Review of Ophthalmology's Retina Online

Volume 1, Number 7

November 2005

Contents:

		WELCOME

		THE LATEST RESEARCH IN THE PEER-REVIEWED JOURNALS

		CONTINUING COVERAGE OF PAPERS PRESENTED DURING THE ANNUAL MEETING OF THE AMERICAN ACADEMY OF OPHTHALMOLOGY IN CHICAGO, ILL

		NOTEWORTHY: ANCHOR TRIAL OF RANIBIZUMAB PRODUCES POSITIVE ONE-YEAR RESULTS; AREDS II DEADLINE APPROACHES; AND MORE ITEMS OF INTEREST

WELCOME

Welcome to Review of Ophthalmology’s Retina Online newsletter. Each month, Medical Editor Philip Rosenfeld, MD, PhD, and our editors provide you with this timely and easily accessible information to keep you up to date on important information affecting the care of patients with vitreoretinal disease.

In this edition:

	The latest research in the peer-reviewed journals
	Continuing coverage of papers presented during the annual meeting of the American Academy of Ophthalmology in Chicago, Ill.
	Noteworthy, items of interest

THE LATEST RESEARCH IN THE PEER-REVIEWED JOURNALS

Triamcinolone Improves Visual Acuity in Large-Cohort DME Study
In a retrospective, interventional clinical case series, intravitreal injection of triamcinolone acetonide significantly improved visual acuity in patients with diffuse diabetic macular edema (DME). The series involved 210 eyes of 174 patients who received 1-mg or 4-mg injections of triamcinolone for macular edema between December 2000 and August 2002. All patients were followed for at least three months, and 77 percent were followed for six months. Median visual acuity improved from 20/200 at baseline to 20/80 at six months (p<0.001). Mean logMAR acuity improved from 0.92 at baseline to 0.82 at six months (p<0.001). Improvement was less over time, but was statistically significant at one, three and six months. The treatment resulted in improved vision for 39 percent of patients at one month, 41 percent at three months and 43 percent at six months.

Mean intraocular pressure increased from 15.4 +/-3.4 mmHg to a maximum of 20.4 +/-6.2 mmHg during the follow-up period. It decreased to 16.7 +/-6.0 mmHg at six months after treatment. One eye with no history of glaucoma required peripheral iridotomy, and one eye with a history of glaucoma underwent a trabeculectomy. Six eyes developed culture-negative sterile endophthalmitis. Cataracts progressed in seven patients; five patients underwent cataract extraction during the six-month follow-up period.

Inclusion criteria for the study were clinically significant macular edema, visual acuity loss and leakage on fluorescein angiography. Seventy percent of patients had previously undergone focal laser treatment; 19.5 percent had previously undergone panretinal photocoagulation; 10 percent had undergone pars plana vitrectomy; and 7.6 percent had been unsuccessfully treated with periocular steroids. During the study, re-treatments were at the discretion of each investigator, and 19 percent of patients were re-treated at least once.

Source: Chieh JJ, Roth DB, Liu M, et al. Intravitreal triamcinolone acetonide for diabetic macular edema. Retina 2005;25:828-834.

Postoperative appearance of closed macular hole following vitrectomy and silicone oil. (Image courtesy of Harry W. Flynn, Jr., MD.)

Study Compares Gas and Oil in Macular Hole Surgery
In a retrospective case control study involving 46 eyes of 44 patients, the outcomes of surgery for macular hole were better when C3F8 gas tamponade, rather than silicone oil, was used. The patients in the study had stage two, three or four macular holes. Silicone oil was used in 23 cases, and gas tamponade was used in 23 cases (controls). Investigators observed anatomic closure in 19 (82.6 percent) of the silicone oil cases and in 20 (86.9 percent) of the controls. Visual acuity improved to 20/70 or better in four (17.3 percent) of the silicone oil cases and in 17 (73 percent) of the C3F8 cases. There were no obvious differences between the two groups at baseline prior to surgery.

Source: Couvillion SS, Smiddy WE, Flynn HW, et al. Outcomes of Surgery for Idiopathic Macular Hole: A Case Control Study Comparing Silicone Oil With Gas Tamponade. Ophthalmic Surg Lasers Imaging 2005;36:365-371.

