Article Date: 10/1/2010

Lucentis Developer Wins Lasker Award
SUBSPECIALTY NEWS

Lucentis Developer Wins Lasker Award

Dr. Napoleone Ferrara is Genentech researcher.

Dr. Napoleone Ferrara is the discoverer of VEGF.

■ The prestigious 2010 Lasker~DeBakey Clinical Medical Research Award has been given to Napoleone Ferrara, MD, PhD, 54, of Genentech, who is credited with discovering vascular endothelial growth factor (VEGF) and using this knowledge to invent ranibizumab (Lucentis), considered a breakthrough treatment for wet AMD.

The Award citation states that “upwards of a million AMD patients worldwide have already received the therapy and scores more will likely benefit in the coming decades, as the world's population ages.”

According to the news release announcing the award, Dr. Ferrara's journey to unlocking the lynchpin for one of the body's most important physiological processes and creating a novel approach to combating AMD began in the early 1980s with his study of cells linked to blood-vessel development. At Genentech in 1989, Dr. Ferrara discovered a substance in humans that spurs growth of vascular endothelial cells and began to investigate whether quelling what he dubbed “VEGF” could thwart troublesome blood vessel formation.

Dr. Ferrara subsequently proved that shutting down VEGF receptors could stem blood vessel formation and went on to develop an antibody to neutralize human VEGF, which choked off the flow of blood, helping stem tumor growth. This led to the creation, in 2000, of the anti-VEGF treatment ranibizumab that slows blood vessel formation in the eye.

The Lasker Awards were established in 1945 by advertising industry pioneer Albert Lasker and his wife, citizenactivist Mary Lasker. The Lasker Foundation celebrates science, educates the public, and advocates for public support of medical research. By showcasing how fundamental discoveries in basic science lead to clinical treatments and therapies, the Lasker Awards illustrate the benefits of investing in science.

The brass Lasker Award statue represents the Greek Winged Victory of Samothrace, symbolizing creative biomedical research that produces, in the words of Mary Lasker, “victory over disability, disease and death.” Each award carries a $250,000 prize that's shared among the winners.

Factors Affecting Success of RD Surgery

A study of 542 eyes from one practice.

■ Researchers from the Robert Wood Johnson Medical School in New Brunswick, NJ, and the University of Miami retrospectively reviewed 542 eyes that underwent surgery for retinal detachment. Their aim was to predict preoperative and surgical features of retinal detachment (RD) that influence success or failure after RD surgery.

“Controversy exists regarding the ideal approach to repair rhegmatogenous retinal detachment: scleral buckle alone, vitrectomy alone or combined scleral buckle and vitrectomy. Preoperative factors may influence outcome as well and deserve study,” wrote the researchers in their presentation at the 2010 ARVO meeting. “Herein, we evaluate preoperative and surgical features of retinal detachment that influence success or failure after retinal detachment surgery.”

A total of 542 consecutive eyes undergoing scleral buckle, vitrectomy or combined scleral buckle-vitrectomy were retrospectively reviewed. Surgery was performed by one of eight vitreoretinal surgeons from a single group retina practice. Primary outcome measures were initial success, final success, visual improvement and development of proliferative vitreoretinopathy (PVR). Preoperative factors evaluated included preoperative visual acuity, lens status, use of glaucoma drops, prior laser or cryotherapy, macular status, the number of clock hours of RD, the number of retinal holes and the presence of inferior holes, lattice degeneration, giant retinal tear or chronic RD.

The review showed that 45% of eyes presented with a macula-on RD and 52% presented with macula-off RD, while 75% of eyes presented with two or fewer retinal holes and 33% of eyes presented with inferior retinal holes. Presenting visual acuity was 20/40 or better in only 36% of eyes. Total cohort initial success was 91%.

After multivariate analysis, no significant difference in initial success was noted between the surgical techniques of scleral buckle alone, vitrectomy alone or combined scleral buckle and vitrectomy. An increased number of clock hours of RD was associated with initial failure: for an additional three clock hours, the odds ratio for initial failure was 1.7 times or 70% higher. Increased number of clock hours of RD was associated with development of PVR.

Final success was decreased in eyes with worse preoperative visual acuity, suggesting chronicity of RD. Larger RD, preoperative visual acuity of 20/200 or worse, and giant retinal tear were associated with a final visual acuity of worse than 20/40.

The researchers concluded that with appropriate case selection, scleral buckle alone, vitrectomy alone or combined scleral buckle-vitrectomy all have a similar primary success rate. Extent of RD was the most important factor in predicting a worse initial anatomical outcome.

