Macular Degeneration: Venkatraman AS

Moshfeghi AA, Rosenfeld PJ, Puliafito CA, Michels S, Marcus EN, Lenchus JD, Venkatraman AS. · Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida 33136, USA. · Ophthalmology. · Pubmed #17027972 No free full text.

Abstract: PURPOSE: To evaluate the safety, efficacy, and durability of bevacizumab for the treatment of subfoveal choroidal neovascularization (CNV) in patients with neovascular age-related macular degeneration (AMD). DESIGN: Open-label, single-center, uncontrolled clinical study. PARTICIPANTS: Age-related macular degeneration patients with subfoveal CNV (n = 18) and best-corrected visual acuity (VA) letter scores of 70 to 20 (approximate Snellen equivalent, 20/40-20/400). METHODS: Patients were treated at baseline with an intravenous infusion of bevacizumab (5 mg/kg) followed by 1 or 2 additional doses given at 2-week intervals. Safety assessments were performed at all visits. Ophthalmologic evaluations included protocol VA measurements, ocular examinations, and optical coherence tomography (OCT) imaging at each visit. Retreatment with bevacizumab was performed if there was evidence of recurrent CNV. MAIN OUTCOME MEASURES: Assessments of safety and changes from baseline in VA scores and OCT measurements were performed through 24 weeks. RESULTS: No serious ocular or systemic adverse events were identified through 24 weeks. The only adverse event identified was a mild elevation of mean systolic and diastolic blood pressure measurements (+11 mmHg, P = 0.004; +8 mmHg, P<0.001) evident by 3 weeks and easily controlled with antihypertensive medications. By 24 weeks, the systolic and diastolic mean blood pressures were at or below baseline measurements. Visual acuity in the study eyes improved within the first 2 weeks, and by 24 weeks, the mean VA letter score increased by 14 letters in the study eyes (P<0.001), and the mean OCT central retinal thickness measurement decreased by 112 microm (P<0.001). By 24 weeks, retreatment was needed for only 6 of the 18 study eyes, and after retreatment, the recurrent leakage was eliminated, with restoration of any lost VA. CONCLUSIONS: Systemic bevacizumab therapy for neovascular AMD was well tolerated and effective for all 18 patients through 24 weeks. By 6 months, most patients did not require any additional treatment beyond the initial 2 or 3 infusions. Despite these impressive results, it is unlikely that systemic bevacizumab will be studied in a large clinical trial because of the potential risks associated with systemic anti-VEGF therapy and the perception that intravitreal therapy is safer.

Michels S, Rosenfeld PJ, Puliafito CA, Marcus EN, Venkatraman AS. · Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami School of Medicine, Miami, Florida 33136, USA. · Ophthalmology. · Pubmed #15936441 No free full text.

Abstract: PURPOSE: To evaluate the short-term safety of systemic bevacizumab (Avastin, Genentech, Inc., South San Francisco, CA) and its effects on visual acuity (VA) and subfoveal choroidal neovascularization (CNV) in patients with neovascular age-related macular degeneration (AMD). DESIGN: Open-label, single-center, uncontrolled clinical study. PARTICIPANTS: Age-related macular degeneration patients with subfoveal CNV (N = 9) and best-corrected VA letter scores of 70 to 20 (approximate Snellen equivalent, 20/40-20/400). METHODS: Patients were treated at baseline with an infusion of bevacizumab (5 mg/kg), followed by 1 or 2 additional doses given at 2-week intervals. Safety assessments were performed at all visits. Ophthalmologic evaluations included protocol VA measurements and ocular examinations, along with optical coherence tomography (OCT) imaging, fluorescein angiography, and indocyanine green angiography. MAIN OUTCOME MEASUREMENTS: Safety assessments were performed, along with assessments of changes from baseline in VA scores, OCT measurements, and angiographic lesion characteristics. RESULTS: There were no serious ocular or systemic adverse events identified. By 6 weeks, the only adverse event identified was a mild elevation of systolic blood pressure (BP) (+12 mmHg; P = 0.035), and this elevation was controlled by either changing or initiating antihypertensive medication. By 12 weeks, the elevation of systolic BP was no longer significant (P = 0.51). In the study eyes, significant increases in VA were evident within 1 week of treatment, and by 12 weeks, the median and mean VA letter scores increased by 8 letters (P = 0.011) and 12 letters (P = 0.008), respectively. The median and mean central retinal thickness measurements decreased by 157 microm (P = 0.008) and 177 microm (P = 0.001), respectively. In the fellow eyes at 12 weeks, the median and mean VA letter scores increased by 27 letters (P = 0.018) and 16 letters (P = 0.012), and the median and mean central retinal thickness measurements decreased by 59 mum (P = 0.028) and 92 microm (P = 0.06). In all study eyes, angiography revealed a marked reduction or an absence of leakage from CNV. CONCLUSION: Overall, bevacizumab therapy was well tolerated, with an improvement in VA, OCT, and angiographic outcomes. Although these preliminary results are promising, a randomized controlled clinical trial is necessary before concluding that systemic bevacizumab therapy is safe and effective for patients with neovascular AMD.