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The Effect of Race and Selective Laser Trabeculoplasty

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The Effect of Race and Selective Laser Trabeculoplasty ADVERTIMENT. Lʼaccés als continguts dʼaquesta tesi queda condicionat a lʼacceptació de les condicions dʼús establertes per la següent llicència Creative Commons: http://cat.creativecommons.org/?page_id=184 ADVERTENCIA. El acceso a los contenidos de esta tesis queda condicionado a la aceptación de las condiciones de uso establecidas por la siguiente licencia Creative Commons: http://es.creativecommons.org/blog/licencias/ WARNING. The access to the contents of this doctoral thesis it is limited to the acceptance of the use conditions set by the following Creative Commons license: https://creativecommons.org/licenses/?lang=en ! ! ! ! Departament de Cirurgia i Ciències Morfològiques Universitat Autònoma de Barcelona ! ! ! ! TESI DOCTORAL ! ! ! ! The Effect Of Race And Selective Laser Trabeculoplasty On The Aqueous Humor Dynamics In Patients With Glaucoma ! ! ! ! Laura Beltran Agulló ! Barcelona, Gener 2017 ! Escola de Doctorat de la Universitat Autònoma de Barcelona Departament de Cirurgia i Ciències Morfològiques ! ! The Effect Of Race And Selective Laser Trabeculoplasty On The Aqueous Humor Dynamics In Patients With Glaucoma ! Memòria presentada per Laura Beltran Agulló ! Per optar al títol de Doctora en Oftalmologia per la Universitat Autònoma de Barcelona Menció Doctor Internacional ! Tesi Doctoral realitzada sota la tutoria del Dr. Miguel Céspedes Castilla i sota la co-direcció de Mr Kin-Sheng Lim i Dr. Alfonso Antón al St. Thomas’ Hospital de Londres i Institut Català de la Retina de Barcelona. ! El tutor, Els directors, L’autora, ! ! ! ! ! ! ! Mr. K.S. Lim ! ! ! ! ! ! ! Dr. M. Céspedes Castilla Dr. A. Antón López Laura Beltran Agulló ! ! Barcelona, Gener 2017 ! ABBREVIATIONS A Area ACD Anterior chamber depth ADP Adenosine diphosphate AFR Aqueous floW rate AH Aqueous humor AHD Aqueous humor dynamics ALT Argon laser trabeculoplasty ANOVA Analysis of variance AP Pressure gradient AQP Aquaporins ATP Adenosine triphosphate AV Aqueous veins AXL Axial length B Ocular rigidity BCE Before the Common Era C Trabecular outfloW facility CC Collector channel CCT Central corneal thickness CDR Cup-to-disc ratio CE Common Era CH Corneal hysteresis CI Confidence interval CNTGS Collaborative normal tension glaucoma study CRF Corneal resistance factor CrI Credible interval dB Decibel EFA Effective filtration area EMGT Early manifest glaucoma trial EPV Episcleral vein pressure F Force Fin Aqueous infloW Ui ABBREVIATIONS FM Fluorotron Master Fout Aqueous outfloW Ft Aqueous floW rate Ftrab Trabecular outfloW Fu Uveoscleral outfloW GAT Goldmann applanation tonometry gr Gram GSTT Guy's and St Thomas' NHS foundation Trust HBonf Bonferroni method of analysis IL Interleukins IOL Intraocular lens IOP Intraocular pressure IQR Interquartile range Ko Loss coefficient LASIK Laser-assisted in situ keratomileusis Max Maximum MD Mean deviation min Minute Min Minimum mJ MilliJoule mL Millilitre mm Millimetre mmHg Millimetre of mercury mW MilliWatt n Number of subjects Nd-YAG Neodymium: yttrium aluminium garnet NHS National Health System NPE Non-pigmented epithelium ns Nanosecond NTG Normotensive glaucoma OAG Open angle glaucoma Uii ABBREVIATIONS OHT Ocular hypertension OHTS Ocular Hypertension study ONT Ocular normotensive (healthy volunteers) P Pressure PACG Primary angle closure glaucoma PE Pigmented epithelium POAG Primary open angle glaucoma PT Pneumotonometry Pv Venous pressure R Resistance S Surface tension SC Schlemm's canal SITA Swedish interactive thresholding algorithm SLT Selective laser trabeculoplasty SS Scleral spur TM Trabecular meshWork TRT Thermal relaxation time μL Microlitre μm Micrometre ! ! Uiii ABBREVIATIONS Uiv TABLE OF CONTENTS ! PROLOGUE! 1! INTRODUCTION! 5! 1. Anatomy of the ocular globe 7 1.1. Anatomy of the ocular chambers 8 1.2. The Iridocorneal Angle 9 1.2.1. The Trabecular meshwork 9 1.2.2. Schlemm’s canal 10 1.2.3. Collector Channels and Aqueous Veins 10 2. The Aqueous Humor 11 2.1. Aqueous Humor Function 11 2.2. Aqueous Humor Composition 11 3. Aqueous Humor Dynamics 12 3.1. Aqueous Humor Production 13 3.2. Aqueous Humor Outhlow 16 3.2.1. Trabecular out@low (conventional pathway) 17 3.2.2. Uveoscleral out@low (nonconventional pathway) 18 3.3. Intraocular pressure: the Goldmann equation 19 4. Aqueous Humor dynamics: Study Methods 21 4.1 Intraocular Pressure: Tonometry 21 4.1.1. Indentation Tonometers 21 4.1.3. Applanation-Identation tonometers 23 4.2 Aqueous Humor Production: Fluorophotometry 24 4.2.2. Fluorotron Master 27 4.3. Aqueous humor outhlow: Tonography 31 4.3.1. Indentation Tonography 31 4.4. Episcleral venous pressure: 33 5. Aqueous Humor Dynamics Alterations 34 5.1. Ocular Hypertension, Primary Angle Glaucoma and Ethnicity 34 5.2. Glaucoma treatment 38 5.2.1. Medical treatment 39 5.2.2. Laser treatment: trabeculoplasty 43 Uv TABLE OF CONTENTS 1. The effect of race on aqueous humor dynamics 49 2. The effect of selective laser trabeculoplasty on aqueous humor dynamics 50 HYPOTHESIS! 51! OBJECTIVES! 55! METHODOLOGY! 59! 