COMMENTARY

Three Keys to Delaying and Preventing Diabetic Retinopathy

John M. Aljian, MD; Ronald C. Gentile, MD

Disclosures

August 28, 2017

Hemoglobin A1c: An Overlooked Target

John M. Aljian, MD: Hello. I'm Dr John Aljian, an anterior segment surgeon and clinical associate professor of ophthalmology at the New York Eye and Ear Infirmary of Mount Sinai in New York City. Joining me today is Dr Ron Gentile, director of the ocular trauma service and surgeon director at the New York Eye and Ear Infirmary of Mount Sinai. Today we will be discussing the importance of systemic control in the management of diabetic retinopathy for Medscape Ophthalmology.

Ron, I feel like every other patient that comes to my office these days has diabetes. They are well aware of the need to check their blood sugar and that eating sugar causes theirs to increase. Yet many of them have no idea of the difference between dietary sugar, protein, and fat, and how that affects their glycemic control. Do you find that in your practice?

Ronald C. Gentile, MD: Yes. I'd like to discuss what I call the 3 H's—hyperglycemia, hypertension, and hyperlipidemia—and how these affect the prognosis of patients with diabetes in terms of their risk of developing diabetic retinopathy or having it progress.

Dr Aljian: It amazes me that many patients have no idea what their hemoglobin A1c is. They are on antiglycemic medications, even insulin, and have never even heard of it, or forgotten it, or just don't feel that it's an important number in their lives.

Dr Gentile: It's important that you bring this up, because I really want to go over with you what effect the hemoglobin A1c has on the progression of diabetic retinopathy. If doctors bring this up to their patients, I think they'll have a better understanding of what that number actually means and how they can get it lower to prevent them from developing retinopathy and going blind.

The first study I want to talk to you about is the Diabetes Control and Complications Trial.[1] This is an old but very important study, which ran from 1983 to 1993 in patients with type 1 diabetes. At that time, the authors wanted to compare intensive control versus what was considered conventional therapy at that time, and to look at the decrease in the hemoglobin A1c and what effect that had on systemic complications. There were about 1400 patients in that study. Those who had intensive control had hemoglobin A1c's of about 7 versus of about 9 in those who had conventional treatment. What's really fascinating is what effect just this 2-point decrease in the hemoglobin A1c had on diabetic retinopathy. They looked at two groups, the first of which had no diabetic retinopathy. Those patients had a 76% reduction of the onset of diabetic retinopathy over 10 years. We don't have treatments like this in ophthalmology. Patients and doctors want to know that this is effective in preventing diabetic retinopathy. The patients in the second group had a minimal degree of diabetic retinopathy. Those who received intensive control had a 54% reduction in the progression of diabetic retinopathy. Even though there was a bit of worsening of diabetic retinopathy the first 3 years when the hemoglobin A1c dropped in those patients with intensive control, overall they did better over the course of the study. This is big data.

There are certain criteria in ophthalmology when we examine a patient... Right next to the intraocular pressure should be the hemoglobin A1c number.

Dr Aljian: It's critically important. There are certain criteria in ophthalmology when we examine a patient, such as visual acuity and slit-lamp exam. Right next to the intraocular pressure should be the hemoglobin A1c number.

Dr Gentile: I agree. Educating the patient about the significant impact of a 1- or 2-point lowering is important. Just to give you an example, we love doing lasers to prevent vision loss. Those patients who had a 2-point decrease in hemoglobin A1c in that study had a 50% reduction in the need for panretinal photocoagulation. Besides retinopathy, [that study] also found a decrease in albuminuria, in neuropathy by 60%, and in macrovascular disease by 41%. If you look at the onset of clinically significant macular edema, those in the intensive group actually had a 15% incident of macular edema versus 27% of the patients who were not well controlled. This is definitely something that affects the visual functioning of patients with diabetes.

There also was a UK study[2] [the United Kingdom Prospective Diabetes Study, or UKPDS] that looked at over 3800 patients with type 2 diabetes and had similar results. Their intensive group had a hemoglobin A1c of 7 versus 7.9 in the conventional group, so only a 1-point difference. Yet, patients with the lower hemoglobin A1c had a 17% decrease in retinopathy progression, 29% less laser was needed, vitreous hemorrhages occurred less, and there were 25% fewer microvascular complications.

