Macular Degeneration: Acharya NR

Kaiser PK, Brown DM, Zhang K, Hudson HL, Holz FG, Shapiro H, Schneider S, Acharya NR. · Cole Eye Institute, Cleveland, OH 44195, USA. · Am J Ophthalmol. · Pubmed #17949673 No free full text.

Abstract: PURPOSE: Subgroup data from a pivotal phase 3 study comparing ranibizumab (LUCENTIS) with verteporfin (VISUDYNE) photodynamic therapy (PDT) in patients with predominantly classic choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) were retrospectively analyzed to identify patient and disease characteristics that may predict visual acuity (VA) treatment outcomes. DESIGN: Retrospective subgroup analysis of 12-month data from the ANCHOR study. METHODS: Univariate analyses were performed to assess VA outcomes across subgroups based on patients' gender and baseline age, VA score, CNV lesion size, CNV lesion type, and duration of neovascular AMD, followed by multivariate analyses to identify predictors of the VA score change from baseline at 12 months. main outcome measures: Proportion of patients losing <15 letters and proportion gaining > or =15 letters from baseline VA; mean change from baseline VA. RESULTS: On average, all subgroups of ranibizumab-treated patients did better than PDT patients for all three VA outcome measures. In the multivariate analysis, lower baseline VA score, smaller baseline CNV lesion size, and younger baseline age were associated with greater gain of letters with ranibizumab treatment and less loss of letters with PDT. CONCLUSIONS: Subgroup analysis of 12-month data from the ANCHOR study showed ranibizumab to be superior to PDT in all subgroups evaluated, and was consistent with the subgroup analysis of 24-month data from the other pivotal phase 3 study of ranibizumab (MARINA) in showing that the most important predictors of VA outcomes were, in decreasing order of impact, the patient's baseline VA score, CNV lesion size, and age.

Kaiser PK, Blodi BA, Shapiro H, Acharya NR, Anonymous00408. · Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA. · Ophthalmology. · Pubmed #17628683 No free full text.

Abstract: OBJECTIVE: To assess pharmacodynamic responses to ranibizumab, an inhibitor of vascular endothelial growth factor A (VEGF-A), in a study of the treatment of minimally classic or occult with no classic choroidal neovascularization secondary to age-related macular degeneration (AMD) (designated MARINA [Minimally Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab in the Treatment of Neovascular AMD]) and to compare these responses with those in a sham-injection control group. DESIGN: Retrospective (prespecified and ad hoc) analyses of 24-month data. PARTICIPANTS: Seven hundred sixteen patients, randomized to 0.3-mg ranibizumab (n = 238), 0.5-mg ranibizumab (n = 240), or a sham injection (n = 238). METHODS: Stereoscopic fundus photography and fluorescein angiography (FA) were done at baseline and months 3, 6, 12, and 24. Optical coherence tomography (OCT) was performed at a subset of investigative sites (46 patients) at baseline, day 7, and months 1 and 12. MAIN OUTCOME MEASURES: Prespecified secondary end points were mean change from baseline in total area of choroidal neovascularization and total area of leakage from choroidal neovascularization at months 12 and 24. Prespecified exploratory FA end points included mean change from baseline in the areas of the choroidal neovascularization lesion and serous sensory retinal detachment (SSRD) at months 12 and 24. Post hoc exploratory FA outcome measures included the proportion of patients with no leakage from choroidal neovascularization and mean change from baseline over time in the area of subretinal fibrous tissue/disciform scar. The prespecified exploratory end point for OCT was mean change from baseline over time in center point thickness. RESULTS: At 12 and 24 months, statistically significant benefits of ranibizumab over sham treatment were observed for mean change from baseline in the areas of choroidal neovascularization lesion, total choroidal neovascularization, leakage from choroidal neovascularization, SSRD, and disciform scar/subretinal fibrosis. At 12 months (final OCT), the mean change in foveal center point thickness on OCT was a significant decrease in the ranibizumab group compared with the sham group. CONCLUSIONS: Patients with minimally classic or occult with no classic neovascular AMD treated with ranibizumab demonstrated improvement that was consistent for visual acuity, FA, and OCT outcomes and superior to that in sham-treated patients.

Boyer DS, Antoszyk AN, Awh CC, Bhisitkul RB, Shapiro H, Acharya NR, Anonymous00222. · Retina-Vitreous Associates, Beverly Hills, California, USA. · Ophthalmology. · Pubmed #17270674 No free full text.

Abstract: OBJECTIVE: An examination of clinically relevant subgroups of patients in the MARINA study of ranibizumab in treatment of minimally classic or occult with no classic choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) was done. Objectives were to determine the effectiveness of ranibizumab across subgroups, compare the effectiveness of ranibizumab with that of sham injection within subgroups, and evaluate the relationship between selected baseline characteristics and visual acuity (VA) outcomes. DESIGN: Retrospective subgroup analyses of 24-month data from the MARINA study. PARTICIPANTS AND CONTROLS: Seven hundred sixteen patients were randomly assigned to 0.3 mg ranibizumab (n = 238), 0.5 mg ranibizumab (n = 240), or sham treatment (n = 238). METHODS: Efficacy outcomes were compared across subgroups based on patients' gender, age, baseline VA score, baseline CNV lesion size, CNV lesion type, and duration of neovascular AMD using univariate analyses. Multivariate analyses were performed on the change from baseline to 24 months in VA score to assess further the correlation between baseline characteristics and VA outcome. MAIN OUTCOME MEASURES: Proportion of patients losing <15 letters from baseline, proportion gaining > or =15 letters from baseline, and mean VA score change from baseline. RESULTS: For each of the 3 VA end points, all subgroups of ranibizumab-treated patients did better on average than the sham-treated patients. Increasing age, larger CNV lesion size at baseline, and a higher baseline VA score were all associated with greater loss of letters in the sham group or less gain of letters in the ranibizumab groups. However, the net benefit of ranibizumab versus sham treatment was greater in patients who scored higher than in those who scored lower in baseline VA. CONCLUSIONS: This subgroup analysis of 24-month data from the MARINA study indicates that ranibizumab treatment was associated with an average increase from baseline VA in all subgroups evaluated, and that ranibizumab treatment was superior to sham treatment across all subgroups. The most important predictors of VA outcomes were, in decreasing order of importance, baseline VA score, CNV lesion size, and age.