Cataract & Refractive Surgery Today

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Abbott to Gain Accommodating IOL in Visiogen Acquisition
Abbott (Abbott Park, IL) announced on September 2 a definitive agreement to acquire Visiogen, Inc. (Irvine, CA), for $400 million in cash. The acquisition will provide Abbott with Visiogen's Synchrony accommodating IOL, which is currently under review by the FDA. The lens received CE marking and has been available commercially in Europe since January 2009.

Designed to deliver improved vision at near, intermediate, and distance, the Synchrony has the potential to eliminate patients' need for glasses or contact lenses, reduce the incidence of glare and nighttime halos, and improve contrast sensitivity.

"We are thrilled to join forces with Abbott to bring this much-anticipated technology to market," said Reza Zadno, founder, president, and chief executive officer of Visiogen, in an article from Medical Device Daily.¹ "The global clinical results with Synchrony are extremely encouraging, and the opportunity to leverage Abbott Medical Optics' [AMO; Santa Ana, CA] extensive commercialization infrastructure means that more patients will benefit from this exciting advancement in cataract and presbyopia correction."

In an interview with Cataract & Refractive Surgery Today, James Mazzo, president of AMO, said the deal is expected to close in the fourth quarter and will better help Abbott compete in the premium IOL category. "I think the practitioners and their patients are ready for accommodating IOLs. Bausch & Lomb's Crystalens [Rochester, NY] has had great success, as well as multifocals from AMO and Alcon [Alcon Laboratories, Inc., Fort Worth, TX], and I think the [multifocal] space is going to continue to grow [because these lenses] are meeting—and in some cases exceeding—the needs of patients," Mr. Mazzo said.

Additional technologies in Visiogen's pipeline, Mr. Mazzo said, add to the attractiveness of the deal. AMO plans to launch an accommodating IOL within the next 5 years that will "complement the Synchrony,"

Mr. Mazzo commented. Details about AMO's future accommodating IOL are not available to the public at this time. FDA approval of the Synchrony is anticipated for the latter half of 2010.

Femtosecond Technology for Anterior Capsulotomy
The FDA has cleared the LenSx femtosecond laser (LenSx Lasers, Inc., Aliso Viejo, CA) for anterior capsulotomy during cataract surgery in the United States.

In an unpublished clinical trial, Zoltan Nagy, MD, found that the LenSx predictably and reliably created circular, smooth-edged capsulorhexes. In addition, significantly more capsulorhexes created with the femtosecond laser (100%) versus manual methods (10%) were within ą0.25 mm of the intended diameter.

"While current cataract surgery techniques can achieve excellent outcomes, the procedure still relies on multiple manual steps," said Stephen G. Slade, MD, medical director of the company, in a news release. "The LenSx femtosecond laser has been designed to advance the precision and reproducibility of key portions of the procedure, something we have seen lasers do repeatedly in other ophthalmic procedures."

The LenSx femtosecond laser is also being evaluated for lens fragmentation.

For more information about femtosecond lasers and cataract surgery, see the September 2009 issue of Cataract & Refractive Surgery Today.

Bernard Becker, MD, Named 2009 AAO Laureate
At this year's joint meeting with the Pan-American Association of Ophthalmology in San Francisco, the AAO will present the 2009 Laureate Recognition Award to Bernard Becker, MD, for his contributions to ophthalmology.

"Dr. Becker is recognized worldwide as a pioneer in ophthalmic research, clinical care, education, and leadership," said AAO President Michael Brennan, MD, in a news release. "In recognition for his commitment to teaching and education, and for his inspiration and encouragement to his students, we acknowledge the debt we all owe to him for his remarkable achievements."

Dr. Becker graduated from Princeton University and Harvard Medical School, and he completed his ophthalmic training at the Wilmer Ophthalmological Institute of the Johns Hopkins University. Dr. Becker served as department chair of ophthalmology at the Washington University School of Medicine in St. Louis for 35 years. He was instrumental in establishing ARVO and served as the organization's president in 1966.

Dr. Becker also played a vital role in establishing the National Eye Institute, where he held a variety of positions. He served as the director of the American Board of Ophthalmology from 1967 to 1974 and was a founding member of the Association of University Professors of Ophthalmology.

Dr. Becker was the first editor-in-chief of Investigative Ophthalmology (now Investigative Ophthalmology and Visual Science). In addition to his nearly 400 publications, Dr. Becker also coauthored the first two editions of Diagnosis and Therapy of the Glaucomas.

