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SOME RECOLLECTIONS FROM MORE THAN HALF A CENTURY OF OPHTHALMOLOGY.

Erik Linnér, M.D. Professor Emeritus of Ophthalmology

At the beginning of their medical training many students are hesitant about which field they most of all would like to choose after completing their training, and I experienced the same problem. When I entered the course of ophthalmology it soon became clear to me, that this speciality could be a good choice. Professor Fredrik Berg, at that time the head of the department in Uppsala, showed a kind and considerate attitude towards the patients, and at the same time a clear and distinct judgment. He also showed a personal interest in us as students and was a good lecturer. The field of ophthalmology included many comparatively accurate and precise methods of examination as basis of the clinical judgement. In the surgical field he demonstrated an accurate and seemingly easy technique, and in some difficult cases he quite simply used two pairs of eyeglasses. An important progress took, indeed, place from his eyeglasses to the present operating microscope.

In the field of research I was early interested in physiology and I was lucky enough to get in contact with Ernst Bárány, who was working on circulatory problems of the eye. Soon afterwards he became professor of pharmacology in Uppsala and I could follow him to his new department. We became very good friends. He was a man with wide interests, a true polyhistor, who created an open and free atmosphere. He had an enormous curiosity and above all research was always a great fun. Many young ophthalmologists received their research training in his department. His personality made a lasting impact on experimental ophthalmology.

My own first project was to develop a technique and an instrument for measuring the pressure in the common, episcleral and in the aqueous veins. Assuming that a direct communication existed between Schlemm´s canal and the aqueous veins visible on the outside of the globe, then the pressure required to block the aqueous flow could indicate the pressure in Schlemm´s canal. Already after my first published, preliminary results I received a travel grant with the purpose to visit professor Hans Goldmann in Bern Switzerland, who simultaneously and independently was working on the same project, but he was using a different technique. Our aim was to compare our two different techniques by measuring on the same group of patients with both instruments.

After being isolated during the Second World War it was with a feeling of curiosity and expectations, that I started on my journey in 1949. Goldmann received me very nicely. He was a kind and friendly person with wide interests, a true polyhistor, and with a deep understanding and knowledge of mathematical and technical problems. He was considered to be one of the most important personalities in ophthalmology in Europe. Both Bárány and Goldmann were of kindred natures and later on became close friends. Together with younger colleagues in Goldmanns clinic we could carry out our comparative investigation.

Later on, back in Uppsala I enlarged my study to a sufficient number of normal individuals and glaucomatous patients using my original technique. The findings were that the pressure in the aqueous veins remained unchanged in glaucomatous eyes with increased intraocular pressure as compared to eyes with normal pressure indicating that the pressure in Schlemm´s canal remained unchanged and also that the increased outflow resistance in glaucomatous eyes was located in the inner wall of Schlemm´s canal.

One summer´s day, when I was working on this aqueous vein project, I was invited to visit Ernst Bárány in his summer house. As usual there was a free and informal discussion about almost everything and I speculated about the well known fact that the concentration of ascorbic acid was much higher in the aqueous humour than in the plasma. It might therefore be possible to use ascorbic acid as a test substance for measuring the plasma flow through the secretory part of the ciliary body in the same way as clearance determination in the kidney. Ernst immediately found this idea very interesting and worth-while to investigate. He placed all the resources of his department at my disposal and taught me all about how to carry out experimental work on rabbits and guinea-pigs. My work about aqueous veins had to wait.

