The Pupil: Anatomy, Physiology, and Clinical Applications - Volume I (Cover; Introduction)

. .. - ""'"'-- . . --------- -· . " 1£ aFIi! Sil! THE PUPIL Anatomy, Physiology, and Clinical Applications A ANTERIOR CHAMBER CORNEA IRIDO RNEAL ANGLE LIMBUS CILIAR -.... ~''f;::§.i~'c·.4···'.~.:~ ·-···l.---~~ MUS VITREOUS B BODY C Iris topography. A: Horizontal section through the human eye. B: Cross-section. of monkey iris, in miosis (1), in moderate mydriasis (2), and in extreme mydriasis (3), camera obscura outlines of photomicrographs published by G.W.H.M. van Alphen. (Arch. Ophthal., Chicago, 69 (1963]:802). C: Sagittal cross-section of human iris in mid-dilation THE PUPIL Anaton1y, Physiology, and Clinical Applications VOLUME I IRENE E. LOEWENFELD, Based on cooperative work with OTrO [I§ Ph.D. LOWENSTEIN, Iowa State University Press / Ames ~ Wayne State University Press/ Detroit M.D. Irene Loewenfeld is Professor of Ophthalmology, Kresge Eye Institute, Wayne State University, retired. Otto Lowenstein was Emeritus Professor of Neuropsychiatry, University of Bonn, and Research Associate at the Eye Institute, Columbia Presbyterian Medical Center. The Pupil evolved from a work begun by Lowenstein on which Irene Locwenfeld collaborated. Upon his death in 1965, she continued research and investigation on her own and brought the work to completion. © 1993 Wayne State University Press, Detroit, Mich. All rights reserved Manufactured in the United States of America Composed and printed by Science Press Tables and illustrations provided by the author 8 This book is printed on acid-free paper. No part of this book may be reproduced in any form or by any electronic or mechanical means, including information storage and retrieval systems, without written permission from the publisher, except for brief passages quoted in a review. This publication was supported in part by NIH Grant LM 03217 from the National Library of Medicine. The work upon which it is based was supported in part by USPHS grants EY-0003 and SK3-EY-16,542. Authorization to photocopy items for internal or personal use, or the internal or personal use of specific clients, is granted by Iowa State University Press, provided that the base fee of $.10 per copy is paid directly to the Copyright Clearance Center, 27 Congress Street, Salem, MA 01970. For those organizations that have been granted a photocopy license by CCC, a separate system of payments has been arranged. The fee code for users of the Transactional Reporting Service is 0-8138-1908-3/93 $.10. First edition, 1993 Library of Congress Cataloging-in-Publication Data Loewenfeld, Irene E. The pupil : anatomy, physiology, and clinical applications / Irene E. Locwenfcld. - 1st ed. p. cm. "Based on cooperative work with Otto Lowenstein." Includes bibliographical references and index. ISB 0-8138-1908-3 (set-alk. paper) I. Pupil (Eye) I. Lowenstein, Otto. II. Title. [DNLM: I. Iris-anatomy & histology. 2. Iris-physiology. 3. Pupil-physiology. 4. Pupillary functions, abnormal. WW 240 L917p] QP476.L69 1993 611 '.84-dc20 DNLM/DLC for Library of Congress 90-5180 Book design by Edgar Frank and Joanne Elkin Kinney The Pupil draws on the research of hundreds of scholars, working in countries throughout the world, over the past centuries. The author and Iowa State University Press have made every effort to trace the ownership of all copyrighted material reprinted in The Pupil. In the event of any question arising as to the use of copyrighted material, the author and publisher, while regretting any inadvertent error, will be happy to make the necessary correction in future printings. To those who came before us and to those who will follow. May this book form a bridge between them. CONTENTS ABOUT THIS BOOK . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . • • • • • • • • ACKNOWLEDGMENTS . .................................••• • • • • • • IX xii PART ONE: Anatomy and Physiology 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. The Iris . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Spontaneous Pupillary Changes in Darkness . . . . . . . The Light Reflex. . . . . . . . . . . . . . . . . . . . . . . . . . Reactions to Darkness . . . . . . . . . . . . . . . . . . . . . . The Reaction to Near Vision. . . . . . . . . . . . . . . . . . Reflex Dilation. . . . . . . . . . . . . . . . . . . . . . . . . . . Effects of Extraocular Movements upon the Pupil. . . . Other Phenomena Listed in the Physiologic Literature: Reflex Integration: Physiologic Mechanisms . . . . . . . Reflex Integration: Pupillary Consequences. . . . . . . . Injury and Repair in the Nervous System. . . . . . . . . . ........ ........ ........ ........ ........ ........ ........ A Glossary ........ ........ ........ ....... ....... ....... ....... ....... ....... ....... of Terms ....... ....... ....... • . . . . . . . . . . 2 76 83 274 295 318 395 403 407 480 518 PART TWO: Special Fields in Pupillary Physiology 12. The Pupil as a Paradigm Example of a Neurological Control System: Mathematical Approaches in Biology, by Lawrence Stark, M.D.. . . . . . . . . 