Analysis of retinal images in glaucoma.

Glaucoma is a leading cause of visual disability. Confocal scanning laser tomography (CSLT) yields reproducible three-dimensional images of the optic nerve head and is widely used in the assessment of the disease. The real promise of this technology may be in evaluating progressive structural deterioration in the optic nerve head (ONH) associated with glaucoma over a patient’s follow-up. This might be possible as the measurements from the technology have been shown to be sufficiently reproducible. The purpose of this thesis is twofold: to investigate statistical techniques for detecting progressive structural glaucomatous damage; and to investigate techniques which improve the repeatability of images obtained from the technology. Proven quantitative techniques, collectively referred to as statistic image mapping (SIM) are widely used in neuro-imaging. In this thesis some of these techniques are adapted and applied to series of ONH images. The pixel by pixel analysis of topographic height over time yields a ‘change map’ flagging areas and intensity of active change in series of ONH images. The technique is compared to the Topographic Change Analysis (TCA superpixel analysis) and to change in summary measures of the three-dimensional ONH (‘stereometric parameters’). The comparisons are made using a novel computer simulation developed in this thesis and further tested on clinical data. A false-positive rate was recorded using testretest data obtained from 74 patients with ocular hypertension (OHT) or glaucoma. A true-positive rate was estimated using a longitudinal dataset of 52 OHT patients classified as having progressed by visual fields during follow-up. Maximum Likelihood (ML) deconvolution is an image processing technique which estimates the original scene from a degraded image using maximum likelihood probability. This technique has been used in other confocal applications to remove ‘out-of-focus’ haze and noise in 3D confocal data. In this thesis the approach is applied to testretest series to evaluate if the technique improves the repeatability of image series. Computer simulation indicated that SIM has better diagnostic precision than TCA in

[1]  David P Crabb,et al.  A new statistical approach for quantifying change in series of retinal and optic nerve head topography images. , 2005, Investigative ophthalmology & visual science.

[2]  R. Klein,et al.  Prevalence of glaucoma. The Beaver Dam Eye Study. , 1992, Ophthalmology.

[3]  A. Reidy,et al.  Prevalence of glaucoma in the west of Ireland. , 1993, The British journal of ophthalmology.

[4]  J. Pawley,et al.  Handbook of Biological Confocal Microscopy , 1990, Springer US.

[5]  M. C. Leske,et al.  Reduction of intraocular pressure and glaucoma progression: results from the Early Manifest Glaucoma Trial. , 2002, Archives of ophthalmology.

[6]  N. Swindale,et al.  Ability of the Heidelberg Retina Tomograph to Detect Early Glaucomatous Visual Field Loss , 1995, Journal of glaucoma.

[7]  David O. Harrington,et al.  The Visual fields , 1971 .

[8]  H. Quigley,et al.  Number of ganglion cells in glaucoma eyes compared with threshold visual field tests in the same persons. , 2000, Investigative ophthalmology & visual science.

[9]  Thomas E. Nichols,et al.  Nonparametric permutation tests for functional neuroimaging: A primer with examples , 2002, Human brain mapping.

[10]  Thomas E. Nichols,et al.  Nonstationary cluster-size inference with random field and permutation methods , 2004, NeuroImage.

[11]  Lucas J. van Vliet,et al.  Application of image restoration methods for confocal fluorescence microscopy , 1997, Photonics West - Biomedical Optics.

[12]  D. Sretavan,et al.  Ganglion cell axon pathfinding in the retina and optic nerve. , 2004, Seminars in cell & developmental biology.

[13]  J. Bueno The influence of depolarization and corneal birefringence on ocular polarization , 2004 .

[14]  J. Caprioli,et al.  Detection of structural damage from glaucoma with confocal laser image analysis. , 1996, Investigative ophthalmology & visual science.

[15]  Donald Allan,et al.  The benefit of early trabeculectomy versus conventional management in primary open angle glaucoma relative to severity of disease , 1989, Eye.

