News
CLINICAL NEWS

VEGF Trap for AMD Enters Phase 3 Trial
Regeneron Pharmaceuticals, Inc. (Tarrytown, NY) and Bayer HealthCare AG (Leverkusen, Germany) have initiated a phase 3 study of VEGF Trap-Eye for treatment of the neovascular form of age-related macular degeneration (AMD).

The study will be a noninferiority comparison of VEGF Trap-Eye and ranibizumab (Lucentis; Genentech, San Francisco) and will be conducted pursuant to a Special Protocol Assessment from the US Food and Drug Administration (FDA), according to a news release. This trial, VIEW 1, or VEGF Trap: Investigation of Efficacy and Safety in Wet Age-Related Macular Degeneration, is the company’s first in a phase 3 global development program in neovascular AMD. The program is to be carried out in the United States, Europe, and other parts of the world.

“The results of early phase studies of VEGF Trap-Eye suggest that it has the potential to be a highly efficacious treatment with less frequent administration. If these results are confirmed in phase 3 trials, it would be important for both patients and physicians and would be a significant advance in the treatment of these patients,” said Jeffrey Heier, MD, from Ophthalmic Consultants of Boston and Chair of the Steering Committee for the trial. Dr. Heier is also a member of the Retina Today editorial board.

The randomized, double-masked phase 3 study is expected to enroll approximately 1,200 patients in more than 200 centers. The study will evaluate the safety and efficacy of the VEGF Trap-Eye at doses of 0.5 and 2.0 mg administered at 4-week dosing intervals, as well as 2.0 mg at an 8-week dosing interval. This will be compared with 0.5 mg of ranibizumab administered every 4 weeks, consistent with its labeled dosing schedule.

The primary endpoint of the study is the proportion of patients treated with VEGF Trap-Eye who maintain or improve vision at the end of 1 year compared with ranibizumab patients.

Visual acuity is defined as the total number of letters read correctly on the Early Treatment of Diabetic Retinopathy Study (ETDRS) chart. Maintenance of vision is defined as losing fewer than three lines (15 letters) on the ETDRS chart. After the first year of treatment, patients will continue to be treated and followed for another year.

In an analysis of interim data from the ongoing phase 2 trial in neovascular AMD, in which patients were treated with VEGF Trap-Eye either monthly or quarterly, combined data for all patients demonstrated a statistically significant reduction in retinal thickness and improvement in visual acuity after 12 weeks compared with baseline. There were no drug-related serious adverse events, and treatment with the VEGF Eye-Trap was generally well tolerated. The most common adverse events were those typically associated with intravitreal injections, according to a company news release.

Regeneron and Bayer HealthCare are collaborating on the global development of VEGF Trap-Eye for the treatment of neovascular AMD, diabetic eye diseases, and other eye diseases and disorders. Bayer HealthCare will market the product outside the United States, where the parties will equally share in any future profits from the sales of VEGF Trap-Eye. Regeneron maintains exclusive rights to the product in the United States.

ADMA Associated With Diabetic Retinopathy
Maciej T. Malecki, MD, PhD, and colleagues, from Jagiellonian University in Poland, examined data from a cross-sectional analysis to determine if there was a relationship between asymmetric dimethylarginine (ADMA) and diabetic retinopathy (DR). ADMA, an endogenous inhibitor of nitric oxide synthase, has previously been associated with vascular diabetic complications (eg, nephropathy).

Their data, presented at the American Diabetes Association’s 67th Scientific Sessions in Chicago, suggest that elevated circulating ADMA levels are associated with the presence of retinopathy in patients with type 2 diabetes.

The study involved 234 people, including 52 healthy well-matched controls (mean age, 54.5 ±7.1 years), 111 patients with type 2 diabetes and no DR, and 71 patients with type 2 diabetes and DR (mean age, 55.7 ±6.2 years; 57.1 ±7.0 years, respectively).

Dr. Malecki and colleagues found that ADMA levels were highest in patients with type 2 diabetes and DR (0.60 ±0.06 µmol/L). ADMA levels were slightly lower in type 2 patients with no DR (0.51 ±0.06 µmol/L) and lowest among the control group (0.45 ±0.05 µmol/L).

“In a stepwise multivariable logistic regression, the level of ADMA remained an independent predictor of the presence of DR in patients with type 2 diabetes,” Dr. Malecki wrote. The elevated circulating ADMA levels seem to be associated with DR, independent of renal function.

Statin Agents May Be Protective Against AMD
Researchers from the Centre of Vision Research at the University of Sydney believe statins (HMG-CoA reductase inhibitors) may offer some protection in the eye from a complication of AMD.

In a population-based cohort study of 1,952 participants enrolled in the Blue Mountain Eye Study (1992-1994), researchers found that statin use was not significantly associated with overall early AMD incidence at
10-year follow-up.

Participants underwent physical examinations and had fasting blood samples taken. Discrete linear logistic models were used to assess the risk of AMD.