630 13. Use of the Pupil in Psychology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 648 14. Pupillary Pharmacology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 683 PART THREE: Methods 15. Methods of Pupil Testing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 828 PART FOUR: Pupillary Pathology: Symptomatology 16. Iris Damage . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17. Afferent Lesions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18. Damage to the Intercalated Pretectal Neuron: Consensual Deficit. . . . . . 19. Midbrain Syndromes: Argyll Robertson Pupils. . . . . . . . . . . . . . . . . . . 20. Midbrain Syndromes: Spastic Miosis . . . . . . . . . . . . . . . . . . . . . . . . . 21. Other Midbrain Syndromes ................................... 22. Efferent Third Nerve Deficit: Uncomplicated Oculomotor Defects ........ 23. Special Oculomotor Syndromes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24. Lesions in the Ciliary Ganglion and Short Ciliary Nerves: The Tonic Pupil ("Arlie's" Syndrome) ...................................... 25. Impairment of Sympathetic Pathways ............................ 26. Defects of Central inhibition. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 902 915 945 956 1002 1011 1025 . . . 1048 1080 1131 . . . 1188 viii 27. 28. 29. 30. / Content The' Dazzling" Syndrome" .................................. 1200 Anisocoria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1204 Wave-like and Episodic Events . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1220 Signs and Syndromes Mentioned in the Clinical Pupil Literature: Fact and Fancy ................................................ 1244 PART FIVE: Pupillary Pathology: Pupillary Signs in Various Diseases 31. 32. 33. 34. 35. 36. 37. 38. 39. 40. 41. 42. 43. 44. 45. 46. Infectious Diseases: Syphilis .................................. Infectious Diseases: Nonspecific Infections ........................ Toxic Conditions .......................................... Metabolic Conditions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Degenerative Conditions .................................... Multiple Sclerosis ......................................... Narcolepsy and Other Sleep Disorders ........................... "Dysautonomic" States . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Congenital Malformations ................................... Glaucoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Ocular and Systemic Diseases Erroneously Attributed to Sympathetic Impairment ............................................ Tumors ................................................ Trauma ................................................ Vascular Conditions ....................................... Psychiatric Conditions ...................................... The Pupils in Coma and Death . . . . . . . . . . . . . . . . . . . . . . . . . . 1266 12 2 1312 . . . . . . 1321 1345 1370 1377 . . . . . . 1382 1389 . . . . . . 1396 1419 1455 1477 1509 1553 . . . . . . 1579 BIBLIOGRAPIIY ............................................................................................ see Volume II INDEX ............................................................................................................. see Volume II ABOUT THIS BOOK Early Times In 1939-1940 Professor Otto Lowenstein rebuilt his Laboratory of Pupillography for the third time. This time it was in the Department of Neurology at New York University School of Medicine. It occupied two rooms in a building on the corner of First Avenue and 26th Street, in a run-down section of New York's East Side. Lowenstein had been interested in the pupil since the early 1920s, and after he had lost his professorship at the University of Bonn due to German political developments in 1933, he had taken up work again at La Metairie, a neuropsychiatric institute in Nyon, near Geneva. This work had been brought to an end once more as World War II approached and he emigrated to the United States. In June 1940 he bad set up shop in New York and hired as technician a 19-year-old kid who knew little about anything except some art and photography-and thus the Lowenstein-Loewenfeld collaboration began. Since up to that time I had thought that the same German political developments had barred my way to a higher eduation, it was with an unforgettable mixture of awe and delight that I climbed the worn steps of the university. Pupillary reactions have been studied for centuries. Their use in physiologic research as indicators of autonomic nervous activity began in the eighteenth century, and interest grew during the nineteenth century. Homer's (and others') description of the effects of peripheral sympathetic lesions in man (1869) and Argyll Robertson's discovery of the syndrome which bears his name (1869) stimulated and sustained it. However, the smallness of the iris, the swiftness of its movements, the impossibility of observing the pupils of the two eyes simultaneously, and a constant background of spontaneous pupillary changes made observation difficult and helped to give rise to a vast, diffuse literature, full of complex controversies. Lowenstein's work was based on the conviction that