May/June 2007 News
CLINICAL NEWS

Beta-Carotene Shows No Benefit for Age-Related Maculopathy
A new study suggests that beta-carotene may not benefit people with eye diseases, as previously thought. William Christen, ScD, OD, the study coauthor and faculty member at Brigham and Women’s Hospital, in Boston, found that among a large population of apparently healthy men, beta-carotene supplementation had no beneficial or harmful effect on the incident of age-related maculopathy (ARM). A previous study found that when taken with other vitamins, beta-carotene could slow or prevent vision loss in patients with age-related macular degeneration (AMD).

The conclusions, published in the Archives of Ophthalmology, were based on a randomized, double-masked, placebo-controlled trial, which followed 22,071 male doctors for 12 years. All participants were aged between 40 and 84 years and were randomly assigned 50 mg of beta-carotene every other day, or placebo.

After 12 years of treatment and follow-up, 162 and 170 cases of ARM reducing BCVA to 20/30 or worse, were reported in the beta-carotene and placebo groups, respectively. The results were similar for the secondary endpoints of ARM with or without vision loss (275 in the beta-carotene group vs 274 cases in the placebo group).

“Long-term supplemental use of beta-carotene neither decreases nor increases the risk of ARM,” researchers concluded.

High-Risk Americans Without Eye Care Access
Data from a national survey suggest that an estimated 60 million American adults are at high risk for vision loss, according to a report published in Archives of Ophthalmology. Of those adults, one in 12 cannot afford spectacles, and approximately 50% do not receive dilated eye examinations on a yearly basis.

In 2000, about 3.3 million Americans aged ≥40 years were visually impaired and >11 million of those aged
≥12 years, needed some form of vision correction. By 2020, these numbers could increase by 50% or more. Eye diseases and vision problems are associated with increased illness, increased risk of death and decreased quality of life.

Xinzhi Zhang, MD, PhD, from Centers for Disease Control and Prevention and colleagues, used data on vision from the 2002 National Health Interview Survey to estimate the number of adults at high risk of vision loss and assess factors associated with the use of eye care services.

A total of 30,920 adults participated in the survey. Sixteen percent of the participants were aged ≥65 years, 6.5% had diabetes and 19.5% had vision or eye problems. Based on these percentages, investigators projected that an estimated 60 million American adults are at high risk for serious vision loss.

“Among the high-risk population, the probability of having a dilated eye examination increased with age, education and income,” the authors wrote. “Approximately 5 million high-risk adults could not afford eyeglasses when needed. Being female, having low-income, not having insurance and having vision or eye problems were each associated with such inability.

“Many conditions causing visual impairment and blindness are often asymptomatic in their early, treatable stages,” they conclude. “There is substantial inequity in access to eye care in the United States. Better targeting of resources and efforts toward people at high risk may help reduce these disparities.”

Stem Cell Therapy Shows Promise for Vision
For the millions of Americans losing sight to degenerative diseases of the eye, the neural progenitor cell may provide answers in the future.

In a study in rats, neural progenitor cells derived from human fetal stem cells have been shown to protect the vision of animals with degenerative eye disease similar to the kinds of diseases that afflict humans. The new study appears in the journal Public Library of Science One.

The lead author of the study, University of Wisconsin-Madison researcher David Gamm, said the cells show “some of the best rescue, functionally and anatomically” of any such work to date. In animals whose vision would typically be lost to degenerative retinal disease, the cells were shown to protect vision and the cells in the eye that underpin sight.

The finding that the brain cells protected the cells in the eye was a surprise, according to study author, Raymond D. Lund, MD, from the University of Utah and the Oregon Health and Sciences University. The neural progenitor cells, which arise from the stem cells and further differentiate into different types of cells found in the central nervous system, were being tested for their ability to deliver another agent, a growth factor that has been shown to be effective in treating some types of degenerative disease.

“On their own, they were able to support retinal cells and keep them alive,” says Dr. Lund. “We did not expect that at all. We have used a number of different cell types from different sources, and these have given us the best results we have got.”

“The idea was to test the cells as a continuous delivery system” to shuttle an agent known as glial cell line-derived neurotrophic factor. “It is not a sensible thing to inject the eyes many times over years. The idea was to use the cells as a continuous delivery system, but we found they work quite well on their own.”

