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Background We compared ranibizumab — a recombinant, humanized, monoclonal antibody Fab that neutralizes all active forms of vascular endothelial growth factor A — with photodynamic therapy with verteporfin in the treatment of predominantly classic neovascular age-related macular degeneration.
Methods During the first year of this 2-year, multicenter, double-blind study, we randomly assigned patients in a 1:1:1 ratio to receive monthly intravitreal injections of ranibizumab (0.3 mg or 0.5 mg) plus sham verteporfin therapy or monthly sham injections plus active verteporfin therapy. The primary end point was the proportion of patients losing fewer than 15 letters from baseline visual acuity at 12 months.
Results Of the 423 patients enrolled, 94.3% of those given 0.3 mg of ranibizumab and 96.4% of those given 0.5 mg lost fewer than 15 letters, as compared with 64.3% of those in the verteporfin group (P<0.001 for each comparison). Visual acuity improved by 15 letters or more in 35.7% of the 0.3-mg group and 40.3% of the 0.5-mg group, as compared with 5.6% of the verteporfin group (P<0.001 for each comparison). Mean visual acuity increased by 8.5 letters in the 0.3-mg group and 11.3 letters in the 0.5-mg group, as compared with a decrease of 9.5 letters in the verteporfin group (P<0.001 for each comparison). Among 140 patients treated with 0.5 mg of ranibizumab, presumed endophthalmitis occurred in 2 patients (1.4%) and serious uveitis in 1 (0.7%).
Conclusions Ranibizumab was superior to verteporfin as intravitreal treatment of predominantly classic neovascular age-related macular degeneration, with low rates of serious ocular adverse events. Treatment improved visual acuity on average at 1 year. (ClinicalTrials.gov number, NCT00061594
[ClinicalTrials.gov]
.)
Photodynamic therapy with verteporfin9,10,11,12 and intravitreal administration of pegaptanib sodium are approved by the Food and Drug Administration (FDA) and the European Agency for the Evaluation of Medicinal Products for the treatment of neovascular age-related macular degeneration.13 Neither treatment has resulted in clinically significant improvements in visual acuity.
Ranibizumab — a recombinant, humanized monoclonal antibody Fab that neutralizes all active forms of vascular endothelial growth factor A (VEGF-A) — was recently approved by the Food and Drug Administration for the treatment of this condition. Elsewhere in this issue of the Journal, Rosenfeld et al. report on a phase 3 study, called the Minimally Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab in the Treatment of Neovascular Age-Related Macular Degeneration (MARINA),14 which demonstrated that monthly intravitreal injections of ranibizumab prevented the loss of visual acuity in approximately 95% of patients and improved visual acuity in one quarter to one third of treated patients during 24 months of treatment. In a similar manner, the addition of ranibizumab to verteporfin photodynamic therapy in patients with predominantly classic choroidal neovascularization was associated with a reduction in the loss of visual acuity, as compared with verteporfin therapy alone, and with an improvement in visual acuity over baseline in many patients.15 We report the first-year results of a 2-year, phase 3 study, which compared the efficacy and safety of repeated intravitreal injections of ranibizumab with that of photodynamic therapy with verteporfin in patients with predominantly classic lesions associated with neovascular age-related macular degeneration.
Methods
Study Design
The Anti-VEGF Antibody for the Treatment of Predominantly Classic Choroidal Neovascularization in Age-Related Macular Degeneration (ANCHOR) trial was an international, multicenter, randomized, double-blind, active-treatment–controlled study. Before the initiation of the study, we obtained approval from institutional review boards or ethics committees at all clinical centers. Patients provided written informed consent for study participation. Screening lasted as long as 28 days.
For inclusion in the study, patients had to be at least 50 years of age; have a lesion whose total size was no more than 5400 µm in greatest linear dimension in the study eye; have best-corrected visual acuity of 20/40 to 20/320 (Snellen equivalent), assessed with the use of Early Treatment Diabetic Retinopathy Study (ETDRS) charts; have no permanent structural damage to the central fovea; and have had no previous treatment (including verteporfin therapy) that might compromise an assessment of the study treatment. No patients were excluded because of preexisting cardiovascular, cerebrovascular, or peripheral vascular conditions.
