Six former Mayo Clinic physicians have contributed gloriously to the history of neuro-ophthalmology. Many have put their stamps-if not their names-on important medical conditions.
The Mayo Clinic tradition of neuro-ophthalmology dates back to the Mayo brothers themselves. Charles H. Mayo, MD, joined his father William W. Mayo, MD, and brother William (Will) J. Mayo, MD, in general practice in 1888 and set aside several hours per week to see patients with eye, ear, nose, and throat problems. Will Mayo attended the University of Michigan Medical School, one of the first medical schools to separate ophthalmology from the discipline of otolaryngology. While Will was a medical student, he had the chance to study anatomy and observe surgery with the University of Michigan ophthalmologists. On a return visit as an alumnus speaker in 1913, he learned that the University of Michigan had given the ophthalmology and otolaryngology departments separate wards to prevent contamination.
In 1915, Will Mayo helped implement a joint Mayo Clinic-University of Minnesota 3-year, university-based graduate school in medical specialties. The graduate physicians did clinical work and medical research and were granted the MS or PhD degrees in clinical specialties. Will organized separate sections of ophthalmology and otolaryngology but needed to replace Carl Fisher, MD, who practiced ophthalmology and otology, with a full-time ophthalmologist. William L. Benedict, MD, was selected to head the section of ophthalmology, which opened in 1917 and included Walter Ivan Lillie, MD, who became Mayo's first neuro-ophthalmologist (Figs. 1 and 2).
Lillie had graduated from the University of Michigan Medical School in 1915, interned at the University Hospital in Ann Arbor, and practiced in Flint, Michigan, before arriving at the Mayo Clinic in 1917. Six weeks later, he was called to active duty in the United States Army, but in 1919 he returned to Mayo as an assistant in ophthalmology. He did not register as a resident in the graduate school until 1920 when he became the seventh postgraduate resident in the ophthalmology department. He supplemented his ophthalmology training with assignments in the neurology department.
In 1921, Lillie joined Benedict and Avery D. Prangen, MD, on the ophthalmology staff at Mayo. At that time, the ophthalmology department was divided into three sections: surgery, strabismus/refraction, and the hospital consult service in medical ophthalmology. Lillie took over the hospital consult service from Prangen and concentrated on referrals from the neurology and neurosurgery services, which were primarily for visual field localization of lesions.
Lillie produced 20 publications, 16 on neuro-ophthalmic topics. One paper emphasized the usefulness of visual fields in localizing brain tumors, although he stated that "the actual occurrence of tumor of the brain is relatively rare" (1). He also wrote about optic neuritis and its recognition by other medical specialists (2). At that time, treatment consisted of pilocarpine sweats, intravenous typhoid or arsphenamine, or removal of infected teeth. In 1933, Lillie left the Mayo Clinic to become the chair of the ophthalmology department at Temple University. He died in Philadelphia while shoveling snow in 1947.
Henry P. Wagener, MD, (Fig. 3) received his undergraduate degree from Charleston College and his medical degree from the Medical College of South Carolina before coming to the Mayo Clinic as an ophthalmology resident in 1920. He joined the staff in 1926 and worked with Lillie on ophthalmology examinations requested by internal medicine or neurology at St. Mary's Hospital (Fig. 4).
Wagener published 100 articles and chapters, concentrating on the retinal vasculature in systemic disease (18 on the effects of hypertension on the eye). Along with internists Norman M. Keith, MD, and Nelson W. Barker, MD, he gained recognition for a classification of hypertensive retinopathy and related survival rates (3) at a time when hypertension therapy consisted solely of salt restriction and sympathectomy.
Wagener continued to work into the 1950s at St. Mary's Hospital, performing visual fields on neurosurgery patients, often spending 6 hours on one visual field. A patient who had had repeated surgery for recurrence of a brain tumor and repeated visual fields performed by Wagener commented that he did not mind the brain surgery nearly as much as the visual field examinations. Wagener retired in 1955.
