IP Library › Granted Patent US 12,685,437
Granted Patent B2
US 12,685,437 · App. 17/604,251 · Granted Jul 21, 2026

Detection, prediction, and classification for ocular disease

Inventors: Shelley Boyd (Toronto, CA); Natalie Pankova (Ottawa, CA); Nehad Hirmiz (Toronto, CA); Huiyuan Liang (Toronto, CA)
Assignee: Tracery Ophthalmics Inc.
A61B3/0025A61B3/12G06T7/0012G06V10/771G06V10/7715G06V10/774G06V10/82G06V40/19G06V40/193G06V40/197G06T2207/10048G06T2207/10101G06T2207/20081G06T2207/20084G06T2207/30041G06V2201/032
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Quick Facts
Patent No.
US 12,685,437
App. No.
17/604,251
Filed
Oct 15, 2021
Granted
Jul 21, 2026
Kind
B2
Art Unit
2672
USPC
382/128
Abstract

Computer systems and computer-implemented methods for performing classification, detection, and/or prediction based on processing of ocular images obtained from various imaging modalities are disclosed. Use of delayed near-infrared analysis (DNIRA) as one of the imaging modality is also disclosed.

Claims (34)

1 . A computer system comprising:

a processor;

a memory in communication with the processor, the memory storing instructions that, when executed by the processor cause the processor to:

at a training phase,

receive training data corresponding to a plurality of ocular images, wherein the plurality of ocular images of the training data correspond to a plurality of imaging modalities, said plurality of imaging modalities including delayed near-infrared analysis (DNIRA) and at least one imaging modality other than DNIRA;

generate delta image data based on a difference between said DNIRA images and images of said at least one imaging modality other than DNIRA;

perform feature extraction and feature selection to generate features based on the training data and the delta image data to build a pattern recognition model;

at a classification phase,

receive a plurality of ocular images corresponding to a plurality of imaging modalities;

classify features of the plurality of ocular images using the pattern recognition model.

2 . The computer system of claim 1 , wherein the pattern recognition model is at least one of a convolutional neural network, machine learning, decision trees, logistic regression, principal components analysis, naive Bayes model, support vector machine model, and nearest neighbor model.

3 . The computer system of claim 1 , wherein the feature extraction generates a masked image of defined shapes.

4 . The computer system of claim 3 , wherein the feature selection is based on at least one of focality of the defined shapes, a number of focal points per unit area of the defined shapes, and a square root of an area of the defined shapes.

5 . The computer system of claim 1 , wherein the features are defined by areas of hypofluorescence.

6 . The computer system of claim 1 , wherein the features are defined by areas of hyperfluorescence.

7 . The computer system of claim 1 , wherein the training phase further comprises building a pattern recognition model for each of the plurality of imaging modalities.

8 . The computer system of claim 1 , wherein the plurality of ocular images comprises a cross-section image.

9 . The computer system of claim 1 , wherein the plurality of ocular images comprises an en face image.

10 . The computer system of claim 1 , wherein the training phase further comprises registering the plurality of ocular images to a common coordinate system.

11 . The computer system of claim 1 , wherein the training phase further comprises cross-modal fusion of the plurality of ocular images to a common coordinate system.

12 . The computer system of claim 1 , wherein the plurality of imaging modalities other than DNIRA comprise at least one of infra-red reflectance (IR), confocal scanning laser ophthalmoscopy (cSLO), fundus autofluorescence (FAF), color fundus photography (CFP), optical coherence tomography (OCT), OCT-angiography, fluorescence lifetime imaging (FLI).

13 . The computer system of claim 1 , wherein the memory stores further instructions that, when executed by the processor cause the processor to:

generate a cross-section segmentation map corresponding to an en face region of an eye, each segment of the cross-section segmentation map corresponding to a cross-section image at that region of the eye;

classify each segment of the cross-section segmentation map as a phenotype of one of normal, drusen, retinal pigment epithelium detachments (RPEDs), pseudodrusen geographic atrophy, macular atrophy, or neovascularization based at least in part on classification of the cross-section image corresponding to that segment using the pattern recognition model.