Study Treatment
We randomly assigned eligible patients in a 1:1:1 ratio to receive either 0.3 or 0.5 mg of ranibizumab (Lucentis, Genentech) plus sham verteporfin therapy or sham intravitreal injections plus active verteporfin therapy. Randomization was stratified according to study center and to visual-acuity scores on day 0 (<45 letters vs. 
45 letters, with a score of 45 letters as the approximate Snellen equivalent of 20/125 vision). In the group that received photodynamic therapy with verteporfin, intravenous administration of verteporfin (Visudyne, Novartis Pharmaceuticals) was followed by laser irradiation of the macula, according to instructions provided in the product package insert (www.visudyne.com). In the ranibizumab groups, sham verteporfin therapy was achieved by an intravenous infusion of saline rather than verteporfin, followed by laser irradiation of the macula identical to that in the active verteporfin-therapy group.
Ranibizumab was injected into the study eye at a monthly interval (ranging from 23 to 37 days, for a total of 12 injections, excluding the injection at month 12) in the first year, beginning on day 0; sham injections were administered on the same schedule. Either verteporfin or sham verteporfin was administered on day 0 and then if needed on the basis of investigators' evaluation of angiography at months 3, 6, 9, or 12.
The study was designed and analyzed by a committee composed of Dr. Brown, representing the academic investigators, and representatives of Genentech. In analyzing the data and writing this manuscript, Dr. Brown had full and unrestricted access to the data, and all coauthors contributed to the interpretation of the data and the writing of the manuscript. The authors vouch for the accuracy and completeness of the reported data.
Statistical Analysis
We performed efficacy analyses on an intention-to-treat basis with the use of a last-observation-carried-forward method for missing data. Pairwise treatment comparisons were performed with the use of statistical methods adjusting for baseline scores of visual acuity (<45 letters vs. 45 letters) and, for lesion morphologic end points, the baseline value of the lesion characteristic. Binary end points were analyzed with the use of the Cochran chi-square test.16 Mean changes from baseline were analyzed with the use of analysis of variance for end points with respect to visual acuity and an analysis of covariance for morphologic end points. The Hochberg–Bonferroni multiple-comparison procedure17 was used to adjust for the two pairwise treatment comparisons of the primary end point. Safety analyses included all treated patients.
The number of patients required for statistical significance was determined on the basis of a 1:1:1 randomization ratio, the Pearson chi-square test for the two pairwise comparisons of the primary end point, and the Hochberg–Bonferroni multiple-comparison procedure at an overall type I error of 0.0497. We estimated that the enrollment of 426 patients would provide the study with a statistical power of 96% to detect a significant difference between one or both ranibizumab groups and the verteporfin group in the percentage of patients losing fewer than 15 letters at 12 months, assuming a rate of 84% in each ranibizumab group and 67% in the sham verteporfin group. (See the Supplementary Appendix, available with the full text of this article at www.nejm.org, for additional information on the study design and analysis.)
Results
Study Patients
Between June 2003 and September 2004, 423 patients were enrolled and randomly assigned to a study treatment (143 to the verteporfin group and 140 to each of the ranibizumab groups). The disposition of the patients is summarized in Table 1 of the Supplementary Appendix. Three patients in the group receiving 0.3 mg of ranibizumab did not receive any treatment: one because of the patient's decision and two because of an investigator's decision. More than 90% of patients in each group (91.5% overall) were receiving treatment at 12 months. Of a possible 12 injections of ranibizumab or sham injections, the mean number administered was 11.1 in the verteporfin group, 11.0 in the 0.3-mg group, and 11.2 in the 0.5-mg group. Including the required administration on day 0 and excluding month 12, active verteporfin therapy was administered a mean of 2.8 times in the verteporfin group, and sham verteporfin was administered a mean of 1.7 times in each of the ranibizumab groups.
