Sensitivity and Specificity of Ophthalmic Practice

Diagnostic technology today is now becoming highly sensitive and specific, such that we are able to detect a disease years before it reveals itself in a patient and starts to cause visual impairment. Dr. Arulmozhi Varman, renowned ophthalmologist who has been at the forefront of utilizing advanced diagnostic technology to improve patient care, elaborates on how science and technology reach out to the patient in delivering appropriate care in a timely fashion.

What does specificity and sensitivity mean in ophthalmology? In the medical field today, tests are just increasing and diagnostic procedures are proliferating. They’re getting better and also expensive. How does a doctor choose a particular procedure? I’m not talking about treatment at all. I’m only talking about diagnosis—it is getting pretty expensive these days. That is when they (the doctors) look at sensitivity and specificity. Sensitivity means the ability of a test to accurately identify a person with a disease or a disorder, and Specificity reveals that a person does not have a disorder. Both should be of a high percentage—before you can pick up a diagnostic procedure and apply it to a particular patient.

True positive is when a person, who undergoes a test, has got a disease and the test accurately diagnoses it. True negative is when a person does not have a disease and the test also confirms it. False positive is when the person does not have a disease but the test has wrongly diagnosed the person; that’s pretty much risky. In the same way, false negative is when a person who has got the disease is diagnosed as not having the disease. We don’t want sensitivity less than 92%. We need to understand this about every diagnostic test and then look at the demographic prevalence of the disorder and apply the test to that particular demographic group. Then you will get better positive results.

Also, we want to have more and more non-invasive tests. MRI is absolutely safe but if you put in a dye to do an angiographic test, then it’s an invasive procedure. When you put a product into the body, there are people who react to it. We want to have more and more tests which are absolutely non- invasive but which can give you results that were obtained only by an invasive procedure.

Three Eye Diseases

Let me discuss about three diseases:

• Keratoconus
• Glaucoma and
• Diabetic retinopathy

India today has the dubious distinction of having the largest number of diabetics in the world. Unfortunately, we also have a whole lot of diabetic complications. The diagnostic tool that’s common to all of these is                    something known as optical coherence tomography (OCT). We know CAT scan, which is computerized axial tomography, where we use X rays and get slices. In OCT, we use light itself and this light source can give sections of the eye, just like you would see on a CAT scan or MRI. It gives unbelievable results. 

The accuracy here is about three microns. One micron is 1,000th of a millimetre and you can look at the retina which has 10 layers. Normally, to see the 10 layers of retina, you have to have a particular tissue, which is taken from a person who has already passed away. You have to put it into a section and put it under a microscope. Only after this, you can make it out. But with OCT, you can make out the 10 layers one by one. 

Each layer has got either cells or nerve fibre bundles. Today, this technology can count the number of cells on the retina and tell you the count per square millimetre, from which you can know if there’s a dropout of cells or the nerve fibres.  That’s the level of accuracy we get and it’s totally non- invasive.

The Doppler Effect

When you stand on a railway track, the train comes in with the horn on. As it comes, the tone gets compressed and as it leaves it gets elongated. You can trace a moving object using this Doppler Effect and that’s how we do Doppler of the carotid or the vertebral arteries and find out the blood flow there. Thanks to the ingenuity of human brain, we use the Doppler using light source and you can delineate the blood vessels brilliantly.

There are people who develop the disorder known as keratoconus. Mostly, this is inherited disorder. It comes out in the teens or at a later age. It can be worsened by allergies and by active rubbing of the eye, but otherwise, it can present itself as a natural course of the disorder. To diagnose keratoconus, we have been looking at the eyes sideways or make the patient look down to spot for a funny looking bulge. To be able to catch this bulge on a slit lamp or with the naked eye, the bulge has to be almost one or two millimetres. That means, the disease is already very advanced. That was how it was done when I was doing my PG in the 80s. 

There was another way of looking at it. If somebody has a high cylinder power that keeps changing and a poor vision, then you say that person has got keratoconus. This disorder is pretty prevalent in India and in the Middle Eastern countries also.

Now with the OCT, the resolution is three microns. When there’s a 10 micron difference in the thickness of the cornea or by looking accurately at the shape of the cornea, you can catch the disease at a very early stage. It’s a totally progressive one and as it progresses, vision drops and eventually we had to do only keratoplasty. We take out that cornea, use a donor cornea and sew it on. That was pretty much a difficult surgery with not so good outcomes. But now we can prevent this from occurring by doing certain treatments, which will strengthen the cornea and prevent it from becoming weaker and bulging. That’s called Collagen Crosslinking. The diagnostic machine gives raw data. Algorithms had to be developed to get to the diagnosis. So we had multiple groups of scientists working on this to come up with algorithms.

