Abstract

We present a fully automatic algorithm to identify fluid-filled regions and seven retinal layers on spectral domain optical coherence tomography images of eyes with diabetic macular edema (DME). To achieve this, we developed a kernel regression (KR)-based classification method to estimate fluid and retinal layer positions. We then used these classification estimates as a guide to more accurately segment the retinal layer boundaries using our previously described graph theory and dynamic programming (GTDP) framework. We validated our algorithm on 110 B-scans from ten patients with severe DME pathology, showing an overall mean Dice coefficient of 0.78 when comparing our KR + GTDP algorithm to an expert grader. This is comparable to the inter-observer Dice coefficient of 0.79. The entire data set is available online, including our automatic and manual segmentation results. To the best of our knowledge, this is the first validated, fully-automated, seven-layer and fluid segmentation method which has been applied to real-world images containing severe DME.

© 2015 Optical Society of America

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2015 (1)

2014 (4)

A. Carass, A. Lang, M. Hauser, P. A. Calabresi, H. S. Ying, and J. L. Prince, “Multiple-object geometric deformable model for segmentation of macular OCT,” Biomed. Opt. Express 5(4), 1062–1074 (2014).
[Crossref] [PubMed]

G. M. Somfai, E. Tátrai, L. Laurik, B. E. Varga, V. Ölvedy, W. E. Smiddy, R. Tchitnga, A. Somogyi, and D. C. DeBuc, “Fractal-based analysis of optical coherence tomography data to quantify retinal tissue damage,” BMC Bioinformatics 15(1), 295 (2014).
[Crossref] [PubMed]

D. A. Sim, P. A. Keane, S. Fung, M. Karampelas, S. R. Sadda, M. Fruttiger, P. J. Patel, A. Tufail, and C. A. Egan, “Quantitative analysis of diabetic macular ischemia using optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 55(1), 417–423 (2014).
[Crossref] [PubMed]

S. Ghosh, P. Bansal, H. Shejao, R. Hegde, D. Roy, and S. Biswas, “Correlation of morphological pattern of optical coherence tomography in diabetic macular edema with systemic risk factors in middle aged males,” Int. Ophthalmol. 35, 3–10 (2014).
[PubMed]

2013 (13)

B. J. Antony, M. D. Abràmoff, M. M. Harper, W. Jeong, E. H. Sohn, Y. H. Kwon, R. Kardon, and M. K. Garvin, “A combined machine-learning and graph-based framework for the segmentation of retinal surfaces in SD-OCT volumes,” Biomed. Opt. Express 4(12), 2712–2728 (2013).
[Crossref] [PubMed]

A. Hunter, E. K. Chin, and D. G. Telander, “Macular edema in the era of spectral-domain optical coherence tomography,” Clin. Ophthalmol. 7, 2085–2089 (2013).
[Crossref] [PubMed]

Y. M. Helmy and H. R. Atta Allah, “Optical coherence tomography classification of diabetic cystoid macular edema,” Clin. Ophthalmol. 7, 1731–1737 (2013).
[PubMed]

B. L. Sikorski, G. Malukiewicz, J. Stafiej, H. Lesiewska-Junk, and D. Raczynska, “The diagnostic function of OCT in diabetic maculopathy,” Mediators Inflamm. 2013, 434560 (2013).
[Crossref] [PubMed]

S. Sonoda, T. Sakamoto, M. Shirasawa, T. Yamashita, H. Otsuka, and H. Terasaki, “Correlation between reflectivity of subretinal fluid in OCT images and concentration of intravitreal VEGF in eyes with diabetic macular edema,” Invest. Ophthalmol. Vis. Sci. 54(8), 5367–5374 (2013).
[Crossref] [PubMed]

A. Lang, A. Carass, M. Hauser, E. S. Sotirchos, P. A. Calabresi, H. S. Ying, and J. L. Prince, “Retinal layer segmentation of macular OCT images using boundary classification,” Biomed. Opt. Express 4(7), 1133–1152 (2013).
[Crossref] [PubMed]

E. H. Sohn, J. J. Chen, K. Lee, M. Niemeijer, M. Sonka, and M. D. Abràmoff, “Reproducibility of diabetic macular edema estimates from SD-OCT is affected by the choice of image analysis algorithm,” Invest. Ophthalmol. Vis. Sci. 54(6), 4184–4188 (2013).
[Crossref] [PubMed]

Y. Huang, R. P. Danis, J. W. Pak, S. Luo, J. White, X. Zhang, A. Narkar, and A. Domalpally, “Development of a semi-automatic segmentation method for retinal OCT images tested in patients with diabetic macular edema,” PLoS ONE 8(12), e82922 (2013).
[Crossref] [PubMed]

J. Y. Lee, S. J. Chiu, P. P. Srinivasan, J. A. Izatt, C. A. Toth, S. Farsiu, and G. J. Jaffe, “Fully automatic software for retinal thickness in eyes with diabetic macular edema from images acquired by cirrus and spectralis systems,” Invest. Ophthalmol. Vis. Sci. 54(12), 7595–7602 (2013).
[Crossref] [PubMed]