Randomized treatment groups were balanced for demographic and baseline ocular and morphologic characteristics (Table 1). The independent reading center subtyped the choroidal neovascularization as predominantly classic in all patients during the expedited screening evaluation. Subsequent reevaluation confirmed the initial classification in 96.9% of patients, and 3.1% were reclassified. In each group, the mean total lesion area was slightly less than 2 optic-disk areas (1 optic-disk area equals 2.54 mm2 on the basis of 1 optic-disk diameter of 1.8 mm).
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All end points with respect to visual acuity in the study eye at 12 months favored ranibizumab treatment over verteporfin therapy. With respect to the primary efficacy end point, 94.3% of patients in the 0.3-mg group and 96.4% in the 0.5-mg group lost fewer than 15 letters from baseline visual acuity, as compared with 64.3% in the verteporfin group (P<0.001 for each comparison) (Figure 1A). In addition, the proportion of patients whose visual acuity improved from baseline by 15 or more letters was significantly greater among those receiving ranibizumab treatment (35.7% in the 0.3-mg group and 40.3% in the 0.5-mg group, as compared with 5.6% in the verteporfin group; P<0.001 for each comparison) (Figure 1B). Significantly greater proportions of ranibizumab-treated patients than patients in the verteporfin group had visual acuity of 20/40 or better (P<0.001 for the comparison of each ranibizumab group with the verteporfin group) (Figure 1C), and smaller proportions had visual acuity of 20/200 or worse (P<0.001 for each comparison) (Figure 1D). A severe loss of visual acuity (defined as a decrease of 30 letters or more) did not occur in any patient in the ranibizumab groups but occurred in 13.3% of patients in the verteporfin group (P<0.001 for each comparison) (Figure 1E). Although no patient had baseline visual acuity of 20/20 or better, at 12 months 7.1% of the patients in the 0.3-mg group and 6.4% in the 0.5-mg group had visual acuity of 20/20 or better, as compared with 0.7% of patients in the verteporfin group.
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Adverse Events
Safety results are summarized in Table 3. Serious ocular adverse events associated with treatment were uncommon. Endophthalmitis, classified as a condition treated with intravitreal or systemic antibiotics, was reported in one patient, who was in the 0.5-mg group (0.7%). An additional patient in the 0.5-mg group (0.7%) had two events of intraocular inflammation that were classified by the investigator as serious uveitis. However, since one of the events was treated with systemic antibiotics (without obtaining ocular culture specimens or treatment with intravitreal antibiotics), this patient was presumed to have had endophthalmitis, and was so classified in Table 3. Rhegmatogenous retinal detachment occurred in one patient (0.7%) in the 0.3-mg group and one in the verteporfin group, and vitreous hemorrhage occurred in one patient (0.7%) in the 0.3-mg group.
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Transient changes in intraocular pressure after injection were common in the ranibizumab-treated patients. The proportion of patients with a postinjection intraocular pressure of 30 mm Hg or more was greater in both ranibizumab groups (8.8% in the 0.3-mg group and 8.6% in the 0.5-mg group) than in the verteporfin group (4.2%). However, very few patients had measurements of 40 mm Hg or more (2.9% in each ranibizumab group vs. 0.7% in the verteporfin group).
The ranibizumab groups had an increased frequency of cataract formation (10.9% in the 0.3-mg group and 12.9% in the 0.5-mg group, as compared with 7.0% in the verteporfin group). With the exception of one severe cataract in the verteporfin group, all adverse events associated with cataracts were mild or moderate. A small number of patients had changes in lens status reported during the first treatment year. Of patients whose study eye was phakic at baseline, five underwent cataract surgery during the 12 months of the study: four (5.3%) in the 0.3-mg group and one (1.2%) in the 0.5-mg group, as compared with none in the verteporfin group. Visual-acuity outcomes of these patients at 12 months were not notably different from those of the respective treatment groups overall. No traumatic lens damage was reported in the study eye of any patient during the first treatment year.