14 . The computer system of claim 1 , wherein the plurality of ocular images comprises multiple cross-section images corresponding to multiple time points and the memory stores further instructions that, when executed by the processor cause the processor to:

generate, for each of the multiple time points, a cross-section segmentation map corresponding to an en face region of an eye, each segment of the cross-section segmentation map corresponding to a cross-section image at that region of the eye;

classify each segment of each cross-section segmentation map as a phenotype of tissue state of one of normal, drusen, retinal pigment epithelium detachments (RPEDs), pseudodrusen geographic atrophy, macular atrophy, or neovascularization, based at least in part on classification of the cross-section image corresponding to that segment using the pattern recognition model; and

generate a time series data model based on the cross-section segmentation map at each of the multiple time points.

15 . The computer system of claim 14 , wherein the time series data model is based at least in part on identified changes in the cross-section segmentation maps over time.

16 . The computer system of claim 14 , wherein the time series data model is used to generate a visual representation of disease progression.

17 . The computer system of claim 14 , wherein the time series data model is based at least in part on elapsed time between the multiple time points.

18 . The computer system of claim 1 , wherein the features selected comprise phenotypes of a user associated with the plurality of ocular images.

19 . The computer system of claim 1 , wherein the memory stores further instructions that, when executed by the processor cause the processor to: correlate the features with stage or grade variants of blinding eye disease including Age Related Macular Degeneration (AMD), monogenic eye disease, inherited eye disease and inflammatory eye disease.

