Lesson 2: The challenge of diabetic retinopathy Copy

Observation: As we know, there is a global epidemic of diabetes with over 340 million people who are affected by diabetes.

In order to understand the ophthalmic complication of diabetic retinopathy, we do know there is an international classification. How useful is this as a case definition for epidemiological studies?

Response: The most important thing that we are to keep in mind is that 90% of the vision loss that occurs in diabetes can be prevented by excellent, adequate, appropriate management of diabetes.

And therefore, classification systems have a great role to play in helping us understand
who needs what treatment so the vision loss can be prevented.

There have been efforts since 1968 to develop classification systems and now we have an international classification system which is used widely across the globe which actually looks at five grades of retinopathy, starting from “no retinopathy” and then going through stages of mild, moderate, proliferative diabetic retinopathy; which actually indicate the severity of the disease.

The big importance of this is, given the lack of ophthalmologists across the globe, it is exceedingly difficult to have people with diabetes being examined only by the ophthalmologist.

So having an opportunity of classifying and a categorisation system which is universally acceptable allows eyecare practitioners to actually play a role in the initial screening of the disease status and therefore it reduces the workload on the ophthalmologist and increases the efficiency of the system which manages individuals with diabetic retinopathy.

The other important thing is prognosis, so there is a natural progression across each of these stages from no retinopathy to proliferative diabetic retinopathy, and therefore it helps us to look at whether treatment is working and what treatment needs to be instituted at what stage.

So therefore the international classification system has a great role to play in managing patients effectively and reducing the workload on an already overloaded eye care system.

Observation: The WHO has said that more than 80% of diabetes is in low and middle-income countries. What do we know about the magnitude of diabetic retinopathy?

Response: That’s something which is very critical because there is this opinion that people share that diabetic retinopathy is not a problem in any of the low and middle-income countries.

The reality is different. At the moment, whatever evidence we have shown that diabetic retinopathy is the commonest cause of blindness amongst the productive age groups in most of the high-income countries.

When it comes to low and middle-income countries, we find that the prevalence of diabetes was very low until about two decades ago. But with the changing lifestyles and life patterns, increasing sedentary lifestyles, no exercise, there is an increasing trend in the prevalence of diabetes in most of the low and middle-income countries.

We now know that two countries, India and China together, have about 170 million people living with diabetes, which is exactly 50% of the global magnitude of diabetes.

Until now they have not had a major epidemic or a high prevalence of diabetic retinopathy because the prevalence of diabetes has been very recent, increasing prevalence has been very recent.

Epidemiological evidence shows that it takes about 15-20 years of the diabetic state to develop changes in the retina. So people have to live long enough to actually manifest the changes that one sees in the retina.

Most of these countries, like India and China, there is a sudden, increase, a
dramatic increase in life expectancies and people with diabetes are now living longer. The minute they live longer the prevalence of diabetic retinopathy is bound to increase.

There has been a recent review of about 35 population-based studies across the globe looking at the prevalence of diabetic retinopathy.

We see that the prevalence in high-income countries of diabetic retinopathy amongst persons with diabetes is about 30-50%. When you look at the low, middle-income countries currently, it is between 10-30%, 10-25% in more instances, so the prevalence at the moment is low, but with increasing life expectancies the prevalence of diabetic retinopathy and the magnitude, the number of people suffering from diabetic retinopathy in the low- and middle-income countries is also bound to increase.

So we actually at the tip of the starting curve of the epidemic of diabetic retinopathy.

In the next two decades, we will see significant changes in the prevalence of diabetic retinopathy in the low- and middle-income countries also.

Observation: Amongst the various study designs that have taken place to understand a bit more about diabetic retinopathy could you highlight how cohort studies have been used to understand the determinants of diabetic retinopathy and what do we already know about the determinants of diabetic retinopathy?

Response: Right, that’s again a very interesting question. The reason why cohort studies are so critical for diabetes is that diabetes is a longstanding, chronic disease.

Changes in risk factors, over a period of a number of years, is critical for changes to occur in the manifestations of either diabetes or diabetic retinopathy.

The risk factors may be actually acting right through the life course, 10 years, 15 years, or there may be a sudden spike in a risk factor. The sudden spike is not as critical as the long exposure to the risk factor.

And therefore to capture events right across the life course as type II diabetes you are looking at all the adult life age groups and in type I diabetes it’s a life course analysis that you need to look at, to try and look at what time of life does a particular risk factor have more influence on the risk of developing vision loss in diabetes.

Unless you look at all these factors, working over a long period of time, collecting data regularly, at periodic intervals, you will not be in position to understand the natural progression of a disease like diabetic retinopathy.

This is contrary to what we see in many of the acute conditions where the risk factors occur suddenly and you see the manifestations immediately, but in the condition like diabetes you need to actually look across the lifespan and therefore cohort disease epidemiology is so critical in understanding diabetic retinopathy.

