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Journal of Neuro-Ophthalmology:
Legacy

Noble J. David, MD, Reminisces

Trobe, Jonathan D. MD

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Departments of Ophthalmology and Neurology, Kellogg Eye Center, University of Michigan, Ann Arbor, MI 48015, USA; E-mail: jdtrobe@umich.edu

Noble J. David, MD, always known to his friends and devotees as “Nobby,” has been a member of the round table of neuro-ophthalmologists who set the tone and ground rules for our subspecialty in the mid-20th century. He came up through the same circuit—Duke, Harvard, and the University of Miami—that prepared many of the other accomplished progenitors. Generally regarded as the most literate raconteur in a field of raconteurs, he can recount his history better than anyone. Written with customary grace and humility, here it is:

“I was born in 1927 in Jacksonville, Florida, the sixth child of Syrian immigrants. My father had come over at age 16 and later gone back and married my mother, who was in nursing school at the time. There were no trained physicians in my family, but my mother's uncle and father were amateur medics in the small mountain village where they lived. My father had a high school education but became very fluent in English and was often a public speaker.

“My mother had apparently run out of `normal' names when she got to me. I've long since become totally accustomed to the confusion of name reversal (David was obviously a first, not a last, name) in school, at airline and hotel desks, and in my dealings with society in general. I was never at all sure that I wanted to be a physician, although a brother ten years my senior became a pediatrician. I went through undergraduate school at Duke waiting to be drafted into the Army but was never taken because of the war's ending. I applied to Duke Medical School, fairly certain of rejection, because I wanted to spend another year studying English and trying my hand at writing. Much to my surprise I was accepted and sternly encouraged by my father to enter medical training.

“In my first day as a medical student in the Duke Class of 1952, I was intrigued by a tall, red-headed, drawling South Carolinian who spoke in unique slang. Lawton Smith was one of a score of memorable students in that class, but it is fair to say that for four years he was usually the center of attention. I would regard Eugene A. Stead, MD, the chief of medicine, and Talmadge Peele, MD, PhD, a splendid neurologist and neuroanatomist, as the most influential amongst many fine teachers at Duke. Lawton collected “Peele's Pearls' in a typed compendium that made the rounds as a study manual. Upon graduation, Lawton and I both ended up in as interns in internal medicine at the Grady Memorial Hospital, and after that year, both of us went to Korea as physicians in service.

“Until that time, I had only considered practicing internal medicine and returned to Duke after military discharge to resume my training. In 1957, Albert Heyman, MD, whom I had known at Grady, invited me to do a 6-month fellowship studying stroke. I was available because a cardiology fellowship had not panned out. Before long, it was clear that I was a neurologist at heart. I completed my training at Duke with a short stint with Raymond Adams, MD, chief of neurology at Massachusetts General Hospital (Harvard). I then became the chief of the neurology service at the VA Hospital in Durham for a couple of years and prepared to enter private practice.

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“Under a barrage of exhortation and suasion from the irrepressible Dr. Smith, I agreed to move to Miami in 1962 to set up a VA neurology service and to continue studies with the technique of fluorescein fundus angiography, which I had begun at Duke with Dr. Heyman. The VA hospital was in Coral Gables, a converted hotel, which has now been mercifully restored to what we know as the Biltmore Hotel. Smith and Edward Norton, MD, chief of ophthalmology at the newly opened Bascom Palmer Eye Institute, were the driving forces behind my recruitment, and I also had a small research space at the BPEI. Shortly after my arrival, Johnny Justice, our ophthalmic photographer at the Durham VA, came down to be interviewed. In the course of his stay he took some beautiful fluorescein pictures on a camera we had assembled. Justice's images fascinated Norton and vindicated Smith's extraordinary efforts to get the technique started at the BPEI.

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“We did experimental fluorescein photography in monkeys, eventually developing cinematography of this contrast method. We also were the first to take infrared pictures with indocyanine dye.

“In 1968, Robert Daroff, MD, joined me at the VA and set up his studies of ocular motility. For the 12 years that he remained in Miami, I enjoyed the company of an ideal colleague and friend. His many successes have not surprised me.

“I suppose you could summarize the rest of my career as a mix of clinical teaching, patient evaluation, and some clinical studies, such as an interest in pituitary apoplexy. I saw my first patient with this fascinating disorder in 1964, and have followed the development of our understanding of this event as a clinical entity, primarily advanced by the remarkable resolution of anatomic detail provided by CT and MRI.

