Department of Ophthalmology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
J Ocul Pharmacol Ther. 2011 Oct;27(5):519-23. doi: 10.1089/jop.2011.0036. Epub 2011 Sep 21.
The purpose of this study was to report a case hypersensitive to topical bimatoprost and dexamethasone, but with no responsiveness to both latanoprost and travoprost.
A 41-year-old Chinese female presented with unilateral glaucoma secondary to iridocyclitis and long-term use of topical steroid. Trabeculectomy only worked for 9 months and then additional topical glaucoma medications were required to control the intraocular pressure (IOP). All commonly used IOP-lowering medications failed, except for bimatoprost, which significantly lowered the IOP. Topical dexamethasone increased IOP and caused ocular hypertension. Ultrasound biomicroscopy (UBM) was used to evaluate the anterior segment of the affected eye. Genomic DNA was extracted for sequence analysis of gene of prostaglandin F receptor (FP), E receptor 1 (EP1) and 2 (EP2) and myocilin.
UBM revealed cyclodialysis in the patient's affected eye after a single dosage of bimatoprost. The cyclodialysis resolved when IOP was elevated with the topical use of dexamethasone. The dexamethasone-induced high IOP could only be controlled by bimatoprost, whereas the bimatoprost-induced low IOP could only be elevated by topical dexamethasone. Allele C of rs3753380 and allele A of rs3766355 in FP gene and a -224T>C variation of myocilin gene were found in this patient. In addition, a novel heterozygous Cys346Tyr mutation was identified in EP2 gene. No sequence variation was found in EP1 gene.
The hypersensitivity of the affected eye to topical bimatoprost may be a result, at least in part, of cyclodialysis. The sequence analysis results suggested that, besides the polymorphism of FP gene, there might be some other mechanisms underlying the irresponsiveness of this patient to both latanoprost and travoprost. The mechanisms underlying the bimatoprost-induced cyclodialysis might correlate with its receptor selectivity. The -224T>C variation in the myocilin gene may affect the regulation of expression of this gene by dexamethasone.
本研究旨在报告一例对局部比马前列素和地塞米松均高度敏感，但对拉坦前列素和曲伏前列素均无反应的病例。
一名 41 岁中国女性因虹膜睫状体炎和长期使用局部类固醇继发单侧青光眼而就诊。小梁切除术仅维持了 9 个月，随后需要额外的局部降眼压药物来控制眼内压（IOP）。除比马前列素外，所有常用的降眼压药物均无效，而比马前列素显著降低了 IOP。局部地塞米松升高了 IOP 并导致了高眼压。超声生物显微镜（UBM）用于评估受影响眼的前段。提取基因组 DNA 用于前列腺素 F 受体（FP）、E 受体 1（EP1）和 2（EP2）和肌球蛋白基因的序列分析。
UBM 显示患者单剂量使用比马前列素后受影响眼出现睫状体分离。当局部使用地塞米松升高 IOP 时，睫状体分离得到解决。地塞米松诱导的高眼压只能用比马前列素控制，而比马前列素诱导的低眼压只能用局部地塞米松升高。在该患者中发现 FP 基因的 rs3753380 等位基因 C 和 rs3766355 等位基因 A 以及肌球蛋白基因的-224T>C 变异。此外，还在 EP2 基因中鉴定出一种新的杂合 Cys346Tyr 突变。EP1 基因未发现序列变异。
受影响眼对局部比马前列素的高度敏感可能至少部分是由于睫状体分离所致。序列分析结果表明，除 FP 基因多态性外，该患者对拉坦前列素和曲伏前列素均无反应可能还有其他机制。比马前列素诱导的睫状体分离的机制可能与其受体选择性有关。肌球蛋白基因的-224T>C 变异可能影响该基因受地塞米松的表达调控。