These experimental results indicated that plasma flow could be estimated by means of ascorbic acid as a test substance. From clinical point of view it seemed to be of major interest to apply these results to a basic problem such as cataract. Professor Marc Amsler in Zürich, whom I knew beforehand, was a man of French charm and at the same time efficient accuracy in his clinical judgment and work. With his approval a study concerning plasma flow in the ciliary processes could be performed on cataract patients in his clinic. The determination of ascorbic acid concentration in the aqueous humour required a puncture of the anterior chamber of the eye. All the punctures of the anterior chamber were done with extreme precautions by himself or one of his senior colleagues and I never saw or heard of any complications in our study or in any other of the studies carried out in the clinic. The material was necessarily limited, but the results indicated that the plasma flow was reduced in eyes with cataract as compared to the control eyes without cataract. Further studies showed that the rate of aqueous flow also was reduced in cataract patients. After unilateral ligation of the carotid artery in rats the blood flow was reduced to about 50 percent and after X-ray exposure the lens opacities were more pronounced on the ligated side. The blood and aqueous flow were found to be reduced, but the requirements concerning blood and aqueous flow for maintaining a clear lens were so far not clarified and further studies were needed.

During my work in Uppsala doctor Bernard Becker from Wilmer Institute, Johns Hopkins University, Baltimore, USA visited Bárány and his department. He became interested in my method of measuring the pressure in episcleral and aqueous veins. After his return to USA I received an invitation to come over and do research work at Wilmer Institute. We were glad to accept the invitation and in 1953 together with my family we travelled 9 days by boat, which was different from the comfortable flights of today. From the beginning it was planned to be a short visit but we stayed 2 years.

It was a most inspiring time due to the unique personality of doctor Jonas S. Friedenwald, the head of research. He had a deep and thorough knowledge and understanding not only of ophthalmology, but also of basic fields like mathematics, physics and biochemistry. He had a deep interest in all human domains and I think especially in basic legal issues. He also was a true polyhistor.

The first project was to measure the episcleral venous pressure during tonography, and other problems related to tonography. Later on we were free to work on other problems too. When some complicated problems arose in the laboratory, he said that he would come back with an answer the following day. So he did. His answer included a full analysis and if possible an answer in his own handwriting. When we visited him in his summerhouse he took our 2 year old daughter on his lap and made some very good sketches of chipmunks. She was thrilled. His untimely illness and death meant a great and irreparable loss to ophthalmology, but also to our family.

Some months after returning to Sweden I came to Göteborg. The clinical work at the Sahlgrens University Hospital was dominated by investigating problems and especially surgical ones of retinal detachment. Ocular hypertension was later on investigated. In 1961 Ulf Strömberg carried out a mass survey of more than 7000 inhabitants, 40 years of age or above, in a small town outside Göteborg. The results showed that 152 individuals were hypertensive. In spite of Strömberg´s untimely death, these individuals could be followed during 20 years without treatment. As soon as the first signs of glaucomatous damage were found treatment was initiated. During up to 20 years without treatment 34 percent in this group of hypertensive individuals developed early signs of glaucoma as compared to about 5 percent in a group of initially normotensive individuals. This study showed that the risk among hypertensive individuals to develop glaucoma was significantly increased, but on the other hand that about two third in this hypertensive group remained undamaged during up to 20 year. The clinical problem was to detect the hypertensive individuals with a high risk for development of glaucoma early enough in order to start treatment, but on the other hand to identify the individuals - in this study about two third - without an increased glaucoma risk at least during 20 years, who did not necessarily need a similar early treatment. At that time we did not have sufficiently reliable criteria to differentiate the individuals according to risk. A lively international discussion has been taking place about the evaluation of ocular hypertension as a risk factor. The argument was on one hand that ocular hypertension meant no essential risk and that treatment could wait, but on the other hand that most of the hypertensive patients should be given glaucoma treatment prophylactically. The identification of risk factors has improved and now there seems to be an agreement to try to identify possible risk factors before starting prophylactic treatment.

In 1967, when I moved to Umeå in northern Sweden as professor, I found that some problems were different in a newly established university located in a sparsely populated, cold area. A positive factor was, that the eye department now could attract some very competent eye doctors. There was a need for modern equipment. When this problem was discussed with the leading politician in Umeå, Gösta Skoglund and I informed him that a modern type of an operating microscope, recently available on the market, had the highest priority he immediately, without hesitation, allowed me to order such an instrument. We were glad to be the first eye clinic in Sweden to start developing surgery of the anterior segment of the eye by the use of a modern operating microscope as a routine procedure.

