Macular Degeneration: Hafiz G

Nguyen QD, Shah SM, Hafiz G, Do DV, Haller JA, Pili R, Zimmer-Galler IE, Janjua K, Symons RC, Campochiaro PA. · Department of Ophthalmology, The Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD 21287, USA. · Am J Ophthalmol. · Pubmed #18054887 No free full text.

Abstract: PURPOSE: To investigate the safety, tolerability, and bioactivity of intravenous infusions of bevacizumab in patients with choroidal neovascularization (CNV) attributable to causes other than age-related macular degeneration. DESIGN: Nonrandomized clinical trial. METHODS: Ten patients with CNV received infusions of 5 mg/kg of bevacizumab. The primary efficacy outcome measure was change in visual acuity (VA; Early Treatment Diabetic Retinopathy Study letters read at 4 meters) at 24 weeks and secondary measures were changes from baseline in excess foveal thickness (center subfield thickness), area of fluorescein leakage, and area of CNV. RESULTS: Infusions were well tolerated and there were no ocular or systemic adverse events. At baseline, median VA was 25.5 letters read at 4 meters (20/80) and median foveal thickness was 346 mum. At the primary endpoint (24 weeks), median VA was 48.5 letters (20/32), representing four lines of improvement from baseline (P = .005), median foveal thickness was 248 mum representing a 72% reduction in excess foveal thickness (P = .007). Four of nine patients had complete elimination of fluorescein leakage, three had near complete elimination (reductions of 91%, 88%, and 87%), two had modest reductions, and one had no reduction. All patients except one showed a reduction in area of CNV with a median reduction of 43%. CONCLUSIONS: Despite the small number of patients studied, the marked improvement in VA accompanied by prominent reductions in foveal thickness, fluorescein leakage, and area of CNV suggest a beneficial effect. It may be worthwhile to consider further evaluation of systemic bevacizumab in young patients with CNV.

Nguyen QD, Shah SM, Hafiz G, Quinlan E, Sung J, Chu K, Cedarbaum JM, Campochiaro PA, Anonymous00330. · Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland MD 21287-9277, USA. · Ophthalmology. · Pubmed #16876249 No free full text.

Abstract: OBJECTIVES: To assess the safety, pharmacokinetics, and biological activity of IV administration of vascular endothelial growth factor trap (VEGF Trap), a recombinant protein containing the binding domains of VEGF receptors 1 and 2, in patients with neovascular age-related macular degeneration (AMD). DESIGN: Randomized, multicenter, placebo-controlled clinical trial. PARTICIPANTS: Twenty-five patients were enrolled (11 male, 14 female); 19 received VEGF Trap (0.3 [n = 7], 1.0 [n = 7], or 3.0 mg/kg [n = 5]), and 6 received a placebo. METHODS: Patients were randomized to receive a placebo or 0.3-, 1.0-, or 3.0-mg/kg VEGF Trap--a single IV dose followed by a 4-week observation period and then 3 doses 2 weeks apart. MAIN OUTCOME MEASURES: Safety and biological activity, including change in excess retinal thickness and volume assessed by optical coherence tomography and visual acuity (VA) measured by the Early Treatment Diabetic Retinopathy Study protocol. RESULTS: The majority of adverse events attributable to VEGF Trap were mild to moderate in severity, but 2 of 5 patients treated with 3.0 mg/kg experienced dose-limiting toxicity (1 with grade 4 hypertension and 1 with grade 2 proteinuria); therefore, all patients in the 3.0 mg/kg-dose group were withdrawn from the study. The mean percent changes in excess retinal thickness were -12%, -10%, -66%, and -60%, respectively, for the placebo and 0.3-, 1.0-, and 3.0-mg/kg groups at day 15 (P<0.02 by analysis of covariance [ANCOVA]) and -5.6%, +47.1%, and -63.3% for the placebo and 0.3- and 1.0-mg/kg groups at day 71 (P<0.02, ANCOVA). A significant change in VA was not noted in this small study. CONCLUSIONS: The maximum tolerated dose of IV VEGF Trap in this study population was 1.0 mg/kg. This dose resulted in elimination of about 60% of excess retinal thickness after either single or multiple administrations. Alternative routes of delivery to increase the therapeutic window are being explored.

Campochiaro PA, Hafiz G, Shah SM, Nguyen QD, Ying H, Do DV, Quinlan E, Zimmer-Galler I, Haller JA, Solomon SD, Sung JU, Hadi Y, Janjua KA, Jawed N, Choy DF, Arron JR. · Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287-9277, USA. · Mol Ther. · Pubmed #18362932 No free full text.

Abstract: Macular edema is a major cause of vision loss in patients with central retinal vein occlusion (CRVO) or branch retinal vein occlusion (BRVO). It is not clear how much of the edema is due to hydrodynamic changes from the obstruction and how much is due to chemical mediators. Patients with macular edema due to CRVO (n = 20) or BRVO (n = 20) were randomized to receive three monthly injections of 0.3 or 0.5 mg of ranibizumab. At the primary endpoint, month 3, the median improvement in letters read at 4 m was 17 in the 0.3-mg group and 14 in the 0.5-mg group for CRVO, and 10 and 18, respectively for the BRVO group. Optical coherence tomography (OCT) showed that compared to injections of 0.3 mg, injections of 0.5 mg of ranibizumab tended to cause more rapid reductions of central retinal thickening that lasted longer between injections, but in 3 months, excess central retinal thickening which is a quantitative assessment of the macular edema, was reduced by approximately 90% in all four treatment groups. There was no correlation between the amount of improvement and duration of disease or patient age at baseline, but there was some correlation between the aqueous vascular endothelial growth factor (VEGF) level at baseline and amount of improvement. These data indicate that excess production of VEGF in the retinas of patients with CRVO or BRVO is a major contributor to macular edema and suggest that additional studies investigating the efficacy of intraocular injections of ranibizumab are needed.