H. Stanley Thompson, the son of Irish missionaries, was born in China. He was educated in China and Ireland and spent the World War II years in a Japanese concentration camp in northern China. After the war, he returned home to Belfast, Ireland, and then, in 1949, he emigrated to the United States. He spent 2 years in the U.S. army as a photographer and then earned BA and MD degrees at the University of Minnesota.
Dr. Thompson's career in neuro-ophthalmology is intertwined with the history of neuro-ophthalmology at the University of Iowa, the subject of his Jacobson Lecture. Being a man of great humility, Dr. Thompson is quick to give credit to his associates and colleagues; but do not be fooled, as he is also an individual of great intellect, and his contributions to neuro-ophthalmology have been tremendous.
Dr. Thompson has published more than 200 manuscripts, many about making careful use of pupillary signs during routine clinical examination. When ophthalmology residents learn about various pupillary signs and pharmacologic tests, they assume that this body of knowledge has been around for at least a hundred years! They are astonished to discover that many of them were emphasized or introduced into clinical practice by Dr. Thompson. One such example is the diagnostic algorithm dealing with anisocoria (1).
In addition to his contributions to neuro-ophthalmology, Dr. Thompson has found time to serve his profession on the American Board of Ophthalmology, the board of the North American Neuro-Ophthalmology Society, and the International Neuro-Ophthalmology Society. He has attended the International Pupil Colloquium since 1963, not missing a single meeting in 44 years, and he has hosted the meeting twice.
Dr. Thompson has been married for 60 years, and he and his wife, Delores, have raised 5 children and have 8 grandchildren.
THE EARLY YEARS
When Cecil O'Brien started the Ophthalmology Department at the University of Iowa in 1928, ophthalmology had just been separated from the Ear, Nose, and Throat Department by L. W. Dean, the Dean of the Medical College. The Dean had been running the EENT department for 20 years without much enthusiasm for the eye side of things. Dr. O'Brien started his teaching program in ophthalmology in the new University of Iowa Medical Center in 1929. At first there were no subspecialty clinics, and O'Brien hired a few professors to help him teach general ophthalmology. One of them was Dr. Placidus Joseph (“P.J.”) Leinfelder, who was to become the University of Iowa's first neuro-ophthalmologist; he came to Iowa City from the University of Wisconsin in 1930, to be one of Dr. O'Brien's ophthalmology residents. When he finished his residency in 1934, O'Brien asked P.J. to join his faculty as an instructor (Fig. 1).
When, in 1938, O'Brien asked P.J. to head a “neuro-ophthalmology” section in the department, Leinfelder resisted. Dr. Leinfelder always thought of himself as a general ophthalmologist and did not want to call himself a “neuro-ophthalmologist.” Like others of his era, he felt that the term implied that he was neither a neurologist nor an ophthalmologist. Nevertheless, O'Brien went on to brag about the “neuro-ophthalmology” section in his department, and the term eventually became popular. The word was used as a book title by Lindsay Rea (1938), Donald Lyle (1945), Alfred Kestenbaum (1946), and then by Frank Walsh in 1947. There is no doubt, however, that Leinfelder was indeed interested in what we now call “neuro-ophthalmology.” His American Ophthalmological Society thesis, accepted in 1938, was on “Retrograde degeneration in the retina and optic nerves.” He gave courses at the Annual meeting of the American Academy of Ophthalmology (AAO) on neuro-ophthalmic topics from 1937 to 1969. During those same years, his talks to various Midwest state medical societies resulted in publications such as “Papilledema and optic neuritis,” “Misconceptions in neuro-ophthalmology,” “Why test visual fields?,” and “The diagnosis and treatment of ocular neuroses.” Leinfelder continued to do general ophthalmology and cataract surgery but, for the next 30 years, he really was the only member of the Iowa Eye faculty who undertook to help residents with neuro-ophthalmic problems.
Dr. Leinfelder retired in 1971, at age 68, but stayed in the department part-time for another 5 years, taking care of some of his old patients who had known no other ophthalmologist for 30–40 years, making himself available to the residents, and serving as the voice of experience at department faculty meetings. P.J. was a model for all retiring professors—wise, alert, ready with sound advice but not offering it until it became perfectly clear that all of us young fools were going to keep blathering along without ever getting to the heart of the problem. He was kind, avuncular, and approachable, and during those years, he earned from the residents their deepest respect for his knowledge, clinical wisdom, and humanity (Fig. 2).
