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Anterior Segment Topography and Aberrations for Clinical Applications

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Anterior Segment Topography and Aberrations for Clinical Applications INSTITUTO DE OFTALMOBIOLOGÍA APLICADA TESIS DOCTORAL: ANTERIOR SEGMENT TOPOGRAPHY AND ABERRATIONS FOR CLINICAL APPLICATIONS Presentada por PABLO PÉREZ MERINO para optar al grado de doctor por la Universidad de Valladolid Dirigida por: SUSANA MARCOS CELESTINO ii Impreso 2T AUTORIZACIÓN DEL DIRECTOR DE TESIS (Art. 2.1. c de la Normativa para la presentación y defensa de la Tesis Doctoral en la Uva) Dña. SUSANA MARCOS CELESTINO con D.N.I. nº 07954600G, Profesora de Investigación en el Instituto de Óptica “Daza de Valdés” del Consejo Superior de Investigaciones Científicas (CSIC), [email protected], como Directora de la Tesis Doctoral titulada “Anterior segment topography and aberrations for clinical applications (Topografía y aberraciones del segmento anterior del ojo en aplicaciones clínicas)”, presentada por D. PABLO PEREZ MERINO, alumno del Programa de Doctorado en CIENCIAS DE LA VISIÓN impartido por el INSTITUTO UNIVERSITARIO DE OFTALMOBIOLOGÍA APLICADA, autoriza la presentación de la misma, considerando que la tesis presenta resultados originales y novedosos para la comprensión de las aplicaciones clínicas de las patologías del segmento anterior más frecuentes del ojo, utilizando tecnologías estado-del-arte (Trazado de Rayos Laser y Tomografía de Coherencia Óptica), con impacto en la comunidad científica, clínica e industrial, a través de publicaciones en revistas internacionales de alto impacto y comunicaciones en congresos nacionales e internacionales. Valladolid, 16 de septiembre de 2015 El Director de la Tesis, Fdo.: Susana Marcos Celestino SRA. PRESIDENTA DE LA COMISIÓN DE DOCTORADO iii iv a mis padres, Pablo y Ramoni, y a mi hermano, David a Ana v vi Table of Contents ANTERIOR SEGMENT TOPOGRAPHY and ABERRATIONS for CLINICAL APPLICATIONS Key words xi List of commonly used abbreviations and variables xiii Motivation xv Chapter I. INTRODUCTION 1.1. The optics of the human eye 1 1.1.1. Historical introduction 1 1.1.2. Cornea 2 1.1.3. Crystalline lens 4 1.1.4. Pupil 7 1.1.5. Axes of the eye 7 1.2. Refractive errors 8 1.3. Optical aberrations 9 1.4. State-of-the-art of aberrometers 12 1.5. State-of-the-art of quantitative anterior segment imaging techniques 14 1.5.1. Elevation-based corneal topography 14 1.5.2. Optical Coherence Tomography (OCT) 16 1.6. Customized eye modeling: linking geometry and aberrations 20 1.7. Anterior segment conditions and clinical applications studied in this thesis 22 1.7.1. Cornea (Keratoconus & Intracorneal Ring Segment (ICRS) treatment) 22 1.7.1.1. Keratoconus: topography and pachymetry 23 1.7.1.2. Keratoconus: aberrations 24 1.7.1.3. Keratoconus treatment: Intracorneal Ring Segments (ICRS) 25 1.7.2. Crystalline lens (Accommodation, Presbyopia, Cataract) 27 1.7.2.1. Accommodation 27 1.7.2.2. Presbyopia 29 1.7.2.2.1. Presbyopia solutions 30 1.7.2.3. Cataract (Intraocular lens) 33 1.8. Open questions addressed in this thesis 35 1.9. Goals of this thesis 37 1.10. Hypothesis 37 1.11. Structure of this thesis 38 Chapter II. MATERIAL AND METHODS 39 2.1. Laser Ray Tracing (LRT): ocular aberrations 41 vii 2.1.1. LRT: basic concepts 41 2.1.2. LRT: setup 42 2.1.3. LRT: control and analysis software 45 2.1.4. LRT: calibration 45 2.2. Spectral Domain Optical Coherence Tomography 47 2.2.2. SD-OCT: custom-setup 47 2.2.3. SD-OCT: distortion correction 50 2.2.4. SD-OCT: image processing 52 2.2.5. OCT-based corneal and ocular aberrometry 57 2.3. Optical quality metrics 59 2.4. Subjects and protocol in measurements (LRT and OCT) 61 Chapter III. KERATOCONUS AND ICRS (OCT-based Topography and Aberrometry in keratoconus with Intracorneal Ring Segments) 65 Introduction 67 3.1. Material and methods 68 3.1.1. Patients 68 3.1.1.1. OCT-based Corneal Topography in keratoconus and ICRS 68 3.1.1.2. OCT-based Corneal Aberrometry in keratoconus and ICRS 69 3.1.2. Custom SD-OCT system 70 3.1.3. OCT image processing: corneal surface analysis & ICRS segmentation 71 3.1.4. OCT image processing: corneal aberration analysis 72 3.1.5. LRT: total aberration analysis 73 3.1.6. Optical quality metrics 73 3.1.7. Visual acuity measurements 73 3.1.8. Statistical analysis 74 3.2. Results 74 3.2.1. OCT-based corneal topography and geometry in keratoconus and ICRS 74 3.2.1.1. Longitudinal changes of anterior corneal geometry and topography 74 3.2.1.2. Longitudinal changes of poserior corneal geometry and topography 77 3.2.1.3. Longitudinal variation of corneal power 79 3.2.1.4. Corneal thickness: pre- and post-ICRS implantation 79 3.2.1.5. 3-D ICRS location 80 3.2.1.6. Correlation between surgical parameters and corneal geometry 82 3.2.2. OCT-based corneal aberrometry in keratoconus and ICRS 82 3.2.2.1. LRT vs OCT aberrometry 82 3.2.2.2. Pre- and post-ICRS aberrations 86 3.2.2.3. Visual acuity vs optical quality 88 3.2.2.4. Posterior corneal surface contribution 88 3.2.3. OCT-based aberrometry vs OCT-based geometry 89 3.3. Discussion 90 Chapter IV. ACCOMMODATION (OCT-based Crystalline Lens Topography in Accommodating Eyes) 95 Introduction 97 4.1. Material and methods 97 viii 4.1.1. Subjects 97 4.1.2. OCT system 98 4.1.3. OCT: Experimental Procedure 98 4.1.4. OCT: Image Processing 99 4.1.5. OCT: Spatial resolution and Accuracy Considerations 100 4.1.6. Biometric, geometric and surface changes with accommodation 101 4.1.7. Accommodative response 102 4.1.8. Corneal and lens surface astigmatism axis 102 4.1.9. Statistics 102 4.2. Results 103 4.2.1. Anterior and posterior lens surface elevation (relaxed state) 103 4.2.2. Comparison of Zernike coefficients of ocular surfaces 104 4.2.3. Phenylephrine vs natural anterior lens surface topography 106 4.2.4. Changes in anterior segment biometry with accommodation 106 4.2.5. Changes in lens surface elevation with accommodation 107 4.2.6. Corneal and lens surface astigmatism with accommodation 109 4.3. Discussion 111 Chapter V. PRESBYOPIA-CATARACT AND IOL (Aberrometry and OCT-based Geometrical Evaluation of Patients Implanted with Accommodative IOLs) 115 Introduction 117 5.1. Material and methods 118 5.1.1. Patients, surgery and A-IOLs 118 5.1.2. OCT: measurements 118 5.1.3. OCT: data analysis 119 5.1.4. LRT: measurements 120 5.1.5. LRT: data analysis 121 5.1.6. Statistical analysis 122 5.2. Results 122 5.2.1. Anterior chamber depth (ACD) 122 5.2.2. Changes in ACD with accommodative effort 123 5.2.3. Lens thickness 125 