• Postphaco Technique Can Lower IOP
• Study Shows Signs of Promise for Gene Therapy
• Some Hemianopic Patients Can Recover Useful Vision
• Kudos for Academy's DC Staff
Postphaco Technique Can Lower IOP
Ophthalmologists have known for years that glaucomatous eyes can show a welcome drop in IOP after cataract surgery. Indeed, there has been an increasing use of lens replacement combined with nonpenetrating trabecular surgery in the last few years to reduce refractory IOP.
One of these nonpenetrating procedures, goniosynechialysis, opens the occluded angle by releasing peripheral anterior synechiae. But this painstaking procedure is not without risk of complications, including hemorrhage, fibrinoid aqueous and hyphema.
Now comes a group of British clinicians who think they may have done goniosynechialysis one better with a method they call viscogonioplasty. This procedure uses a routine cataract surgery tool—heavy viscoelastic—to break synechiae and open occluded angles.
“It’s a relatively simple technique that can be added on as an extra feature to cataract extraction. And it only takes another four or five minutes, if that, at the end of the surgery, using tools that are regularly available,” said Scott G. Fraser, MD, consultant-ophthalmologist and joint head of glaucoma at Sunderland Eye Infirmary, Sunderland, England.
“Our initial results suggest that in eyes with narrow angles, this works very well as an additive IOP-lowering effect,” Dr. Fraser said.
The study’s results are encouraging, said Donald S. Minckler, MD, director of glaucoma services at the University of Southern California. “The outcome in this series is better than has been previously described after goniosynechialysis with instruments or lasers and is quite encouraging, in that it appears to obviate the need for standard filtering procedures,” Dr. Minckler said.
The study, posted online by the British journal Eye,1 involved 15 eyes of patients with symptomatic cataracts as well as primary acute closed-angle glaucoma. High IOP in these patients persisted despite medical therapy and Nd:YAG peripheral iridotomy, and all the angles had iris occluding the trabeculum for at least 270 degrees.
After routine phacoemulsification and intraocular lens placement, the surgeons deepened the anterior chamber with a heavy viscoelastic. Then they injected viscoelastic into the angle for 360 degrees, being careful to avoid directly touching the trabecular meshwork.
“You have to go around 360 degrees,” Dr. Fraser explained. “You’re not just filling up the chamber, you are purposely injecting viscoelastic as near to the angle as possible. The cannula tip remains just visible throughout. This produces a constant wave that gently dissects peripheral anterior synechiae from the trabecular meshwork.”
The patients’ mean preoperative IOP was 27.4 mmHg, and was as high as 56 mmHg in one patient despite two medications. Afterward, the mean postoperative IOP measured 14.6 mmHg at two weeks, 14.1 mmHg at six months and (in six patients followed this long) 13.6 mmHg at one year. Only one patient required medication to maintain normal IOP.
The group plans to publish similar findings later this year for patients with chronic closed-angle glaucoma. A 40-patient randomized trial comparing phaco alone with the combined procedure also is under way. But the early results have made the group optimistic that they have found a simple, low-risk way to open occluded angles.
1 Varma, D. et al. Eye. Published online Jan. 13, 2006.
Go to www.nature.com/eye, click “Advance Online Publication.”
Eye on Trials
Study Shows Signs of Promise for Gene Therapy
Many research groups worldwide have flirted over the last two decades with using gene therapy to heal disease, but very few have been able to demonstrate clinical effects in patients. So U.S. ophthalmic scientists made a bit of history recently when their phase 1 trial of an antiangiogenic agent in humans showed impressive safety and hints of biological activity.
Their study found that patients who received a single intravitreal injection, above a threshold dose, of an adenoviral vector for producing a molecule that inhibits angiogenesis, had no severe toxicity and had a median increase in lesion size of 0 over the course of a year.1 Without a placebo group, it was not possible to evaluate efficacy, but based upon choroidal neovascularization’s natural history, the result was unexpected, said lead researcher Peter A. Campochiaro, MD, professor of ophthalmology and neuroscience at Johns Hopkins University.
This trial was only a small safety study to determine how well adenoviral vectors could be tolerated in the eye. Many observers predicted severe ocular inflammation, but it proved to be relatively infrequent (25 percent), transient and controllable. The signs of biological activity came as a happy surprise, Dr. Campochiaro said.
“[The trial] provides some proof of concept for gene therapy in the eye, and the potential applications are enormous because all sorts of molecules can be delivered this way,” said Dr. Campochiaro.
Only one other application of ocular gene therapy, for retinoblastoma, also with an adenoviral vector, has been tried in patients. That small safety trial also showed hints of efficacy, and no severe toxicity.2 There have been a few success stories in other organs, but too often gene therapy has proven ineffective, problematic or, in a few cases, potentially fatal. The last of these roadblocks occurred in 2003, when French physicians stopped treating a childhood immune-deficiency with gene therapy because, although they cured several children, two developed leukemia.