[16]  Balwantray C. Chauhan,et al.  Effect of the cardiac cycle on topographic measurements using confocal scanning laser tomography , 1995, Graefe's Archive for Clinical and Experimental Ophthalmology.

[17]  H. Dua,et al.  Laser scanning tomography of the optic nerve head in a normal elderly population: the Bridlington eye assessment project. , 2005, Investigative ophthalmology & visual science.

[18]  B. Chauhan,et al.  Longitudinal changes in the visual field and optic disc in glaucoma , 2005, Progress in Retinal and Eye Research.

[19]  Li Deng,et al.  Speech Denoising and Dereverberation Using Probabilistic Models , 2000, NIPS.

[20]  Karl J. Friston,et al.  Statistical parametric maps in functional imaging: A general linear approach , 1994 .

[21]  S. Orgül,et al.  Variability of contour line alignment on sequential images with the Heidelberg Retina Tomograph , 1997, Graefe's Archive for Clinical and Experimental Ophthalmology.

[22]  M. C. Leske,et al.  The epidemiology of open-angle glaucoma: a review. , 1983, American journal of epidemiology.

[23]  B C Chauhan,et al.  Test-retest variability of topographic measurements with confocal scanning laser tomography in patients with glaucoma and control subjects. , 1994, American journal of ophthalmology.

[24]  A E Maumenee,et al.  Optic disc parameters and onset of glaucomatous field loss. I. Methods and progressive changes in disc morphology. , 1979, Archives of ophthalmology.

[25]  P A Sample,et al.  Detection of early glaucomatous structural damage with confocal scanning laser tomography. , 1998, Journal of glaucoma.

[26]  S. Drance,et al.  Neuroretinal rim area in suspected glaucoma and early chronic open-angle glaucoma. Correlation with parameters of visual function. , 1984, Archives of ophthalmology.

[27]  D. R. Anderson,et al.  The mode of progressive disc cupping in ocular hypertension and glaucoma. , 1980, Archives of ophthalmology.

[28]  T. Colton,et al.  The distribution of intraocular pressures in the general population. , 1980, Survey of ophthalmology.

[29]  M. Nicolela,et al.  Comparison of data analysis tools for detection of glaucoma with the Heidelberg Retina Tomograph. , 2003, Ophthalmology.

[30]  K Rohrschneider,et al.  Reproducibility of the optic nerve head topography with a new laser tomographic scanning device. , 1994, Ophthalmology.

[31]  Anja Tuulonen,et al.  Development of the standard reference plane for the Heidelberg retina tomograph , 2000, Graefe's Archive for Clinical and Experimental Ophthalmology.

[32]  David Oliver Harrington,et al.  The visual fields: A textbook and atlas of clinical perimetry , 1976 .

[33]  B C Chauhan,et al.  Optic disc and visual field changes in a prospective longitudinal study of patients with glaucoma: comparison of scanning laser tomography with conventional perimetry and optic disc photography. , 2001, Archives of ophthalmology.

[34]  Ronald B. Rabbetts,et al.  Bennett and Rabbetts' clinical visual optics , 1998 .

[35]  D P Crabb,et al.  Interobserver agreement on visual field progression in glaucoma: a comparison of methods , 2003, The British journal of ophthalmology.

[36]  F. Newell,et al.  DIURNAL TONOGRAPHY IN NORMAL AND GLAUCOMATOUS EYES. , 1965, American journal of ophthalmology.

[37]  J D Watson,et al.  Nonparametric Analysis of Statistic Images from Functional Mapping Experiments , 1996, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[38]  J. Goodman Introduction to Fourier optics , 1969 .

[39]  Thomas E. Nichols,et al.  Combining voxel intensity and cluster extent with permutation test framework , 2004, NeuroImage.

[40]  Thomas Martin Deserno,et al.  Survey: interpolation methods in medical image processing , 1999, IEEE Transactions on Medical Imaging.

