Corneal Neovascularization After Penetrating Keratoplasty

Dana, Mohamad-Reza; Schaumberg, Debra A.; Kowal, Vera O.; Goren, Matthew B.; Rapuano, Christopher J.; Laibson, Peter R.; Cohen, Elisabeth J.

doi:10.1097/00003226-199511000-00014

Cited by 48 publications

(49 citation statements)

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“…It is a major complication of corneal injury from chemical burns due to accidental exposure to solvents, detergents and alkali, and of corneal infections including bacterial, chlamydial, parasitic and viral infections which affect more than 450 million people worldwide [1,2] . In addition, corneal neovascularization represents a major reason for corneal graft rejection [3] .…”

Section: Introductionmentioning

confidence: 99%

Prevention and Treatment of Corneal Neovascularization: Comparison of Different Doses of Subconjunctival Bevacizumab with Corticosteroid in Experimental Rats

et al. 2009

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Background: To evaluate and compare the effect of different doses of subconjunctival bevacizumab with betamethasone on the development of corneal major new vessels in a rat model of corneal chemical injury. Methods: The right eyes of 100 male Sprague-Dawley rats were randomly divided into 10 experimental groups (n = 10 per group). Chemical cauterization of the cornea was performed by using silver nitrate/potassium nitrate sticks. Immediately following corneal cauterization, the animals in groups 1–5 received subconjunctival injections of 0.02 ml of normal saline (control A), betamethasone LA (6 mg/ml) and different doses of bevacizumab (1, 5 and 25 mg/ml), respectively. In another experiment, the animals in groups 6–10 received subconjunctival injections of 0.02 ml of normal saline (control B), betamethasone LA (6 mg/ml) and different doses of bevacizumab (1, 5 and 25 mg/ml), respectively, 7 days following corneal cauterization. The numbers of major thick-walled vessels originating from the limbus reaching the corneal scar were counted 7 days after corneal cauterization in groups 1–5 and 14 days after corneal cauterization in groups 6–10. Results: The number of major vessels in groups 1–5 was 19.63 ± 3.77, 17.25 ± 5.33, 16.10 ± 5.02, 12.89 ± 2.70 and 12.36 ± 4.45 when assessed 7 days after corneal cauterization, respectively. Administration of betamethasone in group 2 had no significant effect on the corneal major vessel count compared to control A. The number of major vessels in groups 4 and 5 (bevacizumab 5 and 25 mg/ml) was significantly lower than that of group 1 (p < 0.01, Student’s t test). The number of vessels in groups 6–10 was 12.55 ± 5.64, 11.30 ± 9.33, 5.50 ± 6.34, 2.73 ± 4.73 and 2.67 ± 3.77 when assessed 14 days after corneal cauterization, respectively. Subconjunctival administration of betamethasone 7 days after corneal cauterization did not reduce the amount of corneal major vessels compared to control B. Administration of 0.02 ml of bevacizumab in doses of 1, 5 and 25 mg/ml 7 days after corneal cauterization significantly reduced the amount of major vessels compared to group 6 (p = 0.01, p < 0.01 and p < 0.01, respectively). There was no significant difference in percent area of corneal scar between different groups. Conclusion: Single subconjunctival injection of bevacizumab is efficacious in the prevention of formation as well as regression of major vessels compared to betamethasone in this rat model of corneal neovascularization. Even lower doses of bevacizumab might be efficacious.

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Section: Introductionmentioning

confidence: 99%

Prevention and Treatment of Corneal Neovascularization: Comparison of Different Doses of Subconjunctival Bevacizumab with Corticosteroid in Experimental Rats

et al. 2009

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“…In normal corneas, angiogenesis is controlled by two counterbalancing systems: proangiogenic factors (vascular endothelial growth factor [VEGF], basic fibroblast growth factor, matrix metalloproteinases, integrins, and cytokines) and antiangiogenic factors (pigment epithelium-derived factor, VEGFR3, soluble VEGFR-1, angiostatin, and endostatin) (19,20). Antiangiogenic therapy may prove a promising direction to reduce graft failure (21). Various chemical compounds and drugs, such as steroids (22), methotrexate (23), heparin (24), and thalidomide (25), are reported to inhibit corneal neovascularization.…”

mentioning

confidence: 99%

Immunological Disruption of Antiangiogenic Signals by Recruited Allospecific T Cells Leads to Corneal Allograft Rejection