We can get accuracy to the specificity of 98% and sensitivity of 92%. That’s really good. So early diagnosis would help preserving vision and preventing surgical intervention.

From Lasik, by Luck

What made the diagnosis of keratoconus bloom and fructify into something that’s phenomenal is simply because a lot of patients were willing to undergo laser treatment that is Lasik or now SMILE, to remove the glasses using laser. You can do it on a person who is 18 years plus who is wearing glasses and if the person’s cornea is stable and if everything is good, you do a five minute laser procedure and no glasses are needed for lifetime. When they started looking at the cornea very carefully, they started catching keratoconus.

So, unless there’s money in something, the industry does not do any study into a particular pathway. Keratoconus by itself was not a money spinning entity. A research cannot start off unless it is going to be funded. Funding does not come in, unless there’s a future to the product. That is how, keratoconus could be diagnosed as a spinoff from Lasik.

Diabetic Retinopathy

Then let’s come to diabetes. India has the largest diabetic population in the world. The Western literature says that almost 30 to 40% of people with diabetes tend to develop diabetic retinopathy. While the Indian demographic data says the percentage is a little lower, on an average, around 20% of people with diabetes develop retinopathy.  

This has to be caught because this is a silent disease. At least in keratoconus, the patient will have blurred vision. Here, it’s absolutely silent. By the time the vision starts to blur, it is too late. Most often, it is very difficult to do anything about the vision already lost and you can prevent further loss of vision by treating appropriately.   

Diabetes affects blood flow. Whether it is the eye, the brain, the heart, the foot or the kidney, it is only the blood flow that is impeded at the capillary level and not at the large vessel level. Once that occurs, blood starts to leak out there. New capillaries try to form to overcome the blocked areas but these are not as structurally strong as the normal capillaries. The normal blood vessels start to leak serum, then blood, followed by other complications. They’re not able to supply oxygen to the tissues, in spite of new vessels forming and the old vessels are blocked. That’s the underlying pathology.

The advantage is that the retina is the only place in the human body where blood circulation can be physically observed. This assumes a huge amount of importance. Though we can look at the blood flow and the structure, we won’t know how the blood is flowing through it. We had to inject a dye called fluorescein into the eye and take serial photographs. This is called fluorescein angiography.  We were not doing it frequently, because it is an invasive procedure. Some people develop allergy to it and can have even a cardiac arrest sometimes. Though the risk is one in 10,000, still, that’s a risk. It is also not practical to do these tests frequently.  

Now we can see the blood flow using OCTA (OCT with angiography), which uses the Doppler principle and light instead of sound. It’s far more accurate and far more details are available. You can do this once in 24 hours, if you wish to, for a patient and it’s absolutely risk free. So we really have a non- invasive procedure, which is brilliantly accurate to diagnose early retinopathy.

Dilemma in Application

Then it comes to how many patients am I going to put on this machine?  

Are we going to put every diabetic patient on this? Or are you going to put only people who you think, have some kind of a problem by looking at the patient with the microscope? It is a very difficult question to answer. Then you have algorithms for this. If you have a patient whose sugar is well controlled and he or she has only three to five years of known diabetes history, maybe the chance of development of retinopathy is low. Anybody over 10 years of known diabetes should have this test done every year. That’s no question at all. Anybody between five to 10 years and poorly controlled diabetes, should have this test done every year.

In spite of all that, if I do 10 patients, I’ll probably catch two or three patients with the disease. That means we are doing more procedures than what is probably warranted. That’s how we it look outwardly. But when you do serially on a person every year, you can catch the person’s disease very easily down the line. So this is where cost comes into play. A low end machine with low resolution costs only 75 lakhs and the high end machine will cost 1.5 crores. The patient has to bear the cost. The doctor is only looking after the machine and using it for the betterment of the patient.

The Management Conundrum

How will you apply the algorithms? And how ethical are you going to be in applying the algorithm? You will find that in India, there is no multi-speciality hospital with a thriving ophthalmology department, except for one or two in the whole country. Management specialists running the hospitals merely go by the returns and do not sanction funds. But if I start using these sophisticated machines, my overall practice changes. More number of patients get diagnosed and then they may go for another procedure. If they go for surgery, it becomes safer and the results get to be superior. So the whole system changes. That’s how we must look at it. 

