Prevalence of Herpes Simplex and Varicella-Zoster Virus DNA in Corneal Grafts Is Higher than Expected.

PURPOSE: (1) To determine the prevalence of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), varicella-zoster virus (VZV), and cytomegalovirus (CMV) DNA in donor corneas; (2) To evaluate the clinical outcome of the grafts with viral DNA and to compare donors with and without viral DNA. METHODS: We analyzed data from all donors and recipients who underwent penetrating keratoplasty (PK) or Descemet membrane endothelial keratoplasty (DMEK) between September 2022 and March 2023. Donor corneoscleral rims and excised recipients' corneal buttons were tested for the presence of HSV-1, HSV-2, VZV, and CMV DNA by polymerase chain reaction (PCR). The results were known 2-3 days after the surgery. We closely followed up on patients whose grafts tested positive for viral DNA. We compared the medical histories of donors with and without viral DNA. RESULTS: We included 85 corneas from 67 donors. Seven (8.2%) donor corneas tested positive for HSV-1 (n = 3) or VZV (n = 4) DNA. We did not detect any HSV-2 or CMV DNA. In the postoperative follow-up of patients with positive PCR, a graft failure was observed in one and infections in two eyes. Re-operation was necessary in three of these cases (42.9%). Patients without herpes DNA in the donor cornea needed reoperation in 7.7% of the cases. Cultural duration, the cause of the donor's death, and the death-to-explantation interval did not differ significantly between donors with and without viral DNA. Additionally, 3 of the 7 (42.9%) donors with positive PCR were in a septic status at the time of death, compared to 21 of the 78 (26.9%) donors with negative PCR (p = 0.52). CONCLUSIONS: The prevalence of herpes DNA in the donor corneas was 8.2% and thus higher than previously reported. We did not notice any evidence for a donor-to-host transmission, but a higher rate of postoperative complications in recipients of the grafts with viral DNA. The donors with and without herpetic DNA did not differ significantly regarding systemic diagnoses or cultural conditions, but sepsis was more frequent in the group with viral DNA.

Neurotrophic keratopathy: Clinical presentation and effects of cenegermin.

Purpose: To report on 4 patients (3 adults, 1 child) with neurotrophic keratopathy (NK) treated with cenegermin 20 µg/ml (Oxervate®), a recombinant human nerve growth factor (rhNGF), which was authorized by the European Medicines Agency for the treatment of neurotrophic keratopathy stage 2 and stage 3 of Mackie Classification in patients over 18 years of age. Observations: Three patients with neurotrophic keratopathy stage 2 and 1 patient with neurotrophic keratopathy stage 3, who were treated with cenegermin eye drops 6 times daily for 8 weeks, were observed. Two patients suffered from herpetic keratitis and 2 patients from neurotrophic keratopathy secondary to orbital radiation. In addition to closure of epithelial defects, an increase of corneal sensitivity and improvement of visual acuity has been shown in all treated patients at the end of therapy. One patient reported on neuralgic pain as a side effect. The corneal epithelium remained closed during the follow-up period of 11 weeks, 31 and 32 months after cessation of therapy in 3 patients, respectively. In one patient, corneal erosion recurred 4 weeks after completion of treatment due to recurrent HSV keratitis, which resolved after therapy adjustment and the corneal epithelium remained closed for 35 weeks. Conclusion: The cases presented suggest that treatment with cenegermin 20 µg/ml not only promotes corneal epithelial wound healing, but also significantly improves corneal sensitivity and visual acuity with minor side effects in adults and children.

Prevalence of Herpesvirus DNA in Corneal Transplant Recipients.

