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What are the primary causes of blindness in the world today? How widespread is the problem?
There are 23-45 million blind people in the world. We define blindness differently for those 2 figures: "economic blindness" and "social blindness". Economic blindness would be less than 6/60th vision, which is the top level on the vision chart. Once you have less than this, it is very difficult to function economically.

Social blindness, which affects nearly 23 million people, is the inability to move around, an activity severely limited with vision less than 3/60th; 80 per cent of blindness is in the developing world.

These figures will double by AD 2025. Cataract, glaucoma, diabetic retinopathy, and macular degeneration are the 4 major culprits. There are 3 causes of blindness indigenous to the developing world. Trachoma, prevalent in West Asia, will disappear over the next decade. Onchocerciasis, river blindness, is prevalent in Africa. If we can figure out how to deliver Ivermectin, a new drug, to every individual once a year, the diseases will be wiped out.

Then, there is blinding malnutrition -- Xerothalmia and Keratomalacia. The solution is not massive distribution of vitamin A but targeting that distribution to children with high risk, plus nutritional education.

What are the priorities in treating cataract?
In the developed world, cataract services keep cataract down to a very low rate. But in the developing world, there are some major problems -- either an absence of humanpower or infrastructure, such as in Africa and in some parts of Latin America; or an absence of managerial skills, like in Southeast Asia. There are very good ophthalmologists and hospitals in India, but the managerial ability is poor.

What are the thrust areas in cataract research?
We cannot, at this stage, talk of preventing cataract. We know that if we could slow down cataract by just 10 years, we will reduce by 45 per cent the number of people who will ever need to come to surgery. The 2 main risk factors are radiation/sunlight and nutrition. Studies in Delhi and Boston and somewhere in Italy that indicate the factors most inversely correlated to cataract are food intake, nutritional status, body fat and socioeconomic indicators like education level, type of work, even the type of fuel used for cooking.

We now have a clinical trial going on in the USA with some 4,600 patients in which they are randomised either to minerals or vitamins or to combinations of vitamins and minerals, or to placebos. We will know in 5 to 6 years whether vitamins slow down cataract. This trial would come under the rubric of operations research -- how to identify the patients who have cataract, convince them to come in for surgery, be sure that the facilities to do safe and effective surgery are in place. We have been encouraging these 4 steps, part of a programme we have in India. We have been most successful in the south, in Madurai, Hyderabad, Madras, and we would like to see the same approach being developed in Delhi, Calcutta and Bombay.

You are doing a study at the Aravind Eye Hospital in Madurai which looks at the 2 alternative techniques of treating cataract...
Yes the question is: how do you measure the output of work done here? We say that 1.3 million operations are performed a year, but there is another way of assessing the cataract programme's success. What you really want to know is how much sight restoration has been accomplished. Cataract removal does not add to sight restoration. So we want to move the ophthalmic community into sight restoration as their goal, rather than dealing in statistics. One of the ways to do that is to assess how satisfied the patient is with the intervention.

Let's say, if you have vision in one eye and cataract in the other, there are 2 types of operation that can be done. One operation is to remove the entire cataractous, opaque lens, and to replace it with a very thick spectacle glass. Now, take a person with good vision in one eye; the other, which has a spectacle glass, will see everything 30 per cent larger than the first eye. You cannot use both eyes together with that discrepancy. We are trying to tell the ophthalmic community not to operate on patients with a good eye, unless they do a different type of cataract operation -- which entails not removing the entire lens but inserting an artificial lens -- the intraocular lens -- inside the eye so that the images in both eyes are of the same size. The intraocular lens operation is being done in about 10 per cent of cataract surgical patients in India.

First, we have to train ophthalmic surgeons to do this new operation. We must have new types of equipment. India manufactures very high quality intraocular lenses and the institution that pioneered this is the Aravind Eye Hospital. G Venkataswamy wanted to do the surgery using the intraocular lens but found it difficult to buy the lenses abroad at $50-80 dollars. His plant is turning out about 100,000 lenses of very high quality every year. He sells them at cost to any charitable institution anywhere in the world. Of course, he uses them himself. They cost $7-8 each to manufacture.

The World Bank has given a loan of $117 million to the government of India for 7 states to reduce blindness by 50 per cent. That will require, over the 5-year period, something like 11 million more operations -- a little over 2 million each year, in addition to 1.3 million already being done, so that's about 3.3 million a year. Since there are about 1.5-1.7 million new cases each year, 3.3 million cataract operations each year will take care of new cases and also reduce the backlog.