Since the time, when measurement of the pressure in the aqueous veins indicated that the glaucomatous increase in aqueous outflow resistance was located in the inner wall of Schlemm´s canal, I was interested in the possibility of improving glaucoma surgery. The operating microscope made it possible to recognize small details in the angle of the anterior chamber and to find Schlemm´s canal. From the beginning I tried to perform trabeculotomies according to Harms, but at least in my hands the results were not satisfactory. After an analysis of the results my conclusion was that it might be better to cut Schlemm´s canal twice and to remove the intermediate piece of the canal, about 4 mm in size, thus creating two openings into the canal. In addition there might be a possibility that a new outflow route into the suprachoroidal space was opened. It could also be a filtering outflow through the scleral flap, which covered the gap in the canal. This was the glaucoma operation, trabeculectomy.

At a microsurgical glaucoma symposium in 1968 it happened that Cairns and myself simultaneously and independently reported about the new method of trabeculectomy. This type of coincidence could happen, when the time was ripe by the general presence of essential knowledge and suitable technical equipment.

In clinical work it is obvious that a detailed analysis of a surgical procedure must be incomplete. An experimental study was therefore desirable and was performed together with Bárány in his department on 17 cynomolgus monkeys. There were some special problems. General anaesthesia was necessary, because it was too dangerous to come close to these monkeys, when awake. The monkey eyes were less accessible. The conjunctiva was thicker and the sclera thinner than in human eyes. The results showed that the cut ends of Schlemm´s canal were closed by scar tissue in most eyes, only in 4 eyes was the canal open and the outflow facility increased. No filtering bleb was observed. It was suggested that a number of small holes in the trabecular meshwork might be better. So far there seemed to be no quite safe and long-lasting improvement of our trabeculectomy, reported 40 years ago. The development of scar tissue could not be controlled in a safe and satisfactory way.

Special medical problems were characterizing the parts of the three Scandinavian countries Finland, Norway and Sweden, located close to or north of the Arctic Circle. The climate was cold and the distances were long, e.g. more than 400 km from Umeå to the Norwegian border. When the influence of the distance was investigated, it was found that fewer number of patients visited the hospital from remote areas, in spite of the fact that the travel expenses were paid. One exception was the diabetics. They had to consider the legal requirement for their drivers licence.

The road quality was important. As an example an accident happened to me on one winter day with lots of snow and 20 degrees below zero Celsius. I travelled by car on the main road. When I met a big truck loaded with timber driving in the middle of the road, I was forced to keep as far right as possible. My two right wheels sank deep into a ditch and the snow covered the car up above the windows. I had no chance to get the car out of the snow by myself, but I was lucky enough that it was less than one kilometer to a house, where they had a tractor and kindly pulled me out and up on the road again. The country was sparsely populated and it could just as well have been a large distance to the nearest house. In such a case it could had been a serious situation if you are not equipped for strong cold.

After the years at Umeå University Hospital, I returned as professor to the eye clinic at Sahlgrens Hospital in Göteborg. My responsibility there laid mainly in the clinical work. As professor emeritus I was assigned as a short-term consultant by WHO to assess glaucoma as a cause of blindness in South-East Asia. It was quite an experience to see the completely different conditions for medical care as compared to Western countries. The access to care of eye diseases was limited, especially for patients from rural areas. At least 50 per cent of the primary glaucomas were of angle-closure type in South-East as well as in Far-East Asia. Often the angles were closed off in a chronic creeping manner without redness and pain forcing the patient to go to the hospital immediately. These patients would therefore come late and some of them were already blind. In one of the hospitals I met a middle-aged woman living in a rural area far from the hospital. Some months earlier she visited the hospital and her first eye was blind because of angle-closure glaucoma of a chronic creeping type. She was told to come back to the hospital without delay if she noticed that anything happened to her second eye. When she finally came she was totally blind in both eyes. At that time a prophylactic iridectomy was the only method available, but often the clinics were reluctant to carry out such a risky operation. The situation has now improved very much, when laser iridotomy has been available.