There was no overall imbalance among groups in the rates of serious nonocular adverse events: 14.6% in the 0.3-mg group and 20.0% in the 0.5-mg group, as compared with 19.6% in the verteporfin group. The numbers of deaths were similar across groups: three patients (2.2%) in the 0.3-mg ranibizumab group and two patients each (1.4%) in the 0.5-mg group and verteporfin group. With respect to specific nonocular adverse events, there were imbalances in back pain and nonocular hemorrhage (a combination of serious and nonserious events). Back pain was less common in the ranibizumab groups (3.6% in the 0.3-mg group and 1.4% in the 0.5-mg group) than in the verteporfin group (9.1%) and is a well-known potential adverse reaction to verteporfin infusion.18 The incidence of nonocular hemorrhage, an adverse event that potentially reflects systemic VEGF inhibition,19 was higher in the ranibizumab groups (5.1% in the 0.3-mg group and 6.4% in the 0.5-mg group, as compared with 2.1% in the verteporfin group). There was no increase in the ranibizumab groups in mean systolic or diastolic blood pressure or in the rates of hypertension and proteinuria, other adverse events potentially reflecting systemic VEGF inhibition.
Serious adverse events of arterial thromboembolism were evaluated with the use of the Antiplatelet Trialists' Collaboration (APTC) criteria, in which an event is defined as a nonfatal myocardial infarction, nonfatal ischemic stroke, nonfatal hemorrhagic stroke, or death owing to vascular or unknown causes.20 Overall, APTC-classified arterial thromboembolic events occurred in three patients (2.2%) in the 0.3-mg group, six patients (4.3%) in the 0.5-mg group, and three patients (2.1%) in the verteporfin group (Table 3). One patient (0.7%) in each group had a nonfatal cerebrovascular event. Nonfatal myocardial infarction occurred in one patient (0.7%) in the 0.3-mg group, three patients (2.1%) in the 0.5-mg group, and in one patient (0.7%) in the verteporfin group. No apparent relationship between the onset of those events and the time of study treatment was observed; the differences were not significant. One patient in the 0.3-mg group who began concomitant treatment with the systemic anti-VEGF agent bevacizumab for metastatic cancer midway through the study and continued to receive ranibizumab had an intestinal perforation, a known risk associated with systemic bevacizumab therapy.19
We observed immunoreactivity to ranibizumab in a percentage of patients in all treatment groups (1.5% in the verteporfin group, 3.2% in the 0.3-mg group, and 0.8% in the 0.5-mg group) before any exposure to ranibizumab. Monitoring of immunoreactivity during the first treatment year revealed no increase from baseline in the number of patients testing positive in the verteporfin group or the 0.3-mg group (1.6% in each group at 12 months), whereas the 0.5-mg group showed an increase to 3.9% of patients at 12 months. Although the small number of patients with immunoreactivity precludes drawing definitive conclusions, proportionately more ranibizumab-treated patients who were immunoreactive at any point had adverse events associated with intraocular inflammation (3 of 6 in the 0.3-mg group and 3 of 5 in the 0.5-mg group, as compared with 0 of 3 in the verteporfin group) than did patients who were never immunoreactive (11 of 127 in the 0.3-mg group and 17 of 129 in the 0.5-mg group, as compared with 3 of 129 in the verteporfin group). The presence or absence of immunoreactivity appeared to be unrelated to end points associated with visual acuity or nonocular adverse events potentially related to immunoreactivity.
Discussion
Our study demonstrated that ranibizumab prevents central vision loss and improves mean visual acuity at 1 year. In this study, monthly intravitreal injections of ranibizumab were superior in efficacy to verteporfin therapy. Although our study was not designed to evaluate the superiority of one ranibizumab dose over the other, efficacy results suggest a dose–response effect.