20 . The computer system of claim 1 , wherein said at least one imaging modality other than DNIRA comprises fundus autofluorescence (FAF), and wherein generating said delta image data comprises a delta analysis comprising DNIRA subtracting FAF.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 23, 2022
From: BOYD, SHELLEY; PANKOVA, NATALIE; HIRMIZ, NEHAD; LIANG, HUIYUAN
To: TRACERY OPHTHALMICS INC.
Reel/Frame 059077/0776 →
Continuity (1)
Related Publication 20220207729A1 · Jun 30, 2022
References Cited (147)
US 4451477A · Silvestrini et al. · 1984 [cited by applicant]
US 4999367A · Baiocchi et al. · 1991 [cited by applicant]
US 5112986A · Baiocchi et al. · 1992 [cited by applicant]
US 5278183A · Silvestrini · 1994 [cited by applicant]
US 6020356A · Guglielmotti et al. · 2000 [cited by applicant]
US 6093743A · Lai et al. · 2000 [cited by applicant]
US 6274627B1 · Lai et al. · 2001 [cited by applicant]
US 6316502B1 · Lai et al. · 2001 [cited by applicant]
US 6319517B1 · Cavallo et al. · 2001 [cited by applicant]
US 6337087B1 · Cavallo et al. · 2002 [cited by applicant]
US 6534534B1 · Guglielmotti et al. · 2003 [cited by applicant]
US 6589991B1 · Lai et al. · 2003 [cited by applicant]
US 6596770B2 · Lai et al. · 2003 [cited by applicant]
US 6649591B2 · Lai · 2003 [cited by applicant]
US 6673908B1 · Stanton, Jr. · 2004 [cited by applicant]
US 7553496B2 · Ambati · 2009 [cited by applicant]
US 7732162B2 · Hoffman et al. · 2010 [cited by applicant]
US 7816497B2 · Ambati · 2010 [cited by applicant]
US 7928284B2 · Ambati · 2011 [cited by applicant]
US 8008092B2 · Ambati · 2011 [cited by applicant]
US 8067031B2 · Daniloff et al. · 2011 [cited by applicant]
US 8158152B2 · Papelu · 2012 [cited by applicant]
US 8198310B2 · Guglielmotti et al. · 2012 [cited by applicant]
US 8232265B2 · Rogers et al. · 2012 [cited by applicant]
US 9016862B2 · Carnevale · 2015 [cited by applicant]
US 9999688B2 · Boyd · 2018 [cited by applicant]
US 10251550B2 · Jia · 2019 [cited by examiner]
US 20030207309A1 · Hageman et al. · 2003 [cited by applicant]
US 20040177387A1 · Jayakrishna · 2004 [cited by applicant]
US 20060067935A1 · Ambati · 2006 [cited by applicant]
US 20060135423A1 · Ambati · 2006 [cited by applicant]
US 20060263409A1 · Peyman · 2006 [cited by applicant]
US 20070190055A1 · Ambati · 2007 [cited by applicant]
US 20070191273A1 · Ambati et al. · 2007 [cited by applicant]
US 20080299130A1 · Ambati · 2008 [cited by applicant]
US 20090123375A1 · Ambati · 2009 [cited by applicant]
US 20090186376A1 · Ambati et al. · 2009 [cited by applicant]
US 20090260091A1 · Ambati · 2009 [cited by applicant]
US 20090304591A1 · Russman et al. · 2009 [cited by applicant]
US 20100260396A1 · Brandt · 2010 [cited by examiner]
US 20110097390A1 · Ambati · 2011 [cited by applicant]
US 20110137157A1 · Imamura et al. · 2011 [cited by applicant]
US 20110182517A1 · Farsiu et al. · 2011 [cited by applicant]
US 20110182908A1 · Hageman et al. · 2011 [cited by applicant]
US 20110234977A1 · Verdooner · 2011 [cited by applicant]
US 20110268723A1 · Ambati · 2011 [cited by applicant]
US 20120064010A1 · Ambati et al. · 2012 [cited by applicant]
US 20130295014A1 · Boyd · 2013 [cited by applicant]
US 20130308094A1 · Mohan et al. · 2013 [cited by applicant]
US 20140029820A1 · Srivastava · 2014 [cited by examiner]
US 20150065868A1 · Liang · 2015 [cited by examiner]
US 20150088870A1 · Jayasundera · 2015 [cited by examiner]
US 20150201829A1 · Yang et al. · 2015 [cited by applicant]
US 20180263490A1 · Jia · 2018 [cited by examiner]
US 20190046030A9 · Jia et al. · 2019 [cited by applicant]
US 20200051259A1 · Sylvestre · 2020 [cited by examiner]
US 20200242763A1 · Bhuiyan · 2020 [cited by examiner]
US 20210279874A1 · Boyd · 2021 [cited by examiner]
CA 3040419A1 · 2018 [cited by applicant]
EP 0131317B1 · 1985 [cited by applicant]
JP 2008029732A · 2008 [cited by applicant]
JP 2011120656A · 2011 [cited by applicant]
JP 2013527775A · 2013 [cited by applicant]
