U'JTERACTlbM me. cl- <*torrr-?ilLS£ LA<,0? RAD'Arf CKI ixjifH ecu la R n*66ua A k, JU n '.cal . IMfU riCiVjS. BXQP«¥g^ A £~inj:ca?an^g^-ciF-euzsvy^Atusn a t »p t t c a inoeuLAfl 3uncm¥r. A thesis submitted in partial satisfaction of the requirements for the degree of Doctor of Philosophy in the University of London by David H. Sliney Institute of Ophthalmology University of London 1991 1 ProQuest Number: U047171 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a com plete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. uest ProQuest U047171 Published by ProQuest LLC(2017). Copyright of the Dissertation is held by the Author. All rights reserved. This work is protected against unauthorized copying under Title 17, United States C ode Microform Edition © ProQuest LLC. ProQuest LLC. 789 East Eisenhower Parkway P.O. Box 1346 Ann Arbor, Ml 48106- 1346 ABSTRACT Traditional laser photocoagulation of the retina requires CW exposures of the order of 0.1 s. An extensive literature exists on thermal damage mechanisms and biological sequellae of coagulation. By contrast, the biophysical mechanisms of pulsed laser interactions are poorly uiiderstood. The use of photodisruption and photoablation by sub­ microsecond laser pulses to cut tissue has recently gained considerable clinical attention. In addition, selective photocoagulation of localized target tissue would also require short-duration pulses. The biophysical mechanisms of short-pulse laser interaction with tissue will influence the surgical outcome. Without a full understanding of these mechanisms, the new and the potential ophthalmic applications of pulsed lasers cannot be optimised, nor can one accurately predict potential delayed effects. The aim of the research reported in this thesis has been first to study the biophysical mechanisms in a series of experiments and then to consider how to optimise laser exposure parameters in relation to the desired surgical effect while minimizing undesirable collateral effects. Focal laser interaction with target tissue may produce adverse effects to non-target tissues from photochemical, thermal and acoustical phenomena. Acoustical, mechanical impulse, and other phenomena which differ between mode-locked and Q-switched exposures were investigated. Optical breakdown, thermo-acoustic effects, photochemical ablation, thermal vaporization and selective photothermal coagulation are all considered. 2 ACKNOWLEDGEMENTS I would like to thank Professor John Marshall for the extensive advice and guidance that he has provided throughout this study. I would also like to thank several other scientists in other universities with whom I have'had much fruitful discussions on this subject of study. These include Professors M. L. Wolbarsht of Duke University, John Mellerio of the London Polytechnic University, Franz Hillenkamp of the University of Muenster, Bjorn Tengroth of the Karolinska Institute, Martin Mainster of the University of Kansas, Carmen Puliafito of Harvard Universtiy, and Stephen Trokel and Ronald Krueger of Columbia University. I greatly appreciate the patience of Mr. Stephen Rothery, Institute of Ophthalmolgy, who aided in several experiments and performed electron microscopy of target tissue specimens. Because of the extensive range of specialised laser equipment needed for some experiments, it was impossible to perform all experiments without making use of equipment from other facillities. Dr. Kieth Evans and G. Thomas, Chalk River Facility, Atomic Energy of Canada, Ltd., Chalk River, Ontario Canada provided access to short-pulse CO-2 and HF lasers. Dr. Brian Norris of Lumonics, Ltd., Kanata, Ontario, Canada provided access to ArF excimer, HF and CO-2 lasers for corneal ablation studies. Dr. John Grindle, Harley Street Clinic, Mr. Bodo Dolch of Medical Lasers, Inc. and Dr. Leeds M. Katzen, Mercy Hospital, Baltimore provided access to photodisruptor lasers. Dr. Leon Esterowitz, Naval Research Laboratory, gave access to an Erbium:YAG laser. 3 PUBLICATIONS MAINSTER MA, SLINEY DH, BELCHER CD III, BUZNEY SM (1983). Laser photodisrupters: damage mechanism, instrument design and safety. Ophthalmology, 90(8): 973-991. SLINEY DH (1983). YAG Laser Safety. In: YAG Laser Ophthalmic Microsurgery (Trokel SL, Ed.), Norwalk, Appleton-Century Crofts. SLINEY DH (1985a). Laser-Tissue Interactions, Clin. Chest Med., 6(2):203. SLINEY DH (1985b). Neodymium:YAG laser safety considerations, International Ophthalmology Clinics (Neodymium:YAG Laser Microsurgery), 25(3): 151-157. DAVI SH, SLINEY DH, NORRIS B> NIP W, CARPENTER PK, MCALPINE RD, THOMAS G, EVANS K (1986). A comparative study of corneal incisions induced by pulsed lasers at infrared and ultraviolet wavelengths. Proc SPIE, (Optical and Laser Technology in Medicine). 