Abstract

We introduce a method to automatically detect drusen in dry age-related macular degeneration (AMD) from optical coherence tomography with minimum need for layer segmentation. The method is based on the en face detection of drusen areas in C-scans at certain distances above the Bruch’s membrane, circumventing the difficult task of pathologic retinal pigment epithelium segmentation. All types of drusen can be detected, including the challenging subretinal drusenoid deposits (pseudodrusen). The high sensitivity and accuracy demonstrated here shows its potential for detection of drusen onset in early AMD.

© 2017 Optical Society of America

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2017 (10)

D. C. Neely, K. J. Bray, C. E. Huisingh, M. E. Clark, G. McGwin, and C. Owsley, “Prevalence of Undiagnosed Age-Related Macular Degeneration in Primary Eye Care,” JAMA Ophthalmol. 135(6), 570–575 (2017).
[PubMed]

A. Ly, L. Nivison-Smith, N. Assaad, and M. Kalloniatis, “Fundus Autofluorescence in Age-related Macular Degeneration,” Optom. Vis. Sci. 94(2), 246–259 (2017).
[PubMed]

L. de Sisternes, G. Jonna, M. A. Greven, Q. Chen, T. Leng, and D. L. Rubin, “Individual Drusen Segmentation and Repeatability and Reproducibility of Their Automated Quantification in Optical Coherence Tomography Images,” Transl. Vis. Sci. Technol. 6(1), 12 (2017).
[PubMed]

J. P. Campbell, M. Zhang, T. S. Hwang, S. T. Bailey, D. J. Wilson, Y. Jia, and D. Huang, “Detailed Vascular Anatomy of the Human Retina by Projection-Resolved Optical Coherence Tomography Angiography,” Sci. Rep.  7, 42201 (2017).

K. B. Schaal, A. D. Legarreta, W. J. Feuer, G. Gregori, Q. Cheng, J. E. Legarreta, M. K. Durbin, P. F. Stetson, S. Kubach, and P. J. Rosenfeld, “Comparison between Widefield En Face Swept-Source OCT and Conventional Multimodal Imaging for the Detection of Reticular Pseudodrusen,” Ophthalmology 124(2), 205–214 (2017).
[PubMed]

J. Mazzaferri, L. Beaton, G. Hounye, D. N. Sayah, and S. Costantino, “Open-source algorithm for automatic choroid segmentation of OCT volume reconstructions,” Sci. Rep. 7, 42112 (2017).

J. Ma, R. Desai, P. Nesper, M. Gill, A. Fawzi, and D. Skondra, “Optical Coherence Tomographic Angiography Imaging in Age-Related Macular Degeneration,” Ophthalmol. Eye Dis. 9, 1179172116686075 (2017).
[PubMed]

C. Dongye, M. Zhang, T. S. Hwang, J. Wang, S. S. Gao, L. Liu, D. Huang, D. J. Wilson, and Y. Jia, “Automated detection of dilated capillaries on optical coherence tomography angiography,” Biomed. Opt. Express 8(2), 1101–1109 (2017).
[PubMed]

J. Wang, M. Zhang, T. S. Hwang, S. T. Bailey, D. Huang, D. J. Wilson, and Y. Jia, “Reflectance-based projection-resolved optical coherence tomography angiography [Invited],” Biomed. Opt. Express 8(3), 1536–1548 (2017).
[PubMed]

L. Fang, D. Cunefare, C. Wang, R. H. Guymer, S. Li, and S. Farsiu, “Automatic segmentation of nine retinal layer boundaries in OCT images of non-exudative AMD patients using deep learning and graph search,” Biomed. Opt. Express 8(5), 2732–2744 (2017).
[PubMed]

2016 (6)

A. Camino, M. Zhang, S. S. Gao, T. S. Hwang, U. Sharma, D. J. Wilson, D. Huang, and Y. Jia, “Evaluation of artifact reduction in optical coherence tomography angiography with real-time tracking and motion correction technology,” Biomed. Opt. Express 7(10), 3905–3915 (2016).
[PubMed]

K. Lee, G. H. S. Buitendijk, H. Bogunovic, H. Springelkamp, A. Hofman, A. Wahle, M. Sonka, J. R. Vingerling, C. C. W. Klaver, and M. D. Abràmoff, “Automated Segmentability Index for Layer Segmentation of Macular SD-OCT Images,” Transl. Vis. Sci. Technol. 5(2), 14 (2016).
[PubMed]

L. Toto, E. Borrelli, L. Di Antonio, P. Carpineto, and R. Mastropasqua, “Retinal vascular plexuses’ changes in dry age-related macular degeneration, evaluated by means of optical coherence tomography angiography,” Retina 36(8), 1566–1572 (2016).
[PubMed]

Z. Wu, L. N. Ayton, C. D. Luu, P. N. Baird, and R. H. Guymer, “Reticular Pseudodrusen in Intermediate Age-Related Macular Degeneration: Prevalence, Detection, Clinical, Environmental, and Genetic Associations,” Invest. Ophthalmol. Vis. Sci. 57(3), 1310–1316 (2016).
[PubMed]

M. A. Guerroudji and Z. Ameur, “A new approach for the detection of mammary calcifications by using the white Top-Hat transform and thresholding of Otsu,” Optik - International Journal for Light and Electron Optics 127, 1251– 1259 (2016).