[41]  Advanced Glaucoma Intervention Study. 2. Visual field test scoring and reliability. , 1994, Ophthalmology.

[42]  A. Patterson,et al.  Improving the repeatability of topographic height measurements in confocal scanning laser imaging using maximum-likelihood deconvolution. , 2006, Investigative ophthalmology & visual science.

[43]  R S Harwerth,et al.  Glaucoma in primates: cytochrome oxidase reactivity in parvo- and magnocellular pathways. , 2000, Investigative ophthalmology & visual science.

[44]  G. Wollstein,et al.  Identification of early glaucoma cases with the scanning laser ophthalmoscope. , 1998, Ophthalmology.

[45]  J. Caprioli,et al.  Prediction of visual field progression in glaucoma. , 2004, Investigative ophthalmology & visual science.

[46]  David Garway-Heath,et al.  Results of the betaxolol versus placebo treatment trial in ocular hypertension , 2003, Graefe's Archive for Clinical and Experimental Ophthalmology.

[47]  Rafael C. González,et al.  Local Determination of a Moving Contrast Edge , 1985, IEEE Transactions on Pattern Analysis and Machine Intelligence.

[48]  P. Artal,et al.  Compensation of corneal aberrations by the internal optics in the human eye. , 2001, Journal of vision.

[49]  H. Schroder,et al.  Confocal Laser Tomographic Scanning Of The Eye , 1989, Optics & Photonics.

[50]  R. Burk,et al.  Clinical detection of optic nerve damage: measuring changes in cup steepness with use of a new image alignment algorithm. , 2001, Survey of ophthalmology.

[51]  William H. Press,et al.  Numerical Recipes Example Book , 1989 .

[52]  Elliot B. Werner Manual of Visual Fields , 1991 .

[53]  P. Diggory,et al.  Glaucoma therapy may take your breath away. , 1997, Age and ageing.

[54]  P. Mitchell,et al.  Prevalence of open-angle glaucoma in Australia. The Blue Mountains Eye Study. , 1996, Ophthalmology.

[55]  R. Hitchings,et al.  Long-term functional outcome after early surgery compared with laser and medicine in open-angle glaucoma. , 1994, Ophthalmology.

[56]  A. Sommer,et al.  Clinically detectable nerve fiber atrophy precedes the onset of glaucomatous field loss. , 1991, Archives of ophthalmology.

[57]  A. Sommer,et al.  Relationship between intraocular pressure and primary open angle glaucoma among white and black Americans. The Baltimore Eye Survey. , 1991, Archives of ophthalmology.

[58]  A. Mermoud,et al.  Retinal Nerve Fiber Layer Measured by Heidelberg Retina Tomograph and Nerve Fiber Analyzer , 2005, European journal of ophthalmology.

[59]  R. T. Hart,et al.  Deformation of the lamina cribrosa and anterior scleral canal wall in early experimental glaucoma. , 2003, Investigative ophthalmology & visual science.

[60]  G. Ravalico,et al.  Comparing Measurements of Retinal Nerve Fiber Layer Thickness Obtained on Scanning Laser Polarimetry with Fixed and Variable Corneal Compensator , 2005, European journal of ophthalmology.

[61]  F W Fitzke,et al.  Early detection of visual field progression in glaucoma: a comparison of progressor and statpac 2 , 1997, The British journal of ophthalmology.

[62]  T Odberg,et al.  Early diagnosis of glaucoma , 1985 .

[63]  P. Foster,et al.  Primary angle closure: epidemiology and mechanism , 2000 .

[64]  A. Davidson Medical treatment of glaucoma. , 1960, North Carolina medical journal.

[65]  F. Fitzke,et al.  Analysis of visual field progression in glaucoma. , 1996, The British journal of ophthalmology.

[66]  D. Garway-Heath,et al.  Factors affecting the test-retest variability of Heidelberg retina tomograph and Heidelberg retina tomograph II measurements , 2005, British Journal of Ophthalmology.

