Gene Therapy To Treat Diseases Of The Eye

The easy accessibility of the eye and the established link between specific genetic defects and ocular disorders offer hope for using gene therapy to provide long-term therapeutic benefit. Two reports in the current issue of Human Gene Therapy, a peer-reviewed journal published by Mary Ann Liebert, Inc., describe the effective replacement of a human gene to preserve photoreceptor function in a mouse model of severe retinal degeneration. The articles are available free online here.

Basil Pawlyk and colleagues from Harvard Medical School and Massachusetts Eye and Ear Infirmary (Boston, MA) delivered the human gene for RGPR-interacting protein-1 to mice affected with Leber congenital amaurosis (LCA), a condition linked to a mutated form of RPGRIP1 that causes degeneration of photoreceptors in the eye. The researchers packaged the gene in an adeno-associated virus (AAV) vector and injected the vector under the retinas of the affected mice. They demonstrated expression of the human gene in the photoreceptors, with correct localization to the cilia. Further evaluation revealed improved function and survival of the photoreceptors in the treated eyes.

The authors conclude that the results of this study, presented in the paper entitled, “Replacement Gene Therapy with a Human RPGRIP1 Sequence Slows Photoreceptor Degeneration in Murine Model of Leber Congenital Amaurosis,” validate a gene therapy design that could serve as the basis for a future clinical trial in patients affected by this form of LCA.

In the same issue, Kamolika Roy, Linda Stein, and Shalesh Kaushal from University of Massachusetts Medical School (Worcester) review the use of recombinant AAV vectors for gene therapy to treat ocular diseases. Based on the success of three early-stage clinical trials in LCA, they conclude that this approach appears “to be a safe, effective, and long-term treatment for LCA, a previously untreatable disorder.” In the article, “Ocular Gene Therapy: An Evaluation of Recombinant Adeno-Associated Virus-Mediated Gene Therapy Interventions for the Treatment of Ocular Disease,” they conclude that rAAV-mediated gene therapy is “the most suitable gene therapy treatment approach for ocular diseases.”

“The successful correction of this photoreceptor defect in a relevant mouse model of LCA should usher in a new wave of translational research in retinal degeneration syndromes,” says James M. Wilson, MD, PhD, Editor-in-Chief of Human Gene Therapy, and Head of the Gene Therapy Program, Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, in Philadelphia.

Vicki Cohn
Mary Ann Liebert, Inc./Genetic Engineering News

Infant vernier acuity is comparable to that of adults

Testing may be substitute for eye chart –

Infant vernier acuity is not as immature as previous research has indicated according to a study published in March in the
Journal of Vision, an online, free access publication of the Association for Research in Vision and Ophthalmology (ARVO). The
data from this study also suggest that vernier testing could be a substitute for the traditional Snellen eye chart test for
children or others who cannot read letters. Vernier acuity is tested by viewing nearly collinear stripes with varying amounts
of spatial phase displacement between them and measuring an individual’s ability to gauge the displacement between the

Angela M. Brown, Veena Adusumilli, and Delwin T. Lindsey of The Ohio State University conducted the study with major funding
from the National Eye Institute and the National Science Foundation. The researchers first set out to establish a “benchmark”
to which vernier acuity could be compared. The benchmark they chose was the ability to see small differences in contrast.
Adults (ages 20 to 48) were tested 6.096 meters (20 feet) from the contrast stimuli, and healthy three-month-old infants were
tested 45.72 centimeters (1.5 feet) from the contrast stimuli, to take into account the underdeveloped vision of infants. The
experiment showed that under these conditions, infants see changes contrast almost as well as adults.

The vernier acuity of the infants and adults was then tested under the same conditions as the contrast discrimination had
been tested. Under these conditions, infant vernier acuity (in degrees of spatial phase displacement) was almost as good as
that of adults. Furthermore, the relation between “benchmark” contrast discrimination ability and vernier acuity was the same
for infants and adults.

During the testing, an adult observer held an infant in her arms using a “baby sling,” standing in a position that allowed
the infant to see the stimulus display, but the adult observer could not. The adult observer watched the infant’s looking
behavior via closed-circuit video and judged whether the test stimulus (the modulation of stimulus displacement or contrast)
was contained in the right- or left-side stripes. This is an objective measure of how well infants can see a stimulus, and is
in common use in the laboratory and the clinic.