CONTINUING COVERAGE OF PAPERS PRESENTED DURING THE ANNUAL MEETING OF THE AMERICAN ACADEMY OF OPHTHALMOLOGY IN CHICAGO, ILL.

Study Implicates AMD as Independent Risk Factor for Stroke
Age-related macular degeneration (AMD) is associated with stroke, independent of other risk factors, according to the results of a population-based cohort study of 10,405 people ages 49 to 73. AMD was graded using retinal photographs. In a 10-year period, 241 stroke events occurred in the cohort. Researchers adjusted for factors other than AMD, including systolic blood pressure, diabetes and smoking, and found that the presence of AMD was associated with a higher risk of stroke (relative risk 1.82 with a confidence interval of 95 percent). The association was present in both ischemic and hemorrhagic stroke. The data were drawn from the Atherosclerosis Risk in Communities Study, a population-based investigation conducted in four U.S. communities.

Source: AMD and risk of stroke: The Atherosclerosis Risk in Communities Study, Wong TY, Klein R, Sun C, et al., 2005 American Academy of Ophthalmology paper presentation, Chicago, Ill.

Complications of 25-Ga. Vitrectomy
Based on their performance of 250 25-ga. pars plana vitrectomies, a group of surgeons concluded that hypotony due to leaking sclerotomies is a potential complication of this relatively new technique. The day after surgery, intraocular pressure was <10 mmHg in 27 percent of the eyes. Two eyes with hypotony required a second procedure. The surgeons also reported that 17 sclerotomies were sutured by the end of the procedure, one persistent bleb was sutured four weeks postoperatively, and three retinal detachments occurred. In addition, the surgeons reported two cases of endophthalmitis, which they characterized as a higher rate than with 20-ga. vitrectomy. Follow-up in the 250 cases ranged from six months to three years.

Source: Complications of 25-ga. pars plana vitrectomy, Jurgens I, Pera P, Jornet M, Catala J, 2005 American Academy of Ophthalmology paper presentation, Chicago, Ill.

Presence of Traction May be Key Factor in Success of Vitrectomy for DME
The results of a prospective interventional case series involving 33 patients who underwent vitrectomy for DME indicated that vitreomacular traction is a predictor of a successful vision outcome. One year after vitrectomy, patients’ overall macular thickness improved significantly, but overall visual acuity deteriorated. However, evidence of vitreomacular traction, observed clinically or on optical coherence tomography, was associated with a 0.08 logMAR improvement in visual acuity, while the absence of traction was associated with a 0.11 logMAR deterioration.

Source: Predictors of success in vitrectomy for diabetic macular edema, Shah SP, Laidlaw DA, 2005 American Academy of Ophthalmology paper presentation, Chicago, Ill.

NOTEWORTHY: ANCHOR TRIAL OF RANIBIZUMAB PRODUCES POSITIVE ONE-YEAR RESULTS; AREDS II DEADLINE APPROACHES; AND MORE ITEMS OF INTEREST

ANCHOR Trial of Ranibizumab Produces Positive One-Year Results
The ANCHOR Phase III clinical trial of ranibizumab (Lucentis, Genentech Inc.) met its primary endpoint of maintaining vision in patients with predominantly classic wet AMD. In addition, during the first year of the two-year study, approximately 94 percent of patients treated with a 0.3-mg dose and 96 percent of patients treated with a 0.5-mg dose of ranibizumab maintained or improved vision compared with approximately 64 percent of those treated with verteporfin (Visudyne) photodynamic therapy (PDT) (p<0.0001). On a key secondary endpoint, mean change in visual acuity from baseline to month 12 improved in patients treated with ranibizumab and declined in patients treated with PDT. The difference was statistically significant.

Endophthalmitis occurred more frequently in the ranibizumab-treated groups (approximately 1 percent), as did conjunctival hemorrhage, eye pain, increased intraocular pressure and vitreous floaters, which were mild to moderate. The frequency of myocardial infarctions was slightly higher in patients treated with 0.5 mg of Lucentis than in the other two arms, although the difference was not statistically significant. The frequency of cerebral vascular events was equal across all three arms.