Z. M. Dong, G. Wollstein, and J. S. Schuman, “Clinical Utility of Optical Coherence Tomography in Glaucoma,” Invest. Ophthalmol. Vis. Sci. 57(9), OCT556 (2016).
[PubMed]

2015 (2)

Y. Jia, S. T. Bailey, T. S. Hwang, S. M. McClintic, S. S. Gao, M. E. Pennesi, C. J. Flaxel, A. K. Lauer, D. J. Wilson, J. Hornegger, J. G. Fujimoto, and D. Huang, “Quantitative optical coherence tomography angiography of vascular abnormalities in the living human eye,” Proc. Natl. Acad. Sci. U.S.A. 112(18), E2395–E2402 (2015).
[PubMed]

M. Zhang, J. Wang, A. D. Pechauer, T. S. Hwang, S. S. Gao, L. Liu, L. Liu, S. T. Bailey, D. J. Wilson, D. Huang, and Y. Jia, “Advanced image processing for optical coherence tomographic angiography of macular diseases,” Biomed. Opt. Express 6(12), 4661–4675 (2015).
[PubMed]

2014 (8)

M. F. Kraus, J. J. Liu, J. Schottenhamml, C. L. Chen, A. Budai, L. Branchini, T. Ko, H. Ishikawa, G. Wollstein, J. Schuman, J. S. Duker, J. G. Fujimoto, and J. Hornegger, “Quantitative 3D-OCT motion correction with tilt and illumination correction, robust similarity measure and regularization,” Biomed. Opt. Express 5(8), 2591–2613 (2014).
[PubMed]

S. Farsiu, S. J. Chiu, R. V. O’Connell, F. A. Folgar, E. Yuan, J. A. Izatt, C. A. Toth, and Age-Related Eye Disease Study 2 Ancillary Spectral Domain Optical Coherence Tomography Study Group, “Quantitative Classification of Eyes with and without Intermediate Age-related Macular Degeneration Using Optical Coherence Tomography,” Ophthalmology 121(1), 162–172 (2014).
[PubMed]

I. I. Bussel, G. Wollstein, and J. S. Schuman, “OCT for glaucoma diagnosis, screening and detection of glaucoma progression,” Br. J. Ophthalmol. 98(Suppl 2), ii15–ii19 (2014).
[PubMed]

G. Trichonas and P. K. Kaiser, “Optical coherence tomography imaging of macular oedema,” Br. J. Ophthalmol. 98(Suppl 2), ii24–ii29 (2014).
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W. L. Wong, X. Su, X. Li, C. M. Cheung, R. Klein, C. Y. Cheng, and T. Y. Wong, “Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis,” Lancet Glob. Health 2(2), e106–e116 (2014).
[PubMed]

S. Boddu, M. D. Lee, M. Marsiglia, M. Marmor, K. B. Freund, and R. T. Smith, “Risk factors associated with reticular pseudodrusen versus large soft drusen,” Am. J. Ophthalmol. 157(5), 985–993.e2, e982 (2014).
[PubMed]

R. P. Finger, Z. Wu, C. D. Luu, F. Kearney, L. N. Ayton, L. M. Lucci, W. C. Hubbard, J. L. Hageman, G. S. Hageman, and R. H. Guymer, “Reticular pseudodrusen: a risk factor for geographic atrophy in fellow eyes of individuals with unilateral choroidal neovascularization,” Ophthalmology 121(6), 1252–1256 (2014).
[PubMed]

Y. Kanagasingam, A. Bhuiyan, M. D. Abràmoff, R. T. Smith, L. Goldschmidt, and T. Y. Wong, “Progress on retinal image analysis for age related macular degeneration,” Prog. Retin. Eye Res. 38, 20–42 (2014).
[PubMed]

2013 (4)

M. J. van Grinsven, Y. T. Lechanteur, J. P. van de Ven, B. van Ginneken, C. B. Hoyng, T. Theelen, and C. I. Sánchez, “Automatic drusen quantification and risk assessment of age-related macular degeneration on color fundus images,” Invest. Ophthalmol. Vis. Sci. 54(4), 3019–3027 (2013).
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Q. Chen, T. Leng, L. Zheng, L. Kutzscher, J. Ma, L. de Sisternes, and D. L. Rubin, “Automated drusen segmentation and quantification in SD-OCT images,” Med. Image Anal. 17(8), 1058–1072 (2013).
[PubMed]

Q. Chen, T. Leng, L. Zheng, L. Kutzscher, J. Ma, L. de Sisternes, and D. L. Rubin, “Automated drusen segmentation and quantification in SD-OCT images,” Med. Image Anal. 17(8), 1058–1072 (2013).
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N. Ueda-Arakawa, S. Ooto, A. Tsujikawa, K. Yamashiro, A. Oishi, and N. Yoshimura, “Sensitivity And Specificity Of Detecting Reticular Pseudodrusen In Multimodal Imaging In Japanese Patients,” Retina 33(3), 490–497 (2013).
[PubMed]

2012 (4)

Y. Jia, O. Tan, J. Tokayer, B. Potsaid, Y. Wang, J. J. Liu, M. F. Kraus, H. Subhash, J. G. Fujimoto, J. Hornegger, and D. Huang, “Split-spectrum amplitude-decorrelation angiography with optical coherence tomography,” Opt. Express 20(4), 4710–4725 (2012).
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M. F. Kraus, B. Potsaid, M. A. Mayer, R. Bock, B. Baumann, J. J. Liu, J. Hornegger, and J. G. Fujimoto, “Motion correction in optical coherence tomography volumes on a per A-scan basis using orthogonal scan patterns,” Biomed. Opt. Express 3(6), 1182–1199 (2012).
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S. J. Chiu, J. A. Izatt, R. V. O’Connell, K. P. Winter, C. A. Toth, and S. Farsiu, “Validated automatic segmentation of AMD pathology including drusen and geographic atrophy in SD-OCT images,” Invest. Ophthalmol. Vis. Sci. 53(1), 53–61 (2012).
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D. Pascolini and S. P. Mariotti, “Global estimates of visual impairment: 2010,” Br. J. Ophthalmol. 96(5), 614–618 (2012).
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2011 (4)