The cost of getting this kind of test depends on the centre and would be anywhere between Rs.2500 to Rs.5000. You must take it as insuring your eyes for Rs.2500 a year. Of course, apart from eyes, we have got many other organs in the body, and medical insurance—unlike in the US or Australia—does not cover the cost of investigations. But once you do that, your premium is going to shoot up and the number of premium paying capable patients or population is still low in India. A sobering thought is you need finance to do anything.

China is Way Ahead

Two decades ago, both India and China were considered poor countries. India has been having the SMILE technology for about 10 years and the total number of SMILE machines in India are about 35. I bought the first generation machine eight years ago and mine was the fourth in the country. I have bought the upgraded version, which is the second in the country. It looks good. But China has 550 machines.

That means the GDP is running the engine. Another aspect is that the oriental race has more minus power than anybody else. That’s the second point. Eight weeks ago, I was in Singapore for a user’s meet. A Chinese guy came up and made presentations and the number of surgeries they have made were mind boggling. What really puts the scale at an even keel is they charge two and a half times of what we charge our patients. So finally, whatever we want to do in technology, technique or delivery of anything to the patient, there has to be finances. And that can only come as our GDP keeps going up.   

Glaucoma

The eye is a fluid filled structure. There is a continuous manufacturing and circulation of fluid and that’s slowly going out through another pathway. The balance between the two keeps up a certain pressure which is normally between 12 to 18 mm of mercury. Anything higher is not good. Lower is not a problem but too low is not good at all. When it goes higher, there is a pressure effect. The optic nerve bulges. As the pressure keeps increasing, the nerve fibres keep dying out. Slowly the patient may lose vision on the sides, while the central vision is still good.  

How does somebody get glaucoma? Most of it is genetically predisposed. If one person in the family has glaucoma, the chances of the siblings having glaucoma are very high and of the next generation are 50% lesser but they are still there. It can be easily detected, provided one makes a visit to the doctor.

When you lose fibres on the top, you lose vision at the bottom and vice-versa. The person cannot see the lower half, but can see up and look straight. When they go down the stairs, they’ll have difficulty; otherwise, they may not even know that they have a problem. The field test is the diagnostic tool and it is considered the gold standard.  

Its prevalence is next only to cataract. This is the most common blinding disorder in the world. In the darker skinned races, it is more prevalent, particularly because our irises are thicker and have more pigments and we are more prone to glaucoma, than a lighter skinned person. The conventional computerised testing procedure is pretty much cumbersome, particularly because most of the patients have glaucoma in their 60s, 70s and 80s. The machine also gives giving false positive and false negative results. So it can be quite confusing and getting accurate results are sometimes difficult.

How do we diagnose glaucoma early with OCT? With OCT, you can actually count the number of cells and the number of nerve fibres and it gives you a graph and an algorithm that tells you if you have or don’t have glaucoma.  OCT can catch glaucoma one to two years before the person comes up with a field defect. This is highly sensitive and highly specific. It is very tempting to use it on a large number of patients. But then, we would like to look at patients who have funnily shaped disks, aged above 45 and patients with a family history and then put them on this. Here again, a large number of patients would come out as negative, which is good, but he or she needs to get these tests repeatedly done. That’s again a burden on the pocket but there’s no excuse for that and they must do it.

ERG or Electro retinogram has pretty much been there for 30 to 40 years. The machines are very expensive and cumbersome to use. You have to put multiple electrodes and it will take 30 to 40 minutes. So the patient will really feel uncomfortable. But now, you can do the same electrophysiology with just two electrodes and it’s fantastic. It doesn’t give you just the raw output. It gives it to you on a number and a colour scale.  

AI, the Next Stop

There are a lot of issues that come into play, and finally, all of it boils down to applicability of a particular test to a particular group of people and how to make it cost effective. There’s only a particular level to which the cost effectiveness can be done by the doctor. The paying capacity of the general population has to increase. When economy improves, health improves, wealth improves and everything improves.