THE THOMPSON YEARS
In 1966, Dr. Fred Blodi was about to become the new head of the Ophthalmology Department, and he knew that one day he would need to find a replacement neuro-ophthalmologist. I was just finishing my residency in the Department and had some interest in pupil function and in neuro-ophthalmology. In fact, I got hooked on the pupil quite early: I was in medical school in Minneapolis in 1957 when Walsh's second edition of Clinical Neuro-Ophthalmology (“Big Red”) appeared. This is the work that, in later editions, was to become “Walsh and Hoyt,” which today is the gold standard for neuro-ophthalmology texts. I had never before seen a medical book so tightly packed with fascinating details. It soon persuaded me that there was enough material in neuro-ophthalmology to last me a lifetime.
Dr. Blodi, who had known the pupil experts Otto Lowenstein and Irene Loewenfeld when he was at Columbia University in New York, saw Loewenfeld at the AAO meeting at the Palmer House in Chicago in 1962. She was demonstrating her new infrared device for continuous recording of both pupils in dark and light. Blodi invited Loewenfeld to visit Iowa City to talk to the Eye Department about her research. I was fascinated and expressed an interest in working with that device. Dr. Blodi and Dr. Maurice W. van Allen of the Neurology Department were, at that moment, applying for National Institutes of Health (NIH) research funds to support a “Neurosensory Center” in Iowa. So soon there were plans to incorporate a Pupillary Research Lab into the University of Iowa Neurosensory Center.
In preparation for this center, Drs Blodi and van Allen purchased a new “electronic pupillograph,” developed by Lowenstein and Loewenfeld. Loewenfeld requested that I go to New York for 3 months to learn some of the intricacies of pupillography. This was arranged, and I worked at pupillography until I finished my residency. Blodi's hope was that I would return to Iowa after spending a year doing a neuro-ophthalmology fellowship with Dr. William Hoyt; and that was indeed the way it worked out. I suspect that Dr. Blodi called Dr. Hoyt and said “You want someone who'll work on your new pupil chapter?”
At the end of my residency in Iowa, I had been working on a pupillographic demonstration of differences in pupillary input between the 2 eyes (2). This observation had a long history. It had apparently been obvious to Galen in the second century CE, that covering both eyes and then uncovering them one at a time, gave information about the potential for vision in each eye, and Galen refused to couch a cataract in an eye that, when uncovered, failed to show a good pupillary constriction. More recently, Marcus Gunn, Kestenbaum, and Levatin had all emphasized the clinical importance of this sign. Dr. Hoyt and his subsequent fellows began to say “relative afferent pupillary defect,” to emphasize the comparison of the pupil reaction in the 2 eyes.
In 1966–1967, Robert Hepler and I were Hoyt's fellows. We were all working on the third edition of Walsh's book, and Hoyt came in every morning with some new gem of knowledge to pass along. At the end of my fellowship in the summer of 1967, Dr. Blodi had just become the new chief at Iowa, and I returned to Iowa City to join the University of Iowa faculty as a neuro-ophthalmologist. When I arrived back to Iowa City, Dr. Blodi said to me “We don't have clinic space for you yet, so just start seeing some patients in the general clinic, and we will send you all the neuro-ophthalmology patients that come along” (Fig. 3). This led, very quickly, to an active “Neuro-ophthalmology Clinic.”
Starting in 1968, ophthalmology residents began doing a 3-month full-time rotation in the Neuro-ophthalmology Clinic, and since 1971, there has been a steady flow of Neuro-ophthalmology fellows through the service (Fig. 4).
In 1969, I objected to the use of the word “hippus” to describe the behavior of the pupils in patients with Cheyne–Stokes respirations, where the pupils became small in the alarming apneic phase and then enlarged as the patient started to breathe again. This led to a pursuit of the elusive word hippus and resulted in an article done with the help of my sinologist brother Paul, and Albert Franceschetti (3).
