More News from the 2007 AAO – Day Three
First, more from Retina 2007:
Lucentis shown to reduce macular thickness more than Avastin
Treating neovascular age-related macular degeneration with Lucentis resulted in a greater reduction in macular thickness but not a better visual outcome compared to treatment with Avastin, according to Adam Martidis, MD, and colleagues.
In an independent retrospective study presented during Retina Subspecialty Day preceding the American Academy of Ophthalmology meeting, Dr. Martidas and his colleagues reviewed outcomes for 176 eyes treated for neovascular AMD with either intravitreal Avastin (Genentech) or Lucentis (Genentech). The treatments were administered at baseline and at months 1 and 2, with the data interpreted at month 3. The data was collected from six centers over a 6-month period.
Patients included in the study had a baseline visual acuity between 20/40 and 20/320. None had been previously treated.
At month 3, patients treated with Avastin showed a 24.7% decrease in absolute central macular thickness, compared with a 32.9% decrease in patients treated with Lucentis. Dr. Martidis said the ideal goal for each patient was a 200-μm thick retina. In patients treated with Avastin, 70.4% achieved this goal, compared to 92.7% of patients treated with Lucentis, he said.
"What most of us were obviously concerned about-both as physicians and our patients are concerned about-is the visual results. I do emphasize that this study was not powered to achieve statistical significance for vision, and indeed we did not achieve a statically significant vision change [between the groups]," Dr. Martidis said.
Patients treated with Avastin achieved a final visual acuity gain of seven letters vs. six letters for patients treated with Lucentis. Additionally, 20.9% of Avastin-treated patients gained three or more lines, compared with 34.2% of Lucentis-treated patients.
"Both Avastin and Lucentis — I think we would all agree — are effective in the treatment of exudative AMD. In this limited sample size, there is no statistically significant difference in visual outcome between the two. However, there is a statically significant difference in anatomic advantage in favor of Lucentis as measured by OCT," Dr. Martidis said.
Despite lack of industry support, CATT will continue as planned
In response to inquiries over the status of the much anticipated Avastin vs. Lucentis study, the lead investigator, Daniel F. Martin, MD, said the study was on track.
Dr. Martin, delivered an update on funding for the Comparison of Age-Related Macular Degeneration Treatment Trials (CATT ) Study. A recently revised Medicare policy will support the use of Lucentis in the trial, and patients will have no out-of-pocket expense, he said.
Genentech decided in July not to support the study or supply either of the drugs. "Despite numerous inquiries, we have been told that the decision is irreparable," Dr. Martin said. However, "we are unaffected by the ... decision," he said, reiterating that CATT is fully funded and ready to begin.
In CATT, Dr. Martin and colleagues will prospectively compare the results of 1,200 patients randomly assigned to receive either Avastin or Lucentis. Enrollment is expected to begin in early 2008, with 1-year results released in early 2010.
(For more on the CATT Study, please see my writeup, "CATT Study Update 4: Avastin vs. Lucentis Study Ready to Roll".)
And, some additional information about the Ellex 2RT laser treatment for retinal diseases:
Clinical results of retina regeneration therapy announced
The initial clinical results were announced of a continuous study for non-thermal Retina Regeneration Therapy (Ellex 2RT, Ellex Medical Lasers Ltd.). The results showed the therapy's potential to make improvements in and stabilize visual acuity, as well as reduce retinal edema in patients with diabetic maculopathy and macular edema without causing any damage to the photoreceptors.
The results were presented by Peter Hamilton, MD, FRCOph, the principal clinical investigator in the Ellex 2RT research program in St. Thomas Hospital, London, at the Retina Subspecialty Day.
"The first phase clinical outcomes have confirmed [the therapy's] ability to treat diabetic maculopathy without damaging the neuro-retina," said John Marshall, PhD, principal investigator of the Ellex 2RT research program, the Frost Professor of ophthalmology at the Rayne Institute, and head of the academic department of ophthalmology at King's College, University of London. "This means that [retina regeneration therapy] may change the way diabetic maculopathy patients are treated and it shows potential for intervention in early stage age-related macular degeneration before significant loss of vision has occurred."
"We are encouraged by the first patient data presented as it provides the assurance we were looking for to expand [retina regeneration therapy] research," said Peter Falzon, Ellex chief executive officer. "The next phase clinical trials will be essential in establishing [its] potential as an early stage therapy for retinal disease."
And, now Day Three of the main AAO Meeting:
Dr. Judah Folkman delivers keynote address during opening session (OSN, OT)
"Ocular angiogenesis in experimental animals has been the bedrock basis of advances across the field of angiogenesis research, and it continues to illuminate future directions of therapy," renowned medical researcher Judah Folkman, MD, said during the keynote speech of the opening session of the annual meeting of the American Academy of Ophthalmology.