J. Tian, P. Marziliano, M. Baskaran, T. A. Tun, and T. Aung, “Automatic segmentation of the choroid in enhanced depth imaging optical coherence tomography images,” Biomed. Opt. Express 4(3), 397–411 (2013).
[Crossref] [PubMed]

M. Pilch, K. Stieger, Y. Wenner, M. N. Preising, C. Friedburg, E. Meyer zu Bexten, and B. Lorenz, “Automated segmentation of pathological cavities in optical coherence tomography scans,” Invest. Ophthalmol. Vis. Sci. 54(6), 4385–4393 (2013).
[Crossref] [PubMed]

S. J. Chiu, Y. Lokhnygina, A. M. Dubis, A. Dubra, J. Carroll, J. A. Izatt, and S. Farsiu, “Automatic cone photoreceptor segmentation using graph theory and dynamic programming,” Biomed. Opt. Express 4(6), 924–937 (2013).
[Crossref] [PubMed]

L. Fang, S. Li, R. P. McNabb, Q. Nie, A. N. Kuo, C. A. Toth, J. A. Izatt, and S. Farsiu, “Fast Acquisition and Reconstruction of Optical Coherence Tomography Images via Sparse Representation,” IEEE Trans. Med. Imaging 32(11), 2034–2049 (2013).
[Crossref] [PubMed]

2012 (5)

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).
[Crossref] [PubMed]

S. J. Chiu, C. A. Toth, C. Bowes Rickman, J. A. Izatt, and S. Farsiu, “Automatic segmentation of closed-contour features in ophthalmic images using graph theory and dynamic programming,” Biomed. Opt. Express 3(5), 1127–1140 (2012).
[Crossref] [PubMed]

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).
[Crossref] [PubMed]

X. Chen, M. Niemeijer, L. Zhang, K. Lee, M. D. Abramoff, and M. Sonka, “Three-dimensional segmentation of fluid-associated abnormalities in retinal OCT: probability constrained graph-search-graph-cut,” IEEE Trans. Med. Imaging 31(8), 1521–1531 (2012).
[Crossref] [PubMed]

J. W. Yau, S. L. Rogers, R. Kawasaki, E. L. Lamoureux, J. W. Kowalski, T. Bek, S. J. Chen, J. M. Dekker, A. Fletcher, J. Grauslund, S. Haffner, R. F. Hamman, M. K. Ikram, T. Kayama, B. E. Klein, R. Klein, S. Krishnaiah, K. Mayurasakorn, J. P. O’Hare, T. J. Orchard, M. Porta, M. Rema, M. S. Roy, T. Sharma, J. Shaw, H. Taylor, J. M. Tielsch, R. Varma, J. J. Wang, N. Wang, S. West, L. Xu, M. Yasuda, X. Zhang, P. Mitchell, T. Y. Wong, and Meta-Analysis for Eye Disease (META-EYE) Study Group, “Global prevalence and major risk factors of diabetic retinopathy,” Diabetes Care 35(3), 556–564 (2012).
[Crossref] [PubMed]

2011 (5)

P. Mitchell, F. Bandello, U. Schmidt-Erfurth, G. E. Lang, P. Massin, R. O. Schlingemann, F. Sutter, C. Simader, G. Burian, O. Gerstner, A. Weichselberger, and RESTORE study group, “The RESTORE study: ranibizumab monotherapy or combined with laser versus laser monotherapy for diabetic macular edema,” Ophthalmology 118(4), 615–625 (2011).
[Crossref] [PubMed]

M. J. Elman, N. M. Bressler, H. Qin, R. W. Beck, F. L. Ferris, S. M. Friedman, A. R. Glassman, I. U. Scott, C. R. Stockdale, J. K. Sun, and Diabetic Retinopathy Clinical Research Network, “Expanded 2-year follow-up of ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema,” Ophthalmology 118(4), 609–614 (2011).
[Crossref] [PubMed]

D. V. Do, U. Schmidt-Erfurth, V. H. Gonzalez, C. M. Gordon, M. Tolentino, A. J. Berliner, R. Vitti, R. Rückert, R. Sandbrink, D. Stein, K. Yang, K. Beckmann, and J. S. Heier, “The DA VINCI Study: phase 2 primary results of VEGF Trap-Eye in patients with diabetic macular edema,” Ophthalmology 118(9), 1819–1826 (2011).
[Crossref] [PubMed]

Q. Yang, C. A. Reisman, K. Chan, R. Ramachandran, A. Raza, and D. C. Hood, “Automated segmentation of outer retinal layers in macular OCT images of patients with retinitis pigmentosa,” Biomed. Opt. Express 2(9), 2493–2503 (2011).
[Crossref] [PubMed]

