Outcomes Worse with Anti-VEGF than PRP in Patients Lost to Follow-Up

Patients with proliferative diabetic retinopathy (PDR) who receive intravitreal injection (IVI) of anti-vascular endothelial growth factor (VEGF) prior to being lost to follow-up had worse outcomes on return compared to similar patients who had received pan-retinal photocoagulation (PRP), according to new study results unveiled at the annual meeting of the Association for Research in Vision and Ophthalmology (ARVO) in Honolulu, HI.

Moreover, while comparable outcomes have been demonstrated in patients receiving anti-VEGF or PRP, those results are contingent upon timely follow-up, according to the study’s lead author Jason Hsu, MD, director of retina research at Wills Eye Hospital in Philadelphia. Therefore, in real-world clinical practice, loss to follow-up in eyes receiving only IVI of anti-VEGF therapies may lead to worse outcomes.

59 eyes that met inclusion criteria for the study, with 32 receiving only IVI of anti-VEGF and 27 only receiving PRP prior to being lost to follow-up (LTFU). Hsu and colleagues found that In the IVI group, mean logarithm of the minimum angle of resolution (logMAR) visual acuity significantly worsened from the initial visit (0.62, Snellen 20/83) to the return visit (1.18, Snellen 20/300, P < .001) and the final visit (1.03, Snellen 20/210, P = .02).

In the PRP group, no significant difference in logMAR VA was found when comparing the initial visit (0.40, Snellen 20/50) to the return visit (0.64, Snellen 20/87).

The findings build on previous findings conducted by Hsu and colleagues from 2017 that help demystify the anti-VEGF versus PRP decision for physicians treating patients with diabetic retinopathy.

In an interview with MD Magazine at the Hawaii Convention Center on April 29, Hsu said the findings have changed the way he manages these patients.

“I'm definitely more wary about going with anti-VEGF monotherapy. Even if I am not planning to do anti-VEGF monotherapy, a lot of us will start treating these eyes with anti-VEGF thinking in the back of our head, ‘Ok, once we stabilize their vitreous hemorrhage or their diabetic macular edema, then we're gonna start the PRP,’” Hsu said. “But we have to keep in mind that there are some patients that even got 1 injection or 2 injections and never came back.”

Jason Hsu, MD:

The whole genesis of the study is the concern that we all have with anti-VEGF therapy in patients with proliferative diabetic retinopathy--that's the more severe stage of diabetic retinopathy. Those eyes are at high risk of progressing to vision loss.

There have been some great studies, randomized clinical trials: there was the DRCR Network protocol S, which clearly showed that ranibizumab monotherapy was equivalent to PRP--probably even better because there were less issues with visual field loss that you see in PRP as well as incidence of diabetic macular edema, which you see with PRP.

And then there was the United Kingdom CLARITY trial, which showed superiority of anti-VEGF for the first time, where they found that aflibercept was better than PRP in terms of visual acuity outcomes.

So there's definitely a big push to going towards anti-VEGF monotherapy for our patients, but we worry about what happens if they don't come back. We know from the early treatment of diabetic retinopathy study from years ago that if you do PRP, those eyes can do very well. About 84% of patients that got PRP end up with 20/40 vision still at a median of 16.5 years after the PRP, so they held up very long.

We have no idea what the long-term durability of anti-VEGF is going to be, especially if patients don't continue to get the injection.

So the genesis of our study was to look at what happens to those eyes that got anti-VEGF versus PRP, and then were lost to follow-up, and then came back? How did they do?

So we actually found that there was quite a big disparity between the 2 groups, which is sort of what we had anticipated as well. In terms of visual acuity outcomes, right before the patients were lost to follow-up, mean visual acuity was about 20/50 in both the anti-VEGF and the PRP only groups. However, when they returned from being lost to follow-up (the mean duration they were actually lost to follow-up was over a year) the anti-VEGF group had lost vision to actually about 20/200 where as the PRP group had also lost vision to about 20/80, however they were followed for an additional amount of time after they returned and got some additional treatments. In the PRP group, they improved back to their baseline about 20/50, whereas the anti-VEGF group remained around 21/50. So definitely worse visual acuity outcomes.

The other issue was with anatomical outcomes. We saw a higher rate of neovascularization of the iris developing in patients that only had anti-VEGF therapy. At the final visit there were 4 of the 30 eyes that had NVI, and of those, 2 of those eyes developed neovasculariz glaucoma, whereas there were no cases of that in the PRP group.

In addition, tractional retinal detachment--so we saw 10 eyes out of 30, so a third of the patients developed TRDs by the final visit in the anti-VEGF group, whereas only 1 out of 47 eyes in the PRP group got tractional retinal detachment.

Of those eyes, 6 patients in the anti-VEGF group ended up being vatrectomy to repair the TRD, so it was that severe, and that's 20% of those eyes versus none in the PRP group required vatrectomy for TRD.

In terms of clinical management, it has changed the way I manage these patients to some extent. I'm definitely more wary about going with anti-VEGF monotherapy, and even if I am not planning to do anti-VEGF monotherapy, a lot of us will start treating these eyes with anti-VEGF thinking in the back of our head, "Ok, once we stabilize their vitreous hemorrhage or their diabetic macular edema then we're gonna start the PRP. But we have to keep in mind that there are some patients that even got 1 injection or 2 injections and never came back.

Not only do we need to be cognizant of that, we also need to explain that to the patients very carefully, of the need to follow up.

I do as a result have a lower threshold for still doing some PRP, probably not as heavy as I used to in the era before we had anti-VEGF, but some PRP to at least give them some sort of durable effect if they don't come back.

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