In 1971, it seemed worthwhile for me to emphasize that a unilateral fixed dilated pupil due to local atropinic action could be quickly distinguished from a neurogenic mydriasis with a drop of pilocarpine (4). In those days, Iowa cornfields were often contaminated with jimson weed, a plant that is rich in belladonna alkaloids (5).
Throughout the 1970s, I continued to be interested in Adie syndrome. I emphasized that there was a characteristic slit-lamp sign: a regional palsy of the iris sphincter in many patients. Sometimes an odd, back and forth, crawling illusion could be seen called “vermiform movements.” When Sattler brought attention to these, “Wurmförmige Zuckungen” in 1911, there was a great deal of head scratching and speculation about their significance. In retrospect, these odd movements may have been nothing more than physiologic hippus in a section of the iris that was still normally innervated (6).
Also at this time I was reviewing possible mechanisms of adrenergic mydriasis Horner syndrome. John Mensher, MD, and I described the utility of topic hydroxyamphetamine drops in differentiating a preganglionic from postganglionic lesion (7).
In 1972, a few months after returning from 6-month training in London at the National Hospital for Neurology and Neurosurgery, Queen Square, I started taking one neuro-ophthalmology fellow per year (see Supplemental Digital Content, Table 1, http://links.lww.com/WNO/A90).
The demand for neuro-ophthalmology service was growing steadily so that, in 1977, James Corbett, a Philadelphia trained neurologist who, like me, had done a fellowship in San Francisco with Dr. Hoyt, joined Dr. Van Allen's Neurology Department at the University of Iowa as a neuro-ophthalmologist. Dr. Corbett came to the Eye Department every morning for our daily “neuro-ophthalmology rounds,” and on certain days he staffed the Neuro-ophthalmology Clinic all day. This was a great addition to our Neuro-ophthalmology Service leading to a very effective and productive long-time collaboration. I continued my interest in the workings of the pupil, and Dr. Corbett became expert in pseudotumor cerebri.
This Thompson–Corbett team ran the Neuro-ophthalmology Clinic from 1977 to 1990 (Fig. 5). We held our daily Neuro-ophthalmology rounds 5 days a week at 9:00 AM, just after the Eye Department's “morning rounds.” These daily “service rounds” continue today.
It was, and still is, a teaching and reviewing session that went on for about an hour before we saw any new patients. We reviewed the patients seen the previous day and made suggestions about their follow-up studies. Sometimes we arranged for some visual fields to be done and went to the coffee shop where we spent half an hour reviewing cases and sometimes discussing on-going research projects.
In 1977, we organized a symposium in Iowa City that covered 5 separate areas of neuro-ophthalmology. Each section was set up and run by a Hoyt-trained neuro-ophthalmologist: Lars Frisen, visual fields; Stan Thompson, pupils; Joel Glaser, optic nerve disease; Robert Daroff, eye movements; Michael Sanders, computed tomography. The presentations were published in 1979 as Topics in Neuro-Ophthalmology (8).
In 1984, a first-year ophthalmology resident named Randy Kardon, who had done a PhD in pharmacology as one of the first combined Medical Scientist Training Program MD–PhD students at the University of Iowa College of Medicine, started his research with the premise that the “visual field” could be mapped using pupillary reactivity as an indicator—something that no one had yet done with fundus-based perimetric instrumentation. We made a bold, and, for us, very instructive, preliminary effort, which formed the basis for the next step, gathering quantitative pupil data.
The most important outcome of this project was that after his residency, Dr. Kardon obtained grants from Fight for Sight and Research to Prevent Blindness to continue this work on pupil perimetry and stayed in Iowa City to take a clinical fellowship in Neuro-ophthalmology with Thompson and Corbett while continuing this research. During these very active clinical and research years in the 1980s, we had a number of outstanding fellows, including Dan Jacobson and Kathleen Digre (Fig. 6).
