Macular Degeneration: Avery RL

Pieramici DJ, Avery RL. · The California Retina Consultants and Research Foundation, 515 East Micheltorena St, Suite C, Santa Barbara, California 93103, USA. · Expert Opin Biol Ther. · Pubmed #17049020 No free full text.

Abstract: Vascular endothelial growth factor (VEGF)-A is a major regulator of angiogenesis and vascular permeability implicated in the development of diseases involving pathological angiogenesis and increased vascular permeability, such as neovascular age-related macular degeneration (AMD). LUCENTIS (ranibizumab), a humanized antigen-binding fragment (Fab) that neutralizes all VEGF-A isoforms and their biologically active degradation products, was recently approved by the FDA. Ranibizumab is the first FDA-approved treatment for neovascular AMD that maintains or improves vision in > or = 90% patients and provides a > or = 15-letter improvement in visual acuity for a quarter to a third of patients with all choroidal neovascularisation subtypes. Ranibizumab was associated with a < or = 1.7% rate of key serious ocular adverse events, such as endophthalmitis and uveitis, in two pivotal Phase III trials.

Pieramici DJ, Rabena M, Castellarin AA, Nasir M, See R, Norton T, Sanchez A, Risard S, Avery RL. · California Retina Consultants and Research Foundation, Santa Barbara, California 93103, USA. · Ophthalmology. · Pubmed #18708258 No free full text.

Abstract: PURPOSE: Assessment of biological effect, visual acuity changes, and safety of intravitreal (IVT) ranibizumab in patients with macular edema associated with perfused central retinal vein occlusion (CRVO). DESIGN: Ongoing, prospective, open-label, single-center, uncontrolled study. PARTICIPANTS: Ten adult patients with macular edema associated with perfused CRVO. METHODS: Patients were randomly assigned to receive 3 monthly IVT injections of either 0.3 or 0.5 mg ranibizumab (n = 5 at each dose). Additional injections were administered quarterly as needed over the ensuing 21 months at the physician's discretion for recurrent or persistent macular edema. MAIN OUTCOME MEASURES: The predetermined primary endpoint was the percentage of patients gaining >or=15 letters of best-corrected Early Treatment of Diabetic Retinopathy Study visual acuity (BCVA). The secondary endpoints include the mean change in BCVA and central retinal thickness (CRT) measured by optical coherence tomography, the rate of progression to ischemic CRVO, extent of intraocular hemorrhage, retinal vein diameter, optic nerve head swelling, and the incidence and severity of ocular and nonocular adverse events. RESULTS: After 3, 6, and 9 months of follow-up, 40%, 10%, and 30% of patients, respectively, gained >or=15 letters in BCVA; mean BCVA improved by 12+/-20 letters, 3+/-21 letters, and 1+/-24 letters, respectively, compared with baseline; CRT showed a mean decrease of 272+/-244 microm, 88+/-178 microm, and 119+/-153 microm, compared with baseline. No significant differences were observed between the 0.3- and 0.5-mg doses. Most patients experienced decreases in the extent of retinal hemorrhage, retinal vein diameter, and optic nerve head swelling at months 3 and 6 compared with baseline. No patients progressed to ischemic CRVO or experienced a severe adverse event that was attributed to ranibizumab. CONCLUSIONS: Ranibizumab is generally well-tolerated and may improve BCVA and decrease CRT. The improvements in BCVA and CRT observed during the initial monthly injection period (0 to 3 months) were possibly lost to the recurrence of macular edema in between ranibizumab injection during the quarterly treatments (3 to 9 months). The extent of retinal hemorrhage, retinal vein diameter, and nerve swelling continued to normalize for most of the patients from baseline to 6 months. Follow-up is ongoing, and alternative dosing regimens are being evaluated.

Rabena MD, Pieramici DJ, Castellarin AA, Nasir MA, Avery RL. · California Retina Consultants and Research Foundation, Santa Barbara, CA 93103, USA. · Retina. · Pubmed #17420692 No free full text.

Abstract: PURPOSE: To report the authors' experience after intravitreal bevacizumab (Avastin, Genentech) injection in patients with macular edema (ME) secondary to branch retinal vein occlusive disease (BRVO). METHODS: A consecutive retrospective review of patients with ME secondary to BRVO who were treated with intravitreal bevacizumab (1.25 mg/0.05 mL). Patients underwent complete ophthalmic evaluation, which included nonstandardized Snellen visual acuity testing, optical coherence tomography (OCT), and/or angiographic testing at baseline and follow-up visits. RESULTS: There were 27 consecutive patients who received intravitreal bevacizumab injections. The mean length of follow-up was 5.3 months (median 6 months, range 3-8 months). The mean visual acuity improved from 20/200(-) at baseline to 20/100(-) at 1 month and 20/100(+) at 3 months and last follow-up (P < 0.001). The mean central 1 mm macular thickness was 478 microm at baseline and decreased to 310, 336, and 332 microm at 1 month, 3 months, and last follow-up (P < 0.001). Patients received an average of two injections (range one to three). No adverse side effects were observed following injections. CONCLUSION: The observed anatomic (by ophthalmic examination, OCT, and/or fluorescence angiography) and visual acuity improvements and lack of serious adverse side effects after intravitreal bevacizumab injection demonstrates, in principle, the potential of bevacizumab for the treatment of ME in this setting.

