Article Date: 6/1/2010

Treating DME in Vitrectomized Eyes
SUBSPECIALTY NEWS

Treating DME in Vitrectomized Eyes

Sustained-release Ozurdex found effective.

BY JERRY HELZNER, SENIOR EDITOR

■ DME patients with vitrectomized eyes present a special challenge to retina specialists. Traditional intravitreal injections have limited effectiveness in vitrectomized eyes because they clear too quickly, thus creating an opportunity for Allergan's recently approved Ozurdex sustained-release implant to play a key role in the medical management of these patients.

In order to determine the effectiveness of the 0.7 mg dexamethasone implant, researchers led by Sunil Gupta, MD, of Pensacola, Fla., and David Boyer, MD, of Los Angeles followed 55 patients with DME who had undergone prior pars plana vitrectomy. All 55 patients were monitored for 26 weeks after receiving the Ozurdex implant.

In a presentation at the recent ARVO meeting, the researchers reported that improvement was seen in DME as early as one week, with overall improvement peaking at week 13. As measured by OCT, mean central retinal thickness decreased from 403 μm at baseline to 113 μm at week 13. BCVA also improved as early as week one and continued to improve out to week 13. At week 13, 30.9% of patients achieved greater than a 10-letter gain and no patient lost more than 10 letters.

The most common adverse events in study eyes were conjunctival hemorrhage (24%), eye pain (13%), and conjunctival hyperemia (7%). Pressure spikes were recorded in 7.5% of patients, peaking at week four, and declining to one patient with continued high IOP at week 13.

The researchers concluded that the Ozurdex implant resulted in significant improvement in DME in vitrectomized eyes and appeared to be well tolerated.

VEGF Trap vs CME, RAP and PEDs

Encouraging results are reported.

■ Many retina specialists view VEGF Trap-Eye, now in phase 3 trials by Regeneron, as a promising therapy for retinal disease. A study of the effectiveness of Trap against cystoid macular edema, retinal angiomatus proliferation and serious pigment epithelial detachments, was presented at the ARVO meeting.

The study was conducted by New York City's Jason Slakter, MD, of Vitreous-Retina-Macula Consultants and editor-in-chief of Retinal Physician.

Dr. Slakter did a sub-analysis of the patient population of the CLEAR-IT 2 study of VEGF Trap-Eye for wet AMD and found that 12 of the total 157 patients in the study were found to have entered with CME, seven with RAP lesions and 10 with serous PEDs.

For all groups combined, of the entire cohort of 157 patients, mean change in visual acuity from baseline at one year was a gain of 5.3 letters, with 63 of the 157 patients (40%) gaining two or more lines. The mean change in central retinal/lesion thickness from baseline was −130 μm at one year.

Dr. Slakter found that for patients with RAP lesions at baseline, the mean change in visual acuity at week 52 was +6.3 letters, with four of seven patients gaining two or more lines.

For patients with CME at baseline, the mean change in visual acuity at week 52 was +12 letters, with eight of the 12 patients gaining two or more lines.

For patients with serous PED at baseline, the mean change in visual acuity at week 52 was +6.7 letters, with five of the 10 patients gaining three or more lines.

Dr. Slakter concluded that VEGF Trap-Eye produced significant improvements in visual acuity in patients with CME, RAP lesions, and serous PEDs similar to those seen with the overall patient population.

OT-551: The Good and Bad News

Mixed results from two trials.

BY JERRY HELZNER, SENIOR EDITOR

■ Earlier this year, Othera Pharmaceuticals reported promising results from a single-site, 10-patient study of OT-551, its topical drug for geographic atrophy (GA). The study, conducted by the National Eye Institute, involved patients with bilateral GA. One eye was dosed with OT-551 and the fellow eye was used as a control. The study demonstrated good results in improving visual function but did not have any measurable effect on reducing the size of the GA lesions.

However, some of the excitement over those findings is being tempered by disappointing results from the larger, phase 2 OMEGA trial of OT-551. Data from the second trial, led by Paul Sternberg, MD, of Vanderbilt University, was presented at the recent ARVO meeting.

This 137-patient study, which focused on employing OT-551 to stop GA progression and reduce the size of the GA lesions, showed no evidence of efficacy in reaching the stated endpoint. During the 18-month duration of what was designed to be a two-year trial, OT-551 was dosed topically four times daily, with one group of patients receiving a 0.30% dose and the other a higher 0.45% dose.

On the plus side, the safety profile of OT-551 was excellent, with adverse events few and mild.

"Geographic atrophy is a straightforward condition from the perspective of measuring progression from a morphologic perspective," said Dr. Sternberg. "However, it is possible that the macular degenerative changes are advanced to the point where interventions like OT-551 are ineffective, and that their benefit may only be demonstrable if used at an earlier stage of the disease."

David Joseph, CEO of Othera Pharmaceuticals, told Retinal Physician that the next OT-551 trial would have visual acuity as an endpoint.

"This is the endpoint for which we have had positive results," he said. "We have learned a lot from these two studies. There is still more to be learned about the differences of biochemistry of geographic atrophy and the photoreceptors in the fovea and also clinical trial design."

