Managing pigment epithelial detachments with ranibizumab

By Michelle Dalton, ELS; Reviewed by Rahul N. Khurana, MD

Mountain View, CA-Large or small pigment epithelial detachments (PED) in neovascular age-related macular degeneration (AMD) can be managed effectively with ranibizumab PRN therapy with regular monitoring, said Rahul N. Khurana, MD.

“There is a common belief out there that PED associated with neovascular AMD are quite challenging to manage,” he said. “The idea behind that is that there are often these large detachments that don't respond as well to anti-VEGF therapy and they don't do as well from a visual acuity perspective. But this belief really stems from our experience and not from a lot of evidence per se.”

Dr. Khurana said the dilemma for most clinicians is how to treat a patient with a large PED. In the HARBOR study, 1,097 patients were randomized to 1 of 4 ranibizumab (RBZ) regimens: 0.5 mg monthly or 2.0 mg monthly and 0.5 mg PRN or 2.0 mg PRN after 3 monthly loading doses for 24 months. PRN treatment was administered based on strict retreatment criteria and guided by spectral domain optical coherence tomography (SD-OCT) disease activity or visual acuity stability.

“Our subgroup analysis reviewed results from patients with or without PED at baseline in both the full study population (all treatment groups pooled) and by treatment regimen,” he said. “Absolute visual acuity, change in visual acuity from baseline, and number of injections in the PRN treatment groups, were summarized.”

Preconceived notions were that patients with a PED would have a worse prognosis in at least one of those variables, and likely all three, he said.

“What we found was almost somewhat the opposite. When it came to visual acuity, the presence of a PED did not preclude a good initial outcome. If you did have a PED, you still had a very robust visual acuity gain of almost essentially 9 letters, which is very similar to the patients who did not have a PED,” he said.

Study results

Of the 1,097 patients in HARBOR, 598 (54.5%) had a PED at baseline. At baseline, the mean visual acuity (ETDRS letters) was higher for patients with PED (55.7 letters) than without PED (51.9 letters). Mean change from baseline in visual acuity at month 24 was 7.9 letters in patients with PED and 9.7 letters in patients without PED, with vision being similar after adjustment for baseline covariates, Dr. Khurana noted.

Before undertaking the study, Dr. Khurana thought those with PED would have worse outcome, and would have told patients “probably going to need more treatment and you're not going to do as well, and that would have been based off my preconceived notions from my past experience or just my own biases.”

Among patients with PED, median visual acuity gains at month 24 were similar across quartiles, when treatments were combined and when analyzed by dose (0.5 mg or 2.0 mg) or by PRN regimen. The number of injections administered in the 0.5 mg PRN arm was slightly higher (14 and 12.5 injections) for patients with PED. Similar results were seen in the 2.0 mg PRN group, 11.6 and 10.7 injections, respectively, in patients with PED and without PED.

There are two real strengths to the study, he said: the substantial number of patients enrolled, and the consistency in imaging through both years (SD-OCT at all time points). The reason using SD-OCT throughout was so important is that “it gives us a lot more detail and allows us to characterize the PEDs much more than previous studies have,” Dr. Khurana said.

Extrapolating the results

Because HARBOR was designed to investigate ranibizumab only, “we can feel confident treating PEDs with ranibizumab,” Dr. Khurana said.

But since there are several other studies that show other anti-VEGFs are effective in treating AMD, “there’s probably only going to be small differences in how these agents treat PED. At the end of the day, they all work well for neovascular AMD, and I would expect the same outcomes for large or small PEDs.”

In the subanalysis, “there was really a difference of only 1.5 injections over 2 years, which is really not relevant,” he said. “Before this study, I would have said the PED group probably averaged 16-17 injections over 2 years and the no-PED group probably would have averaged 10 injections. I had been convinced there's a bigger treatment burden for those with PED and that was not the case.”

What remains unknown and needs further investigation is which of the anti-VEGFs is the most efficacious in treating PED.

“Ultimately it's going to require a study comparing these three agents or two agents head-to-head with spectral domain imaging to measure the response,” he said. “For now, what we’ve shown unequivocally is that having a PED is not going to give patients a worse visual acuity outcome and that ranibizumab is quite effective in treating PEDs. Our patients can do very well being managed either PRN or monthly dosing with ranibizumab.”

Rahul N. Khurana, MD

E: rnkhurana@gmail.com

Dr. Khurana did not indicate any proprietary interest in the subject matter.