After controlling for age, gender, and other confounding factors, statin users had a reduced risk of developing indistinct soft drusen, the principal late AMD precursor lesion (95% confidence interval, 0.13-0.84.).

New Equipment Aids in Scans of Diabetic Patients
The University of Virginia Health System has become the nation’s first academic training facility to install cutting-edge equipment to scan patients’ eyes during medical check-ups.

The Optomap retinal scanner (Optos plc, Scotland, SC) performs fast eye screenings and has been installed at University Medical Associates (UMA), the school’s largest and busiest outpatient clinic, according to a news release. The scanner has been used on 100 patients so far, finding a 20% rate of disease. The speed of the scan helps with noncompliant patients, those who do not have reliable transportation, or who do not wish to have their pupils dilated.

Sara Aldridge, RN, at the UMA clinic, believes that the process itself is very educational. “The conversation we having during the screening leaves a big impression on diabetic patients,” she explained. “Besides giving them a better understanding of the risks they face, patients leave knowing the importance of getting preventive eye exams and then following up when problems are found. No one wants to risk going blind.”

Gene Variant May Double Risk of AMD
Researchers have found a gene variant that can more than double the risk of developing AMD. The initial studies were led by John Yates, MA, MSc, PhD, of Cambridge, and Tony Moore, MA, FRCS, FRCOphth, of the University College of London, Institute of Ophthalmology.

Drs. Yates and Moore found that a variant in the complement C3 gene influenced the risk of developing AMD. Among the 30% of the population who carry one copy of the so-called fast variant, the risk of AMD was increased by 70%. For the 4% of the population with two copies of the fast variant, the risk of AMD was more than doubled.

The results of this research, published in the New England Journal of Medicine and funded by the Medical Research Council (London), provide strong evidence that inflammation is an important part of the disease process in AMD, the researchers concluded.

Vision Restoration Therapy May Improve Sight
Researchers from Columbia University Medical Center have discovered a rehabilitative treatment that uses Vision Restoration Therapy (NovaVision VRT, Boca Raton, FL) helps patients recover vision loss caused by a stroke or traumatic brain injury. The data were published online in Neurorehabilitation and Neural Repair.

Randolph S. Marshall, MD, MS, and colleagues examined the functional magnetic resonance imaging (fMRI) of six patients, aged 35 to 77 years, with vision loss on the same side of both eyes caused by stroke or traumatic brain injury. Vision Restoration Therapy is based on visual stimulation, which the patient performs daily at home on a computer. The fMRI data showed increased activity in visual processing areas of the brain as patients learned to detect stimuli in the zone between the seeing and nonseeing fields. This enhanced activity suggests the brain responded to the treatment, researchers said.

“This study is encouraging because the fMRI technique allowed us to see and compare the activity levels in specific regions of the brain, before and during Vision Restoration Therapy. After examining the images, the increased activity levels demonstrate progress associated with the treatment,” said Dr. Marshall, in a news release. “Based on these initial results, we will continue to investigate the relationship between the imaging findings and the degree to which vision is recovered.”

Through further enhancements of this therapy, the hope is to help the approximately 1 to 2 million stroke and brain injury survivors in the United States. Vision Restoration Therapy is currently offered at 50 neurological, eye, and rehabilitation centers nationwide.

AMD May Have a Zinc Link
A team of US and British researchers have found that the mineral zinc could play a role in the development of AMD. In studying eye tissue samples, the researchers found that the hallmark deposits of AMD contain large amounts of zinc.

The findings, published in the journal Experimental Eye Research, might be particularly important because zinc supplements are widely given to patients to help boost weak immune systems. Additionally, the 2001 National Eye Institute Age-Related Eye Disease Study (AREDS) found that high doses of zinc supplements, combined with antioxidants, may postpone the progression to blindness.

“Because earlier findings have shown that zinc contributes to deposit formation in neurodegenerative diseases (eg, Alzheimer’s, Parkinson’s), we are prompted to test the theory that zinc might be involved in deposit formation in AMD,” said Jane Flinn, PhD, Professor of Psychology at George Mason University.

The double-edged sword is that zinc has been found to enhance the immune system, but could also play a role in the advancement of AMD, researchers said. The team hopes their findings can be useful in the development of new treatments, as well as a more informed approach to zinc intake recommendations.

Study Examines Cataract Surgery in Patients With Diabetes
AquaLase cataract extraction (Infiniti System; Alcon, Fort Worth, TX) may produce less intraocular microtrauma than standard phacoemulsification, according to a study by Allon Barsam, MBBS, MA, MRCOphth, and colleagues. Dr. Barsam further hypothesized that the reduction of microtrauma may result in lower rates of clinical cystoid macular edema (CME).

To study this, 63 patients with diabetes received either AquaLase (n=32) or standard phacoemulsification following cataract surgery (n=31) in a randomized trial. Optical coherence tomography (Stratus OCT model 3000; Carl Zeiss, Jena, Germany) was used to detect subclinical CME in participants preoperatively and 2 and 6 weeks postoperatively. The operated eye was then compared with the nonoperated control eye.