Dr. Folkman, considered to be "the father of angiogenesis," treated attendees to a presentation detailing the history of angiogenesis research, beginning with his introduction of the term in a 1971 New England Journal of Medicine article.
"When this paper was published, I was very happy, and I thought maybe now the field would really take off," he said, "but nothing happened for 10 years." During that time, he added, his laboratory developed bioassays for angiogenesis, including one for cornea.
Today, at least 10 angiogenesis inhibitors, or drugs that have anti-angiogenic activity plus anti-cancer activity from other mechanisms, are approved by the FDA, Dr. Folkman said. "In 2006, 1.2 million people received prescriptions for FDA-approved drugs for the treatment of cancer or for age-related macular degeneration," he added.
As for the future, Dr. Folkman concluded, "There is a need for drugs that could maintain long-term suppression of pathologic angiogenesis [in the eye] without side effects, and we're working on three of those."
Intravitreal drugs appear promising for treatment of diabetic retinopathy
Off-label use of intravitreal drugs may have a promising future in the treatment of patients with diabetic retinopathy, but currently the dosing of these drugs is suboptimal, according to George Williams, MD, of the Beaumont Eye Institute, Royal Oak, MI. Controlled clinical trials are lacking and follow-up periods are often too short to reach any definitive conclusions about safety and efficacy.
Dr. Williams described the use of steroids and anti-vascular endothelial growth factor (VEGF) drugs that can be used as monotherapy, combination therapy, or as adjunctive therapy with laser or vitreous surgery. Steroids down-regulate VEGF production, anti-inflammatory effects, and stabilize cellular membranes, he said.
Triamcinolone acetonide resolves edema following injection, but the side effects include glaucoma and cataract formation. A drug-delivery system (Posurdex, Allergan) allows implantation of dexamethasone with a significant increase in vision at 90 and 180 days after surgery in patients with persistent macular edema. This implant is not associated with the development of glaucoma, but increases in IOP occurred. A fluocinolone acetonide intravitreal implant (Retisert, Bausch & Lomb) has been implanted in 180 patients with diabetic macular edema. Three years after surgery, there was a significant improvement in visual acuity compared with laser, but there was also the associated complication of increased IOP, with 30% of patients requiring filtration surgery, he said.
Anti-VEGF drugs such as pegaptanib sodium (Macugen, OSI/Eyetech/Pfizer) and Avastin (Genentech) are being used in patients with diabetes. Pegaptanib was shown to induce neovascular regression, increase visual acuity, and decrease retinal edema 3 weeks after injection every 6 weeks. However, the results are complicated by rebound of neovascularization after discontinuation of treatment.
Avastin resulted in a short-term increase in visual acuity and decreased edema at 3 weeks but not later and the results were not as good as with laser. Combination treatment composed of laser and intravitreal drugs may increase the efficacy of and reduce the side effects of photocoagulation, according to Dr. Williams.
"The preliminary experience with dosing of intravitreal drugs for diabetic retinopathy is suboptimal," Dr. Williams said. "Improved drug-delivery systems for steroids and anti-VEGF drugs are needed. Longer follow-up is needed to determine the efficacy and safety of treatment."
Intravitreal therapy for vein occlusive disease: promising in the short term
Intravitreal therapy for venous occlusive disease is promising in the short term, however, multiple injections are needed, dosing schedules are presently unclear, and rebound has to be evaluated, said Peter Kaiser, MD, of the Cole Eye Institute, Cleveland Clinic, Cleveland, OH.
"Venous occlusive disease is the second leading cause of decreased visual acuity in diabetic retinopathy, with 25% of patients having worse than 20/200 vision," Dr. Kaiser said. Laser treatment was not effective for these patients in two randomized studies and observation is the only therapy for central vein occlusion, he said. Laser has shown more improvement for branch vein occlusion but, in the long term, results in only a one-line increase in vision, he added.
Steroids are an obvious choice for vein occlusion since they decrease vascular permeability, stabilize the blood-retinal barrier, and address periphlebitis, according to Dr. Kaiser. In all studies, visual acuity improved. However, the drugs are associated with increased IOP and cataract, he said. The Standard Care versus Corticosteroids for Retinal Vein Occlusion Study is taking a close look at the drugs for retinal vein occlusion.
Anti-vascular endothelial growth factor (VEGF) drugs are also being evaluated. Two doses (1 and 0.3 mg) of pegaptanib sodium (Macugen, OSI/Eyetech/Pfizer) were evaluated in a phase II study. After every 6-week dosing (five injections), the visual acuity increased with both doses, but the end result was not much better than that achieved with laser, Dr. Kaiser reported.
One injection of Avastin (Genentech) achieves "very nice" clinical features and optical coherence tomography findings, according to Dr. Kaiser. After 4 months, however, the edema returns, he said. Similar results were achieved with Lucentis (Genentech). The BRAVO and Cruise studies are enrolling patients to evaluate the use of Lucentis versus controls for branch and central retinal vein occlusion.