A. D. Mora, P. M. Vieira, A. Manivannan, and J. M. Fonseca, “Automated drusen detection in retinal images using analytical modelling algorithms,” Biomed. Eng. Online 10, 59 (2011).
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J. H. Acton, R. P. Cubbidge, H. King, P. Galsworthy, and J. M. Gibson, “Drusen detection in retro-mode imaging by a scanning laser ophthalmoscope,” Acta Ophthalmol. 89(5), e404–e411 (2011).
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R. F. Mullins, M. N. Johnson, E. A. Faidley, J. M. Skeie, and J. Huang, “Choriocapillaris Vascular Dropout Related to Density of Drusen in Human Eyes with Early Age-Related Macular Degeneration,” Invest. Ophthalmol. Vis. Sci. 52(3), 1606–1612 (2011).
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G. Gregori, F. Wang, P. J. Rosenfeld, Z. Yehoshua, N. Z. Gregori, B. J. Lujan, C. A. Puliafito, and W. J. Feuer, “Spectral Domain Optical Coherence Tomography Imaging of Drusen in Nonexudative Age-Related Macular Degeneration,” Ophthalmology 118(7), 1373–1379 (2011).
[PubMed]

2010 (8)

F. G. Schlanitz, C. Ahlers, S. Sacu, C. Schütze, M. Rodriguez, S. Schriefl, I. Golbaz, T. Spalek, G. Stock, and U. Schmidt-Erfurth, “Performance of drusen detection by spectral-domain optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 51(12), 6715–6721 (2010).
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S. A. Zweifel, Y. Imamura, T. C. Spaide, T. Fujiwara, and R. F. Spaide, “Prevalence and Significance of Subretinal Drusenoid Deposits (Reticular Pseudodrusen) in Age-Related Macular Degeneration,” Ophthalmology 117(9), 1775–1781 (2010).
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Q. Yang, C. A. Reisman, Z. Wang, Y. Fukuma, M. Hangai, N. Yoshimura, A. Tomidokoro, M. Araie, A. S. Raza, D. C. Hood, and K. Chan, “Automated layer segmentation of macular OCT images using dual-scale gradient information,” Opt. Express 18(20), 21293–21307 (2010).
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R. F. Spaide and C. A. Curcio, “Drusen Characterization with Multimodal Imaging,” Retina 30(9), 1441–1454 (2010).
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S. A. Zweifel, R. F. Spaide, C. A. Curcio, G. Malek, and Y. Imamura, “Reticular pseudodrusen are subretinal drusenoid deposits,” Ophthalmology 117(2), 303–312.e1, e301 (2010).
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C. Köse, U. Sevik, O. Gençalioğlu, C. Ikibaş, and T. Kayikiçioğlu, “A statistical segmentation method for measuring age-related macular degeneration in retinal fundus images,” J. Med. Syst. 34(1), 1–13 (2010).
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N. Jain, S. Farsiu, A. A. Khanifar, S. Bearelly, R. T. Smith, J. A. Izatt, and C. A. Toth, “Quantitative Comparison of Drusen Segmented on SD-OCT versus Drusen Delineated on Color Fundus Photographs,” Invest. Ophthalmol. Vis. Sci. 51(10), 4875–4883 (2010).
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L. Wang, M. E. Clark, D. K. Crossman, K. Kojima, J. D. Messinger, J. A. Mobley, and C. A. Curcio, “Abundant Lipid and Protein Components of Drusen,” PLoS One 5(4), e10329 (2010).
[PubMed]

2009 (2)

R. T. Smith, M. A. Sohrab, M. Busuioc, and G. Barile, “Reticular macular disease,” Am. J. Ophthalmol. 148(5), 733–743 (2009).
[PubMed]

K. Yi, M. Mujat, B. H. Park, W. Sun, J. W. Miller, J. M. Seddon, L. H. Young, J. F. de Boer, and T. C. Chen, “Spectral domain optical coherence tomography for quantitative evaluation of drusen and associated structural changes in non-neovascular age-related macular degeneration,” Br. J. Ophthalmol. 93(2), 176–181 (2009).
[PubMed]

2008 (2)

S. J. C. Sina Farsiu, A. J. Izatt, and C. A. Toth,Proc. SPIE 6844, Ophthalmic Technologies XVIII, 68440D (2008/02/11), “Fast detection and segmentation of drusen in retinal optical coherence tomography images,” Proc. SPIE 6844, Ophthalmic Technologies XVIII, 68440D (2008).

C. Köse, U. Sevik, and O. Gençalioğlu, “Automatic segmentation of age-related macular degeneration in retinal fundus images,” Comput. Biol. Med. 38(5), 611–619 (2008).
[PubMed]

2007 (1)

H. Bartlett and F. Eperjesi, “Use of fundus imaging in quantification of age-related macular change,” Surv. Ophthalmol. 52(6), 655–671 (2007).
[PubMed]

2006 (2)

R. T. Smith, J. K. Chan, M. Busuoic, V. Sivagnanavel, A. C. Bird, and N. V. Chong, “Autofluorescence characteristics of early, atrophic, and high-risk fellow eyes in age-related macular degeneration,” Invest. Ophthalmol. Vis. Sci. 47(12), 5495–5504 (2006).
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M. Anderson, W. W. Dawson, J. Gonzalez-Martinez, and C. A. Curcio, “Drusen and lipid-filled retinal pigment epithelium cells in a rhesus macula,” Vet. Ophthalmol. 9(3), 201–207 (2006).
[PubMed]

2005 (1)

R. T. Smith, J. K. Chan, T. Nagasaki, J. R. Sparrow, and I. Barbazetto, “A method of drusen measurement based on reconstruction of fundus background reflectance,” Br. J. Ophthalmol. 89(1), 87–91 (2005).
[PubMed]

2003 (1)

K. Rapantzikos, M. Zervakis, and K. Balas, “Detection and segmentation of drusen deposits on human retina: potential in the diagnosis of age-related macular degeneration,” Med. Image Anal. 7(1), 95–108 (2003).
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1999 (1)

D. S. Shin, N. B. Javornik, and J. W. Berger, “Computer-assisted, interactive fundus image processing for macular drusen quantitation,” Ophthalmology 106(6), 1119–1125 (1999).
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1996 (1)

