Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ranibizumab therapy is the first treatment for neovascular AMD to improve vision for most patients. The benefits apply to all angiographic subtypes of neovascular AMD and across all lesion sizes. Although the pivotal phase III trials (MARINA and ANCHOR) used monthly injections of ranibizumab for 2 years, the ongoing PIER, PrONTO, and SAILOR trials are investigating less frequent dosing regimens, and preliminary results from the PrONTO study suggest that fewer injections will most likely result in visual acuity improvements similar to the results from the phase III trials. When comparing the ANCHOR results with the FOCUS results, it also becomes apparent that the combination of ranibizumab with PDT does not necessarily result in better visual acuity outcomes, and the use of PDT may even reduce the visual acuity benefits achieved with ranibizumab alone (see Figs. 1-3). It seems unlikely that combination therapy provides any significant advantage over ranibizumab alone unless the combination of PDT and ranibizumab can decrease the need for frequent retreatment. The results from the PrONTO Study already suggest that less frequent treatment with ranibizumab is possible by using a variable dosing regimen with OCT. Ranibizumab also seems to be safe, with the 2-year MARINA data showing no increase in the incidence of systemic adverse events that could be associated with anti-VEGF therapy, such as myocardial infarction and stroke. There was a hint of a safety concern, however, in the pooled 1-year safety results from the MARINA and ANCHOR trials. Although the combined rate of myocardial infarction and stroke during the first year of the ANCHOR and MARINA trials was similar in the control and the 0.3-mg ranibizumab arms (1.3% and 1.6% respectively), these adverse events were slightly higher in the 0.5-mg ranibizumab arm (2.9%). These differences are not statistically significant, however, and probably do not represent a dose-dependent increase in risk because the 2-year results from the MARINA trial with the same monthly injection regimen showed no increased risk of thromboembolic events. In December 2005, Genentech submitted a Biologics License Application to the FDA for the use of ranibizumab in the treatment of neovascular wet AMD based on 1-year clinical efficacy and safety data from the two pivotal phase III trials, ANCHOR and MARINA, and the phase I-II FOCUS trial. Genentech has been granted a 6-month Priority Review from the FDA with a decision anticipated 6 months from the December submission date or by the end of June 2006 [29]. By the summer of 2006, this revolutionary therapy should be available for the treatment of neovascular AMD. At that time, the major dilemma facing most retina specialists will be whether to use intravitreal ranibizumab or intravitreal bevacizumab, the low cost alternative, for the treatment of neovascular AMD.
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PMID:Ranibizumab: Phase III clinical trial results. 1693 11

Ranibizumab (Lucentis), a recombinant monoclonal antibody, blocks all active forms of vascular endothelial growth factor A and was the first treatment for age-related macular degeneration shown to improve visual acuity in a substantial percentage of patients rather than slowing visual loss. Bevacizumab (Avastin) has a similar action, is related to the ranibizumab compound with respect to its structure, but has not been approved by the FDA for intravitreal use and therefore must be utilized only in an off-label setting. While ranibizumab was approved by the FDA at a dose of 0.5 mg per intravitreal injection, the manufacturer recently issued a letter to physicians warning of the increased risk of stroke at the FDA-approved dose as compared to a lower studied dose of 0.3 mg. An interim analysis of the ongoing SAILOR study revealed a 1.2% risk of stroke in the 0.5 mg arm versus 0.3% in the 0.3 mg arm (p = 0.02). It is unclear whether the trend toward a higher risk of stroke in patients receiving 0.5 mg dose of ranibizumab would persist in the final analysis, but details such as causality, topography, and severity of stroke in the SAILOR study should also be delineated. The risks of intraocular use of bevacizumab remain largely unknown at this time.
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PMID:Intravitreal ranibizumab and bevacizumab: a review of risk. 1776 46

(1) Due to a lack of any better alternatives, photodynamic therapy is the standard treatment for subfoveal lesions due to neovascular age-related macular degeneration (AMD). It consists of intravenous injection of a photosensitizer, verteporfin, followed by local red laser activation. This treatment, sometimes repeated every 3 months, stabilises the loss of visual acuity for 2 years in about 50% of patients. Adverse effects are generally acceptable. (2) Ranibizumab is an antibody fragment targeting vascular endothelial growth factor (VEGF). VEGF is implicated in the neovascularisation involved in age-related macular degeneration. Ranibizumab is injected into the vitreous in the same way as pegaptanib, the first VEGF antagonist to be approved for an ocular indication. (3) Clinical evaluation of ranibizumab includes 2 placebo-controlled trials (900 patients in total), a trial versus verteporfin (423 patients), and a trial testing ranibizumab in combination with verteporfin (162 patients). More than 90% of patients treated with ranibizumab in these two trials had no tangible loss of vision for one to two years, compared to about 68% of patients treated with verteporfin (statistically significant difference). These trials did not attempt to determine the optimal interval between intravitreal injections. (4) No trials have directly compared ranibizumab with pegaptanib; indirect comparisons suggest that ranibizumab is better than pegaptanib. (5) Intravitreal injection of ranibizumab can have local adverse effects, similar to pegaptanib. These include inflammatory reactions, infections, and elevated intraocular pressure. Arterial thromboses at distant sites, in particular strokes, have been reported with ranibizumab, at a higher frequency with 0.5 mg per infection (about 1%) than with 0.3 mg per injection. (6) When visual acuity continues to deteriorate in patients with age-related macular degeneration despite treatment with verteporfin, ranibizumab provides an effective alternative for patients with no particular risk factors for stroke.
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PMID:Ranibizumab: new drug. Macular degeneration: second-line use due to risks. 1835 41

A 55-year-old male presented with serous retinal detachment over 3 months in his right eye. His left eye was blind due to retinal pigment epithelium detachment since 1997 with atrophy of the neurosensory retina. Fluorescein angiography had previously shown bilateral polypoidal choroidal vasculopathy (PCV). Optical coherence tomography (OCT) confirmed PCV with central involvement. The patient underwent intravitreal injections of 6x Lucentis, 4x Avastin and one injection of aflibercept. PCV recurred from 1 to 4 months after each treatment. The patient had history of stroke, hypertension, and atrial fibrillation and was started on oral eplerenone 25 mg/day in October 2014, which resulted in a long-term ongoing complete retinal reattachment. OCT ganglion cell and inner plexiform layers showed full recovery of the fovea in the right eye and irreversible in the left eye. Low-dose eplerenone may resolve recalcitrant PCV with central involvement. The duration of treatment remains uncertain.
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PMID:Long-term Resolution of Blinding Polypoidal Choroidal Vasculopathy with Recurrent Bilateral Central Involvement by Low-dose Oral Eplerenone Treatment. 2716 59