美国视网膜专家学会第24届年会和第6届欧洲玻璃体视网膜学会年会热点
Highlights of the 24th Annual American Society of Retina Specialists and 6th Annual European Vitreoretinal Society Meeting

2006年9月9－13日
法国戛纳

September 9 - 13, 2006, Cannes, France

Matthew Benz, MD

Medscape Ophthalmology. 2006;7(2) ©2006 Medscape

Introduction

The combined meetings of the American Society of Retina Specialists (ASRS) and the European Vitreoretinal Society (EVRS) took place in Cannes, France, from September 9-13, 2006. With the recent US Food and Drug Administration (FDA) approval of ranibizumab and the widespread use of bevacizumab for age-related macular degeneration (AMD), a great deal of the program was devoted to antiangiogenesis, highlighted by an outstanding featured guest lecture by Judah Folkman, MD. Other topics of note included advances in surgical instrumentation and treatment of diabetic macular edema.

Antiangiogenic Approaches to AMD
Ranibizumab

Further follow-up on the pivotal phase 3 clinical trials evaluating ranibizumab as treatment for exudative AMD continued to show outstanding efficacy out to 2 years. Anat Loewenstein, MD,[1] of Tel Aviv, Israel, and Ursula Schmidt-Erfurth, MD,[2] of Vienna, Austria, each reviewed some of the continued longer-term positive results. In particular, in the MARINA study looking at occult choroidal neovascular membranes (CNVM) in AMD, the average patient receiving the 0.5-mg dose of ranibizumab over 24 months experienced a gain in vision of 6.6 letters vs a loss of 14.9 letters in the sham control group, a difference of 21.5 letters. Eyes treated with ranibizumab had no growth in size of CNVM and a decreased area of leakage on fluorescein angiography.

Paolo Lanzetta, MD,[3] of Udine, Italy, presented combined safety results for the MARINA and ANCHOR study groups evaluating ranibizumab as treatment for exudative AMD. The per-injection rate of serious ocular adverse events, including endophthalmitis, was very low (< 0.12%). There was no significant imbalance in incidence of systemic serious adverse events, including arterial thromboembolic events such as myocardial infarction and ischemic cerebrovascular stroke, between ranibizumab and control groups.

Prema Abraham, MD,[4] of Rapid City, South Dakota, presented 12-month results from the PIER trial evaluating an alternative dosing regimen of ranibizumab for exudative AMD (3 monthly injections followed by quarterly dosing). Although there was a significant overall difference between the treated group and the sham control group, the PIER patients treated with ranibizumab had less mean gain in visual acuity than what was seen in the ANCHOR[5] and MARINA[6] trials with monthly dosing. In PIER, treated patients lost an average of 0.2 letters of visual acuity. This was significantly better than the control group, who lost an average of 16.3 letters at 12 months. However, in MARINA and ANCHOR, an average improvement in visual acuity was seen by treated patients at 12 months (+6.6 letters in MARINA and +11.3 letters in ANCHOR). There were no significant safety concerns noted in the trial.

The PrONTO study from Bascom Palmer Eye Institute is seeking to replicate the robust visual results of the MARINA and ANCHOR trials while minimizing patient risk of intervention. Dr. Philip Rosenfeld, of Miami, Florida, initiated this investigator-sponsored trial to evaluate variable dosing of ranibizumab for exudative AMD using optical coherence tomography (OCT). Dr. Rosenfeld presented 12-month results.[7] Patients received an initial 3 monthly doses of ranibizumab and then only received retreatment when certain, largely OCT-based, criteria were met. Highlights included a 95% rate of < 15 letter loss of visual acuity and a 35% rate of gain of 15 or more letters. Although this was a much smaller, single-institution trial, visual results are quite comparable to the 12-month results seen in the MARINA and ANCHOR trials. PrONTO provides hope that similarly outstanding visual results may be seen with fewer overall injections of ranibizumab.

Sebastian Wolf, MD,[8] of Bern, Switzerland, reviewed results of the PROTECT trial, evaluating safety and efficacy of same-day administration of intravitreous ranibizumab and verteporfin photodynamic therapy (PDT) for exudative AMD. Prior studies had indicated the possibility of increased risk of intraocular inflammation when these treatments were used on the same day. However, in this study, which used a newer formulation of ranibizumab, no significant safety concerns were noted. It may be that combination therapy with ranibizumab and verteporfin PDT may be an option for treatment of certain patients with exudative AMD.

Bevacizumab

Several groups from around the world presented data on the treatment of CNVM from AMD and other diseases (pathologic myopia, ocular histoplasmosis, multifocal choroiditis, idiopathic CNVM) with intravitreal bevacizumab.[9-13] Although bevacizumab was developed and FDA-approved for intravenous use in colorectal cancer, it has rapidly gained worldwide acceptance in the treatment of a multitude of vitreoretinal disorders. The groups presenting at this meeting showed impressive short-term results with intravitreous bevacizumab in the treatment of CNVM from AMD and other disorders.

At this international meeting, the audience of vitreoretinal specialists from around the world was polled as to their preferred first-line treatment of exudative AMD. Notably, the large majority reported intravitreous bevacizumab to be their first choice. This result is not entirely surprising, given the initial encouraging results, the widespread availability, and the favorable economic profile of intravitreous bevacizumab.

Featured Guest Lecture

The featured guest lecture was given by Judah Folkman, MD,[14] of Boston, Massachusetts. Dr. Folkman, a revered pioneer in angiogenesis research, gave a preview of "Potential Future Advances in Ophthalmology From Research in Tumor Angiogenesis." There are myriad new antiangiogenic targets in different stages of drug development. One that interests Dr. Folkman is endostatin, with its very broad effect on angiogenic stimuli and, possibly, a reduced effect on normal vessels. Dr. Folkman also described how blocking one angiogenic pathway may lead to upregulation of other pathways, suggesting that we may need to block multiple factors in the long run. He also described work being done by a colleague at Harvard, Joseph Italiano, PhD, that indicates angiogenesis markers may be found on platelets. Dr. Folkman proposed the possibility that we may one day test platelets to predict patients with AMD or diabetic retinopathy who may go on to develop pathologic angiogenesis. Perhaps we may selectively treat the patients who are at risk to develop vision loss before they develop pathologic angiogenesis.

Experimental Approaches

Quan Nguyen, MD,[15] of Baltimore, Maryland, reviewed the results of the phase 1 CLEAR-IT trial evaluating an intravitreous vascular endothelial growth factor (VEGF)-Trap in the treatment of exudative AMD. In this small study, patients appeared to have a rapid initial anatomic response to treatment. A phase 2 trial is underway. Larry Singerman, MD,[16] of Cleveland, Ohio, reviewed the phase 2 results of the CARE study looking at the anti-VEGF small interfering (si)RNA bevarsiranib for wet AMD. There are some concerns about a delay in treatment effect with this approach, and future trials will likely be in combination with an initial VE