My ophthalmic research journey and contribution

My objective in this study is not to discuss what scientific research is and how to conduct it-there is a voluminous literature about that. It is more personal to tell, briefly, why and how I got into scientific ophthalmic research, and my contribution to ophthalmology, since 1955. The word “research” has a mythical charm and mystery to the general public. It had it to me when I was a medical student, and pushed me toward research, although I did not have the faintest clue what it involved. Moreover, at that time scientific research was never discussed or taught in medical colleges. After graduation from the medical college, residency in general surgery and service in the Indian Army Medical Corp, in pursuit of my ambition for a research and academic career, I joined the newly opened medical college in Patiala; the only available post was in the anatomy department. I found no one around who knew anything worthwhile about serious scientific research. By chance, I happened to meet the professor of Ophthalmology from my student days. I chanced to mention that I was looking for a research topic. He told me that he had recently seen papers in the British Journal of Ophthalmology on “vascularization of the optic pathway.” Because I was working in the anatomy department, I thought it worth exploring their discovery of a “central artery of the optic nerve.” Because there was no one in the department to help me, I explored the whole thing myself. I had to learn everything the hard way. I became my own investigator, technician, and director of research, without any prior knowledge and training. From the literature, I found that, to study the anatomy of the vascular bed, the first essential was to prepare vascular casts. In India, I could not find any material to do that; liquid latex was the only suitable material for preparing vascular casts, and only the DuPont company in Delaware, USA made it. However, my salary then was only about 200 rupees a month, so I could not afford to buy latex and I had no research funds. (Even if I had had the money, the Government of India at that time did not allow anyone to buy goods from abroad, to save hard currency.) With the faintest hope, I wrote to the DuPont cmpany, asking if they could possibly send me some free samples of liquid latex, and they sent me two gallons, which was enough for my project. With that, I did comprehensive human anatomical studies, not only of 100 central retinal arteries but also of the entire vascular bed of the eye, optic nerve, and the orbit in 59 human orbits; those studies still stand as landmark studies. I showed that the “central artery of the optic nerve” did not exist-it was a scientific fraud! That landed me in a big controversy because Professor Jules Francois, the primary author of multiple studies “claiming” that artery existed, was the secretary general of the International Council of Ophthalmology and politically powerful in international ophthalmology. After initial bad blood for years, he finally met me in London and graciously agreed to repeat the study; then he fully confirmed my findings. Further, after those anatomical studies, I found the subject of pathogenesis of optic disc edema (papilloedema) in raised intracranial pressure fascinating and challenging, since its first discovery in 1853, over a dozen conflicting theories had been postulated, without any definite conclusion. There were no research facilities in Patiala to investigate that complex problem. Then one day, in the Times of India, I read a small announcement by the University of London for the Beit Memorial Research Fellowship for Medical Research. This was a highly-coveted research fellowship in medical sciences in the United Kingdom; previous fellows included many famous names in twentieth-century medicine, and at least 6 former Beit fellows so far have gone on to win Nobel Prizes in Medicine. No one from India had been awarded the Beit fellowship. There were two essential requirements to apply for the fellowship: the candidate must (a) submit his own detailed research plan, and (b) obtain a letter from a research director in Britain agreeing to accommodate the candidate in his laboratory, if he/she obtained the fellowship. I already had my research project, the “pathogenesis of optic disc edema in raised intracranial pressure” in mind and how to tackle it. To get a British research director to accommodate me was the huge problem. I had never met any British! In desperation, I wrote to the famous Sir Stewart Duke-Elder, director of the Institute of Ophthalmology, University of London-he had written many books. He agreed to accept me. In June, 1961 the Beit trust informed me that I was elected as a Beit fellow for 3 years. That was the crucial event in my life-research, professional, and personal future. I wrote to Duke-Elder, and he kindly wrote back the following: “I am delighted to hear that you have got a Beit Fellowship-excellent. We will be glad to see you here on