accurate, simultaneous recording of the movements of both pupils, under stable experimental conditions and with well-defined stimuli, should allow objective analysis of the responses so that given defects in the nervous network of pupillary control could be related to specific changes in the pupillary reflex pattern. In addition, he hoped, such records would reveal lesions early, before the related pupillary defects had become clearly visible to the unaided eye. By 1940, he had collected some five hundred clinical pupil records, using a motion picture technique, and as new films became available, he had graduated from blue-violet to infrared illumination so that brown as well as blue eyes could be tested in virtual darkness. During the following decades many different research projects Otto Lowenstein and Irene Loewenfeld, 1962. were done. In 1948, upon invitation by Ors. Arnold Knapp, John H. Dunnington, and Ludwig von Sallmann, we moved the laboratory to the Eye Institute of the Columbia-Presbyterian Medical Center in New York. The following seventeen years until Lowenstein's death were the happiest and most productive time at the pupil laboratory. In 1957, with the help of George King, our electronic pupillograph was developed and allowed us to experiment freely, relieved of the time-consuming measuring of pupillary records. Why and How This Book Was Written Since the early 1950s Lowenstein had thought of writing a book about the pupil. At that time we were engaged in large-scale physiologic experiments and had collected several thousand clinical records. At first our book was to be a summary of our experimental findings. But soon it became clear that a more extensive text was needed. Existing summary texts were outdated, and there was no comprehensive synthesis of the great mass of findings pertinent to pupillary functions. These observations were spread over many disciplines: "basic" sciences such as anatomy, physiology, or pharmacology as well as clinical specialties such as neurology, ophthalmology, and internal medicine. And authors in one field of inquiry commonly were unaware of facts in another field. To make things worse, each discipline had its own terminology, not readily digestible by the nonspecialist; and further, the articles were written in any of a dozen different languages. Around 1956 we thus began preparations, dividing the material between mainly clinical ix x / About This Book (Lowenstein) and mainly "basic" (Loewenfcld), and by working together on the many overlapping questions inherent in the subject matter, to arrive at an overall plan. In 1964 Lowenstein had written about three thousand pages of manuscript, tables, and graphs for the clinical chapters of the book. We were about to edit and condense this material when we learned that he was fatally ill. After his death in 1965 I found that, being a physiologist, I could not do this revising and pruning alone, without his advice and clinical judgment. But there wa no clinical neurologist or ophthalmologist with the specialized experience and the time to take over the task. I therefore spent the next 6 to 7 years reading and analyzing roughly 80% of the clinical literature in our expanding files and tracking down the chief controversie to their sources. This led me to wider fields of basic anatomy and physiology (see especially Chapters 9, 10, and 11); and under the influence of these studies the book gradually acquired an even more historical character than we had at first intended. In this regard I yielded to my natural inclination: I find disputes about complex questions most easily resolved when they are followed over the years, letting both the convincing and the inadequate experiments, both the clear and the muddled thinking speak for them elves. Also, careful consideration of what has been seen and what has been said right up to the recent past tends to prolong the usefulness of a book after some of the author's conclusions have become outdated by later findings. . I began writing the final text in 1973, about a year after I had moved the laboratory to Wayne State University in Detroit (upon Dr. Robert Jampel's invitation to the Kresge Eye Institute). At that time I hoped to complete it in about 2 years but found that much more time was required. This was due partly to the difficulties inherent in writing a large text (unexpected by a naive author who had never tried this before), and partly due to the financial difficulties affecting American universities after 1973, which made it necessary for me to work without technical or clerical assistance. A grant from the National Library of Medicine (1978 through 1980) helped me over the hump, and the manuscript was completed and turned over to Wayne State University Press in 1984. When publication was delayed due to administrative changes, it underwent two updates (the first in 1986, the second in 1988). Then, to my great delight, Richard Kinney, Director of the Iowa State University Press after having left Wayne State University Press, agreed to co-publication by the two university presses. Organization of the Book, and How It Is Meant to Be Used The book is divided