Bevacizumab for neovascular ocular diseases.

OBJECTIVE: To review the efficacy and safety of off-label use of bevacizumab for neovascular ocular diseases. DATA SOURCES: A PubMed (1966-January 2007) search was conducted using the terms human, intravitreal, bevacizumab, macular, and retinopathy. Meeting abstracts from the American Academy of Ophthalmology, Retina Society, Macula Society, and Association for Research in Vision and Ophthalmology were reviewed. STUDY SELECTION AND DATA EXTRACTION: Controlled studies, unpublished reports involving 100 or more subjects, and published reports describing 5 or more subjects were reviewed. Only English-language articles were considered. DATA SYNTHESIS: Intravitreal bevacizumab has been evaluated in 133 patients in unpublished controlled studies. Over 3500 patients have been evaluated in open-label studies with duration of follow-up ranging from 3 months to 1 year. The most common use was neovascular age-related macular degeneration (AMD). Other conditions studied included diabetic retinopathy, pathological myopia, neovascular glaucoma, and macular edema due to diabetes, retinal vein occlusion, or uveitis. Statistically significant improvements in visual acuity, as well as decreases in retinal thickness and the extent of choroidal neovascularization, were noted. Intravitreal bevacizumab was well tolerated over the short term. In a registry compiling adverse experiences of 7113 intravitreal injections, rates of adverse events were less than or equal to 0.21%. CONCLUSIONS: Uncontrolled studies support a benefit of intravitreal bevacizumab in neovascular AMD for 3 months to 1 year. Low cost is a significant advantage of bevacizumab. Patients should discuss the potential risks and benefits of intravitreal bevacizumab and other available therapies with their physicians before receiving treatment. Controlled trials are needed to characterize the safety and efficacy of intravitreal bevacizumab and determine the optimal treatment regimen.

Intrathecal ziconotide for refractory chronic pain.

OBJECTIVE: To describe the pharmacology, efficacy, and safety of ziconotide for treatment of severe chronic pain in patients who are candidates for intrathecal therapy. DATA SOURCES: A PubMed/MEDLINE search (1966-June 2006) was conducted using the terms ziconotide, Prialt, and SNX-111. Manufacturer-provided data, the Food and Drug Administration medical review of ziconotide, and abstracts presented at American Pain Society meetings (2001-2006) were also reviewed. STUDY SELECTION AND DATA EXTRACTION: Human studies evaluating the efficacy and safety of ziconotide for the treatment of chronic pain were considered. Animal data were excluded. DATA SYNTHESIS: Ziconotide is the first and only neuronal-type (N-type) calcium-channel blocker. Ziconotide must be administered intrathecally via continuous infusion. A programmable implanted variable-rate microinfusion device, or an external microinfusion device and catheter must be utilized. In double-blind, placebo-controlled studies, ziconotide significantly improved patient perception of pain from baseline to the end of the study periods, which ranged from 11 to 21 days. Patients enrolled in clinical trials were intolerant of or refractory to other treatment modalities. There have been no studies that directly compared ziconotide with other intrathecal or systemic analgesics. Key ziconotide-related adverse events are neuropsychiatric, including depression, cognitive impairment, and hallucinations; depressed levels of consciousness; and elevation of creatine kinase levels. Ziconotide is also associated with a risk of meningitis due to possible contamination of the microinfusion device. CONCLUSIONS: Ziconotide is a therapeutic option for treatment of severe chronic pain in patients who have exhausted all other agents, including intrathecal morphine, and for whom the potential benefit outweighs the risks of serious neuropsychiatric adverse effects and of having an implanted device. Further studies are needed to determine the comparative efficacy of ziconotide and other pain therapies.