“I became semiretired in 1999, but still see private consultations and attend the neurology clinic at Jackson Memorial Hospital. I hope to be around long enough to sense the direction and fate of our hybrid specialty. Looking back, I wouldn't want to have missed any of it.”

The following interview of Dr. David was conducted at his home in Miami on February 25, 2002.

JDT: How did you get interested in neuro-ophthalmology?

NJD: In 1960, my future as a Duke faculty member was pretty bleak. I wasn't doing anything they were interested in. But I did have an interest in fluorescein angiography. I'd learned that technique from John Hickam, MD, who had been faculty at Duke and then left to be chairman of medicine at the University of Indiana. Hickam was interested in the ocular circulation for what it would teach him about vascular reactivity to carbon dioxide and oxygen. Novotny and Alvis, who are usually credited with the discovery of fluorescein angiography, were medical students working in his lab on a summer project. Hickam left on sabbatical and told them how to get contrast pictures of the fundus. They perfected the technique. Novotny went on to become a psychiatrist and Alvis a urologist, but Hickam came to Duke in 1960 to give a talk on the technique. He showed Dr. Albert Heyman, a neurologist, and me the pictures and how to do it.

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JDT: By the way, is Hickam the Hickam of “Hickam's dictum,” the axiom you are so fond of quoting?

NJD: Yes, it stands opposite to Occam's razor, also known as “Osler's rule,” or “one disease to a customer.” Hickam's dictum says that a person “can have as many diseases as he damn well pleases.”

JDT: Getting back to fluorescein angiography, would it be correct to say it was discovered at Indiana but not really applied to ophthalmology until you took it on?

NJD: Yes, it's a long story. We had a photographer at the VA hospital in Durham named Leonard Hart who had an old Bausch and Lomb fundus camera. We put filters in it and began to take pictures. Hart had a young man named Johnny Justice running around the lab—the same Johnny Justice who later worked with Don Gass (MD) at the Bascom Palmer Eye Institute. Anyway, I was interested in seeing if we could tell papilledema from congenital disc conditions and whether we could find any difference between inflammatory, ischemic, or other types of disc conditions.

JDT: Did you find anything valuable?

NJD: No. There was nothing fundamentally different about any of the acquired optic nerve conditions. The chief of medicine at Duke—neurology was a division of medicine—was not interested in funding further research in fluorescein angiography. I owe the next move to Lawton Smith (MD).

JDT: How was that?

NJD: I had known Lawton since the beginning of our medical school days at Duke in 1948. He came back to the Duke faculty in ophthalmology in 1960 after finishing his neuro-ophthalmology fellowship with Dr. David Cogan in Boston. I was chief of neurology at the Durham VA hospital, and we would hold neuro-ophthalmology conferences—double podium stuff, Huntley-Brinkley style, two slide projectors—and everyone attended.

Lawton became increasingly chafed at the fact that ophthalmology was a division of surgery. He was looking for another position, and Norton hired him for the Bascom Palmer Eye Institute in 1962. Then Smith proselytized me. He had convinced Norton that he should bring me down to do some neurologic teaching and set up the fluorescein angiography technique.

JDT: Did you hesitate about moving to Miami?

NJD: Yes. I was highly suspicious of any Miami enterprise just because so much in a resort area is apt to bear the earmarks of quackery and sharp dealers. I didn't know much about the University of Miami School of Medicine except that one of their graduates, Marty Liebling, had become a chief resident in medicine at the VA in Durham, and he was a very bright and able man. So I was curious. But there wasn't much history there. The University of Miami School of Medicine opened in 1953. Florida had no anatomy law before that, you see.

JDT: Why should Norton, an ophthalmologist, want to bring down a neurologist when he had barely recruited any faculty in his own specialty?

NJD: Well, Norton had a strong interest in neuro-ophthalmology, and I think Lawton just wanted company. We may have fantasized about writing a neuro-ophthalmology textbook. Lawton and I had been joint authors on some articles—one on skew deviation, one on the corneomandibular reflex, and another on fluorescein angiography of a hemangioma of the choroid. I took the pictures.

JDT: How did the recruitment go?

NJD: I came down to Miami and talked to Norton and to Peritz Scheinberg (MD), chief of neurology, and showed them some of the fluorescein angiography pictures. I think Norton could tell that I wasn't sophisticated about the anatomy and physiology of the eye, which I certainly was not. But Scheinberg was looking for someone to work in his cerebrovascular disease lab, where they were studying animals and doing Fick principle studies on humans, too. I really didn't have any interest in that. But since Norton was acting dean, once Lawton had persuaded him that I should come, he didn't have much trouble persuading Scheinberg. Also, there also was not much going on at the Miami VA Hospital (housed in the Biltmore Hotel—seven miles away from the Medical School and Hospitals) in neurology then—just one full-time resident, supervised at a distance.