By the time Lillie left Mayo in 1934, ophthalmology had moved from the Zumbro Hotel Annex, where it had moved in 1922, to the Plummer Building, where it remained until 1947 (Figs. 5 and 6). Hugo L. Bair, MD, replaced Lillie. Bair had received his undergraduate and medical degrees from Harvard, graduating from its medical school in 1929. After a 1-year internship and 21 months as an ophthalmology intern at the Massachusetts Eye and Ear Infirmary (MEEI), he spent 2 months at the MEEI's Howe Laboratory serving as an ophthalmic research assistant.
At Mayo, Bair introduced the tangent screen. Residents were routinely assigned a rotation in perimetry early in their training and performed all the visual fields. When World War II began, there was a shortage of residents so the paramedical staff took over the performance of visual fields. During Bair's tenure, ophthalmology moved to the Mayo Clinic Annex, where it remained until 1955 (Fig. 7).
Bair published 26 articles, six on topics in neuro-ophthalmology and four on dark adaptation. Aware of the impact of vitamin A on night vision, he tried to verify this by placing three subjects on a vitamin A-restricted diet (100-300 international units daily) for up to 190 days. None of the subjects had abnormal dark adaptation after this deprivation. Bair concluded that vitamin A intake can be deficient for quite some time without causing any physiologic changes in rod or cone sensitivity (4). He retired in 1969 (Fig. 8).
C. Wilber Rucker, MD, graduated from the University of Minnesota medical school in 1926 and was an ophthalmology resident at the Mayo Clinic from 1926 to 1929. He then returned to Minneapolis to practice ophthalmology and work in the student health service at the University of Minnesota while serving as an Instructor in Ophthalmology at the university's medical school.
Joining the Mayo staff in 1934, Rucker was an active participant in morning lectures for the ophthalmology, neurology, and neurosurgery residents on the medical/neuro-ophthalmology service. Rucker once examined a chubby 11-year-old boy with retinitis pigmentosa. Correctly realizing that the boy had Bardet-Biedl syndrome, Rucker turned to the boy's mother and asked rather quietly, "Does your son have six toes?" She remarked "My God, can you see down that far?"
Rucker was the first to write about retinal venous sheathing in patients with multiple sclerosis (5). Wagener had first observed retinal venous sheathing but believed that these changes were congenital. In 1947, Rucker submitted his thesis on 103 cases of venous sheathing in multiple sclerosis to the American Ophthalmological Society (AOS). Edward W. D. Norton, MD, later chair of ophthalmology at the Bascom Palmer Institute, University of Miami, read that paper and was intrigued enough to spend a few months at Mayo after finishing his fellowship training. But during his 3-month stay, he did not see a single case of venous sheathing. On the day that he left for the airport, in walked a patient with that very condition. A squad was sent to the airport to retrieve Norton so that he could see the patient for himself. Frank B. Walsh, MD, later visited the Mayo Clinic to examine multiple sclerosis patients with venous sheathing.
Rucker served as chairperson of ophthalmology from 1949 to 1961. In 1955, he moved ophthalmology to the Mayo Building, where it is still housed (Fig. 9). Rucker published 98 journal articles, chapters, and books. In his first annual review of neuro-ophthalmology for the Archives of Ophthalmology in 1950, he stated that "the literature in this field is composed largely of unrelated and unexplained bits, mostly in the form of case reports" and "much of the literature on neuro-ophthalmology concerns rare diseases of little clinical significance" (6). In 1952 he decided that "during the past year, the number of published papers dealing with some phase of neuro-ophthalmology increased over that of preceding years. This is evidence neither of newly aroused interest in the field nor of any remarkable progress: it is merely that more people are writing papers" (7).
Rucker retired in 1967 and received the Howe Medal from the AOS in 1971 (Fig. 10).
Robert W. Hollenhorst completed medical school at the University of Minnesota, obtaining a BS in 1937, an MB in 1940, and an MD in 1941. A 3-month internship and 1 year of hospital service preceded his service in the army. He completed his ophthalmology residency at the Mayo Clinic in 1948. During that time, he reports that "I didn't get a speck of neuro-ophthalmology experience."
