Effect of Covid-19 on Eye Banks and Corneal Transplantations: Current Perspectives.

The coronavirus disease 2019 (COVID-19) pandemic exerted a great impact on medical practice, which was reframed according to the actual needs. Ophthalmological services and procedures including corneal transplantation did not represent an exception. The adoption and implementation of new standard operating procedures as well as of new technologies for remote consultation and smart-working reshaped daily activities of both eye bankers, physicians, researchers, and patients. Regulatory restrictions were issued redefining corneal donor eligibility criteria, as well as handling and harvesting procedures of donor ocular tissues. Surgical schedules underwent an abrupt contraction with prioritization of urgent procedures. Local lockdowns and confinement strategies resulted in both a reduction and redirection of research activities. The evaluation of SARS-CoV-2 colonization of ocular tissues, long-term corneal storage techniques, new disinfection strategies, split corneal transplants and cell-based therapies for the treatment of corneal disease peaked in the pipeline. Aim of this article is to summarizes the overall impact of the pandemic on the corneal transplantation machinery, and the current and future perspectives for the corneal transplant community.

5†The impact of the pandemic on ocular tissue procurement : the experience of fondazione banca degli Occhi del veneto.

INTRODUCTION: Since 21 February 2020, the day that the first Italian COVID-19 case was identified, the organizational and regulatory conditions for ocular tissue donation have undergone numerous changes in order to guarantee safety and quality. Herewith we report the key responses of the procurement programme to these challenges. MATERIALS AND METHODS: A retrospective analysis of the ocular tissue procured between 1 January 2020 and 30 September 2021 is reported. RESULTS: 9224 ocular tissues were procured during the study period (weekly average: 100 ± 21 tissues, mean ± SD; down to 97 ± 24, if only 2020 is considered). During the first wave, the weekly average reached 80 ± 24 tissues, a significant reduction if compared to the first 8 weeks of the year (124 ± 22 tissues/week, p<0.001), falling to 67 ± 15 tissues/week during the lock-down period. Considering the ocular tissues collected in the Veneto Region alone, the weekly mean was 68 ± 20, a reduction when compared to the first 8 weeks of the year (102 ± 23, p<0.001), arriving at 58 ± 15 tissues/week during the lock-down period. The percentage of healthcare professionals who tested positive during the first wave was on average 12% of the positive cases in the whole country, and equal to 18% in the Veneto Region alone. During the second wave, the mean weekly recovery of ocular tissue was 91 ± 15 and 77 ± 15 in the Veneto Region, compared to positive cases of healthcare professionals of 4% across Italy and in the Veneto Region. During the third wave, the overall weekly mean recovery rate was 107 ± 14, and 87 ± 13 in the Veneto Region, with only 1% of positive cases among healthcare professionals in Italy and in the Veneto Region. CONCLUSIONS: The most dramatic decrease of ocular tissue recovery occurred during the first wave of COVID-19, notwithstanding the lower number of infected people. This phenomenon can be attributed to different factors: a high percentage of positive cases and/or contacts among potential donors; the number of infections among healthcare professionals, favoured by the lack of personal protection equipement and the still partial knowledge of the disease; the exclusion of donors with bilateral pneumonia. Subsequently, the system was better organized with the assimilation of new knowledge about the virus, overcoming the initial fears about transmission and thus guaranteeing the resumption and maintenance of donations.

Presence of SARS-CoV-2 RNA in human corneal tissues donated in Italy during the COVID-19 pandemic.

OBJECTIVE: To analyse corneal tissues from asymptomatic donors with a postmortem nasopharyngeal swab tested positive for the presence of SARS-CoV-2 RNA, and therefore, understand the role that corneal transplantation may have in viral transmission. METHODS AND ANALYSIS: Between March 2020 and October 2021, 101 corneas (out of 8154 collected in Italy) from 51 donors (out of a total of 4155 Italian donors) positive for SARS-CoV-2 after postmortem nasopharyngeal swab tests were analysed for the presence of SARS-CoV-2 RNA through real-time RT-PCR. When available, the corneal tissue storage media were also assessed. Corneas and/or storage media with confirmed presence of SARS-CoV-2 RNA were further investigated by isolating SARS-CoV-2 virions, which were used to infect VeroE6 target cells. RESULTS: Only N=4 corneas and/or storage media out of 101 showed presence of SARS-CoV-2 RNA. No VeroE6 cell infection was detected with viral isolates, thus suggesting no presence of SARS-CoV-2 virions in corneal specimens and storage media. CONCLUSIONS: The presence of SARS-CoV-2 in cornea specimens would seem to be more likely due to prolonged detection of RNA rather than to active viral replication, with very low risk of infectivity and transmission through keratoplasty.