M. R. Hee, C. R. Baumal, C. A. Puliafito, J. S. Duker, E. Reichel, J. R. Wilkins, J. G. Coker, J. S. Schuman, E. A. Swanson, and J. G. Fujimoto, “Optical coherence tomography of age-related macular degeneration and choroidal neovascularization,” Ophthalmology 103(8), 1260–1270 (1996).
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1995 (2)

A. von Rückmann, F. W. Fitzke, and A. C. Bird, “Distribution of fundus autofluorescence with a scanning laser ophthalmoscope,” Br. J. Ophthalmol. 79(5), 407–412 (1995).
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J. J. Arnold, S. H. Sarks, M. C. Killingsworth, and J. P. Sarks, “Reticular pseudodrusen. A risk factor in age-related maculopathy,” Retina 15(3), 183–191 (1995).
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1993 (1)

1991 (1)

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
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1988 (1)

N. M. Bressler, S. B. Bressler, and S. L. Fine, “Age-related macular degeneration,” Surv. Ophthalmol. 32(6), 375–413 (1988).
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1856 (1)

H. Müller, “Anatomische Beiträge zur Ophthalmologie,” Arch. Ophthalmol. 2, 1–69 (1856).

Abràmoff, M. D.

K. Lee, G. H. S. Buitendijk, H. Bogunovic, H. Springelkamp, A. Hofman, A. Wahle, M. Sonka, J. R. Vingerling, C. C. W. Klaver, and M. D. Abràmoff, “Automated Segmentability Index for Layer Segmentation of Macular SD-OCT Images,” Transl. Vis. Sci. Technol. 5(2), 14 (2016).
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Y. Kanagasingam, A. Bhuiyan, M. D. Abràmoff, R. T. Smith, L. Goldschmidt, and T. Y. Wong, “Progress on retinal image analysis for age related macular degeneration,” Prog. Retin. Eye Res. 38, 20–42 (2014).
[PubMed]

Acton, J. H.

J. H. Acton, R. P. Cubbidge, H. King, P. Galsworthy, and J. M. Gibson, “Drusen detection in retro-mode imaging by a scanning laser ophthalmoscope,” Acta Ophthalmol. 89(5), e404–e411 (2011).
[PubMed]

Ahlers, C.

F. G. Schlanitz, C. Ahlers, S. Sacu, C. Schütze, M. Rodriguez, S. Schriefl, I. Golbaz, T. Spalek, G. Stock, and U. Schmidt-Erfurth, “Performance of drusen detection by spectral-domain optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 51(12), 6715–6721 (2010).
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Ameur, Z.

M. A. Guerroudji and Z. Ameur, “A new approach for the detection of mammary calcifications by using the white Top-Hat transform and thresholding of Otsu,” Optik - International Journal for Light and Electron Optics 127, 1251– 1259 (2016).

Anderson, M.

M. Anderson, W. W. Dawson, J. Gonzalez-Martinez, and C. A. Curcio, “Drusen and lipid-filled retinal pigment epithelium cells in a rhesus macula,” Vet. Ophthalmol. 9(3), 201–207 (2006).
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Araie, M.

Arnold, J. J.

J. J. Arnold, S. H. Sarks, M. C. Killingsworth, and J. P. Sarks, “Reticular pseudodrusen. A risk factor in age-related maculopathy,” Retina 15(3), 183–191 (1995).
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Assaad, N.

A. Ly, L. Nivison-Smith, N. Assaad, and M. Kalloniatis, “Fundus Autofluorescence in Age-related Macular Degeneration,” Optom. Vis. Sci. 94(2), 246–259 (2017).
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Ayton, L. N.

Z. Wu, L. N. Ayton, C. D. Luu, P. N. Baird, and R. H. Guymer, “Reticular Pseudodrusen in Intermediate Age-Related Macular Degeneration: Prevalence, Detection, Clinical, Environmental, and Genetic Associations,” Invest. Ophthalmol. Vis. Sci. 57(3), 1310–1316 (2016).
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R. P. Finger, Z. Wu, C. D. Luu, F. Kearney, L. N. Ayton, L. M. Lucci, W. C. Hubbard, J. L. Hageman, G. S. Hageman, and R. H. Guymer, “Reticular pseudodrusen: a risk factor for geographic atrophy in fellow eyes of individuals with unilateral choroidal neovascularization,” Ophthalmology 121(6), 1252–1256 (2014).
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Bailey, S. T.

J. P. Campbell, M. Zhang, T. S. Hwang, S. T. Bailey, D. J. Wilson, Y. Jia, and D. Huang, “Detailed Vascular Anatomy of the Human Retina by Projection-Resolved Optical Coherence Tomography Angiography,” Sci. Rep.  7, 42201 (2017).

J. Wang, M. Zhang, T. S. Hwang, S. T. Bailey, D. Huang, D. J. Wilson, and Y. Jia, “Reflectance-based projection-resolved optical coherence tomography angiography [Invited],” Biomed. Opt. Express 8(3), 1536–1548 (2017).
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Y. Jia, S. T. Bailey, T. S. Hwang, S. M. McClintic, S. S. Gao, M. E. Pennesi, C. J. Flaxel, A. K. Lauer, D. J. Wilson, J. Hornegger, J. G. Fujimoto, and D. Huang, “Quantitative optical coherence tomography angiography of vascular abnormalities in the living human eye,” Proc. Natl. Acad. Sci. U.S.A. 112(18), E2395–E2402 (2015).
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M. Zhang, J. Wang, A. D. Pechauer, T. S. Hwang, S. S. Gao, L. Liu, L. Liu, S. T. Bailey, D. J. Wilson, D. Huang, and Y. Jia, “Advanced image processing for optical coherence tomographic angiography of macular diseases,” Biomed. Opt. Express 6(12), 4661–4675 (2015).
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Baird, P. N.

Z. Wu, L. N. Ayton, C. D. Luu, P. N. Baird, and R. H. Guymer, “Reticular Pseudodrusen in Intermediate Age-Related Macular Degeneration: Prevalence, Detection, Clinical, Environmental, and Genetic Associations,” Invest. Ophthalmol. Vis. Sci. 57(3), 1310–1316 (2016).
[PubMed]

Balas, K.

