INVITED SUBMISSION
COVID and the Cornea: From Controversies to Consensus
Report of the Eye Bank Association of America Medical Advisory
Board Policy and Position Review Subcommittee
Anthony J. Aldave, MD,* Jennifer DeMatteo, MCM, CIC,† Winston D. Chamberlain, MD, PhD,‡
Brian Philippy, BSChE, BS, CEBT,§ Asim V. Farooq, MD,¶ Natalie Buckman, CEBT,k
Downloaded from http://journals.lww.com/corneajrnl by A/nvVbYlBmpeE8zlmuOgQqR3EbrhIbX80eJ8l18vhH8SFjplSVmf/SyrpHOG07m7d/W41EKl9dG5zPOgC18HAECGDfFAWzTo9BbhxD6sc/vCdCS4GIxG8TsA+k+s1Y2o on 06/12/2021
Andrea Crosson, CEBT,** Jennifer Li, MD,†† Eric Meinecke, CEBT,‡‡ and Adam H. Kaufman, MD§§
Key Words: Cornea, COVID-19, SARS-CoV-2, eye banking
(Cornea 2021;40:809–816)
C orneal surgeons in the United States and worldwide have
judiciously proceeded with surgery during the COVID-19
pandemic. As lockdowns progressed in the United States in early
2020, elective surgeries were put on hold, and only emergency
corneal transplants were performed. The Policy and Position
Review Subcommittee (PPRS) of the Eye Bank Association of
America (EBAA) Medical Advisory Board was charged with
developing guidelines for eye banks to determine donor eligibility
in relation to COVID-19 that could ensure the safety of the
corneal tissue that was needed for urgent procedures and that
would be needed for elective keratoplasty procedures once they
could be performed again. The initial and revised EBAA
guidelines have not always been in agreement with those of
other related regulatory bodies because of differing opinions and
conflicting data on a variety of topics, including the utility of
universal testing of donors for SARS-CoV-2, the reliability of
postmortem testing for SARS-CoV-2, and the risk of transmission
of SARS-CoV-2 through corneal transplantation. Although the
performance and reporting of in vitro, in vivo, and postmortem
studies have provided significant insights into the transmission of
SARS-CoV-2 and effectiveness of testing for SARS-CoV-2,
evidence continues to be published each week supporting both
sides of these issues that are of critical importance to ensuring the
Received for publication December 26, 2020; revision received February 21,
2021; accepted February 22, 2021. Published online ahead of print March
26, 2021.
From the *The Stein Eye Institute, David Geffen School of Medicine at UCLA,
Los Angeles, CA; †Eye Bank Association of America, Washington, DC;
‡Casey Eye Institute, Oregon Health & Science University, Portland, OR;
§Lions Medical Eye Bank of Eastern Virginia, Norfolk, VA; ¶Department
of Ophthalmology and Visual Science, University of Chicago Medical
Center, Chicago, IL; kMinnesota Lions Eye Bank, Minneapolis, MN;
**SightLife, Seattle, WA; ††Department of Ophthalmology, University of
California, Davis; ‡‡Georgia Eye Bank, Atlanta, GA; and §§University of
Cincinnati and Cincinnati Eye Institute, Cincinnati, OH.
The authors have no funding or conflicts of interest to disclose.
Correspondence: Anthony J. Aldave, MD, Stein Eye Institute, David Geffen
School of Medicine at UCLA, 100 Stein Plaza, UCLA; Los Angeles, CA
90095 (e-mail: aldave@jsei.ucla.edu).
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Cornea  Volume 40, Number 7, July 2021
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safety of donor corneal tissue. Therefore, this article will present
in 3 sections the areas of controversy and consensus, where it
exists, regarding the transmission of, as well as screening and
testing for, SARS-CoV-2: the development and effectiveness of
the EBAA COVID-19 screening guidelines, arguments for and
against universal testing of donors for SARS-CoV-2, and the risk
of transmission of SARS-CoV-2 through corneal transplantation.