Purpose: Graft failure after penetrating keratoplasty (PK) is a serious complication, especially in eyes with herpetic keratitis (HK). This study evaluated the prevalence and graft survival of herpes simplex virus type 1 (HSV-1) and varicella zoster virus (VZV) DNA in recipient corneas during PK. Methods: The retrospective study was performed at the Department of Ophthalmology at University Hospital in Mainz, Germany. We analyzed data from every patient who underwent PK between January 2020 and June 2021. According to our clinical routine, we performed HSV-1 and VZV polymerase chain reaction (PCR) on all excised corneal buttons regardless of the primary clinical diagnosis. Results: We included 112 eyes of 112 consecutive patients who underwent PK. At the time of PK, 91 (81.25%) patients had no history of HK and 21 (18.75%) patients did. The recipient corneas of 91 patients without a history of HK tested positive for HSV-1 DNA in 12 (13.2%) eyes, for VZV DNA in 3 (3.3%) eyes, and for HSV-1 and VZV DNA simultaneously in 2 (2.2%) eyes. The recipient corneas of 21 patients with a preoperative history of HK tested positive for HSV-1 DNA in 13 (61.9%) eyes and VZV DNA in 1 (4.8%) eye. All patients with positive herpes DNA and no history of HK prior to PK received antiherpetic treatment and had a 100% graft survival rate after 1 year. Conclusions: We found herpesvirus DNA in 18.7% of recipient corneas without clinical suspicion or history of herpes keratitis. This suggests the need of routine HSV-1 and VZV PCR testing in all explanted corneas regardless of clinical suspicion, to detect, treat and prevent possible recurrence of herpes infection in corneal grafts and support graft survival.

How to Predict the Suitability for Corneal Donorship?

BACKGROUND: In Germany, more than one-third of donor corneas harvested are not suitable for transplantation. We evaluated the factors associated with the usability of donor corneas. METHOD: Data from 2032 consecutive donor corneas harvested at the Rhineland-Palatinate Eye Bank in Mainz, Germany, were retrospectively analyzed. Factors of interest were age, sex, lens status, cause of death, cardiopulmonary resuscitation (CPR), death-to-explantation-interval (DEI), and the influence of these factors on the proportion of discarded donor corneas. Factors associated with endothelial cell density (ECD) were analyzed in a linear regression mixed model. RESULTS: Higher donor age, male gender, pseudophakic lens status, and longer DEI were associated with significantly reduced ECD. With respect to DEI, the estimated cell loss was 7 ± 2 cells/mm2/hour (p < 0.001). Age was associated with a lower ECD of 6 ± 2 cells/mm2 per year (p = 0.001). Female ECD was 189 ± 44 cells/mm2 higher than male ECD (p < 0.001). Pseudophakic eyes had 378 ± 42 cells/mm2 less compared with phakic eyes (p < 0.001). Cause of death did not affect the ECD. Of note, 55% and 38% of corneas harvested on the second and third postmortem day, respectively, and 45% of corneas from donors older than 80 years were still suitable for transplantation. CONCLUSIONS: In the context of a growing need for donor corneas, we do not recommend limiting donor age and collection time to 24 h or excluding oncology donors, as is the practice in many countries. Therefore, we propose a mathematical model for better donor preselection.

Comparison of DMEK and DSAEK in Eyes With Endothelial Decompensation After Previous Penetrating Keratoplasty.

PURPOSE: Posterior lamellar keratoplasty is increasingly applied in patients with endothelial decompensation after penetrating keratoplasty (PK). The aim of this study was to compare the results of Descemet membrane endothelial keratoplasty (DMEK) and Descemet stripping automated endothelial keratoplasty (DSAEK) after PK. METHODS: In this retrospective study, clinical data of 30 patients who received DMEK (n = 19) or DSAEK (n = 11) for endothelial decompensation after PK were evaluated. All lamellar keratoplasties were performed at the Department of Ophthalmology at University Hospital Mainz, Germany. Primary end point included best-corrected visual acuity, and secondary end points included endothelial cell density, rebubbling, and rejection rates, all at 6 and 12 months. RESULTS: After 6 months and 12 months, 89% of DMEK and 73% of DSAEK grafts and 63% of DMEK and 64% of DSAEK grafts provided sufficient corneal deturgescence, respectively, represented by improvement in best-corrected visual acuity. DMEK group median preoperative Logarithm of the Minimum Angle of Resolution visual acuity of 1 increased to 0.5 after 6 and 12 months. DSAEK group median Logarithm of the Minimum Angle of Resolution visual acuity increased from 3 to 2 and 1.3 after 6 and 12 months. After 12 months, graft endothelial cell density had decreased by 58% in the DMEK group and by 59% in the DSAEK group. The proportion of patients requiring a rebubbling were 63% in the DMEK and 64% in the DSAEK group. No lamellar graft rejection occurred in either trial arm. CONCLUSIONS: Both DMEK and DSAEK significantly improved visual acuity in patients after PK. Lamellar graft survival, loss of endothelial cells, and mean rebubbling rates were similar in both groups.