The multicenter trial on which Dr. Campochiaro’s team reported was sponsored by GenVec Inc., which modified a common adenovirus so that it could not reproduce and did not produce certain adenoviral proteins. Then they engineered it to carry a gene for an antiangiogenic molecule, pigment epithelium-derived factor (PEDF), into cells. Modified many times, the vector was numbered along the way, and the current version is known as AdPEDF.11.
Studies of the molecular pathways leading to CNV have shown that, while the growth factor VEGF stimulates angiogenesis, PEDF shuts it down. In theory, both lowering levels of the first molecule and raising levels of the second would control CNV better than monotherapy.
In this ocular study, 28 patients each underwent a single intravitreal injection of AdPEDF.11 at one of eight different dose levels. The patients had wet AMD that measured < 12 optic disc areas and had BCVA of 20/200 or worse. Patients treated with the four lowest doses had CNV progression after six months, but most patients (70 percent) receiving the highest doses had no evidence of growth over the course of a year.
In an extension of the phase 1 trial, patients with less severe disease are being treated with two of the higher doses used in the first trial, to gather more safety data and to learn more about AdPEDF.11’s biological activity. These data could provide the foundation for a phase 2 study.
1 Campochiaro, P. A. et al. Hum Gene Ther 2006;17(2):167–176.
2 Chevez-Barrios, P. et al. J Clin Oncol 2005;23:7927–7935.
Some Hemianopic Patients Can Recover Useful Vision
Quietly, neuro-ophthalmologists at a handful of locations around the United States are helping their stroke and brain-injury patients with hemianopia do something that might seem impossible—recover useful vision.
“I certainly went into this somewhat dubious,” said Richard H. Legge, MD, an Omaha, Neb., neuro-ophthalmologist. “But now that I’ve had some experience I’m convinced it works in more than half the patients—and by that I mean improving their ability to function in some aspect of their lives.”
The rehabilitation system Dr. Legge uses has the trademarked name of Vision Restoration Therapy (VRT). Made by NovaVision, it is offered to stroke and traumatic brain injury patients at 19 sites around the nation.
The home-based system uses special software to generate a pattern of light flashes on a laptop screen, with the patient’s eyes at a fixed distance. As with perimetry, the patient pushes a button upon seeing a flash.
The flash pattern is customized to stimulate the margin between functioning and nonfunctioning visual cortex, with the goal of using neural plasticity to restore some level of function there. Patients have two 20-minute sessions a day, six days a week, for six months. The computer records the patients’ responses, providing the information for a monthly update of each patient’s flash pattern.
Dr. Legge began offering the system to his patients in October 2004. “I became interested in it because, based on studies by a German group, it looked like it might be able to improve visual function,” he said. “I see a lot of these patients, week in and week out, and up until that time the therapeutic options we had to offer them were very limited.”
More than a year later, Dr. Legge is a believer based on experience with 20 patients. At the North American Neuro-Ophthalmic Society meeting earlier this spring, he reported improvement in visual functioning by six of his first seven VRT patients.
“We’re seeing people’s lives being changed,” he said—then adds that he understands if other ophthalmologists are skeptical, because standard perimetry frequently doesn’t show changes.
“They improve in activities of daily living like reading speed, reduced collisions with objects when they’re walking and improved ability to acquire targets in their environment,” Dr. Legge said. One of his patients, overwhelmed when confronted with complex environments, regained the ability to navigate a shopping center after VRT, he said. Another was able to play basketball again.
“One young dentist who had been disabled by stroke was able to go back and practice dentistry within two months of being on VRT,” he added. “I’ve had patients who now can go through a whole newspaper comfortably, and before VRT they could only read a couple of pages because they would get so fatigued.”
Yet objective testing in these same patients doesn’t show much change in their visual fields after therapy, he said. Said Dr. Legge: “The conclusion I’m coming to is that VRT helps a patient’s visual system in ways that we can’t measure well with the visual field device. I think it works on areas that just are not demonstrable on perimetry.”
Kudos for Academy’s DC Staff
Cathy G. Cohen, the Academy’s vice president of Governmental Affairs, and her staff in the Academy’s Washington, D.C., office earned praise in the Feb. 1 The Hill, a newspaper that carries a biweekly section on the best lobbyists in various industries. The brief write-up included a quote from one Washington insider who mentioned the Academy’s team is “very smart and very good at what they do.” H. Dunbar Hoskins Jr., MD, the Academy’s executive vice president said, “This is gratifying recognition of the hard work the entire Academy and its members invest in being advocates for our profession.”