DEVELOPMENT OF THE EBAA COVID-19
SCREENING GUIDELINES
The PPRS of the EBAA Medical Advisory Board issued its
first guidelines for EBAA member eye banks regarding COVID-
19 screening on February 3, 2020. The initial guidelines consisted
of a list of 5 criteria, any one of which would exclude a potential
ocular tissue donor: travel to mainland China, travel to another
geographic area designated as an area of active transmission by
the Centers for Disease Control and Prevention (CDC) with
symptoms consistent with COVID-19 infection or exposure to a
person suspected to have COVID-19 infection, close contact with
a person confirmed to have COVID-19 infection, positive test for
COVID-19, and symptoms consistent with COVID-19 infection
without a plausible alternative etiology. As local transmission
replaced foreign travel as the cause of the majority of cases in the
United States, and as reverse transcriptase-polymerase chain
reaction (RT-PCR) testing for SARS-CoV-2 became more readily
available and more commonly performed, updated guidelines
issued biweekly from March 3, 2020, to April 14, 2020, reflected
the evolving donor eligibility criteria. The revised guidelines
issued on May 14, 2020, were the first to include a decision table
that used the result of RT-PCR testing as the primary determi-
nation of eligibility for ocular tissue donation. Although a positive
RT-PCR test within 28 days of death indicated that the donor was
not eligible, a negative RT-PCR test did not necessarily indicate
eligibility. The presence of signs and/or symptoms of COVID-19,
the existence of a plausible alternative etiology for the signs and
symptoms, and having close contact with an infected individual
were taken into consideration when determining eligibility in
situations in which the RT-PCR test was negative, indeterminate,
or not performed. Medical director review was recommended to
determine eligibility in a number of such scenarios, primarily
when the RT-PCR test was negative, indeterminate, or not
performed in the presence of signs and/or symptoms of
COVID-19, with a plausible alternative etiology.
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Aldave et al
As eye bank technicians, eye bank medical directors, and
others who used the EBAA donor eligibility guidelines provided
feedback to the EBAA, and as additional information was
obtained regarding the risk factors for COVID-19 transmission,
the guidelines were revised further. The most significant changes
to the guidelines released on July 31, 2020, and October 20, 2020,
were to allow for medical director review for eligibility in the
presence of signs and/or symptoms of COVID-19, the existence
of a plausible alternative etiology for the signs and symptoms, and
the absence of close contact with an infected individual (Fig. 1).
The PPRS expects to continue to revise the EBAA donor
eligibility guidelines as more information is obtained regarding
its effectiveness in practice. A study conducted by Eversight
Eye Bank that involved routine postmortem SARS-CoV-2 RT-
PCR testing of all donors deemed eligible by the EBAA donor
eligibility guidelines found that 4.8% (15/314) of the donors
tested positive (Dena Ballouz, The Impact of the COVID-19
Pandemic on the Cornea Donor Pool and the Role of Routine
COVID-19 Testing for all Donors. Cornea and Eye Banking
Forum, November 7, 2020). Six of these 15 donors had a
negative RT-PCR test before death (range 4–13 d before
death), raising the question of the accuracy of premortem
negative results and postmortem testing. Regardless, this study
does raise concerns regarding the effectiveness of the EBAA
donor eligibility guidelines in practice.
Impact of EBAA COVID-19
Screening Guidelines
Without universal testing of all donor corneas for SARS-
CoV-2, screening guidelines play a vital role in maintaining the
safety of the donor pool. As mentioned above, the current EBAA
COVID-19 screening guidelines rely heavily on eye bank medical
directors to review donor information and determine donor
eligibility in certain cases. The medical director’s unique role in
the eye bank provides a mechanism to evaluate donors on a case-
by-case basis and helps to increase tissue utilization, given the
many nonspecific signs and symptoms of COVID-19 infections.
Based on an EBAA COVID-19 Impact Survey for US eye
banks, placement of tissue for domestic surgeries was approxi-
mately 6% to 7% of prepandemic volume during the height of the
shutdown in March and April 2020; international placement was
essentially nonexistent during that period (Kevin Corcoran, CAE,
oral communication, February 19, 2021). With the help of medical
directors, the strict guidelines put in place at the beginning of the
COVID-19 shutdown could be more safely relaxed to allow for an
expansion of the donor pool without requiring universal testing of
donors for SARS-CoV-2. As a result, placement of tissue for
domestic and international surgeries has recovered to about 80%
and 50% of prepandemic volumes, respectively.
This level of near daily involvement from medical directors
to assist with questions of donor eligibility is a distinct departure
from prepandemic practice patterns where medical directors were
consulted only occasionally. EBAA medical directors have risen
to the challenge, but, ultimately, they are volunteers with their
own busy clinical and surgical practices. Thus, the need for
medical director consultation can potentially lead to delays in
releasing tissue to surgeons. In addition, as ophthalmologists,
medical directors may be less comfortable determining donor
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Cornea  Volume 40, Number 7, July 2021
eligibility in cases with complex medical histories and thus may
need to consult specialists in other fields, such as infectious
disease and pulmonary and critical care, to determine eligibility.
