CRSToday Europe News — March 2008

First US Corneal Collagen Crosslinking Trials Begin
The first US Food and Drug Administration (FDA)-approved clinical study of corneal collagen crosslinking with riboflavin (C3 riboflavin) for patients with keratoconus is underway.

According to already completed European studies led by Theo Seiler, MD, PhD, of Switzerland, and others, C3 riboflavin strengthens the cornea by increasing the amount of collagen crosslinking. The use of riboflavin and UVA light limits crosslinking to the anterior 300 µm of the cornea, avoiding damage to the corneal endothelium. The idea is that a stronger cornea will be less prone to cone formation than a diseased cornea.

"Crosslinking is already a mainstay in Europe. I am aware of approximately 1,000 units available worldwide, and I personally have been involved in this treatment via my European practice for 5 years," A. John Kanellopoulos, MD, of Greece, stated in an e-mail to CRST Europe. "I think that the FDA trial will further validate the process in the United States, which in turn will amplify the consensus we have already come to in Europe." Dr. Kanellopoulos is the Director of the Laservision Eye Institute in Athens, Greece and is a member of the CRST Europe Editorial Board.

The US trial will enroll approximately 300 patients and will be spearheaded by corneal specialist R. Doyle Stulting, MD, PhD, of Emory Eye Center, in Atlanta. The trial is expected to include 160 patients with keratoconus and 160 patients with corneal ectasia. Half of the patients will be treated with corneal collagen crosslinking and half will serve as the control group. The trials will use identical procedures and protocol. The change in corneal curvature in the treated group will be compared with that in the untreated group. UCVA and BCVA will be secondary outcome measures.

Additionally, two other crosslinking trials, sponsored by Peschke Meditrade GmbH (Huenenberg, Switzerland), will be conducted at up to 10 facilities throughout the United States.

MICS Created Little Corneal Aberration
Microincision cataract surgery (MICS) does not degrade the optical quality of the cornea or induce a modification of corneal astigmatism, according to a study published in the Journal of Cataract and Refractive Surgery.

Jorge L. Alió, MD, PhD, of Spain, and colleagues examined 25 eyes with nuclear or corticonuclear cataracts (grades 2 to 4). MICS was performed using low ultrasound power through a 1.6- to 1.8-mm clear corneal incision placed on the axis of the positive corneal meridian.

Postoperative follow-up included slit-lamp biomicroscopy, applanation tomometry, and measurement of UCVA and BCVA.

Statistical analysis showed no significant difference in corneal power between 1 and 3 months postoperatively (P=1.00) or between follow-up visits (P>.05). Additionally, there were no statistically significant changes in mean corneal astigmatism.

"We believe the main tool to neutralize the effect of corneal incisions on induced aberrations and stabilize corneal optics postoperatively is to continue to decrease the size of the incision until successful cataract surgery with IOL implantation can be performed through a sub–2-mm incision, perfecting the MICS technique," the study's authors wrote. "This goes hand-in-hand with new advances in IOL technology (eg, IOLs with different aberration profiles) that compensate for and reduce ocular aberrations, thus improving retinal image quality."

Donors' Health Associated With Risk of Infection
Corneal grafts obtained from donors dying in the hospital or with cancer may be associated with an increased risk of infection for the recipient, according to a report in Archives of Ophthalmology.

"Infection is an uncommon but serious complication of corneal transplant," the authors wrote. "Most infected eyes lose vision or become blind." Various practices have been instituted to reduce the risk of infection, including refusing donors who have blood or other infections and retrieving and preserving tissue with antiseptic tools.

Sohela S. Hassan, DrPH, of the Baylor College of Medicine, Houston, and colleagues used data from a surveillance registry to determine whether the donor's health status was associated with risk of infection in the recipient. The researchers collected donor information for all cases of endophthalmitis reported for transplants performed between 1994 and 2003. They then selected two patients for each case who had the same surgery date but did not develop an infection.

During the 10 years of the study, eye banks distributed 340,174 donor corneas in the United States and 109,009 internationally. A total of 162 cases of endophthalmitis were reported. The odds of infected recipients having received a cornea from a hospitalized donor were three times that of noninfected recipients, the authors reported. Additionally, death of the donor from cancer was considerably more likely among the recipients who developed infections. The cause is unclear, but donors could acquire harmful microorganisms in the hospital and transmit them to recipients, the authors hypothesized.

The results provide evidence that donors' health before death may affect their eye tissue; however the authors note that it does not warrant excluding broad categories of donors.

"Efforts are needed to determine what illnesses, interventions, or other reasons might explain the pathway linking certain donors with recipient infection," the authors wrote.

Update on Industry Consolidation
Bausch & Lomb (Rochester, New York) has completed its acquisition of Eyeonics, Inc. (Aliso Viejo, California), the medical device company that manufacturers the Crystalens accommodating IOL. The advanced-technology implantable lens has been reported to restores accommodation and reduces presbyopic patients' dependence on spectacles after cataract surgery.

Alcon Laboratories, Inc. (Fort Worth, Texas), announced it is taking over the sales, service, and support functions in the United States for the technology produced by WaveLight AG (Erlangen, Germany). WaveLight manufactures the Allegretto Wave Eye-Q, an excimer laser system featuring a 400-Hz repetition rate that delivers 1.00 D of correction in 2 seconds. Alcon acquired 77.4% of the German laser manufacturer's stock in the fourth quarter of 2007.

Additionally, during an interview with CNBC Europe, Peter Brabeck, Chief Executive Officer (CEO) of Nestlé SA (Zurich, Switzerland), hinted that the Swiss food giant could soon end its 31-year-old deal with Alcon Laboratories, Inc. Nestlé currently controls a 76% stake in Alcon.