Tan

Cruz-Guilloty

Medina-Mendez

et al. 2012

The Journal of Immunology

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Corneal transplantation is the most common solid organ transplantation. The immunologically privileged nature of the cornea results in high success rates. However, T cell-mediated rejection is the most common cause of corneal graft failure. Using antiangiogenesis treatment to prevent corneal neovascularization, which revokes immune privilege, prevents corneal allograft rejection. Endostatin is an antiangiogenic factor that maintains corneal avascularity. In this study, we directly test the role of antiangiogenic and immunological signals in corneal allograft survival, specifically the potential correlation of endostatin production and T cell recruitment. We report that 75% of the corneal allografts of BALB/c mice rejected after postoperative day (POD) 20, whereas all syngeneic grafts survived through POD60. This correlates with endogenous endostatin, which increased and remained high in syngeneic grafts but decreased after POD10 in allografts. Immunostaining demonstrated that early recruitment of allospecific T cells into allografts around POD10 correlated with decreased endostatin production. In Rag−/− mice, both allogeneic and syngeneic corneal grafts survived; endostatin remained high throughout. However, after T cell transfer, the allografts eventually rejected, and endostatin decreased. Furthermore, exogenous endostatin treatment delayed allograft rejection and promoted survival secondary to angiogenesis inhibition. Our results suggest that endostatin plays an important role in corneal allograft survival by inhibiting neovascularization and that early recruitment of allospecific T cells into the grafts promotes destruction of endostatin-producing cells, resulting in corneal neovascularization, massive infiltration of effector T cells, and ultimately graft rejection. Therefore, combined antiangiogenesis and immune suppression will be more effective in maintaining corneal allograft survival.

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“…10.1) (Cursiefen et al 2003). Even in the low-risk setting of corneal transplantation without preexisting corneal blood and lymphatic vessels, moderate (mainly iatrogenic) corneal hem-and lymphangiogenesis develops after grafting and can even reach the host-graft interface under certain circumstances, also increasing the risk for subsequent immune-mediated graft rejection (Cursiefen et al 2002a;Cursiefen et al 2001;Dana et al 1995).…”

Section: Importance Of Hem-versus Lymphangiogenesis In Corneal Transpmentioning

confidence: 99%

Lymphatic Vessels in the Development of Tissue and Organ Rejection

Hos

Cursiefen

2013

Developmental Aspects of the Lymphatic Vascular System

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The lymphatic vascular system-amongst other tasks-is critically involved in the regulation of adaptive immune responses as it provides an important route for APC trafficking to secondary lymphatic organs. In this context, the cornea, which is the transparent and physiologically avascular "windscreen" of the eye, has served as an excellent in vivo model to study the role of the blood and lymphatic vasculature in mediating allogenic immune responses after transplantation. Especially the mouse model of high-risk corneal transplantation, where corneal avascularity is abolished by a severe inflammatory stimulus prior to keratoplasty, allows for comparison to other transplantations performed in primarily vascularized tissues and solid organs. Using this model, we recently demonstrated that especially lymphatic vessels, but not blood vessels, define the high-risk status of vascularized corneas and that anti(lymph)angiogenic treatment significantly promotes corneal allograft survival. Since evidence for lymphangiogenesis and its potential association with graft rejection is nowadays also present in solid organ transplantation, studies are currently addressing the potential benefits of anti(lymph)angiogenic treatment as a novel therapeutic concept also in solid organ grafting with promising initial results.

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Corneal Neovascularization After Penetrating Keratoplasty

Cited by 48 publications

References 0 publications

Prevention and Treatment of Corneal Neovascularization: Comparison of Different Doses of Subconjunctival Bevacizumab with Corticosteroid in Experimental Rats

Prevention and Treatment of Corneal Neovascularization: Comparison of Different Doses of Subconjunctival Bevacizumab with Corticosteroid in Experimental Rats

Immunological Disruption of Antiangiogenic Signals by Recruited Allospecific T Cells Leads to Corneal Allograft Rejection

Lymphatic Vessels in the Development of Tissue and Organ Rejection

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