1. Study design and recruitment 61 2. Inclusion and Exclusion Criteria 61 3. Data Collection and Outcome Measures 62 4. Measurements 63 5. Selective laser trabeculoplasty treatment 70 6. Data Analysis 71 RESULTS! 73! 1. Patient description 75 2. Aqueous humor dynamics comparison between black and white subjects and its relationship with intraocular pressure 75 2.1. Out@low facility 75 2.2. Intraocular pressure 77 2.3. Aqueous @low rate 77 2.4. Uveoscleral out@low 78 3. Age 78 4. Ocular Hypertension versus Primary Open Angle Glaucoma 78 5. Axial length, anterior chamber depth & central corneal thickness 78 6. Selective Laser Trabeculoplasty 80 DISCUSSION! 83! CONCLUSIONS! 91! EPILOGUE! 95! ANNEX! 99! REFERENCES! 111 ! Uvi ! ! PROLOGUE PROLOGUE ! ! ! ! ! ! ! PROLOGUE "1 PROLOGUE ! ! ! ! ! ! ! ! ! ! ! PROLOGUE Why is glaucoma much more common and aggressive in patients of African descent? Unfortunately, We are not capable of ansWering this question just yet. Glaucoma is the leading cause of irreversible blindness Worldwide and individuals of African descent are not only disproportionally affected by primary open angle glaucoma (POAG), the most common form of glaucoma, but also their disease develops earlier, presents with greater severity and progresses more rapidly. Thus, the management of this patients, at higher risk of blindless, is a challenge. Poor understanding of its aetiology has hindered attempts to early identihication and treatment of disease. All studies agree that POAG is a complex and multivariate disease. This thesis has two parts and each, tries to ansWer a different question. First, We Wanted to know Whether African descent individuals had a greater imbalance in the production and outhlow of the aqueous humor than White-Caucasians, since a greater aqueous production or a loWer drainage could lead to a higher intraocular pressure (IOP). As of noW, elevated IOP remains the only treatable factor of this disease. IOP can be reduced using medical treatment, surgically or with laser therapy. Selective laser trabeculoplasty (SLT), with a good safety prohile and efhicacy loWering IOP, has gained popularity during the last decade since its approval by the FDA in 2001. But… how does SLT work? Does it increase the trabecular out@low? We attempted to ansWer this question in the second part of this research. ! This research Was my introduction to the science of Aqueous Dynamics. It Was an enriching learning experience that alloWed me to understand glaucoma in a more “basic” level. I Was able to use techniques such as Tonography and Fluorophotomtery Which are otherwise not available in a normal clinical setting. The results from comparing the IOP, outhlow facility and aqueous production between black and White individuals and the changes caused by SLT are presented and discussed in detail. At the end, the two papers published in two different peer-reviewed journals, resulting from this work have been attached. ! ! 3 INTRODUCTION ! INTRODUCTION ! ! ! INTRODUCTION INTRODUCTION 5 INTRODUCTION 5 INTRODUCTION 1. Anatomy of the ocular globe The eyeball is covered by three layers or tunics (cornea and sclera, retina and uvea) and contains three compartments (anterior chamber, posterior chamber and vitreous cavity). ! The outermost layer, the hibrous tunic is composed anteriorly by the cornea and posteriorly by the sclera. The sclera is an opaque White layer that covers the outer part of the globe, With an anterior opening for the cornea and a posterior one for the optic nerve. Not only protects the intraocular structures, but also maintains along with the intraocular pressure (IOP) the appropriate shape of the eye for a correct visual function. The thinnest and most fragile part of sclera is located just behind the insertion of the rectus (0.3 mm) reaching approximately 1 mm thick at the back around the optic nerve. The cornea, hoWever, is a transparent and avascular tissue that occupies the centre of the anterior pole of the eye. This structure, convex on the outside and concave on the inside, has manly an optical function since it is the structure with more refractive poWer of the eye. The corneal thickness is approximately 0.7 mm in the periphery and 0.5 mm in the central area. The limbus, the transition zone between the cornea and sclera, is grey and translucent. In the innermost part of the corneoscleral limbus are the trabecular meshWork and Schlemm’s canal. ! The vascular tunic or uvea is the middle layer of the eye and consists of the choroid, ciliary body and iris. It is characterised by being highly vascularised and pigmented. The choroid extends from the insertion point of the optic nerve to the limit with the ciliary body, the ora serrata. Its main function is to nourish outer layers of the retina. It consists of 3 layers of blood vessels: the innermost layer or choriocapillaris, a middle layer of small calibre vessels and the outermost layer of large calibre vessel. The blood supply to the choroid comes from the long and short posterior ciliary arteries and anterior ciliary arteries. The venous drainage is through the vortex veins. The ciliary body, of triangular section, serves as a bridge between the anterior and posterior segment of the eye.
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