Subspecialty News

Fellows Forum; VEGF Trap; Avastin vs Lucentis


Fellows Forum Marks 10th Year

Dr. Steve Charles is Guest Lecturer.

■ The tenth annual Retina Fellows' Forum took place on Jan. 29 and 30 at the Westin River North in frigid Chicago. Eighty North American fellows participated in an educational and social program that has become a much-anticipated fixture of the final year of vitreoretinal training.

As in past years, the fellows spent considerable time in the lecture hall with a panel of volunteer faculty, led by Course Director David Chow, MD, and co-directors Carl Awh, MD, and Tarek Hassan, MD. Ophthalmologists Dean Eliott, Phil Ferrone, Jeff Heier, Nancy Holekamp and Peter Kaiser completed the faculty.

From left, Drs. Carl Awh, Steve Charles (Distinguished Guest Lecturer), Tarek Hassan and David Chow.

The meeting began on Friday evening with an AMD Symposium and sessions on Diagnostic Instrumentation and Pediatric Retina. New to the meeting were the inaugural “Faculty Debates,” in which the faculty debated the following topics: Avastin vs. Lucentis; Pneumatic Retinopexy vs. Scleral Buckle vs. Vitrectomy, and Fluorescein Angiography vs. OCT. Topics were assigned to the faculty, who relied upon clinical data, personal experience, and (most effectively) humor to defend their positions.

A Friday evening reception and dinner provided the first opportunity for the “graduating class” of 2010 fellows to socialize with their peers, the faculty, and representatives from industry.

Saturday offered a full day of panel-driven discussions on Diabetic Retinopathy, Retinal Vascular Occlusion, Medical and Surgical “Pearls,” “News You Can Use,” and advice on career and lifestyle management. As always, a highlight of the meeting was the Distinguished Guest Lecture, this year delivered by Steve Charles, MD. Dr. Charles captivated and inspired the audience with his talk on “Technology, Technique, and the Pursuit of Happiness.”

For the 10th consecutive year, Bausch & Lomb provided essential support as the major sponsor of the Retina Fellows' Forum. Genentech provided a generous educational grant to support the opening AMD symposium. Thirteen additional companies representing a cross-section of devices and services important to vitreoretinal practice provided financial support and presented updates to the group about their businesses.

The prestigious and competitive Bausch & Lomb Retina Fellows' Forum Research award went to Arghavan Almony, MD, of the Barnes Retina Institute for her paper, “Small-Gauge Vitrectomy Does Not Protect Against Nuclear Sclerotic Cataract.” Dr. Almony will present her paper at the 2010 Annual Meeting of the American Society of Retina Specialists as a specially recognized lecture.

The Fellows Forum faculty, from left, Drs. Phil Ferrone, Jeff Heier, Dean Eliott, David Chow, Steve Charles, Tarek Hassan, Carl Awh, Peter Kaiser, and Nancy Holekamp.

The meeting concluded with dinner, an informal awards ceremony, and the 5th Annual Retinal Fellows' Forum Bowling Tournament. Fellows and corporate representatives were divided into teams captained by the faculty. Phil Ferrone's team emerged victorious, aided in no small measure by his score of 220, the highest of the evening.

The 11th Annual Retina Fellows Forum will be held in Chicago on Friday, Jan. 28 through Saturday, Jan. 29, 2011.

In addition to Bausch & Lomb and Genentech, corporate support for the event was provided by Alcon, Alimera Sciences, Allergan, Carl Zeiss Meditec, Dutch Ophthalmic, Insight Instruments, Iridex, MedOne Surgical, Neovista, QLT, Quantel Medical, Synergetics and Volk Optical.

VEGF Trap Has Positive DME Data

Study Compared Drug to Laser.

■ Regeneron Pharmaceuticals and Bayer HealthCare AG reported that VEGF Trap-Eye showed positive interim results versus laser in a phase 2 study in patients with diabetic macular edema.

The primary endpoint of the study, a statistically significant improvement in visual acuity over 24 weeks compared to the standard of care in DME — macular laser therapy — was met. Visual acuity improvement was measured by the mean number of letters gained over the initial 24 weeks of the one-year study.

“The magnitude of the gain in visual acuity achieved with VEGF Trap-Eye in this phase 2 study demonstrates the biologic activity of VEGF Trap-Eye in treating diabetic macular edema, a disease in which high levels of vascular endothelial growth factor are present,” said Diana Do, MD, the principal investigator for the study and assistant professor of Ophthalmology at the Wilmer Eye Institute of the Johns Hopkins University School of Medicine in Baltimore.

Patients in each of the four dosing groups receiving VEGF Trap-Eye achieved statistically significantly greater mean improvements in visual acuity (8.5 to 11.4 letters of vision gained) compared to patients receiving macular laser therapy (2.5 letters gained) at week 24. VEGF Trap-Eye was generally well tolerated, and there were no drug-related serious adverse events.

In this double-masked, prospective, randomized, multicenter phase 2 trial, entitled DA VINCI, 219 patients with clinically significant DME with central macular involvement were randomized to five groups. The control group received macular laser therapy at week one, and patients were eligible for repeat laser treatments, but no more frequently than at 16-week intervals. Two groups received monthly doses of 0.5 or 2.0 mg of VEGF Trap-Eye throughout the six-month dosing period. Two groups received three initial monthly doses of 2.0 mg of VEGF Trap-Eye (at baseline and weeks 4 and 8), followed through week 24 by either every eight-week dosing or as-needed dosing with specific repeat dosing criteria. Patients are continuing on the same dosing regimens for an additional 24 weeks.