JP 2013542840A · 2013 [cited by applicant]
JP 2014217441A · 2014 [cited by applicant]
JP 2015523546A · 2015 [cited by applicant]
JP 2016509914A · 2016 [cited by applicant]
JP 2016107148A · 2016 [cited by applicant]
WO WO9716185A2 · 1997 [cited by applicant]
WO WO9836735A1 · 1998 [cited by applicant]
WO WO9836736A1 · 1998 [cited by applicant]
WO WO03053230A1 · 2003 [cited by applicant]
WO WO2004041160A2 · 2004 [cited by applicant]
WO WO2005108431A1 · 2005 [cited by applicant]
WO WO2007079207A2 · 2007 [cited by applicant]
WO WO2007098113A2 · 2007 [cited by applicant]
WO WO2007133800A2 · 2007 [cited by applicant]
WO WO2008061671A2 · 2008 [cited by applicant]
WO WO2009104528A1 · 2009 [cited by applicant]
WO WO2009105260A2 · 2009 [cited by applicant]
WO WO2010044791A1 · 2010 [cited by applicant]
WO WO2010138591A1 · 2010 [cited by applicant]
WO WO2011036047A1 · 2011 [cited by applicant]
WO WO2011119602A2 · 2011 [cited by applicant]
WO WO2011153234A2 · 2011 [cited by applicant]
WO WO2012061835A3 · 2012 [cited by applicant]
WO WO2012068408A1 · 2012 [cited by applicant]
WO WO2013163758A1 · 2013 [cited by applicant]
WO WO2014140258A2 · 2014 [cited by applicant]
WO WO2015173786A1 · 2015 [cited by applicant]
WO WO2016073556A1 · 2016 [cited by applicant]
WO WO2016203313A1 · 2016 [cited by applicant]
WO WO2018069768A2 · 2018 [cited by examiner]
Pankova, Natalie, et al. “Delayed near-infrared analysis permits visualization of rodent retinal pigment epithelium layer in vivo.” Journal of Biomedical Optics 19.7 (2014): 076007-076007. (Year: 2014). [cited by examiner]
Tou, Jing Yi, Yong Haur Tay, and Phooi Yee Lau. “One-dimensional grey-level co-occurrence matrices for texture classification.” 2008 International Symposium on Information Technology. vol. 3. IEEE, 2008. (Year: 2008). [cited by examiner]
Rahebi, Javad, and Frat Hardalaç. “Retinal blood vessel segmentation with neural network by using gray-level co-occurrence matrix-based features.” Journal of medical systems 38.8 (2014): 85. (Year: 2014). [cited by examiner]
Ambati, et al., “An animal model of age-related macular degeneration in senescent Cc1-2 or Ccr-2-deficient mice,” Nature Medicine, 2003, vol. 9, No. 11, pp. 1390-1397. [cited by applicant]
Arnold, J., et al., “Indocyanine Green Angiography of Drusen,” American Journal of Ophthalmology, 1997, vol. 124, No. 3, pp. 344-356. [cited by applicant]
Arnold, J.J., et al., “Reticular Pseudodrusen. A Risk Factor in Age-Related Maculopathy,” Retina, vol. 15, pp. 183-191 (1995). [cited by applicant]
Beckmann, N., et al., “In vivo visualization of macrophage infiltration and activity in inflammation using magnetic resonance imaging,” WIREs Nanomed. Nanobiotechnol., vol. 1, pp. 272-298 (2009). [cited by applicant]
Bindewald, A., et al., “Classification of abnormal fundus autofluorescence patterns in the junctional zone of geographic atrophy in patients with age related macular degeneration,” Br. J. Ophthalmol., vol. 89, pp. 874-8… [cited by applicant]
Bindewald, A., et al., “Classification of Fundus Autofluorescence Patterns in Early Age-Related Macular Disease,” Invest. Ophthalmol. Vis. Sci., vol. 46, pp. 3309-3314 (2005). [cited by applicant]
Boretsky, A., et al., “Quantitative Evaluation of Retinal Response to Laser Photocoagulation Using Dual-Wavelength Fundus Autofluorescence Imaging in a Small Animal Model,” Invest. Ophthalmol. Vis. Sci., vol. 52, pp. 63… [cited by applicant]
Boyd, S. R., et al., “Reticular Fundus Autofluorescence (FAF) in the Evolution of Geographic Atrophy (GA) in a Rat Model of RPE Toxicity,” 2012 ARVO Annual Meeting, Abstract of Program#/Poster# 6504/A430, 2 pages (May 1… [cited by applicant]
Brayton, “Spontaneous Diseases in Commonly Used Mouse Strains / Stocks,” 2014, 85 pages. [cited by applicant]
Buono, C., et al., “Fluorescent pegylated nanoparticles demonstrate fluid-phase pinocytosis by macrophages in mouse atherosclerotic lesions,” J. Clin. Invest., vol. 119, No. 5, pp. 1373-1381 (2009). [cited by applicant]