Pieramici DJ, Avery RL, Castellarin AA, Nasir MA, Rabena M. · California Retina Consultants and Research Foundation, Santa Barbara, California 93103, USA. · Retina. · Pubmed #16963867 No free full text.

This publication has no abstract.

Shahar J, Avery RL, Heilweil G, Barak A, Zemel E, Lewis GP, Johnson PT, Fisher SK, Perlman I, Loewenstein A. · Department of Ophthalmology, Tel-Aviv Medical Center, Israel. · Retina. · Pubmed #16508424 No free full text.

Abstract: PURPOSE: Intravitreal bevacizumab (Avastin; Genentech Inc., San Francisco, CA) is a new treatment for age-related macular degeneration. The aim of this study was to evaluate retinal penetration and toxicity of bevacizumab. METHODS: Ten albino rabbits were injected intravitreally with 0.1 mL (2.5 mg) of Avastin into one eye and 0.1 mL saline into the fellow eye. The electroretinogram (ERG) was recorded after 3 hours, 3 days, and 1, 2, and 4 weeks. The visual evoked potential (VEP) was recorded after 4 weeks. Confocal immunohistochemistry was used to assess retinal penetration. RESULTS: The ERG responses of the control and experimental eyes were similar in amplitude and pattern throughout the follow-up period. The flash VEP responses of the experimental eyes were of normal pattern and amplitude and did not differ from those recorded by stimulation of the control eye alone. Full thickness retinal penetration was present at 24 hours and was essentially absent at 4 weeks. CONCLUSIONS: Bevacizumab was found to be nontoxic to the retina of rabbits based on electrophysiologic studies. Full thickness retinal penetration may explain observed clinical effects of intravitreal bevacizumab. Although it is difficult to directly extrapolate to humans, our study supports the safe use of intravitreal bevacizumab injection.

Avery RL, Pieramici DJ, Rabena MD, Castellarin AA, Nasir MA, Giust MJ. · California Retina Consultants, Santa Barbara, California 93103, USA. · Ophthalmology. · Pubmed #16458968 No free full text.

Abstract: PURPOSE: To report the short-term safety, biologic effect, and a possible mechanism of action of intravitreal bevacizumab in patients with neovascular age-related macular degeneration (AMD). DESIGN: Interventional, consecutive, retrospective case series. PARTICIPANTS: Eighty-one eyes of 79 patients with subfoveal neovascular AMD. METHODS: Patients received intravitreal bevacizumab (1.25 mg) on a monthly basis until macular edema, subretinal fluid (SRF), and/or pigment epithelial detachment (PED) resolved. Ophthalmic evaluations included nonstandardized Snellen visual acuity (VA), complete ophthalmic examination, fluorescein angiography, and optical coherence tomography (OCT). MAIN OUTCOME MEASURES: Assessments of safety, changes in Snellen VA, OCT retinal thickness, and angiographic lesion characteristics were performed. RESULTS: No significant ocular or systemic side effects were observed. Most patients (55%) had a reduction of >10% of baseline retinal thickness at 1 week after the injection. At 4 weeks after injection, 30 of 81 eyes demonstrated complete resolution of retinal edema, SRF, and PEDs. Of the 51 eyes with 8 weeks' follow-up, 25 had complete resolution of retinal thickening, SRF, and PEDs. At 1, 4, 8,and 12 weeks, the mean retinal thickness of the central 1 mm was decreased by 61, 92, 89, and 67 mum, respectively (P<0.0001 for 1, 4, and 8 weeks and P<0.01 for 12 weeks). At 4 and 8 weeks, mean VA improved from 20/200 to 20/125 (P<0.0001). Median vision improved from 20/200 to 20/80(-) at 4 weeks and from 20/200 to 20/80 at 8 weeks. CONCLUSIONS: Short-term results suggest that intravitreal bevacizumab (1.25 mg) is well tolerated and associated with improvement in VA, decreased retinal thickness by OCT, and reduction in angiographic leakage in most patients, the majority of whom had previous treatment with photodynamic therapy and/or pegaptanib. Further evaluation of intravitreal bevacizumab for the treatment of choroidal neovascularization is warranted.

Avery RL. · No affiliation provided · Lancet. · Pubmed #17964341 No free full text.

This publication has no abstract.