A news release from Dow Jones quoted Mr. Brabeck as stating, "Alcon does not need Nestlé, and Nestlé does not need Alcon anymore." The report also suggests that analysts expect Nestlé to divest Alcon over time.

Ziemer Presented Update on Femto LDV Laser
Recent advances in femtosecond laser technology have made Ziemer's Femto LDV femtosecond surgical laser (Ziemer Ophthalmic Systems AG, Port, Switzerland) more safe, precise, and user-friendly, according to Werner Bernau, PhD, of Switzerland. Dr. Bernau presented at the first European z-LASIK Symposium, sponsored by Ziemer during the 12th Annual European Society of Cataract and Refractive Surgeons (ESCRS) Meeting, in Barcelona, Spain.

New developments for the laser will occur in three stages the first of which will begin in the next few months. The second and third stages of the product changes will occur this year, or after, and include updated software for performing corneal implants and lamellar keratoplasty, reduction of the external dimensions of the laser-beam delivery system (ie, the handpiece), and procedure time. The handpiece will also be available with an optional lens that permits use of the femto laser without a surgical microscope. "This is helpful especially in the case of surgeons who are using the Visx laser [Advanced Medical Optics, Inc. (Santa Ana, California)]," Dr. Bernau said.

Included in the second round of changes is a new handpiece. With an increased focal width and 400-µm cutting depths, the handpiece will offer the capability to perform corneal surgery techniques such as lamellar keratoplasty. In a third step of development, a handpiece with adjustable focal width is planned. While maintaining reduced external dimensions, this handpiece will offer a z-axis (vertical) scanning range of up to 1,000 µm.

The machine's upgraded software program and a new TopView camera will assist the surgeon when performing lamellar keratoplasty, or incisions for corneal implants. "This assists in better centration, especially in dark eyes with dark pupils that are sometimes difficult to see," Dr. Bernau said. The software upgrade also includes the implementation of TeamViewer, a system diagnostic application. It allows Ziemer's support specialists to remotely access, operate, and diagnose LDV systems via an internet connection.

Modes for corneal rings and inlays will be available in the second stage of development. Additionally, the Femto LDV's view enhancements with the TopView camera can aid the surgeon in viewing dark eyes or dark pupils. A fixation light will be added also to assist centration and patient fixation on the optical axis of the eye.

The Femto LDV features a short focal length and a large aperture, for extreme cutting precision. This was shown in a statistical evaluation of over 500 eyes treated on a variety of different femtosecond lasers. Femtolasers by other manufacturers all have smaller aperture optics, which can lead to photodisruption and an optical breakdown outside the cutting plane, Dr. Bernau said.

With the latest improvements, cutting times are now under 30 seconds, down from 45 seconds observed with earlier units, Theo Seiler, MD, PhD, of Switzerland said in the discussion. This brings suction times and total treatment times to under a minute, making z-LASIK the fastest LASIK procedure currently available, according to the company.

Additionally, the articulated arm of the LDV is now available with shorter shoulder height and a longer forearm, to better fit under excimer lasers with a low-profile overhead transom.

With the continuous stream of system improvements, the capabilities of the Femto LDV are expanding into new applications for corneal surgery, and the precision and quality of achieved stromal dissection keeps improving, Dr. Bernau added.

Cyclosporine Implant Received Fast Track Designation
The FDA has granted Lux Biosciences, Inc. (Jersey City, New Jersey), a fast-track designation for LX201. This experimental silicone matrix ocular implant continuously releases therapeutic levels of cyclosporine A directly into the eye for up to 12 months postoperatively. The LX201 is implanted under the conjunctiva of patients who have a high risk of rejecting corneal grafts. Current strategies for preventing graft rejection include systemic cyclosporine, which is associated with renal toxicity in animal studies, and treatment with topical steroids, which can delay healing and cause cataracts with prolonged use.

Lux Biosciences is currently investigating the safety and efficacy of LX201 in two randomized, double-blind, placebo-controlled, parallel-assignment, phase 3 clinical trials that are scheduled to conclude in March 2009.

AMO Announced Fourth Quarter Increase in Sales, Net Loss
Advanced Medical Optics, Inc. (Santa Ana, California), posted a 25% increase in net sales for the fourth quarter; nonetheless, the company—valued at a reported $1.3 billion—saw a net loss of $12.3 million in the last quarter and a total $192.9 million net loss at the close of 2007. This is compared with a quarterly net loss of $7.6 million for the same period in 2006 and an overall net income of $79.6 million that same year, according to company reports. A product recall in May 2007, along with approximately $16 million in taxes related to the acquisition of IntraLase Corp. (Irvine, California) and WaveFront Sciences, Inc. (Albuquerque, New Mexico), were major factors, the company said in a news release.

The company's stock value rose, however, after details emerged on cost-cutting methods to be implemented in 2008. According to the company, these included cutting approximately 150 jobs (4% of the global workforce) and consolidation of certain operations, for a savings ranging of $25 to $30 million this year.

New Postsurgical Hybrid Contact Lens Launched
SynergEyes, Inc. (Carlsbad, California), launched a hybrid contact lens designed for people who need further vision correction after undergoing refractive vision surgery. SynergEyes PS (postsurgical) is also designed for people who have experienced corneal trauma or who suffer from certain degenerative vision conditions.

SynergEyes PS hybrid contact lenses combine two materials: a rigid gas-permeable center and a soft lens outer skirt. The hybrid design bonds a hard and soft contact lens together, resulting in a vision correction option that provides clear vision for surgically altered corneas in a comfortable, healthy contact lens, according to the company.

–Compiled by Leah D. Farr, News and Industry Editor