K. A. Vermeer, J. van der Schoot, H. G. Lemij, and J. F. de Boer, “Automated segmentation by pixel classification of retinal layers in ophthalmic OCT images,” Biomed. Opt. Express 2(6), 1743–1756 (2011).
[Crossref] [PubMed]

2010 (9)

M. J. Elman, L. P. Aiello, R. W. Beck, N. M. Bressler, S. B. Bressler, A. R. Edwards, F. L. Ferris, S. M. Friedman, A. R. Glassman, K. M. Miller, I. U. Scott, C. R. Stockdale, J. K. Sun, and Diabetic Retinopathy Clinical Research Network, “Randomized trial evaluating ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema,” Ophthalmology 117(6), 1064–1077 (2010).
[Crossref] [PubMed]

S. J. Chiu, X. T. Li, P. Nicholas, C. A. Toth, J. A. Izatt, and S. Farsiu, “Automatic segmentation of seven retinal layers in SDOCT images congruent with expert manual segmentation,” Opt. Express 18(18), 19413–19428 (2010).
[Crossref] [PubMed]

A. I. Kotsolis, E. Tsianta, M. Niskopoulou, P. Masaoutis, S. Baltatzis, and I. D. Ladas, “Ranibizumab for diabetic macular edema difficult to treat with focal/grid laser,” Graefe's archive for clinical and experimental ophthalmology = Albrecht Von Graefes Arch. Klin. Exp. Ophthalmol. 248(11), 1553–1557 (2010).
[Crossref]

Q. D. Nguyen, S. M. Shah, A. A. Khwaja, R. Channa, E. Hatef, D. V. Do, D. Boyer, J. S. Heier, P. Abraham, A. B. Thach, E. S. Lit, B. S. Foster, E. Kruger, P. Dugel, T. Chang, A. Das, T. A. Ciulla, J. S. Pollack, J. I. Lim, D. Eliott, P. A. Campochiaro, and READ-2 Study Group, “Two-year outcomes of the ranibizumab for edema of the mAcula in diabetes (READ-2) study,” Ophthalmology 117(11), 2146–2151 (2010).
[Crossref] [PubMed]

P. Massin, F. Bandello, J. G. Garweg, L. L. Hansen, S. P. Harding, M. Larsen, P. Mitchell, D. Sharp, U. E. Wolf-Schnurrbusch, M. Gekkieva, A. Weichselberger, and S. Wolf, “Safety and efficacy of ranibizumab in diabetic macular edema (RESOLVE Study): a 12-month, randomized, controlled, double-masked, multicenter phase II study,” Diabetes Care 33(11), 2399–2405 (2010).
[Crossref] [PubMed]

M. A. Mayer, J. Hornegger, C. Y. Mardin, and R. P. Tornow, “Retinal Nerve Fiber Layer Segmentation on FD-OCT Scans of Normal Subjects and Glaucoma Patients,” Biomed. Opt. Express 1(5), 1358–1383 (2010).
[Crossref] [PubMed]

G. Quellec, K. Lee, M. Dolejsi, M. K. Garvin, M. D. Abràmoff, and M. Sonka, “Three-dimensional analysis of retinal layer texture: identification of fluid-filled regions in SD-OCT of the macula,” IEEE Trans. Med. Imaging 29(6), 1321–1330 (2010).
[Crossref] [PubMed]

S. J. Chiu, X. T. Li, P. Nicholas, C. A. Toth, J. A. Izatt, and S. Farsiu, “Automatic segmentation of seven retinal layers in SDOCT images congruent with expert manual segmentation,” Opt. Express 18(18), 19413–19428 (2010).
[Crossref] [PubMed]

H. J. Seo and P. Milanfar, “Training-Free, Generic Object Detection Using Locally Adaptive Regression Kernels,” IEEE Trans. Pattern Anal. Mach. Intell. 32(9), 1688–1704 (2010).
[Crossref] [PubMed]

2009 (3)

M. C. Gillies, J. M. Simpson, C. Gaston, G. Hunt, H. Ali, M. Zhu, and F. Sutter, “Five-year results of a randomized trial with open-label extension of triamcinolone acetonide for refractory diabetic macular edema,” Ophthalmology 116(11), 2182–2187 (2009).
[Crossref] [PubMed]

D. C. DeBuc, G. M. Somfai, S. Ranganathan, E. Tátrai, M. Ferencz, and C. A. Puliafito, “Reliability and reproducibility of macular segmentation using a custom-built optical coherence tomography retinal image analysis software,” J. Biomed. Opt. 14(6), 064023 (2009).
[Crossref] [PubMed]

A. Mishra, A. Wong, K. Bizheva, and D. A. Clausi, “Intra-retinal layer segmentation in optical coherence tomography images,” Opt. Express 17(26), 23719–23728 (2009).
[Crossref] [PubMed]

2008 (2)

D. J. Browning, M. M. Altaweel, N. M. Bressler, S. B. Bressler, I. U. Scott, and Diabetic Retinopathy Clinical Research Network, “Diabetic macular edema: what is focal and what is diffuse?” Am. J. Ophthalmol. 146(5), 649–655 (2008).
[Crossref] [PubMed]

H. Takeda, S. Farsiu, and P. Milanfar, “Deblurring Using Regularized Locally Adaptive Kernel Regression,” IEEE Trans. Image Process. 17(4), 550–563 (2008).
[Crossref] [PubMed]

2007 (2)

H. Takeda, S. Farsiu, and P. Milanfar, “Kernel regression for image processing and reconstruction,” IEEE Trans. Image Process. 16, 349–366 (2007).