605: 25-27. SLINEY DH (1986). Report on the proposed standard test procedure for ophthalmic Nd:YAG photodisruptors, Ophthalmic Laser Therapy, 1(2): 107-110. 4 SLINEY DH, MAINSTER MA (1987). Potentially hazardous reflections to the clinician during photocoagulation. Ophthalmology, 106(3): 758-760. SLINEY DH (1988a), New chromophores for ophthalmic laser surgery, Lasers in Ophthalmology, 2(1):53-61. SLINEY DH (1988b). Interaction mechanisms of laser radiation with ocular tissues. In: Procedings of the First International Symposium on Laser Biological Effects and Exposure Limits: Lasers et Normes de Protection, Paris, Court LA, Duchene A, Courant D, Eds. pp. 64-83, Commissariat a l'Energie Atomique, Departement de Protection Sanitaire, Fontenay-aux-Roses. LUND DJ, BEATRICE EA, SLINEY DH (1988). Near Infrared Laser Ocular Bioeffects. In: Procedings of the First International Symposium on Laser Biological Effects and Exposure Limits: Lasers et Normes de Protection, Paris, Court LA, Duchene A, Courant D, Eds. pp. 246-255, Commissariat a l'Energie Atomique, Departement de Protection Sanitaire, Fontenay-aux-Roses. HAM WT, MUELLER HA, WOLBARSHT ML, SLINEY DH (1988). Evaluation of retinal exposures from repetitively pulsed and scanning lasers, Health Physics, 54(3):337-344 . 5 MELLERIO J, CAPON MRC, DOCCHIO F, SLINEY D, KRAFFT J (1988). A new form of damage to PMMA intraocular lenses by DdsYAG laser photodisruptors, Eye, 2:376-381. SLINEY DH, DOLCH BR, ROSEN A, DEJACMA FW (1989). Damage to IOL's by NdsYAG laser pulses focused in the vitreous II. Mode locked lasers, J Cataract Refract Surg 14:530-532, 1988. DOCCHIO F, MELLERIO J, SLINEY DH, REGONDI P, CAPON MRC (1989). A study of laser-induced damage mechaisms in plastics used for intraocular lenses, Lasers and Light in Ophthalmology, 2(3):149-156. SLINEY DH (1990). Laser phacoemulsification: considerations of safety and effectiveness, Lasers and Light in Ophthalmology, 3(4):267-276. 6 ABBREVIATIONS cm centimetre CO-2 carbon-dioxide DF deuterium-fluoride Er erbium FDA Food and Drug Administration (US) FWHM full-width at half maximum (of a pulse) Ho holmium J Joule (also uJ and mJ for micro- & millijoule) Hz Hertz (cylces per second) HF hydrogen-flouride mm millimetre NIH National Institutes of Health (US) nm nanometre ns nanosecond Nd neodymium ps picosecond pW picowatt PRF pulse repetition frequency (in Hz) RPE retinal pigment epithelium s second (also ps, ns, jis, and ms subunits) Th thulium W Watt (also nW and mW for micro- and milliwatt) YAG yttrium-aluminium-garnet YLF yttrium-lithium-flour ide jim micrometre j i s microsecond 7 TABLE OF CONTENTS Page Title 1 Abstract 2 Acknowledgements 3 Publications 4 Abbreviations 7 Table of Contents 8 List of Tables 17 List of Figures 18 Chapter 1. Introduction and Aims 23 1.1 Background 24 1.1.1 Introduction 24 1.1.2 Principal Interaction Mechanisms 28 1.1.3 Methods of Investigating Laser Injury 31 1.1.4 Unresolved Issues 38 1.2 Thermal Interactions with Ocular Tissue 40 1.2.1 Background 40 1.2.2 Retinal Photocoagulation 41 1.2.3 Time Dependence of Retinal Injury Threshold 46 1.2.4 Nanosecond Retinal Injury Thresholds 50 1.2.5 Repetitive Pulse Injury Thresholds 51 1.2.6 Near-Infrared Laser Retinal Effects 52 1.3 Photochemical Interaction Mechanisms 55 1.3.1 Background 55 1.3.2 The Time Course of Events and Photochemically Induced Effects 57 1.3.3 Classical Photobiologic Studies 60 8 1.3.4 Photochemical Cataractogenesis 60 1.3.5 Photochemical Retinal Damage 63 1.3.6 Selective Laser Photochemical Reactions 68 1.4 Laser Induced Optical Breakdown 69 1.4.1 Background 69 1.4.2 Laser Photodisruption 71 1.4.3 Retinal Damage from Optical Breakdown Mechanisms 72 1.5 Laser Interactions with the Cornea— Implications for Refractive Surgery 72 1.5.1 Background 7 2 1.5.2 Infrared Laser Radiation Studies 73 1.5.3 Ultraviolet Laser Radiation Studies 77 1.6 Research Needs 81 1.7 Aims of the Current Study 85 Chapter 2 Historical Review of Laser Applications 88 2.1 Introduction 89 2.2 Photocoagulation 91 2.3 Photodisruption 96 2.4 Photoradiation Therapy and Photochemical Effects 98 2.5 Photoablation 99 2.6 Diagnostic Laser Applications 100 2.7 Future Applications 100 2.8 Conclusions 102 Chapter 3 Radiometric Measurements of Laser Photo- disruptors 104 3.1 Background 105 3.2 Energy Output Measurements 105 9 3.2.1 Introduction 105 3.2.2 Materials and Methods 106 3.2.3 Measurement of the He-Ne Laser 109 3.2.4 Results of Intercomparison 109 3.2.5 Conclusions 113 3.3 Detector Linearity Tests 114 3.3.1 Introduction 114 3.3.2 Materials and Methods 114 3.3.3 Results 115