Teens Not Aware of Smoking, Blindness Link
Although most teenagers are unaware of the link between smoking and blindness, the information could motivate them to abstain from smoking more than the fear of lung or heart disease.

According to a cross-sectional survey of 260 teenagers published in the British Journal of Ophthalmology, making teenagers aware of ocular risks associated with cigarettes could decrease smoking rates.

Of the participants, aged 16 to 18 years, 15%, 27% and 81% believed that smoking caused stroke, heart disease and lung cancer, respectively. Only 5% believed smoking causes blindness. The teenagers were also asked to rank their fear of each of the five previously mentioned conditions—blindness ranked as the number one fear. The teens ranked lung cancer as their second highest fear.

Teens are not aware that smoking is linked to AMD, the investigators wrote. “We believe that increasing the knowledge about the link between smoking and blindness would provide more incentive for both teenagers and adults to give up smoking.”

Retinal Disease Linked to Migraines
Abnormalities in the small blood vessels around the retina in middle-aged men and women are a cause of migraines and headaches, according to data from the Atherosclerosis Risk in Communities Study, published in Neurology.

The study examined 10,902 black and white patients. Of this group, 22% had a history of migraine or headache with or without aura. The study found patients with a history of headaches were between 1.3 and 1.5 times more likely to also have signs of retinopathy, after controlling for age, race, gender, and heart disease risk.
Among patients without hypertension or diabetes (n=5,539), patients with migraine or other aura or nonaura headaches were 79% and 74% more likely to have signs of retinopathy, respectively.

Investigators from the University of North Carolina at Chapel Hill said the findings suggest problems in the circulatory system of small blood vessels may be an underlying factor. “It is possible given that anatomically and physiologically small blood vessels in the retina and brain are similiar.”

Researchers Hypothesize DR is an Autoimmune Disease
Although the pathogenesis of diabetic retinopathy (DR) is not fully understood, the finding of antipericyte and antiendothelial cell autoantibodies in the circulation of diabetic patients strongly suggests that some autoimmune activity has been involved in early pathophysiology of DR, doctors from the Clinical Hospital Center in Zagreb, Croatia, hypothesize. “There is increasing evidence of the presence of some autoimmune processes in the early stages of DR.”

Published in Medical Hypotheses, the article’s authors continued, “There is even more evidence that implicates the presence of autoimmune mechanisms in the proliferative stage of this disease.” These include elevated levels of tumor necrosis factor-a, interleukin-8, and soluble interleukin-2 receptor in the serum of diabetic patients, as well as several other factors also found in patients with DR.

Additionally, “preretinal membranes in diabetic patients contain deposits of immunoglobulin, activated complement components, monocytes, T and B lymphocytes, fibroblasts, and lymphokines. In diabetic patients, human leukocyte antigen DR and DQ expression was found on the retinal vascular endothelial cells, as well as on pigment and nonpigment epithelial cells,” they wrote.

“These antigens are normally restricted in immunocompetent cells and play an important regulatory role in the immune system. Their aberrant expression has been found on nonlymphoid cells in various autoimmune diseases, while abnormal expression of DR and DQ antigens at sites where they do not normally exist would result in autoimmunity by converting the target cells into a functional antigen-presenting cell,” authors concluded.

Researchers Making Significant Strides in DR Research
Research is increasingly showing promise to both slow and relieve the effects of DR, the most common complication of diabetes, according to scientists from the Juvenile Diabetes Research Foundation (JDRF). Published in the quarterly JDRF journal Countdown, JDRF touts a study led by Lloyd Aiello, MD, PhD, of the Joslin Diabetes Center, which shows that the compound ruboxistaurin (Eli Lilly and Company, Indianapolis) slowed the progress of retinopathy by inhibiting an enzyme in protein kinase C beta. This is the first time a drug has been shown to protect against the complication in a human clinical trial. Dr. Aiello found that the compound does not inhibit the progression of DR, but does prevent worsening of visual acuity and macular edema. The study found that ruboxistaurin could lead to 40% reduction in vision loss in patients.

Thomas Gardner, MD, and director of the JDRF Center for Mechanisms and Intervention of Diabetic Retinopathy at Penn State University, is also looking into changes in the nerve cells of the retina resulting from the condition, according to the journal.

A network of more than 1,000 researchers at 150 community-based and academic specialist groups, under the branch of Diabetic Retinopathy Clinical Research Network, has also been evaluating the effectiveness of different laser surgeries to treat macular edema, as well as injecting microscopic amounts of steroids into the eye.