Nevertheless, increased medical director involvement in the donor
eligibility determination during the COVID-19 pandemic has
been essential in maximizing tissue utilization and the resumption
of elective corneal surgery in the United States.
Comparison With Other Regulatory
Body Guidelines
The US Food and Drug Administration (FDA) most
recently updated its guidance regarding the COVID-19 pan-
demic to tissue banks on January 4, 2021, stating that it does not
recommend the performance of routine SARS-CoV-2 RT-PCR
testing of asymptomatic donors of human cells, tissues, or
cellular or tissue-based products.1 Instead, when considering
whether to perform testing and determine candidacy of potential
donors, the FDA recommends taking into account donor risk
factors for infection, such as having been diagnosed with
COVID-19 or suspected of having COVID-19, or close contact
with someone else who was, within 4 weeks of recovery. These
recommendations are based on the fact that respiratory viruses
are not known to be transmitted by the implantation, trans-
plantation, infusion, or transfer of these products and the fact that
screening measures are already in place and being used to
identify clinical signs of COVID-19 in potential donors.
The American Association of Tissue Banks has not issued
recommendations regarding donor screening for COVID-19,
instead choosing to issue a bulletin describing the aforementioned
FDA recommendations.2 The American Society of Transplant
Surgeons issued a guidance document on March 27, 2020,
recommending that screening for COVID-19 be performed for all
potential donors but did not comment on other COVID-
19–related criteria to be used to determine donor eligibility.3
The Association of Organ Procurement Organizations (AOPO)
most recently issued guidance regarding COVID-related eye and
tissue donation on its Web site on July 15, 2020.4 The criteria
used to determine eligibility, other than travel history, are the
same as those in the most recent EBAA donor eligibility
guidance document, specifically, the result of SARS-CoV-2
diagnostic testing, symptoms consistent with COVID-19 infec-
tion, the presence or absence of another explanatory diagnosis,
and close contact as defined by the CDC. Both the EBAA and
AOPO eligibility criteria exclude potential donors with a positive
RT-PCR test within 28 days of recovery and potential donors
with symptoms of COVID-19 infection without a plausible
alternative etiology. However, although the EBAA eligibility
criteria allow for medical director review in cases of close contact
in the setting of a negative RT-PCR test in asymptomatic donors
and symptomatic donors with a plausible alternative etiology, the
AOPO eligibility criteria exclude these potential donors.
SHOULD ALL DONORS BE TESTED FOR
COVID-19?
Although SARS-CoV-2 has been a strain on the eye
banking system and individual banks around the globe, the
screening demands on potential donors related to this
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Cornea  Volume 40, Number 7, July 2021 EBAA MAB COVID and the Cornea

FIGURE 1. Eye Bank Association of America COVID-19 eligibility criteria for ocular tissue donation. (The full color version of this
figure is available at www.corneajrnl.com.)

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Aldave et al
infection may be the greatest burden. The potential dread of
virus transmission during a routine corneal transplant surgery
has led to multiple international proposals/guidelines by eye
banking organizations with several subsequent revisions that
have been influenced by transplant societies and governmen-
tal regulatory authorities such as the US CDC and FDA.
One of the more controversial points of donor screening is
the requirement, or lack thereof, for universal SARS-CoV-2
testing of the donor. Early in the pandemic, testing was not
widely available in the United States.5 With limited supplies and
reagents for performing RT-PCR SARS-CoV-2 testing on
patients and the population in general, it was felt that implement-
ing a universal requirement to test all donors postmortem would
potentially be an irresponsible use of resources. These supply
chain issues for COVID-19 testing persisted months into the
pandemic causing backlogs in testing and delaying results.
Fortunately, testing capabilities have improved and are now
broadly available in the United States and elsewhere.