Hollenhorst joined the Mayo staff as a general ophthalmologist in 1949, and after 8 years in practice, decided that he did not enjoy surgery because there were "too many weekend and night worries." He had become adept at ophthalmoscopy, so he fastened onto vascular disease and the eye, developing an interest in the ophthalmodynamometer, which had been popularized by Wagener. Hollenhorst had seen cholesterol emboli in many patients with stroke for approximately 10 years before publishing his observations (8,9). (It was J. Lawton Smith, MD, who later coined the term "Hollenhorst plaque.") Hollenhorst went on to prove in the laboratory that cholesterol crystals released into the carotid circulation would lodge within the retinal vessels in monkeys, dogs, cats, and rabbits (10). He considers these studies his most significant contribution to neuro-ophthalmology.
Along with Henderson, Hollenhorst reported the first uses of intramuscular and topical cortisone in eye diseases (11,12). After publishing 11 chapters and 85 journal articles, he retired in 1979. He was awarded the Howe Medal of the AOS in 1986 (Fig. 11).
Originally from Kentucky, Thomas P. Kearns, MD, went to the University of Louisville for undergraduate studies (AB, 1943) and medical school (MD, 1946). He had learned about retinoscopy from an uncle and performed plane mirror and streak retinoscopic refractions in the army. After a locum tenens spent delivering babies, he was convinced that ophthalmology was the field to pursue. After his ophthalmology residency at Mayo, Kearns joined the staff in 1949 in the medical/neuro-ophthalmology, perimetry, and hospital consultation sections.
Rucker prompted Kearns (Fig. 12) to learn pathology, the basis for his later work on flat retinal preparations and the demonstration of fat emboli in the retina (13). He collaborated with Dale C. Smith, MD, an ophthalmology fellow, to produce Terson syndrome in monkeys and optic nerve sheath hemorrhage without direct connection to a subarachnoid hemorrhage (14). Working with William B. Glew, MD, a Mayo ophthalmology resident and later chair of ophthalmology at the Washington Hospital Center, and Hiram E. Essex, PhD, chair of the physiology department, Kearns tried to duplicate work performed at the beginning of the twentieth century in Germany, in which intracranial hypertension was produced in dogs with intracranial sponges. Unable to duplicate this work in dogs, they developed a better model using intracranial balloons to produce intracranial hypertension in monkeys (15). In 1958 they published the first photograph of experimental papilledema (16). This publication stimulated later work by Sohan S. Hayreh, MD, and Thomas R. Hedges, Jr, MD.
Kearns considers his greatest personal achievement the description of the syndrome that now bears his name, the Kearns-Sayre syndrome, reported in 1958 in conjunction with Mayo neuropathologist George P. Sayre, MD (17). Their original patients presented with syncopal spells that had been assumed to be psychogenic. Kearns noted peculiar retinal pigment epithelial changes and ophthalmoplegia. He submitted his paper on the Kearns-Sayre syndrome as his AOS thesis with seven additional cases. It was turned down for lack of electrophysiologic and pupillographic testing. After learning about electro-oculography and electroretinography, he asked patients to return to complete electro-oculography, electroretinography, and dark adaptation studies, the results of which were added to his manuscript. This version was published by the AOS (18).
Kearns coined the term "bull's-eye maculopathy" as a description for chloroquine retinopathy in an article published in 1966 and co-authored with Hollenhorst (19). Presenting a case at a meeting at the Wilmer Ophthalmological Institute of Johns Hopkins University, Kearns declared the findings to be pathognomonic for chloroquine retinopathy. But A. Edward Maumenee, MD, then chair of ophthalmology, pulled out a slide showing a very similar finding in a patient with macular degeneration. Kearns was forced to concede that the "bull's eye" was not entirely pathognomonic for chloroquine retinopathy.
Hollenhorst and Kearns noticed that several nondiabetic patients manifested a unilateral retinopathy similar to that seen in diabetic patients. Rucker suggested that diabetes would develop in these patients later in life. But Kearns argued that these findings were secondary to hypoxia of the retina from carotid artery stenosis. At an AOS meeting, he defended his view that these findings were not a manifestation of a retinal vein occlusion (20). Rucker had called this finding "venous stasis retinopathy," a term that Kearns accepted, although he says that he would have preferred to call it "chronic ischemic retinopathy."
Kearns recalls that one day, as he was trying to determine whether to prescribe single reading glasses or bifocals, he asked his patient what kind of work he did. The answer came back as "Wahl, I'm the senior Senatuh [sic] from Texas." The speaker was, of course, Lyndon B. Johnson.