In 1989, Randy Kardon joined the Iowa faculty. He continued to work with pupillary projects and became an active clinical neuro-ophthalmologist, and a much-admired and busy investigator. He was the first ophthalmologist to receive a Career Development Award through the Department of Veterans Affairs. This was later renewed for a second cycle, and it supported his salary and research during his first 9 years on the faculty. This was followed by continuous extramural funding from the Department of Veterans Affairs (VA), Department of Defense, and NIH, which helped define a new model for how a group of academic neuro-ophthalmologists at Iowa could work together in both clinical and research endeavors and receive extramural financial support. In 2008, in recognition for his ongoing research and clinical contributions to neuro-ophthalmology and to the University of Iowa, Dr. Kardon was named as the inaugural appointee to the Pomerantz Family Chair in ophthalmology; thanks to a 2 million dollar gift from the Marvin Pomerantz Family to support research and clinical excellence in neuro-ophthalmology and to find cures for vision loss.
In 1990, after 13 active years on the faculty at Iowa, Dr. Corbett received an attractive offer to become the chair of the Neurology Department at the University of Mississippi in Jackson, MS, and moved to Jackson in July 1991. Dr. Corbett and Dr. Kardon continued to collaborate on a number of projects and published together even after 1991. Dr. Corbett has returned to Iowa numerous times as a lecturer or visiting faculty.
Michael Wall joined the Neurology Department as a neuro-ophthalmologist in 1991, after 10 years at Tulane University, and about 2 months after Dr. Corbett left for Mississippi. Dr. Wall's research was a good fit for Iowa as like Dr. Corbett, one of his main interests was idiopathic intracranial hypertension (IIH). While at Iowa, he has gone on to direct the National Eye Institute–sponsored Idiopathic Intracranial Hypertension Treatment Trial. The goal of this trial is to identify the cause of IIH and to develop evidence-based treatment strategies for the disease. He has also been an investigator in other multi-center investigations, including the Optic Neuritis Study Group. Dr. Wall's other area of research is studying mechanisms of perimetric variability. While at Iowa, he has developed motion perimetry and has identified using larger kinetic stimulus sizes as a way to reduce variability. This research has been funded since 1994 with a VA Merit review. He has been active in the International Perimetry Society (now the Imaging and Perimetry Society) serving as its President for 8 years and was a leader in the group drafting standards of perimetry practice. Dr. Wall has published extensively on such topics as variability and dynamic range for peripheral visual stimuli of various sizes, IIH, comparisons of sensitivity and specificity of different types of perimetry in disorders, such as glaucoma, homonymous hemianopia, and optic nerve and chiasmal disorders.
After 30 years on the Eye Department faculty (1967–1997), Dr. Thompson retired, to devote himself to projects dealing with the history of ophthalmology, and Dr. Kardon became head of the Neuro-ophthalmology section.
In 2004, the Neuro-ophthalmology Clinic was named “The H. Stanley Thompson Neuro-Ophthalmology Clinic” (Fig. 7). Under Kardon's direction, both the clinical practice and the associated research have grown vigorously.
THE POST-THOMPSON YEARS
Dr. Kardon's recent research has involved using the pupillary light reflex to measure rod, cone, and melanopsin-mediated responses. He and his colleagues also have measured electromyography of the orbicularis oculi muscle and skin conductance in patients to characterize photosensitivity. Much of this work stems from Dr. Kardon's role as the Director of The Iowa City VA Center for Prevention and Treatment of Vision Loss. This Center is funded by the Department of Veterans Affairs to study optic nerve and retinal disorders that have relevance to the military population, especially in relation to traumatic brain injury. Kardon concentrates a good deal of his research and clinical efforts on visual disorders related to traumatic brain injury, especially the neuroprotection and treatment of vision loss and the detection, monitoring, and treatment of ocular and central nervous system diseases. The Neuro-ophthalmology service has seen the addition of several faculty members under the direction of Dr. Kardon.