Intravitreal injections of ranibizumab were associated with a low rate of serious ocular adverse events, including such key events as presumed endophthalmitis, severe intraocular inflammation, and retinal detachment (each of which was reported in less than 1% of the pooled ranibizumab-treated patients and in less than 0.1% of ranibizumab injections). The ocular safety profiles for the three treatment groups revealed no overall imbalance in serious and nonserious adverse events, although there were trends toward increased rates of intraocular inflammation (generally mild), cataract (consistently mild or moderate), and nonocular hemorrhage with ranibizumab. The rates of intraocular inflammation and cataract in the ranibizumab groups were similar to those for ranibizumab-treated patients in the MARINA study.14 However, the rates of these events in the verteporfin group in our study were lower than the rates in the sham-injection group in the MARINA study.14
Regarding adverse events that potentially reflect systemic VEGF inhibition, no adverse events of proteinuria were reported and no imbalance in adverse events of hypertension or in blood-pressure measurements was noted in either our study or the MARINA study. In both studies, ranibizumab-treated patients had a higher percentage of nonocular hemorrhages than did patients who did not receive ranibizumab, and patients treated with a 0.5-mg dose had a higher rate of APTC-classified arterial thromboembolic events than did those who received a 0.3-mg dose or verteporfin therapy (Table 3). Since our study was not designed to distinguish small differences in rare adverse events among treatment groups, the clinical significance of these trends is unclear and requires further attention. In the MARINA study, with 2 years of study treatment, the rates of events classified as arterial thromboembolism according to APTC criteria were similar among the treatment groups.13 Follow-up is continuing through 2 years of treatment in our study to identify these events. The clinical significance of immunoreactivity to ranibizumab observed with the assay method used in our study and in the MARINA study is also not clear.
In summary, the ANCHOR study showed that ranibizumab administered monthly by intravitreal injection was superior in efficacy to photodynamic therapy with verteporfin in patients with subfoveal, predominantly classic choroidal neovascularization associated with age-related macular degeneration. The first-year results of our study and the 2-year results of the MARINA study, considered together, demonstrate that ranibizumab was effective with an acceptable adverse-event profile in the treatment of all angiographic subtypes of choroidal neovascularization associated with age-related macular degeneration.
Supported by Genentech and Novartis Pharma.
Dr. Brown reports having received consulting fees from Genentech, Alcon, Eyetech, Novartis, and Allergan; lecture fees from Genentech and Eyetech; and grant support from Alcon, Acuity Pharmaceuticals, Allergan, Alimera, Eyetech, Pfizer, Novartis, Genentech, Eli Lilly, Oxigene, and the Diabetic Retinopathy Clinical Research network; and having an equity interest in Pfizer. Dr. Kaiser reports having received consulting fees from Genentech, Alcon, Allergan, and Novartis and having received lecture fees from Novartis and Genentech. Dr. Michels reports having received consulting fees from Genentech and Pfizer–(OSI) Eyetech and lecture fees from Pfizer–(OSI) Eyetech, Novartis, and Genentech. Dr. Soubrane reports having received consulting fees from Alcon, Allergan, Thea, Alimera, Pfizer–(OSI) Eyetech, and Novartis and lecture fees from Pfizer, Alcon, Thea, and Novartis. Dr. Heier reports having received consulting fees from Genentech, Eyetech, Oxigene, Novartis, Allergan, Genzyme, iScience, ISTA, Pfizer, Regeneron, Theragenics, VisionCare, and Jerini; lecture fees from Genentech, Eyetech, Jerini, and Allergan; and grant support from Genentech, Eyetech, Pfizer, and Eli Lilly Theragenics. Dr. Kim reports being a full-time employee of Genentech and having received stock options. Dr. Sy and Dr. Schneider report being full-time employees of Genentech, holding an equity interest in the company, and having received stock options. No other potential conflict of interest relevant to this article was reported.
