BLOG: Intractable diabetic macular edema: A desperate unmet need

Read more blog posts from Pravin U. Dugel, MD

Ask a retina specialist how she treats patients with diabetic macular edema, and more than likely she will reply that she follows the DRCR.net Protocol I. Really? How many retina specialists know that to follow Protocol I, patients are seen not monthly but every 4 weeks for more than a year? Or that the first opportunity to not treat the patient with ranibizumab on an every-4-week basis was at week 16?

Approximately 25% of patients met the criteria not to be treated at week 16; however, more than 90% of these patients recurred and had to be re-treated. How many retina specialists know that in Protocol I the first opportunity to not see the patient and thereby decrease the treatment burden of being seen on an every-4-week basis was after week 60? And the bottom line is that as important a study as Protocol I is, it is largely a hypothetical study and rarely, if ever, is it followed in clinical practice because it is simply not sustainable. Remember that patients with diabetic macular edema are often young patients in the workforce who are historically noncompliant.

Even if Protocol I were to be followed strictly for 2 years, few retina specialists know that more than 50% of patients did not achieve a two or more lines improvement in visual acuity from baseline. To me, this is astonishing. Not only is this a protocol that is entirely not sustainable, but even if it is followed, the chance of improving two or more lines after 2 years is less than 50%. Truly astonishing. Why is this? What happens to these patients?

The answer is simple, and we see it every day in clinical practice. These are patients with intractable diabetic macular edema who slowly but surely go blind either in our practice or in their home. The sooner we as a specialty own up to this, the sooner these patients will be properly managed. There is a preponderance of basic science and animal and human data to show that chronic diabetic macular edema is a multifactorial disease that involves inflammation.

What is chronic diabetic macular edema? The FAME studies and the RIDE and RISE studies suggest that it is diabetic macular edema of 2 to 3 years’ duration. Anti-VEGF monotherapy does not address the inflammatory component. The negative press regarding corticosteroids has overshadowed the rationale for addressing this desperate patient population. Not all corticosteroids are the same. It is not so much the selection of the corticosteroids as it is the distribution of the corticosteroids. The single worst method of administering corticosteroids is with a large bolus injection. This has the least efficacy and the most complications. The best method of administering corticosteroids is in a controlled fashion with a delivery device. As I said, not all corticosteroids are the same. We must consider corticosteroid drug delivery devices such as the Ozurdex (Allergan) and the Iluvien (Alimera Sciences) to treat this large unmet need of desperate patients.

Disclosure: Dugel is a consultant for Alimera, Allergan, Genentech and Regeneron and participates in the DRCR.net trials.

Read more blog posts from Pravin U. Dugel, MD

Ask a retina specialist how she treats patients with diabetic macular edema, and more than likely she will reply that she follows the DRCR.net Protocol I. Really? How many retina specialists know that to follow Protocol I, patients are seen not monthly but every 4 weeks for more than a year? Or that the first opportunity to not treat the patient with ranibizumab on an every-4-week basis was at week 16?

Approximately 25% of patients met the criteria not to be treated at week 16; however, more than 90% of these patients recurred and had to be re-treated. How many retina specialists know that in Protocol I the first opportunity to not see the patient and thereby decrease the treatment burden of being seen on an every-4-week basis was after week 60? And the bottom line is that as important a study as Protocol I is, it is largely a hypothetical study and rarely, if ever, is it followed in clinical practice because it is simply not sustainable. Remember that patients with diabetic macular edema are often young patients in the workforce who are historically noncompliant.

Even if Protocol I were to be followed strictly for 2 years, few retina specialists know that more than 50% of patients did not achieve a two or more lines improvement in visual acuity from baseline. To me, this is astonishing. Not only is this a protocol that is entirely not sustainable, but even if it is followed, the chance of improving two or more lines after 2 years is less than 50%. Truly astonishing. Why is this? What happens to these patients?

The answer is simple, and we see it every day in clinical practice. These are patients with intractable diabetic macular edema who slowly but surely go blind either in our practice or in their home. The sooner we as a specialty own up to this, the sooner these patients will be properly managed. There is a preponderance of basic science and animal and human data to show that chronic diabetic macular edema is a multifactorial disease that involves inflammation.

What is chronic diabetic macular edema? The FAME studies and the RIDE and RISE studies suggest that it is diabetic macular edema of 2 to 3 years’ duration. Anti-VEGF monotherapy does not address the inflammatory component. The negative press regarding corticosteroids has overshadowed the rationale for addressing this desperate patient population. Not all corticosteroids are the same. It is not so much the selection of the corticosteroids as it is the distribution of the corticosteroids. The single worst method of administering corticosteroids is with a large bolus injection. This has the least efficacy and the most complications. The best method of administering corticosteroids is in a controlled fashion with a delivery device. As I said, not all corticosteroids are the same. We must consider corticosteroid drug delivery devices such as the Ozurdex (Allergan) and the Iluvien (Alimera Sciences) to treat this large unmet need of desperate patients.

Disclosure: Dugel is a consultant for Alimera, Allergan, Genentech and Regeneron and participates in the DRCR.net trials.