K. Rapantzikos, M. Zervakis, and K. Balas, “Detection and segmentation of drusen deposits on human retina: potential in the diagnosis of age-related macular degeneration,” Med. Image Anal. 7(1), 95–108 (2003).
[PubMed]

Barbazetto, I.

R. T. Smith, J. K. Chan, T. Nagasaki, J. R. Sparrow, and I. Barbazetto, “A method of drusen measurement based on reconstruction of fundus background reflectance,” Br. J. Ophthalmol. 89(1), 87–91 (2005).
[PubMed]

Barile, G.

R. T. Smith, M. A. Sohrab, M. Busuioc, and G. Barile, “Reticular macular disease,” Am. J. Ophthalmol. 148(5), 733–743 (2009).
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Barrett, W. A.

E. N. Mortensen and W. A. Barrett, “Intelligent scissors for image composition,” in Proceedings of the 22nd annual conference on Computer graphics and interactive techniques, (ACM, 1995), pp. 191–198.

Bartlett, H.

H. Bartlett and F. Eperjesi, “Use of fundus imaging in quantification of age-related macular change,” Surv. Ophthalmol. 52(6), 655–671 (2007).
[PubMed]

Baumal, C. R.

M. R. Hee, C. R. Baumal, C. A. Puliafito, J. S. Duker, E. Reichel, J. R. Wilkins, J. G. Coker, J. S. Schuman, E. A. Swanson, and J. G. Fujimoto, “Optical coherence tomography of age-related macular degeneration and choroidal neovascularization,” Ophthalmology 103(8), 1260–1270 (1996).
[PubMed]

Baumann, B.

Bearelly, S.

N. Jain, S. Farsiu, A. A. Khanifar, S. Bearelly, R. T. Smith, J. A. Izatt, and C. A. Toth, “Quantitative Comparison of Drusen Segmented on SD-OCT versus Drusen Delineated on Color Fundus Photographs,” Invest. Ophthalmol. Vis. Sci. 51(10), 4875–4883 (2010).
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Beaton, L.

J. Mazzaferri, L. Beaton, G. Hounye, D. N. Sayah, and S. Costantino, “Open-source algorithm for automatic choroid segmentation of OCT volume reconstructions,” Sci. Rep. 7, 42112 (2017).

Berger, J. W.

D. S. Shin, N. B. Javornik, and J. W. Berger, “Computer-assisted, interactive fundus image processing for macular drusen quantitation,” Ophthalmology 106(6), 1119–1125 (1999).
[PubMed]

Bhuiyan, A.

Y. Kanagasingam, A. Bhuiyan, M. D. Abràmoff, R. T. Smith, L. Goldschmidt, and T. Y. Wong, “Progress on retinal image analysis for age related macular degeneration,” Prog. Retin. Eye Res. 38, 20–42 (2014).
[PubMed]

Bird, A. C.

R. T. Smith, J. K. Chan, M. Busuoic, V. Sivagnanavel, A. C. Bird, and N. V. Chong, “Autofluorescence characteristics of early, atrophic, and high-risk fellow eyes in age-related macular degeneration,” Invest. Ophthalmol. Vis. Sci. 47(12), 5495–5504 (2006).
[PubMed]

A. von Rückmann, F. W. Fitzke, and A. C. Bird, “Distribution of fundus autofluorescence with a scanning laser ophthalmoscope,” Br. J. Ophthalmol. 79(5), 407–412 (1995).
[PubMed]

Bock, R.

Boddu, S.

S. Boddu, M. D. Lee, M. Marsiglia, M. Marmor, K. B. Freund, and R. T. Smith, “Risk factors associated with reticular pseudodrusen versus large soft drusen,” Am. J. Ophthalmol. 157(5), 985–993.e2, e982 (2014).
[PubMed]

Bogunovic, H.

K. Lee, G. H. S. Buitendijk, H. Bogunovic, H. Springelkamp, A. Hofman, A. Wahle, M. Sonka, J. R. Vingerling, C. C. W. Klaver, and M. D. Abràmoff, “Automated Segmentability Index for Layer Segmentation of Macular SD-OCT Images,” Transl. Vis. Sci. Technol. 5(2), 14 (2016).
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Borrelli, E.

L. Toto, E. Borrelli, L. Di Antonio, P. Carpineto, and R. Mastropasqua, “Retinal vascular plexuses’ changes in dry age-related macular degeneration, evaluated by means of optical coherence tomography angiography,” Retina 36(8), 1566–1572 (2016).
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Branchini, L.

Bray, K. J.

D. C. Neely, K. J. Bray, C. E. Huisingh, M. E. Clark, G. McGwin, and C. Owsley, “Prevalence of Undiagnosed Age-Related Macular Degeneration in Primary Eye Care,” JAMA Ophthalmol. 135(6), 570–575 (2017).
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Bressler, N. M.

N. M. Bressler, S. B. Bressler, and S. L. Fine, “Age-related macular degeneration,” Surv. Ophthalmol. 32(6), 375–413 (1988).
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Bressler, S. B.

N. M. Bressler, S. B. Bressler, and S. L. Fine, “Age-related macular degeneration,” Surv. Ophthalmol. 32(6), 375–413 (1988).
[PubMed]

Budai, A.

Buitendijk, G. H. S.

K. Lee, G. H. S. Buitendijk, H. Bogunovic, H. Springelkamp, A. Hofman, A. Wahle, M. Sonka, J. R. Vingerling, C. C. W. Klaver, and M. D. Abràmoff, “Automated Segmentability Index for Layer Segmentation of Macular SD-OCT Images,” Transl. Vis. Sci. Technol. 5(2), 14 (2016).
[PubMed]

Bussel, I. I.