In addition to his 86 publications, Kearns taught at the Lancaster Course in Maine for 15 years and was the first to use the Perkins tonometer at Mayo. He served as a member of the American Board of Ophthalmology and the Residency Review Committee for Ophthalmology and as president of the American Academy of Ophthalmology in 1986. He retired from the Mayo Clinic in 1987, receiving the Howe Medal from the AOS in 1994.
James C. Trautmann, MD, started his residency in ophthalmology at the Mayo Clinic in 1964. Before his residency, he had attended the University of Minnesota for his BA (1950) and MD (1954). After finishing his residency, he joined the Mayo staff in the section of medical and neuro-ophthalmology.
Trautmann wrote his master's thesis on the velocity of the pursuit phase of optokinetic nystagmus in 13 healthy subjects in 1966. His 41 publications concentrated on neuro-ophthalmology with an emphasis on ocular manifestations of diabetes, reflected in eight journal articles. He retired from Mayo in 1991 (Fig. 13).
The Mayo tradition in neuro-ophthalmology continues to be strong under the auspices of Brian R. Younge, MD, Shelley A. Cross, MD, and Jacqueline A. Leavitt, MD, who are grateful for the legacy of their predecessors and hopeful that they can transmit as much as they have received.
This work was profoundly influenced by the personal interviews with John W. Henderson, MD, William B. Glew, MD, Thomas P. Kearns, MD, and Robert W. Hollenhorst, MD. A special thanks to Kristi Hunter for her assistance with archived photographs and to Renee Ziemer for historic data from the Mayo Historical Unit. Thanks also to Jay C. Erie, MD, for his help and expertise with the manuscript.
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2. Lillie WI. The clinical significance of retrobulbar and optic neuritis. Am J Ophthalmol
3. Keith NM, Wagener HP, Barker NW. Some different types of essential hypertension: their course and prognosis. Am J Med Sci
4. Steffens LF, Bair HL, Sheard C. Dark adaptation and dietary deficiency in Vitamin A. Am J Ophthalmol
5. Rucker CW. Sheathing of retinal veins in multiple sclerosis. Proceedings of the Staff Meetings of the Mayo Clinic
6. Rucker CW. Annual Reviews: Neuro-ophthalmology. Arch Ophthalmol
7. Rucker CW. Annual Reviews: Neuro-ophthalmology. Arch Ophthalmol
8. Hollenhorst RW. Significance of bright plaques in the retinal arterioles. Trans Am Ophth Soc
9. Hollenhorst RW. Significance of bright plaques in the retinal arterioles. JAMA
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11. Henderson JW, Hollenhorst RW. Effects of cortisone on certain ophthalmic diseases. Proceedings of the Staff Meetings of the Mayo Clinic
12. Henderson JW, Hollenhorst RW. Clinical observations on the use of cortisone in ophthalmic diseases, preliminary report. Proceedings of the Staff Meetings of the Mayo Clinic
13. Kearns TP. Fat embolism of the retina, demonstrated by a flat retinal preparation. Am J Ophthalmol
14. Smith DC, Kearns TP, Sayre GP. Preretinal and optic nerve sheath hemorrhage, pathologic and experimental aspects in subarachnoid hemorrhage. Trans Am Acad Ophthalmol Otolaryngol
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16. Glew WB, Kearns TP, Rucker CW, et al. The experimental production of papilledema. Arch Ophthalmol
17. Kearns TP, Sayre GP. Retinitis pigmentosa, external ophthalmoplegia, and complete heart block, unusual syndrome with histologic study in one of two cases. Arch Ophthalmol
18. Kearns TP. External ophthalmoplegia, pigmentary degeneration of the retina and cardiomyopathy, a newly recognized syndrome. Trans Am Ophthalmol Soc
19. Kearns TP, Hollenhorst RW. Chloroquine retinopathy: evaluation by fluorescein fundus angiography. Trans Am Ophthalmol Soc
20. Kearns TP, Hollenhorst RW. Venous-stasis retinopathy of occlusive disease of the carotid artery. Proceedings of the Staff Meetings of the Mayo Clinic