We are indebted to the patients who participated in this study, their families, and the research teams at each site; to the members of the data and safety monitoring committee: Frederick L. Ferris III, M.D. (chair), Susan B. Bressler, M.D., Stuart L. Fine, M.D., and Marian Fisher, Ph.D.; to the members of the University of Wisconsin Fundus Photograph Reading Center; to the members of the data-coordinating center (Statistics Collaborative); to members of the Genentech Clinical Operations organization for their invaluable assistance in the conduct of this study; to Charles Semba, M.D., Naveed Shams, M.D., Ph.D., James F. Ward, Ph.D., Lisa Damico, Ph.D., and Steven Butler, Ph.D., of Genentech for their critical comments and review throughout the design, conduct, and analysis of the study; and to staff members at Genentech for their assistance in the preparation of the manuscript.
Source Information
From Vitreoretinal Consultants, Methodist Hospital, Houston (D.M.B.); the Cole Eye Institute, Cleveland Clinic Foundation, Cleveland (P.K.K.); Retina Care Specialists, Palm Beach Gardens, FL (M.M.); the Clinique d'Ophtalmologie, University of Paris XII, Créteil, France (G.S.); Ophthalmic Consultants of Boston, Boston (J.S.H.); and Genentech, South San Francisco, CA (R.Y.K., J.P.S., S.S.).
Address reprint requests to Dr. Brown at Vitreoretinal Consultants, 6560 Fannin St., Suite 750, Houston, TX 77030, or at dmbmd{at}houstonretina.com.
References
The following principal investigators were members of the ANCHOR Study Group: T. Aaberg, Associated Retinal Consultants, Grand Rapids, MI; P. Abraham, Black Hills Regional Eye Institute, Rapid City, SD; L. Akduman, Saint Louis University Eye Institute, St. Louis; D. Alfaro III, Retina Consultants of Charleston, Charleston, SC; A. Antoszyk, Southeast Clinical Research Associates, Charlotte, NC; J. Arnold, Marsden Eye Research, Parramatta, Australia; C. Awh, Retina Vitreous Associates, Nashville; P. Beer, New Lions Eye Institute, Slingerlands, NY; J. Belmont, Retina Diagnostic and Treatment, Philadelphia; B. Berger, Retina Research Center, Austin, TX; D. Berinstein, Retina Group of Washington, Fairfax, VA; R. Bhisitkul, University of California at San Francisco School of Medicine, San Francisco; D. Boyer, Retina–Vitreous Associates, Beverly Hills, CA; W. Bridges, Western Carolina Retinal Associates, Asheville, NC; H. Brooks, Jr., Southern Vitreoretinal Associates, Tallahassee, FL; D. Brown, Vitreoretinal Consultants, Houston; T. Ciulla, Midwest Eye Institute, Indianapolis; W. Clark, Palmetto Retina Center, Columbia, SC; T. Connor, Medical College of Wisconsin, Milwaukee; S. Cousins, Bascom Palmer Eye Institute, Palm Beach Gardens, FL; F. Devin, Clinique Monticelli, Marseilles, France; W. Dunn, Florida Retina Institute, Daytona Beach; A. Eaton, Retina Health Center, Fort Myers, FL; S. Fekrat, Duke University Eye Center, Durham, NC; C. Foja, Universitätsklinikum Leipzig, Leipzig, Germany; B. Foster, New England Retina Consultants, West Springfield, MA; A. Gaudric, Hôpital Lariboisière, Paris; M. Gilles, Save Sight Institute, Sydney; D. Glaser, Retina Associates of St. Louis, Florissant, MO; B. Godley, Retina Specialists, Desoto, TX; V. Gonzalez, Valley Retina Institute, McAllen, TX; R. Goodart, Rocky Mountain Retina Consultants, Salt Lake City; R. Guymer, University of Melbourne, Centre for Eye Research Australia, East Melbourne, Australia; L. Halperin, Retina