Evaluation of Verteporfin as a Novel Antifibrotic Agent in a Rabbit Model of Glaucoma Filtration Surgery
Purpose: Verteporfin is a benzoporphyrin derivative which is Food and Drug Administration-approved for treatment of choroidal neovascularization in conjunction with photodynamic therapy. It has been shown to prevent fibrosis and scar formation in several organs and represents a promising novel antif...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2024-05-01
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| Series: | Ophthalmology Science |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S266691452300180X |
| _version_ | 1797352634681655296 |
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| author | Michelle T. Sun, MBBS, PhD Renee M. Cotton, VMD Chaow Charoenkijkajorn, MD Julian Garcia-Sanchez, MD Roopa Dalal, MSc Xin Xia, MD, PhD Jonathan H. Lin, MD, PhD Kuldev Singh, MD Jeffrey L. Goldberg, MD, PhD Wendy W. Liu, MD, PhD |
| author_facet | Michelle T. Sun, MBBS, PhD Renee M. Cotton, VMD Chaow Charoenkijkajorn, MD Julian Garcia-Sanchez, MD Roopa Dalal, MSc Xin Xia, MD, PhD Jonathan H. Lin, MD, PhD Kuldev Singh, MD Jeffrey L. Goldberg, MD, PhD Wendy W. Liu, MD, PhD |
| author_sort | Michelle T. Sun, MBBS, PhD |
| collection | DOAJ |
| description | Purpose: Verteporfin is a benzoporphyrin derivative which is Food and Drug Administration-approved for treatment of choroidal neovascularization in conjunction with photodynamic therapy. It has been shown to prevent fibrosis and scar formation in several organs and represents a promising novel antifibrotic agent for glaucoma surgery. The goal of this study is to determine the effect of verteporfin on wound healing after glaucoma filtration surgery. Design: Preclinical study using a rabbit model of glaucoma filtration surgery. Subjects: Eight New Zealand white rabbits underwent glaucoma filtration surgery in both eyes. Methods: Eyes were randomized into 4 study groups to receive a postoperative subconjunctival injection of 1 mg/mL verteporfin (n = 4), 0.4 mg/mL mitomycin C (MMC; n = 4), 0.4 mg/mL MMC + 1 mg/mL verteporfin (n = 4), or balanced salt solution (BSS) control (n = 4). Bleb survival, vascularity, and morphology were graded using a standard scale over a 30-day period, and intraocular pressure (IOP) was monitored. At 30 days postoperative or surgical failure, histology was performed to evaluate for inflammation, local toxicity, and scarring. Main Outcome Measures: The primary outcome measure was bleb survival. Secondary outcome measures were IOP, bleb morphology, and bleb histology. Results: Compared to BSS control blebs, verteporfin-treated blebs demonstrated a trend toward increased surgical survival (mean 9.8 vs. 7.3 days, log rank P = 0.08). Mitomycin C-treated blebs survived significantly longer than verteporfin-treated blebs (log rank P = 0.009), with all but 1 MMC-treated bleb still surviving at postoperative day 30. There were no significant differences in survival between blebs treated with combination verteporfin + MMC and MMC alone. Mitomycin C-treated blebs were less vascular than verteporfin-treated blebs (mean vascularity score 0.3 ± 0.5 for MMC vs. 1.0 ± 0.0 for verteporfin, P < 0.01). Bleb histology did not reveal any significant toxicity in verteporfin-treated eyes. There were no significant differences in inflammation or scarring across groups. Conclusions: Although verteporfin remained inferior to MMC with regard to surgical survival, there was a trend toward increased survival compared with BSS control and it had an excellent safety profile. Further studies with variations in verteporfin dosage and/or application frequency are needed to assess whether this may be a useful adjunct to glaucoma surgery. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article. |
| first_indexed | 2024-03-08T13:19:45Z |
| format | Article |
| id | doaj.art-87aec2eb8c6c44b7af2ff9bbb4e59a9d |
| institution | Directory Open Access Journal |
| issn | 2666-9145 |
| language | English |
| last_indexed | 2024-03-08T13:19:45Z |
| publishDate | 2024-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ophthalmology Science |
| spelling | doaj.art-87aec2eb8c6c44b7af2ff9bbb4e59a9d2024-01-18T04:18:41ZengElsevierOphthalmology Science2666-91452024-05-0143100448Evaluation of Verteporfin as a Novel Antifibrotic Agent in a Rabbit Model of Glaucoma Filtration SurgeryMichelle T. Sun, MBBS, PhD0Renee M. Cotton, VMD1Chaow Charoenkijkajorn, MD2Julian Garcia-Sanchez, MD3Roopa Dalal, MSc4Xin Xia, MD, PhD5Jonathan H. Lin, MD, PhD6Kuldev Singh, MD7Jeffrey L. Goldberg, MD, PhD8Wendy W. Liu, MD, PhD9Spencer Center for Vision Research, Byers Eye Institute, Stanford University School of Medicine, Palo Alto, CaliforniaDepartment of Comparative Medicine, Stanford University, Palo Alto, CaliforniaSpencer Center for Vision Research, Byers Eye Institute, Stanford University School of Medicine, Palo Alto, CaliforniaSpencer Center for Vision