Angela Brown, lead researcher of the study, says the data suggest that vernier acuity of human infants and adults is quite
similar, contrary to past studies conducted in this area. The similarity of infant and adult vernier acuity suggests that
vernier acuity might be a sensitive test for strabismic amblyopia and other visual disorders that normally must be diagnosed
using an eye chart. “The data from this study also suggest that vernier testing could be a substitute for eye chart testing
for children and others who cannot read an eye chart,” says Brown.

You can read this article online in Journal of Vision at journalofvision/5/3/7/. Journal of Vision is published by ARVO, the Association for Research in
Vision and Ophthalmology. All articles are free and open to anyone.

The Association for Research in Vision and Ophthalmology, Inc. (ARVO) is a 77-year-old membership organization of more than
11,200 eye and vision researchers from over 70 countries. The Association encourages and assists its members and others in
research, training, publication and dissemination of knowledge in vision and ophthalmology. ARVO’s headquarters are located
in Rockville, Maryland. The Association’s Web site is arvo.

Contact: Alice O’Donnell
Association for Research in Vision and Ophthalmology

Recovery Of Sight In Mice

Retinitis pigmentosa affects over one million people worldwide and is manifested by a progressive loss of sight, eventually leading to blindness. Retinitis pigmentosa is a form of inherited retinal degeneration that affects the light-sensitive cells : photoreceptors. Photoreceptors are a special type of neuron which convert light into nervous impulses. These impulses are then processed by the retina and transmitted along the nerve fibres to the brain. There are two types of photoreceptors: rods and cones.

As the disease progresses, it leads initially to degeneration of the rods which are responsible for night vision. Then the cones, which are responsible for diurnal vision, become affected. Whereas the rods are destroyed, the cones survive in the organism for extended periods, even after the occurrence of blindness as they cease to function. This inspired the researchers from the Friedrich Miescher Institute (FMI) and the Institut de la Vision to develop a genetic therapy to restore the visual function of the cones which were defective (dormant) but remained present.

Recreating a biological photoelectric system

At the stage of the disease where the researchers have intervened, although the defective cones no longer possess the ability to respond to a luminous stimulation (photo reception function) they do still retain some electrical properties and their connections with the neurons of the inner retina which normally transmit visual information to the brain. Hence, they are able to be activated artificially. Earlier work, carried out by the same team under the direction of Botond Roska (FMI), had shown that light-sensitive ionic channels, identified by the team of Ernst Bamberg (Max Planck Institute, Frankfurt), had the ability to modulate electrical activity from various neurons into which they had been introduced, in response to the level of light.

By combining these two observations, the researchers have succeeded in reactivating cones and thus allowing re-stimulation of the mice’s ON/OFF transmission channels. To achieve this, they have introduced a protein, via a genetic therapy vector, which is capable of coupling luminous stimulation to ionic transport, hence reintroducing the phototransduction cascade required for vision. The researchers have therefore recreated a genuine biological photoelectric system.

These results are very promising, particularly as they have been confirmed by Serge Picaud and researchers at the Institut de la Vision using human retina in cultures and therapeutic vectors for which human compatibility has already been demonstrated. The photosensitive protein can be expressed in human cone photoreceptors to which it confers a new sensitivity to light.

“We integrated the clinical approach as soon as we obtained the first fundamental results of this work. So, at the national reference center for rare diseases of the retina, thanks to non-invasive high-resolution retinal imaging techniques, we can now target patients to whom this therapy could be applied” explains Jos?� Alain Sahel, who points out that the transition from mice to man always carries many uncertainties. ?� The results are also very complementary to the research which has been carried out at the Institute and the CIC by the team of Serge Picaud, which aims to test and improve an artificial retina as well as our research on RdCVF protein which protects the activity of cones “.


Genetic reactivation of cone photoreceptors restores complex visual responses in Retinitis pigmentosa
Volker Busskamp1,2,#, Jens Duebel1,#, David Balya1,#, Mathias Fradot3,4,5, Tim James Viney1, Sandra Siegert1, Anna C. Groner2,6, Erik Cabuy1, Valerie Forster3,4,5, Mathias Seeliger7, Martin Biel8, Peter Humphries9, Michel Paques3,4,5,10,11, Saddek Mohand- Said3,4,5,10, Didier Trono2,6, Karl Deisseroth12 Jose A. Sahel3,4,5,10,11, Serge Picaud3,4,5,11 & Botond Roska1