J. A. Davidson, T. A. Ciulla, J. B. McGill, K. A. Kles, and P. W. Anderson, “How the diabetic eye loses vision,” Endocrine 32(1), 107–116 (2007).
[Crossref] [PubMed]

2006 (1)

A. Bringmann, T. Pannicke, J. Grosche, M. Francke, P. Wiedemann, S. N. Skatchkov, N. N. Osborne, and A. Reichenbach, “Müller cells in the healthy and diseased retina,” Prog. Retin. Eye Res. 25(4), 397–424 (2006).
[Crossref] [PubMed]

2005 (5)

D. Cabrera Fernández, H. M. Salinas, and C. A. Puliafito, “Automated detection of retinal layer structures on optical coherence tomography images,” Opt. Express 13(25), 10200–10216 (2005).
[Crossref] [PubMed]

E. T. Cunningham, A. P. Adamis, M. Altaweel, L. P. Aiello, N. M. Bressler, D. J. D’Amico, M. Goldbaum, D. R. Guyer, B. Katz, M. Patel, S. D. Schwartz, and Macugen Diabetic Retinopathy Study Group, “A phase II randomized double-masked trial of pegaptanib, an anti-vascular endothelial growth factor aptamer, for diabetic macular edema,” Ophthalmology 112(10), 1747–1757 (2005).
[Crossref] [PubMed]

M. Shahidi, Z. Wang, and R. Zelkha, “Quantitative thickness measurement of retinal layers imaged by optical coherence tomography,” Am. J. Ophthalmol. 139(6), 1056–1061 (2005).
[Crossref] [PubMed]

H. Ishikawa, D. M. Stein, G. Wollstein, S. Beaton, J. G. Fujimoto, and J. S. Schuman, “Macular Segmentation with Optical Coherence Tomography,” Invest. Ophthalmol. Vis. Sci. 46(6), 2012–2017 (2005).
[Crossref] [PubMed]

M. Mujat, R. Chan, B. Cense, B. Park, C. Joo, T. Akkin, T. Chen, and J. de Boer, “Retinal nerve fiber layer thickness map determined from optical coherence tomography images,” Opt. Express 13(23), 9480–9491 (2005).
[Crossref] [PubMed]

2004 (2)

L. A. Paunescu, J. S. Schuman, L. L. Price, P. C. Stark, S. Beaton, H. Ishikawa, G. Wollstein, and J. G. Fujimoto, “Reproducibility of Nerve Fiber Thickness, Macular Thickness, and Optic Nerve Head Measurements Using StratusOCT,” Invest. Ophthalmol. Vis. Sci. 45(6), 1716–1724 (2004).
[Crossref] [PubMed]

A. Bringmann, A. Reichenbach, and P. Wiedemann, “Pathomechanisms of cystoid macular edema,” Ophthalmic Res. 36(5), 241–249 (2004).
[Crossref] [PubMed]

2003 (1)

I. Guyon and A. Elisseeff, “An introduction to variable and feature selection,” J. Mach. Learn. Res. 3, 1157–1182 (2003).

2002 (1)

M. J. Tolentino, D. S. McLeod, M. Taomoto, T. Otsuji, A. P. Adamis, and G. A. Lutty, “Pathologic features of vascular endothelial growth factor-induced retinopathy in the nonhuman primate,” Am. J. Ophthalmol. 133(3), 373–385 (2002).
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1999 (1)

M. F. Marmor, “Mechanisms of fluid accumulation in retinal edema,” Doc. Ophthalmol. 97(3/4), 239–249 (1999).
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1997 (2)

A. Jain and D. Zongker, “Feature selection: evaluation, application, and small sample performance,” IEEE Trans. Pattern Anal. Machine Intell. 19(2), 153–158 (1997).
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R. Kohavi and G. H. John, “Wrappers for feature subset selection,” Artif. Intell. 97(1-2), 273–324 (1997).
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1996 (1)

J. Pe’er, R. Folberg, A. Itin, H. Gnessin, I. Hemo, and E. Keshet, “Upregulated expression of vascular endothelial growth factor in proliferative diabetic retinopathy,” Br. J. Ophthalmol. 80(3), 241–245 (1996).
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1994 (1)

D. Ruppert and M. P. Wand, “Multivariate locally weighted least squares regression,” Ann. Stat. 22(3), 1346–1370 (1994).
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1987 (2)