Impact of the COVID-19 Pandemic on Corneal Transplantation: A Report From the Italian Association of Eye Banks.

Purpose: To analyze the impact of COVID-19 on Italian corneal transplantation from March-2020 to February 2021 compared to the same timeframe of the 2 previous years, in order to identify potential consequences of a global pandemic on corneal procurement and transplantation services during this time. Methods: This national, multicentric, retrospective cohort study evaluated data collected from 12 (100%) Italian eye banks from March 2020 to February 2021 (Group A). The number of tissues collected, distributed and discarded were compared with the same time-frame of the 2 previous years: 2019 and 2018 (group B and C, respectively). The different type of transplants performed were reported. Data were analyzed using a non-parametric Friedman test. Results: Corneal procurement and the percentage of distributed tissues reduced in 2020 by more than 30 and 15%, respectively, compared to the 2 previous years. During the pandemic corneal transplant surgery showed only a modest drop: the number of the penetrating keratoplasties (PKs) and the anterior lamellar keratoplasties (ALKs) decreased by about 30 and 20% in comparison with groups B and C, respectively; between the Endothelial Keratoplasties (EKs), the Descemet membrane endothelial keratoplasty (DMEK) increased slightly from March 2020 to February 2021. Conclusions: Italy was one of the first countries most affected by the outbreak of COVID-19, and the Italian government adopted severe measures to limit viral transmission. The pandemic generated several implications in corneal transplant activity during the first lockdown. Then an efficacious reaction with constant, vigorous work led to a resumption of transplant surgery to a near-normal standard. The increase of EKs, despite the pandemic, is a sign that the advance in corneal transplantation has gone ahead and it continues to evolve.

Tracing the SARS-CoV-2 infection on the ocular surface: Overview and preliminary corneoscleral transcriptome sequencing.

COVID-19's impact on the ocular surface has already been recognized, however the molecular mechanisms induced by the infection on the ocular surface are still unclear. The aim of this paper is to provide a first overview of the transcriptional perturbations caused by SARS-CoV-2 on the ocular surface by analyzing gene expression profile of corneoscleral ring samples from post-mortem SARS-CoV-2 positive donors (PD). The presence of SARS-CoV-2 on the ocular surface, in tears and corneal tissues has rarely been detected in infected individuals in both the presence and the absence of ocular manifestations. In this preliminary study, 6 human corneoscleral tissues of 3 PD and two tissues from a negative donor (CTRL) were obtained at the local eye bank. The presence of genomic and sub-genomic SARS-CoV-2 RNAs was assessed by qRT-PCR, while transcriptome analysis (RNA-sequencing) was performed by Illumina. Principal Component Analysis (PCA), search for differentially expressed genes (DEGs) and Gene Ontology (GO)-enrichment analysis were performed. Three samples from PD were found positive for SARS-CoV-2 genomic RNA, although the absence of sub-genomic RNAs indicated an inactive virus. PCA analysis grouped 3 different clusters, one including CTRL, and the other two including, respectively, PD with undetected SARS-CoV-2 (PD-SARS-neg) and PD with detected SARS-CoV-2 (PD-SARS-pos). The DEGs in common with the 2 PD clusters included several genes associable to the interferon pathway, such as ADAMTS4, RSAD2, MMP1, IL6, ISG15 and proinflammatory cytokines. Among the down-regulated genes we found AQP5. GO analysis revealed 77 GO terms over-represented in PD-SARS-neg vs. CTRL, and 17 GO terms in PD-SARS-pos vs. CTRL. The presence of SARS-CoV-2 RNA and RNA-sequencing reads in ocular surface tissues supports the possibility that the eye acts as an entry route. The modulation of early responsive genes, together with several ISGs suggests a potential protective responsiveness of the ocular tissues to SARS-CoV-2.

Corneal transplant during COVID-19 pandemic: the Italian Eye Bank national report.