I. I. Bussel, G. Wollstein, and J. S. Schuman, “OCT for glaucoma diagnosis, screening and detection of glaucoma progression,” Br. J. Ophthalmol. 98(Suppl 2), ii15–ii19 (2014).
[PubMed]

Busuioc, M.

R. T. Smith, M. A. Sohrab, M. Busuioc, and G. Barile, “Reticular macular disease,” Am. J. Ophthalmol. 148(5), 733–743 (2009).
[PubMed]

Busuoic, M.

R. T. Smith, J. K. Chan, M. Busuoic, V. Sivagnanavel, A. C. Bird, and N. V. Chong, “Autofluorescence characteristics of early, atrophic, and high-risk fellow eyes in age-related macular degeneration,” Invest. Ophthalmol. Vis. Sci. 47(12), 5495–5504 (2006).
[PubMed]

Camino, A.

Campbell, J. P.

J. P. Campbell, M. Zhang, T. S. Hwang, S. T. Bailey, D. J. Wilson, Y. Jia, and D. Huang, “Detailed Vascular Anatomy of the Human Retina by Projection-Resolved Optical Coherence Tomography Angiography,” Sci. Rep.  7, 42201 (2017).

Carpineto, P.

L. Toto, E. Borrelli, L. Di Antonio, P. Carpineto, and R. Mastropasqua, “Retinal vascular plexuses’ changes in dry age-related macular degeneration, evaluated by means of optical coherence tomography angiography,” Retina 36(8), 1566–1572 (2016).
[PubMed]

Chan, J. K.

R. T. Smith, J. K. Chan, M. Busuoic, V. Sivagnanavel, A. C. Bird, and N. V. Chong, “Autofluorescence characteristics of early, atrophic, and high-risk fellow eyes in age-related macular degeneration,” Invest. Ophthalmol. Vis. Sci. 47(12), 5495–5504 (2006).
[PubMed]

R. T. Smith, J. K. Chan, T. Nagasaki, J. R. Sparrow, and I. Barbazetto, “A method of drusen measurement based on reconstruction of fundus background reflectance,” Br. J. Ophthalmol. 89(1), 87–91 (2005).
[PubMed]

Chan, K.

Chang, W.

D. Huang, E. A. Swanson, C. P. Lin, J. S. Schuman, W. G. Stinson, W. Chang, M. R. Hee, T. Flotte, K. Gregory, C. A. Puliafito, and J. G. Fujimoto, “Optical coherence tomography,” Science 254(5035), 1178–1181 (1991).
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Chen, C. L.

Chen, Q.

L. de Sisternes, G. Jonna, M. A. Greven, Q. Chen, T. Leng, and D. L. Rubin, “Individual Drusen Segmentation and Repeatability and Reproducibility of Their Automated Quantification in Optical Coherence Tomography Images,” Transl. Vis. Sci. Technol. 6(1), 12 (2017).
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Q. Chen, T. Leng, L. Zheng, L. Kutzscher, J. Ma, L. de Sisternes, and D. L. Rubin, “Automated drusen segmentation and quantification in SD-OCT images,” Med. Image Anal. 17(8), 1058–1072 (2013).
[PubMed]

Q. Chen, T. Leng, L. Zheng, L. Kutzscher, J. Ma, L. de Sisternes, and D. L. Rubin, “Automated drusen segmentation and quantification in SD-OCT images,” Med. Image Anal. 17(8), 1058–1072 (2013).
[PubMed]

Chen, T. C.

K. Yi, M. Mujat, B. H. Park, W. Sun, J. W. Miller, J. M. Seddon, L. H. Young, J. F. de Boer, and T. C. Chen, “Spectral domain optical coherence tomography for quantitative evaluation of drusen and associated structural changes in non-neovascular age-related macular degeneration,” Br. J. Ophthalmol. 93(2), 176–181 (2009).
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Cheng, C. Y.

W. L. Wong, X. Su, X. Li, C. M. Cheung, R. Klein, C. Y. Cheng, and T. Y. Wong, “Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis,” Lancet Glob. Health 2(2), e106–e116 (2014).
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Cheng, Q.

K. B. Schaal, A. D. Legarreta, W. J. Feuer, G. Gregori, Q. Cheng, J. E. Legarreta, M. K. Durbin, P. F. Stetson, S. Kubach, and P. J. Rosenfeld, “Comparison between Widefield En Face Swept-Source OCT and Conventional Multimodal Imaging for the Detection of Reticular Pseudodrusen,” Ophthalmology 124(2), 205–214 (2017).
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A. D. Mora, P. M. Vieira, A. Manivannan, and J. M. Fonseca, “Automated drusen detection in retinal images using analytical modelling algorithms,” Biomed. Eng. Online 10, 59 (2011).
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J. Wang, M. Zhang, T. S. Hwang, S. T. Bailey, D. Huang, D. J. Wilson, and Y. Jia, “Reflectance-based projection-resolved optical coherence tomography angiography [Invited],” Biomed. Opt. Express 8(3), 1536–1548 (2017).
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S. J. Chiu, J. A. Izatt, R. V. O’Connell, K. P. Winter, C. A. Toth, and S. Farsiu, “Validated automatic segmentation of AMD pathology including drusen and geographic atrophy in SD-OCT images,” Invest. Ophthalmol. Vis. Sci. 53(1), 53–61 (2012).
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W. L. Wong, X. Su, X. Li, C. M. Cheung, R. Klein, C. Y. Cheng, and T. Y. Wong, “Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis,” Lancet Glob. Health 2(2), e106–e116 (2014).
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K. Yi, M. Mujat, B. H. Park, W. Sun, J. W. Miller, J. M. Seddon, L. H. Young, J. F. de Boer, and T. C. Chen, “Spectral domain optical coherence tomography for quantitative evaluation of drusen and associated structural changes in non-neovascular age-related macular degeneration,” Br. J. Ophthalmol. 93(2), 176–181 (2009).
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S. A. Zweifel, Y. Imamura, T. C. Spaide, T. Fujiwara, and R. F. Spaide, “Prevalence and Significance of Subretinal Drusenoid Deposits (Reticular Pseudodrusen) in Age-Related Macular Degeneration,” Ophthalmology 117(9), 1775–1781 (2010).
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Acta Ophthalmol. (1)