P. C. Hansen, “The truncated svd as a method for regularization,” BIT Numerical Mathematics 27(4), 534–553 (1987).
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Early Treatment Diabetic Retinopathy Study Research Group, “Treatment techniques and clinical guidelines for photocoagulation of diabetic macular edema. Early Treatment Diabetic Retinopathy Study Report Number 2,” Ophthalmology 94(7), 761–774 (1987).
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1983 (1)

A. Negi and M. F. Marmor, “The resorption of subretinal fluid after diffuse damage to the retinal pigment epithelium,” Invest. Ophthalmol. Vis. Sci. 24(11), 1475–1479 (1983).
[PubMed]

1982 (1)

S. Lloyd, “Least squares quantization in PCM,” IEEE Trans. Inf. Theory 28(2), 129–137 (1982).
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1971 (1)

R. M. Cormack, “A review of classification,” J. R. Stat. Soc. [Ser A] 134(3), 321–367 (1971).
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1959 (1)

E. W. Dijkstra, “A note on two problems in connexion with graphs,” Numerische Mathematik. 1(1), 269–271 (1959).
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1948 (1)

T. Sørensen, “A method of establishing groups of equal amplitude in plant sociology based on similarity of species and its application to analyses of the vegetation on Danish commons,” Biol. Skr. 5, 1–34 (1948).

1945 (1)

L. R. Dice, “Measures of the amount of ecologic association between species,” Ecology 26(3), 297–302 (1945).
[Crossref]

Abraham, P.

Q. D. Nguyen, S. M. Shah, A. A. Khwaja, R. Channa, E. Hatef, D. V. Do, D. Boyer, J. S. Heier, P. Abraham, A. B. Thach, E. S. Lit, B. S. Foster, E. Kruger, P. Dugel, T. Chang, A. Das, T. A. Ciulla, J. S. Pollack, J. I. Lim, D. Eliott, P. A. Campochiaro, and READ-2 Study Group, “Two-year outcomes of the ranibizumab for edema of the mAcula in diabetes (READ-2) study,” Ophthalmology 117(11), 2146–2151 (2010).
[Crossref] [PubMed]

Abramoff, M. D.

X. Chen, M. Niemeijer, L. Zhang, K. Lee, M. D. Abramoff, and M. Sonka, “Three-dimensional segmentation of fluid-associated abnormalities in retinal OCT: probability constrained graph-search-graph-cut,” IEEE Trans. Med. Imaging 31(8), 1521–1531 (2012).
[Crossref] [PubMed]

Abràmoff, M. D.

E. H. Sohn, J. J. Chen, K. Lee, M. Niemeijer, M. Sonka, and M. D. Abràmoff, “Reproducibility of diabetic macular edema estimates from SD-OCT is affected by the choice of image analysis algorithm,” Invest. Ophthalmol. Vis. Sci. 54(6), 4184–4188 (2013).
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B. J. Antony, M. D. Abràmoff, M. M. Harper, W. Jeong, E. H. Sohn, Y. H. Kwon, R. Kardon, and M. K. Garvin, “A combined machine-learning and graph-based framework for the segmentation of retinal surfaces in SD-OCT volumes,” Biomed. Opt. Express 4(12), 2712–2728 (2013).
[Crossref] [PubMed]

G. Quellec, K. Lee, M. Dolejsi, M. K. Garvin, M. D. Abràmoff, and M. Sonka, “Three-dimensional analysis of retinal layer texture: identification of fluid-filled regions in SD-OCT of the macula,” IEEE Trans. Med. Imaging 29(6), 1321–1330 (2010).
[Crossref] [PubMed]

Adamis, A. P.

E. T. Cunningham, A. P. Adamis, M. Altaweel, L. P. Aiello, N. M. Bressler, D. J. D’Amico, M. Goldbaum, D. R. Guyer, B. Katz, M. Patel, S. D. Schwartz, and Macugen Diabetic Retinopathy Study Group, “A phase II randomized double-masked trial of pegaptanib, an anti-vascular endothelial growth factor aptamer, for diabetic macular edema,” Ophthalmology 112(10), 1747–1757 (2005).
[Crossref] [PubMed]

M. J. Tolentino, D. S. McLeod, M. Taomoto, T. Otsuji, A. P. Adamis, and G. A. Lutty, “Pathologic features of vascular endothelial growth factor-induced retinopathy in the nonhuman primate,” Am. J. Ophthalmol. 133(3), 373–385 (2002).
[Crossref] [PubMed]

Aiello, L. P.

M. J. Elman, L. P. Aiello, R. W. Beck, N. M. Bressler, S. B. Bressler, A. R. Edwards, F. L. Ferris, S. M. Friedman, A. R. Glassman, K. M. Miller, I. U. Scott, C. R. Stockdale, J. K. Sun, and Diabetic Retinopathy Clinical Research Network, “Randomized trial evaluating ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema,” Ophthalmology 117(6), 1064–1077 (2010).
[Crossref] [PubMed]

E. T. Cunningham, A. P. Adamis, M. Altaweel, L. P. Aiello, N. M. Bressler, D. J. D’Amico, M. Goldbaum, D. R. Guyer, B. Katz, M. Patel, S. D. Schwartz, and Macugen Diabetic Retinopathy Study Group, “A phase II randomized double-masked trial of pegaptanib, an anti-vascular endothelial growth factor aptamer, for diabetic macular edema,” Ophthalmology 112(10), 1747–1757 (2005).
[Crossref] [PubMed]

Akkin, T.