Avastin Seen as Equal to Lucentis

But Genentech Takes Issue With Study.


■ Researchers at Kaiser Permanante Southern California who treated 324 wet AMD patients with Avastin (bevacizumab) and 128 patients with the same disease with Lucentis (ranibizumab) found little difference between the two Genentech drugs after 12 months, both in terms of stabilizing visual acuity and in reported side effects.

Genentech was quick to point out factors that could have biased the data.

The researchers, who reported their results in the February issue of Ophthalmology, acknowledged the observational and nonrandomized nature of the study. However, lead author Donald Fong, MD, said that the study “should reassure patients and ophthalmologists that bevacizumab appears to be just as effective as ranibizumab.”

Though the Permananente study was uncontrolled and the bevacizumab patients had an average age of 78, significantly younger than the ranibizumab patients, the researchers found that approximately one-quarter of all patients achieved close to 20/40 vision at 12 months, with little difference in adverse events.

The larger and more rigorous CATT study, which will compare Avastin and Lucentis on a head-to-head basis, is currently underway. Initial results are expected sometime in 2011.

Genentech took issue with some aspects of the Kaiser Permanente study. In a prepared statement, the company said:

“We are aware of the retrospective analysis published in the journal Ophthalmology titled ‘Intravitreal Bevacizumab and Ranibizumab for Age-Related Macular Degeneration.’ Genentech continues to believe Lucentis is the most appropriate medicine for people with wet age-related macular degeneration because it was specifically designed, formally studied, manufactured for intraocular delivery and is approved by FDA. At the same time, Genentech does not interfere with doctors' prescribing choices and believes that they should be able to prescribe the treatment they believe is most appropriate for their patients.”

Genentech further asserted that “this was an uncontrolled and unmasked retrospective case analysis, with too few patients and too short a duration to adequately assess differences between the two treatment groups.”

Genentech quoted Dr. Fong as stating in the article that “the sample size of the current study does not have sufficient power to determine whether there are any differences in safety.” The author also notes in the conclusion of the paper, “Because the study is a nonrandomized comparison, selection bias could mask a true treatment difference.”

According to Genentech, “The results beg the question as to why a higher percentage of patients switched off of Avastin than Lucentis (23% vs. 3% initially treated with Lucentis); however, the author offers only a limited explanation of this occurrence stating, ‘the availability of ranibizumab most likely accounted for some of the changes observed in the bevacizumab group.’”


VEGF Trap a future gold standard therapy? In a survey of 91 US and European retina specialists, Regeneron/Bayer's as yet unapproved aflibercept (VEGF Trap-Eye) was named as a therapy for wet AMD that has the potential to reach gold-standard status. VEGF Trap-Eye is currently completing its pivotal phase 3 trials.

Decision Resources, a leading research and advisory firm for pharmaceutical and healthcare issues, reported that both Genentech's Lucentis and Regeneron/Bayer's VEGF Trap-Eye can be expected to earn Decision Resources' proprietary clinical gold standard status for wet AMD in 2013 and 2018.

A unique future gold standard cannot be identified because neither thought-leader opinion nor available clinical data can show that VEGF Trap-Eye has any advantages or disadvantages relative to Lucentis in terms of efficacy, safety and tolerability or delivery attributes.

However, Decision Resources believes that are still unmet medical needs in the treatment of wet AMD.

Lux files for uveitis drug approval. Lux Biosciences, Inc. has submitted regulatory filings to both the FDA and European Medicines Agency (EMA) seeking marketing approval for its investigational drug Luveniq (LX211) oral voclosporin for the treatment of noninfectious uveitis involving the intermediate or posterior segments of the eye.

Lux said efficacy of LX211 was demonstrated in two controlled, randomized, multicenter trials including data from 450 patients at 56 sites in seven countries. The safety data include a total of 2,110 subjects who received voclosporin during its clinical development in uveitis and psoriasis, about 500 of whom were treated for more than 36 weeks and about 200 for more than 52 weeks.

LX211 had previously received orphan drug status from the FDA and EMA, and fast-track status from the FDA. Based on the latter, Lux Biosciences has requested priority review from the FDA.

Wnt pathway plays role in DR. Scientists have identified a molecular pathway that appears to play a vital role in diabetic retinopathy. In a study appearing in the American Journal of Pathology, researchers show that retinal levels and nuclear translocation of beta-catenin, a key effector in the canonical Wnt pathway, were increased in humans with DR and in three DR models. Retinal levels of low-density lipoprotein receptor-related proteins 5 and 6, coreceptors of Wnts, were also elevated in the DR models.

The high glucose-induced activation of beta-catenin was attenuated by aminoguanidine, suggesting that oxidative stress is a direct cause for the Wnt pathway activation in diabetes. Indeed, Dickkopf homolog 1, a specific inhibitor of the Wnt pathway, ameliorated retinal inflammation, vascular leakage, and retinal neovascularization in the DR models. Dickkopf homolog 1 also blocked the generation of reactive oxygen species induced by high glucose, suggesting that Wnt signaling contributes to the oxidative stress in diabetes. This indicates that the Wnt pathway plays a pathogenic role in DR and represents a novel therapeutic target. RP


In the article “Short-pulse Laser Treatment: Redefining Retinal Therapy,” in the January/February 2010 issue of Retinal Physician, Figure 1 was mislabeled. The image is not of a rabbit eye, but of a human eye. Retinal Physician regrets the error.