About 35 years ago both doctor Bernard Schwartz from USA and I participated in a congress in the South of France. We soon found that that we had a common interest in aqueous flow and corticosteroids. Since then we have been in touch with each other and some years later we could start working together on a common project. He had developed a method of scanning the optic disc for differences in colour between pale and pink on disc photos, and I had a material of hypertensive individuals with disc photos of good quality. About 1000 of these disc photos were mailed to him in a masked manner. In one project one group with and one without the exfoliation syndrome were compared. The result was that the pallor of the disc was significantly larger in the exfoliative group. Our conclusion was that the exfoliative process probably had extended to the posterior segment of the eye including the optic nerve. Soon afterwards our conclusion was confirmed by electron-microscopic findings of exfoliative material in the walls of the vessels leading to the optic nerve.

These results led to the hypothesis that the exfoliative process might extend still further backwards into the brain. In the first part of our study a group of patients suffering from dementia was investigated. The number of positive ocular exfoliation syndrome was significantly higher than in the control group. A following not yet completed study of the cerebrospinal fluid showed, that there was a damaging effect on the blood-brain barrier in the exfoliative group as compared to the control group. The study is still going on.

Looking back on my own experiences during more than half a century I can only say, that it has been a great pleasure and privilege to learn to know personally and to work with some of the leading personalities in eye research both in Sweden and abroad. They made a deep impression on me. It was a most stimulating, personal experience and research is still fascinating and great fun.

For the future I can only wish that as many as possible in the younger generations get the opportunity to travel to different countries and cultures and to meet different personalities. It can give a lot of information and stimulation not least to those interested in and fascinated of research as in my case. Everybody can benefit from close international contacts.

Address: Lilla Danska vägen 6, SE 412 74 Göteborg, Sweden, Phone/Fax: +46 31 404154

GOTO PAGE 1

E.L., probably prescribing

Erik Linnér, M.D. Professor Emeritus of Ophthalmology

At the beginning of their medical training many students are hesitant about which field they most of all would like to choose after completing their training, and I experienced the same problem. When I entered the course of ophthalmology it soon became clear to me, that this speciality could be a good choice. Professor Fredrik Berg, at that time the head of the department in Uppsala, showed a kind and considerate attitude towards the patients, and at the same time a clear and distinct judgment. He also showed a personal interest in us as students and was a good lecturer. The field of ophthalmology included many comparatively accurate and precise methods of examination as basis of the clinical judgement. In the surgical field he demonstrated an accurate and seemingly easy technique, and in some difficult cases he quite simply used two pairs of eyeglasses. An important progress took, indeed, place from his eyeglasses to the present operating microscope.

In the field of research I was early interested in physiology and I was lucky enough to get in contact with Ernst Bárány, who was working on circulatory problems of the eye. Soon afterwards he became professor of pharmacology in Uppsala and I could follow him to his new department. We became very good friends. He was a man with wide interests, a true polyhistor, who created an open and free atmosphere. He had an enormous curiosity and above all research was always a great fun. Many young ophthalmologists received their research training in his department. His personality made a lasting impact on experimental ophthalmology.

My own first project was to develop a technique and an instrument for measuring the pressure in the common, episcleral and in the aqueous veins. Assuming that a direct communication existed between Schlemm´s canal and the aqueous veins visible on the outside of the globe, then the pressure required to block the aqueous flow could indicate the pressure in Schlemm´s canal. Already after my first published, preliminary results I received a travel grant with the purpose to visit professor Hans Goldmann in Bern Switzerland, who simultaneously and independently was working on the same project, but he was using a different technique. Our aim was to compare our two different techniques by measuring on the same group of patients with both instruments.