into four main sections: (1) anatomy of the human and animal iris and of all other structures that are components of the pupillary reflex arcs, and physiology of pupillary reflex and other movements (Chapters 1 through 11); (2) special and applied fields of pupillary physiology, that is, mathematical modeling (Chapter 12), psychologic experiments concerned with perception, emotions, and other mental processes (Chapter 13), and pharmacology (Chapter 14); (3) methods for stimulating, observing, and recording pupillary movements (Chapter 15); and (4) clinical applications, namely, pupillary signs and syndromes (Chapters 16 to 29) and pupillary changes in different pathologic conditions (Chapters 30 through 46). These four parts are collected in Volume I of the book, with cross-references between physiologic and clinical chapters, in the hope that "basic" scientists might become interested in the clinical significance of pupillary anomalies and that clinicians may become aware of the large mass of physiologic evidence that can explain some otherwise puzzling pupillary syndromes. A review on mathematical modeling (Chapter 12) exceeded my competence. I therefore turned for help to Professor Lawrence Stark (University of California at Berkeley), the most prominent and consistent authority among investigators of this school of thought. He wrote Chapter 12, for which I am deeply grateful. The Bibliography is printed separately in Volume II to save the reader from handling some extra pounds of book while reading the text, to avoid duplication in this already oversized section, and to prevent the annoyance of constantly losing one's place in the text while looking up references. In Volume I the literature is treated chronologically in tables. Descriptions and opinions, usually given by many authors again and again throughout the years, can thus be presented fully without interrupting the train of thought of the text; and those who do not need these details can simply ignore the tables. In the text of Volume I only those publications are included that were too infrequent to form a table or that were historically interesting or otherwise important. The Bibliography contains all titles available to me at the time of writing: good, bad, or indifferent. I have been asked why I have not limited the literature to those publications I found worthwhile instead of loading down the book with hundreds of titles that should best be forgotten. Much reading has taught me that this kind of limitation of the literature may be desirable in research papers about new subjects not yet enmeshed in controversy but does not suffice to settle the matter for long-standing disputes. Throughout the history of the pupil such discussions have been perpetuated by a relatively small number of authors with an unfailing attraction for faulty assumptions and misinterpretations, brought forth with much vigor and stuck to tenaciously in the face of the most convincing evidence to the About This Book contrary. Usually these writers had no trouble coming up with a few dozen citations said to support their claims. UnJess these are analyzed critically to reveal their shoddy base, the argument revolves from decade to decade until its very bulk impedes clear thinking. On the other hand an inferior paper may contain an important fact, even if the author was not aware of its meaning and had drawn erroneous conclusions. Further, many times a correct finding has been forgotten or ignored by later authors, erasing history by carelessness or ambition. Long lists of repetitive findings are not without value: an observation made seventy-eight times by competent investigators appears more convincing than an observation mentioned just once in a cursory note. Omitting the bulk of earlier work while presenting the same facts as one's own because they are now, supposedly, corroborated "with modern methods': not only is dishonest but tends to weaken rather than strengthen support. As shown by some of the tables of this book, careful study of previous authors' statements may indicate how certain trains of thought evolved with time and may reveal the sources of insight or of confusion. I have tried to render the literature accurately and to weigh different facts and theories without curtailing those that argued against our views. But I have maintained a critical stance and have stated my personal conclusions. Complete objectivity changes a text into ·an annotated bibliography, drained of life and confusing to all except experts in the field. And while some of my conclusions undoubtedly will be disproven or modified by findings not yet available, I believe it behooves an author to take a stand. I am grateful to my friends for having toned down my wrath on occasion. In Stan Thompson's words: "It is enough to shoot down an author; you don't have to hop up and down on the corpse." Because of the history of this book, I have not been consistent in the use of the words we and J. I have used we and our when referring to experiments or theories I remember having discussed with Lowenstein or other co-workers, and the word I when I alone was responsible. While