IN BRIEF
■ RVO and incidence of stroke. A large-scale study of approximately 18,000 people indicates that individuals with retinal vein occlusion have about twice the risk of having a cerebro-vascular accident as individuals who have no history of RVO. However, no increased risk was found among RVO patients for myocardial infarction.
The study was presented at the recent ASRS meeting by Nancy M. Holekamp, MD, of St. Louis. It involved comparing 4,500 patients with RVO against an age-matched control group of 13,500 people.
■ Iluvien receives priority review. Alimera Sciences said its New Drug Application (NDA) for Iluvien (fluocinolone acetonide intravitreal insert) has been accepted for filing and granted Priority Review status by the FDA. Iluvien is Alimera's investigational, sustained drug-delivery system for the treatment of DME.
With priority review, Alimera could receive a response from the FDA in the fourth quarter regarding its NDA for Iluvien, which was submitted at the end of June 2010.
In other Alimera news, the company has promoted Richard S. Eiswirth, Jr. to COO, and David R. Holland to senior vice president of sales and marketing. Mr. Eiswirth, who retains the position of CFO in addition to his new role, will continue to oversee Alimera's finances and growth strategy implementation. Mr. Holland, a co-founder of Alimera who has served as vice president of marketing since 2003, will manage corporate communications and product sales and marketing.
■ Surgical simulators gain advocates. Ophthalmology residency and training programs should be incorporating surgical simulators into their teaching methods, said a speaker at the recent Euretina meeting.
Ophthalmologists can benefit from performing simulated procedures “much as pilots have to practice many hours in a flight simulator that can realistically emulate almost any weather condition and mechanical problem that they are likely to face,” said British ophthalmologist Brian Little, MD, at the recent Euretina meeting.
VR Magic, headquartered in Germany, now offers both vitreoretinal and phaco simulators. The company says its Eyesi simulators provide a lifelike learning environment — making it possible for trainees to effectively gain medical experience with no risk to patients. The simulators provide trainees with the opportunity to deal with a wide range of pathologies and complications that can be trained at any time and independently of patient flow.
VR Magic says frequent practice using retinal modules improves proficiency in complex tasks such as posterior hyaloid detachment, peripheral vitrectomies, internal limiting membrane peeling or the removal of epiretinal membranes. A realistic posterior segment surgical simulation environment is provided through the use of scleral indentation, a vitrectomy machine, variable illumination intensity of the light pipe and an endolaser.
■ Ozurdex approved for noninfectious posterior uveitis. Allergan announced that the FDA has approved Ozurdex (dexamethasone intravitreal implant) 0.7 mg for the treatment of noninfectious posterior uveitis.
Ozurdex, a sustained-release biodegradable implant, was earlier approved for treating macular edema associated with RVO.
The efficacy of Ozurdex for the uveitis indication was assessed in a 26-week, multicenter, doublemasked, randomized clinical study in which 77 patients received Ozurdex 0.7 mg and 76 patients received sham injections.
After a single injection of Ozurdex, the percent of patients reaching a vitreous haze score of zero (a score of zero represents no inflammation) was statistically significantly greater for patients in the Ozurdex-treated group vs sham (47% vs 12%, respectively) at the week eight primary endpoint. In addition, the percent of patients achieving a three-line improvement in BCVA was 43% in the Ozurdextreated group vs 7% for the sham group at week eight.
In other Ozurdex news, the European Medicines Agency has granted marketing authorization for Ozurdex in the 27 member states of the European Union for the treatment of macular edema associated with RVO.
■ Peripheral abnormalities identified. Peripheral retinal abnormalities were found in 76% of AMD patients who received ultra-widefield autofluorescence imaging, according to a retrospective analysis of 122 patients seen at USC's Doheny Eye Institute. The data were presented at the recent ASRS conference. Autofluorescence is believed to help in AMD detection. Manufacturer Optos says its ultrawidefield technology will now join the AREDS2 study to aid in monitoring the effectiveness of treatment to forestall AMD progression.
“With this large, four thousandstrong patient cohort, we will be able to investigate age-related changes in the periphery and their possible prognostic significance,” said Srinivas Sadda, MD, lead investigator of the Doheny study.
Optos said this study follows the recently published results from the Reykjavik/Moorfields study and adds to the growing body of evidence of the importance of studying the periphery of the retina in the diagnosis and management of AMD.
■ Valproic acid studied for RP. Valproic acid, which is commonly used to treat epilepsy and bipolar disorders, may have a future in the treatment of retinitis pigmentosa (RP), according to an early-stage study recently reported in the British Journal of Ophthalmology.
The retrospective chart review included 13 eyes with RP examined before and after an average of four months of valproic acid therapy. Mean patient age was 36.
Study results showed improved visual fields in nine of the eyes, worse visual field results in two of the eyes and no measurable change in two eyes. Based on typical visual field loss without treatment, the improvement was statistically significant. The average improvement of all 13 eyes was from 20/47 to 20/32.
A 90-patient clinical trial is now planned to further determine any future role for valproic acid as a treatment for RP.
■ IMT trial in the UK. A team of researchers from Moorfields Eye Hospital in London, England, and three other eyecare centers in the United Kingdom are conducting their own independent study of the Im plantable Miniature Telescope (IMT), a device intended to help restore sight in patients with severe vision loss from retinal disease. The IMT was recently approved in the US.
In the UK, six participants (mean age 77, five female) with mean VA 1.06 logMAR (range 0.88 - 1.34) have been implanted and followed up for at least three months. No surgical complications have been encountered to date. The researchers reported that mean distance VA improved significantly by 0.36 logMAR at three months after surgery. Modest improvements were also seen in reading performance but these failed to reach statistical significance. Contrast sensitivity was significantly reduced at three months by 0.40 log units. Results from VFQ and AI questionnaires suggest an overall improvement in self-reported visual disability, but again these were not statistically significant.
The UK researchers concluded that the IMT significantly improves distance VA but reduces contrast sensitivity at three months. Reading per formance and self-reported visual disability measures show a trend towards improvement. Overall these results suggest that the IMT may be of benefit to carefully selected patients as part of a program of rehabilitation.
■ OptoVue OCT database approved. Optovue has received 510(k) clearance on its Normative Database (NDB) for the RTVue SDOCT device.
“This affirms that our protocols and management of this large international, multisite normative population are at the level that FDA regulatory guidelines require,” said Mike Sinai, PhD, senior director of clinical research for Optovue. “Most importantly, this demonstrates the safety and efficacy of our NDB based on the FDA current standard for its intended uses.” RP


Retinal Physician, Issue: October 2010