Nancy A. Melville

May 30, 2014

ORLANDO, Florida — For patients with neovascular age-related macular degeneration, regular rather than as-needed treatment with a vascular endothelial growth-factor (VEGF) inhibitor improves outcomes, according to a new study.

And in a separate study, researchers found that baseline predictors of the fewest injections required included treatment with the VEGF inhibitor ranibizumab, as opposed to bevacizumab, and did not include treatment with beta blockers, despite expectations.

Both studies were presented here at the Association for Research in Vision and Ophthalmology 2014 Annual Meeting.

A regular regimen could improve patient management and reduce the need for exams, said Paul Bishop, PhD, professor of ophthalmology and matrix biology at the University of Manchester in the United Kingdom, who was lead investigator of first study.

"Our routine treatment strategy produced results that are broadly similar to other studies using anti-VEGF drugs, with a mean gain in vision of 5.5 letters," Dr. Bishop told Medscape Medical News.

"However, our patients required less frequent assessments than those in other studies or receiving other treatment protocols," he reported. "A majority only needed to be seen and treated once every 3 months after the 3 monthly loading doses."

Better Outcomes

Dr. Bishop and his colleagues enrolled 331 patients at the Manchester Royal Eye Hospital in a 92-week study. All received loading doses of intravitreal bevacizumab at week 0, week 4, and week 8.

Thereafter, 165 patients were randomized to receive an injection of bevacizumab every 12 weeks, regardless of clinical signs, and 166 patients were randomized to be assessed every 12 weeks and treated only as needed.

When patients were stable, they were seen at 12-week intervals; when active disease was present, they were seen at 6-weeks intervals.

Indications for treatment were similar in the as-needed group and for additional treatment in the regular treatment group. They included a loss of at least 5 letters since the previous appointment, evidence of retinal fluid, an increase in central macular thickness, and fluorescein angiogram findings.

During the study period, the mean number of injections was 10.3 in the regular group and 8.7 in the as-needed group.

However, after 92 weeks, the gain in letters was significantly better in the regular group than in the as-needed group (5.7 vs 0.1 letters; P = .001).

In addition, the number of patients who achieved improvements of 5, 10, and 15 letters was significantly higher in the regular group than in the as-needed group.

"In all cases, the routine injection arm was superior to the PRN arm," Dr. Bishop said.

At 20 weeks, the increase in best-corrected visual acuity was similar in the regular and as-needed groups. However, from 44 weeks to the end of the study period, the increase in visual acuity was significantly better in the regular group (P = .001).

"The routine group had an increase of 5.5 letters by week 20, and that was sustained until the end of the 92-week study," Dr. Bishop reported.

"Because we did not compare different drugs, only limited conclusions can be derived from the safety data," he told Medscape Medical News. However, "I think that we can conclude that no particular safety issues for the use of intravitreal bevacizumab were raised by this study."

Fewer Injections

A separate 2-year study looked at baseline predictors of the number of anti-VEGF injections — bevacizumab or ranibizumab — required by patients with neovascular age-related macular degeneration.

These researchers also found some improvement with regular rather than as-needed injections.

"Our group found that when patients were examined monthly, those treated PRN did not improve as much, on average, as patients treated monthly, by about one-half line on the visual acuity chart," said investigator Maureen Maguire, PhD, from the Department of Ophthalmology at the University of Pennsylvania in Philadelphia.

She suggested that the frequency of examinations could have played a role in the weaker improvements seen in the as-needed group in the study by Dr. Bishop's team.

Those patients were examined less frequently — at 6- to 12-week intervals," she explained, "so it is not surprising that the PRN group lost more vision than the group with regular injections."

Nevertheless, as-needed treatment might be preferable in many situations, she told Medscape Medical News.

"Ophthalmologists and patients may choose a PRN approach after weighing the discomfort and cost of more injections against the size of the average visual acuity advantage," she explained.

In the randomized Comparison of AMD Treatment Trials (CATT), Dr. Maguire and her colleagues evaluated patients with neovascular age-related macular degeneration. All were assessed every 28 days; 236 patients were treated with ranibizumab and 224 were treated with bevacizumab.

The key baseline factors associated with the fewest injections during the 2-year period were retinal angiomatous proliferation lesions (P = .001), treatment with ranibizumab (P = .002), the absence of subretinal fluid (P = .04), and the absence of subretinal pigment epithelium fluid (P < .001).

Previous research has shown that more injections of bevacizumab than of ranibizumab are required for improvement in macular degeneration, so that finding was not a surprise. However, the fact that beta blockers were not predictors of fewer injections over the 2-year period was unexpected, Dr. Maguire reported.

"Because beta blockers are effective in reducing the area of cutaneous capillary hemangiomas and have been shown to have antiangiogenic effects in animal models of neovascularization, many thought that patients using either topical or systemic beta blockers would need fewer injections; this was not true," she explained.

These findings can provide clinicians and patients alike with useful information on their likely course of treatment, Dr. Maguire noted.

She added that "clinicians may want to advise patients who have 1 or more of the risk factors that they might need more injections than the average patient."

Dr. Bishop and Dr. Maguire have disclosed no relevant financial relationships. Some of Dr. Bishop's coauthors report relationships with Novartis and Bayer.

Association for Research in Vision and Ophthalmology (ARVO) 2014 Annual Meeting: Abstracts 1646 and 869. Presented May 5, 2014.

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