typing the Bibliography in Volume II, I realized that a certain number of citations were not limited to the pupils, or not directly concerned with them at all. They had to do with structures such as the retina, various nerves, or areas of the brain that form part of the pupillary pathways but were studied mainly in their relation to other functions (vision, extraocular movements, and so on). Or they dealt with fundamental processes such as growth and ageing or the effects of injuries upon neurons, but the work was done using other effectors (nictitating membrane, blood vessels). Since the results of these studies are vital to an understanding of parallel pupillary mechanisms, I felt they must be included. On the other hand, I did not relish the thought of being accused of having inflated the Bibliog- / xi raphy beyond strict bounds. I theref?re decided_ to mark these citations as not concerned with the pupils per se (i.e., "no pupils"), adding a note about their contents (if not evident from the title) and where they were used. I must admit that annotation--once started-proved irresistible during the monotonous task of typing the Bibliography so that some expressions of admiration or of irritation slipped through. Rendering the Bibliography in full also seemed necessary to indicate to the reader which parts of the literature I have read ( entirely, in part, or in abstract) in order to show what source material influenced my thinking. We decided to place the Index in Volume II for the same reasons the Bibliography is assembled there, namely, to slim down Volume I, to keep all supporting material in Volume II, and to avoid the annoyance of constantly losing one's place in the Index while looking up various subjects in the text. The book is designed as a reference text for readers with different interests and at different levels of expertise: (1) students who have been confused by the controversial literature and want to inform themselves about the main features of given phenomena, (2) physicians who see patients with pupillary syndromes and want to read about these, and (3) investigators in clinical or basic sciences who need a comprehensive reference with an extensive bibliography. To accommodate these different kinds of readers, the book is written on three levels. First, each chapter is headed by a thumbnail summary, designated by a grey band in the margin. It is short and dogmatic, and no reasons or detail are given (i.e., "This is all if you want to take our word for it"). For readers who venture on to the main text it probably is preferable not to read the summaries immediately before. I, at least, have disconcerting feelings of deja vu when a summary and the corresponding chapter are read immediately in succession. Second, the main text contains more elaborate descriptions, together with the historical background and with discussions about the mechanisms at work. And third, additional detail that is nice to read about, proves a statement, or is indirectly related to the matter at hand, is printed in sections with shorter lines (i.e., "You can skip this if you are in a hurry"). Further, each chapter is provided with a fairly detailed table of contents to help the reader to find certain information or to skim through in order to decide which part to read in summary or in full. The tables of content also serve to simplify the Index in that they list-in logical order-all structures and mechanisms that are dealt with in particular in a chapter. These structures and mechanisms thus need to be listed in detail in the Index only when they are discussed in chapters other than the ones devoted to them specifically. I hope that this treatment, together with the use of deliberately numerous titles and subti- ,. xii / Acknowledgments ties, will mitigate the frightening aspect of a large text. It is dismaying to have to plow through pages and pages of solid text in order to grope toward a given fact or conclusion. Throughout the book I have tried to keep specialized words to a minimum, and have avoided abbreviations altogether. These save virtually no space and serve only to confuse all but those to whom the shoptalk of their own field has become second nature. For literature citations my abbreviations do not follow any of the modern lists because none of these cover more than about half of the journals used. Instead (with the help of Irene Skolnick), I have developed a hybrid system that combines the features I liked best of the World List of Scientific Periodicals (4th edition, 1963) and of World Medical Periodicals (3rd edition, 19611963). This system is described in the Introduction of Volume II. ACKNOWLEDGMENTS This book is based upon studies that stretched over most of Otto Lowenstein's and alJ of my professional life, and preparations for the manuscript from start until publication from the mid-1950s to the present. Clearly, it is impossible to thank in detail all those who helped us by their friendship and support and by direct action during this long period. Those whose work with one or with both of us has resulted in publications included A Westphal in Bonn (1927-1933); at New York