization. Optom Vis Sci. 2014;91(8):950-5. doi: 10.1097/OPX.0000000000000321.

Lindner M, Boker A, Mauschitz MM, et al. Directional kinetics of geographic atrophy progression in age-related macular degeneration with foveal sparing. Ophthalmology. 2015;122(7):1356-65. doi: 10.1016/j.ophtha.2015.03.027.

Chakravarthy U, Williams M, AMD Guidelines Group. The Royal College of Ophthalmologists Guidelines on AMD: Executive Summary. Eye. 2013;27(12):1429-31. doi:10.1038/eye.2013.233.

Novotny HR, Alvis DL. A method of photographing fluorescence in circulating blood in the human retina. Circulation. 1961;24:82-6.

Vujosevic S, Vaclavik V, Bird AC, Leung I, Dandekar S, Peto T. Combined grading for choroidal neovascularisation: colour, fluorescein angiography and autofluorescence images. Graefes Arch Clin Exp Ophthalmol. 2007;245(10):1453-60.

MPSG. Subfoveal neovascular lesions in age-related macular degeneration. Guidelines for evaluation and treatment in the macular photocoagulation study. Macular Photocoagulation Study Group. Arch Ophthalmol 1991; 109(9): 1242-57.

Barbazetto I, Burdan A, Bressler NM, Bressler SB, Haynes L, Kapetanios AD, et al. Photodynamic therapy of subfoveal choroidal neovascularization with verteporfin: fluorescein angiographic guidelines for evaluation and treatment-TAP and VIP report No. 2. Arch Ophthalmol. 2003; 121(9): 1253-68. doi: 10.1001/archopht.121.9.1253.

Laser photocoagulation of subfoveal neovascular lesions of age-related macular degeneration. Updated findings from two clinical trials. Macular Photocoagulation Study Group. Arch Ophthalmol. 1993; 111(9): 1200-9.

Sivaprasad S, Bird A, Nitiahpapand R, Nicholson L, Hykin P, Chatziralli I, et al. Perspectives on reticular pseudodrusen in age-related macular degeneration. Surv Ophthalmol. 2016; 61(5):521-37. doi: 10.1016/j.survophthal.2016.02.005.

Kwan AS, Barry C, McAllister IL, Constable I. Fluorescein angiography and adverse drug reactions revisited: the Lions Eye experience. Clin Exp Ophthalmol. 2006; 34(1): 33-8. doi: 10.1111/j.1442-9071.2006.01136.x.

Slakter JS, Yannuzzi LA, Guyer DR, Sorenson JA, Orlock DA. Indocyanine-green angiography. Curr Opin Ophthalmol. 1995;6(3):25-32.

Holz FG, Bellmann C, Rohrschneider K, Burk RO, Völcker HE. Simultaneous confocal scanning laser fluorescein and indocyanine green angiography. Am J Ophthalmol. 1998;125(2):227-36.

Pauleikhoff D, Spital G, Radermacher M, Brumm GA, Lommatzsch A, Bird AC. A fluorescein and indocyanine green angiographic study of choriocapillaris in age-related macular disease. Arch Ophthalmol. 1999;117(10):1353-8.

Yannuzzi LA, Negrao S, Iida T, Carvalho C, Rodriguez-Coleman H, Slakter J, et al. Retinal angiomatous proliferation in age-related macular degeneration. Retina. 2001;21(5):416-34.

Spaide RF, Yannuzzi LA, Slakter JS, Sorenson J, Orlach DA. Indocyanine green videoangiography of idiopathic polypoidal choroidal vasculopathy. Retina. 1995;15(2):100-10.

Gallego-Pinazo R, Dolz-Marco R, Gómez-Ulla F, Mrejen S, Freund KB. Pachychoroid Diseases of the Macula. Med Hypothesis Discov Innov Ophthalmol. 2014;3(4):111-5.

Huang D, Swanson EA, Lin CP, Schuman JS, Stinson WG, Chang W, et al. Optical coherence tomography. Science. 1991; 254(5035):1178-81.

Zhao R, Camino A, Wang J, Hagag AM, Lu Y, Bailey ST, et al. Automated drusen detection in dry age-related macular degeneration by multiple-depth, en face optical coherence tomography. Biomed Opt. Express. 2017;8(11):5049-64. doi: 10.1364/BOE.8.005049.

de Sisternes L, Simon N, Tibshirani R, Leng T, Rubin DL. Quantitative SD-OCT imaging biomarkers

as indicators of age-related macular degeneration progression. Invest Ophthalmol Vis Sci. 2014;55(11):7093-103. doi:10.1167/ iovs.14-14918.

