Elsevier

Ophthalmology

Volume 117, Issue 7, July 2010, Pages 1300-1305.e7
Ophthalmology

Original article
Corneal Neovascularization as a Risk Factor for Graft Failure and Rejection after Keratoplasty: An Evidence-Based Meta-analysis

https://doi.org/10.1016/j.ophtha.2010.01.039Get rights and content

Topic

Preoperative corneal neovascularization (CNV) is thought to be associated with an increased rate of corneal graft failure and potentially also graft rejection.

Clinical Relevance

New therapeutic options that offer differential influence on the ingrowths or regression of either corneal blood or lymphatic vessels force us to re-evaluate the known data about the role of CNV in keratoplasty.

Methods

Electronic databases and corneal registries were searched (up through September 2008). Results were reported both descriptively for each study and using random effects meta-analysis. Potential moderating factors for the association between vascularization and graft failure and rejection were examined using metaregression analysis.

Results

Nineteen studies reporting on a total of 24 944 grafts undergoing keratoplasty were included. An increase in the risk of graft failure and rejection in the presence of pathologic CNV was seen in studies with a pooled risk ratio of 1.32 (95% confidence interval [CI], 1.15–1.49) for graft failure and 2.07 (95% CI, 0.98–3.15) for graft rejection. There was evidence of incremental increase of risk for graft failure and rejection as more corneal quadrants were affected by neovascularization. The 2 factors predictive of increased risk of neovascularization and graft failure were increased recipient age (P = 0.003) and male gender (P = 0.046).

Conclusions

Graft failure and rejection risk increase with an increasing number of corneal quadrants affected by neovascularization before keratoplasty. These data support the study of novel topical antiangiogenic therapies at the cornea to precondition such a cornea for future corneal grafting.

Financial Disclosure(s)

Proprietary or commercial disclosure may be found after the references.

Section snippets

Materials and Methods

The study was undertaken in accord with both the Cochrane Collaboration methods for systematic reviews and previous meta-analyses of surrogate outcomes.9, 10, 11

Identification and Selection of Studies

More than 4415 titles were retrieved from the various search sources, and 43 full articles were identified for possible inclusion. Full articles were excluded for a number of reasons: multiple registry or cohort report (8 articles), no measure of association reported (8 articles), patients undergoing repeated grafting (1 article), and no neovascularization outcome and no graft failure or rejection outcome (4 articles). In total, 19 eligible studies (22 publications) remained.

Study Characteristics and Quality

The 19 studies

Discussion

The current systematic review of 19 studies comprising 24 944 keratoplasties allows several important conclusions to be drawn. First, there exists a strong association between loss of corneal angiogenic privilege, i.e., pathologic CNV, and increased risk for graft failure with a pooled hazard ratio of 1.32 (95% CI, 1.15–1.49). Second, in addition and in contrast to the Collaborative Corneal Transplantation Study data,2 there was evidence of an association between CNV and graft rejection after

References (40)

  • K.A. Williams et al.

    The Australian Corneal Graft Registry 2007 Report

  • The Collaborative Corneal Transplantation Studies (CCTS): effectiveness of histocompatibility matching in high-risk corneal transplantation

    Arch Ophthalmol

    (1992)
  • C. Cursiefen et al.

    Inhibition of hemangiogenesis and lymphangiogenesis after normal-risk corneal transplantation by neutralizing VEGF promotes graft survival

    Invest Ophthalmol Vis Sci

    (2004)
  • V.M. Lam et al.

    Surgery-related factors influencing corneal neovascularization after low-risk keratoplasty

    Am J Ophthalmol

    (2006)
  • H. Kubo et al.

    Blockade of vascular endothelial growth factor receptor-3 signaling inhibits fibroblast growth factor-2-induced lymphangiogenesis in mouse cornea

    Proc Natl Acad Sci U S A

    (2002)
  • F. Bock et al.

    Blockade of VEGFR3-signalling specifically inhibits lymphangiogenesis in inflammatory corneal neovascularisation

    Graefes Arch Clin Exp Ophthalmol

    (2008)
  • Y. Jin et al.

    The chemokine receptor CCR7 mediates corneal antigen-presenting cell trafficking

    Mol Vis [serial online]

    (2007)
  • J.P. Higgins et al.

    Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.2.Part 2: General methods for Cochrane reviews

  • R.S. Taylor et al.

    Spinal cord stimulation for chronic back and leg pain and failed back surgery syndrome: a systematic review and analysis of prognostic factors

    Spine (Phila Pa 1976)

    (2005)
  • A. Vail et al.

    Conclusions of the Corneal Transplant Follow up Study

    Br J Ophthalmol

    (1997)
  • Cited by (0)

    Manuscript no. 2009-807.

    Financial Disclosure(s): The author(s) have made the following disclosure(s):

    Rod S. Taylor - Consultant - Gene Signal

    Claus Cursiefen - Consultant - Gene Signal

    Supported by the Interdisciplinary Center for Clinical Research Erlangen, Erlangen, Germany; the German Research Foundation (SFB 643), Bonn, Germany; and GeneSignal, Evry (Paris), France. Gene Signal, France, funded the study. The planning of this study, interpretation of findings, and writing and conclusions of manuscript were undertaken entirely independently of the company interests.

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