Review of Ophthalmology's Retina Online

Volume 3, Number 7

July 2007

Contents:

		WELCOME

		THE LATEST PUBLISHED RESEARCH

		NOTEWORTHY: FDA APPROVES NEW FOURIER-DOMAIN OCT SYSTEM; OMEGA TRIAL IN DRY AMD BEGINS; 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 report to keep you up to date on important information affecting the care of patients with vitreoretinal disease.

In this edition:

	The latest published research
	Noteworthy, items of interest

THE LATEST PUBLISHED RESEARCH

Bevacizumab and PDT for AMD: Three-Month, Randomized, Controlled Study
In a randomized, controlled pilot study, treatment of neovascular age-related macular degeneration with a combination of bevacizumab (Avastin) and verteporfin (Visudyne) photodynamic therapy resulted in significant improvements in mean visual acuity that were maintained for three months.

The study involved 165 eyes of 165 patients with minimally classic or occult choroidal neovascularization that had not been treated previously. Patients were randomized to receive either a single PDT session (n=55), a single 1.25-mg intravitreal injection of bevacizumab (n=55), or a combination of the two (n=55). Patients in the combination group received bevacizumab within one hour of PDT.

All patients completed the study. At one month, 46 patients experienced a >0.2 improvement in best-corrected logMAR visual acuity--29 in the combination group, 16 in the bevacizumab group, and one in the PDT group. At three months, mean acuity slightly worsened in the PDT group but improved by 0.223 in the combination group and by 0.079 in the bevacizumab group (p<0.0001). Acuity improvement was maintained at three months in 23 patients, 22 in the combination group, one in the bevacizumab group, and none in the PDT group. Also at three months, significant (p<0.0001) reductions in mean central foveal thickness occurred in all groups: -59.6 µm in the combination group, -50.5 µm in the PDT group, and -34.0 µm in the bevacizumab group.

Source: Lazic R, Gabric N. Verteporfin therapy and intravitreal bevacizumab combined and alone in choroidal neovascularization due to age-related macular degeneration. Ophthalmology 2007;114:1179-1185.

Statin Use and AMD Status after Five Years
A recently completed analysis from a population-based cohort study found no association between statin use and the five-year incidence or progression of AMD. The study population included 2,204 of the 2,962 people originally examined from 1998 to 2000 in Beaver Dam, Wis. The 2,204 people in this analysis were examined again five years later.

The researchers used standardized procedures for physical examinations, blood collection and questionnaire administration. They graded AMD based on standard protocol and posterior pole images. They performed univariate and multivariate analyses.

When age, gender, smoking status and multivitamin use were controlled for, statin use was not associated with the five-year incidence of early AMD (p=.55), progression of AMD (p=.51) or incidence of late AMD (p=.53). The unadjusted five-year incidence of early AMD was 5.9 percent among people not using statins and 6.8 percent among those using statins. The unadjusted five-year incidence of late AMD was 1.8 percent among people not using statins and 2.3 percent among those using statins.

Source: Klein R, Knudtson MD, Klein BEK. Statin use and the five-year incidence and progression of age-related macular degeneration. Am J Ophthalmol 2007;144:1-6.

Bevacizumab Appears Effective against Radiation Retinopathy

A case of radiation retinopathy before (top) and eight months after treatment (bottom) with bevacizumab. (Images courtesy of Paul T. Finger, MD, and Kimberly Chin, OD)

According to results in six patients, intravitreal bevacizumab may be an effective treatment for radiation retinopathy. After eight months of receiving bevacizumab (1.25 mg in 0.05 mL) every six to eight weeks, visual acuity stabilized or improved in all cases. Decreased macular edema was the most common finding. In addition, based on fundus photography, optical coherence tomography/scanning laser ophthalmoscope imaging and angiography, the treatment progressively reduced cotton-wool spots, exudates, hemorrhages and microangiopathy. No bevacizumab-related ocular or systemic adverse events occurred.

Source: Finger PT, Chin K. Anti-vascular endothelial growth factor bevacizumab (Avastin) for radiation retinopathy. Arch Ophthalmol 2007;125:751-756.

Novel Delivery of Basic Fibroblast Growth Factor for Photoreceptor Protection
To investigate the effect of basic fibroblast growth factor (bFGF) on photoreceptor degeneration, researchers impregnated nanoparticles (NPs) with bFGF (2.5 µg) and injected them intravitreally into Royal College of Surgeons experimental rats. For comparison, they injected other RCS rats with either phosphate-buffered saline, blank NPs or 2.5 µg of bFGF. In addition, the bFGF-NPs were labeled with rhodamine so their location in the retina could be determined. The rat retinas underwent several types of testing for the next eight weeks.

BFGF-NPs were found in the outer nuclear layer six and eight weeks after they were injected. Compared with the other injected retinas, those receiving bFGF-NPs had greater electroretinogram a- and b-wave amplitudes and greater opsin preservation. Also, a significantly higher number of photoreceptors and significantly fewer TUNEL-positive cells were present after bFGF-NP treatment than after bFGF treatment.

In their paper, the researchers stated that this bFGF delivery system could potentially serve as a short-term treatment for photoreceptor degeneration in humans.

Source: Sakai T, Kuno N, Takamatsu F, et al. Prolonged protective effect of basic fibroblast growth factor–impregnated nanoparticles in Royal College of Surgeons rats. Invest Ophthalmol Vis Sci 2007;48:3381-3387.

Long-Term Results of PPV and ILM Removal for DME
In a retrospective study of 27 eyes of 27 patients followed for up to 38 months, pars plana vitrectomy with removal of the internal limiting membrane reduced diabetic macular edema and positively affected visual acuity, although recurrence of DME was observed in three eyes.