After being isolated during the Second World War it was with a feeling of curiosity and expectations, that I started on my journey in 1949. Goldmann received me very nicely. He was a kind and friendly person with wide interests, a true polyhistor, and with a deep understanding and knowledge of mathematical and technical problems. He was considered to be one of the most important personalities in ophthalmology in Europe. Both Bárány and Goldmann were of kindred natures and later on became close friends. Together with younger colleagues in Goldmanns clinic we could carry out our comparative investigation.

Later on, back in Uppsala I enlarged my study to a sufficient number of normal individuals and glaucomatous patients using my original technique. The findings were that the pressure in the aqueous veins remained unchanged in glaucomatous eyes with increased intraocular pressure as compared to eyes with normal pressure indicating that the pressure in Schlemm´s canal remained unchanged and also that the increased outflow resistance in glaucomatous eyes was located in the inner wall of Schlemm´s canal.

One summer´s day, when I was working on this aqueous vein project, I was invited to visit Ernst Bárány in his summer house. As usual there was a free and informal discussion about almost everything and I speculated about the well known fact that the concentration of ascorbic acid was much higher in the aqueous humour than in the plasma. It might therefore be possible to use ascorbic acid as a test substance for measuring the plasma flow through the secretory part of the ciliary body in the same way as clearance determination in the kidney. Ernst immediately found this idea very interesting and worth-while to investigate. He placed all the resources of his department at my disposal and taught me all about how to carry out experimental work on rabbits and guinea-pigs. My work about aqueous veins had to wait.

These experimental results indicated that plasma flow could be estimated by means of ascorbic acid as a test substance. From clinical point of view it seemed to be of major interest to apply these results to a basic problem such as cataract. Professor Marc Amsler in Zürich, whom I knew beforehand, was a man of French charm and at the same time efficient accuracy in his clinical judgment and work. With his approval a study concerning plasma flow in the ciliary processes could be performed on cataract patients in his clinic. The determination of ascorbic acid concentration in the aqueous humour required a puncture of the anterior chamber of the eye. All the punctures of the anterior chamber were done with extreme precautions by himself or one of his senior colleagues and I never saw or heard of any complications in our study or in any other of the studies carried out in the clinic. The material was necessarily limited, but the results indicated that the plasma flow was reduced in eyes with cataract as compared to the control eyes without cataract. Further studies showed that the rate of aqueous flow also was reduced in cataract patients. After unilateral ligation of the carotid artery in rats the blood flow was reduced to about 50 percent and after X-ray exposure the lens opacities were more pronounced on the ligated side. The blood and aqueous flow were found to be reduced, but the requirements concerning blood and aqueous flow for maintaining a clear lens were so far not clarified and further studies were needed.

During my work in Uppsala doctor Bernard Becker from Wilmer Institute, Johns Hopkins University, Baltimore, USA visited Bárány and his department. He became interested in my method of measuring the pressure in episcleral and aqueous veins. After his return to USA I received an invitation to come over and do research work at Wilmer Institute. We were glad to accept the invitation and in 1953 together with my family we travelled 9 days by boat, which was different from the comfortable flights of today. From the beginning it was planned to be a short visit but we stayed 2 years.

It was a most inspiring time due to the unique personality of doctor Jonas S. Friedenwald, the head of research. He had a deep and thorough knowledge and understanding not only of ophthalmology, but also of basic fields like mathematics, physics and biochemistry. He had a deep interest in all human domains and I think especially in basic legal issues. He also was a true polyhistor.

The first project was to measure the episcleral venous pressure during tonography, and other problems related to tonography. Later on we were free to work on other problems too. When some complicated problems arose in the laboratory, he said that he would come back with an answer the following day. So he did. His answer included a full analysis and if possible an answer in his own handwriting. When we visited him in his summerhouse he took our 2 year old daughter on his lap and made some very good sketches of chipmunks. She was thrilled. His untimely illness and death meant a great and irreparable loss to ophthalmology, but also to our family.