Cone, R. E., et al., “Regulation of Experimental Autoimmune Uveitis (EAU) Induction in Mice by the Phosphodiesterase Inhibitor Dipyrimidol and of Active EAU by Bindarit, an Inhibitor of Monocyte Chemotactic Proteins,” 2… [cited by applicant]
Duker, J.S., “The complete trial for dry AMD: Results,” Review of Ophthalmology, Sep. 6, 2012, 3 pages. [cited by applicant]
Enzmann, V., et al., “Behavioral and anatomical abnormalities in a sodium iodate-induced model of retinal pigment epithelium degeneration,” Exp. Eye Res., vol. 82, pp. 441-448 (2006). [cited by applicant]
Eter, N., et al., “In Vivo Visualization of Dendritic Cells, Macrophages, and Microglial Cells Responding to Laser-Induced Damage in the Fundus of the Eye,” Invest. Ophthalmol. Vis. Sci., vol. 49, No. 8, pp. 3649-3658 (… [cited by applicant]
Fleckenstein, M., et al., “Fundus Autofluorescence and Spectral-Domain Optical Coherence Tomography Characteristics in a Rapidly Progressing Form of Geographic Atrophy,” Invest. Ophthalmol. Vis. Sci., vol. 52, No. 6, pp… [cited by applicant]
Fleckenstein, M., et al., “High-Resolution Spectral Domain-OCT Imaging in Geographic Atrophy Associated with Age-Related Macular Degeneration,” Invest Ophthalmol Vis Sci. 2008, vol. 49, pp. 4137-4144. [cited by applicant]
Franco, L. M., et al., “Decreased Visual Function after Patchy Loss of Retinal Pigment Epithelium Induced by Low-Dose Sodium Iodate,” Invest. Ophthalmol. Vis. Sci., vol. 50, No. 8, pp. 4004-4010 (2009). [cited by applicant]
Hua, et al., “In vivo imaging of choroidal angiogenesis using fluorescence-labeled cationic liposomes,” Molecular Vision 2012, vol. 18, pp. 1045-1054. [cited by applicant]
International Search Report & Written Opinion, PCT Application No. PCT/CA2013/050335, dated Aug. 23, 2013, 12 pages. [cited by applicant]
International Search Report dated Sep. 19, 2018, for International Application No. PCT/IB2017/001399. [cited by applicant]
International Preliminary Report on Patentability, issued Apr. 16, 2019, for International Application No. PCT/IB2017/001399. [cited by applicant]
Kiuchi, K., et al., “Morphologic characteristics of retinal degeneration induced by sodium iodate in mice,” Curr. Eye Res., vol. 25, No. 6, pp. 373-379 (2002). [cited by applicant]
Ladewig, M. S., et al., “Prostaglandin E1 infusion therapy in dry age-related macular degeneration,” Prostaglandins, Leukotrienes and Essential Fatty Acids, vol. 72, pp. 251-256 (2005). [cited by applicant]
Lois, N., et al., “Fundus Autofluorescence in Patients With Age-related Macular Degeneration and High Risk of Visual Loss,” Am. J. Ophthalmol., vol. 133, pp. 341-349 (2002). [cited by applicant]
Luhmann, U. F. O., et al., “The Drusenlike Phenotype in Aging Ccl2-Knockout Mice is Caused by an Accelerated Accumulation of Swollen Autofluorescent Subrelinal Macrophages,” Invest. Ophthalmol. Vis. Sci., vol. 50, pp. 5… [cited by applicant]
Mattapallil, et al., “The Rd8 Mutation of the Crb1 Gene is Present in Vendor Line of C57BL/6N Mice and Embryonic Stem Cells, and Confounds Ocular Induced Mutant Phenotypes,” IOVS, May 2012, vol. 53, No. 6, pp. 2921-2927. [cited by applicant]
Mendes-Jorge, L., et al., “Scavenger Function of Resident Autofluorescent Perivascular Macrophages and Their Contribution to the Maintenance of the Blood-Retinal Barrier,” Invest. Ophthalmol. Vis. Sci., vol. 50, No. 12,… [cited by applicant]
Mizota, A., et al., “Functional Recovery of Retina After Sodium Iodate Injection in Mice,” Vision Res., vol. 37, No. 14, pp. 1859-1865 (1997). [cited by applicant]
Mori, et al., “The Ultra-Late Phase of Indocycanine Green Angiography for healthy subjects and patients with age-related macular degeneration,” Retina, vol. 22, pp. 309-316, 2002. [cited by applicant]
Obata, R., et al., “Retinal degeneration is delayed by tissue factor pathway inhibitor-2 in RCS rats and a sodium-iodate-induced model in rabbits,” Eye, vol. 19, pp. 464-468 (2005). [cited by applicant]