5.2.4. IOL tilt 125 5.2.5. Capsulorhexis and haptic axis 127 5.2.6. Individual aberrations: unaccommodative state 127 5.2.7. Individual aberrations: changes with accommodative stimulus 129 5.2.8. Wave aberrations with phenylephrine and natural viewing conditions 132 5.2.9. Change in accommodative response with accommodative demand 132 5.2.10. Depth-of-focus 133 5.3. Discussion 135 Chapter VI. CATARACT AND IOL (Chromatic aberration with 141 IOLs) Introduction 143 6.1. Material and methods 144 ix 6.1.1. Patients, surgery and IOLs 144 6.1.2. LRT: total aberration analysis 145 6.1.3. Data analysis 146 6.2. Results 147 6.2.1. Monochromatic aberrations 147 6.2.2. Chromatic difference of focus 148 6.2.3. Effect of chromatic difference of focus on retinal image quality 149 6.3. Discussion 151 Epilogue: CONCLUSIONS AND FUTURE WORK 155 Achievements 157 Conclusions 159 Clinical impact 161 Future work 161 RESÚMENES EN ESPAÑOL 163 List of PUBLICATIONS 179 Publications included in this thesis 179 Other publications 179 International congress contributions 180 Invited talks 183 Other information that might be relevant 183 Honors 183 BIBLIOGRAPHY 185 ACKNOWLEDGEMENTS 205 x Key words xi xii List of commonly used abbreviations and variables Abbreviations Imaging Techniques Clinical treatments OCT = Optical Coherence Tomography TD-OCT = Time-Domain OCT IOL = Intraocular Lens SD-OCT = Spectral-Domain OCT A-IOL = Accommodative-IOL SS-OCT = Swept-Source OCT ICRS = Intracorneal ring segment LRT = Laser Ray Tracing CL = Contact Lens H-S = Hartmann-Shack PPMA = Polymethyl-methacrilate UBM = Ultrasound biomicroscopy Wavefront Analysis MRI = Magnetic Resonance Imaging PCI = Partial Coherence Interferometry FFT = Fast Fourier Transform FWHM = full-width-half-minimum Optical Terms RMS = Root Mean Square IR = Infrared PSF = Point Spread Function CCD = Charge Couple Device SR = Strehl Ratio LED = Light Emitting Diode MTF = Modulation Transfer Function SLD = Superluminiscent Diode CSF = Contrast Sensitivity Function DLP = Digital-Light-Processing OTF = Optical Transfer Function NA = Numerical Aperture VSOTF = Visual Strehl OTF BS = Beam Splitter FC = Fiber Coupler OI = Optical Isolator PC = Polarization Controller M = Mirror L = Lens NDF = Neutral Density Filter SNR = Signal-to-Noise Ratio HOAs = High-Order Aberrations LCA = Longitudinal Chromatic Aberration TCA = Transverse Chromatic Aberration GRIN = Gradient Index DoF = Depth-of-Focus General 2-D = Two-dimensions 3-D = Three-dimensions i.e. = id est, this is e.g. = exempli gratia, for example vs = versus, compared to VA = Visual Acuity BCVA = Best-Corrected VA D = Diopters N = Nasal T = Temporal S = Superior I = Inferior H = Horizontal V = Vertical AL = Axial Length ACD = Anterior Chamber Depth LT = Lens Thickness xiii Variables Coefficients and indices n, m, j, … = index names N, M = maximum index/number General Optical Variables λ = Wavelength κ = Wavenumber (propagation constant) ω = angular frequency υ = frequency R, r = Radius C = Curvature (=1/R) K = Conic constant p = p-value, asphericity Q = Q-value, asphericity W(x,y) = Wave aberration in Cartesian coordinates 푚 푍푛 = Zernike polynomial in Cartesian coordinates 푚 푐푛 = Zernike coefficient (order, n; frequency, m).
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