Ophthalmology
Volume 116, Issue 7 , Pages 1301-1305, July 2009

Herpes Simplex Virus Keratitis:

Histopathologic Inflammation and Corneal Allograft Rejection

Presented at: the Annual Meeting of the American Ophthalmological Society and subsequently published in the Transactions of the American Ophthalmological Society in May 2008, Colorado Springs, Colorado.

  • Roni M. Shtein, MD

      Affiliations

    • Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan
    • ,
  • Denise D. Garcia, MD

      Affiliations

    • Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan
    • ,
  • David C. Musch, PhD

      Affiliations

    • Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan
    • Department of Epidemiology, University of Michigan, Ann Arbor, Michigan
    • ,
  • Victor M. Elner, MD, PhD

      Affiliations

    • Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan
    • Department of Pathology, University of Michigan, Ann Arbor, Michigan
    • Corresponding Author InformationCorrespondence: Victor M. Elner, MD, PhD, University of Michigan, Kellogg Eye Center, 1000 Wall Street, Ann Arbor, Michigan 48105

Received 17 September 2008; received in revised form 16 March 2009; accepted 18 March 2009.

Objective

To identify whether histopathologic and immunoassay biomarkers of inflammation are predictive for allograft rejection after penetrating keratoplasty (PKP) for herpes simplex virus (HSV) keratitis.

Design

Retrospective, interventional case series with prospective component of pathologic evaluation of frozen tissue.

Participants

Sixty-two consecutive patients with HSV keratitis who underwent PKP.

Methods

A chart review and histopathologic examination of the excised host corneal button was performed to identify associations between clinical data and histopathologic presence of inflammation. Enzyme-linked immunosorbent assay for interleukin (IL)-8 and monocyte chemotactic protein-1 (MCP-1) chemokines and immunohistochemical staining for human leukocyte antigen (HLA)-DR and intercellular adhesion molecule-1 (ICAM-1) antigens was also performed in inflamed and noninflamed specimens.

Main Outcome Measures

To determine whether the presence of subclinical inflammation at the time of PKP predicts allograft rejection.

Results

Although 81% of patients had clinically quiescent disease, histopathology revealed that 74% had active corneal inflammation, a finding that was associated with the presence of clinical neovascularization (P = 0.01). Allograft rejections were experienced by 34% of the patients in this cohort. The histopathologic presence of inflammation was a risk factor for allograft rejection (P = 0.02). Corneal specimens demonstrating inflammation had significantly increased IL-8 (P = 0.0005) and MCP-1 (P = 0.003) levels, and greater immunoreactivity for HLA-DR and ICAM-1 when compared with specimens without inflammation. Treatment with IL-10 ex vivo significantly inhibited IL-8 (P = 0.006), and MCP-1 (P = 0.01) chemokines, and qualitatively substantially reduced HLA-DR, but not ICAM-1, expression.

Conclusions

Histopathologic inflammation is a risk factor for corneal allograft rejection.

Financial Disclosure(s)

The authors have no proprietary or commercial interest in any of the materials discussed in this article.

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 Manuscript no. 2008-1120.

 Financial Disclosure(s): Supported by EY017885 (RMS) and EY7003 and EY9441 (VME). Dr Elner is the recipient of a Senior Scientific Award from Research to Prevent Blindness.

PII: S0161-6420(09)00295-4

doi:10.1016/j.ophtha.2009.03.031

Ophthalmology
Volume 116, Issue 7 , Pages 1301-1305, July 2009

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