So in summary, advanced technologies are available for early diagnosis of potentially blinding diseases. They have high sensitivity and specificity. They are totally safe and non-invasive. They are rapid tests and will take less than 10 to 15 minutes. There is no great discomfort. Now artificial intelligence is coming in. As I told you, the retina is the only place where you can look at the blood vessels. You can now see how blood is flowing. AI is now able to compute miniscule micron level changes on the retinal vasculature and predict if the person is going to develop renal disease, cardiac disease or neurological disease. Google is working on this.

Q&A Session

Q: Will exclusive ophthalmologic diagnostic centres in public space, just like the scan centres available now, help in bringing down the diagnostic cost?

Dr: There are centers like that in Chennai itself but that does not make it any cheaper and does not reduce the cost to the patient eventually. What we all have to work towards is increasing the paying capacity of the general population.

Q: Can cataract be prevented?

 Dr: Cataract is an aging process. It varies across races. For the Indian race, cataract occurrence between the age of 65 and 75 is the most common. It could come earlier or later. But the point is, you cannot prevent cataract. It can be dealt with. 

Q: Does yoga help in preventing eye diseases like cataract and glaucoma?  

 Dr: Yoga will make you healthy and better health will reduce a lot of diseases. But, I don’t believe that yoga is going to reduce the chances of developing cataract or glaucoma.  

Q: How safe is it to do eye testing in optical retail outlets? Why does the government permit this?

Dr: Yes, it is safe and you can’t get into any trouble because of that, because testing vision is just one part of testing the eye. If you come to the doctor, the vision will be tested, intraocular pressure will be tested and the optic nerve and all the structures of the eye will be looked at by the doctor. If something is not alright, then further tests will be done. So you’re able to stop a problem at the first level. But imagine a person has got early glaucoma. The optical outlet will not be able to diagnose it. They can only tell you if the vision is normal or not. So it would be much better to visit an ophthalmologist and get a proper eye test, particularly for anybody over 40 years of age.

Q: Are contact lenses safe?  How often are they to be changed?

Dr: Contact lenses are safe if they are clean; unsafe, if dirty. The person who’s using it either has not been trained to maintain it or has become lackadaisical in the maintenance. That’s where it starts to go haywire. Usually, we prescribe monthly disposable lenses. To be 100% safe, you can use daily disposable lenses but it’s a little expensive and absolutely safe. But contact lens is only a temporary solution. If you are looking for permanent solutions, go for Lasik.

Q: How do computers, mobiles and other devices impact vision? 

 Dr: The common misconception is that we are getting rays from cell phones and laptops. There are no rays coming out from any of these products. All over the world, myopia is on the increase and which is corrected with minus power glasses. Why is that on the increase? One explanation that is given

is that evolution wise, we were hunters always looking at the distance and that brings in myopia. Today, we look closely at the text books, laptops and mobile phones. To counter this, a growing child needs at least one to two hours of natural sunlight exposure. We must encourage our kids to go out and play and get more exposure to sunlight.

The reason why a doctor normally advises not to use a cell phone is it is too small and because it is smaller, we bring it closer and that causes eye strain. It is better to work on a laptop or a desktop computer than working on the mobile.  We have to learn to live with these products. All of us are going to use computers a lot and people in the software industry must follow the 20:20 rule. Every 20 minutes, get up and stop working. Look at the distance for 20 seconds. That’s what we want you to do.

Q: How do you promote patient education?

 Dr: We have a whole bunch of YouTube and Instagram videos for patient education. That’s the easiest way to reach out to the population.  

Q: In Pondicherry, there is an organization that can treat the eye problems through a simple two weeks session using ball and oil. Is it useful to take the session?

Dr: Twenty-five years ago, I’ve sent my people to get trained there for one whole month and we tried to replicate it here. But none of these exercises can reduce the glass power. Let’s be very clear. But these exercises really do wonders for non-specific discomforts. There’s no harm in doing that and it probably does some good. But if your aim is to reducing or getting rid of your glasses, it doesn’t work.

Q: How safer is Lasik? If safe, why do many ophthalmologists wear glasses?

Dr: I wear glasses and that’s for reading. Anybody over 40 needs to wear glasses for reading. Lasik is safe and it works as of now, with close to 99.8% success rate, for distant vision. Not for reading and that’s why most doctors continue to wear glasses. My daughter-in-law has Lasik done by me. My daughter has undergone Lasik and it is very safe as long as your cornea is fit to undergo the treatment. Lasik is about 30 years old. Now we have got something called SMILE, which has taken out all the small niggling issues in Lasik. There are different technologies available and depending on the technology that’s used, it can cost anywhere between 50K and 60K.