Science 24 June 2010

1 Neural Circuit Laboratories, Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland
2NCCR Frontiers in Genetics Program
3 Inserm, UMR_S968, Institut de la Vision, Paris, France
4 UPMC Univ Paris 06, UMR_S 968, Institut de la Vision, Paris, F-75012, France
5 CNRS, UMR_7210,Institut de la Vision, Paris, F-75012, France
6School of Life Sciences, Ecole Polytechnique F?�d?�rale de Lausanne, Lausanne, Switzerland
7Diagnostics Research Group, Department of Ophthalmology II, Eberhard-Karls University, T??bingen, Germany
8Center for Integrated Protein Science CIPS-M and Department of Pharmacy, Ludwig- Maximilians-Universit?�t M??nchen, Munich, Germany
9Smurfit Institute of Genetics, Trinity College, Dublin, Ireland
10 Centre d’Investigation Clinique 503, Inserm-Centre Hospitalier National d’Ophtalmologie des Quinze-Vingts, Paris, France
11 Fondation Ophtalmologique Adolphe de Rothschild, Paris, France
12 Department of Bioengineering, Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, USA

Jos?� Alain SAHEL
INSERM (Institut national de la sant?� et de la recherche m?�dicale)

Fewer Elderly Road Deaths After Driver’s License Renewal Law In Florida

Although there is little evidence to support an association between
vision and car accidents, a vision screening law in Florida that
targets drivers age 80 and older seems to have reduced the number of
adults in this age range who die from motor vehicle collisions. The
findings are published in the November issue of Archives of

“Older drivers represent the fastest-growing segment of the driving
population,” write Gerald McGwin Jr., M.S., Ph.D. (University
of Alabama at Birmingham) and colleagues. “As this segment of the
population expands, so too have public safety concerns, given older
drivers’ increased rate of motor vehicle collision involvement per mile
driven. Research has suggested that this increase may be partly
attributed to medical, functional and cognitive impairments.”

Visual acuity has not been firmly linked to involvement in motor
vehicle collisions, but that did not stop the State of Florida from
implementing a law that required vision tests for drivers 80 years and
older before renewing licenses in 2004. This change in law combined
with data from the National Highway Traffic Safety Administration and
the U.S. Census Bureau on rates of motor vehicle collision deaths from
2001 to 2006 provided McGwin Jr. and colleagues the necessary tools for
a quasi-experimental analysis. The researchers also looked at death
rates from motor vehicle accidents in Alabama and Georgia, neighboring
states that had no change in license renewal policy.

Between 2001 and 2006, Florida saw an overall but non-significant
increase in its overall death rate from motor vehicle collisions.
However, drivers age 80 and older demonstrated a linear decrease in
this rate. Compared to the period before the law (from 2001 to
2003), the fatality rate in the period after the law (from
2004 to 2006) among all drivers increased from 14.61 per 100,000
per year to 14.75 per 100,000 – a 6% increase. The rate specific to
older drivers decreased from 16.03 per 100,000 persons per year to
10.76 per 100,000 – a 17% decrease. In the comparison states, Alabama
and Georgia, there was no change in death rates among older drivers.

The authors try to explain the decrease in the decrease in death rates
among older Floridian drivers: “Perhaps the most apparent reason is
that the screening law removed visually impairment drivers from the
road…However, in reality, the situation is significantly more

According to the authors, only 7% of drivers were unable to receive a
license renewal. This means that only a small percentage of drivers
were removed from the road because of failure to meet vision standards.
In addition, it is possible that many drivers who did not pass the
vision requirement sought vision care and were able to receive a
license after being treated. This could have improved overall vision
function of drivers. A third suggestion is that drivers with poor
vision selected themselves to be removed from the road because they
assumed that they would not receive a renewal.

“Ultimately, whether the vision screening law is responsible for the
observed reduction in fatality rates because of the identification of
visually impaired drivers or via another, yet related, mechanism may be
inconsequential from a public safety perspective,” conclude the
researchers. “However, the importance of driving to the
well-being of older adults suggests that isolating the true mechanism
responsible for the decline is in fact important.”

The Impact of a Vision Screening Law on Older Driver Fatality
Gerald McGwin Jr; Scott A. Sarrels; Russell Griffin; Cynthia Owsley;
Loring W. Rue III
Archives of Ophthalmology (2008).
126[11]: pp. 1544 – 1547.
Here to View Abstract

: Peter M Crosta

Headaches, Eye Haemorrhages, Sleep Disruption – The Effects On The Brain Of Ascent To High Altitude

Headaches, eye haemorrhages, and sleep disruption are just some of the effects on the brain caused by ascent to high altitude. These and other effects are discussed in a Review published in the February edition of The Lancet Neurology, Dr Mark Wilson, Centre for Altitude, Space and Extreme Environment Medicine, University College London, UK, and colleagues. The authors are part of the Caudwell Extreme Everest team, which visited Mount Everest in 2007 and are in the process of reporting data from a number of experiments from that expedition.