Alcon Acquires Swiss Biotechnology Firm
Alcon, Inc. (Huenenberg, Switzerland), has agreed to purchase Swiss biotechnology developer ESBATech AG (Zurich, Switzerland) for $150 million. According to a news release, Alcon will also "be responsible for contingent payments of up to $439 million based on the achievement of future research and development milestones that would be expected to create value for [the buyer]."¹

Under the terms of the agreement, Alcon acquires the rights to ESBATech's proprietary single-chain antibody fragment technology. Phase 1 and 2 clinical trials of experimental agents suggest that this therapeutic platform may enhance the treatment of age-related macular degeneration, diabetic macular edema, glaucoma, dry eye, and uveitis by facilitating the topical and local delivery of therapeutic agents.

A news release from the companies states that ESBATech's previous shareholders will retain the rights to nonophthalmic products and applications under the auspices of a new company called Delenex Therapeutics AG.

CDC Approve Substitution for Erythromycin Ophthalmic Ointment
InSite Vision Incorporated (Alameda, CA) has accelerated the production of AzaSite (azythromycin ophthalmic solution 1%) to compensate for a shortage of erythromycin ophthalmic ointment in the United States. Due to a change in manufacturers, the FDA anticipated the limited availablilty of 1.0- and 1.3-g tubes of the ointment in the near future and recommended that practitioners reserve all existing supplies for prophylactic use in neonates.

Although no clinical studies have supported the use of AzaSite for the prevention of ophthalmia neonatorum in newborns, the Centers for Disease Control and Prevention have "recommended [the drug] as an acceptable substitute for neonatal prophylaxis use where erythromycin ointment is not available."¹ The Centers' support for this substitution is based on existing data about AzaSite's pharmacology and sensitivity to gonococcal bacteria.

Inflammation Cleared, BCVA Improved With Ketorolac 0.45%
Twice-daily, preservative-free ketorolac 0.45% (Acuvail; Allergan, Inc., Irvine, CA) was well tolerated and effectively treated inflammation and pain after cataract surgery, said Eric D. Donnenfeld, MD, during a presenatation at the annual meeting of the European Society of Cataract & Refractive Surgeons in Barcelona.¹

Patients (N = 511) were randomized to receive twice-daily ketorolac 0.45% (n = 330) or vehicle (n = 163) for 16 days, beginning 1 day before cataract surgery. On day 1, 72.4% of ketorolac patients and 39.7% of vehicle patients had a summed ocular inflammation score of 0 (P < .001). On day 14, 52.5% of ketorolac patients and 26.5% of vehicle patients had a pain score of 0 (P < .001). Median time to pain resolution was 1 day in the ketorolac group and 2 days in the vehicle group (P < .001). Overall, 60.5% of ketorolac patients and 44% of vehicle patients gained three or more lines of BCVA on day 14 (P = .002).

Adverse events were reportedly mild to moderate and more prevalent in the vehicle group (48.5%) than in the ketorolac group (35.2%) (P = .004). Burning or stinging was reported by 1.5% of ketorolac patients and 0.6% of vehicle patients.

Eric D. Donnenfeld is a consultant to Allergan, Inc.

FDA Approves Ophthalmic Gel for Herpes Keratitis
Sirion Therapeutics, Inc. (Tampa, FL), announced FDA approval of Zirgan 0.15% (ganciclovir ophthalmic gel) as a treatment for acute herpetic keratitis. The FDA granted an orphan drug designation to Zirgan for this indication in April 2007. Ganciclovir has been used in Europe for more than 10 years.

The approval was based on the results of clinical trials conducted by Laboratoires Théa SA (Clermont Ferrand, France) in Europe, Asia, and Africa that compared the efficacy and tolerability of Zirgan with acyclovir ophthalmic ointment 3% in patients with herpetic keratitis.

In an open-label, randomized, controlled, multicenter clinical trial, which enrolled 164 patients with herpetic keratitis, ganciclovir was not inferior to acyclovir in patients with dendritic ulcers. Clinical resolution, or the percentage of healed ulcers, at day 7 was achieved in 77% (55 of 71) of patients treated with ganciclovir compared with 72% (48 of 67) treated with acyclovir.

In three randomized, single-masked, controlled, multicenter clinical trials (N = 213), ganciclovir was not inferior to acyclovir in patients with dendritic ulcers. Clinical resolution at day 7 was achieved in 72% (41 of 57) of patients in the ganciclovir group compared with 69% (34 of 49) in the acyclovir group.

Sirion recommends one drop of ganciclovir be administered to the affected eye five times per day until the ulcer heals and then one drop three times per day for 7 days. Zirgan will reportedly be supplied in a 5-g tube and will be available by prescription through retail pharmacies in early 2010.