University (1940-1948, in alphabetical order) E.D. Friedman, Kenneth Gang, Isadore Givner, AS. Levine, N.S. Jaffee, and Mark J. Schoenberg; and at the Columbia-Presbyterian Medical Center in New York (1948-1972, also alphabetically) Ronald Altman, Peter W. Carmel, Richard Feinberg, Ira S. Jones, Heiichiro Kawabata, George W. King, Lillian Kumnick, Sean D. Murphy, David A Newsome, Heinz Rosskothen, Shinji Oono, Ludwig von Sallmann, and H. Stanley Thompson. During my stay at the Kresge Eye Institute in Detroit (1972-1989), R.P. Friedlaender and Pauline F.M. McKinnon worked with me, and Albert Kirby, Jr. did the experiments on latent periods with me, which were not published until now (see Figures 3-54, 3-55, and 3-57). Among those who worked with us informally on various experiments were M.A. Kennard, who allowed us to study her fascinating decerebrate cats (see Figure 3-93); Ernst Simonson (University of Minnesota), with whom we shared many years of common interest in problems of fatigue and arousal (Chapter 10); Gertrude Rand (at the Columbia University Eye Institute), who never lost patience answering questions about optics and who allowed us to study her patients with albinism (Figure 16-3); Arthur Linksz (New York), my steady anchor when I ventured with trepidation into problems of vision (Chapter 3); William S. Masland, with whom we collected cases of diabetes during his stay at the Neurological Institute of Columbia University (Chapter 34) and whose sunny presence cheered me during a most difficult time; Peter W. Carmel (neurosurgery, Columbia University), with whom we studied interesting neurosurgical patients with sympathetic deficits due to rostral brainstem lesions (Chapters 6 and 25) and whose keen questions never failed to demolish a wobbly conclusion ("thin ice"); Robert S. Jampel, who had let us observe his interesting experiments on the monkey brain for years (Figures 3-79 and 5-6) and who allowed us to examine patients with oculomotor defects during his time at the Columbia Eye Institute; Myles M. Behrens, who immersed himself in pupillary matters when he took over from Jampel as neuro-ophthalmologist at the Eye Institute and who has conscientiously taught his many excellent Fellows how to discover and interpret the clinical pupil syndromes encountered in practice; Richard Feinberg, who continued our common studies on pupillary functions as related to vision, age, and tiredness at the Federal Aviation Agency in Bethesda, Md. (see Figures 3-47, 22-13, and 43-15, and Chapter 10); and David A Newsome, who worked with me on iris mechanics (Chapter 9) and on the behavior of pilocarpine (Chapter 14). In Detroit, Natraj Sitaram (Department of Psychiatry, Wayne State University) extended to me the hospitality of his Department of Affective Disorders at the Lafayette Clinic, for cooperative studies in psychopharmacology. He also introduced me to the language of computers in a clinical setting. John Grabowski and I spent many happy months on this work, in harmonious collaboration. Our dear friend Heiichiro Kawabata stayed almost two years with us (1958-1959). He had previously studied light-induced iris action potentials (Table 3-17) and the electroretinogram (Figure 4-13). Among other work, he took part in our pupillary experiments concerned with vision, which are described in Chapter 3. Shinji Oono worked with me for two years, just before and after Lowenstein's death. He helped with our many, interminable pharmacologic experiments (see Chapter 14), and after his return to Japan has continued with interesting pupillary studies, both basic and clinical, up to the present. Acknowledgments Others among our friends also continued work at their home in titutions, building up laboratories which soon buzzed with re earch, clinical work, and teaching. Although ome were far di tant, they all enriched our lives by keeping up firm cordial relations and active exchange of information with us over many years. They are listed chronologically. Giulio Morone collected much work and a great deal of literature in his large text La Pupilla (1959) and with his collaborators at the University of Pavia (F. Andreani, G. Berlucci, G. Bietti, I. Borsotti, V. Cima, M. Citroni, P. Marucci, A. Nicolato, A. Sano, F. Trimarchi, and L. Venco) produced many pupillary studies from the 1940s to the present. Gad Hakerem found us across the garden during his time at the Psychiatric Institute on 168th Street in New York, and has remained a friend since. His meticulous work, and that of his fine co-workers and students, demonstrated how sensitive and reliable pupillary reactions can be for identification and quantification of mental processes (see especially work with J. Friedman, S. Kugelmass, A. Lidsky, S. Levine, S.R. Steinhauer, S. Sutton, and everyone's fatherly teacher, J. Zubin, in Chapters 3 and 13). C.W. Rucker introduced our electronic pupillograph to the Mayo Clinic shortly after its completion (1959). The Mayo Pupil Laboratory has since enjoyed many busy and productive years, used by a large group of investigators, including Richard F. Brubaker, J.W. Henderson, R.W. Hollenhorst, Theodore