SUBSPECIALTY NEWS

Vision Loss With Lucentis

Study: Data Point to Geographic Atrophy.

JERRY HELZNER, SENIOR EDITOR

■ In the pivotal phase 3 MARINA and ANCHOR trials for Lucentis, the great majority of patients showed improved or stable vision. However, 9% of the patients in the MARINA trial and 10% of the patients in the ANCHOR trial lost 15 letters or more after 2 years of treatment with the drug.

A team of investigators headed by Philip Rosenfeld, MD, PhD, of the Bascom Palmer Eye Institute initiated a study to attempt to determine why a small minority of patients did so poorly with Lucentis therapy.

In a poster presentation at the 2007 ARVO meeting in May, the investigators found that "while ranibizumab therapy results in similar decreases in the area of CNV leakage in >15-letter losers and >15-letter gainers, there is a paradoxical increase in total lesion area in >15-letter-losers compared to >15-letter-gainers. "According to the reading center, an increase in total lesion area without an increase in CNV leakage suggests that the change in lesion area is the result of an increase in fibrosis, blood, serous pigment epithelial detachment (PED), blocked fluorescence, geographic atrophy, or a combination of those features.

"Because the area of fibrosis, blood, and PED did not significantly differ between the 2 groups, the most likely cause of vision loss is an increase in the area of geographic atrophy — a feature of dry AMD that could increase in area as part of disease progression."

The investigators do not believe the treatment caused the geographic atrophy, because the visual acuity (VA) improvement in the MARINA and ANCHOR trials was sustained through 2 years while receiving monthly injections of Lucentis. If Lucentis was in any way responsible, they would have expected a loss of efficacy over time. The investigators concluded that VA loss among patients receiving Lucentis could be linked to progression of dry AMD once neovascularization has been arrested.

The investigators are now reviewing the color photographs of patients in the MARINA and ANCHOR studies to assess the change in geographic atrophy over 2 years.

Dr. Freund's Rx for Type 3 CNV

Avastin and Lucentis Prove Highly Effective.

JERRY HELZNER, SENIOR EDITOR

■ Little more than a decade ago, type 3 neovascularization, also known as retinal angiomatous proliferation, commonly known as RAP, was first identified as a specific form of neovascularization. Given its brief history, it is no surprise that retina specialists have been grappling with such issues as how the type 3 vessels originate and how to best eliminate them.

Type 3 disease represents about 15% of all neovascular AMD and is typically found in patients who are Caucasian and older than the general AMD population. Type 3 lesions found in 1 eye almost always soon progress to the fellow eye.

At the recent Retinal Physician Symposium, K. Bailey Freund, MD, of Vitreous-Retina-Macula Consultants of New York, who has done significant work with type 3 patients, not only offered compelling evidence that type 3 disease begins in the choroid, he also offered a treatment regimen that he has been using consistently and with great success over the past 2 years.

Though the origin of type 3 disease does not affect Dr. Freund's suggested treatment regimen, he has used extensive OCT imaging on numerous patients to determine that it is the early formation of retinal choroidal anastomosis that is the "spark of life" for type 3 lesions. He says that his reading of typical type 3 OCT images "looks very suggestive for neovascularization originating from the choroidal circulation" and invading the retina from below.

In regard to treatment approaches, Dr. Freund reports that a combination of intravitreal triamcinolone to reduce the intraretinal cyst, followed a week later with standard-fluence PDT, produced excellent short-term results, with 92% of patients demonstrating stable or improved vision with an average of 2 treatments in the first year.

"Unfortunately, despite the sequence approach, the need for repeated treatments still led to collateral damage in the form of atrophy in many of these patients," Dr. Freund told his audience.

In 2005, Dr. Freund began using Avastin (and subsequently Lucentis) in type 3 patients in order to avoid the atrophy and collateral damage associated with other treatments. Of the first 23 type 3 patients treated with Avastin, 9 had pigment epithelial detachment (PED) and almost half of the patients had lost the central vision in the fellow eye. Eleven of the patients had already had other treatments, primarily triamcinolone and PDT, with 3 of the patients having received 5 or more rounds of PDT.

At 1 month after treatment with Avastin, improvements in both OCT measurement and vision were noted. By 3 months and after an average of 2 treatments, all the PEDs had resolved. No complications were observed.

Dr. Freund has since further refined his first-line type 3 treatment regimen. He suggests either an initial Avastin or Lucentis injection (he finds them equally effective), with OCT follow-up at 5 weeks, then another injection, with OCT imaging again at 7 weeks. He typically "injects and extends" until a maintenance injection can be given every 11 weeks.

"This approach allows for fewer office visits, better visual results and greater compliance than with combination therapy, with [Avastin] drug costs of only about $100 a year," Dr. Freund asserted. "After years of frustration, I'm happy to finally be able to offer my [type 3] patients truly effective treatment which preserves their vision and quality of life."