J. H. Acton, R. P. Cubbidge, H. King, P. Galsworthy, and J. M. Gibson, “Drusen detection in retro-mode imaging by a scanning laser ophthalmoscope,” Acta Ophthalmol. 89(5), e404–e411 (2011).
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Biomed. Opt. Express (7)

M. F. Kraus, B. Potsaid, M. A. Mayer, R. Bock, B. Baumann, J. J. Liu, J. Hornegger, and J. G. Fujimoto, “Motion correction in optical coherence tomography volumes on a per A-scan basis using orthogonal scan patterns,” Biomed. Opt. Express 3(6), 1182–1199 (2012).
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M. F. Kraus, J. J. Liu, J. Schottenhamml, C. L. Chen, A. Budai, L. Branchini, T. Ko, H. Ishikawa, G. Wollstein, J. Schuman, J. S. Duker, J. G. Fujimoto, and J. Hornegger, “Quantitative 3D-OCT motion correction with tilt and illumination correction, robust similarity measure and regularization,” Biomed. Opt. Express 5(8), 2591–2613 (2014).
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M. Zhang, J. Wang, A. D. Pechauer, T. S. Hwang, S. S. Gao, L. Liu, L. Liu, S. T. Bailey, D. J. Wilson, D. Huang, and Y. Jia, “Advanced image processing for optical coherence tomographic angiography of macular diseases,” Biomed. Opt. Express 6(12), 4661–4675 (2015).
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A. Camino, M. Zhang, S. S. Gao, T. S. Hwang, U. Sharma, D. J. Wilson, D. Huang, and Y. Jia, “Evaluation of artifact reduction in optical coherence tomography angiography with real-time tracking and motion correction technology,” Biomed. Opt. Express 7(10), 3905–3915 (2016).
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C. Dongye, M. Zhang, T. S. Hwang, J. Wang, S. S. Gao, L. Liu, D. Huang, D. J. Wilson, and Y. Jia, “Automated detection of dilated capillaries on optical coherence tomography angiography,” Biomed. Opt. Express 8(2), 1101–1109 (2017).
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J. Wang, M. Zhang, T. S. Hwang, S. T. Bailey, D. Huang, D. J. Wilson, and Y. Jia, “Reflectance-based projection-resolved optical coherence tomography angiography [Invited],” Biomed. Opt. Express 8(3), 1536–1548 (2017).
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L. Fang, D. Cunefare, C. Wang, R. H. Guymer, S. Li, and S. Farsiu, “Automatic segmentation of nine retinal layer boundaries in OCT images of non-exudative AMD patients using deep learning and graph search,” Biomed. Opt. Express 8(5), 2732–2744 (2017).
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K. Yi, M. Mujat, B. H. Park, W. Sun, J. W. Miller, J. M. Seddon, L. H. Young, J. F. de Boer, and T. C. Chen, “Spectral domain optical coherence tomography for quantitative evaluation of drusen and associated structural changes in non-neovascular age-related macular degeneration,” Br. J. Ophthalmol. 93(2), 176–181 (2009).
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Invest. Ophthalmol. Vis. Sci. (8)

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R. T. Smith, J. K. Chan, M. Busuoic, V. Sivagnanavel, A. C. Bird, and N. V. Chong, “Autofluorescence characteristics of early, atrophic, and high-risk fellow eyes in age-related macular degeneration,” Invest. Ophthalmol. Vis. Sci. 47(12), 5495–5504 (2006).
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Z. M. Dong, G. Wollstein, and J. S. Schuman, “Clinical Utility of Optical Coherence Tomography in Glaucoma,” Invest. Ophthalmol. Vis. Sci. 57(9), OCT556 (2016).
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S. J. Chiu, J. A. Izatt, R. V. O’Connell, K. P. Winter, C. A. Toth, and S. Farsiu, “Validated automatic segmentation of AMD pathology including drusen and geographic atrophy in SD-OCT images,” Invest. Ophthalmol. Vis. Sci. 53(1), 53–61 (2012).
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Z. Wu, L. N. Ayton, C. D. Luu, P. N. Baird, and R. H. Guymer, “Reticular Pseudodrusen in Intermediate Age-Related Macular Degeneration: Prevalence, Detection, Clinical, Environmental, and Genetic Associations,” Invest. Ophthalmol. Vis. Sci. 57(3), 1310–1316 (2016).
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Lancet Glob. Health (1)

W. L. Wong, X. Su, X. Li, C. M. Cheung, R. Klein, C. Y. Cheng, and T. Y. Wong, “Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis,” Lancet Glob. Health 2(2), e106–e116 (2014).
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Med. Image Anal. (3)

Q. Chen, T. Leng, L. Zheng, L. Kutzscher, J. Ma, L. de Sisternes, and D. L. Rubin, “Automated drusen segmentation and quantification in SD-OCT images,” Med. Image Anal. 17(8), 1058–1072 (2013).
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S. A. Zweifel, Y. Imamura, T. C. Spaide, T. Fujiwara, and R. F. Spaide, “Prevalence and Significance of Subretinal Drusenoid Deposits (Reticular Pseudodrusen) in Age-Related Macular Degeneration,” Ophthalmology 117(9), 1775–1781 (2010).
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S. A. Zweifel, R. F. Spaide, C. A. Curcio, G. Malek, and Y. Imamura, “Reticular pseudodrusen are subretinal drusenoid deposits,” Ophthalmology 117(2), 303–312.e1, e301 (2010).
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Optom. Vis. Sci. (1)

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PLoS One (1)

L. Wang, M. E. Clark, D. K. Crossman, K. Kojima, J. D. Messinger, J. A. Mobley, and C. A. Curcio, “Abundant Lipid and Protein Components of Drusen,” PLoS One 5(4), e10329 (2010).
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Proc. Natl. Acad. Sci. U.S.A. (1)