JDT: Did the salary offer come from Norton in ophthalmology or Scheinberg in neurology?

NJD: From Norton. But it didn't sound much better than what I had made as a neurology resident. I told Lawton to forget about it. He called Norton and said, “The guy's gotta have more oxygen.” So the offer finally got up to where I figured I could do it. I was hired to a start a neurology service at the VA, teach neurology, and set up the fluorescein technique. When my father heard I'd accepted the offer, he wrinkled up his nose and said, “If Sodom and Gomorrah were near Miami, the residents would come over from there to Miami on Saturday night.”

JDT: Your first impressions of Miami?

NJD: At first I was a little intimidated by the place because I'm not that much of a sharpie. Here were all these big hotels on the beach, where they would set up the Bascom Palmer Annual Neuro-Ophthalmology Symposia. At first I was self-conscious out in that social setting, but then it got to be fun. Go to an elegant hotel, live there for a couple of days, have a little resort life, meet all these interesting people . . . it didn't take me long to get excited about it.

JDT: How did the job turn out?

NJD: Well, I saw private patients in the Rare Book Room of the Bascom Palmer Eye Institute Library. This was all Norton could spare. I'd seat the patients in a library chair. I never needed to undress them. I thought you learned more from talking to them. I didn't use much equipment—a pin, a piece of cotton, a hammer, an optokinetic tape. And if I needed a slit lamp or ophthalmoscope, I could take the patient into a nearby examining room. If I said something droll while I was dictating, Reva Hurtes (the BPEI librarian then and now), sitting a few paces away, would laugh! I always felt I was something of an orphan over there seeing patients at Bascom Palmer.

JDT: When did your research get started?

NJD: Norton suggested I put in a grant to NIH to fund experimental research in fluorescein angiography. I got money approved there and separately at the VA and set to work ordering Zeiss fundus cameras. The only Zeiss camera was one that had been smuggled in from Havana by Olga Ferrer (MD). It was sitting unused in a back room at Bascom Palmer. A couple of months after I got there, I assembled my filters and I got Al Weinberg, the chief of medical illustration at the VA, to help me take the side off Olga's camera, and install the filters. Olga walked in while we were working on this dismembered camera, and I thought she would have a stroke. “What are you doing with my camera?” she said. “Olga,” I said, “don't jump to conclusions. You're going to love this thing.”

I could never get it to work, but Johnny Justice came down a few weeks later and got the focus right. He took a series of pictures that Norton swooned over. Everyone was set in motion. Don Gass (MD) was interested, and within a few months, they held the first fluorescein angiography conference that is still a weekly tradition at the Institute.

JDT: In what direction did the research go?

NJD: I went on to study retinal artery occlusions. The article we published (Gass and Smith were authors, too) was the first new descriptive material since von Graefe had done his very thorough original description. We saw the early filling of the retinal veins, ciliary circulation, and that dye was still flowing in the occluded central retinal artery but that it was greatly slowed. We could see sparing of the cilioretinal circulation.

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In 1969, by the time the first International Conference on Fluorescein Angiography was held at Albi, France, I had completed most of my experimental work on fluorescein angiography—air embolism, autologous clot embolization, the effect of CO2 and oxygen on the reactivity of the retinal vessels, and the effect of raising intraocular pressure by Dr. Tadashi Fujino's method (with a fine needle placed in the anterior chamber). With high intraocular pressure, we demonstrated the ischemic ring around the disc in the choroidal circulation. Doug Anderson (MD) got interested in this for glaucoma research.

JDT: Weren't you also the first one to perform indocyanine dye retinal angiography?

NJD: Yes. Along about 1968, my photographer, Earl Choromokos, on loan from the laboratory of research neurologist Kyuya Kogure, MD, came upon this indocyanine dye that they were using for cardiac output studies. Looking at its spectral characteristics, Choromokos wondered why we couldn't get an angiogram of the choroidal vessels unobscured by the pigment epithelium if we used infrared filters and film with this dye. So we did. First we took pictures of the surface of the monkey's brain circulation, but then we went to fundus pictures of the monkey and got those pictures that showed the choroidal pattern so well. We got some pictures in humans too, and reported this at Albi in 1969, but the amounts you needed to inject in man were too large, so after many futile attempts to make the technique clinically useful, we abandoned it. Three years ago, Larry Yannuzzi (MD) told me they were using indocyanine to distinguish wet from dry macular degeneration. They had discovered new techniques, but the principles were the same. Yannuzzi asked if I had any of the old pictures. I found them and sent them to him.

