Viewpoint Clinical Conference
May 4, 2022 • 10 minutes read

Researching real-life protocols for the treatment of diabetic retinopathy

Dr Marko Lukic

May 4, 2022 • 10 minutes read

Introduction

Diabetic patients can develop severe eye complications if a professional does not spot their symptoms or clinical signs and start treatment early. Yet, few studies have hitherto been done on advancing from a more pragmatic protocol that is easy to use in a busy hospital.

So says consultant ophthalmologist at Moorfields Eye Hospital, Dr Marko Lukic, who spent five years researching the topic. And more specifically, the effect of injections with a particular anti-VEGF remedy.

In this interview, he shares his main findings and advises optometrists on how to examine for signs of diabetic retinopathy. The first part zooms in on his PhD work, while the latter delves more broadly into diabetic macular oedema and how to prevent a decrease in vision.

Read Marko’s bio here

What is the subject of your research?

Marko Lukic

My PhD examines the short- and long-term outcomes of intravitreal aflibercept injections in the treatment of patients with diabetic macular oedema, in real-life settings. And the impact of switching between two anti-VEGF (vascular endothelial growth factor) agents.

Retina specialists in Europe, such as myself and my colleagues at Moorfields Eye Hospital, face the challenge that the treatment protocols suggested by landmark trials are difficult to implement in a real-life hospital setting. Therefore, I found a need to examine whether protocols from our clinical services were non-inferior to the landmark trials. That is if they could match the results.

So, you wanted to help establish a more practical protocol for treating diabetic patients?

Marko Lukic

Yes. There are very strict inclusion and exclusion criteria whenever you do a randomised clinical landmark trial. However, when a patient comes to your clinic in real life, those criteria can create obstacles. For example, you cannot tell a patient that you’re not allowed to treat them simply because of uncontrolled blood pressure levels or increased haemoglobin HbA1c.

That is just one of the shortcomings of the established protocols. Another is the high number of suggested injections, which would eventually lead to an overburdening of the health care system.

We wanted to test whether the anti-VEGF remedy (intravitreal aflibercept) used in our hospital can lead to a faster vision recovery and thus limit the need for injections. Unfortunately, not much real-life data on intravitreal aflibercept existed in this field when we started our research.

Why did you choose that topic?

Marko Lukic

We analysed diabetic patients who developed macular oedema. That is a fluid in the very central part of the retina, which, if not recognised in time, can cause irreversible vision loss. The condition is the number one cause of legal blindness amongst the working-age population in Western countries, and it hits primarily young or middle-aged people.

Diabetes mellitus is a major global health challenge. The number of patients is rising, with just under five million currently suffering from the condition in the UK alone. In addition, the International Diabetes Federation has published data that indicates that the disease is present in eight per cent of Europeans between 20 and 79 years.

The treatment costs of diabetes and its complications are enormous – accounting for a tenth of the total NHS budget (ed. National Health Service in the UK). So, I say that we live in a pandemic of diabetes. However, it is a silent disease that we often forget about.

I like to highlight the message that nine out of 10 patients suffer from diabetes 2, which can be prevented by changing one’s lifestyle. The role of eye health professionals is crucial in recognising early signs of disease, which may save patients’ sight.

My research has contributed to that.

Let's jump to it. What did your findings show?

Marko Lukic

We proved our hypothesis and showed that treatment results based on our protocol, which is more applicable for real-life settings, are non-inferior compared to landmark clinical trials. That means that our protocol, which we already use in a real-life environment at Moorfields Eye Hospital, can significantly improve vision with fewer injections in the long term. As a result, we can maintain patients’ good vision.

Secondly, we have shown in real-life that those whose baseline vision is better to begin with, have achieved better visual acuity at the end of follow-up than those whose baseline vision was initially worse. So that means that it is crucial to start treatment early when vision is still very good.

A third important finding, which I would like to highlight, is that those who switched from the anti-VEGF intravitreal ranibizumab to the anti-VEGF intravitreal aflibercept got some additional benefit in vision, regardless of the time of switching between the two agents.

Which research methods did you use?

Marko Lukic

My colleagues and I conducted a retrospective study of diabetic patients at Moorfields Eye Hospital in London, UK. We used electronic medical records and data on visual acuity, medical history, and OCT-based anatomical variables for our analysis.

We selected a cohort of diabetic patients based on a specific treatment period with anti-VEGF. Each patient had visual acuity, intraocular pressure and OCT scans done at each visit. Patients followed the Moorfields’ protocol for treatment.

Do the results prompt important messages to eye care professionals?

Marko Lukic

The data shows the importance of starting treatment when the visual acuity is still very good. Our studies’ range was between 69 and 80 ETDRS letters. The point is – don’t wait until it gets worse.

Screening plays a huge role in catching patients early on, just when they start developing initial changes in their vision.

Are there any specific changes optometrists should look for when seeing diabetic patients?

Marko Lukic

Good training is paramount for recognizing the small changes in a diabetic patient’s eyes. My advice is to:

  • Look for vascular abnormalities like new vessels on the optic disc or retina.
  • Check the macula for potential signs of maculopathy (microaneurysms and lipid exudates).
  • Ask patients about their blood pressure and kidney function.
  • Check for retinal vein beading – it is irregular constriction and dilation of retinal venules specific for diabetic retinopathy.

These indicators help you measure the severity of the diabetic disease and its potential for further progression of the eye disease. But bear in mind that retinal changes might not be caused only by diabetes.

Diabetic patients may have coexisting systemic conditions, such as hypertension. Here, retinal veins (if blood pressure is high or uncontrolled) are more dilated and tortuous, whilst in purely diabetic retinopathy, they are irregularly constricted and dilated.

In other words, you need to account for the complexity of symptoms?

Marko Lukic

I recommend that all optometrists familiarise themselves with the sinister eye features of diabetes. That includes learning about the pathophysiology, how to rate diabetic retinopathy, and the different treatment options.

The knowledge will ease both patient communication and referrals. For example, a common mistake, likely due to similar clinical findings, is referring patients with retinal vein occlusion rather than with diabetic retinopathy.

Currently, what's the standard treatment for diabetic macular oedema?

Marko Lukic

In the past, laser was the favoured treatment method.

Nowadays, the golden treatment standard is intravitreal injections. We have two major groups of medical drugs: anti-VEGF molecules and steroids. We expect new molecules, which entered the second or third phase of our clinical trials, to be available soon.

Those will help us reduce the number of injections per patient.

What tasks do you think optometrists can perform in diabetic retinopathy care?

Marko Lukic

I see optometrists as very important partners in providing good eye care to diabetic patients. With proper training and supervision, they can monitor patients safely in the optometry clinic, especially using new equipment like fundus cameras and OCT machines that provide good eye examinations.

Today, optometrists and ophthalmologists can use teleophthalmology platforms to communicate directly with each other and share images. That way, we can limit the number of false referrals and secure swift treatment when needed.

Even though we may be far from each other geographically, I encourage close collaboration.

One final question. Would you recommend doing a PhD?

Marko Lukic

I learned a lot from it: From how to do proper data search analysis over working in a team to eventually writing publications on the topic. You gain vast experience.

When that is said, a PhD is by no means mandatory to do your clinical work. But it opens a lot of doors to the academic world. You can be invited to review articles in prestigious journals and do lectures around the world.,

I always encourage peers to be as ambitious as possible.