As air travel provides easier access to mountains, millions of people now travel to high altitudes each year for holidays, expeditions and work. Although oxygen concentration at altitude remains consistent at 21%, its partial pressure decreases as atmospheric pressure decreases. This “hypobaric hypoxia” can result in inadequate supply of oxygen to tissues, in particular to the highly oxygen-dependent brain.

High altitude illness has classically been thought of as a spectrum of disease from high altitude headache (HAH – occurring in up to 80% of travellers to high altitude and responding to simple analgesia such as paracetamol), through to acute mountain sickness (AMS – a more severe headache associated with gastrointestinal disturbance, lethargy or difficulty sleeping) to finally high altitude cerebral oedema (HACE – a condition that can progress from confusion and an unsteady gait to coma and death). In workers on the Qinghai-Tibetan Railway the incidence for AMS is 45-95% and 0.5% for HACE. Slow ascent can help prevent all the above conditions, but when symptoms develop, descent is a priority with the consideration of oxygen and dexamethasone for more severe cases.

This Review explains new concepts in the pathogenesis of these illnesses. An individual’s susceptibility to AMS may be more complex than the simple physiological (ability to maintain oxygen levels) and anatomical (the “tighter” brain – with less surrounding cerebrospinal fluid to buffer swelling causing increased susceptibility) theories might suggest. The role of genetic predisposition, factors such as hypoxia inducible factor and the venous system are discussed.

The neuropsychological effects of ascent to high altitude (with or without formal illness) also vary greatly on an individual level. Slowing of reflexes (such as pupil reaction) and motor skills and reduction in short term memory are all reported. Anxiety disorders and hallucinations (e.g. “third man” phenomenon where the presence of another imaginary climbing companion is convincing) are also noted especially at extreme altitude.

Investigations into high altitude illness predisposition include genetic work targeting specific genes, each thought to have a small but contributory role. The authors discuss investigation of the “tight-fit” hypothesis – the idea that people cope less well with the expansion of their brain at lower pressures. Measuring intracranial pressure has been attempted invasively and non-invasively. The invasive technique, which used a telemetric radio device, found that in three subjects the one who developed AMS also had a rise in intracranial pressure on minimal exertion (even head turning).

The authors conclude: “Investigation of the mechanisms that underlie differences in susceptibility to hypoxia-induced injury, whether they are physiological pathways, such as those that regulate compensatory oxygen delivery, pathophysiological pathways that affect oedema formation, or anatomical factors that affect cerebral or cranial compliance, might suggest novel prophylactic or therapeutic targets that are of broad clinical relevance.”

“The cerebral effects of ascent to high altitudes”
Mark H Wilson, Stanton Newman, Chris H Imray
Lancet Neurol 2009; 8: 175-91
The Lancet Neurology

Tony Kirby
Press Officer
The Lancet
32 Jamestown Road

ISTA Pharmaceuticals Highlights Bepreve(TM) Clinical Data At The American College Of Clinical Pharmacy (ACCP) 2009 Annual Meeting

ISTA Pharmaceuticals, Inc. (Nasdaq: ISTA) announced poster presentations of results from the Company’s Bepreve(TM) (bepotastine besilate ophthalmic solution) 1.5% Phase 3 clinical studies in allergic conjunctivitis. The studies demonstrated Bepreve was safe and well-tolerated when given twice daily for six weeks in a healthy pediatric population as young as three years of age. The clinical findings were presented at the American College of Clinical Pharmacy (ACCP) 2009 Annual Meeting in Anaheim, CA, and were encore presentations from earlier meetings in 2009.

In a poster previously presented at the American Academy of Allergy Asthma & Immunology 2009 Annual Meeting titled, “The Ocular Comfort and Safety of the Novel Anti-Histamine Bepotastine Besilate Ophthalmic Solution 1.5% in a Healthy Pediatric Population”, ISTA presented results from a 6-week, multi-center, randomized, double-masked, placebo-controlled, parallel-group safety study. The study enrolled 861 individuals, of whom approximately 15% (127 subjects) were pediatric subjects. Subjects were randomized to receive either Bepreve or placebo twice daily. Following test drop instillation for each eye at study visit 2 (one week of dosing) and visit 3 (three weeks of dosing), the overall comfort of the investigational product was graded using a quantitative scale. The study showed there was no clinically or statistically significant difference in the ocular comfort of Bepreve and placebo among pediatric subjects, either immediately after or five minutes following instillation.