Mr. Joseph said that Othera is interested in acquiring a partner to continue the development of OT-551.

Laser-triggered Sustained Release

An implant with multiple doses.

■ On Demand Therapeutics, Inc. (ODTx) has announced plans to develop the first multi-reservoir implantable device for laser-activated, on-demand release of drug therapies to the posterior segment. The device was discussed by Prof. Robert Langer, ScD in the keynote lecture at the recent ARVO meeting.

The ODTx device is a biocompatible, non-resorbable injectable rod comprised of multiple discrete reservoirs designed to release specific drugs in clinically optimized doses when activated by a clinician. ODTx says each reservoir can safely store smallor large-molecule drugs in the eye until release is initiated using a standard ophthalmic laser during a simple, routine office-based procedure.

ODTx was formed in 2009 as a unique joint venture between Microchips, Inc., a developer of intelligent implant systems, and InterWest Partners, a leading diversified venture capital firm.

ODTx notes that typical retinal drug-delivery procedures require monthly intravitreal needle injections. ODTx further notes that current implantable devices are largely focused on steroids and deliver sustainedrelease formulations that have no mechanism for control of dosing, leading to significant side effects such as glaucoma or cataracts.

In contrast, once the ODTx device is implanted during an in-office procedure, the ophthalmologist can control drug delivery by focusing a laser beam on one of multiple sealed reservoirs. Administering a laser pulse will create an opening in the device that releases the drug into the eye. Unactivated reservoirs remain intact until those doses are indicated. ODTx asserts that there is no need for monthly injections and the patient is easily maintained through regular follow-up visits and subsequent noninvasive laser activation procedures.

According to Gil Kliman, MD, managing director at InterWest, "The need for sustainable and interactive therapies is critical to effectively treat severe, sight-threatening diseases in the back of the eye. In the US alone, almost two million patients suffer from age-related macular degeneration and as our population ages, the demand for AMD and other retinal therapies will grow dramatically. The current standard of care of monthly intravitreal injections is unsustainable given the treatment burdens and safety issues for patients and doctors."

IN BRIEF

FA enhances fluid detection in wet AMD. Researchers from Retina Vitreous Associates in Los Angeles and New England Retina Associates of Hamden, CT tested 31 eyes to determine if patients receiving anti-VEGF therapy for wet AMD were actually fluid-free when OCT showed a complete absence of fluid.

Patients who demonstrated resolution of subretinal and retinal fluid on time-domain or spectral-domain OCT underwent fundus fluorescein angiograpghy prior to considering a drug-free interval. Outcome measures included presence of leakage on FA and change in the size and composition of the CNV complex.

Of the 31 eyes in the study, eight (26%) demonstrated active leakage on FA that OCT had not shown.

The researchers, who presented their findings at the recent ARVO meeting, concluded that, with wet AMD, subtle leakage from CNV may not result in fluid accumulation detectable by OCT. Thus, FA can be valuable in detection of this leakage.

Swapping anti-VEGF drugs. Researchers at Stavanger University Hospital in Norway sought to determine if patients who were nonresponders on one of two anti-VEGF therapies could be successfully treated with the other.

At ARVO, they reported on 29 eyes that had treatment changed from 1.25 mg Avastin to 0.5 mg Lucentis, or vice versa.

All 11 patients who were switched from Avastin to Lucentis maintained stable visual acuity and central retinal thickness three months after the change of treatment.

However, two of the 18 patients switched to Avastin gained three or more lines after three months, while the other 16 remained stable.

The researchers concluded that while "most patients have a similar response to the two anti-VEGF agents, a few might benefit from changing treatment when the initial response is not satisfactory."

Avastin used with pregnant women. The potential risks associated with using intravitreal injections of anti-VEGF drugs during pregnancy have not yet been quantified but have been the subject of discussion.

Researchers at the University of Iowa reported at ARVO that they treated four pregnant wet AMD patients with Avastin, with the number of injections ranging from one to six. Two patients had been treated with Avastin prior to pregnancy.

All four patients had multi-line improvement in visual acuity, avoiding irreversible vision loss, and all delivered healthy full-term babies. No ocular complications were reported.

Smaller SD-OCT approved. Optovue has received 510(k) clearance for a compact SD-OCT device called the iVue. The company says that the iVue "offers the benefits of advanced OCT imaging to more segments within eye care, where the economic feasibility of the larger systems simply did not work."

Macugen as maintenance therapy. The British Journal of Ophthalmology recently published online results from the LEVEL study evaluating Macugen (pegaptanib sodium) as a maintenance therapy in wet AMD.

This large, open-label, uncontrolled, exploratory study enrolled 568 patients who had been treated one to three times, primarily with ranibizumab or bevacizumab. During this induction phase, mean visual acuity im proved by 15.9 letters (from 49.6 letters to 65.5 letters).

After entering the study, patients were switched to Macugen, with the possibility of using additional treatments if needed. At the end of this 54-week Macugen maintenance phase, mean final VA remained relatively stable at 61.8 letters. From the start of the induction phase to the end of the maintenance phase, an approximately 16-month follow-up, 41% of patients gained at least three lines of VA.



Retinal Physician, Issue: June 2010