Macular Degeneration: Goldberg MF

Kaiser PK, Goldberg MF, Davis AA, Anonymous00002. · Cleveland Clinic Foundation, Cole Eye Institute, Cleveland, Ohio 44195, USA. · Surv Ophthalmol. · Pubmed #17240258 No free full text.

Abstract: OBJECTIVE: To develop a safe and effective transcleral delivery of anecortave acetate, a novel angiostatic cortisene, in therapeutic concentrations to the choroid and retina in the region of the macula in patients with age related macular degeneration. METHODS: In pre-clinical studies with rabbits and monkeys, several routes of delivery were studied including oral and other systemic routes as well as topical, subconjunctival, intravitreal injections and posterior juxtascleral administration. In addition, posterior juxtascleral depot administration using a specially designed blunt cannula was evaluated in humans. RESULTS: Oral and other systemic routes were not acceptable due to rapid systemic metabolism. Topical and subconjunctival administrations resulted in subtherapeutic concentrations in the macular region (<0.1 microm). Intravitreal injections resulted in adequate drug levels, but the visual axis was obscured due to the opaque nature of the drug, and this method carries risks of endophthalmitis and retinal detachment. Posterior juxtascleral depot administration in rabbits and monkeys resulted in adequate retinal and choroidal drug levels (>or=0.1 microm) up to 6 months after administration. In clinical studies, this administration technique was found to be safe. CONCLUSIONS: Posterior juxtascleral depot administration of anecortave acetate onto the scleral surface near the macula is a safe and effective method for delivering therapeutic concentrations of drug to the macular region of the choroid and retina for up to 6 months.

D'Amico DJ, Goldberg MF, Hudson H, Jerdan JA, Krueger DS, Luna SP, Robertson SM, Russell S, Singerman L, Slakter JS, Yannuzzi L, Zilliox P, Anonymous00262. · No affiliation provided · Ophthalmology. · Pubmed #14644721 No free full text.

Abstract: PURPOSE: To evaluate safety and efficacy of the angiostatic agent anecortave acetate, compared with a placebo, for treatment of subfoveal choroidal neovascularization (CNV). DESIGN: Ongoing masked, randomized, placebo-controlled, parallel evaluation of anecortave acetate (30 mg, 15 mg, and 3 mg) versus a placebo. PARTICIPANTS: There were 128 eyes of 128 patients with subfoveal CNV secondary to age-related macular degeneration who were enrolled and treated, with 80% (102/128) of eyes presenting with predominantly classic lesions at baseline. METHODS: All eyes received a posterior juxtascleral depot application of masked study medication or a placebo, with retreatment at 6-month intervals if the masked investigator believed the patient could benefit. Patients received periodic detailed ophthalmic examinations with both fluorescein and indocyanine green angiography, general physical examinations with electrocardiograms, and hematology/serum chemistry/urinalysis. All ophthalmic and systemic safety data were periodically reviewed by the Independent Safety Committee overseeing the study. MAIN OUTCOME MEASURES: Best-corrected logarithm of the minimum angle of resolution (logMAR) vision and fluorescein angiographic lesion characteristics were compared over time and among treatment groups. RESULTS: At month 12, anecortave acetate (15 mg) administered at 6-month intervals was statistically superior to the placebo for 3 measures of clinical efficacy: mean change from baseline vision (P = 0.0131), stabilization of vision (<3 logMAR line change; P = 0.0323), and prevention of severe vision loss (decrease of > or = 6 logMAR lines from baseline; P = 0.0224). Subgroup analysis of predominantly classic lesions revealed that anecortave acetate (15 mg) was also superior to the placebo at 1 year for each of these 3 measures of visual outcome (Ps = 0.0022, 0.0100, and 0.0299, respectively). Anecortave acetate (15 mg) trended toward significance over the placebo at month 12 for inhibition of total lesion growth and for inhibition of both the total CNV component and the classic CNV component in both the overall and subgroup analyses. The Independent Safety Committee identified no clinically relevant treatment-related safety issues. CONCLUSIONS: Anecortave acetate (15 mg) is safe and clinically efficacious at 1 year for maintaining vision, preventing severe vision loss, and inhibiting subfoveal CNV lesion growth.

D'Amico DJ, Goldberg MF, Hudson H, Jerdan JA, Krueger S, Luna S, Robertson SM, Russell S, Singerman L, Slakter JS, Sullivan EK, Yannuzzi L, Zilliox P, Anonymous00326. · No affiliation provided · Retina. · Pubmed #12652226 No free full text.

Abstract: PURPOSE: To evaluate clinical safety and efficacy of the angiostatic agent anecortave acetate for treatment of subfoveal choroidal neovascularization secondary to AMD. METHODS: 128 patients were randomized to placebo treatment or one of three anecortave acetate doses. Study medication was administered as a posterior juxtascleral injection onto the posterior scleral surface. Best-corrected logMAR vision was obtained at baseline and follow-up visits. Fluorescein angiograms were evaluated for eligibility before enrollment and posttreatment. RESULTS: Six months after a single treatment, visual acuity (mean change from baseline logMAR values) was significantly better (P = 0.003) after anecortave acetate 15 mg than placebo. More patients treated with anecortave acetate 15 mg than placebo maintained vision (88% versus 70%, P = 0.080), especially those with predominantly classic lesions (92% versus 65%, P = 0.021). Anecortave acetate 15 mg inhibited lesion growth significantly better than placebo (P = 0.001). Trends favoring the other doses over placebo were observed for vision preservation and lesion inhibition, but statistical significance was not achieved. The Independent Safety Committee overseeing this study identified no clinically relevant treatment-related changes. CONCLUSION: Anecortave acetate 15 mg is safe and effective for preserving or improving vision and for inhibiting lesion growth in patients with subfoveal AMD.

DiLoreto DA, Goldberg MF, Bressler NM. · Wilmer Eye Institute, Johns Hopkins University School of Medicine, 550 N. Broadway, Baltimore, MD 21205, USA. · Arch Ophthalmol. · Pubmed #15364727 No free full text.

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