Triple therapy for neovascular age-related macular degeneration using single-session photodynamic therapy combined with intravitreal bevacizumab and triamcinolone.

AIM: To evaluate the efficacy and safety of triple therapy consisting single-session photodynamic therapy (PDT), intravitreal bevacizumab (IVB) and intravitreal triamcinolone (IVTA) for treatment of neovascular age-related macular degeneration (AMD) METHODS: Consecutive patients with subfoveal choroidal neovascularisation (CNV) secondary to AMD were treated with PDT using a standard protocol immediately followed by 1.25 mg of IVB and 4 mg of IVTA. 1.25 mg of IVB was given at 3 months for residual leakage. Best-corrected Snellen visual acuity (BCVA) and fluorescein angiography (FA) were performed prior to treatment. BCVA, intraocular pressure (IOP) and presence of vitritis were documented at 1 and 6 weeks, 3 and 6 months. FA was repeated at 3 and 6 months. Outcome measures included visual improvement measured by logMAR equivalent, angiographic evident of leakage and safety profile. RESULTS: 36 eyes of 33 patients, aged 76.4 (SD 10.5) years with mean follow-up of 14.7 (6.9-19.2) months were analysed. Baseline logMAR acuity was 1.22 (0.71). The mean logMAR acuity was 1.14 (0.62) and 1.18 (0.63) at 3 and 6 months respectively. At 6 months, 61.1% (22/36) showed stable or gaining vision, and 27.8% (10/36) gained three or more lines. Twenty-eight eyes (77.8%) achieved CNV resolution by single session of triple therapy. One eye lost more than six lines due to retinal pigment epithelium rip, three eyes showed a significant cataract requiring surgery, and two showed persistent raised IOP at 6 months. None resulted in endophthalmitis or reported thromboembolic event. CONCLUSIONS: Short-term results of single session triple therapy suggested that it might be a useful treatment option for neovascular AMD based on its low retreatment rates, sustainable CNV eradication result and visual gain achievement. However, the risk and benefits of using intravitreal triamcinolone in addition to combined PDT and IVB warrant further evaluation.

Mitotic arrest and enhanced nuclear protein phosphorylation in human leukemia K562 cells by okadaic acid, a potent protein phosphatase inhibitor and tumor promoter.

We investigated the effects of the non-phorbol tumor promoter okadaic acid on human leukemia K562 cells. It was found that okadaic acid potently and reversibly inhibited cell growth, with a nearly complete inhibition of thymidine uptake seen at about 10 nM. The cytotoxicity of okadaic acid was characterized by a marked mitotic arrest of the cells exhibiting scattered chromosomes and abnormal anaphase-like structures, a phenomenon distinct from the typical metaphase arrest caused by colchicine. Okadaic acid (10-1,000 nM) greatly stimulated phosphorylation of a number of nuclear proteins in K562 cells. Phosphorylation of many of the same proteins was also stimulated by 12-O-tetradecanoylphorbol-13-O-acetate, a protein kinase C activator. The present findings, consistent with recent reports that okadaic acid is a potent inhibitor of protein phosphatases 1 and 2A (PP1 and PP2A) shown to be essential for normal mitosis, provided evidence for the first time that okadaic acid inhibition of PP1/PP2A resulted in enhanced nuclear protein phosphorylation and subsequent mitotic arrest.