Clinical News: MEDICAL AND PRODUCT UPDATES 

UPDATE FROM ARVO
New data on products and health issues presented

The annual Association for Research in Vision and Ophthalmology (ARVO) conference in May produced numerous reports of new research and medical breakthroughs. Highlights included:

• NSAIDs may prevent herpes recurrences. Herbert E. Kaufman, M.D., outgoing chairman of the Louisiana State University Eye Center in New Orleans and winner of the 2001 Weisenfeld Award at ARVO, presented new research indicating that NSAIDs may be an effective weapon against herpes eye infections.
  Herpes simplex type one, the same virus that causes cold sores and fever blisters, is responsible for more than 500,000 cases of ocular herpes each year in the United States, and often leads to blindness. The virus may remain dormant in the body for years before something reactivates it.
  Typically, treatment for herpes involves the use of antiviral medications. Dr. Kaufman's work demonstrated that a cellular gene, when triggered, can cause a virus to activate and recur. This led Dr. Kaufman to test the idea that drugs could be used to inhibit the gene, instead of attacking the virus itself.
  Dr. Kaufman found that NSAIDs such as aspirin, Celebrex or DFU, which are known to inhibit certain genes, can prevent 70 to 80% of herpes recurrences in mice. (More expensive antiviral drugs typically prevent only 40 to 60% of recurrences.) The NSAIDs also make the virus less productive, lessening the likelihood it will infect others.
  Dr. Kaufman believes that targeting genes may help prevent recurrences of other viral diseases, such as herpes-2, which causes genital herpes. He's also found preliminary evidence that a similar strategy can be used to interfere with the growth of cytomegalovirus, which can cause retinal damage or blindness, especially in people whose immune systems have been damaged.
• Alzheimer gene may decrease risk of age-related macular degeneration. A new study combining data from two U.S. and one European study found that the apolipoprotein E-4 (ApoE-4) allele, which has been

  

  linked with an increased risk of late-onset Alzheimer's disease, appears to decrease the risk of developing age-related macular degeneration in persons with a family history of this vision disorder.
  The study, conducted by Dr. Margaret A. Pericak-Vance of Duke University Medical Center in Durham, N.C., found that individuals with the ApoE-4 variant had half the usual risk of developing the disease, regardless of gender or age. However, the protective effect was only found in cases of AMD with a family etiology.
  Also, according to the data, a variant of this gene (the ApoE-2) nearly doubles the risk of developing AMD -- but only for males.
• New therapies retard blood vessel growth. Several studies reported progress in this area:
  • Data from two preclinical studies suggest that squalamine, an anti-angiogenic agent produced by Genaera Corporation, may be an effective treatment for ocular neovascularization.
    In one study, squalamine systematically administered to monkeys resulted in inhibition of the development of iris neovascularization and partial regression of new vessels. A second study, involving rabbits, found that potentially therapeutic levels of squalamine remained in eye tissues for long periods of time after systemic delivery.
    The research was conducted in collaboration with Tulane University Health Sciences Center of New Orleans, La.
  • Researchers from The Wilmer Eye Institute in Baltimore, Md., reported data showing that gene therapy could be used to regulate pigment epithelium-derived factor (PEDF) in the eye, causing a substantial reduction in new blood vessel formation. PEDF, a secreted protein normally produced in the eye, is the most potent known natural inhibitor of blood vessel growth. The studies, which used preclinical animal models of macular degeneration and diabetic retinopathy, indicated that PEDF inhibits both retinal and choroidal neovascularization.
    The therapy was developed by GenVec, a biotechnology company focused on developing gene-based therapies that produce medically beneficial proteins at the site of disease.
  • Dr. Lloyd Paul Aiello, of Boston's Joslin Diabetes Center, reported data showing that administration of naturally occurring and synthetic derivatives of bactericidal/permeability-increasing protein (BPI), a human protein found in neutrophils that stops abnormal vascular growth in the retina, suppressed abnormal vascularization in mice by 40%. The investigators were also able to halt nearly 100% of the growth of vascular endothelial cells in culture using BPI derivatives.
    BPI administration also stimulated the growth of pericytes, which support small blood vessels in the eye. (Normally, pericytes only replicate every 20 years in the human body.) Pericytes are almost entirely lost in early diabetes, leading to retinopathy.
• New products for dry eye, retinal detachment. Inspire Pharmaceuticals, Inc., reported results from the 
  • consistent improvement of both signs and symptoms of dry eye
  • significant improvement in conjunctival staining, tear breakup time and unanesthetized Schirmer tests
  • statistically significant decrease in ocular burning.