JDT: What about your role in carotid artery thromboembolism and the eye?

NJD: It began way back in 1957, when Dr. Al Heyman, one of the neurologists at Duke, learned that I had failed to get a cardiology fellowship (I was in training in internal medicine). He asked me if I wanted to spend six months seeing neurology patients. He aimed to collect 100 consecutive patients with stroke and characterize them as thoroughly as possible. So that became my first endeavor in neurology. It produced a paper that helped predict outcome in stroke. For instance, we showed that a well-lateralized brainstem stroke had a better prognosis. Bilateral signs raised the suspicion, I suppose, of truncal basilar involvement. And this was ominous in terms of survival.

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Fluorescein Angiography in Central Retinal Artery Occlusion

Noble J. David, MD; Edward W. D. Norton. MD; J. Donald Gass, MD; and Joseph Beauchamp, MD, Miami

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In 1959, Miller Fisher published his observations about the fundus oculi during amaurosis fugax (and showed traveling intravascular particles). Heyman and I were very interested in his stuff. A patient of ours had had a bad stroke after carotid endarterectomy. He died, and we were able to obtain the eye, the brain, and the carotid artery, and show that the material in the carotid bifurcation, the retinal vessels, and the brain vessels was the same—cholesterol esters.

JDT: Where did that observation lead?

NJD: It further heightened suspicions that more strokes than we had previously imagined might be from emboli that came from the carotid. Some literature had sprung up tying angiographic carotid stenosis and stroke. DeBakey and others were beginning to operate on these arteries. We began to inject fluorescein into the arm vein, and two observers, each looking into one eye of the patient with an ophthalmoscope, would watch for the appearance of dye—and signal it by hitting a switch. So, we did the first arm-to-retina circulation time and reported it in 1961. You needed to have advanced carotid stenosis before you could appreciate a relative delay between the two eyes.

JDT: What else was going on here in Miami in those early years?

NJD: In 1962, when I came, there was almost no VA service in neurology. With a lot of help, especially from Dr. Scheinberg, I eventually got together a 30-bed neurology ward and a solid resident rotation from neurology and internal medicine, neurosurgery, and psychiatry. As this was developing, Bob Daroff (MD) came down to spend six months as a fellow with Lawton Smith in 1965. Lawton would come to the VA once a week, have rounds, and then go off to lunch. We'd show him our best cases, and he'd tune into whatever kind of research we were doing.

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Shortly after that, Norman Schatz (MD) came down to spend six months with Smith. In 1966, Daroff, who was in the military, told me he'd like to come back to Miami to work with me at the VA. When Daroff got out of the army, he spent a year with Bill Hoyt in San Francisco. And when he finished, although San Francisco had offered him a position, he elected to come back here in 1968. He was my first faculty recruit. Several years later, Todd Troost (MD) joined us at the VA. In 1968, we had moved over to the present Miami VA Hospital. Small amounts of research money were easy to get then. Daroff wanted to study ocular motion. We got the money for him, and soon Lou Dell'Osso (PhD) and Larry Abel (PhD) and others joined him. By 1968, the VA neurology program had a research budget of over $500,000. We had become half the staff and research budget of the department of neurology of which we were an integral part.

JDT: How many people were doing neuro-ophthalmology at the University of Miami in those years?

NJD: Dr. Stanley Thompson has said that in the 1970s, we had the largest stable of neuro-ophthalmologists in the world: Smith, Glaser, Daroff, Troost, and me in clinical work, and a lot of others doing research. Troost left in the late 1970s for the University of Pittsburgh, and when Daroff left in the early 1980s to be chief of neurology at Case Western Reserve, Troost joined him. Troost later became chief of neurology at Bowman-Gray. Lawton retired in 1994, and Joel Glaser left the Bascom Palmer with Norman Schatz several years later. Now they are back in a part-time role.

JDT: What do you remember about the give-and-take between the Miami neuro-ophthalmologists?

NJD: There was a kind of rivalry. We were given to pranks. For instance, things usually happened at Lawton's Saturday neuro-ophthalmology conference. It was a show you didn't want to miss. Norton usually came if he was in town. In fact, most of the ophthalmology faculty came. Lawton ran those conferences with total influence over the course of events. He'd bring patients in, just as his mentor, Frank Walsh, had done at Wilmer. One morning, Lawton was showing a patient with a peculiar type of nystagmus. He was in the middle of his spiel when I grabbed my penlight and, while Lawton still had his hand on the top of the patient's head, I asked if I could just peek into his throat. “Lawton,” I said, “he's got palatal myoclonus.” And without losing a beat, Lawton continued, ”I'm glad you mentioned that, because palatal myoclonus has an important place in the differential diagnosis!”