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Proc. SPIE 6844, Ophthalmic Technologies (1)

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Figures (12)

Fig. 1
Fig. 1 Challenges faced by drusen detection from cross-sectional segmentation of the retinal pigment epithelium (RPE). (A) Representative cross-sectional scan. Subretinal drusenoid deposits are white arrows and a region of no elevation between two soft drusen domes is indicated by the yellow arrow. (B) Segmentation of eight retinal layer interfaces performed automatically without manual correction by an algorithm based on directional graph search [42]. According to the position detected for the inner RPE interface, drusen would be likely undetected at the white arrows due to minimal elevation of the interface and overestimated at the yellow arrow positions. ILM – Inner limiting membrane. NFL – Nerve fiber layer. GCL - Ganglion cell layer. IPL – Inner plexiform layer. INL – Inner nuclear layer. OPL – Outer plexiform layer. ONL – Outer nuclear layer. EZ – Ellipsoid zone of the photoreceptors. RPE – Retinal pigment epithelium. BM – Bruch’s membrane. CH – choriocapillaris.
Fig. 2
Fig. 2 Flow chart of the drusen detection algorithm.
Fig. 3
Fig. 3 Drusen visualization of C-scans contained in two slabs at different depths. (A) B-scan of a normal eye (B) B-scan of an eye with dry AMD containing soft drusen and subretinal drusenoid deposits. (A1, B1) The innermost C-scan contained in the blue slab. Drusen area appears hyper-reflective compared to the background in (B1). (A2, B2) The outermost C-scan contained in the red slab. Soft drusen areas and vessel shadows appear hypo-reflective compared to the background in (B2) but subretinal drusenoid deposits are only evident in the blue slab. Yellow dashed lines indicate the position of the representative B-scans. Green arrows indicate soft drusen positions and yellow arrows indicate subretinal drusenoid deposits.
Fig. 4
Fig. 4 Representation of how three types of drusen are observed in each slab. Inner slab (blue) is located right above the ellipsoid zone (EZ) interface, and only appears bright in the event of drusen. If the outer boundary of RPE in a soft drusen region is above the inner slab, a black region surrounded by bright pixels is observed. The outer slab (red) appears normal in the event of subretinal drusenoid deposits because they locate above the RPE, and dark for other types of drusen. IZ – Interdigitation zone.
Fig. 5
Fig. 5 The bar graph of mean maximum hybrid contrast ratio in a scan of each participant. Thirteen participants were imaged in each group. A threshold at 3.5 can completely separate the normal eyes (green bars) and the drusen eyes (red bars).
Fig. 6
Fig. 6 3D mean filter indicated in operation 6 of Fig. 2. Panel (A) describes the steps followed. Each slab contains seven consecutive C-scans, each containing the reflectance data at a different distance from the Bruch’s membrane. Every trio of adjacent C-scans is averaged, resulting in five averaged C-scans per slab. Panel B shows an example of one trio of adjacent C-scans from the inner slab containing drusen, before and after averaging and normalization.
Fig. 7
Fig. 7 Dual-scale filtering step. (A1) The averaged C-scan obtained in Fig. 6(B) was processed by a 5 × 5 median filter and Top-Hat transform (disk of radius 60 pixels). (B1) The binary image of (A1) after Otsu thresholding. (A2) The same processing in (A1) but using a disk of radius 15 pixels. (B2) The binary image of (A2) after Otsu thresholding. The areas enclosed by red circles are examples of regions detected in (B2) better than in (B1). (A3) The combination of (B1) and (B2) by a logical OR. (B3) The binary image (A3) after filtering by 5 × 5 median filter.
Fig. 8
Fig. 8 (A) An averaged C-scan corresponding to the inner slab. (B) One of the five binary images in the inner slab. (C) The inner slab mask after continuity detection.
Fig. 9
Fig. 9 Post processing step. (A1) Average of C-scans in the outer slab. (A2) Outer slab mask after large vessel shadow removal and continuity detection. (B1) Average of C-scans in the inner slab. (B2) Drusen mask of the inner slab (same as Fig. 8(C)). (C) The final segmentation result. (D) A representative B-scan showing a large soft drusen region to the right of a small drusen region (indicated by a yellow arrow) that does not significantly elevates the RPE (E) and is better detected by the outer slab in A1-A2.
Fig. 10
Fig. 10 Demonstration of three types of drusen detected by the algorithm in two dry AMD cases. (A1, B1) en face images representing the mean of C-scans in the inner slab. (A2, B2) representative B-scans. Soft drusen observed as an isolated structure with significant RPE elevation is indicated by a green arrow in A2. Subretinal drusenoid deposits above the intact RPE are indicated by blue arrows in B2. A white arrow in B2 indicates cuticular drusen, evidenced by its saw-tooth appearance connected to adjacent structures. (A3, B3) the drusen regions automatically detected by the algorithm.
Fig. 11
Fig. 11 Overlap between manually segmented drusen after interpolating missing frames and morphological opening vs automatically detected drusen in two scans. Yellow region represents overlapping areas, red region represents areas detected only by manual segmentation and green regions represent areas detected by automatic segmentation only.
Fig. 12
Fig. 12 Drusen area (gray) overlaid on en face angiograms. A1,A2 show the drusen detected by the current algorithm overlaid on the inner retinal angiogram. B1, B2 show the drusen overlaid on the deep plexus angiogram. A3, B3 show the drusen overlaid on the choriocapillaris angiogram.

Tables (1)

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Table 1 Comparison of drusen area between automatic segmentation and manual grading by certified graders AMH and YL.*

Equations (7)

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GC(x,y)= I(x,y) mean(I)
LC(x,y)= w c (x,y) w s (x,y)
J=| W 1 W 2 W 1 W 2 |
TPAF= A TP A MG
FPAF= A FP A A MG
ACC= A TP + A TN A
DSC=| 2× A am A a + A m |

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