In a separate poster previously presented at the Association for Research in Vision and Ophthalmology 2009 Annual Meeting titled, “The Safety of the Anti-Histamine Bepotastine Besilate Ophthalmic Solution in a Healthy Pediatric Population from Ten to Seventeen Years of Age”, ISTA presented subpopulation data from the 6-week, placebo-controlled, parallel-group safety study. The proportion of pediatric subjects in this age group instilling Bepreve and with an adverse event (22.5%) was similar to that seen for subjects 10-17 years of age instilling placebo (20.0%).

No severe adverse events were reported during the 6-week safety trial and all pediatric patients completed the trial.

In addition, ISTA presented additional efficacy results from placebo-controlled conjunctival allergen challenge (CAC) clinical trials with Bepreve 1.0% and 1.5%. The positive results for some non-ocular symptoms considered secondary endpoints in the CAC trials were presented in the following encore poster presentations:

Bepotastine Besilate Ophthalmic Solution Reduces Nasal Symptoms in the Conjunctival Allergan Challenge (CAC) Clinical Model

Authors: G.L. Torkildsen, P.J. Gomes, J.I. Williams, J.A. Gow, M.B. Abelson, T.R. McNamara

Bepotastine Besilate Ophthalmic Solution 1% Reduces Ear or Palate Pruritus with Rapid Onset in a Clinical Model of Allergic Conjunctivitis

Authors: G.L. Torkildsen, P.J. Gomes, J.I. Williams, J.A. Gow, M.B. Abelson, T.R. McNamara

Bepotastine Besilate Ophthalmic Solution 1% Reduces Ear or Palate Pruritus with Rapid Onset in a Clinical Model of Allergic Conjunctivitis

Authors: G.L. Torkildsen, P.J. Gomes, J.I. Williams, J.A. Gow, M.B. Abelson, T.R. McNamara

About Bepreve(TM) (bepotastine besilate ophthalmic solution) 1.5%

Bepreve is a non-sedating, highly selective antagonist of the histamine (H1) receptor. It has a stabilizing effect on mast cells, and it suppresses the migration of eosinophils into inflamed tissues. The compound’s primary mechanisms of action are believed to make it an effective treatment against ocular itching associated with allergic conjunctivitis.

Bepotastine was approved in Japan for use as a systemic drug in the treatment of allergic rhinitis and urticaria/pruritus in July 2000 and January 2002, respectively, and is marketed by Mitsubishi Tanabe Pharma Corporation (formerly Tanabe Seiyaku Co., Ltd.) under the brand name TALION®. TALION was co-developed by Tanabe Seiyaku and Ube Industries, Ltd., who discovered bepotastine. In 2001, Tanabe Seiyaku granted Senju Pharmaceutical Co., Ltd., exclusive worldwide rights, with the exception of certain Asian countries, to develop, manufacture and market bepotastine for ophthalmic use. In 2006, ISTA licensed the exclusive North American rights from Senju to an eye drop formulation of bepotastine for the treatment of allergic conjunctivitis. In 2007, ISTA licensed exclusive North American rights to nasal dosage forms of bepotastine from Tanabe Seiyaku and obtained a future right to negotiate for a North American license to oral dosage forms of bepotastine for allergy treatment.

About ISTA Pharmaceuticals

ISTA Pharmaceuticals is the fourth largest branded ophthalmic pharmaceutical business in the U.S. ISTA’s four marketed products plus its product candidates include therapies for inflammation, ocular pain, glaucoma, allergy, and dry eye. The Company is developing a strong product pipeline to fuel future growth and market share, thereby continuing its growth to become the leading niche ophthalmic pharmaceutical company in the U.S.

Bepreve(TM) (bepotastine besilate ophthalmic solution) 1.5%, Xibrom(TM) (bromfenac ophthalmic solution) 0.09%, and Istalol® (timolol maleate ophthalmic solution) 0.5% are trademarks of ISTA Pharmaceuticals.

Source: ISTA Pharmaceuticals, Inc

View drug information on Bepreve; Bromfenac.

2007 InfantSEE(R) Data Magnifies The Need For Early Eye And Vision Screenings For Infants, According To American Optometric Association

Eye assessments from one in nine
infants have shown an overall need for concern, according to new data
collected by the American Optometric Association (AOA) via 10,000
InfantSEE(R) assessments conducted during 2006 and 2007. The overall need
for concern has increased from one in 14 last year and clearly reveals a
growing need for early vision examination in infants.

