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

Xu K, McDermott M, Villanueva L, Schiffman RM, Hollander DA - Clin Ophthalmol (2011)

Bottom Line: 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%.In study 1, the mean remaining wound areas at 48 hours in pixels were 2969 ± 1633 with MEM, 586 ± 299 with ketorolac 0.45% (significantly reduced, P < 0.05 vs all other treatments), 10,228 ± 7541 with ketorolac 0.4%, and 50,674 ± 33,409 with ketorolac 0.5% (significantly enlarged, P < 0.05 vs MEM).In study 2, the mean remaining wound areas at 48 hours were 565 ± 1263 with MEM, 322 ± 229 with ketorolac 0.45% (significantly reduced, P < 0.01 vs bromfenac 0.09% and nepafenac 0.1%), 29,093 ± 14,295 with bromfenac 0.09% (significantly enlarged, P <0.01 vs MEM) and 47,322 ± 13,736 with nepafenac 0.1% (significantly enlarged, P < 0.01 vs MEM and vs bromfenac 0.09%).

View Article: PubMed Central - PubMed

Affiliation: The Kresge Eye Institute, Department of Ophthalmology, Wayne State University School of Medicine, Detroit, MI, USA;

ABSTRACT

Purpose: 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 (±SD) original wound area was 200,506 ± 4,363 pixels, which was reduced to 59,509 ± 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 ± 1633 with MEM, 586 ± 299 with ketorolac 0.45% (significantly reduced, P < 0.05 vs all other treatments), 10,228 ± 7541 with ketorolac 0.4%, and 50,674 ± 33,409 with ketorolac 0.5% (significantly enlarged, P < 0.05 vs MEM). In study 2, the mean remaining wound areas at 48 hours were 565 ± 1263 with MEM, 322 ± 229 with ketorolac 0.45% (significantly reduced, P < 0.01 vs bromfenac 0.09% and nepafenac 0.1%), 29,093 ± 14,295 with bromfenac 0.09% (significantly enlarged, P <0.01 vs MEM) and 47,322 ± 13,736 with nepafenac 0.1% (significantly enlarged, P < 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%.

No MeSH data available.


Related in: MedlinePlus

Representative images of corneas with original wound and those following treatment with Triton X-100 1%.
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f1-opth-5-269: Representative images of corneas with original wound and those following treatment with Triton X-100 1%.

Mentions: The mean (SD) original wound area induced by the 5 mm trephine was 200,506 ± 4363 pixels. At 48 hours, corneas treated with Triton X-100 1% had a mean (SD) remaining wound area of 59,509 ± 4850 pixels (Figure 1). In study 1, the mean (SD) remaining wound areas at 48 hours following treatment with MEM control, ketorolac 0.45%, ketorolac 0.4%, and ketorolac 0.5% were 2969 ± 1633 pixels, 586 ± 299 pixels, 10,228 ± 7541 pixels, and 50,674 ± 33,409 pixels, respectively (Figure 2). Corneas treated with ketorolac 0.45% had a significantly smaller mean remaining wound area than did corneas treated with MEM control, ketorolac 0.4%, and ketorolac 0.5% (P < 0.05). In contrast, the mean remaining wound area of corneas treated with ketorolac 0.5% was not statistically different than those treated with Triton X-100 1%.


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

Xu K, McDermott M, Villanueva L, Schiffman RM, Hollander DA - Clin Ophthalmol (2011)

Representative images of corneas with original wound and those following treatment with Triton X-100 1%.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3065566&req=5

f1-opth-5-269: Representative images of corneas with original wound and those following treatment with Triton X-100 1%.
Mentions: The mean (SD) original wound area induced by the 5 mm trephine was 200,506 ± 4363 pixels. At 48 hours, corneas treated with Triton X-100 1% had a mean (SD) remaining wound area of 59,509 ± 4850 pixels (Figure 1). In study 1, the mean (SD) remaining wound areas at 48 hours following treatment with MEM control, ketorolac 0.45%, ketorolac 0.4%, and ketorolac 0.5% were 2969 ± 1633 pixels, 586 ± 299 pixels, 10,228 ± 7541 pixels, and 50,674 ± 33,409 pixels, respectively (Figure 2). Corneas treated with ketorolac 0.45% had a significantly smaller mean remaining wound area than did corneas treated with MEM control, ketorolac 0.4%, and ketorolac 0.5% (P < 0.05). In contrast, the mean remaining wound area of corneas treated with ketorolac 0.5% was not statistically different than those treated with Triton X-100 1%.

Bottom Line: 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%.In study 1, the mean remaining wound areas at 48 hours in pixels were 2969 ± 1633 with MEM, 586 ± 299 with ketorolac 0.45% (significantly reduced, P < 0.05 vs all other treatments), 10,228 ± 7541 with ketorolac 0.4%, and 50,674 ± 33,409 with ketorolac 0.5% (significantly enlarged, P < 0.05 vs MEM).In study 2, the mean remaining wound areas at 48 hours were 565 ± 1263 with MEM, 322 ± 229 with ketorolac 0.45% (significantly reduced, P < 0.01 vs bromfenac 0.09% and nepafenac 0.1%), 29,093 ± 14,295 with bromfenac 0.09% (significantly enlarged, P <0.01 vs MEM) and 47,322 ± 13,736 with nepafenac 0.1% (significantly enlarged, P < 0.01 vs MEM and vs bromfenac 0.09%).

View Article: PubMed Central - PubMed

Affiliation: The Kresge Eye Institute, Department of Ophthalmology, Wayne State University School of Medicine, Detroit, MI, USA;

ABSTRACT

Purpose: 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 (±SD) original wound area was 200,506 ± 4,363 pixels, which was reduced to 59,509 ± 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 ± 1633 with MEM, 586 ± 299 with ketorolac 0.45% (significantly reduced, P < 0.05 vs all other treatments), 10,228 ± 7541 with ketorolac 0.4%, and 50,674 ± 33,409 with ketorolac 0.5% (significantly enlarged, P < 0.05 vs MEM). In study 2, the mean remaining wound areas at 48 hours were 565 ± 1263 with MEM, 322 ± 229 with ketorolac 0.45% (significantly reduced, P < 0.01 vs bromfenac 0.09% and nepafenac 0.1%), 29,093 ± 14,295 with bromfenac 0.09% (significantly enlarged, P <0.01 vs MEM) and 47,322 ± 13,736 with nepafenac 0.1% (significantly enlarged, P < 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%.

No MeSH data available.


Related in: MedlinePlus