Lucentis in Vitrectomized Eyes
Small study finds good duration of response.
BY JERRY HELZNER, SENIOR EDITOR
■ It is generally believed by retina specialists that intravitreal injections of all drugs are not as effective in vitrectomized eyes as they are in non-vitrectomized eyes. This is due to the fact that studies have shown that antibiotics and steroids clear more quickly in a vitrectomized eye and thus have a shorter duration of response in those eyes.
However, a small study of 10 patients (six women, four men) undertaken by Thomas B. Connor Jr., MD, a retina specialist at the Medical College of Wisconsin, found that patients with vitrectomized eyes who were given Lucentis injections for wet AMD demonstrated a similar response as patients with nonvitrectomized eyes.
“I was a bit surprised by the results,” Dr. Connor told Retinal Physician. “This opens up questions about the pharmacokinetics of intravitreal injections.” Comparing the rate of clearance for antibiotics to the duration of response for anti-VEGF agents “is really not apples to apples,” he says. Antibiotics have a target of eliminating bacteria, he notes, while anti-VEGF agents are targeting a receptor. “The fact that the eye is vitrectomized may not preclude the anti-VEGF agent from successfully binding with the receptor,” Dr. Connor says. “In any case, this whole question of clearance needs further study.”
The study began with a review of medical records from July 2006 to July 2009 of patients who received intravitreal Lucentis for neovascular AMD and who had previously undergone pars plana vitrectomy (PPV) in that same eye for a different indication. Patients with diabetic retinopathy or retinal vein occlusion were excluded.
The 10 patients who met the selection criteria ranged from 61 to 92 years, with a mean age of 80.6 years. Reasons for previous PPV included retained lens material following cataract surgery (3), retinal detachment (2), epiretinal membrane (2), nonclearing vitreous hemorrhage from posterior vitreous separation (2) and dislocated intraocular lens (1). Time from PPV to diagnosis of neovascular AMD was two to 12 years, with a mean of 5.8 years.
Visual acuity at time of diagnosis of wet AMD ranged from 20/60 to 20/400, with a mean of 20/182. The number of monthly injections of Lucentis until retinal hemorrhage, edema and subretinal fluid had resolved and was confirmed with time-domain OCT ranged from three to nine injections, with a mean of 5.6 injections. Vision at this time point ranged from 20/30 to 20/150, with a mean of 20/74. Snellen lines gained ranged from one to five lines, with a mean of three lines. Six patients gained three or more lines.
Dr. Connor concludes that intravitreal injection of Lucentis may be quite helpful in patients with neovascular AMD who have had previous vitrectomy. He says the vitrectomized state did not require more frequent treatment than standard therapy. The favorable treatment response in this group may warrant further investigation.
A Safer Way to Treat Eye Cancer
Silicone oil blocks damaging radiation.
■ Researchers at UCLA have discovered that silicone oil shields the eye and appears to protect vision in patients undergoing radiation therapy for ocular melanoma.
The American Medical Association's Archives of Ophthalmology published the researchers' findings in a recent issue.
“Vision loss is a devastating yet common side effect of radiation therapy,” notes Tara McCannel, MD, assistant professor of ophthalmology and director of the UCLA Ophthalmic Oncology Center at the Jules Stein Eye Institute. “Until recently, physicians focused on killing the tumor and considered vision loss secondary. Our results suggest that silicone oil offers a safe tool for protecting the patient's vision during radiation.”
Surgeons normally treat ocular melanoma by stitching a gold plaque containing radioactive seeds to the white of the eye and removing it a few days later. While radiation kills the cancer cells, it also causes irreversible injury to the optic nerve fibers and macula. Radiation damage to the macula weakens the blood vessels feeding the eye, causing bleeds and wiping out circulation. Even when the radiation successfully destroys the tumor, the eye structures remain extremely fragile and prone to atrophy, which can lead to vision loss.
“If patients survive the cancer, more than half will suffer vision loss in the treated eye six months to three years later,” says Dr. McCannel, a vitreoretinal surgeon who is also a member of UCLA's Jonsson Comprehensive Cancer Center. The risk for blindness increases over time.
The UCLA technique takes place immediately before the patient's eye is exposed to radiation.
Patients first undergo an exam to measure baseline vision before treatment. Dr. McCannel next removes the vitreous gel. She then replaces the gel with silicone oil.
After removing the radiation plaque from the treated eye, she flushes the oil away with saline, which is eventually replaced by the patient's natural fluids.
“We discovered that silicone oil absorbs nearly 50% of the radiation,” she says. “The substance acts like a physical shield, reducing the amount of radioactive rays that reach the back and sides of the eye. We hope that silicone oil's ability to block radiation translates into better vision for patients down the road.”
Widely used in other types of retinal surgery, the oil doesn't interfere with the tumor's treatment and its transparency allows both the surgeon and the patient to see through it.
The UCLA team used three approaches to demonstrate that silicone oil absorbs 50% of the residual radiation. While more long-term research is needed, early follow-up with Dr. McCannel's patients showed that their vision returned to baseline levels without interfering with their tumors' response to radiation therapy.
Ozurdex/Anti-VEGF Therapy in Wet AMD
Implant reduces injection frequency.
■ Researchers from Israel and the US led by A. Loewenstein, MD, of the Tel Aviv Medical Center, conducted a 243-patient study to determine if Allergan's sustained-release, biodegradable Ozurdex (dexamethasone intravitreal implant) 0.7 mg could have a beneficial effect in treating CNV secondary to wet AMD.