The data also showed that the two groups at greatest risk for abnormal
prescription status were those born prematurely and those from ethnic
minority backgrounds.

InfantSEE(R), a public health program developed by the AOA in
partnership with The Vision Care Institute of Johnson & Johnson Vision
Care, Inc., was designed to provide professional eye care for infants
nationwide at no cost regardless of family income. The program launched in
2005 with support from former President Jimmy Carter, honorary national
chair and spokesman. To date an estimated 125,000 to 150,000 babies have
had their eye health and vision assessed.

“These results magnify the growing need for early eye and vision
assessments for infants, particularly in premature and minority babies,”
said Scott Jens, O.D., F.A.A.O. and InfantSEE(R) chairman. “InfantSEE is
growing to meet that need, and I encourage all parents to take their babies
to any of the more than 7,600 optometrists nationwide who provide InfantSEE
assessments to detect the risk for potential eye and vision problems.”

According to this year’s data the majority of vision problems detected
include retinoblastoma (eye cancer), severe hyperopia (farsightedness),
myopia (nearsightedness), congenital glaucoma and congenital cataract.

Public health experts agree that visual development is most dramatic
between 6 and 12 months of age and that early detection can prevent and
help reduce the threat of serious vision impairments. In fact, one in every
10 children is at risk from undiagnosed eye and vision problems.

InfantSEE(R) assessments are complementary to the routine well-care
exams a baby receives from a pediatrician or family physician. Infants have
long received eye screenings for strabismus and leukocoria from their
trusted pediatricians as part of a full well-care check-up to detect a host
of large- scope health problems. Many cases of successful intervention have
resulted from this process. However, optometrists have the time to perform
a comprehensive eye and vision assessment, the instrumentation to identify
areas of risk that are critical to a child’s vision development and the
skills to identify conditions that might not be detected in a routine
pediatric wellness exam and that may need to be monitored, immediately
treated or referred to a pediatric eye specialist. InfantSEE(R) aims to
detect more subtle problems earlier, so infants can be managed by
optometrists, ophthalmologists or other medical specialists as necessary.

Although infants cannot respond verbally, the first year of life is an
ideal time to conduct an extensive eye assessment. Not only is this a
critical time for eye and vision development, but generally children at
this age do not yet fear doctor visits and find the assessment painless and
often enjoyable. Typically, infants sit on their parent’s lap during the
assessment, in which the optometrist uses lights and other hand-held
objects to check that their eyes are working together and that there are no
significant refractive or health issues that will impede proper vision

To learn more about InfantSEE(R), visit InfantSEE.

About the American Optometric Association

American Optometric Association doctors of optometry are highly
qualified, trained doctors, on the frontline of eye health and vision care,
who examine, diagnose, treat, and manage diseases and disorders of the eye.
In addition to providing eye and vision care, optometrists play a major
role in an individual’s overall health and well-being by detecting systemic
diseases. Doctors of optometry have the skills and training to provide more
than two- thirds of all primary eye care in the United States. The American
Optometric Association represents more than 34,000 doctors of optometry,
optometry students and paraoptometric assistants and technicians in nearly
6,500 communities across the country. For more information, visit

About The Vision Care Institute

The Vision Care Institute of Johnson & Johnson Vision Care Inc. is an
innovative educational resource created to prepare optometry students for a
successful transition into the real world of delivering quality eye care,
as well as to assist practicing Eye Care Professionals in the growth and
development of their practice. The state-of-the-art facility gives
participants a rare opportunity to gain first-hand experience with the
latest in vision diagnostic and treatment technologies through hands-on
contact lens instruction. Besides clinical training, participants also
concentrate on communication skills. The curriculum, taught by leading eye
care practitioners from around the country, gives participants the skills
and confidence necessary to excel in today’s professional practice. The
Vision Care Institute has hosted students from all 19 of the schools and
colleges of optometry throughout North America at its headquarters in
Jacksonville, Florida.

American Optometric Association

Eye Specialist Sees Improvement For His Patients Following Approval Of Macular Degeneration Drug Lucentis, England

Consultant Ophthalmologist Mr Arun Gupta has successfully operated on the first two patients to be treated at the Ashford and St. Peter’s Hospitals NHS Trust following approval of the drug Lucentis, for use on people suffering from Macular Degeneration.