The Neuro-Ophthalmology service has seen the addition of several faculty members under the direction of Dr. Kardon. Dr. Andrew G. Lee moved to Iowa City from Houston, TX, to join the neuro-ophthalmology faculty in 2000. His wife, Dr. Hilary Beaver practiced in our Comprehensive Ophthalmology Service and also was the director of medical student education. During his time in Iowa, Dr. Lee was very active clinically and also published in several areas of neuro-ophthalmology, including IIH, giant cell arteritis, Leber hereditary optic neuropathy, Charles Bonnet syndrome, infectious neuroretinitis, and neuroimaging. Dr. Lee showed considerable interest in and an aptitude for teaching residents. He was extensively involved in the development and implementation of the Accreditation Council for Graduate Medical Education residency competencies at the University of Iowa and in publications regarding the competencies. In March 2009, Dr. Lee returned to Texas, accepting a position in Houston as Chairman of Ophthalmology at Houston Methodist Hospital where he is a Professor of Ophthalmology, Neurology, and Neurosurgery at Weill Cornell College and on the faculty at Baylor College of Medicine (Adjunct Professor), The University of Texas Medical Branch, Galveston, TX (Clinical Professor), and the UT MD Anderson Cancer Center. Dr. Lee is still an adjunct professor with our Ophthalmology Department at Iowa.
In 1999, Chris A. Johnson, PhD, came to Iowa from Devers Eye Institute and the Discoveries in Sight Research Labs in Portland, OR At first glance, a PhD in Psychology seems an unlikely addition to a neuro-ophthalmology service, but, in fact, Dr. Johnson's expertise in visual fields was a natural fit. Dr. Johnson had more than 20 years of experience in developing and managing visual field reading centers at several locations before his arrival at the University of Iowa. He has published extensively on many topics related to visual fields and has had more than 30 years of research funding from the National Eye Institute and other extramural sources. His research interests include perimetry, visual field testing and psychophysical evaluation of eye diseases, development of automated diagnostic test procedures, imaging and topography of the optic nerve head and retinal nerve fiber layer, visual factors related to task performance in transportation/aviation and industry, and motion and flicker perception. He has established a Visual Field Reading Center at the University of Iowa, which evaluates, documents, and stores visual field results from multicenter trials.
In July of 2007, Dr. Steve Stasheff joined the Pediatric Faculty in Neurology with a joint appointment in ophthal-mology. Dr. Stasheff completed residencies in pediatrics and pediatric neurology followed by a postdoctoral fellowship in retinal neurophysiology. He simultaneously completed a neuro-ophthalmology fellowship at Beth Israel-Deaconess Medical Center and New England Medical Center under former Iowa neuro-ophthalmology fellows, Jason Barton and Thomas Hedges, III. Before moving to Iowa, Dr. Stasheff was an instructor at Harvard Medical School/Children's Hospital-Boston/Beth Israel-Deaconess Medical Center in Boston. He sees neuro-ophthalmology patients in the Ophthalmology Department with a special interest in pediatric neuro-ophthalmology and serves as the Medical Director of the Electrophysiology Service in the Eye Department. He has published articles on retinal vs optic nerve disease, cortical visual deficits, ocular motor neuromuscular disease, light adaptation, the pupillary light reflex, retinal degenerations, retinal ganglion cells, and the inner retinal pathways.
In July 2008, Dr. Reid Longmuir joined the faculty. He completed an ophthalmology residency at Iowa, and two 12-month Iowa fellowships, one in neuro-ophthalmology and one in glaucoma. He now functions as neuro-ophthalmology faculty at the University of Iowa and staffs both neuro-ophthalmology and glaucoma patients at the Veterans Administration Medical Center. He is the director of medical student education in the Ophthalmology Department. Dr. Longmuir has published articles on neuro-ophthalmological disorders associated with systemic diseases, such as muscular dystrophy and systemic lupus erythematosis as well as an IIH, Horner syndrome, and optic disc edema.
In December 2010, Dr. Matthew Thurtell was welcomed as the newest addition to the Iowa Neuro-ophthalmology group with a joint appointment in Neurology and the Department of Veterans Affairs Medical Center. Dr. Thurtell trained in Neurology in Sydney, Australia, under the mentorship of Dr. G. Michael Halmagyi, a well-known expert in ocular motility and the vestibular system. He then completed a clinical fellowship with Drs. John Leigh and Robert Tomsak at Case Western Reserve in Cleveland, OH. Dr. Thurtell continued to develop his expertise in eye movement and in the afferent visual system, with special interest in pathophysiology and treatment of raised intracranial pressure as it pertains to the visual system. Dr. Thurtell has added important expertise to the Iowa Neuro-ophthalmology service in central and peripheral aspects of ocular motility physiology and pathology. He also continues his interest and expertise in the afferent visual system, including IIH, which follows a long history of interest in this area at Iowa by Dr. Michael Wall and Dr. James Corbett. And of course, Dr Hayreh's clinic was always adjacent to ours, and patients with anterior ischemic optic neuropathy were always a shared area of interest. Figure 8 includes the current members of the “neuro-ophthalmology team” at the University of Iowa.
