Caroline Helwick

November 20, 2012

CHICAGO — Patients with neovascular (wet) age-related macular degeneration (AMD) who are treated with ranibizumab are at risk for substantial vision loss late in the treatment course. This may be mediated in part by the frequency of the intravitreal injections.

These were the main findings from a long-term follow-up of pivotal trial populations from ranibizumab studies presented here at the American Academy of Ophthalmology (AAO) 2012 Annual Meeting.

"Active choroidal neovascularization leakage was present in the majority of patients in year 7," said Soraya Rofagha, MD, of the University of California, San Francisco, who presented the analysis that assessed the long-term visual outcomes and their anatomic correlates in the ANCHOR/MARINA ranibizumab-treated cohorts.

"Exudative AMD is chronic, persistent, and lifelong. High level of evidence for anti-VEGF (vascular endothelial growth factor) treatment is limited to the 1- and 2-year follow-up of ranibizumab studies (ANCHOR, MARINA, EXCITE, SUSTAIN, PrONTO, CATT, IVAN, and VIEW), and the 4-year follow-up of HORIZON," she said. "By now, our clinical experience with ranibizumab has surpassed these time limits."

ANCHOR and MARINA were initiated 9 years ago, and ranibizumab was approved by the US Food and Drug Administration 6 years ago.

The current study, termed SEVEN UP, was a multicenter, cross-sectional cohort study. The study population comprised patients in the noninterventional, noncontrolled ranibizumab groups in ANCHOR and MARINA who continued to receive the drug throughout the HORIZON trial. Final enrollment included 65 patients (42% of 155 enrolled in ANCHOR/HORIZON).

Patients returned for a single visit 7 or more years after ANCHOR/MARINA entry (3 - 4 years post-HORIZON) to be evaluated for the following:

  • Visual acuity by Early Treatment Diabetic Retinopathy Study (ETDRS), complete ophthalmic examination

  • Imaging: photo/fluorescein angiography, optical coherence tomography (OCT), autofluorescence

  • Treatment course after leaving HORIZON: ranibizumab, bevacizumab, photodynamic therapy, steroids, other treatment

Need for Monitoring Seen

After a mean of 7.3 years from entry to ANCHOR/MARINA, patients demonstrated a mean 8.6-letter loss from baseline and a median visual acuity of 20/100, Dr. Rofagha reported.

Visual acuity at 7 years was as follows: ≥ 20/40 (15%), ≥ 20/70 (37%), ≥ 20/100 (46%), < 20/100 (55%), and ≤ 20/200 (37%).

"Since their exit from HORIZON, half the patients were stable or better, but half the patients were worse," she said.

The researchers found that 48% of patients lost fewer than 5 letters, and 52% lost 5 or more letters; 22% gained 5 or more letters.

Treatment with ranibizumab or bevacizumab was fairly infrequent since HORIZON, she noted. Patients received a mean of 6.8 injections over a period of 3.4 years, and more than one half of the patients received 5 or more injections.

"Patients in the highest quartile of injections after HORIZON (≥ 10 injections) actually gained vision during years 4 to 7," she added. "[In the patients who lost vision] I think we are not injecting these patients as frequently as we did in the randomized trials, and we are seeing an effect of this."

The mean letter change was −8.7 for patients with no further injections, −10.8 for those with 1 to 5 injections, −6.9 for those with 6 to 10 injections, and +3.9 for those with 10 or more injections after the studies ended.

"Long-term visual outcomes at year 7 were associated with the quality of vision after intensive treatment [in the trials], the amount of exudation on OCT (thinning predicted better vision), and area of decreased autofluorescence," she added.

"The study shows there is a continued need for clinical monitoring to evaluate the need for ongoing treatment," she concluded.

K. Bailey Freund, MD, of Vitreous-Retina-Macula Consultants of New York, in New York City, who was a a panelist at the session, commented that since these studies were published, physicians have learned a lot about how to optimize the use of ranibizumab.

"But I see patients 5 or 6 years into treatment, and they ask whether they are improving, when will they see better, and so forth. This gives us a realistic assessment of what we can expect for these patients in real-world practice. That's the take-home message from this study," Dr. Freund said.

Dr. Rofagha indicated a financial relationship with Genentech, which funded these trials. Dr. Freund reported consulting fees and research support from Bayer, Genentech, Regeneron, and Novartis.

American Academy of Ophthalmology (AAO) 2012 Annual Meeting. Abstract PA058. Presented November 12, 2012.