Ali, H.

M. C. Gillies, J. M. Simpson, C. Gaston, G. Hunt, H. Ali, M. Zhu, and F. Sutter, “Five-year results of a randomized trial with open-label extension of triamcinolone acetonide for refractory diabetic macular edema,” Ophthalmology 116(11), 2182–2187 (2009).
[Crossref] [PubMed]

Al-Louzi, O.

Altaweel, M.

E. T. Cunningham, A. P. Adamis, M. Altaweel, L. P. Aiello, N. M. Bressler, D. J. D’Amico, M. Goldbaum, D. R. Guyer, B. Katz, M. Patel, S. D. Schwartz, and Macugen Diabetic Retinopathy Study Group, “A phase II randomized double-masked trial of pegaptanib, an anti-vascular endothelial growth factor aptamer, for diabetic macular edema,” Ophthalmology 112(10), 1747–1757 (2005).
[Crossref] [PubMed]

Altaweel, M. M.

D. J. Browning, M. M. Altaweel, N. M. Bressler, S. B. Bressler, I. U. Scott, and Diabetic Retinopathy Clinical Research Network, “Diabetic macular edema: what is focal and what is diffuse?” Am. J. Ophthalmol. 146(5), 649–655 (2008).
[Crossref] [PubMed]

Anderson, P. W.

J. A. Davidson, T. A. Ciulla, J. B. McGill, K. A. Kles, and P. W. Anderson, “How the diabetic eye loses vision,” Endocrine 32(1), 107–116 (2007).
[Crossref] [PubMed]

Antony, B. J.

Atta Allah, H. R.

Y. M. Helmy and H. R. Atta Allah, “Optical coherence tomography classification of diabetic cystoid macular edema,” Clin. Ophthalmol. 7, 1731–1737 (2013).
[PubMed]

Aung, T.

Baltatzis, S.

A. I. Kotsolis, E. Tsianta, M. Niskopoulou, P. Masaoutis, S. Baltatzis, and I. D. Ladas, “Ranibizumab for diabetic macular edema difficult to treat with focal/grid laser,” Graefe's archive for clinical and experimental ophthalmology = Albrecht Von Graefes Arch. Klin. Exp. Ophthalmol. 248(11), 1553–1557 (2010).
[Crossref]

Bandello, F.

P. Mitchell, F. Bandello, U. Schmidt-Erfurth, G. E. Lang, P. Massin, R. O. Schlingemann, F. Sutter, C. Simader, G. Burian, O. Gerstner, A. Weichselberger, and RESTORE study group, “The RESTORE study: ranibizumab monotherapy or combined with laser versus laser monotherapy for diabetic macular edema,” Ophthalmology 118(4), 615–625 (2011).
[Crossref] [PubMed]

P. Massin, F. Bandello, J. G. Garweg, L. L. Hansen, S. P. Harding, M. Larsen, P. Mitchell, D. Sharp, U. E. Wolf-Schnurrbusch, M. Gekkieva, A. Weichselberger, and S. Wolf, “Safety and efficacy of ranibizumab in diabetic macular edema (RESOLVE Study): a 12-month, randomized, controlled, double-masked, multicenter phase II study,” Diabetes Care 33(11), 2399–2405 (2010).
[Crossref] [PubMed]

Bansal, P.

S. Ghosh, P. Bansal, H. Shejao, R. Hegde, D. Roy, and S. Biswas, “Correlation of morphological pattern of optical coherence tomography in diabetic macular edema with systemic risk factors in middle aged males,” Int. Ophthalmol. 35, 3–10 (2014).
[PubMed]

Baskaran, M.

Beaton, S.

H. Ishikawa, D. M. Stein, G. Wollstein, S. Beaton, J. G. Fujimoto, and J. S. Schuman, “Macular Segmentation with Optical Coherence Tomography,” Invest. Ophthalmol. Vis. Sci. 46(6), 2012–2017 (2005).
[Crossref] [PubMed]

L. A. Paunescu, J. S. Schuman, L. L. Price, P. C. Stark, S. Beaton, H. Ishikawa, G. Wollstein, and J. G. Fujimoto, “Reproducibility of Nerve Fiber Thickness, Macular Thickness, and Optic Nerve Head Measurements Using StratusOCT,” Invest. Ophthalmol. Vis. Sci. 45(6), 1716–1724 (2004).
[Crossref] [PubMed]

Beck, R. W.