Portions of an Interview With Dr. Thompson Conducted by Dr. Kardon
Kardon: What was the best thing that has happened in neuro-ophthalmology in the last 30 years?
Thompson: That would be the clear emergence of neuro-ophthalmology as a subspecialty. Drs. Walsh, Hoyt, Smith, and Cogan were the first sparks to ignite an interest in the subspecialty; and neuro-ophthalmology has now come of age and has become an accepted division of both Neurology and Ophthalmology.
This process seems natural enough: if you take an interest in a certain medical topic, and pursue it, then soon other doctors will be referring certain patients to you, or sending someone to you for training. Lawton Smith (who had been a resident at Wilmer when William Hoyt was a fellow with Walsh) started to hold a neuro-ophthalmology course in Miami every winter and had some of his colleagues give lectures.
The Annual Walsh Meeting emphasized neuropathologic correlations, and soon Tom Carlow organized the Rocky Mountain Neuro-Ophthalmology Meeting, which grew into the North American Neuro-Ophthalmology Society (NANOS). There was an exciting novelty to it all. The dynamic personality of Lawton Smith had great audience appeal, and he helped to sell neuro-ophthalmology as a worthwhile subspecialty; and the encyclopedic, serious-minded approach of William Hoyt gave it further credibility. So the best thing that happened to neuro-ophthalmology was that it came together as a subspecialty due to the influence of a number of notable people (9).
Kardon: And for the other side of the coin, what would be the worst thing that has happened in neuro-ophthalmology in the last 30 years?
Thompson: One of the burdens that we have to carry in our subspecialty is that our work requires time and thought; and that makes us vulnerable to the economic pressures. The practice of medicine is inevitably influenced by insurance companies who want doctors to provide a prompt answer and move onto the next patient. A neuro-ophthalmologist needs time to put things together while trying to solve the patient's problems, and time to test various possibilities. If all neuro-ophthalmologists were given only seven minutes per patient, our subspecialty would crumble. So, the worst thing has been the “hurry-up” pressure.
A neuro-ophthalmology fellowship should be like any apprenticeship. The fellow in training recognizes that the partnership with his teacher gradually evolves from the teacher-to-student kind, into a colleague-to-colleague relationship. When the teacher and fellow are working together in the same room, the fellow sees how the mentor talks to the patient and how situations are handled, and understands the thought process. The fellow also needs to understand the anxieties of the patient and family, and how this impacts the history as the clinical problem comes to medical attention (especially with “functional” cases) and needs to learn how to effectively communicate with the patient and family. Time constraints interfere with this process. In certain complicated or unusual cases, the fellow will call in the teacher early in the evaluation to see how his teacher handles difficult situation.
Kardon: What makes for the best neuro-ophthalmologist?
Thompson: The best: may be unreachable, but an academic neuro-ophthalmologist should, ideally, be a caring physician willing to be considerate and helpful to patients, and ready and able to explain things to them. There should be a solid knowledge base in ophthalmology, neurology, and neurosurgery that will help to bring together key bits of information to solve clinical problems. In an academic job there needs to be an eagerness to find answers to weird questions, and a willingness to dig vigorously for new knowledge.
An academic neuro-ophthalmologist should also recognize the value of expanding and broadening his or her knowledge in different directions to form useful “knowledge appendages.” This knowledge might then connect with people in other areas of expertise (eg, biostatisticians, biologists, biochemists). This is, of course, one of the reasons for valuing collegiality in an academic institution. An example from my career was working with Michael Brody, PhD, a Professor of Pharmacology, who helped me in differentiating preganglionic from postganglionic lesions in patients with Horner syndrome.