According to Richard Insel, MD, executive vice president of research for JDRF, “Because retinopathy is the most common and serious eye-related complication of those with type 1 and type 2 diabetes—and is the leading cause of adult blindness in Americans—the outstanding research being done in this area will have a significant impact on the millions of people with diabetes.”

Clinical Results Presented for AMD Implant
Results for a second-generation intraocular telescope implant were presented at the 2007 ASCRS Symposium on Cataract and Refractive Surgery, in San Diego. The Lipshitz Macular Implant (LMI) is a new optical device that is completely implanted in the bag, creating a magnified image on the center of the retina, while preserving the natural peripheral visual field, according to Isaac Lipshitz, MD. The LMI incorporates miniature mirrors that are embedded inside a regular IOL.

According to the clinical data, magnified central image and normal peripheral field were demonstrated, with the first two LMI patients showing considerable improvement in distance and near visual acuity.

The first patient improved from 20/120 to 20/60 and achieved J3 for near vision. The second patient to receive the implant improved from counting fingers at 1 meter to 20/120 and achieved J5 for near vision. In both cases, the LMI was perfectly centered and positioned in the bag, and no medical side effects were seen.

“The concept of the LMI is to magnify central vision by 2.5 times,” said Dr. Lipshitz. “This implant could be useful in up to 70% or 80% of patients with AMD.”

According to clinical results, recovery time was equal to a normal cataract surgery, he added. Additionally, no area in the field of vision was found to be missing with the intraocular telescope implant.

Dr. Lipshitz says he expects approval of the device in Europe by the end of the year.

Laser Offers 3-D Images of Retina
Striving to help ophthalmologists improve diagnosis of eye diseases, researchers will introduce a new three-dimensional, high-resolution laser for optical coherence tomography (OCT). While conventional OCT produces a two-dimensional cross-sectional image of the retina, researchers believe the new three-dimensional images will prove even more helpful for diagnosis.

Robert Hubert, of Ludwig Maximillians University, in Germany, and colleagues from Massachusetts Institute of Technology have reported retinal scans at record speeds of up to 236,000 lines per second, or ten times faster than current OCT technology. With their technique, which uses a frequency-tunable laser to achieve fast scan speeds, they obtained a three-dimensional retinal image consisting of 512 times 512 times 400 volume elements of data in a human subject in just 0.87 seconds.

Future clinical studies, as well as further developments, may someday enable ophthalmologists to routinely obtain high-resolution snapshots, according to a paper, which was presented at the 2007 Conference on Lasers and Electro-Optics/Quantum Electronics Laser Science Conference, in Baltimore.

INDUSTRY AND BUSINESS NEWS

Bausch & Lomb Acquired by Private Investors
Bausch & Lomb (Rochester, NY) has reported that Warburg Pincus, a multinational private equity firm, acquired the eye care company for an estimated $4.5 billion. Under the terms of the agreement, Warburg Pincus will pay $65 in cash for each of Bausch & Lomb’s outstanding shares and assume an existing debt of $83 million.

According to a news release from Bausch & Lomb, the company is free to solicit superior proposals from third parties and to respond to unsolicited proposals for the next 50 calendar days. If the company finalizes another agreement during this period, it will pay Warburg Pincus a $40 million break-up fee.

“After extensive negotiations and careful and thorough analysis, together with our independent advisors, the Special Committee and our board have unanimously endorsed this transaction as in the best interest of the company and our shareholders,” said William H. Waltrip, lead director and chairman of the Special Committee of Bausch & Lomb’s Board of Directors, in a Marketwatch news release. “We are pleased that this transaction appropriately recognizes the value of Bausch & Lomb’s highly respected brand and innovative products in the eye care industry, while providing our shareholders with an immediate and substantial cash premium for their investment.”

News of the buyout boosted the value of shares in Bausch & Lomb by 8.5% from $61.50 at closing on May 15 to $66.74 in morning trading on May 16.

Stem Cell Pharma Recommends RP Treatment
Stem Cell Pharma, Inc., (Seattle), uncovered evidence that retinitis pigmentosa (RP) is two diseases in one: The initial retina damages, due to genetics, are rather mild, while the most damage is perpetrated by superimposed autoimmune disease identified through the presence of antiretinal antibodies and the powerful immunosuppressive hormone cortisol. This super-imposed autoimmune component can be treated with the potential of partial eyesight recovery.

