title: Histological features of Cytomegalovirus-related corneal graft infections, its associated features and clinical significance.
abstract: OBJECTIVE
  To describe the histological features of ITALIC! 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.
  
  
  CONCLUSIONS
  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.
authors: Singapore National Eye Centre, Singapore, Singapore Histopathology, Pathology Department, Singapore General Hospital, Singapore, Singapore Singapore Eye Research Institute, Singapore, Singapore Ophthalmology & Visual Sciences Academic Clinical Program, Duke-NUS Graduate Medical School, Singapore, Singapore.
authors: Anita S Y
authors: AS
authors: Chan
authors: Singapore National Eye Centre, Singapore, Singapore Singapore Eye Research Institute, Singapore, Singapore Ophthalmology & Visual Sciences Academic Clinical Program, Duke-NUS Graduate Medical School, Singapore, Singapore Nanyang Technological University, Singapore, Singapore.
authors: Jodhbir S
authors: JS
authors: Mehta
authors: Histopathology, Pathology Department, Singapore General Hospital, Singapore, Singapore.
authors: Issam
authors: I
authors: Al Jajeh
authors: Histopathology, Pathology Department, Singapore General Hospital, Singapore, Singapore.
authors: Jabed
authors: J
authors: Iqbal
authors: Singapore National Eye Centre, Singapore, Singapore Singapore Eye Research Institute, Singapore, Singapore.
authors: Arundhati
authors: A
authors: Anshu
authors: Singapore National Eye Centre, Singapore, Singapore Singapore Eye Research Institute, Singapore, Singapore Ophthalmology & Visual Sciences Academic Clinical Program, Duke-NUS Graduate Medical School, Singapore, Singapore Nanyang Technological University, Singapore, Singapore Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors: Donald T H
authors: DT
authors: Tan
mesh_terms: D000368:Aged; D064591:Allografts; D000914:Antibodies, Viral / Q000097:blood; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D000998:Antiviral Agents / Q000627:therapeutic use; D003316:Corneal Diseases / Q000188:drug therapy / Q000473:pathology* / Q000821:virology; D003587:Cytomegalovirus / Q000276:immunology / Q000302:isolation & purification*; D003586:Cytomegalovirus Infections / Q000188:drug therapy / Q000473:pathology* / Q000821:virology; D015828:Eye Infections, Viral / Q000188:drug therapy / Q000473:pathology* / Q000821:virology; D015774:Ganciclovir / Q000031:analogs & derivatives / Q000627:therapeutic use; D006084:Graft Rejection / Q000188:drug therapy / Q000473:pathology* / Q000821:virology; D006801:Humans; D015948:Keratoplasty, Penetrating; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011956:Receptors, Cell Surface / Q000378:metabolism; D012008:Recurrence; D012086:Reoperation; D012189:Retrospective Studies; D000077562:Valganciclovir; D000098902:CD163 Antigen; D000097382:CD68 Molecule
chemical_list: D000914:Antibodies, Viral; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000998:Antiviral Agents; D015774:Ganciclovir; D011956:Receptors, Cell Surface; D000077562:Valganciclovir; D000098902:CD163 Antigen; C067980:CD68 antigen, human; D000097382:CD68 Molecule
keywords: Cornea; Infection; Pathology