Macular Degeneration is the commonest cause of blindness in UK. It usually affects patients over 50, and rises with age. Every year 26,000 patients in the UK are diagnosed with this condition and it presents itself in two forms: dry and wet.

The dry form is more common and progresses slowly and causes blind in some of the affected patients after many years.

The wet form is more aggressive. It progresses quite rapidly and causes blindness in most patients within months.

Said Mr Gupta: “The National Institute for Clinical Excellence (NICE) have approved a new treatment for wet Macular Degeneration called Lucentis. This is given by injection into the eye (intravitreal injections) as a day surgery procedure. Multiple injections are required over a period of months. The Lucentis treatment helps to decrease the progression of disease very significantly, and reduces the incidence of blindness.

“This is a very welcome step forward for our patients, and I am pleased to have been able to carry out this treatment on two patients at Ashford Hospital and we hope there will be more to follow.”

For people suffering from Macular Degeneration Mr Gupta has the following advice: Patients with the dry form should take diet supplements which contain vitamin C, Vitamin E, Zinc, b-carotene and lutein.

If patients notice rapid deterioration or distortion of vision they should see their GP immediately because this could mean the onset of the wet form, which needs treatment.

The Eye department at Ashford and St. Peter’s Hospitals NHS Trust also offers low visual aids for patients who have advanced or untreatable disease. These aids include such things as telescopic glasses, magnifying screens for television sets and hand-held magnifying glasses. In addition they can provide a Certificate of Visual Impairment in untreatable patients who have very poor vision, and offer them support.

Ashford and St. Peter’s Hospitals, NHS Trust

View drug information on Lucentis.

Major Visual Disorders In People Over 40 May Be Costing The US Economy Billions

Major visual disorders in Americans older than 40 years may cost the U.S. economy an estimated $35.4 billion a year, according to a report in the December issue of Archives of Ophthalmology, one of the JAMA/Archives journals.

Millions of Americans have visual impairment, blindness or other eye diseases, according to background information in the article. These diseases include age-related macular degeneration (AMD), cataracts, diabetic retinopathy, primary open-angle glaucoma and refractive errors, which are correctable with glasses or contact lenses. In addition to direct medical costs, other direct costs, such as nursing home health care, are related to these major visual disorders. Productivity losses also occur when individuals with visual impairment cannot work or earn lower wages.

David B. Rein, Ph.D., of RTI International, Research Triangle Park, N.C., and colleagues analyzed the financial burden of eye diseases in 2004. The researchers used private insurance and Medicare claim data to approximate direct medical costs. Evidence from published sources provided information about other direct costs, consisting of nursing home care, government purchase programs and guide dogs for the blind. Data from a national survey about labor and income were used to estimate productivity losses.

Researchers found that major visual disorders cost the U.S. an estimated $16.2 billion in direct medical costs, $11.1 billion in other direct costs and $8 billion in productivity losses, bringing the total annual financial burden to an estimated $35.4 billion. The annual governmental budgetary impact, calculated by adding the portion of the financial burden estimate produced by the government to additional amounts of social welfare payments from the federal treasury to people with visual impairment and blindness, was found to be $13.7 billion.

Direct medical costs were estimated to be approximately $6.8 billion for cataracts, $5.5 billion for refractive error, $2.9 billion for glaucoma, $575 million for AMD and $493 million for diabetic retinopathy. The majority of direct medical costs included outpatient services and medications, while inpatient costs accounted for almost no costs. Refractive error made up the largest share of direct medical costs for those age 40 to 64 (46.2 percent), while cataracts accounted for the largest portion among patients 65 years and older (56.2 percent). “Increased overall costs for AMD and cataracts among patients aged 65 years and older were attributable to increased numbers of patients who use outpatient services for these conditions,” the authors write.

Many costs are expected to increase in the future as the American population ages, the authors note. “Public health efforts to screen for and treat currently undiagnosed disease may be likely to increase direct medical care costs, but if effective, they will also improve visual outcomes, and potentially reduce productivity losses and nursing home placements associated with visual impairment and blindness,” they conclude. “Technological advancements that lead to reductions in the unit costs of glasses, cataract surgery and medications to treat glaucoma have the potential to lead to substantial direct medical cost savings.”

(Arch Ophthalmol. 2006;124:1754-1760.)

