Ex vivo corneal epithelial wound healing following exposure to ophthalmic nonsteroidal anti-inflammatory drugs

Keping Xu1, Mark McDermott1, Linda Villanueva2, Rhett M Schiffman2, David A Hollander21The Kresge Eye Institute, Department of Ophthalmology, Wayne State University School of Medicine, Detroit, MI, USA; 2Allergan, Inc., Irvine, CA, USAPurpose: Ketorolac 0.45% is a new formulation of topical ketorola...

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Autores principales:	Keping Xu, Mark McDermott, Linda Villanueva, et al
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2011
Materias:	Ophthalmology RE1-994
Acceso en línea:	https://doaj.org/article/20eb768859774c7da1f35b0c0363fd5f
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spelling	oai:doaj.org-article:20eb768859774c7da1f35b0c0363fd5f2021-12-02T05:03:30ZEx vivo corneal epithelial wound healing following exposure to ophthalmic nonsteroidal anti-inflammatory drugs1177-54671177-5483https://doaj.org/article/20eb768859774c7da1f35b0c0363fd5f2011-02-01T00:00:00Zhttp://www.dovepress.com/ex-vivo-corneal-epithelial-wound-healing-following-exposure-to-ophthal-a6487https://doaj.org/toc/1177-5467https://doaj.org/toc/1177-5483Keping Xu1, Mark McDermott1, Linda Villanueva2, Rhett M Schiffman2, David A Hollander21The Kresge Eye Institute, Department of Ophthalmology, Wayne State University School of Medicine, Detroit, MI, USA; 2Allergan, Inc., Irvine, CA, USAPurpose: Ketorolac 0.45% is a new formulation of topical ketorolac in which preservative (benzalkonium chloride, BAK) was removed and carboxymethylcellulose (CMC) was added to improve tolerability and reduce dosing frequency. This study compared the effects of ketorolac 0.45% on corneal wound healing to prior ketorolac formulations (0.4% and 0.5%), bromfenac 0.09%, and nepafenac 0.1%.Methods: Two parallel-group comparisons were performed in series. A 5-mm central epithelial wound was made in fresh porcine corneas. After 24 hours in minimum essential medium (MEM), corneas were incubated for 10 minutes with study drugs, Triton X-100 1% (positive control), or MEM (negative control), followed by 24 hours in MEM. The remaining wound area was stained, photographed, and quantified (pixels). Study 1 compared ketorolac 0.45% to ketorolac 0.4% and ketorolac 0.5%. Study 2 compared ketorolac 0.45% to bromfenac 0.09% and nepafenac 0.1%.Results: The mean (&plusmn;SD) original wound area was 200,506 &plusmn; 4,363 pixels, which was reduced to 59,509 &plusmn; 4850 at 48 hours after exposure to Triton X-100 1%. In study 1, the mean remaining wound areas at 48 hours in pixels were 2969 &plusmn; 1633 with MEM, 586 &plusmn; 299 with ketorolac 0.45% (significantly reduced, P &lt; 0.05 vs all other treatments), 10,228 &plusmn; 7541 with ketorolac 0.4%, and 50,674 &plusmn; 33,409 with ketorolac 0.5% (significantly enlarged, P &lt; 0.05 vs MEM). In study 2, the mean remaining wound areas at 48 hours were 565 &plusmn; 1263 with MEM, 322 &plusmn; 229 with ketorolac 0.45% (significantly reduced, P &lt; 0.01 vs bromfenac 0.09% and nepafenac 0.1%), 29,093 &plusmn; 14,295 with bromfenac 0.09% (significantly enlarged, P &lt; 0.01 vs MEM) and 47,322 &plusmn; 13,736 with nepafenac 0.1% (significantly enlarged, P &lt; 0.01 vs MEM and vs bromfenac 0.09%).Conclusion: Corneas treated with ketorolac 0.45% healed as rapidly as those treated with MEM, likely secondary to addition of CMC and removal of BAK. In the ex vivo corneal organ culture model, ketorolac 0.45% had statistically less impact on corneal re-epithelialization than prior ketorolac formulations (0.4% and 0.5%), bromfenac 0.09%, and nepafenac 0.01%.Keywords: bromfenac 0.09%, corneal epithelial wound healing, epithelial toxicity, ketorolac 0.45%, nepafenac 0.1%, ocular surgery Keping XuMark McDermottLinda Villanuevaet alDove Medical PressarticleOphthalmologyRE1-994ENClinical Ophthalmology, Vol 2011, Iss default, Pp 269-274 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Ophthalmology RE1-994
spellingShingle	Ophthalmology RE1-994 Keping Xu Mark McDermott Linda Villanueva et al Ex vivo corneal epithelial wound healing following exposure to ophthalmic nonsteroidal anti-inflammatory drugs
