RESUMO
OBJECTIVE: To assess the influence of drug; dosing regimen; and traditional, nontraditional, and genetic risk factors on the incidence of choroidal neovascularization (CNV) in the fellow eye of patients treated for CNV with ranibizumab or bevacizumab. DESIGN: Cohort study of patients enrolled in a multicenter, randomized clinical trial. PARTICIPANTS: Patients with no CNV in the fellow eye at the time of enrollment in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT). METHODS: Eligibility criteria for the clinical trial required that study eyes have evidence on fluorescein angiography and optical coherence tomography of CNV secondary to age-related macular degeneration (AMD) and visual acuity between 20/25 and 20/320. Treatment for the study eye was assigned randomly to either ranibizumab or bevacizumab and to 3 different regimens for dosing over a 2-year period. The genotypes for 4 single nucleotide polymorphisms (SNPs) associated with risk of AMD were determined. Only patients without CNV in the fellow eye at baseline were considered at risk. The CATT ophthalmologists examined patients every 4 weeks through 2 years and recorded treatment for CNV in the fellow eye. MAIN OUTCOME MEASURES: Development of CNV in the fellow eye. RESULTS: Among 1185 CATT participants, 727 (61%) had no CNV in the fellow eye at enrollment. At 2 years, CNV had developed in 75 (20.6%) of 365 patients treated with ranibizumab and in 60 (16.6%) of 362 patients treated with bevacizumab (absolute difference, 4.0%; 95% confidence interval [CI], -1.7% to 9.6%; P = 0.17). The risk ratio for pro re nata dosing relative to monthly dosing was 1.1 (95% CI, 0.8-1.6). Greater elevation of the retinal pigment epithelium and fluid in the foveal center of the study eye were associated with increased incidence of CNV in the fellow eye. Incidence was not associated with genotype on rs1061170 (CFH), rs10490924 (ARMS2), rs11200638 (HTRA1), and rs2230199 (C3; P>0.35). CONCLUSIONS: Through 2 years, there was no statistically significant difference between ranibizumab and bevacizumab in incidence of CNV in the fellow eye. Genotype on 4 SNPs previously found to be associated with AMD did not affect the risk of CNV in the fellow eye among CATT patients. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.
Assuntos
Inibidores da Angiogênese/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Neovascularização de Coroide/epidemiologia , Degeneração Macular/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Bevacizumab , Neovascularização de Coroide/tratamento farmacológico , Neovascularização de Coroide/genética , Neovascularização de Coroide/patologia , Estudos de Coortes , Complemento C3/genética , Fator H do Complemento/genética , Relação Dose-Resposta a Droga , Feminino , Predisposição Genética para Doença , Genótipo , Serina Peptidase 1 de Requerimento de Alta Temperatura A , Humanos , Incidência , Injeções Intravítreas , Degeneração Macular/complicações , Degeneração Macular/genética , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Proteínas/genética , Ranibizumab , Serina Endopeptidases/genéticaRESUMO
OBJECTIVE: To describe characteristics of the Age-Related Eye Disease Study (AREDS) 9-step severity scale applied to participants in the Complications of Age-related Macular Degeneration Prevention Trial (CAPT). METHODS: Eligibility criteria for CAPT required 10 or more large (>or=125 microm) drusen in each eye. Readers graded baseline photographs from all participants and all follow-up photographs from 402 untreated eyes. Drusen and pigment characteristics were used to assign the AREDS scale score. Choroidal neovascularization was identified from fluorescein angiograms. Geographic atrophy involving the macular center was identified from color photographs. RESULTS: Among 1001 untreated eyes, 90% were at steps 5 to 7 at baseline. The 5-year incidence of advanced age-related macular degeneration (AMD) increased with each step from 8% (step 4) to 40% (steps 8 and 9 combined). These rates were similar to those reported in AREDS. Among 261 eyes with all 5 annual photograph gradings available and without progression to advanced AMD, 55% of eyes had scores that indicated improvement at least once. Before progression to advanced AMD, only 32% of 141 eyes either went through step 8 or 9 or had an increase of 2 or more steps from baseline. CONCLUSIONS: The AREDS 9-step severity scale was predictive of development of advanced AMD. The AREDS scale has deficiencies as a surrogate outcome for progression to advanced AMD.