Some months after returning to Sweden I came to Göteborg. The clinical work at the Sahlgrens University Hospital was dominated by investigating problems and especially surgical ones of retinal detachment. Ocular hypertension was later on investigated. In 1961 Ulf Strömberg carried out a mass survey of more than 7000 inhabitants, 40 years of age or above, in a small town outside Göteborg. The results showed that 152 individuals were hypertensive. In spite of Strömberg´s untimely death, these individuals could be followed during 20 years without treatment. As soon as the first signs of glaucomatous damage were found treatment was initiated. During up to 20 years without treatment 34 percent in this group of hypertensive individuals developed early signs of glaucoma as compared to about 5 percent in a group of initially normotensive individuals. This study showed that the risk among hypertensive individuals to develop glaucoma was significantly increased, but on the other hand that about two third in this hypertensive group remained undamaged during up to 20 year. The clinical problem was to detect the hypertensive individuals with a high risk for development of glaucoma early enough in order to start treatment, but on the other hand to identify the individuals - in this study about two third - without an increased glaucoma risk at least during 20 years, who did not necessarily need a similar early treatment. At that time we did not have sufficiently reliable criteria to differentiate the individuals according to risk. A lively international discussion has been taking place about the evaluation of ocular hypertension as a risk factor. The argument was on one hand that ocular hypertension meant no essential risk and that treatment could wait, but on the other hand that most of the hypertensive patients should be given glaucoma treatment prophylactically. The identification of risk factors has improved and now there seems to be an agreement to try to identify possible risk factors before starting prophylactic treatment.

In 1967, when I moved to Umeå in northern Sweden as professor, I found that some problems were different in a newly established university located in a sparsely populated, cold area. A positive factor was, that the eye department now could attract some very competent eye doctors. There was a need for modern equipment. When this problem was discussed with the leading politician in Umeå, Gösta Skoglund and I informed him that a modern type of an operating microscope, recently available on the market, had the highest priority he immediately, without hesitation, allowed me to order such an instrument. We were glad to be the first eye clinic in Sweden to start developing surgery of the anterior segment of the eye by the use of a modern operating microscope as a routine procedure.

Since the time, when measurement of the pressure in the aqueous veins indicated that the glaucomatous increase in aqueous outflow resistance was located in the inner wall of Schlemm´s canal, I was interested in the possibility of improving glaucoma surgery. The operating microscope made it possible to recognize small details in the angle of the anterior chamber and to find Schlemm´s canal. From the beginning I tried to perform trabeculotomies according to Harms, but at least in my hands the results were not satisfactory. After an analysis of the results my conclusion was that it might be better to cut Schlemm´s canal twice and to remove the intermediate piece of the canal, about 4 mm in size, thus creating two openings into the canal. In addition there might be a possibility that a new outflow route into the suprachoroidal space was opened. It could also be a filtering outflow through the scleral flap, which covered the gap in the canal. This was the glaucoma operation, trabeculectomy.

At a microsurgical glaucoma symposium in 1968 it happened that Cairns and myself simultaneously and independently reported about the new method of trabeculectomy. This type of coincidence could happen, when the time was ripe by the general presence of essential knowledge and suitable technical equipment.

In clinical work it is obvious that a detailed analysis of a surgical procedure must be incomplete. An experimental study was therefore desirable and was performed together with Bárány in his department on 17 cynomolgus monkeys. There were some special problems. General anaesthesia was necessary, because it was too dangerous to come close to these monkeys, when awake. The monkey eyes were less accessible. The conjunctiva was thicker and the sclera thinner than in human eyes. The results showed that the cut ends of Schlemm´s canal were closed by scar tissue in most eyes, only in 4 eyes was the canal open and the outflow facility increased. No filtering bleb was observed. It was suggested that a number of small holes in the trabecular meshwork might be better. So far there seemed to be no quite safe and long-lasting improvement of our trabeculectomy, reported 40 years ago. The development of scar tissue could not be controlled in a safe and satisfactory way.

