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Noriaki Takase, Tsutomu Yasukawa, Aki Kato, Ayae Kubota, Tomoaki Hattori, Yuichiro Ogura; Impacts Of Tissue Plasminogen Activator On Type 2 Choroidal Neovascularization. Invest. Ophthalmol. Vis. Sci. 2012;53(14):2037.
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© ARVO (1962-2015); The Authors (2016-present)
Anti-vascular endothelial growth factor (VEGF) therapies such as intravitreal ranibizumab can effectively suppress development and progression of choroidal neovascularization (CNV). However, they possess little ability to regress once-developed fibrovascular tissue. Tissue plasminogen activator (tPA) is a fibrinolytic compound, utilized as an adjuvant for displacement of submacular hemorrhage. The purpose of this study is to evaluate the impacts of fibrinolysis with tPA on type 2 CNV.
Five eyes of 5 patients with type 2 CNV underwent intravitreal injection of tPA (4x104 IU) combined with intravitreal ranibizumab (IVR). Two of 5 eyes were treatment-naïve. For retreatment, IVR monotherapy was performed. Other 5 eyes of 5 patients with type 2 CNV were treated with IVR only. The ILM-RPE thickness at the thickest point of the subretinal fibrinous and/or fibrovascular tissues as well as macular volume (MV) were measured by optical coherence tomography before and within 1 week after injections of the first IVR and, if any, intravitreal tPA/ranibizumab. Best-corrected visual acuity (BCVA) was recorded periodically.
The mean follow up period was 14.8 months in the combination therapy group and 16.8 months in the monotherapy group. In month 6, total injection number of IVR was 2.8 in eyes with combination therapy and 3.4 in eyes with IVR only. In eyes with the intravitreal injection of tPA/ranibizumab, remarkable regression of subretinal fibrinous and/or fibrovascular tissue was observed even on day 1. In eyes with tPA/ranibizumab, the ILM-RPE thickness at the center of subretinal CNV was significantly decreased 740 μm to 536 μm (P<0.05, paired t-test). The reduction rate was 0.75 in the combination therapy group, significantly lower than 0.96 in the monotherapy group (p=0.002, unpaired t-test). The reduction rate of MV in months 3 and 6 and at the best were 0.77, 0.78, and 0.73 in the combination therapy group, significantly lower than 0.97, 0.99, and 0.90 in the monotherapy group (p<0.05 at each time point, unpaired t-test). In both groups, the average of best BCVA was significantly improved from the baseline: -0.27 in the combination therapy group, -0.20 in the monotherapy group (P<0.05) in the logarithm of minimum angle of resolution unit.
These results suggested that tPA had a specific ability to regress once-formed subretinal fibrinous and/or fibrovascular tissues in eyes with type 2 CNV. This effect was not observed after IVR only. The combination therapy of tPA and an anti-VEGF drug may synergistically reduce exudative change and be a new treatment modality for the treatment of type 2 CNV itself as well as submacular hemorrhage.
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