Patients were divided into two groups. Both groups received an initial intravitreal injection of ranibizumab. Four weeks later, at the baseline day, 123 patients who would normally have been scheduled for another ranibizumab injection were implanted with the Ozurdex device instead. The 120 patients in the second group were given a sham treatment. Patients in both groups did receive another rani bizumab injection seven to 14 days after the baseline day.
From that point on, ranibizumab retreatment was provided to patients in both groups on an as-needed basis for the duration of the 25-week study. In totaling the number of additional ranibizumab injections, the 75th percentile of injection-free interval was 12 weeks in the dexamethasone implant group vs eight weeks in the control group over six months.
Treatment-related adverse events were similar between groups, except for in creased IOP (9.9% vs 3.4%) and conjunc tival hemorrhage (6.6% vs 0.8%) in the Ozurdex group vs the control group.
The researchers concluded that Ozurdex delayed the time to as-needed injection of ranibizumab and reduced the need for repeated ranibizumab treatment in patients with CNV secondary to AMD.
Studies such as this one continue to reinforce various recent data in dicating that the biodegradable Ozurdex implant (with about a six-month period of effectiveness) may be useful in the treatment of a broad range retinal diseases, in addition to its FDA-approved indication for the treatment of macular edema associated with retinal vein occlusion.
The study results were presented at the 2010 ARVO meeting.
|■ OptiMedica sells Pascal business. OptiMedica has signed a definitive agreement to sell its retina and glaucoma assets to Topcon, a move that positions OptiMedica to focus exclusively on the continued development of advanced cataract surgery technologies, notably in the emerging area of femto-phaco.
OptiMedica is best known in retina for its Pascal method of retinal photocoagulation, a semiautomated pattern-generation technique that allows rapid delivery of laser pulses in a predetermined sequence.
Until now, Topcon had been a distribution partner for the Pascal laser. The acquired business will be managed by the newly established Topcon Medical Laser Systems, Inc.
■ Micropulse laser patent. Iridex was granted a patent that enables it to add the tissue-sparing micropulse technology currently used on the company's infrared lasers to its visible light lasers as well. Micropulse mode can be activated at the touch of a button, allowing the surgeon to switch between conventional and micropulse energy deliver as needed.
A study of micropulse delivery of 577nm light from Iridex's IQ 577 laser to treat central serous chorioretinopathy presented at this year's ARVO showed favorable results with no induced scarring of treated areas.
■ B+L introduces combination phaco/vitreoretinal instrument. Bausch + Lomb has introduced the Stellaris PC (Procedural Choice) Vision Enhancement System. B+L says the new, state-of-the-art combined vitrectomy and phacoemulsification system allows surgeons to have true “procedural choice” by providing the most advanced technology for both vitreoretinal and cataract surgery in a single system.
The Stellaris PC provides surgeons with a platform for the smallest incisions for both retinal and cataract surgeries. It is capable of 1.8 mm MICS phacoemulsification, as well as being a complement with Bausch+Lomb's TSV 25-gauge system of instruments for retinal surgery, along with the 23- and standard 20-gauge instruments.
■ Santen acquires MacuSight drug. Santen has acquired the development, manufacturing and marketing rights to MacuSight's proprietary formulation of sirolimus (rapamycin), which has been in clinical trials for the treatment of retinal diseases, including wet AMD, DME and uveitis. Santen has recently been listed on www.clinicaltrials.gov as the sponsor of studies using MacuSight's version of sirolimus to treat wet AMD and DME. Johns Hopkins is listed as the sponsor of the uveitis trial.
MacuSight had been focusing its attention on the development of sirolimus and currently has no other drugs in clinical trials.
Letter to the Editor:In your July/August issue (“Great Debates in RVO Therapy”), I discussed my algorithm using a combination of bevacizumab and Ozurdex for treatment of retinal vein occlusions. My algorithm was based on a research study that I am conducting using the therapy that was available at the time.
The study was initiated in September of 2009. One of our findings was that not all patients treated with bevacizumab had resolution of edema with their first injection. I thought at the time that when I saw patients at four-to-six weeks who had persistent edema, it was because of rebound edema after the anti-VEGF effect had worn off. What we found was that patients examined at two weeks could be divided into two groups. One group had complete resolution of edema and the other group did not. It turns out that only 50% of the patients had resolution of edema when examined at the two-week interval, regardless of whether they were treated initially or had repeated injections.
Now that ranibizumab has been ap proved for RVO, we have examined patients at two-week post-injection intervals and found that a higher percentage of patients (75% to 80%) have resolution of macular edema. This fact is also substantiated by the six- and 12-month BRAVO and CRUISE data, which show substantial decrease in macular edema as early as one week in both new and chronic vein occlusions.
Earlier resolution of edema has been correlated with better visual prognosis. This finding has been demonstrated in the BRAVO, CRUISE and Ozurdex studies. It has been shown by looking at the visual acuity of the groups randomized to sham vs initially treated and measuring their vision at the end of 12 months. It has also been shown in the subgroup analyses of patients with disease of less than three months duration vs those with greater than three months duration. The patients with disease of less than three months had better vision than those who were recruited with disease of longer than three month duration.
As a result, my current anti-VEGF treatment of choice in RVO disease is ranibizumab.
—Michael Singer, MD