description	Keping Xu1, Mark McDermott1, Linda Villanueva2, Rhett M Schiffman2, David A Hollander21The Kresge Eye Institute, Department of Ophthalmology, Wayne State University School of Medicine, Detroit, MI, USA; 2Allergan, Inc., Irvine, CA, USAPurpose: Ketorolac 0.45% is a new formulation of topical ketorolac in which preservative (benzalkonium chloride, BAK) was removed and carboxymethylcellulose (CMC) was added to improve tolerability and reduce dosing frequency. This study compared the effects of ketorolac 0.45% on corneal wound healing to prior ketorolac formulations (0.4% and 0.5%), bromfenac 0.09%, and nepafenac 0.1%.Methods: Two parallel-group comparisons were performed in series. A 5-mm central epithelial wound was made in fresh porcine corneas. After 24 hours in minimum essential medium (MEM), corneas were incubated for 10 minutes with study drugs, Triton X-100 1% (positive control), or MEM (negative control), followed by 24 hours in MEM. The remaining wound area was stained, photographed, and quantified (pixels). Study 1 compared ketorolac 0.45% to ketorolac 0.4% and ketorolac 0.5%. Study 2 compared ketorolac 0.45% to bromfenac 0.09% and nepafenac 0.1%.Results: The mean (&plusmn;SD) original wound area was 200,506 &plusmn; 4,363 pixels, which was reduced to 59,509 &plusmn; 4850 at 48 hours after exposure to Triton X-100 1%. In study 1, the mean remaining wound areas at 48 hours in pixels were 2969 &plusmn; 1633 with MEM, 586 &plusmn; 299 with ketorolac 0.45% (significantly reduced, P &lt; 0.05 vs all other treatments), 10,228 &plusmn; 7541 with ketorolac 0.4%, and 50,674 &plusmn; 33,409 with ketorolac 0.5% (significantly enlarged, P &lt; 0.05 vs MEM). In study 2, the mean remaining wound areas at 48 hours were 565 &plusmn; 1263 with MEM, 322 &plusmn; 229 with ketorolac 0.45% (significantly reduced, P &lt; 0.01 vs bromfenac 0.09% and nepafenac 0.1%), 29,093 &plusmn; 14,295 with bromfenac 0.09% (significantly enlarged, P &lt; 0.01 vs MEM) and 47,322 &plusmn; 13,736 with nepafenac 0.1% (significantly enlarged, P &lt; 0.01 vs MEM and vs bromfenac 0.09%).Conclusion: Corneas treated with ketorolac 0.45% healed as rapidly as those treated with MEM, likely secondary to addition of CMC and removal of BAK. In the ex vivo corneal organ culture model, ketorolac 0.45% had statistically less impact on corneal re-epithelialization than prior ketorolac formulations (0.4% and 0.5%), bromfenac 0.09%, and nepafenac 0.01%.Keywords: bromfenac 0.09%, corneal epithelial wound healing, epithelial toxicity, ketorolac 0.45%, nepafenac 0.1%, ocular surgery
format	article
author	Keping Xu Mark McDermott Linda Villanueva et al
author_facet	Keping Xu Mark McDermott Linda Villanueva et al
author_sort	Keping Xu
title	Ex vivo corneal epithelial wound healing following exposure to ophthalmic nonsteroidal anti-inflammatory drugs
title_short	Ex vivo corneal epithelial wound healing following exposure to ophthalmic nonsteroidal anti-inflammatory drugs
title_full	Ex vivo corneal epithelial wound healing following exposure to ophthalmic nonsteroidal anti-inflammatory drugs
title_fullStr	Ex vivo corneal epithelial wound healing following exposure to ophthalmic nonsteroidal anti-inflammatory drugs
title_full_unstemmed	Ex vivo corneal epithelial wound healing following exposure to ophthalmic nonsteroidal anti-inflammatory drugs
title_sort	ex vivo corneal epithelial wound healing following exposure to ophthalmic nonsteroidal anti-inflammatory drugs
publisher	Dove Medical Press
publishDate	2011
url	https://doaj.org/article/20eb768859774c7da1f35b0c0363fd5f
work_keys_str_mv	AT kepingxu exvivocornealepithelialwoundhealingfollowingexposuretoophthalmicnonsteroidalantiinflammatorydrugs AT markmcdermott exvivocornealepithelialwoundhealingfollowingexposuretoophthalmicnonsteroidalantiinflammatorydrugs AT lindavillanueva exvivocornealepithelialwoundhealingfollowingexposuretoophthalmicnonsteroidalantiinflammatorydrugs AT etal exvivocornealepithelialwoundhealingfollowingexposuretoophthalmicnonsteroidalantiinflammatorydrugs
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Ex vivo corneal epithelial wound healing following exposure to ophthalmic nonsteroidal anti-inflammatory drugs

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