[67]  B. R. Hunt,et al.  Digital Image Restoration , 1977 .

[68]  C. Bunce,et al.  The influence of central corneal thickness and age on intraocular pressure measured by pneumotonometry, non-contact tonometry, the Tono-Pen XL, and Goldmann applanation tonometry , 2005, British Journal of Ophthalmology.

[69]  A. Sommer,et al.  Hypertension, perfusion pressure, and primary open-angle glaucoma. A population-based assessment. , 1995, Archives of ophthalmology.

[70]  A Sommer,et al.  Interobserver and Intraobserver Variability in the Detection of Glaucomatous Progression of the Optic Disc , 1996, Journal of glaucoma.

[71]  Pablo Artal,et al.  Blind deconvolution for high-resolution confocal scanning laser ophthalmoscopy* , 2005 .

[72]  Airaksinen Pj,et al.  Neuroretinal rim area and retinal nerve fiber layer in glaucoma. , 1985 .

[73]  S. Duman,et al.  Central Corneal Thickness in Primary Open Angle Glaucoma, Pseudoexfoliative Glaucoma, Ocular Hypertension, and Normal Population , 2005, European journal of ophthalmology.

[74]  Rafael C. González,et al.  Digital image processing using MATLAB , 2006 .

[75]  S. Drance,et al.  The effect of optic disc size on diagnostic precision with the Heidelberg retina tomograph. , 1997, Ophthalmology (Rochester, Minn.).

[76]  Alan C. Evans,et al.  A Three-Dimensional Statistical Analysis for CBF Activation Studies in Human Brain , 1992, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[77]  RBalwantray C. Chauhan,et al.  Influence of Time Separation on Variability Estimates of Topographic Measurements with Confocal Scanning Laser Tomography , 1995, Journal of glaucoma.

[78]  Roger A Hitchings,et al.  Approach for identifying glaucomatous optic nerve progression by scanning laser tomography. , 2003, Investigative ophthalmology & visual science.

[79]  Wilfried Philips,et al.  Estimation of anisotropic blur for the restoration of confocal images , 2004, SPIE Optics East.

[80]  R N Weinreb,et al.  Effect of cataract and pupil size on image quality with confocal scanning laser ophthalmoscopy. , 1997, Archives of ophthalmology.

[81]  R N Weinreb,et al.  Effect of repetitive imaging on topographic measurements of the optic nerve head. , 1993, Archives of ophthalmology.

[82]  Badrinath Roysam,et al.  Light Microscopic Images Reconstructed by Maximum Likelihood Deconvolution , 1995 .

[83]  Michael G Anderson,et al.  Complex genetics of glaucoma susceptibility. , 2005, Annual review of genomics and human genetics.

[84]  W Adler,et al.  Simulation based analysis of automated, classification of medical images. , 2004, Methods of information in medicine.

[85]  R. P. Mills,et al.  A comparison of experienced clinical observers and statistical tests in detection of progressive visual field loss in glaucoma using automated perimetry. , 1988, Archives of ophthalmology.

[86]  P T de Jong,et al.  The prevalence of primary open-angle glaucoma in a population-based study in The Netherlands. The Rotterdam Study. , 1994, Ophthalmology.

[87]  L Brigatti,et al.  Regional test-retest variability of confocal scanning laser tomography. , 1995, American journal of ophthalmology.

[88]  Hans G Lemij,et al.  Diagnostic accuracy of the GDx VCC for glaucoma. , 2004, Ophthalmology.

[89]  Karl J. Friston,et al.  Human Brain Function , 1997 .

[90]  William H. Richardson,et al.  Bayesian-Based Iterative Method of Image Restoration , 1972 .

[91]  D. Rubin,et al.  Maximum likelihood from incomplete data via the EM - algorithm plus discussions on the paper , 1977 .

[92]  J. Katz,et al.  Analysis of progressive change in automated visual fields in glaucoma. , 1996, Investigative ophthalmology & visual science.