M. J. Elman, N. M. Bressler, H. Qin, R. W. Beck, F. L. Ferris, S. M. Friedman, A. R. Glassman, I. U. Scott, C. R. Stockdale, J. K. Sun, and Diabetic Retinopathy Clinical Research Network, “Expanded 2-year follow-up of ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema,” Ophthalmology 118(4), 609–614 (2011).
[Crossref] [PubMed]

M. J. Elman, L. P. Aiello, R. W. Beck, N. M. Bressler, S. B. Bressler, A. R. Edwards, F. L. Ferris, S. M. Friedman, A. R. Glassman, K. M. Miller, I. U. Scott, C. R. Stockdale, J. K. Sun, and Diabetic Retinopathy Clinical Research Network, “Randomized trial evaluating ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema,” Ophthalmology 117(6), 1064–1077 (2010).
[Crossref] [PubMed]

Beckmann, K.

D. V. Do, U. Schmidt-Erfurth, V. H. Gonzalez, C. M. Gordon, M. Tolentino, A. J. Berliner, R. Vitti, R. Rückert, R. Sandbrink, D. Stein, K. Yang, K. Beckmann, and J. S. Heier, “The DA VINCI Study: phase 2 primary results of VEGF Trap-Eye in patients with diabetic macular edema,” Ophthalmology 118(9), 1819–1826 (2011).
[Crossref] [PubMed]

Bek, T.

J. W. Yau, S. L. Rogers, R. Kawasaki, E. L. Lamoureux, J. W. Kowalski, T. Bek, S. J. Chen, J. M. Dekker, A. Fletcher, J. Grauslund, S. Haffner, R. F. Hamman, M. K. Ikram, T. Kayama, B. E. Klein, R. Klein, S. Krishnaiah, K. Mayurasakorn, J. P. O’Hare, T. J. Orchard, M. Porta, M. Rema, M. S. Roy, T. Sharma, J. Shaw, H. Taylor, J. M. Tielsch, R. Varma, J. J. Wang, N. Wang, S. West, L. Xu, M. Yasuda, X. Zhang, P. Mitchell, T. Y. Wong, and Meta-Analysis for Eye Disease (META-EYE) Study Group, “Global prevalence and major risk factors of diabetic retinopathy,” Diabetes Care 35(3), 556–564 (2012).
[Crossref] [PubMed]

Berliner, A. J.

D. V. Do, U. Schmidt-Erfurth, V. H. Gonzalez, C. M. Gordon, M. Tolentino, A. J. Berliner, R. Vitti, R. Rückert, R. Sandbrink, D. Stein, K. Yang, K. Beckmann, and J. S. Heier, “The DA VINCI Study: phase 2 primary results of VEGF Trap-Eye in patients with diabetic macular edema,” Ophthalmology 118(9), 1819–1826 (2011).
[Crossref] [PubMed]

Bhargava, P.

Biswas, S.

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Hegde, R.

S. Ghosh, P. Bansal, H. Shejao, R. Hegde, D. Roy, and S. Biswas, “Correlation of morphological pattern of optical coherence tomography in diabetic macular edema with systemic risk factors in middle aged males,” Int. Ophthalmol. 35, 3–10 (2014).
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J. Pe’er, R. Folberg, A. Itin, H. Gnessin, I. Hemo, and E. Keshet, “Upregulated expression of vascular endothelial growth factor in proliferative diabetic retinopathy,” Br. J. Ophthalmol. 80(3), 241–245 (1996).
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Figures (9)

Fig. 1
Fig. 1 Second order iterative Gaussian steering KR of an SD-OCT image with DME. a) Automatically flattened image, b,d) zoomed-in images of the pink and green boxes in (a), c,e) Gaussian steering kernels used to denoised the central pixel of (b) and (d), and f) KR-denoised image of (a). In (f), regions external to the retina (black) were not denoised with the exception of a padded boundary surrounding the retina required for feature vector computation.
Fig. 2
Fig. 2 Flowchart of the KR-based classification and GTDP-based segmentation algorithm for identifying fluid-filled regions and eight retinal layer boundaries on images with DME pathology.
Fig. 3
Fig. 3 Target retinal layer boundaries and fluid to segment on an SD-OCT B-scan of an eye with DME. A flattened version of the image without markings is shown in Fig. 1(a).
Fig. 4
Fig. 4 KR-based classification of retinal layers and fluid-filled regions. a) Manual classification of the image in Fig. 1(a) with the classes defined in Table 1. b) Automatic classification using the merged DME classifier.
Fig. 5
Fig. 5 Laws’ E 5 T E5 texture feature computed for the image in Fig. 1(a) with (a) and without (b) KR-based denoising. Both feature images have been enhanced using adaptive histogram equalization.
Fig. 6
Fig. 6 Visual example of features selected for the DME classifiers. a-l) Features computed for the image in Fig. 1(a).
Fig. 7
Fig. 7 Qualitative results for the identification of fluid and eight retinal layer boundaries on SD-OCT images of eyes with DME. a-c) Images with significant, moderate, and no visible fluid, respectively, d-f) their corresponding automatic segmentation result using the GTDP algorithm developed for normal eyes, and g-i) the automatic KR + GTDP segmentation result.
Fig. 8
Fig. 8 Automatic and manual segmentation comparison. a) An SD-OCT B-scan with DME pathology, b) the fully automatic segmentation result, and c-d) the segmentation results completed by two different graders.
Fig. 9
Fig. 9 Automatic fluid detection errors. Top) Cropped portions of SD-OCT B-scans with DME, middle) manual segmentation of fluid-filled regions by a grader, and bottom) automatic fluid-filled classification. a) An image with hyper-reflective deposits, b) a dim image with a hyper-reflective outlier, and c) a high quality image.