Ohtaka, K., et al., “Protective Effect of Hepatocyte Growth Factor Against Degeneration of the Retinal Pigment Epithelium and Photoreceptor in Sodium Iodate-Injected Rats,” Curr. Eye Res., vol. 31, pp. 347-355 (2006). [cited by applicant]
Pankova, N., et al., “Delayed near-infrared analysis permits visualization of rodent retinal pigment epithelium layer In vivo,” Journal of Biomedical Optics, 2014, vol. 19, No. 7, 9 pages. [cited by applicant]
Pankova, N., et al., “Delayed Near-Infrared Analysis (DNIRA) is a Novel Technique That Permits Visualization of Rat Retinal Pigment Epithelium (RPE) Layer In Vivo,” ARVO Annual Meeting Abstract, 2014, 2 pages. [cited by applicant]
Pankova, N., et al., “Immuno-DNIRA (ImmunoD) is a novel imaging technique that identifies ex vivo labelled macrophages in the eye with confocal Scanning Laser Ophthalmoscopy (cSLO),” ARVO Annual Meeting Abstract, 2015, … [cited by applicant]
Pankova, N., “Innate Immune Response Polarization and Treatment Potential in a Preclinical Model of Dry Age-Related Macular Degeneration,” Doctor of Philosophy, Laboratory Medicine and Pathobiology, 2016. [cited by applicant]
Rodrigues, E.B., et al., “The Use of Vital Dyes in Ocular Surgery”, Survey of Ophthalmology, 2009, vol. 54, No. 5, pp. 576-617. [cited by applicant]
Ross, R. J., et al., “Immunological protein expression profile in Ccl2/Cx3cr1 deficient mice with lesions similar to age-related macular degeneration,” Exp. Eye Res., vol. 86, No. 4, pp. 675-683 (2008). [cited by applicant]
Sarks, J., et al., “Evolution of reticular pseudodrusen,” Br. J. Ophthalmol., vol. 95, pp. 979-985 (2011). [cited by applicant]
Spencer, D. B., et al., “In vivo imaging of the immune response in the eye,” Semin. Immunopathol., vol. 30, pp. 179-190 (2008). [cited by applicant]
Supplementary European Search Report, dated May 13, 2020, for Application No. EP 17860434, (10 pages). [cited by applicant]
Tanaka, M., et al., “Third-Order Neuronal Responses Contribute to Shaping the Negative Electroretinogram in Sodium Iodate-Treated Rats,” Curr. Eye Res., vol. 30, pp. 443-453 (2005). [cited by applicant]
Weinberger, A., et al., “Fundus Near Infrared Fluorescence Correlates with Fundus Near Infrared Reflectance,” Invest. Opthlamol. Vis. Sci., 2006, vol. 47, No. 1, pp. 3098-3108. [cited by applicant]
Written Opinion of the International Searching Authority, dated Sep. 19, 2018, for International Application No. PCT/IB2017/001399. [cited by applicant]
Wroblewski, et al., “Indocyanine Green Angiography in Stargardt's Flavimaculatus,” Am. J Ophthalmolgy, 1995, vol. 120, pp. 208-218. [cited by applicant]
Wu, Dezheng “Ocular Indocyanine Green Angiography,” Liaoning Science and Technology Press, 2002, 17 pages. [cited by applicant]
Yam, H., et al., “Effect of Indocyanine Green and Illumination on Gene Expression in Human Retinal Pigment Epithelial Cells,” IOVS, 2003, vol. 44, No. 1, pp. 370-377. [cited by applicant]
Zeng, X-X, et al., “Labelling of retinal microglial cells following an intravenous injection of a fluorescent dye into rats of different ages,” J. Anat., vol. 196, pp. 173-179 (2000). [cited by applicant]
Zhao, X., et al., “Patches of RPE Loss Can Be Detected In Vivo in the Rat Eye Using Confocal Scanning Laser Ophthalmoscopy,” 2011 ARVO Annual Meeting, Abstract of Program#/Poster# 969/A161, 2 pages (May 1, 2011). [cited by applicant]
Zweifel, S. A., et al., “Prevalence and Significance of Subretinal Drusenoid Deposits (Reticular Pseudodrusen) in Age-Related Macular Degeneration,” Ophthalmology, vol. 117, No. 9, pp. 1775-1781 (2010). [cited by applicant]
Zweifel, S. A., et al., “Reticular Pseudodrusen are Subretinal Drusenoid Deposits,” Ophthalmology, vol. 117, No. 2, pp. 303-312 (2010). [cited by applicant]
International Search Report & Written Opinion PCT Application No. PCT/CA2019/050495, dated Dec. 16, 2019, 10 pages. [cited by applicant]