Gene therapy transforms eyesight for 12

By Thomas H. Maugh II
Los Angeles Times

Pennsylvania researchers using gene therapy have made significant improvements in vision in 12 patients with a rare inherited visual defect, a finding that suggests it may be possible to produce similar improvements in a much larger number of patients with retinitis pigmentosa and macular degeneration.

The team last year reported success with three adult patients. They have now treated an additional nine patients, including five children. The best results were achieved in the youngest patients, whose defective retinal cells have not had time to die off.

The youngest patient, 9-year-old Corey Haas, was considered legally blind before the treatment began. He was confined largely to his house and driveway when playing and had immense difficulties in navigating an obstacle course.

Today, after a single injection of a gene-therapy product in one eye, he rides his bike around his neighborhood, navigates the obstacle course quickly and has even played his first game of softball.

The results are "astounding," said Stephen Rose, at the Foundation Fighting Blindness, which supported the study. "Every individual had improvement ... and there were no safety issues at all."

The study was published online Saturday by the journal Lancet. The 12 patients suffered from Leber's congenital amaurosis, which affects about 3,000 people in the U.S. Victims are born with severely impaired vision that deteriorates until they are blind, usually in childhood or adolescence. There is no treatment.
Leber's is a good candidate for gene therapy because most of the visual apparatus is intact, particularly at birth and in childhood. All 12 of the patients suffered a defect in a gene called RPE65 that produces a vitamin A derivative crucial for detecting light.

That specific defect, which was chosen because researchers at the Children's Hospital of Philadelphia and the University of Pennsylvania School of Medicine had cloned the gene, making copies available for use.

The study, led by Dr. Katherine High, Dr. Albert Maguire and Dr. Jean Bennett of those two institutions, enrolled five people in the United States, five from Italy and two from Belgium. Five were children, and the oldest was 44.

The good copy of the RPE65 gene was inserted into a defanged version of a human adenovirus.

The engineered virus then invaded retinal cells and inserted the gene into the cells' DNA.

All the patients' vision improved. They were able to navigate obstacle courses, read eye charts and perform most tasks of daily living. The improvement has now persisted for as long as two years.

The children who were treated "are now able to walk and play just like any normally sighted child," Maguire said.

There are clear limitations to the study. The patients' vision was not corrected to normal because of the damage that had already been done to the retina, and only one eye was treated.

"The big elephant in the room is: Can you treat the other eye?" Rose said. The foundation will put more funding into the research "to make sure that if you go back and treat the other eye, it won't ablate the positive results in the first eye due to an immune reaction or something else."

Researchers also hope they will be able to translate the results to other congenital conditions using different genes. Leber's is one form of retinitis pigmentosa, which affects an estimated 100,000 Americans.

The findings might be applicable to macular degeneration, which affects an estimated 1.25 million Americans and is the major cause of visual impairment in the elderly.

For more information go to www.maculardegenerationassociation.org

A New Point-of-Care Indicator System for Dry Eye Syndrome

Auxano Diagnostics, LLC, a subsidiary of Auxano Biomedical, LLC, has announced
the application of the company`s breakthrough wound care technology to the
treatment of dry eye syndrome (DES) with the Auxano point-of-care indicator
system. Dry eye syndrome (DES) is a condition that affects millions of people
worldwide. According to the Centers for Disease Control (CDC), DES can be a
serious condition, which, if left untreated, can damage ocular structures.

Brian Windsor, Ph.D., Chief Technical Officer for Auxano Biomedical, said, "We
are excited that the advances of our wound care technology can be applied to the
treatment of DES and other ophthalmic diseases. Our point-of-care indicator
system has the potential to provide earlier and more accurate guidance to
millions of DES sufferers."

Market Dynamics

Primary ophthalmic disorders associated with inflammation currently affect over
20 million people in the US. The CDC reports that the most prevalent disorders
in this category include DES, age-related macular degeneration (AMD) and
proliferative diabetic retinopathy (PDR). According to Business Insights, the
ophthalmic pharmaceutical market registered sales of $13.5 billion in 2008.

A challenge encountered in the treatment and management of ophthalmic care is
the identification between acute and chronic inflammatory diseases that lead to
visual impairment. Currently, there are no diagnostics focused on inflammatory
eye disease, and the primary way to detect inflammation is through purely
empirical methods. Misdiagnosis can lead to additional tissue damage and
potential blindness.

A solution to proper discernment between inflammatory and non-inflammatory
conditions would result in early and correct guidance towards the appropriate
therapeutic regimen, effective tracking of treatment, enhanced patient
satisfaction, and improved outcomes.

Auxano`s system is a rapid point-of-care diagnostic indicator for ophthalmic
inflammatory diseases and has the potential to provide for accurate indications
of DES within minutes.

New Ophthalmic Focus for Auxano Diagnostics

Auxano Diagnostics has developed a similar point-of-care product for wound care
that is based on the efficient and accurate detection of active enzymes in
biological samples. This product provides detection of inflammation through
targeting matrix metalloproteinases (MMPs) in wound fluids that can be obtained
by non-invasive sampling techniques. This MMP indicator is in clinical trials
through a partnership with a global technology company with the expectation of a
CE mark in December 2009, followed by FDA 510(k) approval.

Auxano`s primary focus is the adaptation, optimization and commercialization of
the existing technology for acute and chronic inflammatory diseases of the eye,
in particular, dry eye syndrome. Initial data indicates positive results for
detecting physiologically relevant MMP levels in dry eye syndrome.

For more information go to www.maculardegenerationassociation.org

OCT-guided intravitreal injection of VEGF therapy may result in less vision gain

Intravitreal injection therapy with an anti-VEGF agent that is guided by optical coherence tomography may under-treat patients and result in less visual gain, according to a study.

In a population of 131 treatment-naïve eyes of 124 patients with wet age-related macular degeneration treated with Lucentis (ranibizumab, Genentech) on an as-needed basis guided by clinical examination and OCT imaging, visual improvement correlated with the number of injections delivered but not to resolution of fluid.

At baseline, the mean visual acuity for the group was 20/110, which improved at 6 months to 20/80. At last follow-up, mean visual acuity was 20/90. Also, at 6 months, 31% of eyes had gained three lines of visual acuity and 90.5% had avoided a loss of three lines.

However, eyes that received injections at an interval less than 2 months gained more vision than eyes that received injections with a greater interval. Eyes receiving injections with less than 2 months mean inter-injection interval gained 2.3 lines at 6 months compared with 0.46 lines gained among eyes with less frequent injections. Only 3.1% of patients in the more frequent injection group lost three or more lines of vision compared with 15.9% in the less frequent injection group.

For more information go to www.maculardegenerationassociation.org

Combination brachytherapy and anti-VEGF therapy demonstrates long-term safety and efficacy

NEW YORK — The use of epimacular brachytherapy combined with bevacizumab appears safe for treatment of neovascular age-related macular degeneration and reduces the dosing burden of anti-VEGF therapy.

Pravin U. Dugel

After 2 years of follow-up in 34 patients treated with strontium 90 and Avastin (bevacizumab, Genentech) in a phase 2 study, 80% of patients who had cataract surgery before the study maintained vision and 30% gained significant vision. When compared with patients who had their natural lens, 65% of patients maintained vision and 20% gained significant vision.

Overall, patients received a mean 2.4 injections, including loading doses, and 76% of patients required no additional doses beyond the two required injections of bevacizumab, Pravin U. Dugel, MD, said here at the Retina Congress 2009.

For more information go to www.maculardegenerationassociation.org