[93]  J. Jonas,et al.  Ophthalmoscopic evaluation of the optic nerve head. , 1999, Survey of ophthalmology.

[94]  H. Rootzén,et al.  A new generation of algorithms for computerized threshold perimetry, SITA. , 2009, Acta ophthalmologica Scandinavica.

[95]  B. Prum,et al.  The advanced glaucoma intervention study (AGIS): 7. the relationship between control of intraocular pressure and visual field deterioration , 2000 .

[96]  John G Flanagan,et al.  Comparison of Heidelberg Retina Tomograph II and Retinal Thickness Analyzer in the assessment of diabetic macular edema. , 2004, Investigative ophthalmology & visual science.

[97]  Robert N Weinreb,et al.  Use of progressive glaucomatous optic disk change as the reference standard for evaluation of diagnostic tests in glaucoma. , 2005, American journal of ophthalmology.

[98]  P. Pohjanpelto,et al.  OCULAR HYPERTENSION AND GLAUCOMATOUS OPTIC NERVE DAMAGE , 1974, Acta ophthalmologica.

[99]  R N Weinreb,et al.  Reproducibility of topographic measurements of the normal and glaucomatous optic nerve head with the laser tomographic scanner. , 1991, American journal of ophthalmology.

[100]  Karl J. Friston,et al.  Combining Spatial Extent and Peak Intensity to Test for Activations in Functional Imaging , 1997, NeuroImage.

[101]  M. C. Leske,et al.  The Barbados Eye Study. Prevalence of open angle glaucoma. , 1994, Archives of ophthalmology.

[102]  B C Chauhan,et al.  Technique for detecting serial topographic changes in the optic disc and peripapillary retina using scanning laser tomography. , 2000, Investigative ophthalmology & visual science.

[103]  Tom Davis,et al.  Opengl programming guide: the official guide to learning opengl , 1993 .

[104]  E. Etchells,et al.  Laser scanning tomography of the optic nerve head in ocular hypertension and glaucoma , 1997, The British journal of ophthalmology.

[105]  A. Schwartz,et al.  Long-term follow-up of argon laser trabeculoplasty for uncontrolled open-angle glaucoma. , 1985, Archives of ophthalmology.

[106]  L. Lucy An iterative technique for the rectification of observed distributions , 1974 .

[107]  N. Swindale,et al.  Automated analysis of normal and glaucomatous optic nerve head topography images. , 2000, Investigative ophthalmology & visual science.

[108]  R. Klein,et al.  The Beaver Dam Eye Study. Retinopathy in adults with newly discovered and previously diagnosed diabetes mellitus. , 1992, Ophthalmology.

[109]  M. Niknian,et al.  Randomization and Monte Carlo Methods in Biology , 1993 .

[110]  Alon Harris,et al.  Retina and optic nerve imaging , 2003 .

[111]  Richard M. Jones Introduction to MFC Programming with Visual C , 2000 .

[112]  W. Press,et al.  Numerical Recipes Example Book (C). , 1989 .

[113]  G E Trope,et al.  Interobserver agreement of Heidelberg retina tomograph parameters. , 1999, Journal of glaucoma.

[114]  M Schulzer,et al.  Reproducibility of topographic parameters obtained with the heidelberg retina tomograph. , 1993, Journal of glaucoma.

[115]  P. Jansson Deconvolution of images and spectra , 1997 .

[116]  Neuroretinal rim area and retinal nerve fiber layer in glaucoma. , 1985, Archives of ophthalmology.

[117]  F W Fitzke,et al.  Use of sequential Heidelberg retina tomograph images to identify changes at the optic disc in ocular hypertensive patients at risk of developing glaucoma , 2000, The British journal of ophthalmology.

[118]  B Schwartz The optic disc in glaucoma: introduction. , 1976, Transactions. Section on Ophthalmology. American Academy of Ophthalmology and Otolaryngology.

[119]  L. Zangwill,et al.  Ranked‐Segment Distribution Curve for Interpretation of Optic Nerve Topography , 1996, Journal of glaucoma.

