Cluster of Symptomatic Graft-to-Host Transmission of Herpes Simplex Virus Type 1 in an Endothelial Keratoplasty Setting

José Afonso Guerra-Assunção,Jeroen J.A Van Kampen,Sunando Roy,Lies Remeijer,Judy Breuer,Georges M.G M Verjans

doi:10.1016/j.xops.2021.100051

José Afonso Guerra-Assunção, Jeroen J.A Van Kampen + Show 4 more

Open Access

https://doi.org/10.1016/j.xops.2021.100051

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Abstract

PurposeDescemet's membrane endothelial keratoplasty (DMEK) is becoming the gold standard to treat corneal endothelial dysfunctions worldwide. Compared with conventional penetrating keratoplasty, infectious complications after DMEK are ill defined. We describe the clinical picture of 2 DMEK recipients, operated on the same day and in the same clinic, who developed atypical herpes simplex virus type 1 (HSV-1) infection in the transplant recipient eye within days post-DMEK. Because recipients received cornea tissue from 2 different donors prepared by the same eye bank, the likelihood of a common HSV-1 source was determined.DesignCase series.ParticipantsTwo DMEK recipients who developed atypical intraocular HSV-1 disease shortly after surgery and surplus cornea specimens of 6 donors.MethodsSurplus cornea donor (pre-DMEK cornea remnants and conditioned cornea storage and transport media) and recipient samples (post-DMEK aqueous humor) were assayed for HSV-1 DNA and infectious virus by real-time polymerase chain reaction (RT-PCR) and cell culture, respectively. Target-enriched whole viral genome sequencing was performed on HSV-1 DNA–positive ocular specimens.Main Outcome MeasuresClinical picture of atypical intraocular HSV-1 infection post-DMEK and presence and homology of HSV-1 genomes between ocular specimens of DMEK donors and recipients.ResultsHerpes simplex virus type 1 DNA was detected in aqueous humor and donor cornea specimens of both DMEK cases, but not in the cornea remnants of 6 randomly selected donors processed by the same eye bank. Infectious HSV-1 was isolated from the cornea remnant and corresponding culture medium of 1 cornea donor. Notably, whole-genome sequencing of virus DNA-positive specimens demonstrated exceptionally high genetic similarity between HSV-1 strains in recipient and donor specimens of both DMEK cases.ConclusionsData indicate cross-contamination of cornea grafts during DMEK preparation with subsequent graft-to-host HSV-1 transmission that caused atypical sight-threatening herpetic eye disease shortly after DMEK. Ophthalmologists should be aware that HSV-1 transmission by DMEK is possible and can lead to atypical ocular disease, a condition that can easily be prevented by taking appropriate technical and clinical measures at both eye bank and surgical levels.

Highlights

Herpes simplex virus type 1 seroprevalence was determined on serum by enzyme-linked immunosorbent assay (Zeus Scientific)
Descemet’s membrane endothelial keratoplasty, first described by Melles et al in 2006,4 has developed into a common therapeutic intervention to restore corneal clarity in patients with endothelial disorders worldwide.[1]
Descemet’s membrane endothelial keratoplasty (DMEK) is technically more challenging than conventional PKP for both eye banks and surgeons in graft preparation, storage, and transplantation, which pose a higher risk of microbialcontamination.[1,3,5,6]

Summary

Introduction

Surplus cornea donor and recipient samples were sent by the eye bank to the Viroscience laboratory (Erasmus MC; Rotterdam, The Netherlands) to determine if the ocular HSV-1 complications were due to reactivation of latent recipient’s virus (both recipients were HSV-1 immunoglobulin-G positive at the time of DMEK; Table 1) or graftto-host HSV-1 transmission.[9,10,11,12,13] The sample set included corneal remnants from donors A and B used to prepare DMEK grafts for patients 1 and 2, respectively, conditioned culture media in which the donor corneas were cultured for several days, and media used to transport the prepared DMEK grafts to the operating room.

Results

Conclusion