This study was supported by the Centers for Disease Control and Prevention’s Division of Diabetes Translation. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Contact: Lisa Bistreich
JAMA and Archives Journals

EVIZON(TM) Phase II Clinical Trial Begins Enrollment Of Patients With Wet Age-Related Macular Degeneration

Corporation (Nasdaq: GENR) today announced that the first patient has been
enrolled in a multi-center, open-label, pharmacodynamic Phase II clinical
trial, MSI-1256F-212 (“Study 212”), to explore the efficacy and safety of
EVIZON(TM) (squalamine lactate) at higher doses. Study 212 is designed to
evaluate up to 140 patients with wet age-related macular degeneration
(“AMD”) treated with EVIZON(TM) at four dose levels (40 mg, 80 mg, 120 mg
and 160 mg) over a 20 week period.

“Genaera is pleased to announce the beginning of active enrollment in
Study 212,” commented Jack Armstrong, President and Chief Executive
Officer. “We have assembled an outstanding group of investigators and study
sites and are looking forward to obtaining additional information on the
most effective dose of EVIZON. This study will provide more detailed
information on EVIZON’s effects on visual acuity in both affected eyes of
patients with exudative AMD. There is a significant medical need for a drug
that treats wet AMD in both eyes simultaneously, while avoiding the
complications of intravitreal injections. EVIZON is differentiated from
other competitor drugs having demonstrated a positive effect in both study
and fellow affected eyes in previous clinical trials. We look forward to
confirming that EVIZON is the treatment to meet that medical need.”

For information about participation in EVIZON(TM) clinical trials,
patients and physicians may call Genaera’s Clinical Trial Hotline at (800)

Genaera Corporation is a biopharmaceutical company committed to
developing medicines to address substantial unmet medical needs in major
pharmaceutical markets. The Company has products in development for the
treatment of eye, cancer, respiratory disorders and metabolic syndrome.
EVIZON(TM) (squalamine lactate) is Genaera’s lead product in development
for ophthalmic indications, specifically wet age-related macular
degeneration (AMD). Genaera’s other programs include: squalamine for the
treatment of cancer; interleukin-9 antibody, a respiratory treatment based
on the discovery of a genetic cause of asthma; LOMUCIN(TM), a mucoregulator
to treat the overproduction of mucus and secretions involved in many forms
of chronic respiratory disease; and trodusquemine (MSI-1436) for the
treatment of obesity.

This announcement contains forward-looking statements within the
meaning of the Private Securities Litigation Reform Act of 1995 that are
subject to risks and uncertainties, known and unknown. Forward-looking
statements reflect management’s current views and are based on certain
expectations and assumptions. Such statements include, among others,
statements regarding preliminary results, future clinical development plans
and prospects for Genaera’s programs, including EVIZON(TM) (squalamine
lactate), squalamine, LOMUCIN(TM), IL-9 antibody and trodusquemine
(MSI-1436). You may identify some of these forward-looking statements by
the use of words in the statements such as “anticipate,” “believe,”
“continue,” “develop,” “expect,” “plan” and “potential” or other words of
similar meaning. Genaera’s actual results and performance could differ
materially from those currently anticipated and expressed in these and
other forward-looking statements as a result of a number of risk factors,
including, but not limited to: Genaera’s history of operating losses since
inception and its need for additional funds to operate its business; the
costs, delays and uncertainties inherent in scientific research, drug
development, clinical trials and the regulatory approval process; the risk
that clinical trials for Genaera’s product candidates, including EVIZON,
may be delayed or may not be successful; the risk that Genaera may not
obtain regulatory approval for its products, whether due to adequacy of the
development program, the conduct of the clinical trials, changing
regulatory requirements, different methods of evaluating and interpreting
data, regulatory interpretations of clinical risk and benefit, or
otherwise; the risk that EVIZON ceases to meet the criteria for CMA2 Pilot
or Fast Track designation at some point in the future; Genaera’s reliance
on its collaborators, in connection with the development and
commercialization of Genaera’s product candidates; market acceptance of
Genaera’s products, if regulatory approval is achieved; competition;
general financial, economic, regulatory and political conditions affecting
the biotechnology and pharmaceutical industry; and the other risks and
uncertainties discussed in this announcement and in Genaera’s filings with
the U.S. Securities and Exchange Commission, all of which are available
from the Commission in its EDGAR database at sec as well as
other sources. You are encouraged to read these reports. Given the
uncertainties affecting development stage pharmaceutical companies, you are
cautioned not to place undue reliance on any such forward-looking
statements, any of which may turn out to be wrong due to inaccurate
assumptions, unknown risks, uncertainties or other factors. Genaera does
not intend (and it is not obligated) to publicly update, revise or correct
these forward-looking statements or the risk factors that may relate

Genaera Corporation