Vitreous Consultants, Fort Lauderdale, FL; J. Heier, Ophthalmic Consultants of Boston, Boston; F. Holz, Universitätsklinikum Bonn, Bonn, Germany; B. Hubbard, Emory University, Atlanta; H. Hudson, Retina Centers, Tucson, AZ; D. Ie, Delaware Valley Retina Associates, Lawrenceville, NJ; M. Johnson, University of Michigan, Ann Arbor; A. Joussen, Universitätsklinikum Köln, Cologne, Germany; P. Kaiser, Cleveland Clinic Foundation, Cole Eye Institute, Cleveland; B. Kuppermann, University of California at Irvine, Irvine; M. Lomeo, Midwest Retina, Columbus, OH; C. MacDonald, University of Texas Health Science Center, San Antonio; D. Marcus, Southeast Retina Center, Augusta, GA; A. Martidis, Retina Diagnostic and Treatment, Philadelphia; J. Martinez, Austin Retina Associates, Austin, TX; D. Maxwell, Jr., Retinal Associates of Oklahoma, Oklahoma City; T. McMillan, Southeastern Retina Associates, Knoxville, TN; M. Michels, Palm Beach Gardens, FL; D. Miller, Retina Associates of Cleveland, Beachwood, OH; P. Michell, Westmead Hospital, Westmead, Australia; I. Orgel, Retina Vitreous Associates, Toledo, OH; R. Park, University of Arizona, Tucson; M. Paul, Danbury Eye Physicians and Surgeons, Danbury, CT; P. Pavan, University of South Florida, Tampa; M. Petersen, Cincinnati Eye Institute, Cincinnati; J. Prensky, Pennsylvania Retina Specialists, Camp Hill, PA; P. Raskauskas, Retina Consultants of Southwest Florida, Fort Myers; E. Reichel, New England Eye Center, Boston; D. Reid, Retina Associates, Annapolis, MD; P. Richmond, Central Florida Retina, Orlando; W. Rodden, Retina and Vitreous Center of Southern Oregon, Ashland, OR; P. Rosenfeld, Bascom Palmer Eye Institute, Miami; P. Runge, Ophthalmic Consultants, Sarasota, FL; S. Sadda, Doheny Eye Institute, Los Angeles; S. Sanislo, California Vitreoretinal Research Center, Menlo Park; S. Schwartz, Bascom Palmer Eye Institute, Palm Beach Gardens, FL; A. Seres, Semmelweis University, Budapest, Hungary; M. Singer, Medical Center Ophthalmology Associates, San Antonio, TX; G. Soubrane, Clinique d'Ophtalmologie, University of Paris XII, Créteil, France; P. Soucek, University Hospital Vinohrady, Prague, Czech Republic; W. Stern, Northern California Retina-Vitreous Associates, Mountain View; G. Stoller, Ophthalmic Consultants of Long Island, Rockville Centre, NY; J. Thompson, Retina Specialists, Towson, MD; D. Tom, New England Retina Associates, Hamden, CT; R. Torti, Retina Specialists, Desoto, TX; M. Trese, Associated Retinal Consultants, Royal Oak, MI; E. van Kuijk, University of Texas Medical Branch, Galveston; T. Verstaeten, Allegheny General Hospital, Pittsburgh; K. Warren, University of Kansas Medical Center, Kansas City; H. Weiss, Retina Consultants of Michigan, Southfield; J. Weiss, Retina Associates of South Florida, Margate, FL; C. Wells, Vitreoretinal Associates, Seattle; S. Wolf, Universitätsklinikum Leipzig, Leipzig, Germany; and K. Zhang, John Moran Eye Center, University of Utah, Salt Lake City.
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Related Letters:
Ranibizumab for Neovascular Age-Related Macular Degeneration
Liew G., Mitchell P., Gillies M. C., Wong T. Y., Rosenfeld P. J., Brown D. M., Schneider S., the MARINA and ANCHOR Study Groups
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N Engl J Med 2007;
356:747-750, Feb 15, 2007.
Correspondence
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