SEP 2012

EyeWorld is the official news magazine of the American Society of Cataract & Refractive Surgery.

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Page 87 of 103

88 EW RESIDENTS September 2012 Review of "Effects of tamsulosin and silodosin on isolated albino and pigmented rabbit iris dilators: by Daniel L. Chao, M.D., Yasha S. Modi, M.D., Bradford Lee, M.D., Jayanth Sridhar, M.D., Ajay E. Kuriyan M.D., and Steven J. Gedde, M.D., Bascom Palmer Eye Institute, Miami, Fla. Steven J. Gedde, M.D. This month, an important paper on the mechanism of IFIS appears in JCRS. I invited the Bascom Palmer residents to review it, and their analysis will help our clinician readers to better understand the findings and their significance. —David F. Chang, M.D., EyeWorld chief medical editor The residents from Bascom Palmer Eye Institute Source: Steven J. Gedde, M.D. Effects of tamsulosin and silodosin on isolated albino and pigmented rabbit iris dilators: Possible mechanism of intraoperative floppy-iris syndrome Toshiaki Goseki, M.D., Hitoshi Ishikawa, M.D., Shiori Ogasawara, M.S., Kimiyo Mashimo, B.S., Noriko Nemoto, B.S., Yuko Taguchi, M.S., Kazuo Yago, Ph.D., Kimiya Shimizu, M.D. J Cataract Refract Surg (September) 2012; 38: 1643-1649 Purpose: To determine the mechanism of intraoperative floppy-iris syndrome (IFIS) by examining the binding affinity of tamsulosin and silodosin to α-receptors and melanin pigment using control and α2-blocker chronically administered in rabbit models. Setting: Department of Ophthalmology, Kitasato University School of Medicine, Kanagawa, Japan. Design: Experimental study. Methods The study was performed in isolated albino and pigmented rabbit iris dilators using pharmacologic and morphologic examinations. Results: For pharmacologic examinations, the mean pKB values (pKB = −log KB, where −log KB is the equilibrium dissociation constant of the antagonist-receptor complex) of tamsulosin in albino and pigmented rabbits were 9.10 and 8.08 and those of silodosin, 10.3 and 8.11, respectively. The pKB values of tamsulosin and silodosin in albino rabbits were significantly higher than in pigmented rabbits. In the isolated rabbit iris dilator, the maximum contrac- tion evoked by 10−3 mol/L phenylephrine gradually decreased by repetitive application in the chronic α-blocker-ad- ministered models. For morphologic examinations, the sizes of the pigment granules of pigment epitheliums for the α-blocker-administered models were irregular. The shape of shared nucleus of dilator muscles and pigment epitheli- ums changed to lobular, and the dilator muscle layer was thinner than in the control. Conclusions: The high affinity of α-blockers for α1-adrenoreceptors is important in the analysis of the mecha- nism of IFIS. However, IFIS should not be attributed to long-term binding with receptors alone; the drug-melanin interaction causing dilator muscle atrophy is probably the other important factor in the mechanism of IFIS. Financial disclosure: No author has a financial or proprietary interest in any material or method mentioned. I ntraoperative floppy iris syndrome (IFIS) is a recently described condition that may present significant challenges during cataract surgery. IFIS is defined by three intraoperative fea- tures: billowing of the iris stroma in response to intraocular microfluidic currents, an increased tendency for the iris to prolapse through the phaco and/or sideport incisions, and an abnormal predisposition toward progressive intraoperative miosis de- spite standard techniques for pre-op dilation.1,2 IFIS has been strongly associated with use of α1 adrenergic antagonists, medications commonly used to treat benign prostatic hyper- plasia. This association is particu- larly strong with tamsulosin, a long-acting α1A receptor antagonist. The pathophysiology of tamsulosin- mediated IFIS remains poorly under- stood. Because of the long half-life of tamsulosin, one hypothesis is that prolonged α1A receptor blockade may lead to chronic inhibition of the iris dilator muscle with resultant "disuse atrophy." Both cadaveric and anterior segment ocular coherence tomography (OCT) studies have demonstrated significantly de- creased iris dilator muscle thickness in eyes of patients who previously

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