The eyes included in the study underwent PPV with ILM removal at one center. None of the eyes exhibited evidence of anteroposterior vitreomacular traction.

Patients were followed for a mean of 27.6 +/-7.2 months (12 to 38 months). Mean foveal thickness decreased by 178 +/-164 µm (p<0.001). Foveal thickness decreased by at least 20 percent in 22 eyes (81.4 percent) and increased by at least 20 percent in three eyes (11.1 percent). Mean best-corrected logMAR visual acuity changed from 0.75 +/-0.35 preoperatively to 0.63 +/-0.33 postoperatively (p=0.033). Acuity improved by two or more lines in 10 eyes (37 percent) and decreased by two or more lines in three eyes (11.1 percent). DME recurred 24 months after surgery in two eyes and 30 months after surgery in one eye.

Source: Yanyali A, Horozoglu F, Celik E, Nohutcu AF. Long-term outcomes of pars plana vitrectomy with internal limiting membrane removal in diabetic macular edema. Retina 2007;27:557-566.

Vitreous Bands Observed after Retisert Implantation
Doctors from the Cole Eye Institute in Cleveland reported that four of the 33 (12 percent) patients who received a fluocinolone acetonide implant (Retisert) at the facility developed a complication that has not been described previously in the literature. The patients, identified through a retrospective chart review, developed vitreous bands from the posterior pole to the implant. The bands are sheetlike opacities in the vitreous appearing denser than typical inflammatory vitreous condensations. They were visible on clinical examination.

The doctors wrote that the etiology of the bands is likely multifactorial. In the first three patients, depletion of steroid in the implant led to recurrence of inflammation, and the presence of a foreign body may have incited the band formation. In the fourth patient, they reported, a perioperative vitreous hemorrhage was most likely the main contributor to the band formation.

The authors of the report suggested that patients may benefit from vitreoretinal surgery when the vitreous bands cause visually significant traction. They also recommended that the procedure for implant removal or exchange in patients with clinically visible vitreous bands should be modified to include a complete vitrectomy to avoid retinal traction at the time of implant removal.

Source: Galor A, Margolis R, Kaiser PK, Lowder CY. Vitreous band formation and the sustained-release, intravitreal fluocinolone (Retisert) implant. Arch Ophthalmol 2007;125:836-838.

NOTEWORTHY: FDA APPROVES NEW FOURIER-DOMAIN OCT SYSTEM; OMEGA TRIAL IN DRY AMD BEGINS; AND MORE ITEMS OF INTEREST

Topcon reports that its 3D OCT-1000 enables more precise comparison of data between patient visits than previously available time-domain-based systems.

FDA Approves New Fourier-Domain OCT System
The FDA approved Topcon Medical Systems’ 3D OCT-1000, a Fourier-domain-based optical coherence tomography instrument combined with a color non-mydriatic retinal camera. Topcon said the instrument provides a true three-dimensional view of the mapped area and accurate retinal registration of the OCT image and the fundus image.

For more information, visit www.topconmedical.com/3doct.

Source: Topcon Medical Systems, July 2007.

OMEGA Trial in Dry AMD Begins
The first patient has been treated in the OMEGA clinical trial, a Phase II, two-year study evaluating Othera Pharmaceuticals’ OT-551 therapy for geographic atrophy. OT-551 is a small molecule that acts through multiple pathways to downregulate the disease-induced overexpression of nuclear factor kappa B, a key player in human inflammatory disease, and to reduce oxidative stress.

The study, which includes 198 patients, is employing a new, anatomical clinical endpoint recently developed for clinical trials in human retinal disease. The endpoint is based on objective changes in the area of atrophy of the retinal pigment epithelial cells.

Source: Othera Pharmaceuticals, June 2007.

Study Indicates Omega-3 Fatty Acids Protect Against Retinopathy
In a study published in the July issue of the journal Nature Medicine, omega-3 polyunsaturated fatty acids protected against the development and progression of retinopathy in mice. The researchers found that increasing omega-3 fatty acids and decreasing omega-6 fatty acids in the diet reduced the area of vessel loss that ultimately causes the growth of abnormal vessels and blindness.

"It is remarkable that with only a 2 percent change in dietary omega-3 intake, we observed an approximate 40 to 50 percent decrease in retinopathy severity," said lead author and NEI fellowship recipient Kip M. Connor, PhD, a postdoctoral research fellow at Children’s Hospital Boston. According to John Paul SanGiovanni, ScD, NEI staff scientist and the other lead author of the study, "This is a major conceptual advance in the effort to identify modifiable factors that may influence inflammatory processes implicated in the development of common sight-threatening retinal diseases."

The study was a collaborative effort by researchers at Children’s Hospital Boston, the primary pediatric teaching affiliate of Harvard Medical School, Brigham and Women’s Hospital, Massachusetts General Hospital, the University of Goteborg in Sweden, and the National Eye Instituteand National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health.

Source: National Institutes of Health, National Eye Institute, June 2007.

SurModics, Merck Partner on Drug Delivery System
SurModics and Merck announced a license and research collaboration agreement to pursue the joint development and commercialization of the I-vation sustained drug delivery system containing triamcinolone acetonide and other products that combine Merck proprietary drug compounds with the I-vation system for the treatment of serious retinal diseases.

The I-vation Intravitreal Implant is capable of delivering a variety of drugs on a sustained-release basis for well over a year. It can be implanted in a minimally invasive procedure and may be removed once the drug has been fully released. The implant with triamcinolone is currently being studied in a Phase I human clinical trial called STRIDE, which is assessing its safety and tolerability in patients with DME.

Source: SurModics, June 2007.

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