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 VEGF blocker.

Anthony Adamis, MD,[17] of New York, NY, reviewed work looking at the combined effects of inhibiting VEGF-A and platelet-derived growth factor-B (PDGF-B) in an animal model. PDGF-B signaling is essential for the recruitment of pericytes to mature blood vessels. Concurrent inhibition of both PDGF-B and VEGF-A showed greater efficacy in treating neovascularization than either did alone in an animal model. A phase 1 combination trial with a PDGF-B and VEGF-A blocker is planned for early 2007.

Surgical Devices and Instrumentation

Recent ASRS Preferences and Trends survey results have indicated that many vitreoretinal surgeons are moving to smaller 25-gauge vitrectomy instrumentation for an increasing number of their surgical cases. Carl Regillo, MD, and colleagues,[18] from Wills Eye Hospital in Philadelphia, Pennsylvania, reviewed results from 25-gauge surgery and found a reasonable rate of complications in their cases. In contrast, Rob Mittra, MD, and colleagues,[19] from Minneapolis, Minnesota, expressed concern about a statistically significant increase in retinal detachment and endophthalmitis after 25-gauge surgery when compared with 20-gauge surgery.

Due to some concerns about 25-gauge surgery, such as instrument flex and intraocular fluidics, 23-gauge systems and instruments have been developed. Keith Warren, MD,[20] of Overland Park, Kansas, and Harinderjit Singh, MD,[21] of Augusta, Georgia, reviewed their use of the 23-gauge system developed by DORC. Both presenters felt the 23-gauge system to be a viable alternative with comparable outcomes to 20- or 25-gauge surgery. Claus Eckardt, MD,[22] of Frankfurt, Germany, reviewed his experience with 23-gauge vitrectomy surgery and expressed his belief that 23-gauge systems can be used in place of 20-gauge instrumentation in the large majority of surgical cases.

Diabetic Macular Edema

Jonathan Prenner, MD,[23] of New Brunswick, New Jersey, reviewed results from the siRNA bevarsiranib blocking VEGF in the treatment of diabetic macular edema. In this small phase 2 study, treated patients had the same outcome as controls at 12 weeks. Again, concerns about a lag in treatment effect persist with the siRNA technology.

Dean Elliott, MD,[24] of Los Angeles, California, reviewed 3-year results of a clinical trial evaluating the implantable, long-acting (30 months) fluocinolone implant in the treatment of diabetic macular edema. Treated patients showed a higher rate of resolution in macular edema (58% vs 30%) and visual improvement of 3 or more lines (28% vs 10%). However, 95% of phakic patients required cataract extraction over the 3-year study and 35% experienced an intraocular pressure rise significant enough to either remove the implant or warrant a glaucoma filtering surgical procedure during the course of the trial.

Diana Do, MD,[25] of Baltimore, Maryland, reviewed the interim results of the READ trial evaluating ranibizumab in the treatment of diabetic macular edema. Patients received monthly doses of ranibizumab for 2 months and then switched to an every-2-months dosing schedule. Interim results showed good initial anatomic response as measured by OCT and a nice improvement in visual acuity. Further studies of ranibizumab in diabetic macular edema are planned.

Conclusions

This truly international meeting of vitreoretinal specialists fostered further growth in the specialty. Ranibizumab and bevacizumab have revolutionized the treatment of AMD around the world. Further refinement of these therapies and newer therapies to reduce patient risk continues. Management of retinal vascular disease and diabetic retinopathy is rapidly moving toward pharmacotherapy, as evidenced by new clinical trial results in the management of diabetic macular edema. During the coming months and years, we will hear more and more about new therapies for these potentially blinding diseases. The surgical management of vitreoretinal disease continues to advance, with further refinements offering improved safety and a move toward minimally invasive procedures.

References

1.Loewenstein A. Combined efficacy of intravitreal ranibizumab in two phase III studies of choroidal neovascularization secondary to age-related macular degeneration. Program and abstracts of the 24th Annual American Society of Retina Specialists and 6th Annual European Vitreoretinal Society Meeting; September 9-13, 2006; Cannes, France.

2.Schmidt-Erfurth U. Two-year efficacy and safety results from the MARINA study. Program and abstracts of the 24th Annual American Society of Retina Specialists and 6th Annual European Vitreoretinal Society Meeting; September 9-13, 2006; Cannes, France.

3.Lanzetta P. Combined safety of intravitreal ranibizumab in two phase III studies of choroidal neovascularization secondary to age-related macular degeneration. Program and abstracts of the 24th Annual American Society of Retina Specialists and 6th Annual European Vitreoretinal Society Meeting; September 9-13, 2006; Cannes, France.

4.Abraham P. PIER: Year 1 results of a phase IIIB study of ranibizumab efficacy and safety in choroidal neovascularization due to age-related macular degeneration. Program and abstracts of the 24th Annual American Society of Retina Specialists and 6th Annual European Vitreoretinal Society Meeting; September 9-13, 2006; Cannes, France.

5.Miller J, Chung CY, Kim RY, MARINA Study Group. Randomized, controlled phase III study of ranibizumab (Lucentis) for minimally classic or occult neovascular age-related macular degeneration. Program and abstracts of the American Society of Retina Specialists 23rd Annual Meeting; July 16-20, 2005; Montreal, Canada.

6.Kaiser P. Anchor data. Program of Macula 2006; January 13-14, 2006; New York, NY.

