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Continuous AMD treatment favorable over the long term


Marc C. Peden, MD, presented data from his fixed interval dosing (FIDO) study that suggests continuous dosing results in favorable long-term preservation at 7 years with more than 43% of patients maintaining driving vision.


Take home message: Marc C. Peden, MD, presented data from his fixed-interval dosing (FIDO) study that suggests continuous dosing results in favorable long-term preservation at 7 years with over 43% of patients maintaining driving vision.


By Michelle Dalton, ELS; Reviewed by Marc C. Peden, MD

Tampa, FL-When it comes to treating wet age-related macular degeneration (AMD), there remains no consensus on the best treatment regimen for the anti-vascular endothelial growth factor (VEGF) injections.

The seminal studies, ANCHOR and MARINA, demonstrated the profound benefit of ranibizumab when administered monthly over 2 years, whereas others have indicated essentially similar outcomes when dosing anti-VEGF on a p.r.n. regimen (as suggested by the CATT and IVAN studies). In an effort to combine the efficacy of monthly dosing with a balance of decreasing injection frequency,  a treat-and-extend has evolved and felt by many to be a reasonable compromise.

Marc C. Peden, MD, Retina Associates of Florida, presented data from his fixed-interval dosing (FIDO) study that suggests continuous dosing “results in favorable long-term preservation at 7 years with [more than] 43% of patients maintaining driving vision. Our data suggest better outcomes with continuous therapy over as-needed regimens,” he said.1

Because there is no “gold standard” for long-term treatment regimens in wet AMD, Dr. Peden and his group wanted to compare their real-world data to the SEVEN-UP study (which also presented 7-year data, but without a mandated treatment interval).2

“That was really what we wanted to get at-there was a lot of concern after CATT about progressive geographic atrophy and ensuing vision loss with sustained exposure to anti-VEGF agents, but we just hadn't observed this in our own," Dr. Peden said. "While we believed we were offering our patients the best possible treatment long-term, it wasn’t until the release of the SEVEN-UP data that we realized there was a real difference in what they had reported and what we were seeing in our patient population. Therefore, we chose to retrospectively review our patient charts to ensure what we thought was happening with vision improvements were backed up by our patients’ results.”

Why continuous dosing?

In Florida, a large number of seasonal patients (“snowbirds”) head North during the summer months and would have lapses in their treatment, Dr. Peden said.

“It wasn’t uncommon to see patients followed p.r.n. while away for the summer only to return to us in the fall with fluid and a drop in vision or, in some cases, large hemorrhages because they had allowed a large gap between their last visit to their physician in the North and their follow-up visit with us,” he said. “For the most part, once we started them back on regular therapy, their macula would dry out and vision would improve again, but not always to the same level we had seen the winter before, especially if they had a hemorrhage.”

The late-founding member of Dr. Peden’s practice, W. Sanderson Grizzard, MD, had a poor experience and poor outcomes with treat-and-extend “early on. He tried to extend patients a little bit more rapidly and a couple of his patients had devastating macular hemorrhages. It became our practice philosophy that monthly seems to be the best treatment for our patients,” Dr. Peden said. “FIDO is sort of a modified, very gradual treat and extend.”

Essentially, the practice starts patients on a monthly therapy during the first 1 to 2 years.

At that point, “if everything looks stable, we may extend patients out to 5 weeks, do that for a period, then to 6 weeks. While treatment is individualized to each patient, it is unusual that we would recommend extending beyond 8 weeks,” he said.

That’s “much more conservative than the treat-and-extend protocols like that seen in LUCAS where patients are treated until they appear dry, and then the patients are rapidly extended out 2 weeks at a time, for up to 12 weeks in between dosing,” Dr. Peden said. Although discussed on the podium over the past few years, the 1-year outcomes under the LUCAS protocol have just been published.3

FIDO study details

FIDO retrospectively evaluated only patients with 5 years or more of continuous fixed-interval anti-VEGF injections (ranging from every 4 to every 8 weeks). Patients were excluded if they received concomitant photodynamic therapy or averaged less than 6.5 treatments per year. Changes from baseline were calculated at yearly intervals. There were 109 eyes with 5 years’ data, 74 eyes with 6 years, and 44 eyes with 7 years’ data.

A peak letter gain of 16.1 letters was seen at 2 years, followed by a mean average decline of approximately 0.54 letters per year over the next 5 years, Dr. Peden wrote.

Patients with baseline acuities of 20/200 or worse had the greatest visual gains at 5 and 7 years (+ 24.5 and + 25.5 letters), followed by those with 20/50 to 20/100 vision (+ 6.7 and + 6.9 letters), and finally those with 20/20 to 20/40 (+ 3.7 and +3 .4 letters).

In the study, the mean number of yearly injections was 10.5, which corresponds to an every-5-weeks injection schedule, Dr. Peden said, adding that while the study used primarily ranibizumab (Lucentis, Genentech) he would expect “fairly similar” results with Eylea (aflibercept, Regeneron). Currently, about 90% of Dr. Peden’s patients receive ranibizumab.

“Overall, 93% of patients either stabilized or improved,” he said. “Only 3 eyes lost 3 or more lines of vision, two in one patient,” which may indicate disease progression and not a lack of treatment efficacy, he said.

With better outcomes than those reported in SEVEN-UP, “superior long-term gains can be obtained with continuous, fixed-interval dosing in a real-world setting,” Dr. Peden said. “Anything else may be undertreating patients and may end up costing them some of their initial visual gains.”



1.     Peden MC, Suner IJ, Hammer ME, Grizzard WS. Long-term visual outcomes in patients receiving continuous, fixed-interval dosing of anti-VGF agents for wet age-related macular degeneration. Paper presented at: American Society of Retinal Specialists. 2014:San Diego, CA.

2.     Rofagha S, Bhisitkul RB, Boyer DS, Sadda SR, Zhang K; SEVEN-UP Study Group. Seven-year outcomes in ranibizumab-treated patients in ANCHOR, MARINA, and HORIZON: A Multicenter Cohort Study (SEVEN-UP). Ophthalmology. 2013;120:2292-2299

3.     Berg K, Pedersen TR, Sandvik L, Bragadottir R. Comparison of ranibizumab and bevacizumab for neovascular age-related macular degeneration according to LUCAS treat-and-extend protocol. Ophthalmology. 2015;122:146-152.


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