Ocular safety comparison of non-steroidal anti-inflammatory eye drops used in pseudophakic cystoid macular edema prevention

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• 作者：Anxo Ferná ; ndez-Ferreiro^a ; ^b ; ^g ; Marí ; a Santiago-Varela^c ; Marí ; a Gil-Martí ; nez^c ; Tomas Garcí ; a-Caballero Parada^d ; Marí ; a Pardo^e ; Miguel Gonzá ; lez-Barcia^b ; ^g ; Antonio Piñ ; eiro-Ces^c ; Marí ; a Teresa Rodrí ; guez-Ares^c ; José ; Blanco-Mendez^a ; ^f ; M.J. Lamas^b ; ^g ; Francisco J. Otero-Espinar^a ; ^f ; ^{Francisco.otero@usc.es" class="auth_mail" title="E-mail the corresponding author}
• 关键词：PCME ; pseudophakic cystoid macular edema ; NSAID ; non-steroidal anti-inflammatory drug ; WST-1 ; water soluble tetrazolium salts assay ; RTCA ; xCELLigence Real-Time Cell Analyzer System ; HET-CAM ; Hen&rsquo ; s Egg Test-chorioallantoic membrane ; CAM ; vasculated chorioallantoic membranes ; KCH ; human corneal keratocytes ; CI ; cell index ; NCI ; normal cell index ; WHA ; wound healing assay ; IS ; irritation score ; OCT ; original concentration of eye drops
• 刊名：International Journal of Pharmaceutics
• 出版年：2015
• 出版时间：30 November 2015
• 年：2015
• 卷：495
• 期：2
• 页码：680-691
• 全文大小：2437 K

文摘

Non-steroidal anti-inflammatory drug (NSAID) eye drops are widely used to treat ocular inflammatory conditions related to ophthalmic surgical procedures, such as pseudophakic cystoid macular edema, and they have been used for off-label treatments. The most commonly used NSAIDs are diclofenac and ketorolac and the new molecules bromfenac and nepafenac have also been used. We used primary human keratocytes in cell culture in combination with a novel technology that evaluates dynamic real-time cytotoxicity through impedance analysis. This study also included classic cell viability tests (WST-1^® and AlamarBlue^®), wound healing assay, Hen’s Egg Test and an ex vivo histopathological assay. NSAIDs were shown to have important cytotoxicities and to retard the healing response. Furthermore, the new eye drops containing bromfenac and nepafenac were more cytotoxic than the more classical eye drops. Nevertheless, no immuno-histochemical changes or acute irritation processes were observed after the administration of any eye drops tested. Due to cytotoxicity and the total absence of discomfort and observable injuries after the administration of these drugs, significant corneal alterations, such as corneal melts, can develop without any previous warning signs of toxicity.