Journal of Neuro-Ophthalmology, December 2004, Volume 24, Issue 4

Neuro-Opthalmology at the Mayo Clinic

LEGACY Neuro- Ophthalmology at the Mayo Clinic Jacqueline A. Leavitt, MD and Brian R. Younge, MD 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. From Department of Ophthalmology ( JAL, BRY), Mayo Clinic and Mayo Foundation Rochester, Minnesota. Supported in part by an unrestricted grant from Research to Prevent Blindness, Inc, New York, New York. Address correspondence to Jacqueline A. Leavitt, MD, Department of Ophthalmology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905; E- mail: leavitt. Jacqueline@ mayo. edu FIG. 1. Walter " Ivan" Lillie, MD. ( Courtesy of H. Stanley Thompson, MD.) FIG. 2. The 1914 Building photographed in 1924. Built in 1914 as the original Mayo Clinic building, it housed oph­thalmology from 191 7 to 1922. It was torn down in 1986. ( Courtesy of the Mayo Archives.) J Neuro- Ophthalmol, Vol. 24, No. 4, 2004 337 JNeuro- Ophthalmol, Vol. 24, No. 4, 2004 Leavitt and Younge FIG. 3. Henry P. Wagener, MD, in 1932. ( Courtesy of the Mayo Archives.) 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 Lemple 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 338 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 FIG. 4. St. Mary's Hospital in 1909. Opened in 1889, it is still in use. Inpatient ophthalmology consults, weighted to­ward neurology and neurosurgery, are performed here. ( Courtesy of the Mayo Archives.) © 2004 Lippincott Williams & Wilkins Neuro- Ophthalmology at the Mayo Clinic JNeuro- Ophthalmol, Vol. 24, No. 4, 2004 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. FIG. 5. Zumbro Hotel Annex in 1929. Built in 1917, seven of its rooms served as ophthalmology's headquarters from 1922 to 1929. It was demolished in 1987. ( Courtesy of the Mayo Archives.) FIG. 6. Plummer Building in 1928. Built in that year, it housed ophthalmology in 14 rooms from 1929 until 1947. ( Courtesy of the Mayo Archives.) 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 339 JNeuro- Ophthalmol, Vol. 24, No. 4, 2004 Leavitt and Younge FIG. 7. Mayo Clinic Annex in 1955. Originally a dental clinic built in 1919, it was acquired by Mayo and demol­ished in 1967. Ophthalmology lived here in 28 rooms from 1947 to 1955. ( Courtesy of the Mayo Archives.) 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 FIG. 8. Hugo L. Bair, MD, in 1950. ( Courtesy of the Mayo Archives.) FIG. 9. The Mayo Building in 1989. When it was built in 1955, the Department of Ophthalmology moved here to 46 rooms. ( Courtesy of the Mayo Archives.) 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). 340 © 2004 Lippincott Williams & Wilkins Neuro- Ophthalmology at the Mayo Clinic JNeuro- Ophthalmol, Vol. 24, No. 4, 2004 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). FIG. 10. C. Wilber Rucker, MD, in 1961, seated at the control panel of the electronic pupillograph. Mary Cronin, an ophthalmic technician, is the subject, and Kenneth N. Ogle, PhD, is looking on. ( Reproduced with permission from Henderson JW. Ophthalmology at Mayo, Historical Perspectives 1883- 1972, private publication, 1981.) FIG. 11. Robert W. Hollenhorst, MD, in 1982, wearing the presidential medal of the American Ophthalmological So­ciety. ( Reproduced with permission from the Transactions of the American Ophthalmological Society, 1982; LXXX: xii.) 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 341 JNeuro- Ophthalmol, Vol. 24, No. 4, 2004 Leavitt and Younge FIG. 12. Thomas P. Kearns, MD, in 1990. ( Reproduced with permission from the American Academy of Ophthalmology.) 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 elec-troretinography, 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 non-diabetic 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. 342 © 2004 Lippincott Williams & Wilkins Neuro- Ophthalmology at the Mayo Clinic JNeuro- Ophthalmol, Vol. 24, No. 4, 2004 FIG. 13. James C. Trautmann, MD, in 2000. ( Courtesy of the Mayo Archives.) 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. Acknowledgments 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. REFERENCES 1. Shelden WD, Lillie WI. Importance of visual fields as an aid in localization of brain tumors. JAMA 1930; 94: 677- 83. 2. Lillie WI. The clinical significance of retrobulbar and optic neuritis. Am J Ophthalmol 1934; 17: 110- 9. 3. Keith NM, Wagener HP, Barker NW. Some different types of es­sential hypertension: their course and prognosis. Am J Med Sci 1939; 197: 332^ 13. 4. Steffens LF, Bair HL, Sheard C. Dark adaptation and dietary defi­ciency in Vitamin A. Am J Ophthalmol 1940; 23: 1325- 40. 5. Rucker CW. Sheathing of retinal veins in multiple sclerosis. Pro­ceedings of the Staff Meetings of the Mayo Clinic 1944; 19: 176- 8. 6. Rucker CW. Annual Reviews: Neuro- ophthalmology. Arch Oph­thalmol 1950; 44: 733- 43. 7. Rucker CW. Annual Reviews: Neuro- ophthalmology. Arch Oph­thalmol 1952; 48: 639- 56. 8. Hollenhorst RW. Significance of bright plaques in the retinal arte­rioles. Trans Am OphthSoc 1961; 59: 252- 73. 9. Hollenhorst RW. Significance of bright plaques in the retinal arte­rioles. JAMA 1961; 178: 23- 9. 10. Hollenhorst RW, Lensink ER, Whisnant JP. Experimental embo­lization of the retinal arterioles. Trans Am Ophth Soc 1962; 60: 316- 34. 11. Henderson JW, Hollenhorst RW. Effects of cortisone on certain ophthalmic diseases. Proceedings of the Staff Meetings of the Mayo Clinic 1950; 25: 490- 1. 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 1950; 25: 459- 62. 13. Kearns TP. Fat embolism of the retina, demonstrated by a flat retinal preparation. Am J Ophthalmol 1956; 41: 1- 2. 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 1957; 61: 201- 11. 15. Glew WB, Kearns TP, Rucker CW, et al. Experimental production of papilledema. Arch Ophthalmol 1958; 60: 1074- 9. 16. Glew WB, Kearns TP, Rucker CW, et al. The experimental produc­tion of papilledema. Arch Ophthalmol 1958; 60: 1074- 9. 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 1958; 60: 280- 9. 18. Kearns TP. External ophthalmoplegia, pigmentary degeneration of the retina and cardiomyopathy, a newly recognized syndrome. Trans Am Ophthalmol Soc 1965; 63: 559- 625. 19. Kearns TP, Hollenhorst RW. Chloroquine retinopathy: evaluation by fluorescein fundus angiography. Trans Am Ophthalmol Soc 1966; 64: 217- 31. 20. Kearns TP, Hollenhorst RW. Venous- stasis retinopathy of occlu­sive disease of the carotid artery. Proceedings of the Staff Meetings of the Mayo Clinic 1963; 38: 304- 12. 343