Special medical problems were characterizing the parts of the three Scandinavian countries Finland, Norway and Sweden, located close to or north of the Arctic Circle. The climate was cold and the distances were long, e.g. more than 400 km from Umeå to the Norwegian border. When the influence of the distance was investigated, it was found that fewer number of patients visited the hospital from remote areas, in spite of the fact that the travel expenses were paid. One exception was the diabetics. They had to consider the legal requirement for their drivers licence.

The road quality was important. As an example an accident happened to me on one winter day with lots of snow and 20 degrees below zero Celsius. I travelled by car on the main road. When I met a big truck loaded with timber driving in the middle of the road, I was forced to keep as far right as possible. My two right wheels sank deep into a ditch and the snow covered the car up above the windows. I had no chance to get the car out of the snow by myself, but I was lucky enough that it was less than one kilometer to a house, where they had a tractor and kindly pulled me out and up on the road again. The country was sparsely populated and it could just as well have been a large distance to the nearest house. In such a case it could had been a serious situation if you are not equipped for strong cold.

After the years at Umeå University Hospital, I returned as professor to the eye clinic at Sahlgrens Hospital in Göteborg. My responsibility there laid mainly in the clinical work. As professor emeritus I was assigned as a short-term consultant by WHO to assess glaucoma as a cause of blindness in South-East Asia. It was quite an experience to see the completely different conditions for medical care as compared to Western countries. The access to care of eye diseases was limited, especially for patients from rural areas. At least 50 per cent of the primary glaucomas were of angle-closure type in South-East as well as in Far-East Asia. Often the angles were closed off in a chronic creeping manner without redness and pain forcing the patient to go to the hospital immediately. These patients would therefore come late and some of them were already blind. In one of the hospitals I met a middle-aged woman living in a rural area far from the hospital. Some months earlier she visited the hospital and her first eye was blind because of angle-closure glaucoma of a chronic creeping type. She was told to come back to the hospital without delay if she noticed that anything happened to her second eye. When she finally came she was totally blind in both eyes. At that time a prophylactic iridectomy was the only method available, but often the clinics were reluctant to carry out such a risky operation. The situation has now improved very much, when laser iridotomy has been available.

About 35 years ago both doctor Bernard Schwartz from USA and I participated in a congress in the South of France. We soon found that that we had a common interest in aqueous flow and corticosteroids. Since then we have been in touch with each other and some years later we could start working together on a common project. He had developed a method of scanning the optic disc for differences in colour between pale and pink on disc photos, and I had a material of hypertensive individuals with disc photos of good quality. About 1000 of these disc photos were mailed to him in a masked manner. In one project one group with and one without the exfoliation syndrome were compared. The result was that the pallor of the disc was significantly larger in the exfoliative group. Our conclusion was that the exfoliative process probably had extended to the posterior segment of the eye including the optic nerve. Soon afterwards our conclusion was confirmed by electron-microscopic findings of exfoliative material in the walls of the vessels leading to the optic nerve.

These results led to the hypothesis that the exfoliative process might extend still further backwards into the brain. In the first part of our study a group of patients suffering from dementia was investigated. The number of positive ocular exfoliation syndrome was significantly higher than in the control group. A following not yet completed study of the cerebrospinal fluid showed, that there was a damaging effect on the blood-brain barrier in the exfoliative group as compared to the control group. The study is still going on.

Looking back on my own experiences during more than half a century I can only say, that it has been a great pleasure and privilege to learn to know personally and to work with some of the leading personalities in eye research both in Sweden and abroad. They made a deep impression on me. It was a most stimulating, personal experience and research is still fascinating and great fun.

For the future I can only wish that as many as possible in the younger generations get the opportunity to travel to different countries and cultures and to meet different personalities. It can give a lot of information and stimulation not least to those interested in and fascinated of research as in my case. Everybody can benefit from close international contacts.

Address: Lilla Danska vägen 6, SE 412 74 Göteborg, Sweden, Phone/Fax: +46 31 404154