ANCHOR is comparing two different doses (0.3 mg or 0.5 mg) of ranibizumab to PDT in 423 patients with predominantly classic wet AMD. Patients were randomized 2:1 to receive intravitreal ranibizumab injections once a month or PDT every three months for two years. Genentech plans to submit data from ANCHOR and another Phase III trial, MARINA, to the Food and Drug Administration in December and will request Priority Review status.

Source: Genentech, Inc., November 2005.

AREDS II Deadline Approaches
The deadline for applying to be an investigation site for the National Eye Institute’s AREDS II Phase III clinical trial is Nov. 23 at 5 p.m. Eastern Standard Time. The trial will evaluate the effects of oral supplements containing lutein/zeaxanthin, omega-3 fatty acids, and a combination of those ingredients on the development of advanced AMD and on moderate vision loss. It will also examine the effects of the supplements on cataract surgery and will provide an opportunity to refine the current AREDS formulation.

The design of AREDS II will be similar to the original AREDS design, with 25 percent of patients taking placebo, 25 percent taking a supplement containing lutein and zeaxanthin, 25 percent taking a supplement containing omega-3 fatty acids, and 25 percent taking a combination of the two. The original AREDS formulation will also be offered to study participants, and it is estimated that 65 percent to 75 percent will take it as well. A secondary randomization will evaluate elimination of beta-carotene and lower zinc levels in the AREDS formula.

AREDS II is scheduled to start in 2006, and the NEI expects 40-60 clinical and academic sites to be involved. Study-site applications must be submitted online and can be found at www.areds2.org.

Source: AREDS II, Chew EY and the Age-Related Eye Diseases Study II Research Group, 2005 American Academy of Ophthalmology Subspecialty Day paper presentation, Chicago, Ill.

Topically administered OT-551 metabolizes to TP-H in the eye. TP-H is a small molecule that mimics the antioxidant activity of superoxide dismutase, converting toxic free radicals into harmless molecules suitable for normal metabolism.

Trial to Explore Cataract Prevention in Post-Vitrectomy Patients
Othera Pharmaceuticals has initiated a Phase II clinical trial of its catalytic antioxidant molecule OT-551 for preventing or inhibiting the progression of cataracts in patients who have undergone vitrectomy. The trial of the topically administered compound is double-masked, randomized and placebo-controlled and will follow 100 patients for 12 months. OT-551 met all of the safety and comfort endpoints in a recently completed Phase I trial in healthy patients.

Othera executives said preclinical research suggests that OT-551 could be useful as a treatment for early-stage and advanced dry AMD. The company plans to file a supplement to its OT-551 Investigational New Drug application for indications in AMD and dry eye syndrome in 2006.

Source: Othera Pharmaceuticals, Inc., November 2005.

Acquisition of Eyetech Complete
On Nov. 14, OSI Pharmaceuticals Inc. completed its acquisition of Eyetech Pharmaceuticals Inc. for approximately $685 million in cash and approximately 5.7 million shares of OSI's common stock. The transaction creates a company focused on three disease areas--oncology, eye diseases and diabetes--with two major marketed products, pegaptanib sodium (Macugen) for AMD and erlotinib (Tarceva) for the treatment of advanced non-small cell lung cancer and pancreatic cancer.

The closing of the acquisition had been delayed for two days when, on Nov. 10, the OSI board of directors chose to use the time available to it under the merger agreement to "fully digest and debate the potential impact" of Phase III data on ranibizumab that Genentech Inc. released on Nov. 7 as well as other developments in the AMD marketplace.

During a Nov. 14 conference call, an OSI executive stated that while the company believes a 2006 launch of ranibizumab may have some bearing on pegaptanib sales, "We also believe strongly, as we have previously stated, that there is still much to unfold in the emerging wet age-related macular degeneration market. Only when the full efficacy and safety profiles of the competitive agents are fully elucidated through extensive clinical trials and with widespread use in the market will we all be able to fully understand the relative benefits of the respective competitive agents in meeting the needs of patients that suffer from this serious disease… We also continue to believe there is a meaningful place in the AMD marketplace for a highly selective VEGF target agent like Macugen, that has demonstrated in both clinical trials and through widespread use in the marketplace efficacy in the treatment of wet AMD, most importantly in early lesions, and has also established an outstanding safety profile."

Source: OSI Pharmaceuticals, Inc., November 2005.

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