	The Panoramic200 Non-mydriatic Scanning Laser Ophthalmoscope from Optos

Ocular tolerability was excellent.
The company also announced the launch of a Phase I/II clinical trial for INS37217 Ophthalmic, for treating retinal detachment. The trial will evaluate the effectiveness of this agent in removing subretinal fluid build-up in patients with detachments resulting from breaks or tears in the retina. (Preclinical studies have demonstrated that intravitreal administration of the drug enhances reattachment of the retina.)

• Studies support efficacy of Panoramic200. One study, conducted at the Eye and Ear Institute at the University of Pittsburgh, demonstrated that an examination using the Panoramic200 Non-mydriatic Scanning Laser Ophthalmoscope can effectively detect diabetic retinopathy. (The Pano-ramic200 produces a digital high-resolution image of almost the entire retina without the need for pupil dilation.)
  Sixty-six patients with and without diabetic retinopathy were evaluated by retinal specialists using the instrument, prior to a full, dilated clinical examination. Resulting images were reviewed by three independent retinal specialists. The Panoramic200 exam achieved an average sensitivity of 85%, with no false positives, and 91% of patients found the test to be easy and simple.
  A second study, conducted at New England Eye Center (NEEC) in Boston, compared the exam to dilated and undilated clinical examinations of 300 eyes conducted by clinical optometrists:
  • Both the Panoramic200 and the dilated exam achieved a sensitivity of 74%, while the undilated exam had a sensitivity of only 29%.
  • Clinical application and interpretation of the Panoramic200 images were consistent between practitioners. Sensi-tivity scores from two optometrists using the Optomap exam were 73% and 76%; sensitivity scores from three optometrists performing standard clinical evaluation were 79%, 56% and 42%.
  • A standard dilated exam, from administration of the drops to the completion of the clinical exam, took an average of 37 minutes; the Optomap exam took an average of 14 minutes.

PHOTODYNAMIC THERAPY
New data on Visudyne benefits

New data from a Phase III clinical trial indicates that Visudyne (verteporfin for injection) therapy may benefit age-related macular degeneration (AMD) patients presenting with occult (not classic) choroidal neovascularization (CNV). Visudyne is currently approved only for patients with predominantly classic CNV. Data showed:

• 55% of the Visudyne group lost at least 15 letters or three lines of vision, compared to 68% of the placebo group
• 29% of the Visudyne group lost at least 30 letters or 6 lines of vision, compared to 47% of the placebo group.

Further analysis showed that the benefits were greater for patients with either smaller lesions or lower levels of visual acuity at baseline.

This came on the heels of data showing that average visual acuity remained stable during the third year of Visudyne therapy. (Following the conclusion of the Phase III clinical trial, 78% of the original 609 patients were offered Visudyne therapy in an ongoing open-label extension trial.)

At the same time, the number of Visudyne treatments required continued to decrease. Patients received an average of 1.4 treatments, a decrease from the 3.4 and 2.1 treatments received in the first and second year, respectively.

The favorable safety profile previously demonstrated with Visudyne continued throughout the third year.

GLAUCOMA
A possible connection to H. Pylori

A recent study conducted at the Ippokration Hospital in Thessaloniki, Greece, found a correlation between the presence of Helicobacter Pylori (H. Pylori) bacteria and glaucoma. The study compared 32 patients with chronic open-angle glaucoma (COAG) and 9 patients with pseudoexfoliation glaucoma (PEG) to 30 age-matched anemic control participants. Results included:

• Histological exam found H. Pylori in 87.5% of COAG patients, 88.9% of PEG patients and 46.7% of controls.
• Gastric mucose contained H. Pylori in 71.9% of COAG patients, 77.8% of PEG patients and 46.7% of controls.
• H. Pylori was found in the saliva of 37.5% of COAG patients, 55.6% of PEG patients and 30% of controls.
• Blood tests found antibodies specific to H. Pylori in 68% of glaucoma patients and 30% of controls.

This could indicate the presence of a factor making patients susceptible to both H. Pylori infection and glaucoma -- or that H. Pylori is a causal factor in the development of glaucoma.

ALLERGY MEDICATION
Zaditor gets high marks in survey

A recent survey found that 85% of more than 2,700 patients suffering from eye allergies preferred Zaditor (ketotifen fumarate solution) to their previous allergy eye drop. Close to 90% indicated they would ask their doctors to prescribe it again. Other survey results:

A 100% of more than 650 eyecare providers said they were satisfied with the results achieved by their patients.

A 95% of providers who have prescribed this product said that it's as effective or more effective than any other product currently on the market.