October 1st, and I should imagine that the best thing you could do in the meantime is to read up the enormous literature on papilloedema; most of it is old, for, unfortunately for ophthalmology, nothing of importance has emerged lately. In a way that is fortunate for you, and we are all looking forward to you solving a very important problem.” I arrived at the Institute of Ophthalmology, University of London, on October 1, 1961. At that time, the Institute was the premier and most coveted ophthalmic research institute in the world. As a Beit fellow, following distinguished previous Beit fellows, I was determined to “measure up.” Therefore, I put in my best effort in my research on a very difficult project, and devoted 100% of my time to it. For me, Duke-Elder was not only very kind but also extremely generous with his time and provided all possible facilities and complete freedom to pursue my research plans. I was the only researcher at the Institute for whom he was director of research. He was always ready to give advice when asked, despite being very busy. Since, at that time, no experimental method existed to produce raised intracranial pressure and optic disc edema, I first had to devise a method. I discovered that a gradually inflated intracranial balloon (simulating a rapidly growing intracranial tumor) successfully produced raised intracranial pressure and optic disc edema experimentally in rhesus monkeys. After overcoming teething troubles, my studies started to yield new important information. For instance, that fenestration of the optic nerve sheath relieved optic disc edema in raised intracranial pressure. This observation formed the basis of the procedure now frequently used in idiopathic intracranial hypertension. During that period, I also investigated the histological structure of the optic nerve and discovered that central retinal vein occlusion was of two types, ischemic and non-ischemic-which has important clinical implications in its diagnosis, visual outcome, and management. I also investigated posterior drainage of fluid from the vitreous and found that it played no role in the pathogenesis of optic disc edema, contradicting previous views. Some years after the Beit fellowship, when more advanced technology became available, I did further studies on this topic that finally showed that optic disc edema in raised intracranial pressure is because of the axoplasmic flow stasis caused by raised cerebrospinal fluid pressure in the sheath of the optic nerve. Therefore, I finally solved this mystery dating from 1853, as Duke-Elder originally predicted I would. When my Beit fellowship finished after 3 years, I had to make a tough choice-go back to India and say good-bye to any serious ophthalmic research for lack of facilities and funds, or stay in Britain and try to make a career in British ophthalmology. I decided for the latter, despite the very heavy odds against me. I would have to undertake local clinical training and pass the two examinations for the fellowship of the Royal College of Surgeons; I knew that the pass rate in fellow of the royal college of surgeons (FRCS) was only about 25%. Otherwise, I would have no future in patient care, research, and academic career in Britain. Hence, at age 37 with my Ph.D. from University of London, research credentials, and the prestigious Beit fellowship, I went back and started as a clinical trainee. All the other clinical trainees with me were young, new medical graduates. However, I knew I had to swallow my pride and start from the bottom, if I wanted to achieve what I coveted. After my early clinical job, because of my research credentials, I was appointed Lecturer in Clinical ophthalmology at the University of London-doing research at the Institute of ophthalmology and clinical work at the Moorfields Eye Hospital. Fluorescein fundus angiography was a brand new test started in 1963. I became one of the first pioneer investigators of that. With that as a research tool, I investigated retinal and optic nerve head circulation. I discovered the following for the first time: The blood supply of the optic nerve head is entirely by the posterior ciliary artery circulation that completely changed the entire concept about its circulatory disorders-most importantly, about the pathogenesis of anterior ischemic optic neuropathy and glaucomatous optic neuropathy In glaucoma, there is vascular insufficiency in the optic nerve head. I showed that, also, with my experimental glaucoma studies, contradicting the centuries-old concept that glaucoma was purely a mechanical phenomenon due to raised intraocular pressure. From that, I introduced the vasogenic concept of optic nerve damage in glaucoma, which initially attracted strong objections but is now a seminal concept in glaucoma research I showed the angiographic pattern of choroidal melanomas and of radiation retinopathy. At Moorfields, working with Dr. Peter Watson in the scleritis and episcleritis clinic,

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