Congenital glaucoma gene discovered; Gene identity may lead to early diagnosis of blinding infant eye disease.

ALAMEDA, Calif.--(BW HealthWire)--March 19, 1997--InSite Vision Inc. (NASDAQ:INSV) and the University of Connecticut Health Center (UCHC) today announced that Mansoor Sarfarazi, Ph.D., a research scientist at UCHC, has identified the major gene responsible for primary congenital glaucoma.

The findings of the study will be published in the April issue of the journal Human Molecular Genetics. InSite Vision holds an option to secure an exclusive license to this technology.

"This is a very significant breakthrough which will provide a new dimension to neonatal care throughout the world," said Jay Wisnicki, M.D., chairman of ophthalmology at the Beth Israel Medical Center, New York.

"As practicing pediatric ophthalmologists, we will now have the tools to detect more accurately and recognize this blinding disease in newborns and conduct corrective surgery early when the eye is most receptive. Currently, diagnosis is highly subjective, resulting in many cases being overlooked."

Richard Lewis, M.D., clinical professor of ophthalmology at the University of California at Davis and a practicing glaucoma specialist, commented that: "One of the major concerns of pediatric ophthalmologists is only seeing a patient when loss of vision has already occurred. This genetic approach has the potential to avoid that problem and reassure parents that the condition can be found and corrected early."

Commenting on the discovery, Kumar Chandrasekaran, Ph.D., chairman and chief executive officer of InSite Vision, remarked: "This discovery is a dramatic leap forward, and we believe it will allow us to develop the tools to detect approximately 85% of all newborns with this disease.

"The incidence rates of primary congenital glaucoma are comparable to other congenital diseases that are routinely screened in newborns, although for some of these diseases, no current treatment exists. Primary congenital glaucoma, however, if diagnosed early, can be successfully treated by glaucoma specialists and blindness prevented. A diagnostic test based on this genetic discovery is being developed."

Primary Congenital Glaucoma: A Silent Disease

Primary congenital glaucoma is an inherited eye disorder believed to result from developmental defects in the anterior eye segment. A common feature of this and other forms of glaucoma is atrophy of the optic nerve that ultimately leads to progressive vision loss and total blindness. The incidence of congenital glaucoma ranges from 1:2,000 to 1:10,000 births. One of the most damaging problems is that, typically, symptoms do not manifest themselves until one is older. Therefore, treatment is not sought until considerable damage has already occurred.

Dr. Sarfarazi, senior author of the paper, remarked, "We are very excited with this new research. As a result of this knowledge, we will be able to develop diagnostic tests that allow the physicians to detect and, therefore, to treat early in life this serious eye disorder."

In their study titled "Identification of Three Different Truncating Mutations in Cytochrome P4501B1 (CYP1B1) as the Principal Cause of Primary Congenital Glaucoma (Buphthalmos) in Families Linked to the G1C3A Locus on 2p21," Sarfarazi and his associates have identified CYP1B1 as the major gene which appears to be responsible for 85% of primary congenital glaucoma, and have pinpointed the first ever reported mutations in families with this pediatric condition. Support for this research was provided by grants from the National Institutes of Health's National Eye Institute (Grant No. EY-11095), and the International Glaucoma Association of London.

"With this breakthrough in detecting primary congenital glaucoma comes the hope that we may be able to identify the genes associated with adult-onset primary open angle glaucoma which represents a much larger patient population," said Maurice H. Luntz M.D., chief of glaucoma at Manhattan Eye, Ear and Throat Hospital, New York.

"This would enable practicing ophthalmologists to intervene early, treat the patient and provide them with a better long term outcome."

InSite Vision

InSite Vision is an ophthalmic pharmaceutical company focused on the development of improved and new eye medications based on its proprietary DuraSite(R) drug delivery platform, and on the development of genetically-based tools for the diagnosis and prognosis of glaucoma. DuraSite-based products are designed to permit the gradual release of drug into the eye over a period of hours, thereby overcoming various treatment problems common with conventional ophthalmic drug delivery.