What is the relationship between the nutritional status of a person and cataract?
The hypothesis of cataract formation, as indeed it is for many other chronic diseases, is oxidative stress. The lens has a very interesting structure. The lens fibres are continually replenished throughout life -- the lens actually grows; its surface keeps getting compressed into the interior and new lens fibres grow outside. Once the lens fibre reaches its full length it begins to lose all its organelles, its mitochondria, its nucleus, its enzymes. So it is very vulnerable to any damage to its structure.

The lens proteins have a certain size and what is thought to happen, at least at the centre of the lens, is that they have S-H or sulphur-hydrogen groups, and with oxidation the S-H group drops its hydrogen and you get S-S linkages. So you get 2 molecules then 4 then 8 then 16. You begin to get this huge aggregation of proteins and at some point the distance between these aggregates is smaller than the wavelength of light. So light can't pass through. And a cataract is formed.

In the case of the newly laid down lens fibres, there is a different hypothesis, because they have all the organelles. They have high levels of chemicals which are antioxidant in activity. But it is thought that the membranes of the lens fibres are damaged and even the DNA in the cell layer which is laying down these fibers can be damaged by ultraviolet light, and by poor nutritional levels. With the damage, there are osmotic changes: the lens fibres swell and burst, which can actually be seen clinically.

What are the priorities concerning the control of diabetic retinopathy?
I trust you are aware that 50 years ago, diabetes was very rare in India but now it has become very common, particularly among the middle class -- largely due to dietary changes. The sad thing about diabetic changes in the eye is that simple laser treatment can prevent blindness in 95 per cent of the cases. Even with this information, in the US 50 per cent of diabetics will become blind because they have high risk characteristics but are not being treated.

What do scientists know about glaucoma?
Glaucoma is primarily a problem of age, but it is particularly prevalent among Blacks. We have just completed a study in Barbados in the West Indes, where the population is homogenous. In the age group of over 52, 13 per cent have glaucoma.

Glaucoma is a condition where the pressure in the eye is too high. We do not know how the elevated pressure does its damage. We think it effects the nutrition of the optic nerve, and therefore the nerve dies. We have no cure, but think we know how to control it, by lowering pressure in the eye.

But we are doing a series of clinical trials which I think will answer 2 very important questions: which is better -- immediate surgical treatment to lower the pressure or medical treatment followed by surgery if the pressure cannot be lowered?

How are you so sure that trachoma will be eradicated in 10 years? How is water a factor?
There are 3 approaches to the problem. The easiest is to improve the economic situation. In Tunisia in North Africa, trachoma disappeared as their economic wellbeing improved. The second finding that was really followed up in Egypt was to show that if one washed children's faces once a day even with dirty water, trachoma's spread from person to person would decrease.

So far, all trachoma treatment has been directed at the eye. But trachoma patients have a systemic disease -- the organism is in their lungs, in their gastrointestinal tract. You may sterilise the eye but the infection comes back. A new antibiotic which can apparently clear the body of infection with one dose is now being tested in Egypt.

What is the research in macular degeneration?
Macular degeneration is very rare among Blacks, prevalent among Caucasians -- and certainly prevalent in India. It is a degeneration of that part of retina called the macula, which enables us to have the highest vision. If we lose that function, we never go blind, in the sense that all our peripheral vision is intact -- but we do lose the ability to see minute details except with very high magnification. Macular degeneration is the main cause of loss of vision over the age of 60.

We still do not understand macular degeneration. A which involves 4,600 patients in whom we are looking at nutritional factors related to cataract, also involves patients with changes in the retina suggestive of very early macular degeneration. We will determine whether vitamins and/or minerals affect the development of macular degeneration.

What are the presumed causes of this disease?
The presumed cause is some sort of breakdown among the cells that nourish the retina. There is a single layer of cells underneath the retina, the retinal pigment epithelial (RPE). The cells of the retina where the pigment captures light and converts it into electrical impulses, are nourished by these RPE cells. In macular degeneration, just that one little area which is about half a millimetre in diameter is affected.

In that area, the RPE cells undergo degeneration and some things happen. Either the cells just disappear (the "dry form") or, with their disappearance, blood vessels that are underneath begin to proliferate and begin to grow in and bleed (the "wet form"). Both forms lead to decreased vision. Ninety-nine per cent of light that falls on our retina is absorbed by the RPE cells. Only 1 per cent is actually absorbed by the retina. So perhaps this continual absorbance of light causes some change. It may be that these RPE cells have a very important role: the rods and cones -- the elements that contain the pigment -- are continually being renewed; and the way they are renewed is that the RPE cells actually phagocytose, or eat up, the outer segments of the rods and cones and continually chew them up and convert them into debris. If this function of the RPE cells is impaired, the rods and cones may die.