[120]  Ravi Thomas,et al.  Primary open angle glaucoma. , 1990, The National medical journal of India.

[121]  J V Forrester,et al.  Tomographic reconstruction of the retina using a confocal scanning laser ophthalmoscope. , 1999, Physiological measurement.

[122]  Brian Everitt,et al.  Statistical analysis of medical data : new developments , 2000 .

[123]  A C Viswanathan,et al.  Detection of optic disc change with the Heidelberg retina tomograph before confirmed visual field change in ocular hypertensives converting to early glaucoma , 1999, The British journal of ophthalmology.

[124]  D. Garway-Heath,et al.  Improving the repeatability of Heidelberg retina tomograph and Heidelberg retina tomograph II rim area measurements , 2005, British Journal of Ophthalmology.

[125]  John Suckling,et al.  Global, voxel, and cluster tests, by theory and permutation, for a difference between two groups of structural MR images of the brain , 1999, IEEE Transactions on Medical Imaging.

[126]  Robert J. Hanisch,et al.  Deconvolution of Hubbles Space Telescope images and spectra , 1996 .

[127]  Drance Sm,et al.  Optic disc in glaucoma. , 1975 .

[128]  Jonathan Bates,et al.  Practical Visual C++ 6 , 1999 .

[129]  S. Kiebel,et al.  An Introduction to Random Field Theory , 2003 .

[130]  G A Cioffi,et al.  Optic nerve blood flow in glaucoma. , 1999, Seminars in ophthalmology.

[131]  Chris A. Johnson,et al.  The Ocular Hypertension Treatment Study: baseline factors that predict the onset of primary open-angle glaucoma. , 2002, Archives of ophthalmology.

[132]  S M Drance,et al.  The use of visual field indices in detecting changes in the visual field in glaucoma. , 1990, Investigative ophthalmology & visual science.

[133]  S. Tsukahara,et al.  Epidemiology of glaucoma in Japan--a nationwide glaucoma survey. , 1991, Japanese journal of ophthalmology.

[134]  R A Hitchings,et al.  The optic disc in glaucoma: pathogenetic correlation of five patterns of cupping in chronic open-angle glaucoma. , 1976, Transactions. Section on Ophthalmology. American Academy of Ophthalmology and Otolaryngology.

[135]  L. Chylack,et al.  Lens autofluorescence and light scatter in relation to the lens opacities classification system, LOCS III. , 1999, Acta ophthalmologica Scandinavica.

[136]  N C Andreasen,et al.  Tests for Comparing Images Based on Randomization and Permutation Methods , 1996, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[137]  S. Gardiner,et al.  Examination of different pointwise linear regression methods for determining visual field progression. , 2002, Investigative ophthalmology & visual science.

[138]  P. Good,et al.  Permutation Tests: A Practical Guide to Resampling Methods for Testing Hypotheses , 1995 .

[139]  Thomas E. Nichols,et al.  Validating cluster size inference: random field and permutation methods , 2003, NeuroImage.

[140]  R. Pandey,et al.  Variables Affecting Test-Retest Variability Of Heidelberg Retina Tomograph II Stereometric Parameters , 2002, Journal of glaucoma.

[141]  G. Dunkelberger,et al.  Retinal ganglion cell atrophy correlated with automated perimetry in human eyes with glaucoma. , 1989, American journal of ophthalmology.

[142]  A. Sommer,et al.  Racial variations in the prevalence of primary open-angle glaucoma. The Baltimore Eye Survey. , 1991, JAMA.

[143]  C. Bunce,et al.  A comparison of four methods of tonometry: method agreement and interobserver variability , 2005, British Journal of Ophthalmology.

[144]  Robert H. Webb,et al.  Scanning Laser Ophthalmoscope , 1981, IEEE Transactions on Biomedical Engineering.

[145]  H. V. Trees Detection, Estimation, And Modulation Theory , 2001 .