To investigate the impact of Coronavirus Disease-2019 lockdown on the Italian Eye Bank organization. In this national retrospective, multicentric, cohort study, data from the Italian Eye Bank during both the lockdown and the first month after the lockdown period were retrieved. We compared the Italian Eye Bank metrics with the same timeframe of 2019 and 2018. Data from 13 out of 13 (100%) Italian Eye Banks were included in the analysis. A statistically significant reduction in the number of donor corneas retrieved in 2020 was found as compared to the same period in 2019 and in 2018, respectively (2020 = 1284; 2019 = 3088; 2018 = 3221; ANOVA: p < 0.0001). Only 534 corneas have been distributed by Eye Banks during the COVID-19-lockdown period (2020 = 534; 2019 = 1220; 2018 = 1237. ANOVA: p < 0.0001). Similarly, the number of wasted corneas due to postponed or cancelled surgeries was 421, resulting in a considerable increase as compared to the previous 2 years (2020 = 421; 2019 = 67; 2018 = 84; ANOVA: p = 0.0035). Overall, 45 donor corneas were rejected in accordance with the guidance of the Italian National Health Institute Italian National Transplant Centre (CNT). SARS-CoV-2 pandemic has profoundly affected every social and medical field, including the Eye Bank procurement and distribution programs. The current data collected from all the Italian Eye Banks highlights the present and the forthcoming difficulties that the Eye Bank community is going to experience, as for the ongoing pandemic.

Corneal transplantation during the COVID-19 pandemic: An operational guide.

PURPOSE: To provide an operational guide for corneal transplantation during the COVID-19 pandemic aimed to maintain surgery and avoid spreading of SARS-CoV-2. METHODS: Prospective observational case series study in patients requiring corneal graft manage toward separate free and restricted pathways for those COVID-19 negative or positive, respectively. RESULTS: During the national lockdown, 30 consecutive patients underwent endothelial (n = 16), penetrating (n = 9), and anterior lamellar keratoplasty (n = 5). Two patients followed the COVID-19 restricted pathway, as they were considered positive while waiting for test results. Nine patients were hospitalized one night in the hospital. On admission to the hospital before surgery, at surgery, the day after surgery and at 7 and 30 days all patients and health-care personnel showed no symptoms and resulted negative at risks factors/exposure to the SARS-CoV-2 infection and occurrence of COVID-19. Nucleic acid testing resulted not detectable in all patients and SARS-CoV-2 antibodies quantification showed IgG and IgM below the positive predicted value in 29 patients. One patient showed IgM above the cut-off of significance (1.21 and 1.03 preoperative and 1-month postoperative, respectively) that were considered irrelevant because of the absence of symptoms and exposure risks. CONCLUSIONS: The concept of donor emergency (i.e. short-term availability of transplant tissues), makes corneal transplantation an always-urgent activity because it is related to the availability of the corneal tissue from a donor. Modest adjustments to ophthalmic clinic and eye surgery organization are required to maintain surgery and care of eye patients in a safe environment.

One threat, different answers: the impact of COVID-19 pandemic on cornea donation and donor selection across Europe.

OBJECTIVES: To assess to which extent the COVID-19 pandemic affected corneal transplantation by virtue of donor selection algorithms in different European countries. DESIGN: Survey. SETTING: 110 eye banks in 26 European countries. PARTICIPANTS: 64 eye banks covering 95% of European corneal transplantation activity. INTERVENTIONS: A questionnaire listing the number of corneas procured and distributed from February to May 2018-2020 was circulated to eye banks. MAIN OUTCOME MEASURES: The primary outcome was the number of corneal procurements. Additional outcomes were national algorithms for donor selection, classified according to their stringency (donors with COVID-19 history, suspected for COVID-19, asymptomatic, PCR testing) and the pandemic severity in each country. We calculated Spearman's correlation coefficient to determine, two by two, the relationship between the 3-month decline in eye banking activity (procurement), the stringency of donor selection algorithm and the grading of pandemic severity (cases and deaths). A partial correlation was run to determine the relationship between decline and stringency while controlling for pandemic severity. RESULTS: Procurements decreased by 38%, 68% and 41%, respectively, in March, April and May 2020 compared with the mean of the previous 2 years, while grafts decreased, respectively, by 28%, 68% and 56% corresponding to 3866 untreated patients in 3 months. Significant disparities between countries and the decrease in activity correlated with stringency in donor selection independent of pandemic severity. CONCLUSIONS: Our data demonstrate significant differences between countries regarding donor screening algorithms based on precautionary principles and, consequently, a decrease in the donor pool, already constrained by a long list of contraindications. Fundamental studies are needed to determine the risk of SARS-CoV-2 transmission by corneal transplantation and guide evidence-based recommendations for donor selection to justify their substantial medical and economic impact.