How do you see the global future of blinding eye diseases?
I think the next 2 decades will give us the opportunity to really make a major impact on reducing these major causes of blindness, either by developing new ways of delivering services such as making use of information we have on diabetic retinopathy, or by improving the delivery of cataract surgery, or by actually interfering with the development of the disease. In the case of onchocerciasis and trachoma, and vitamin A deficiency, we do have technology on the shelf which is simple and inexpensive. But there should be a commitment to put the resources in to develop these technologies and deliver them to the public.

What about alternative systems of medicine to treat eye diseases?
There is an office of alternative medicine now at the NIH. I am not terribly knowledgeable about alternative systems, but certainly in terms of naturally occurring plants and fungi, I think that is something that really should be followed up. But in terms of other forms of treatment, I am a little less enthusiastic.

In India, several homoeopathic preparations are available which claim to retard the growth of cataracts. Are they any good?
There are 85 treatments for cataract growth and not a single one of them has been proved to work. I am in favour of alternative medicine provided they are subjected to scientific evaluation.

Is there any evidence that eye exercises retard myopia?
When you do an eye exercise, the only thing you are doing is exercising the muscles that move your eye. Myopia is a condition that depends almost solely upon the size of your eye and you cannot change that.

What are the factors?
Well, interestingly enough, the factor is a blurred image on the retina. If you take a chick and glue half of a ping-pong ball on one eye so that light can reach it but not form an image, that eye will grow and grow and will be very myopic. You can do another experiment: put a portion of a ping-pong ball on the front of the face, so that one half of the retina receives formed images and other half receives unformed images; the half receiving the unformed images will be enlarged and the half receiving formed images will be of a normal size. But the question is: precisely what is happening in the human eye?

Could you tell us something about squint correction?
There are 2 aspects of the central nervous system that are particularly attractive. The first is how to bring back to the central nervous system the ability of nerves to regenerate. If you cut a nerve in the peripheral nervous system, it is going to regenerate, but if you cut a nerve in the central nervous system, it won't. It does have the capacity to regenerate during the development of the foetus and, in fact, for a short period after birth. It is thought that the genes that control regeneration are turned off soon after birth.

One of the approaches has been the ability to allow nerve fibres into the spinal cord after the backbone has been crushed to re-grow. There are 2 problems: one is that as scar tissues forms, it presents a physical obstruction to nerve fibres growing in. So you want to prevent scar tissues from developing. The second is to allow the nerve fibres to develop what is called a "growth cone" and grow and make attachments. The next thing is to figure out how to turn on the genes that will allow the nerve cells to grow.

The second area is what we refer to as the plasticity, or the adaptability, of the nervous system. We know there is a tremendous amount of redundancy and we know that the brain can take over functions when other parts are lost, especially in infants. Eyes that squint are not properly aligned. Alignment is thought to be a function of the brain -- what is called "supranuclear control". It's not a problem regarding the nuclei in the brain which control the eye movements. It is a problem of the co-ordination of the 2 eyes, which is taking place at a higher level. And I think that if we can understand what that control involves, it would be possible to correct it medically rather than surgically, in an infant.

What are the trends in basic eye research?
The tremendous movement in molecular biology and genetics is taking place in ophthamology. Retinal degeneration, even macular degeneration, will be approached through genetic and molecular biology rather than some sort of applied approach. This is moving very rapidly and for every 1 dollar we put into applied approach, we are putting 9 dollars into this very basic research. We have a $300 million budget every year at the National Eye Institute NEI), of which approximately $30 million is applied and $270 million in basic research.

At the same time, genetic research is becoming extremely controversial. The ability to interfere even in the somatic cells genetically is fraught with all sorts of concerns. It's a very complex issue. At the NEI, there is probably the largest collection of patients who have a very specific retinal degeneration in which there is an enzyme defect. We are probably 5 years from curing these patients by replacing the defective gene with a normal gene in their cells.

Does the NEI deal primarily with the health problems of the US population?
We support research outside the United States -- to a limited extent, because most eye researchers outside the US have their own support. D Balusubramaniam, director of Celluler and Molecular Biology in Hyderabad is about to receive a research grant from us. Interestingly enough, it is the first research grant given solely to an Indian researcher by the National Institutes of Health since about 1970.

How do other US institutions react to a very broadbased funding priority?
It's getting more difficult. We are only funding about 1/3rd of American investigators. So when we want to fund someone outside the United States, we have to be absolutely certain and this is a unique opportunity. We recognise that research is international.

What proportion of the world's eye research is funded by the National Eye Institute?
Globally, we would account for somewhere between 50-65 per cent of the funds available for eye research.