Tables (8)

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Table 2 Kernel regression-based DME training features

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Table 3 Position-based DME training features

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Table 4 Laws’ texture training features

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Table 5 Selected DME classifier features and weights

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Table 6 Dice coefficients for DME segmentation

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Table 7 Layer thickness differences for DME segmentation in µm

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Table 8 Wilcoxon matched-pairs test p-values

Equations (28)

Equations on this page are rendered with MathJax. Learn more.

y p =f( z p )+ n p ,p=1,,P,
f( z p ) β 0 + β 1 T ( z p z)+ β 2 T vech[ ( z p z) ( z p z) T ],
where β 0 =f(z), β 1 = [ f(z) i f(z) j ] T ,
β 2 = 1 2 [ 2 f(z) i 2 2 f(z) ij 2 f(z) j 2 ] T ,
vech( [ a b b d ] )= [ a b d ] T .
b ^ = argmin b [ ( yZb ) T D( yZb ) ],
where y= [ y 1 , y 2 ,, y P ] T ,
b= [ β 0 , β 1 T , β 2 T ] T ,
D=diag[ K ^ ( z 1 z), K ^ ( z 2 z),, K ^ ( z P z) ],
Z=[ 1 ( z 1 z) T vech( z 1 z) ( z 1 z) T 1 ( z 2 z) T vech( z 2 z) ( z 2 z) T 1 ( z P z) T vech( z P z) ( z P z) T ],
b ^ = ( Z T DZ) 1 Z T DZy
US T T =[ G i ( z 1 ) G j ( z 1 ) G i ( z 2 ) G j ( z 2 ) G i ( z P ) G j ( z P ) ],whereS=[ S 11 0 0 S 22 ],T=[ T 11 T 12 T 21 T 22 ] .
θ=arctan( T 12 T 22 ),σ= S 11 +λ' S 22 +λ' ,γ= ( S 11 S 12 +λ'' P ) 1 2 .
K GS ( z p z)=exp[ ( z p z) T Σ( z p z) 2 h 2 ],
where Σ=γ Θ T ΛΘ,Θ=[ cos(θ) sin(θ) sin(θ) cos(θ) ],Λ=[ σ 0 0 σ 1 ] .
v ^ l (z)= p=1 P v l ( z p ) K ^ ( z p -z),
c ^ =φ(v).
φ wNG (v)={ c k | argmin k [ 1exp( 1 2 [ ε k ω( v μ k ) ] [ ε k ω( v μ k ) ] T ) ] 1 2 }
w ab = I a + I b + w min ,
w ab = I a + I b +#{ n| C n c k }+ w min ,
w ab =LinNorm( G a DL G b DL ,0,1 )+ w min ,
w ab =LinNorm( G a DL G b DL ,0,1 )+LinNorm( D ab ,0,0.1 )+ w min
w ab =LinNorm( G a LD G b LD ,0,1 )+LinNorm( D ab ,0,0.4 )+ LinNorm( I a I b ,0,0.4 )+ w min
E(V')= { 2 1 K k{ 1K } T N k T N k +F P k , 2 1 K k{ 1K } ( T N k T N k +F P k +1 ) 2 1 K k{ 1K } ( T N k T N k +F P k + T P k T P k +F N k ) if T P k =0,F P k >0,F N k =0 if T P k =0,F P k =0,F N k =0 otherwise
T P k =#{ r| φ(v ' r )= c k and c k = c r },r=1,,R T N k =#{ r| φ(v ' r ) c k and c k c r },r=1,,R F P k =#{ r| φ(v ' r )= c k and c k c r },r=1,,R F N k =#{ r| φ(v ' r ) c k and c k = c r },r=1,,R
w ab =LinNorm( G a DL G b DL ,0,1 )+LinNorm( D ab ,0, d max )+ LinNorm( B a B b ,0, b max )+ w min
w ab =LinNorm( G a sqLD G b sqLD ,0,1 )+LinNorm( D ab ,0,0.1 )+ LinNorm( B a B b ,0,0.1 )+ w min ,
w ab =LinNorm( G a LD G b LD ,0,1 )+LinNorm( D ab ,0,0.1 )+ LinNorm( B a B b ,0, b max )+LinNorm( I a + I b ,0, i max )+ w min

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