Early Impact of COVID-19 Outbreak on the Availability of Cornea Donors: Warnings and Recommendations

Corneal blindness is the fourth leading cause of blindness worldwide; however, nearly 80% of all corneal blindness cases are avoidable and reversible. To date, keratoplasty is the most commonly performed allogenic transplant worldwide, with a success rate of 90–95%.¹ Thus, the treatment of acute corneal diseases, mainly trauma or infectious keratitis, is an urgent or emergent care issue that can involve aggressive surgery, requiring the availability of optimal eye-banked tissues, by trained personnel.¹ Reports from the Eye Bank Association of America (EBAA) show an increase in the number of whole globe and cornea donations in recent years, with a +1.9% change in 2019 compared to 2018.²

In response to the COVID-19 pandemic, ophthalmology departments have been either placed in lockdown or reorganized into COVID-19 units³ to cater to the lack of infrastructure and resources in many regions. It has been reported that patient encounters have drastically decreased, by 57% in cardiology-related cases and by 55% in breast health-related cases, with a 37% decline in cancer care.⁴ Moreover, the percentage of ophthalmological treatments decreased by about 81% in March and April 2020 in comparison with the same period in 2019.⁴ This includes a 97% reduction in cataract surgery volume — the largest reduction of any surgical routine procedure — until its total blockage and a delay of urgent proceduresdue to the need for prioritizing emergencies.^4–6 In several countries, reduced access to emergency care for diseases, such as retinal detachment, thrombotic events and trauma, as well as reduced cornea donations, have been observed (almost 60% less than in the same period of 2019 at the Eye Bank of Lublin, Poland).⁷ This has resulted in a significant reduction, leading to a complete suspension of transplantations in many departments. This process, if not reversed, could lead to disability and may severely affect access to sight-saving cures for many patients.

Moreover, the increasing number of reported COVID-19 cases after solid organ transplantation emphasizes an urgent need for protocol modifications based on donor–recipient selection, postoperative screening and treatment.⁸ Indeed, all urgent surgeries involving the use of donor tissues could be a potential route of virus transmission for both medical personnel and recipients.

We have agreed to consult with a group of surgeons and experts from 10 European countries, called the European COVID-19 Cataract Group (EUROCOVCAT). We have organized call conferences and shared experiences and perspectives on the current scenario. An in-depth analysis of the current situation in eye care has been merged with updated literature and available recommendations from scientific ophthalmic societies and healthcare institutions.

Currently, there is no evidence to substantiate that harvested corneal grafts from COVID-19 patients can contain SARS-CoV-2 and lead to a systemic infection. Although the risk of transmission through corneal stromal tissue is low, it potentially exists owing to the presence of ACE2 and TMPRSS2 expressions in cornea.^9,10 For these reasons, stable recommendations on corneal transplant procedures are highly demanded but still controversial.

A survey conducted in the USA revealed the heterogeneous guidelines and approaches among different transplant centers, but COVID-19 is, undoubtedly, a major threat in transplantation. The survey also revealed the variations in screening, testing algorithms, clinical practice and policies, and the differences in transplanted organs and types of transplant.¹¹ The lowest rates of reduction in organ transplantations were observed for heart, lung and deceased donor kidney, whereas the highest rates of reduction were observed for transplantations of live donor kidney, live donor liver and pancreas. Suspected COVID-19 testing algorithms for deceased donors and recipients also varied among respondents. Almost half of respondents suggested simultaneous full respiratory viral panel (RVP) with COVID-19 testing. Others suggested that common algorithms were isolated COVID-19 testing (in almost 30%) and reflex COVID-19 testing if influenza, respiratory syncytial virus or full RVP tests were negative.¹¹ The most frequently proposed tests for deceased donors were the nasopharyngeal nucleic acid test and bronchoalveolar lavage nucleic acid test, which is the rarest blood nucleic acid test. However, in almost 4% of respondents, no test was proposed. More than half of respondents reported changes in outpatient practices, from stopping or reducing visits to switching to telemedicine.¹¹

The specifics of keratoplasty differ from transplantation of other organs, especially with respect to the general condition of the recipient. Thus, some analogies and conclusions should be made and applied in ophthalmology. In the COVID-19 pandemic, safety as a principal goal of any medical intervention (primum non nocere) is axiomatic. The risk of contamination of the recipient must be eliminated, considering deficient knowledge about donor-derived infection and imperfections in diagnostic tests.¹² Although the existing protocols of tissue preparation provide full protection for medical personnel and recipients, additional security measures must be applied. The epidemiological history of the donor, potential contact with SARS-CoV-2 carriers and onset of typical COVID-19 symptoms must be screened. In all donors, a nasopharyngeal swab RT-PCR test for SARS-CoV-2 should be mandatory. Asymptomatic or subclinical patients with SARS-CoV-2 infections pose particular risks for recipients, especially when reputable RT-PCR tests for SARS-CoV-2 do not rule out the possibility of COVID-19 virus infection. The false-negative tests (in the range of 17–63% of cases^13,14) can be a consequence of many factors: poor quality of the specimen containing insufficient patient material, late or very early collection of specimens with respect to infection stage, or mishandling or inappropriate shipping of specimens.¹⁵ To eliminate the risk of potential transmission, special efforts should be undertaken with respect to the technical aspects of nasopharyngeal swabs. To determine the presence of an adequate amount of material in the sample, a PCR testing human DNA target should be included as a control.¹⁵ In addition, in donors with preserved circulation, chest CT scans should be performed, even if the donor has a negative clinical and epidemiological history.

EBAA has listed some of the potential viruses that can transmit via ocular tissues (West Nile virus, Vaccinia virus, Ebola virus and Zika virus). This is because of their high prevalence in the donor pool and their fatal or life-threatening status. Such infection could result in permanent impairment or damage of a body function, or could necessitate medical or surgical intervention to preclude it. However, there is insufficient evidence to substantiate such transmission.¹⁶ A single post-mortem RT-PCR for SARS-CoV-2 should eliminate the risk of transmission in a deceased donor.

The COVID-19 pandemic has recently forced governing bodies to revise their recommendations for corneal transplantation (Table 1).^17–19 Such recommendations should eliminate the risk of transmission, according to previous experiences based on similar viruses.

Table 1 Guidelines of the Eye Bank Association of America (EBAA), Global Alliance of Eye Bank Associations (GAEBA) and European Association of Tissue Banks