Research, Byers Eye Institute, Stanford University School of Medicine, Palo Alto, CaliforniaSpencer Center for Vision Research, Byers Eye Institute, Stanford University School of Medicine, Palo Alto, CaliforniaSpencer Center for Vision Research, Byers Eye Institute, Stanford University School of Medicine, Palo Alto, CaliforniaSpencer Center for Vision Research, Byers Eye Institute, Stanford University School of Medicine, Palo Alto, CaliforniaSpencer Center for Vision Research, Byers Eye Institute, Stanford University School of Medicine, Palo Alto, CaliforniaSpencer Center for Vision Research, Byers Eye Institute, Stanford University School of Medicine, Palo Alto, CaliforniaSpencer Center for Vision Research, Byers Eye Institute, Stanford University School of Medicine, Palo Alto, California; Correspondence: Wendy W. Liu, MD, PhD, Spencer Center for Vision Research, 2370 Watson Court, Palo Alto, CA 94303.Purpose: Verteporfin is a benzoporphyrin derivative which is Food and Drug Administration-approved for treatment of choroidal neovascularization in conjunction with photodynamic therapy. It has been shown to prevent fibrosis and scar formation in several organs and represents a promising novel antifibrotic agent for glaucoma surgery. The goal of this study is to determine the effect of verteporfin on wound healing after glaucoma filtration surgery. Design: Preclinical study using a rabbit model of glaucoma filtration surgery. Subjects: Eight New Zealand white rabbits underwent glaucoma filtration surgery in both eyes. Methods: Eyes were randomized into 4 study groups to receive a postoperative subconjunctival injection of 1 mg/mL verteporfin (n = 4), 0.4 mg/mL mitomycin C (MMC; n = 4), 0.4 mg/mL MMC + 1 mg/mL verteporfin (n = 4), or balanced salt solution (BSS) control (n = 4). Bleb survival, vascularity, and morphology were graded using a standard scale over a 30-day period, and intraocular pressure (IOP) was monitored. At 30 days postoperative or surgical failure, histology was performed to evaluate for inflammation, local toxicity, and scarring. Main Outcome Measures: The primary outcome measure was bleb survival. Secondary outcome measures were IOP, bleb morphology, and bleb histology. Results: Compared to BSS control blebs, verteporfin-treated blebs demonstrated a trend toward increased surgical survival (mean 9.8 vs. 7.3 days, log rank P = 0.08). Mitomycin C-treated blebs survived significantly longer than verteporfin-treated blebs (log rank P = 0.009), with all but 1 MMC-treated bleb still surviving at postoperative day 30. There were no significant differences in survival between blebs treated with combination verteporfin + MMC and MMC alone. Mitomycin C-treated blebs were less vascular than verteporfin-treated blebs (mean vascularity score 0.3 ± 0.5 for MMC vs. 1.0 ± 0.0 for verteporfin, P < 0.01). Bleb histology did not reveal any significant toxicity in verteporfin-treated eyes. There were no significant differences in inflammation or scarring across groups. Conclusions: Although verteporfin remained inferior to MMC with regard to surgical survival, there was a trend toward increased survival compared with BSS control and it had an excellent safety profile. Further studies with variations in verteporfin dosage and/or application frequency are needed to assess whether this may be a useful adjunct to glaucoma surgery. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.http://www.sciencedirect.com/science/article/pii/S266691452300180XAntifibroticVerteporfinGlaucoma filtration surgeryScarringRabbit model |
| spellingShingle | Michelle T. Sun, MBBS, PhD Renee M. Cotton, VMD Chaow Charoenkijkajorn, MD Julian Garcia-Sanchez, MD Roopa Dalal, MSc Xin Xia, MD, PhD Jonathan H. Lin, MD, PhD Kuldev Singh, MD Jeffrey L. Goldberg, MD, PhD Wendy W. Liu, MD, PhD Evaluation of Verteporfin as a Novel Antifibrotic Agent in a Rabbit Model of Glaucoma Filtration Surgery Ophthalmology Science Antifibrotic Verteporfin Glaucoma filtration surgery Scarring Rabbit model |
| title | Evaluation of Verteporfin as a Novel Antifibrotic Agent in a Rabbit Model of Glaucoma Filtration Surgery |
| title_full | Evaluation of Verteporfin as a Novel Antifibrotic Agent in a Rabbit Model of Glaucoma Filtration Surgery |
| title_fullStr | Evaluation of Verteporfin as a Novel Antifibrotic Agent in a Rabbit Model of Glaucoma Filtration Surgery |
| title_full_unstemmed | Evaluation of Verteporfin as a Novel Antifibrotic Agent in a Rabbit Model of Glaucoma Filtration Surgery |
| title_short | Evaluation of Verteporfin as a Novel Antifibrotic Agent in a Rabbit Model of Glaucoma Filtration Surgery |
| title_sort | evaluation of verteporfin as a novel antifibrotic agent in a rabbit model of glaucoma filtration surgery |
| topic | Antifibrotic Verteporfin Glaucoma filtration surgery Scarring Rabbit model |
| url | http://www.sciencedirect.com/science/article/pii/S266691452300180X |
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