Phase 3 study shows efficacy of VEGF therapy in CRVO

NEW YORK – Here at the Retina Congress 2009, a presenter stated that inhibition of VEGF in macular edema secondary to central retinal vein occlusion provides rapid and sustained visual acuity improvements through 6 months.

These data from the phase 3 CRUISE trial on Lucentis (ranibizumab, Genentech) vs. sham will be presented to the U.S. Food and Drug Administration soon, David M. Brown, MD, said.

Patients treated either with a 0.3-mg dose (n = 132) or a 0.5-mg dose (n = 130) were three times more likely to gain 15 letters of vision than sham-treated patients (n = 130).

“While the sham-treated arm had little improvement, both ranibizumab-treated arms had robust and significant improvements, as seen by an eight-letter improvement as soon as day 7,” Dr. Brown said.

Patients in the treatment arms also demonstrated a rapid decrease in central foveal thickness, with a reduction of 400 µm on day 7 and 433.7 µm (0.3-mg group) and 452.3 µm (0.5-mg group) at the end of the study; by comparison, there was a reduction in central foveal thickness of only 167.7 µm in the sham group.

The treatment arm was well-tolerated with no serious adverse events reported, as well as a lower rate of ocular complications compared with the sham arm, Dr. Brown said.

Bilateral same-day anti-VEGF injection safe for AMD

Bilateral same-day injection of anti-VEGF agents appears to be a safe management strategy for age-related macular degeneration presenting in both eyes.

Bilateral presentation of wet AMD is not an uncommon problem, but scheduling staggered injections may prove challenging, Sundeep Dev, MD, said.

In a retrospective review of 800 bilateral same-day procedures in 191 patients with a median age of 80 years, there was only one patient with a notable ocular complication, unilateral iritis that required steroid therapy. Dr. Dev said the patient successfully underwent three subsequent injections of an anti-VEGF agent after resolution of the iritis.

Notably, he said, this patient had a history of vitrectomy, and further studies would help elucidate whether that is a risk factor for an adverse response.

Future studies may also help clarify predicted blood levels of anti-VEGF agents after intraocular injection, which may be important for determining systemic safety. In the study, one patient reported an increase in use of anti-hypertensive medication after the fifth dose of bilateral injections.

Search for optimal anti-VEGF dosing strategy in AMD continues

Although the optimal dosing of anti-VEGF therapy remains unknown, pharmacokinetics of the two most popular agents suggest that adjusting the current dosing strategies may better serve patient needs.

Philip J. Rosenfeld

Head-to-head trials of Lucentis (ranibizumab, Genentech) and Avastin (bevacizumab, Genentech) should help steer future treatment decisions, Philip J. Rosenfeld, MD, PhD, said during the J. Donald M. Gass Award Lecture, sponsored by the Retina Society.

Yet, despite the absence of definitive clinical trials at the present time, there is suggestive evidence that either shortening the dosing frequency to 2 weeks, at least during the loading phase, or increasing the dose strength may result in significantly improved biological activity, Dr. Rosenfeld said.

Ranibizumab has a 5- to 20-fold higher binding affinity than bevacizumab, and bevacizumab has a longer half-life than ranibizumab; correspondingly, studies have shown that ranibizumab has greater biological activity on day 0 than bevacizumab.

“But it’s not how we start the month, it’s how we finish the month,” Dr. Rosenfeld said.

Studies of decay kinetics suggest similar activity of the two agents out to 30 days. However, Dr. Rosenfeld said, increasing either the dosing strength or dosing frequency of ranibizumab or bevacizumab, provided it is safe, would yield significantly higher biological activity at 30 days.

A novel anti-VEGF agent, VEGF Trap-Eye (Regeneron and Bayer), may convey even greater affinity and result in 450 times the amount of biological activity at the end of 1 month than either bevacizumab or ranibizumab.

SCORE studies: Triamcinolone a benefit for CRVO but not BRVO

In separately conducted studies, triamcinolone therapy proved more efficacious than standard therapy for patients with central retinal vein occlusion but not for patients with branch retinal vein occlusion.

At 1 year, 7% of patients in the observation group of the SCORE-CRVO study had an improvement of 15 ETDRS letters or more compared with 27% of patients treated with 1-mg triamcinolone and 26% treated with 4-mg triamcinolone.

Michael S. Ip

“The 1-mg dose has a safety profile superior to that of the 4-mg group, and the 1-mg dose has a safety profile similar to the observation group,” Michael S. Ip, MD, said.

At 12 months in the SCORE-BRVO study, 29% of patients treated with grid laser photocoagulation had a 15 ETDRS letter or better improvement compared with 26% treated with 1-mg triamcinolone and 27% treated with 4-mg triamcinolone, according to Ingrid U. Scott, MD, MPH.

OCT showed reduction in retinal thickness in all three groups, with the greatest benefit seen in the grid laser photocoagulation group. The grid laser photocoagulation group also had a superior safety profile, Dr. Scott said.

Retinal implant offers the potential for sight to blind patients

A prosthetic device surgically implanted on the retina at the macula offers the potential for visual perception for patients with retinitis pigmentosa, and future engineering may offer even greater visual performance.

The implant, called the Argus II (Second Sight Medical Products), combines an electrode array that is tacked to the retina in the macula and a camera that is worn on a special pair of glasses. Signals from the camera are transmitted to the implant and processed through the patient’s own neural network.

In clinical testing with the Argus II, which contains 60 electrodes — an upgrade from the 16 electrodes in the Argus I — 59% of 17 patients with light perception or worse vision who completed 6 months of follow-up were able to find and walk to a door unassisted. Before being implanted, just 32% were able to perform the same task.

The creator of the device, Mark S. Humayun, MD, PhD, was awarded the Retina Research Foundation Award of Merit, sponsored by the Retina Society.

“We’re trying to jump start the blind eye,” Dr. Humayun said. “We’re trying to stimulate the remaining neurons by a new genre of bioelectronics. We’re taking someone who initially is completely blind, hooking them up to a camera in real time, and having those camera images be sent via a code and electrical stimulation up the retina to the brain. If we do this for the totally blind, then can we get it to higher resolution imagery so people can actually read and recognize faces?”

Work is now under way on a 128-electrode device that may offer even greater visual sensation, Dr. Humayun said.