The unprecedented global spread of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its resultant cardiopulmonary disease, COVID-19, has radically altered a multitude of global practices. As we seek the appropriate adjustments to the practice of ophthalmology, we will be constantly challenged to both confront the current disease burden and shape its future curvature. In doing so, we must incorporate a knowledge base that is both as young and dynamic as the pandemic itself. Additionally, we must be prepared to serve the emergent needs of the population in as safe a manner as possible. A significant issue at present is the inevitable interaction of the cornea donor pool with SARS-CoV-2. Even with our currently limited testing capacity, the confirmed US and global case numbers are significant, and trending towards an unknown peak . The number of recent case contacts is further expected to be significantly higher than the total confirmed case number. The current annual US all-cause mortality rate is approximately 867 per 100,000 . In addition to deaths directly caused by COVID-19, it is expected that a significant number of individuals dying from all other causes will be infected by or exposed to COVID-19. It is therefore probable that a sizable fraction of donated corneas will soon meet a donation exclusion parameter set out by a tissue banking governing body (Table 1).
Current guidance from the Eye Bank Association of America (EBAA) and the Global Alliance of Eye Bank Associations (GAEBA) is crafted in a prudently conservative manner that largely excludes donors positive for, or in recent close contact with, COVID-19 [3, 4]. These recommendations are congruent with U.S. Food and Drug Administration (FDA) guidance on human cell, tissue, and cellular or tissue-based products (HCT/P), which call for careful consideration of whether HCT/P donors have been infected or in contact with COVID-19 within the past 28 days. The FDA guidelines further indicate that there is currently no evidence for transmission of respiratory viruses in general through tissue transplantation, implantation, or infusion, and therefore do not recommend tissue banking establishments use additional laboratory screening for asymptomatic HCT/P donors. .
In the US alone in 2018, all-cause mortality claimed the lives of approximately 2.8 million residents . Of these deaths, 168,569 were determined eligible for corneal donation by the EBAA, and 123,222 corneas were ultimately recovered and banked for intended transplant. Thus, even prior to the COVID-19 pandemic, an already small proportion of potential donor corneas make it to the donor pool after being filtered through a series of stringent eligibility criteria that include several viral contraindications .
At present, the EBAA excludes corneas from donors affected by HIV types 1 and 2, hepatitis B virus (HBV), hepatitis C virus (HCV) herpes simplex virus (HSV), human T-cell lymphotropic virus (HTLV)-1, HTLV-2, rabies, West Nile, vaccinia, Zika, and Ebola virus disease (EVD). Other communicable agents that may be transmitted by ocular tissue and pose a risk to recipients and tissue handlers or have insufficient evidence of risk are also excluded, especially if such agents possess the potential for a high prevalence in the donor pool .
These exclusion criteria are based on an approach that attempts to weigh the risks of a virus’s transmissibility, prevalence, and recipient effects. Exclusion criteria are easily drawn for viruses such as HSV, which is transmissible through penetrating keratoplasty (PK), is prevalent in the general population, and is a known contributor to primary graft failure (PGF) [8,9,10]. Although low in prevalence, rabies virus bears a similar risk profile to HSV in that it has known transmissibility through corneal transplantation and a significant potential host effect [11, 12]. Some viruses with no known transmissibility through corneal donation, such as HIV, HCV, and West Nile virus, are excluded for their potentially devastating recipient effects and transmissibility by non-ocular routes, even in the absence of observed transmissibility through corneal donation . Additionally, for HIV, corneal epithelial detection alone has been sufficient to raise concern for corneal donation , even in the absence of seroconversion in corneal recipients from known HIV-positive donors, and a known lack of transmissibility through ocular tissues or tears [8, 14,15,16,17]. Conversely, donor cytomegalovirus (CMV) infection does not preclude corneal donation, even though CMV affects up to 60% of the US population , can be transmitted through corneal donation, presents low but unclear risks for PGF [19, 20], and can be problematic for immunosuppressed recipients [21, 22]. This is likely due to a lack of significant recipient effect in a vast majority of cases and ease of treatment with antivirals . Adenovirus affected individuals without keratitis are similarly not excluded due to a lack of significant recipient effect, despite its high prevalence and role in keratoconjunctivitis in the general population. Influenza virus, too, is not a current eye banking exclusion parameter despite being a significant cause of global morbidity and mortality. In the 2018–2019 flu season, 34,200 people died from viral influenza in the US alone, generating 68,400 total corneas. . Approximately 5.6 million corneas were generated by all-cause mortality in the US in 2018, 123,122 (2.2%) of which ultimately met EBAA eligibility and were recovered for intended transplant. At a rate of 2.2%, an estimated 1500 corneas from influenza-deceased individuals were potentially recovered for intended transplant in the US in 2018. In reality, this number is likely lower due to EBAA exclusion of deaths due to sepsis. Although COVID-19 is a considerably more significant pandemic than the current influenza burden, influenza remains a valid example of a deadly, primarily respiratory, virus that is capable of causing conjunctivitis and is detectable by conjunctival swabbing . Despite the potential illness severity of influenza, corneas generated by non-septic influenza deaths are still considered suitable for donation, and have not been shown to pose a significant risk to corneal tissue recipients.
The exclusion of SARS-CoV-2-affected corneas from the donor pool is appropriate at present given its relatively high transmissibility, possible conjunctival presence, and the possible severity of resultant infection. However, while the exclusion of individuals infected with or exposed to COVID-19 from the donor pool may be currently appropriate, the rate of spread of this disease, in conjunction with its relatively high mortality, may unfortunately preclude the outright avoidance of this potentially vast donor pool moving forward. Moreover, while tissue availability is currently sufficient in the US, especially with reductions in non-essential operative volume, the avoidance of COVID-19-affected tissues could disproportionally affect import-reliant countries that source tissues from surplus nations .
It is therefore imperative that we characterize the theoretical risks posed to recipients of corneas from COVID-19-affected donors so that informed decisions can guide practice in the midst of this pandemic. In this article, we attempt to frame a discussion about the theoretical risks of transplanting corneal tissue from donors infected with or exposed to COVID-19, by compiling lessons from prior global coronavirus outbreaks and describing what is currently known about the interaction of this disease with ocular tissues. While relevant and highly important, the additional risks posed to tissue recovery personnel, eye bank staff, and surgeons are outside of the scope of this article. Furthermore, this article is based on previously conducted studies and does not contain any studies with human participants or animals performed by any of the authors.