7.Rosenfeld PJ. An OCT-guided variable-dosing regimen with Lucentis(TM) (ranibizumab) in neovascular AMD: one year results from the PrONTO study. Program and abstracts of the 24th Annual American Society of Retina Specialists and 6th Annual European Vitreoretinal Society Meeting; September 9-13, 2006; Cannes, France.

8.Wolf S. Open-label, multicenter, phase II study assessing the safety and efficacy of same-day verteporfin and liquid ranibizumab 0.5mg (PROTECT study). Program and abstracts of the 24th Annual American Society of Retina Specialists and 6th Annual European Vitreoretinal Society Meeting; September 9-13, 2006; Cannes, France.

9.Dev S. Intravitreal bevacizumab for the treatment of choroidal neovascularization secondary to ocular histoplasmosis and multifocal choroiditis. Program and abstracts of the 24th Annual American Society of Retina Specialists and 6th Annual European Vitreoretinal Society Meeting; September 9-13, 2006; Cannes, France.

10.Muldoon TO. Short-term outcomes in over 500 intravitreal bevacizumab treatments for retinal or choroidal vascular disease at the New York Eye & Ear Infirmary. Program and abstracts of the 24th Annual American Society of Retina Specialists and 6th Annual European Vitreoretinal Society Meeting; September 9-13, 2006; Cannes, France.

11.Fromow-Guerra J. Primary intravitreal bevacizumab (Avastin) for the treatment of CNV secondary to AMD: results of the Pan-American Collaborative Retina Study Group. Program and abstracts of the 24th Annual American Society of Retina Specialists and 6th Annual European Vitreoretinal Society Meeting; September 9-13, 2006; Cannes, France.

12.Castellarin AA. Intravitreal bevacizumab (Avastin) for the treatment of neovascular age-related macular degeneration (AMD). Program and abstracts of the 24th Annual American Society of Retina Specialists and 6th Annual European Vitreoretinal Society Meeting; September 9-13, 2006; Cannes, France.

13.Spaide RF. Intravitreal bevacizumab (Avastin) treatment of choroidal neovascularization secondary to age-related macular degeneration. Program and abstracts of the 24th Annual American Society of Retina Specialists and 6th Annual European Vitreoretinal Society Meeting; September 9-13, 2006; Cannes, France.

14.Folkman J. Potential future advances in ophthalmology from research in tumor angiogenesis. Program and abstracts of the 24th Annual American Society of Retina Specialists and 6th Annual European Vitreoretinal Society Meeting; September 9-13, 2006; Cannes, France.

15.Nguyen QD. C.L.E.A.R - IT 1: a phase I safety, tolerability, and bioactivity study of intravitreal VEGFTrap in patients with neovascular AMD. Program and abstracts of the 24th Annual American Society of Retina Specialists and 6th Annual European Vitreoretinal Society Meeting; September 9-13, 2006; Cannes, France.

16.Singerman LJ. VEGF small interfering (si) RNA, for treatment of wet age-related macular degeneration (AMD). Program and abstracts of the 24th Annual American Society of Retina Specialists and 6th Annual European Vitreoretinal Society Meeting; September 9-13, 2006; Cannes, France.

17.Adamis AP. The effects of combined inhibition of platelet-derived growth factor (PDGF)-B and VEGF-A signaling in murine models of ocular neovascularization. Program and abstracts of the 24th Annual American Society of Retina Specialists and 6th Annual European Vitreoretinal Society Meeting; September 9-13, 2006; Cannes, France.

18.Regillo CD. 25 gauge vitrectomy: outcomes and complications. Program and abstracts of the 24th Annual American Society of Retina Specialists and 6th Annual European Vitreoretinal Society Meeting; September 9-13, 2006; Cannes, France.

19.Mittra RA. Complications of 25-gauge vitrectomy surgery. Program and abstracts of the 24th Annual American Society of Retina Specialists and 6th Annual European Vitreoretinal Society Meeting; September 9-13, 2006; Cannes, France.

20.Warren KA. 23-gauge vitrectomy as an effective and safe alternative for sutureless vitreous surgery. Program and abstracts of the 24th Annual American Society of Retina Specialists and 6th Annual European Vitreoretinal Society Meeting; September 9-13, 2006; Cannes, France.

21.Singh H. 23-Gauge vitrectomy in 100 eyes: short-term visual outcomes and complications. Program and abstracts of the 24th Annual American Society of Retina Specialists and 6th Annual European Vitreoretinal Society Meeting; September 9-13, 2006; Cannes, France.

22.Eckardt C. Further experience with 23-gauge transconjunctival vitrectomy. Program and abstracts of the 24th Annual American Society of Retina Specialists and 6th Annual European Vitreoretinal Society Meeting; September 9-13, 2006; Cannes, France.

23.Prenner JL. VEGF small interfering (si) RNA, Cand5, for treatment of diabetic macular edema (DME). Program and abstracts of the 24th Annual American Society of Retina Specialists and 6th Annual European Vitreoretinal Society Meeting; September 9-13, 2006; Cannes, France.

24.Eliott D. Three-year results of a multicenter clinical trial of the fluocinolone acetonide intravitreal implant to treat diabetic macular edema. Program and abstracts of the 24th Annual American Society of Retina Specialists and 6th Annual European Vitreoretinal Society Meeting; September 9-13, 2006; Cannes, France.

25.Do DV. Interim results of the R.E.A.D. study: ranibizumab for edema of the macula in diabetes. Program and abstracts of the 24th Annual American Society of Retina Specialists and 6th Annual European Vitreoretinal Society Meeting; September 9-13, 2006; Cannes, France.