Not only do we have good data showing that the lower the hemoglobin A1c, the better your chances of not going blind from diabetic retinopathy, but a 1% drop also actually reduces the risk for microvascular complications by 37%-40%.

Dr Aljian: Amazing.

Dr Gentile: One of the things we have to remember is that there are complications from lowering your hemoglobin A1c, which has to do with hypoglycemia. When you do this, you want to make sure that the patient's doctor is aware of this because there are cases of too much hypoglycemia. There are some cardiovascular risk factors on the other side of lowering it too much. We want their doctor to understand that it decreases the progression of diabetic retinopathy. We also want to look at some of the risks, too.

Dr Aljian: When the blood sugar is out of control and then all of a sudden it is tightly controlled, retinopathy may progress for some reason. How does that occur?

Dr Gentile: One theory out there is that with the change in metabolism and sugar control, the microvasculature becomes more leaky. The one thing to remember is that even if the diabetic retinopathy does get worse for the first 2 or 3 years, the long-term result is that the patient ends up better off. It's well known that patients who have preexisting diabetic retinopathy and go from poorly controlled to better controlled diabetes can end up with a bit of worsening of diabetic retinopathy.

Taking the Pressure Off

Dr Aljian: Tell me a little bit about the effect of hypertension on diabetic retinopathy?

Dr Gentile: Hypertension is an independent risk factor for the progression of diabetic retinopathy. Let's look at the [UKPDS] study.[3] [Editor's note: The speaker misspoke and cited the ADS study; the correct one is the UKPDS.] This is another UK-based investigation that looked at patients who had tight control versus less tight control. Remember: All of the patients' hemoglobin A1c's were similar and were at about 7.

Dr Aljian: Blood pressure is a variable here?

Dr Gentile: Yes. In terms of reducing blood pressure, those who had tight control had a mean blood pressure of 144/82 mm Hg (which some people might say is borderline high). Then you had those patients with less tightly controlled blood pressure, and their mean blood pressure was 154/87 mm Hg. You're talking about a 10-point decrease in the systolic blood pressure mean and a 5-point decrease in the diastolic. The results are pretty remarkable, with a 34% reduction in the progression of diabetic retinopathy just by getting the blood pressure under tighter control. What's interesting too is that glucose control and hemoglobin A1c's were equal in both groups. There was a 47% decrease in moderate vision loss in patients who had tight control and a 12% decrease in the need for laser treatment. Controlling hypertension is another important factor.

Keeping Cholesterol in Check

Dr Aljian: What is the third H?

Dr Gentile: The third one is hyperlipidemia (hypercholesterolemia). This is also very important.

Patients who have high cholesterol are more likely to get retinal exudates and in turn are more likely to lose vision. Exudates increase the chance of vision loss in patients who have hypercholesterolemia versus in those who do not.[4]

Moderate vision loss is also dependent on the amount of exudates, so the greater the exudates, the greater the chance that patients have moderate vision loss. This is another important factor for patients to be aware of, as well as ophthalmologists and any medical doctor that deals with a patient who has diabetes.

We want to get to patients before they have diabetic retinopathy. If a patient comes in to the office with no diabetic retinopathy, we don't want to forget to mention the importance of the 3 H's.

We want to get to patients before they have diabetic retinopathy. If a patient comes in to the office with no diabetic retinopathy, we don't want to forget to mention the importance of the 3 H's.

Dr Aljian: That's a very common visit, where a patient who is newly diagnosed with diabetes comes in to have the retina checked. Statistically, it's most likely that a patient is not going to have any diabetic retinopathy at that first visit. It may take years to develop. You're saying that it's at that point that we should make the attempt to control the hemoglobin A1c, the blood pressure, and the lipid profile?

Dr Gentile: Yes. The best way to treat a patient with diabetic retinopathy is to prevent their diabetic retinopathy. These are the tools that we can use to prevent diabetic retinopathy.

Dr Aljian: I think it's important that patients know that. What you said earlier is that there is nothing more powerful—no medication, injectable, laser, whatever—to prevent a vision loss from diabetic retinopathy than control of the blood sugar, the blood pressure, and the lipid profile.

Dr Gentile: Yes, that's true, John.

Dr Aljian: Thank you for joining us. I'm Dr John Aljian and this is Dr Ron Gentile, at the Medscape studios in New York City. We hope you found this helpful.

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