title: Ocular safety comparison of non-steroidal anti-inflammatory eye drops used in pseudophakic cystoid macular edema prevention.
abstract: 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.
authors.affiliation: Pharmacy and Pharmaceutical Technology Department, Faculty of Pharmacy, University of Santiago de Compostela (USC), Praza Seminario de Estudos Galegos s/n, Santiago de Compostela 1570, Spain; Pharmacy Department, Xerencia de Xestión Integrada de Santiago de Compostela, SERGAS, Travesía Choupana s/n, Santiago de Compostela 15706, Spain; Clinical Pharmacology Group, Health Research Institute of Santiago de Compostela (IDIS-ISCIII), SERGAS, Travesía da Choupana s/n, Santiago de Compostela 15706, Spain.
authors.forename: Anxo
authors.initials: A
authors.lastname: Fernández-Ferreiro
authors.affiliation: Ophthalmology Department, Xerencia de Xestión Integrada de Santiago de Compostela, SERGAS, Rua Ramón Baltar s/n, Santiago de Compostela 15706, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Santiago-Varela
authors.affiliation: Ophthalmology Department, Xerencia de Xestión Integrada de Santiago de Compostela, SERGAS, Rua Ramón Baltar s/n, Santiago de Compostela 15706, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Gil-Martínez
authors.affiliation: Pathological Anatomy Department, Xerencia de Xestión Integrada de Santiago de Compostela, SERGAS, Travesía Choupana s/n, Santiago de Compostela 15706, Spain.
authors.forename: Tomas García-Caballero
authors.initials: TG
authors.lastname: Parada
authors.affiliation: Obesidomic Group Instituto de Investigación Sanitaria (IDIS-ISCIII), SERGAS, Travesía da Choupana s/n, Santiago de Compostela 15706, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Pardo
authors.affiliation: Pharmacy Department, Xerencia de Xestión Integrada de Santiago de Compostela, SERGAS, Travesía Choupana s/n, Santiago de Compostela 15706, Spain; Clinical Pharmacology Group, Health Research Institute of Santiago de Compostela (IDIS-ISCIII), SERGAS, Travesía da Choupana s/n, Santiago de Compostela 15706, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: González-Barcia
authors.affiliation: Ophthalmology Department, Xerencia de Xestión Integrada de Santiago de Compostela, SERGAS, Rua Ramón Baltar s/n, Santiago de Compostela 15706, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Piñeiro-Ces
authors.affiliation: Ophthalmology Department, Xerencia de Xestión Integrada de Santiago de Compostela, SERGAS, Rua Ramón Baltar s/n, Santiago de Compostela 15706, Spain.
authors.forename: María Teresa
authors.initials: MT
authors.lastname: Rodríguez-Ares
authors.affiliation: Pharmacy and Pharmaceutical Technology Department, Faculty of Pharmacy, University of Santiago de Compostela (USC), Praza Seminario de Estudos Galegos s/n, Santiago de Compostela 1570, Spain; Industrial Pharmacy Institute, Faculty of Pharmacy, University of Santiago de Compostela (USC), Praza Seminario de Estudos Galegos s/n, Santiago de Compostela 15701, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Blanco-Mendez
authors.affiliation: Pharmacy Department, Xerencia de Xestión Integrada de Santiago de Compostela, SERGAS, Travesía Choupana s/n, Santiago de Compostela 15706, Spain; Clinical Pharmacology Group, Health Research Institute of Santiago de Compostela (IDIS-ISCIII), SERGAS, Travesía da Choupana s/n, Santiago de Compostela 15706, Spain.
authors.forename: M J
authors.initials: MJ
authors.lastname: Lamas
authors.affiliation: Pharmacy and Pharmaceutical Technology Department, Faculty of Pharmacy, University of Santiago de Compostela (USC), Praza Seminario de Estudos Galegos s/n, Santiago de Compostela 1570, Spain; Industrial Pharmacy Institute, Faculty of Pharmacy, University of Santiago de Compostela (USC), Praza Seminario de Estudos Galegos s/n, Santiago de Compostela 15701, Spain. Electronic address: Francisco.otero@usc.es.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Otero-Espinar
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D002645:Chickens; D017097:Electric Impedance; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism; D008269:Macular Edema / Q000517:prevention & control; D009883:Ophthalmic Solutions; D019591:Pseudophakia / Q000517:prevention & control; D018675:Toxicity Tests / Q000379:methods; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D009883:Ophthalmic Solutions
keywords: Bromfenac sodium (CID: 11954316); Diclofenac sodium (CID: 5018304); Ketorolac tromethamine (CID: 6850754); NSAIDs; Nepafenac (CID: 151075); Ocular toxicity; Pseudophakic cystoid macular edema; Real-Time Cell Analyzer