G. Martens, F.C. Riley, J.C. Trautmann, and especially the steadfast and skillful Norma-Jean Moyer as well as Robert E. Yoss and Kenneth N. Ogle and his Fellows (W.D. Baacker, D.W. Burke, S. Lowe, S.S. Morgan, R.A. Whisnant). Some of these experiments are shown in Chapters 3, 5, 29, and 37. Close by, in the Mayo Clinic Department of Neurosurgery, F.W.L. Kerr and his co-workers did their masterful experiments on the efferent path of the light reflex and the descending sympathetic pathways in the brainstem (see Figures 3-94, 6-32, 6-33, and 6-34). Lawrence Stark had been interested in mathematical analysis and computer modeling of pupillary movements ever since his residency at the Columbia-Presbyterian Neurological Institute, when he first visited our laboratory. His work has attracted a large number of bright and active young physiologists, engineers, and mathematicians to this field. He has remained our kind and helpful friend (despite my woeful lack of talent for cybernetics) and has generously taken the time to write Chapter 12 of this book, which deals with the subject (see also Figures 3-34, 3-51, 3-92, 4-14, and Table 3-20). H. Stanley Thompson came to our laboratory in 1962 as Alson Braley's Pre-Resident Fellow, preparing to introduce pupillography to the University of Iowa Hospitals (Ophthalmology). During the following years his pupil group has flourished there, in alliance with the Department of Neurology (M.W. Van Allen and James J. Corbett). With the collaboration of many colleagues and Fellows (at least 55 co-authors by my count), the Iowa pupil laboratory has become the most productive of all (see / xiii the Bibliography). After Lowenstein's death Stan most unselfishly took almost three months of his crow?ed time helping me to pick up the pieces for t~e orga~ization of this book. Our collaboration on vanous projects has continued since, with clinical and experiment~! material, experience, and plans shared. Some of his work is included in Chapters 3, 17, 22, 23, 24, 25, 29, 32, 35, and 40. I am especially grateful to those friends who too~ ~he trouble of reading various portions of the book, g1vmg many helpful suggestions and doing much-needed pruning. These were Peter Carmel, Bill Masland, Gad Hakerem, Stan Thompson, and Jim Corbett (already mentioned) as well as H. Saul Sugar (Detroit), Michael C. Koss (pharmacology, University of Oklahoma), Fred Zwas (visual physiology, Kresge Eye Institute) and Shiro Usui (Toyohashi University of Technology in Japan). We are indebted to our own Home Universities, especially the Eye Institute of the Columbia-Presbyterian Medical Center in New York, where the bulk of preparations were done in an atmosphere of good will, and with complete freedom for research, thanks largely to Dr. John H. Dunnington's (and later Dr. A Gerard DeVoe's) kindly protection. I am also grateful to Dr. Robert S. Jampel at the Kresge Eye Institute of Wayne State University for having given me time-so much longer than we had expected-to shape the unwieldy mass of material into a workable manuscript, and for having used departmental funds to help with the book's high cost of production. Preparations for the book were also funded by grants from the Harriman Fund in New York (1948-1972) and from the National Institutes of Health (Numbers NB-00253, later EY-00003 [19531972], and K3-EY 16,542 [1963-1972]. At Wayne State University a grant from the National Library of Medicine (LM-0327) helped with completion of the manuscript and with publication costs. Since the book is based on history, we have used many illustrations published by others in the past. We thank all the publishers who generously allowed us to reprint these pictures. Most important in any endeavor such as this book are those who worked with the authors on a daily basis. Some took part in the work of the laboratory that laid the groundwork upon which the book could grow. Others were involved in its actual production. Among the first group, Lowenstein surely would have wanted me to mention Matthias Hoppe, who constructed the early pupillographs in Bonn before 1933 (see Figures 15-37 through 15-39) as well as his secretary, Margarete Weicht, and his technician, Mr. Driessen, who both courageously followed him to Switzerland in 1933 so that he could resume work without delay. In New York, Helen Lang took over as his secretary, presiding as the good spirit of orderliness among his many papers and manuscripts. At the Eye Institute, Margaret Kane, the departmental secretary and the best-organized person I ever met, always knew which administrative job I had xiv / Acknowledgments done wrong and how to fix it. In Detroit, Mary (Molly) Morrison, departmental secretary, and Lee Sutton, Dr. Jampel's research assistant, out of the goodness of their hearts helped me over many difficulties. In the laboratory (in chronological order) Eric Klapper, Halyna Maystrenko, James Goode, Mary Bacchi (Haunold), and Barbara Smith (Goode) helped us, making the place happy and busy with their hard work and friendly companionship. I owe special thanks to James Goode, whose unfailing, considerate support helped me during the difficult time during