Wintergerst MWM, Schultz T, Birtel J, Schuster AK, Pfeiffer N,Schmitz-Valckenberg S, Holz FG, Finger RP. Algorithms for the automated analysis of age-related macular degeneration biomarkers on optical coherencetomography: a systematic review. Trans Vis Sci Tech. 2017;6(4):10. doi:10.1167/ tvst.6.4.10.

Holtz FG, Sadda SR, Staurenghi G, Lindner M, Bird AC, Blodi BA, et al. Imaging protocols in clinical studies in advanced age-related macular degeneration: recommendations from Classification of Atrophy Consensus Meetings. Ophthalmology. 2017;124(4):464-78. doi: 10.1016/j.ophtha.2016.12.002.

Kaiser PK, Blodi BA, Shapiro H, Acharya NR, Group MS. Angiographic and optical coherence tomographic results of the MARINA study of ranibizumab in neovascular agerelated macular degeneration. Ophthalmology. 2007; 114(10):1868-75. doi: 10.1016/j.ophtha.2007.04.030.

Wilde C, Patel M, Lakshmanan A, Amankwah R, Dhar-Munshi S, Amoaku W, et al. The diagnostic accuracy of spectraldomain optical coherence tomography for neovascular agerelated macular degeneration: a comparison with fundus fluorescein angiography. Eye (Lond). 2015; 29(5):602-10. doi: 10.1038/eye.2015.44.

Freund KB, Zweifel SA, Engelbert M. Do we need a new classification for choroidal neovascularization in age-related macular degeneration? Retina 2010;30(9):1333-49. doi: 10.1097/IAE.0b013e3181e7976b.

Freund KB, Ho IV, Barbazetto IA, Koizumi H, Laud K, Ferrara D, et al. Type 3 neovascularization: the expanded spectrum of retinal angiomatous proliferation. Retina. 2008;28(2):201-11.

Do DV, Gower EW, Cassard SD, Boyer D, Bressler NM, Bressler SB, et al. Detection of new-onset choroidal neovascularization using optical coherence tomography: the AMD DOC Study. Ophthalmology. 2012; 119(4):771-8. doi: 10.1016/j.ophtha.2011.10.019.

Mokwa NF, Ristau T, Keane PA, Kirchhof B, Sadda SR, Liakopoulos S. Grading of age-related macular degeneration: comparison between color fundus photography, fluorescein angiography, and spectral domain optical coherence tomography. J Ophthalmol. 2013; 2013:385915. doi: 10.1155/2013/385915.

Sandhu SS, Talks SJ. Correlation of optical coherencetomography, with or without additional colour fundus photography, with stereo fundus fluorescein angiography in diagnosing choroidal neovascular membranes. Br J Ophthalmol. 2005; 89(8): 967-70. doi: 10.1136/bjo.2004.060863.

Giovannini A, Amato GP, Mariotti C, Scassellati-Sforzolini B. OCT imaging of choroidal neovascularization and its role in the determination of patients` eligbility for surgery. Br J Ophthalmol. 1999; 83(4):438-42.

Choi W, Mohler KJ, Potsaid B, Lu CD, Liu JJ, Jayaraman V, et al. Choriocapillaris and choroidal microvasculature imaging with ultrahigh speed OCT angiography. PLoS One. 2013;8:e81499. doi: 10.1371/journal.pone.0081499.

Мoult E, Choi W, Waheed NK, Adhi M, Lee B, Lu CD, et al. Ultrahigh-Speed Swept-Source OCT Angiography in Exudative AMD. Ophthalmic Surg Lasers Imaging Retina. 2014;45(6):496-505. doi: 10.3928/23258160-20141118-03.

Huang S, Shen M, Zhu D, Chen Q, Shi C, Chen Z, et al. In vivo imaging of retinal hemodynamics with OCT angiography and Doppler OCT. Biomed Opt Express. 2016; 7(2):663-76. doi: 10.1364/BOE.7.000663.

Matsunaga D, Yi J, Puliafito CA, Kashani AH. OCT angiography in healthy human subjects. Ophthalmic Surg Lasers Imaging Retina 2014;45(6):510-5. doi: 10.3928/23258160-20141118-04.