At the outset, we need to actually look at the risk factors for diabetes as being different from the risk factors or determinants for diabetic retinopathy. They may not be the same; in fact, some of the risk factors, for diabetes, for example, do not influence the course of the disease like diabetic retinopathy.

Some of the important determinants, the duration of diabetes, how long the individual has been having the diabetic state, how good has been the control of diabetes, what we call the glycaemic state, has the individual been able to control his or her diabetes effectively, that is another important determinant.

The presence of co-morbidities, like hypertension, like renal disease, elevated lipids and conditions like increasing age, gender, access to healthcare, especially in rural populations, where getting medication or coming to the attention of an eye care provider may be compromised, are important determinants. Amongst all these, the most important perhaps is the duration of the diabetic state as well as how effectively has the diabetes been controlled.

Observation: Based on what we already understand about diabetic retinopathy, what are the priorities and challenges for action to address this diabetic retinopathy need across all populations?

Response: The main challenge is a big challenge for looking at diabetic retinopathy, the most important thing that we need to look at is how do we prevent the loss of vision in diabetes?

So programmes which look at screening out individuals who are at higher risk of developing vision loss
are the more important programmes to look at.

These are what we generally call screening programmes where we try and look at the retina of eyes, the retina of people with diabetes so that those individuals who have advanced stages of retinopathy are immediately brought in for treatment.

And this screening programme has been used effectively in a number of places across the world and has been found to be effective not only in the high-income countries but also in the low and middle-income countries.

We have screening programmes in India, in China, in addition to the high-income countries like the United Kingdom. That is one of the most important priorities, to institute screening programmes which can effectively pick up individuals who are at high risk of losing vision because of diabetes.

There is a scarcity of ophthalmologists across the globe and if eyecare practitioners were only to look at diabetic retinopathy it would mean that all the other eye diseases would suffer.

So we need a system of task shifting and what we could do in a screening programme is to use imaging techniques which can then give the responsibility of screening out those who are at risk of vision loss early enough by using digital imaging technology and using personnel like optometrists, ophthalmic assistants, ophthalmic nurses and that has been seen to be a very effective strategy going forward.

The most important thing we have to remember is that diabetes and its management is not for the ophthalmologist. It is a physician or a diabetologist who is actually managing diabetes and its complications in individuals.

So unless we have a comprehensive programme where the physicians are equally involved with the management of diabetic retinopathy we may not be able to achieve much. Just treating somebody with a laser is not going to be adequate to control the diabetic state and therefore involving physicians is again a critical step as the way going forward.

The other important thing that we just learned from a big study in India, where we had 11 cities being surveyed, what we found, which was actually astonishing to most of us, was that 50% of the diabetics, or persons with diabetes, the first time they came to an eye care practitioner, they were
already blind or visually impaired. It, therefore, means that people come to eyecare practitioners very late in the disease.

You need then to be proactive and go out into the community, go into the physician clinics and try and screen for diabetic retinopathy at a very early stage before the eye has been damaged beyond repair. So that is a paradigm shift. Innovation, in terms of involving physicians and other community
representatives who treat diabetes, rather than depend on the person with diabetes actually come to an eye clinic, which is normally very late in disease.

The other important thing is that a large number of people with diabetes do not actually seek treatment or do not comply with treatment, and therefore any of the strategies that we look at has to have a strong educational and counselling component which looks at not only the persons with
diabetes but also families where individuals have diabetes so that effective action can be instituted.

So a number of ways in which we need to move forward and not just depend on the individual actually walking into an eye clinic very late in the disease.

Observation: So what would we say are the key research questions that we need to urgently address in diabetic retinopathy?

Response: In terms of the research priorities in diabetic retinopathy. We could actually categorize them into two boxes. The first is in terms of the clinical management of diabetes and diabetic retinopathy.

And the second is the operational and epidemiological research priorities so that access to services can improve.

If we look at the first box which is the clinical management the priorities, we are to try and bring in technology which can enable in the identification of retinal changes without having to dilate the pupil.

This way, non-mydriatic digital imaging systems will go a long way in actually improving screening, increasing the reach of technology and allowing people to agree to be screened for possible ocular complications.

Secondly, current technological advances are not so patient friendly. FOr instance, laser treatments or vitrectomy is more destructive rather than constructive. Therefore, we have to explore other non-invasive treatment options that are eaiser to deliver with better long term prognosis.

There have been significant improvements with the use of intravitreal injections. A lot of patients seem to accept this mode of treatment since it is less invasive. We need to preserve this sought of treatment options and even improve on them since it has the potential for changing the management of diabetic retinopathy.

We also have to device a means of screening persons with little or no access to eye care practitioners; particularly during the early phases of suspected disease. For instance, we can leverage on the use of smartphones as imaging systems.

If we are able to manage the use of android platforms, smartphones, and if we could use the potential to improve the imaging techniques. In fact, there over ten companies across the globe which are toying with different digital imaging techniques for diabetic retinopathy.

These innovations can help in task shifting because a smartphone
can be used by anybody who has minimal skills. Aside from the ease of use, these technological approaches can help in reducing the cost of treatment.