Skipping Treatment for Diabetic Retinopathy Carries Risks

Editor's Note: This video first appeared on the Wills Eye Hospital website and is being republished on Medscape with permission.

Jason Hsu, MD: Hello. I'm Jason Hsu, co-director of retinal research at Wills Eye Hospital in Philadelphia, Pennsylvania. I'm here in the Wills Eye Newsroom with Anthony Obeid, our clinical research fellow here.

We're here to talk about the very important issue of patients being lost to follow-up (LTFU). We're seeing that a lot of patients with the severest form of diabetic retinopathy—proliferative diabetic retinopathy—are not coming back for treatment.

Anthony, why don't you tell us a little bit about the first study we did on the issue of LTFU.

A Quarter of Patients Don't Return

Anthony Obeid, MD, MPH: Thank you, Dr Hsu. The original study^[1] evaluated LTFU immediately post-treatment with either panretinal photocoagulation or anti-vascular endothelial growth factor (VEGF) injections in patients with proliferative diabetic retinopathy. Over 4 years, we evaluated approximately 2000 patients. We found that around 1 in 4 patients, or 25%, did not return after receiving treatment for proliferative diabetic retinopathy.

Hsu: Wow. That's quite alarming to think that a quarter of patients are not coming back after receiving treatment, particularly as they have the highest risk for vision loss in this disease.

What's the difference between these anti-VEGF injections that we're hearing about and laser treatment for proliferative diabetic retinopathy?

Obeid: Laser is somewhat the gold standard. It is known to have a durable effect many years after treating eyes with proliferative diabetic retinopathy. Now recent clinical trials, such as Protocol S^[2] and CLARITY,^[3] are showing that anti-VEGF therapy, a new form of treatment, is comparable to panretinal photocoagulation in treating proliferative diabetic retinopathy. However, it is commonly believed that these anti-VEGF injections require consistent follow-up post-treatment as compared to panretinal photocoagulation. Because we had no definite evidence of this at that time, we conducted the next study^[4] with a primary goal of comparing outcomes between both treatments in eyes that were LTFU after therapy.

Hsu: How did we define LTFU in these studies?

Obeid: For the first study,^[1] LTFU was defined as a minimum of 12 months with no show after any treatment. A patient might have received five anti-VEGF injections or five sessions of panretinal photocoagulation, and all that was required was that there was 12 months of no show right after treatment.

In our second study,^[4] we shortened the interval a bit. We defined LTFU as occurring more than 6 months after that last treatment, given that the patients can experience adverse events in less than a year. Basically, we found a slightly higher number of patients who were LTFU, and we found some significant disparities in the anatomic and functional outcomes between two treatments.

How LTFU Affects Different Treatments

Hsu: That's really the biggest question: How did the anti-VEGF group do after they were LTFU versus the patients who had the panretinal photocoagulation? Was there a difference between the two groups?

Obeid: In terms of vision, both groups showed a significant decline upon return from LTFU. However, the really interesting part is the differences experienced after returning and receiving additional treatment. The panretinal photocoagulation group actually recovered most of its vision, and the average visual acuity returned to what it was prior to their being LTFU. On the other hand, the anti-VEGF group remained at that decreased vision. Even after several treatment sessions with panretinal photocoagulation and additional injections, they were unable to recover the vision.

Hsu: Can you highlight the major differences we saw between the two groups in terms of anatomic outcomes?

Obeid: There were two major differences that were quite worrying. First, the anti-VEGF group actually experienced greater incidence of tractional retinal detachment, a known adverse event of proliferative diabetic retinopathy that can be vision-threatening, especially if it involves the part of the retina that's responsible for center vision. Second, they also experienced a high incidence of neovascularization of the iris. Basically, there was increased amount of blood vessels in the interior section of the eye that can lead to neovascular glaucoma. In fact, around two eyes experienced neovascular glaucoma in the anti-VEGF group compared with no eyes in the panretinal photocoagulation group.

Hsu: That's very worrisome, as that's a potentially blinding disorder if you get that kind of neovascular glaucoma. Can you tell us a little more about the risk for tractional retinal detachments?

Obeid: The tractional retinal detachment difference was quite striking. Around 30% of eyes receiving anti-VEGF therapy prior to being LTFU experienced a tractional retinal detachment by the final visit after returning for follow-up. This is compared to one eye in the panretinal photocoagulation group, representing less than 5% of eyes in that cohort.

Hsu: Wow—so, quite a big difference between the two groups.

Putting It Into Practice

Hsu: Anthony, what do you think are some of the take-home messages for our audience?

Obeid: The first take-home message obviously is that we have a good portion of our patients who are LTFU post-treatment. Another important message is that given that we have this high rate of LTFU, it's more crucial that we evaluate which treatment is more appropriate for our patients, especially given the disparities in adverse events post-LTFU.

Hsu: I just wanted to reiterate that because of this high LTFU, patients must understand that it's critical to have ongoing care with your physician, because we can have much worse outcomes, especially if you're receiving injections for proliferative diabetic retinopathy. In our own practice, I think a lot of us are thinking twice now about starting with those injections and really thinking more about whether we should go back to the gold standard of laser treatment for these eyes.

I'm Jason Hsu and this is Anthony Obeid, from the Wills Eye Newsroom. Thank you for joining us, and we hope to see you again in the near future.