Jia Y, Bailey ST, Wilson DJ, Tan O, Klein ML, Flaxel CJ, et al. Quantitative optical coherence tomography angiography of choroidal neovascularization in age-related macular degeneration. Ophthalmology. 2014;121(7):1435-44. doi: 10.1016/j.ophtha.2014.01.034.

Jia Y, Tan O, Tokayer J, Potsaid B, Wang Y, Liu JJ, et al. Split-spectrum amplitude-decorrelation angiography with optical coherence tomography. Opt Express. 2012;20(4):4710-25. doi: 10.1364/OE.20.004710.

Spaide R, Fujimoto JG, Waheed NK. Optical coherence tomography angiography. Retina. 2015;35(11):2161-2. doi: 10.1097/IAE.0000000000000881.

Spaide RF, Fujimoto JG, Waheed NK. Image artifacts in optical coherence tomography angiography. Retina. 2015;35(11):2163-80. doi: 10.1097/IAE.0000000000000765.

Mastropasqua R, Di Antonio L, Di Staso S, Agnifili L, Di Gregorio A, Ciancaglini M, et al. Optical coherence tomography angiography in retinal vascular diseases and choroidal neovascularization. J Ophthalmol. 2015;2015:1-8. doi: 10.1155/2015/343515.

Waheed NK, Moult EM, Fujimoto J, Rosenfeld PJ. Optical coherence tomography angiography of dry age-related macular degeneration. Dev Ophthalmol. 2016;56:91-100. doi: 10.1159/000442784.

Unterhuber A, Povazay B, Hermann B, Sattmann H, Chavez-Pirson A, Drexler W. In vivo retinal optical coherence tomography at 1,040 nm - enhanced penetration into the choroid. Opt Express. 2005;13(9):3252-8.

Corbelli E, Sacconi R, Rabiolo A, Mercuri S, Carnevali A, Querques L, et al. Optical coherence tomography angiography in the evaluation of geographic atrophy area extension. Invest Ophthalmol Vis Sci. 2017;58(12):5201-8. doi: 10.1167/iovs.17-22508.

de Carlo TE, Bonini Filho MA, Chin AT, Adhi M, Ferrara D, Baumal CR, et al. Spectral-domain optical coherence tomography angiography (OCTA) of choroidal neovascularization. Ophthalmology. 2015;122(6):1228-38. doi: 10.1016/j.ophtha.2015.01.029.

Coscas G, Lupidi M, Coscas F, Français C, Cagini C, Souied EH. Optical coherence tomography angiography during follow-up: qualitative and quantitative analysis of mixed type I and II choroidal neovascularization after vascular endothelial growth factor trap therapy. Ophthalmic Res. 2015;54(2):57-63. doi: 10.1159/000433547.

Coscas G, Lupidi M, Coscas F, et al. Optical coherence tomography angiography versus traditional multimodal imaging in assessing the activity of exudative age-related macular degeneration: a new diagnostic challenge. Retina. 2015;35(11):2219-28. doi: 10.1097/IAE.0000000000000766.

Spaide RF, Klancnik JM Jr, Cooney MJ. Retinal vascular layers imaged by fluorescein angiography and optical coherence tomography angiography. JAMA Ophthalmol. 2015;133(1):45-50. doi: 10.1001/jamaophthalmol.2014.3616.

Palejwala NV, Jia Y, Gao SS, Liu L, Flaxel CJ, Hwang TS, et al. Detection of non-exudative choroidal neovascularization in age-related macular degeneration with optical coherence tomography angiography. Retina (Philadelphia, Pa). 2015;35(11):2204-11. doi: 10.1097/IAE.0000000000000867.

Sarks SH. Ageing and degeneration in the macular region: a clinic-pathological study. Br J Ophthalmol. 1976; 60(5):324-41.

Miller H, Miller B, Ryan SJ. Newly-formed subretinal vessels. Fine structure and fluorescein leakage. Invest Ophthalmol Vis Sci. 1986; 27(2):204-13.

Lumbroso B, Huang D, Jian Y, Fujimoto JG, Rispoli M. Clinical guide to Angio-OCT. Jaypee Brothers Medical Publisher; 2015.



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About The Authors

Vladimir Stavrev
Department of Ophthalmology, Faculty of Medicine, Medical University of Plovdiv

Medical University of Plovdiv

Nelly Sivkova
Department of Ophthalmology, Faculty of Medicine, Medical University of Plovdiv

Medical University of Plovdiv

Desislava Koleva-Georgieva
Department of Ophthalmology, Faculty of Medicine, Medical University of Plovdiv

Medical University of Plovdiv