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Biomedical subjects

Deeba Husain

Publications and source records attributed to Deeba Husain.

6 recordsLinked to original sources

Effect of intravitreal injection of ranibizumab in combination with verteporfin PDT on normal primate retina and choroid.

PURPOSE: To evaluate the effect of intravitreal injection of a monoclonal antibody fragment (ranibizumab, also known as rhuFab V2 and Lucentis; Genentech, S. San Francisco, CA) directed against vascular endothelial growth factor (VEGF) in combination with verteporfin photodynamic therapy (PDT) on normal primate retina and choroid. METHODS: Eight cynomolgus monkeys were treated with intravitreal ranibizumab in one eye and placebo in the other, alternating with verteporfin PDT in both eyes on a weekly basis for 6 to 7 weeks. Treatment effects were evaluated by color fundus photography, fluorescein angiography, and light and electron microscopy. RESULTS: Over the course of the study, increasing retinal pigment epithelial changes, with corresponding window defects, developed in both eyes of all animals on fluorescein angiography over the course of the study. No complications attributable to the intravitreal injection of ranibizumab were observed. Histologic analysis revealed a similar reduction in choriocapillaris density in the irradiated area of eyes treated with PDT alone compared with those that received combination treatment. CONCLUSIONS: In this limited study of normal monkey eyes, no severe adverse effects from the combination of intravitreal ranibizumab and verteporfin PDT were demonstrated compared with PDT alone.

Animals↗

Investigating the effect of ciliary body photodynamic therapy in a glaucoma mouse model.

PURPOSE: To investigate the morphologic and functional effects of verteporfin ciliary body photodynamic therapy (PDT) in a murine glaucoma model and normal mouse eyes. METHODS: A glaucomatous mouse strain, DBA/2J and a normal control mouse strain (C57BL/6) were used in the study. Verteporfin was injected intravenously at doses of 1.0 (DBA/2J) or 2.0 or 4.0 (C57BL/6) mg/kg. Transscleral irradiation of the ciliary body was performed with light at a wavelength of 689 nm delivered through an optical fiber, with irradiance of 1800 mW/cm2 and fluence of 100 J/cm2. Laser irradiation was applied for 360 degrees of the corneoscleral limbus in C57BL/6 normal mice and for 180 degrees in DBA/2J mice. Retreatment was performed in C57BL/6 normal mice that had been treated with 2.0 mg/kg of verteporfin at post-PDT day 7. One eye of each animal was treated, and the fellow eye served as the control. The morphologic effect of PDT on the ocular structures was assessed by light and electron microscopy. The IOP was measured using an applanation tonometer with a fiber-optic pressure sensor. Surviving retinal ganglion cells (RGCs) in DBA/2J mice eyes were retrogradely labeled with a neurotracer dye at 12 weeks after PDT. RESULTS: In all groups, almost all ciliary body blood vessels in the treated area were thrombosed 1 day after PDT. In DBA/2J mice, ciliary epithelium and stroma were severely damaged 1 day after PDT. The mean IOP in treated eyes was significantly reduced compared with that in the control eyes in all groups. The reduction of mean IOP in DBA/2J mouse eyes persisted for 7 weeks, although the mean IOP in normal mouse eyes treated with 2 or 4.0 mg/kg verteporfin returned to the level of the fellow control eyes by 7 and 17 days after treatment, respectively. The mean number of RGCs in the DBA/2J treated eyes was significantly higher than in control eyes. CONCLUSIONS: Ciliary body PDT resulted in morphologic changes in the ciliary body, significant reduction of IOP, and prevention of ganglion cell loss in a mouse glaucoma model. These results suggest that ciliary body PDT is a more selective cyclodestructive technique with potential clinical application in the treatment of glaucoma.

Animals↗

Safety and efficacy of intravitreal injection of ranibizumab in combination with verteporfin PDT on experimental choroidal neovascularization in the monkey.

OBJECTIVE: To study the safety and efficacy of intravitreal injections of anti-vascular endothelial growth factor antibody fragment (ranibizumab [formerly known as rhuFabV2], Lucentis; Genentech, South San Francisco, Calif) in combination with intravenous verteporfin (Visudyne; Novartis, East Hanover, NJ) photodynamic therapy (PDT) on experimental choroidal neovascularization in the monkey eye. METHODS: Choroidal neovascularization was induced by laser injury in both eyes of cynomolgus monkeys and followed with weekly fundus photography and fluorescein angiography. Two weeks after induction, weekly treatments were initiated. These treatments included using either an intravitreal injection of ranibizumab (previously known as rhuFabV2) in combination with verteporfin PDT or a ranibizumab vehicle (placebo) in combination with verteporfin PDT (PDT only). Six animals (group 1) initially received intravitreal injections followed 1 week later by PDT. Four animals (group 2) initially received PDT followed 1 week later by intravitreal injection. Two animals (group 3) received injections and PDT on the same day at 2-week intervals. Photodynamic therapy was applied in all 3 groups every 2 weeks for 3 treatments with follow-up through 2 weeks after the last PDT treatment. Fluorescein angiograms were graded using a masked standardized protocol. The data were analyzed using the McNemar chi(2) test for matched pairs. RESULTS: No choroidal neovascularization leakage was observed in the eyes of animals treated with ranibizumab and PDT at day 21 or 42 after the start of the first treatment. Leakage persisted in eyes treated with PDT alone at 21 days (3 of 12 eyes) and 42 days (2 of 12 eyes). At all time points studied, the ranibizumab and PDT-treated eyes experienced better angiographic outcomes than the eyes receiving PDT alone. CONCLUSION: These preliminary data indicate that an intravitreal ranibizumab injection in combination with verteporfin PDT (ranibizumab and PDT) causes a greater reduction in angiographic leakage than PDT and intravitreal vehicle injection (PDT only) in experimental choroidal neovascularization. CLINICAL RELEVANCE: This combination therapy can potentially offer a new treatment modality for choroidal neovascularization in patients with macular degeneration and other diseases.

Animals↗

Mechanisms of age-related macular degeneration.

AMD is a poorly understood disease at this time. Since it is the leading cause of blindness in the elderly in the developed world, there is a pressing need for better treatment. Therefore, there is extensive ongoing research in both pathogenesis and therapy of AMD. Epidemiological studies have shown significant risk associated with increasing age and cigarette smoking, future studies may identify environmental risk factors though at present studies have been inconclusive. Genetic studies may identify subgroups of disease and thus help provide a selective approach to treatment. The vascular model of AMD may provide better understanding of the blood flow and post capillary resistance and help in early and newer intervention in the disease. Vascular endothelial growth factor has been extensively studied in choroidal neovascularization. It has been demonstrated in human and animal models of CNV and VEGF antagonists are currently in clinical trial. Extensive work is ongoing to prevent and treat CNV with antiangiogenic agents.

Humans↗