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Purpose: 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. Case: 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. Results: 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. Conclusions: 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. [ABSTRACT FROM AUTHOR]