作者： Lit ES,Lu L,Cooke JP,et al.

　　出处：American journal of ophthalmology.2010-05;149(5):839-51.e1.

　　文献类型：临床试验 PUBMED链接：PMID 20189159

　　Abstract：PURPOSE:Stimulation of nicotinic acetylcholine (nACh) receptors on vascular endothelial ce... PURPOSE:Stimulation of nicotinic acetylcholine (nACh) receptors on vascular endothelial cells promotes angiogenesis and vascular permeability in animal models. The safety and bioactivity of topical mecamylamine, an antagonist of nACh receptors, was tested in patients with diabetic macular edema.

　　DESIGN:A multicenter phase I/II clinical trial.METHODS:Twenty-three patients with chronic diabetic macular edema received 1% mecamylamine topically twice daily for 12 weeks, the primary end point. Patients underwent safety assessments, measurement of best-corrected visual acuity (BCVA), and measurement of foveal thickness using optical coherence tomography at baseline, 1, 4, 8, 12, and 16 weeks.

　　RESULTS:Mecamylamine drops were well tolerated and there were no drug-related safety problems. Mean improvement in BCVA at 1, 4, 8, 12, and 16 weeks was 2.8, 1.9, 2.4, 0.8, and 3.1 letters, respectively. There was little change in mean excess foveal thickness. There was substantial heterogeneity in response, because 8 patients showed convincing improvement in BCVA, foveal thickness, or both, 9 patients showed equivocal or no substantial changes, and 4 patients showed worsening. Five patients showed a substantial improvement in BCVA, foveal thickness, or both between their last visit while receiving mecamylamine and 1 month after stopping mecamylamine.

　　CONCLUSIONS:This study suggested that administration of topical mecamylamine, a nonspecific nACh receptor blocker, may have heterogeneous effects in patients with diabetic macular edema. Variable expression of nACh receptor subtypes on endothelial cells that have different effects on permeability would provide an explanation for these results and should be investigated, because more specific nACh receptor blockers may dissociate antipermeability and propermeability effects.

　　中文摘要：

　　目的：血管内皮细胞的烟碱乙酰胆碱(nACh)受体兴奋促进动物模型血管新生和血管通透性增加。检测局部美加明(乙酰胆碱受体拮抗剂)在糖尿病黄斑水肿患者的安全性和生物活性。

　　设计：多中心I / II期临床试验。

　　方法：23位慢性糖尿病黄斑水肿患者接受12周(主要终点)的1%美加明局部治疗，每天两次。对患者进行安全评估，测量最佳矫正视力(BCVA)，光学相干断层扫描测量基线、1、4、8、12和16周黄斑厚度。

　　结果：美加明滴眼液耐受性好，没有药物相关安全性问题。1，4，8，12和16周最佳矫正视力平均提高分别为2.8，1.9，2.4，0.8和3.1。平均黄斑厚度几乎没有增加。但同时存在一定的个体差异，因为8例患者最佳矫正视力或/和黄斑中心凹厚度均有明显的改善，9例变化不明显或没有实质性的变化，4例情况恶化。 5例患者在接受美加明治疗期间最好一次随访和停药后1月后最佳矫正视力、黄斑中心凹厚度明显改善，或两者均有改善。

　　结论：本研究表明，局部美加明(非特异性nACh受体阻断剂)对糖尿病黄斑水肿患者治疗反应不一。nACh受体亚型在内皮细胞的变异表达对渗透性的不同作用可以解释这一结果，并值得进一步研究，因为更多特异性nACh受体阻滞剂可能分离抗通透性和促通透性作用。

　　主题词：Administration, Topical; Adolescent; Adult; Aqueous Humor; Chronic Disease; Diabetic Retinopathy; Enzyme-Linked Immunosorbent Assay; Fluorescein Angiography; Fovea Centralis; Humans; Intraocular Pressure; Macular Edema; Mecamylamine; Nicotinic Antagonists; Tomography, Optical Coherence; Treatment Outcome; Vascular Endothelial Growth Factor A; Visual Acuity;