I remember a patient on Lawton's rounds with complete abduction deficits in both eyes. We knew the diagnosis was myasthenia gravis, but we didn't tell Lawton. Lawton looked at him and said, “These pupils aren't equal. Now in multiple sclerosis, it is not uncommon to see unequal pupils.” While he was going on about this, a resident was sneaking in some Tensilon, and pretty soon his eye movements were completely normal! You see, Lawton noticed everything, and sometimes that was a handicap.

JDT: What was Daroff's contribution?

NJD: He legitimized research on eye movements, particularly in the interface between experimental and clinical research. I think he was a leader—maybe the leader—in clinical research in this area. When he was getting started, he told me how little enthusiasm the big names “up east” had about this field. This was true of neurologists from 1955 to 1970. Their eyes would glaze over when you began to talk about eye movements.

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JDT: What about Lawton Smith's contribution?

NJD: What Lawton made clear to me and to Daroff was what Cogan and Walsh had impressed on him, namely, that there were a number of pathognomonic neuro-ophthalmic signs that had not been well studied up to that time—like internuclear ophthalmoplegia and ischemic optic neuropathy. And you had to study many patients to recognize the signs—you couldn't just come to them intuitively. Finding 95% rules in neurology is not that easy, but in neuro-ophthalmology there are a lot of phenomena that approach that in reliability.

JDT: What do you remember about Lawton Smith before his religious conversion?

NJD: I remember everything, but I can't reveal it! Let's put it this way: I don't think his hypothalamus has changed, just that his superego has got control over it. He was outrageous and virtually unpredictable. As medical students, we'd go out to drive a bucket of golf balls at his invitation—he had a car and I didn't—and we'd end up in South Carolina looking for co-eds. He'd have nicknames for everyone; he called me “Nobster the Lobster.”

He loved to pull pranks on people—I mean large pranks. He volunteered for the Air Force and was asked to look at possible assignments in Korea. There was one base right up near the parallel—K-47. And he found out that the commanding officer there was Ken Baldwin, who had been a medical school classmate of ours. Lawton had gone into the service about three days before Baldwin had. So Lawton asked the recruiting officer, “Who would be commanding officer up there if my date of entry into service is earlier than Baldwin's?” “You would be,” he was told. So he said, “I want THAT job. And I want you to radio Dr. Baldwin that his new commanding officer will be there on the 5 o'clock gooney bird (C-43).”

Baldwin was notified that a new C.O. was coming. He spiffed up in his Class A uniform for the first time—he'd been there but a few weeks—and he came out to meet the gooney bird. As the ladder dropped, there was Lawton Smith with a big cigar wiggling in his mouth, saying “Howdy, Ken, I'm your new C.O.” Ken walked back to his tent and wouldn't come out for about two days!

Lawton's stories were a bit bawdy. At one of the Miami Neuro-ophthalmology Symposia, they were debating a case of “functional visual loss,” and Lawton said it reminded him of the story of a paratrooper from Fort Bragg who came in feigning blindness. His doctors couldn't get him to follow anything; yet, his pupils reacted well. So, as Lawton tells it, they brought in a stripper, spotlighted her in a dimly lit room, and had her go through her routine in front of this paratrooper. Once she got started, they turned to the man and asked him, “What do you see now?” And he replied, “My vision is all blurry.” So one of the doctors said, “Your vision may be blurry, but your indicator is pointing back to duty at Bragg.”

Lawton's teaching, which in the end is going to eulogize him more than his research, is synonymous with his clinical observations. And that teaching was based on strengthening memories through a strong dramatic impact—skits and things. He demonstrated that the hypothalamus, not the cerebral cortex, was the way to the hippocampus.

He was up there on stage giving the part all he had. People who regarded him as a buffoon did so at their own risk. I always envied him. His stuff used to ooze out of every pore. I watched him with an audience of ophthalmologists in Cincinnati once. He ended up rolling around on the floor. Everyone was laughing and having a wonderful time.

Lawton wasn't the only remarkable talent. Norton was knowledgeable enough to talk about anything with you. And Curtin (Victor Curtin, MD, faculty ophthalmic pathologist at BPEI) and Gass (Donald Gass, MD, faculty retinal specialist at BPEI) also knew about neurologic disease. They were just good doctors all the way around.

© 2002 Lippincott Williams & Wilkins, Inc.

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