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Histological features of Cytomegalovirus-related corneal graft infections, its associated features and clinical significance
  1. Anita SY Chan1,2,3,4,
  2. Jodhbir S Mehta1,3,4,5,
  3. Issam Al Jajeh2,
  4. Jabed Iqbal2,
  5. Arundhati Anshu1,3,
  6. Donald TH Tan1,3,4,5,6
  1. 1Singapore National Eye Centre, Singapore, Singapore
  2. 2Histopathology, Pathology Department, Singapore General Hospital, Singapore, Singapore
  3. 3Singapore Eye Research Institute, Singapore, Singapore
  4. 4Ophthalmology & Visual Sciences Academic Clinical Program, Duke-NUS Graduate Medical School, Singapore, Singapore
  5. 5Nanyang Technological University, Singapore, Singapore
  6. 6Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
  1. Correspondence to Professor Donald TH Tan, Singapore National Eye Center, 11 Third Hospital Avenue, Singapore 168751, Singapore; donald.tan.t.h{at}


Aim To describe the histological features of Cytomegalovirus (CMV)-related corneal graft infections, its associated features and clinical significance.

Methods This was a retrospective histological study of 48 consecutive cases of failed repeat penetrating keratoplasty cases with a clinical diagnosis of allograft rejection from 2011 to 2013. CMV infection was confirmed with CMV antibody immunohistochemistry (IHC) and electron microscopy. Additional CD163 and CD68 IHCs for macrophages were also performed. Clinical data and previous graft histology were then reviewed.

Results Mean incidence of CMV infection in corneal graft rejection buttons was 6.3% per year. 3/48 graft buttons were CMV antibody positive. Histological features of CMV graft infection include: (1) stromal keratocytes with cytopathic changes; (2) lack of inflammation, only occasional macrophages present and (3) absence of vascularisation. None of the patients had a history of active CMV infection.

Conclusion CMV infection is not limited as endotheliitis, but extends into the corneal stroma, and is a potential reservoir for graft infection, especially in partial thickness endothelial surgery. Clinical features are often non-specific, although glaucoma was present in our patients. CMV-infected grafts showed CD163-positive M2 macrophages in close association with the infected keratocytes, suggesting that the macrophage may be important in CMV graft infection. Histological examination with CMV IHC is a useful method to detect CMV infection postoperatively. Post penetrating keratoplasty, CMV systemic treatment with valganciclovir can prevent graft infection and failure. Boston keratoprosthesis may be a potential alternative surgery in active CMV infections that obviates the need for systemic therapy.

  • Cornea
  • Pathology
  • Infection

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