Dr. Barsam found that although AquaLase cataract extraction resulted in less risk of CME then standard phacoemulsification, especially in diabetic patients, the difference was not statistically significant.

“Further studies with greater numbers of patients are required in order to confirm whether AquaLase should be considered as the surgical modality of choice in diabetic patients,” Dr. Barsam wrote.

Diabetes Screening Continues in UK
The Staffordshire Diabetic Retinopathy Screening Service, a community-based digital eye screening program designed to detect and treat DR, is on track to exceed its target of screening 35,000 diabetes patients this year in the English county of Staffordshire.

The screening program, launched in 2006, was one of the first in the country and has since screened 28,000 diabetes patients across Staffordshire. The service now averages 4,000 screenings per month, and is part of a Department of Health national screening program. The Department of Health requires 100% of the diabetic population to have access to a digital scan of their eyes by the end of 2007.

Community screening clinics, which use OptoMize iP, a digital imaging software and electronic patient record system (Digital Healthcare, Cambridge, UK), are held in 60 optometry practices across Staffordshire.

The service is responsible for the care of approximately 41,000 diabetes patients who are invited to attend a screening clinic at a practice near their home. An optometrist uses the software to review digital images of their eyes and establish if there are signs of DR.

Diabetes currently affects 1.8 million people in the United Kingdom, and that figure is expected to increase to >3 million by 2010.

INDUSTRY AND BUSINESS NEWS

German Research Facility for Eye Disorders Opened
Carl Zeiss Meditec AG (Jena, Germany) and the Ilmenau Technical University (Ilmenau, Germany) have joined in opening the Institute for Biomedicine Technology and Information in Ilmenau. Both partners will also sign a partnership agreement.

Ulrich Krauss, President and CEO of Carl Zeiss Meditec AG said in a news release: “This lab represents a high point in the successful collaboration between our company and the university. It represents a continuation of our strategy to offer innovative device systems that incorporate the latest scientific and research findings to doctors.”

The new lab is distinguished by the excellence of its diagnostic systems, particularly for the examination of the posterior eye segment. The complex research work has three main aims: (1) to combine previously independent examination methods, (2) to develop even more powerful systems with easily interpretable diagnostic data for the early detection of eye disorders, and (3) to integrate diagnosis and therapy in a comprehensive patient-oriented treatment approach. The research team is working, for instance, on generating new data analysis procedures for such comprehensive diagnosis. The aim is to facilitate early diagnosis and improved monitoring of eye disorders.

The technology in the new research facility lays the foundation for current research projects in the field of eye diagnosis, including projects sponsored by the Federal Ministry for Education and Research. The laboratory is also helping to extend the range of high-quality education for students in the field of biomedical technology.

Horizon Grant Program Accepting Applications
Allergan, Inc. (Irvine, CA) announced it is now accepting applications for its Horizon Grant Program. The company established the award in 2006 to “fund fellowship programs that conduct clinical research in the diagnosis or pharmacological treatment of glaucoma and retinal diseases.”

All applications should be submitted to Allergan Medical Affairs via e-mail: horizongrantapplications@allergran.com. Entries are due by Sept. 28, 2007. Allergan will announce the recipient in November during the American Academy of Ophthalmology 2007 Annual Meeting in New Orleans. Applications for the Horizon Grant Program and additional information are available at www.allerganhorizongrants.com/index.htm.

FDA to Utilize UltraShort Pulse Lasers in New Medical Applications
Raydiance, Inc. (Petaluma, CA) has entered into a
2-year cooperative research and development agreement with the FDA. Under the terms of the agreement, the FDA will utilize the company’s UltraShort Pulse (USP) laser platform to evaluate the safety and effectiveness of high-power laser-tissue interaction. The collaboration will involve the FDA’s Division of Physics, Office of Science and Engineering Laboratories, and Center for Devices and Radiological Health, with hardware, software, applications and research support provided by Raydiance.

“We are delighted to be collaborating with the FDA on this project, which represents an important first step in the potential development of new commercial medical applications that harness the transformational properties of USP laser technology,” said Barry Schuler, Raydiance Chairmen and CEO.

The FDA’s research on the USP laser platform will initially focus on the use, safety, and effectiveness of USP lasers in:

• Ophthalmic applications, including tissue interactions that occur with ablation of corneal tissues associated with USP laser applications in refractive surgery and corneal repair;

• Light therapy applications, including kinetic processes of light therapy that may be employed in new treatments for diseases such as cancer, cardiovascular disease, and diabetes; and

• Dental applications.

First developed in the 1980s, USP lasers are extremely brief light pulses of power that, unlike continuous wave lasers, instantly vaporize any material without heat or residual damage to surrounding areas at very precise scales, down to the micron level. Experimentation has been limited to highly specialized university and government research labs, until recently.