Resolvin-Based Therapy Improved Dry Eye Symptoms
RX-10045 (Resolvyx Pharmaceuticals, Inc., Bedford, MA), a topical eye drop made of a resolvin compound, produced dose-dependent, statistically significant improvement in the signs and symptoms of dry eye, according to the results of a phase 2 study. The compound was also generally safe and well tolerated, the company said in a news release.

The 28-day, randomized, multicenter, placebo-controlled study included 232 patients with moderate dry eye. RX-10045 was administered to patients twice daily. Three doses of RX-10045 were evaluated during the study.

RX-10045 produced a significant dose-dependent improvement from baseline in symptoms recorded in patients' daily diaries. The improvement was observed across all symptoms evaluated in the study, including dryness, stinging, burning, grittiness, ocular discomfort, and the composite of each patient's most severe symptom (Worst Symptom Score) as recorded in their diary. RX-10045 was superior to placebo on the Worst Symptom Score (P < .02) as well as on several individual symptoms. The onset of symptomatic relief occurred within the first week of treatment, and symptoms continued to improve over the course of the 28-day study.

RX-10045 also produced a 75% reduction from baseline in controlled adverse environment-induced staining of the central cornea (P < .00001). This improvement was greater than that observed for placebo (P = .11). RX-10045 also produced a significant improvement in controlled adverse environment-induced staining in the inferior cornea and in the composite of central and inferior cornea (P = .09).

Preliminary Results of Investigational T-Pred Ophthalmic Suspension
Ista Pharmaceuticals, Inc. (Irvine, CA), announced the preliminary results of two recently completed studies of T-Pred (prednisolone acetate 1.0% and tobramycin 0.3% ophthalmic suspension), an investigational ophthalmic product for inflammatory ocular conditions.

The first study, which evaluated the antimicrobial equivalence between T-Pred and a tobramycin-containing reference product, reportedly demonstrated the antimicrobial bioequivalence of T-Pred to the reference product in 26 required tests.

The second study, a phase 3 clinical study of 172 patients undergoing bilateral cataract surgery, was designed to determine the bioequivalence of prednisolone concentrations between T-Pred and a reference product containing prednisolone acetate 1.0%. Although T-Pred's prednisolone concentrations in this study were reportedly similar to those of the reference product, bioequivalence was not demonstrated, the company said. Ista believes there are two contributing factors to this outcome: (1) the prednisolone reference product contained a higher drug concentration, and (2) a change was recently made to the reference product commercial product delivery dose.

Ista said it is working with the FDA to determine the appropriate clinical study or studies to perform in lieu of an additional prednisolone bioequivalence study.

Link Between Beta-Blockers and Cataract Found in Large Study
Topical and oral beta-blocker medications are associated with a higher incidence of nuclear cataract and cataract surgery.¹

At baseline, researchers at the Centre for Vision Research in Sydney, Australia, examined 3,654 individuals aged

49 years and older. At the 5- and 10-year follow-up, 2,454 participants were re-examined. Interviewer-administered questionnaires on the use of medications were evaluated, and lens photographs were taken and graded at each visit.

At 10 years, the use of either oral or topical beta-blockers had a borderline association with nuclear cataract and significantly predicted incident cataract surgery after adjustments for age, gender, blood pressure, IOP, myopia, diabetes, smoking, and steroid use, the study's authors said.

"Further studies are warranted to confirm and understand this finding," the investigators concluded.

Comparison Indicates Zigzag Incision More Effective Than Conventional Incision
A retrospective study that evaluated visual outcomes and astigmatism in patients who underwent penetrating keratoplasty (PKP) showed that a zigzag pattern produced better outcomes compared with trephination using a conventional blade.¹

The study included 57 consecutive patients. Forty-three patients (49 eyes) received a zigzag PKP incision created by a femtosecond laser, and 14 patients (17 eyes) underwent conventional Barron suction trephination PKP. Follow-up ranged from 1 to 12 months.

The investigators observed a significant difference in average astigmatism between the groups at postoperative months 1 (P = .013) and 3 (P = .018). By month 3, the average amount of astigmatism was 3.00 D in the zigzag group and 4.46 D in the conventional group. A significant difference in BSCVA was seen at month 1 (P = .0003) and month 3 (P = .006) between patients with normal macular and optic nerve function (zigzag group, n = 32; conventional group, n = 14). By month 3, 81% of the zigzag group compared with 45% of the conventional group had achieved a BSCVA of 20/40 or better (P = .03).