An over-the-counter DuraSite-based product, AquaSite(R) dry eye treatment is currently marketed by CIBA Vision Ophthalmics. Two pharmaceutical product candidates based on DuraSite, PilaSite(R) and BetaSite(TM) have completed Phase III clinical studies for the treatment of glaucoma. Other product candidates are in various stages of development.

University of Connecticut Health Center

The University of Connecticut Health Center, an academic health center of national stature, is a state-of-the-art teaching, research and clinical facility with more than 1,100 students and a full-time faculty of more than 400 located in the community of Farmington.

Biomedical sciences graduate programs fall under the purview of the Life Sciences Committee of the Graduate School, and therefore, a close working relationship has developed between the Health Center in Farmington and the University at the main campus in Storrs.

This educational facility is comprised of the medical school, dental school, graduate school, administration, teaching and research areas, hospital and clinics, and the animal quarters (vivarium). The Health Center's Lyman Maynard Stowe Library is the Region 8 Medical Library for New England under the National Library of Medicine and provides both computer services and interlibrary loan services. External grant support at the Health Center exceeded $40 million in the fiscal year ending June 30, 1996. -0-

This press release contains, among other things, certain statements of a forward-looking nature relating to future events or the future business performance of InSite Vision Inc. Such statements involve a number of risks and uncertainties, including those inherent in developing a genetic discovery into a commercially viable diagnostic product, which include issues of manufacturability, proving the validity of the diagnostic, preclinical and clinical studies and obtaining necessary approvals from the U.S. Food and Drug Administration, as well as the Risk Factors listed from time to time in the company's SEC filings, including, but not limited to, its report on Form 10-K for the fiscal year ended Dec. 31, 1996. -0-

Primary Congenital Glaucoma Backgrounder

Disease Description

Primary congenital glaucoma is an optic neuropathy in which elevated intraocular pressure (IOP) is an important or essential factor, secondary to an inherited or sporadic failure of development of the outflow pathway of the anterior chamber of the eye. In a normal eye, aqueous humor (a clear fluid) is constantly formed in the anterior chamber and exits through a very narrow channel in the angle between the iris and the cornea.

In congenital glaucoma, this channel is either not developed at all, or incomplete. As a result, aqueous humor accumulates in the eye causing pressure within the eye (IOP) to rise. Since the eye is immature, the pressure stretches the eye ball resulting in a big eye, or buphthalmos. The pressure will also damage the nerves which carry the visual images from the eye to the brain, resulting in visual field loss.

Inheritance of Congenital Glaucoma

The condition affects 1:2,000 to 1:10,000 newborns and is passed to offspring as a mendelian recessive with incomplete penetrance. Both normal parents must be a carrier, i.e., have the recessive gene for congenital glaucoma, in order to produce an affected child. Even so, the chances are slightly less than 1:4 that the child will inherit the gene from both parents resulting in congenital glaucoma.

Clinical Presentation

In a small number of cases, the elevated IOP is present at birth, and even prior to birth. In the majority of cases, the disease manifests itself during the first three years of life. The presenting features include an increase in diameter of the cornea and iris (often mistakenly regarded as a very desirable and beautiful feature in a baby or young child), corneal clouding photophobia.

Once the disease is suspected, it is relatively easy to confirm it by the examination of the anterior chamber angle of the eye using gonioscopy and by checking the IOP. In infants and toddlers, the procedures are done under anesthesia, thus physically and economically precluding the examination of every newborn.

A degree of visual function loss is invariably associated with the disease by the time of first diagnosis, but it is not an early symptom at birth, due primarily to the infant's immaturity and the insidious nature of the loss. The abnormality is bilateral in 75% of cases.

Current Treatment

Treatment is by surgical opening of the anterior chamber angle and IPO lowering drugs. In most patients, the progression of the disease can be halted, although it is not uncommon for a child to have multiple operations before the IOP is adequately controlled.

CONTACT: InSite Vision

Kumar Chandrasekaran, 510/865-8800 ext. 1203

or

University of Connecticut 

Patrick Keefe, 860/679-2447

or

Russell-Welsh Inc.

Barbara Heineback, 415/312-0700 ext. 21