The presence of the antiretinal antibodies has been found by a number of eye researchers, and cortisol in the retina has been identified by a team from the National Eye Institute. Cortisol is usually manufactured solely by the adrenal cortex on the top of the kidneys; however, tiny amounts of cortisol can be manufactured in areas outside the adrenal cortex, including in the retina.

According to the company, a comprehensive approach to treating RP should be directed at both its cause, by using cortisol modulators and immunomodulators and stem cells to repair the damages induced by the cause. Complementary treatments included in the Stem Cell Pharma’s RP program are intended to open the retinal arteries (eg, vasodilator therapy) in order to facilitate easier access of the stem cells and to bring the much-needed oxygen to areas previously deprived.

Apodized Diffractive IOLs for AMD
AMD patients implanted with the Restor IOL (Alcon Laboratories, Inc., Fort Worth, TX) showed a postoperative improvement in near visual acuity and visual functioning, postoperatively, according to a presentation by Johnny Gayton, MD, at the 2007 ASCRS Symposium on Cataract and Refractive Surgery.

In an evaluation of 29 consecutive eyes of cataract patients with visual loss from AMD, observations also showed an improvement in the quality of life and self-sufficiency of patients implanted with the Restor lens.

All eyes received the lens following phacoemulsification, and a postoperative refraction of -2.00 D was planned, according to Dr. Gayton. Subjective patient functional disability was assessed at the preoperative, 1-month, and 6-month postoperative examinations. Implantation of the Restor IOL added a 5.20-D equivalent and also improved near vision according to Snellen distance equivalents.

Phase 1 siRNA Trial for AMD
Phase 1 of a clinical trial with RTP-80i, a small interfering RNA therapeutic product that targets neovascular AMD, has begun. RTP-80i is based on Atugen AG’s (Berlin) proprietary siRNA technology and modifies the expression or function or one specific gene target. The study is currently being funded by Pfizer (New York, NY), which in-licensed RTP-80i from Atugen AG, a subsidiary of SR Pharma plc (London).

“These developments further demonstrate our ability to design siRNA molecules, based on our own patented siRNA chemistry, which can address specific disease targets. This capability means that we are able to generate new molecules for our development programs in the cancer field, while concurrently offering collaboration partners access to stabilized siRNA molecules for use against other targets and indications,” said Klaus Giese, MD, chief scientific officer.

SR Pharma is a leader in RNAi therapeutics, which is a Nobel Prize winning technology that silences genes linked to the onset of disease. The company has developed novel, chemically modified proprietary siRNA molecules, which have a number of advantages over conventional siRNA molecules, (eg, enhanced stability against nuclease degradation).

23-Gauge Surgical Instrument Line Launched
Synergetics USA, Inc., (O’Fallon, MO) launched its line of 23-gauge retina surgical instruments.

For the past 5 years, a debate has raged in retina surgery over whether cases should be done through three 20-gauge (0.89 mm) incisions or three 25-gauge (0.50 mm) incisions. The 20-gauge proponents point to stiffer, more maneuverable and more robust instrumentation, as well as improved flow rates and minimized surgical time. The 25-gauge proponents point to no-stitch, rapid wound healing and less trauma to the eye. While the debate continues, Synergetics is offering customers something in the middle—a 23-gauge (0.65 mm) line of instrumentation, which might offer the advantages of both, according to a news release.

“Synergetics was a leader in the move to 25-gauge [surgery] and we are proud to announce the largest line of instrumentation for 23-gauge surgery,” said Gregg D. Scheller, Chief Executive Officer and President of Synergetics. “Synergetics is committed to providing our customers with the options that they have become accustomed to in both 20- and 25- gauge surgery.

Company Reaches Benchmark for Eye Disease Treatment
Carl Zeiss Meditec (Jena, Germany) has reached a benchmark, having shipped 15,000 of its ophthalmic lasers, which are used to perform retinal, cataract and glaucoma disease therapy, around the globe. The lasers have been installed in major teaching institutions, as well as leading eye care centers worldwide, according to a company news release.

The company’s lasers, which offer photocoagulation, postcataract treatments, laser trabeculoplasty and combined iridotomy, will be showcased at the upcoming American Academy of Ophthalmology meeting, November 10 to 13, in New Orleans.