Lowenstein's illness and after his death. Barbara and James Goode also helped me in drawing and labelling the many illustrations for the clinical chapters of the book. At the Lafayette Clinic in Detroit, Julie Geist assisted in difficult experiments and saved me from the idiosyncrasies of the computer. Siri Jayaratne carried on the population study we did in New York (1969-1971) with patience, ingenuity, and good humor, and Brian Wantuck continued this work (1971-1973) with great energy and resourcefulness. Harvey Witover, and later Heinz Rosskothen, saved us frustration by skillful construction and modification of instruments. Besides other fine machine work, Harvey built the cinematographic pupillograph shown in Figure 15-41, and Heinz the population-survey camera of Figures 15-28 through 15-31. Entirely new advances in technique resulted from the work of Semyon Krewer, who designed our electronic film-measuring machine (built in 1943 to 1945, Figures 15-48 to 15-51). It not only saved time by allowing relatively fast processing of filmed pupillograms, but showed us the optical conditions obtainable with low-intensity infrared light in about 2000 patients, under clinical conditions. These results led to the development of our electronic pupillograph, designed and completed by George King in 1957 (Figures 15-56 through 15-59). This instrument, still in use after 33 years, has never failed us and has extended our work to many times what could have been done without it. During the years in Detroit, Carl Vette helped by maintaining it in good health. The staff of the Columbia-Presbyterial Medical Library, and the libraries of the Neurological Institute, the Psychiatric Institute, and the Eye Institute were helpful, checking out shopping-cart-loads of books we would borrow a few times a week. In addition, Harold Bloomquist of the Medical Library spent much time pinning down some of the old Latin references. Eloise Crowley (Morehouse) worked a full year patiently and meticulously checking thousands of references against the library originals (see the Bibliography). Vera Ortynsky and Irene Skolnick helped with this work, verifying or obtaining many of the more elusive titles with their librarians' skills. Irene would sniff out obscure publications with bloodhound tenacity. She also collected a large file of the often complex history and interrelations between journal series, some of which had baffled us. This information allowed us to settle upon a style of abbreviations for the bibliography that extended and simplified the rules of existing lists. Several people took part in the production of the book. In Detroit Leslie Leach helped me to complete the pharmacologic chapter by digging up the multitude of working names, chemical names, and trade names for various drugs, helping me to order these into tables (see Chapter 14), and by advising me on numerous points. Kathy Morehead copied most of the illustrations from the originals and from books with great skill and patience. Barbara Tilly taught me word processing for the Bibliography and then rescued me whenever the computer tried to wipe me out. Jean Owen edited the text of Volume I, and Susie Sims the figure legends with their frustrating citations. In Ames, Iowa, Marilyn Keller with eagle eyes spotted remaining errors and inconsistencies in the manuscript, and Joanne Kinney designed the book. Stanley Thompson, wearing his hat as neuroopthalmic historian, and using the superb library at the University of Iowa, found and copied many of the portraits reprinted in Volume II. During the time I wrote the text in Detroit, Richard Kinney, then Acting Director of the Wayne State University Press, encouraged me whenever I lost courage, with his steady, kindly, good humored understanding. I don't know how I could have persevered through these years without his help. After he left the WSU Press to become Director of the Iowa State University Press, Alice M. Nigoghosian, Assistant Director and later Acting Director of the WSU Press, went to much trouble to advance publication. After many difficulties, she and Richard Kinney succeeded in arranging for joint publication by the two presses. They deserve the credit of having kept the book from shriveling on the vine. It is hard to find words to express our indebtedness to everyone named, and to others too numerous to be mentioned here. They gave us joy by their fellowship, and they added spice to our pursuits by their interesting thoughts and findings, their challenging questions, their healthy criticism. They invested time from their lives to support our work and to help this book to completion. Our thanks to all. Some of our old friends are no longer living, and it is with bitter regret that I find myself unable to place the book in their hands, or in Lowenstein's hands. But could I do so, I hope they would approve. Throughout the many years of preparation and writing of this book, and during the seemingly endless heartbreak and frustration of the publication process, my sisters, Anne M. Neustaetter and Eva M. Goldschmidt and their families, have stood by me with patient, understanding, and loving support.