TESTING APPROACHES
RT-PCR and Antigen Testing
Diagnostic testing for SARS-CoV-2 includes nucleic
acid amplification and antigen tests, with the former being the
gold standard. The most commonly performed nucleic acid
amplification test, RT-PCR, amplifies and detects SARS-
CoV-2 RNA from oropharyngeal (OP), nasal (N), nasopha-
ryngeal (NP), or other anatomic sites. The commercially
available tests are performed by a variety of companies and
have a broad range of sensitivities (OP: 35%–77%; N:
59%–94%; and NP: 92%–100%) but with uniformly high
specificity (99%–100%).5,6 However, as RT-PCR can detect
levels of viral nucleic acid that cannot be cultured, a positive
result does not necessary indicate contagiousness.7
Antigen testing involves the use of an immunoassay to
detect the presence of a particular viral antigen and is authorized
to diagnose SARS-CoV-2 using OP and NP swab specimens.
Although antigen testing is relatively inexpensive and can provide
results in just minutes, it is generally less sensitive than RT-PCR,
and thus, the CDC recommends confirming negative antigen
testing results in symptomatic patients and positive antigen testing
results in asymptomatic patients with nucleic acid amplification
testing.7 We are not aware of any organ procurement organization
or eye bank using antigen testing for donor screening because of
its lower sensitivity compared with RT-PCR.
Serum Antibody Testing
A different category of tests screen for serological evidence
of current or past infection by detecting SARS-CoV-2 antibodies
in an individual. In the broadest understanding of infections, the
IgM antibody response is expected to rise during an acute
infection and decline during infection resolution, whereas the IgG
antibody response is expected to rise later and remain present for
an extended period after the resolution of infection.8 However,
there is no significant difference in the sensitivity of serologic
testing for IgM antibodies compared with IgG antibodies in the
first 2 weeks after SARS-CoV-2 infection.9 In addition, the
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Cornea  Volume 40, Number 7, July 2021
relatively low sensitivity of serologic testing in published studies
(23%–63% at 1 wk and 68%–96% at 2 wk after symptom onset)
indicates that the false-negative rate associated with serologic
testing is too high to be an acceptable means of screening
potential tissue donors. Although the specificity of serologic tests
in published series is much higher (96%–100%), false-positive
results are still a concern, albeit less so in the setting of donor
screening than are false-negative results. Because symptomatic
donors will be excluded by COVID-19 screening criteria, the
lower prevalence of SARS-CoV-2 infection in the population of
asymptomatic donors in whom serologic testing would be
performed means that a significant percentage of the positive
serologic tests will be false positives, resulting in unnecessary
donor exclusion. For these reasons, the EBAA and other organ
procurement organizations are not recommending serological
testing to screen for donor infection, which is in line with FDA
recommendations for asymptomatic human cell, tissue, or
cellular or tissue-based product donors.1
THE ARGUMENT AGAINST UNIVERSAL TESTING
Positive RT-PCR Results Do Not Necessarily
Indicate Viral Shedding
Application of RT-PCR screening in eye banking must
still be approached with caution because of the lack of
understanding on how to interpret the test results. For instance,
testing in early infection may give a negative result.10 Some
testing results are classified as inconclusive or indeterminate,
which suggests that although viral RNA was detected, it was at a
level below that considered to be a true positive.11 Under the
current EBAA recommendations, tissue from a donor with an
indeterminate result would be considered ineligible because
repeat testing would not be possible. The fact that the incidence
of a false-positive RT-PCR test result has been reported to be as
low as 0.9% for OP swabs and 0% for N and NP swabs provides
reassurance that transplantable tissue will not be disposed of
because of erroneous results.5 However, the proportion of
wasted tissue could be much higher considering that 18% of
recovered COVID-19 patients will test positive again, although
they are not shedding replicating virus.12 Given the increase in
the number of infected donors in early 2021, the number of
tissues disposed of because of a false positive or true positive not
associated with active infection is concerning. Although the
domestic tissue supply may not be affected significantly, the
supply of corneas for international distribution from US eye
banks, accounting for one-third of all corneas that are distributed
for transplantation by domestic eye banks, may be.
False-Negative RT-PCR Results
False-negative results in RT-PCR testing are equally
troublesome. False-negative rates can be as high as 6.5% for
OP swabs and 0.8% for NP swabs, leading to the errant
utilization of a small percentage of tissues from donors with
true infections.5,13 Given a high prevalence of asymptomatic
SARS-CoV-2 infections, it is an increasing concern that
ocular tissue from an infected individual could pass screening
criteria and be transplanted.14
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Cornea  Volume 40, Number 7, July 2021
SARS-CoV-2 Testing Is Not Validated for
Cadaveric Donors
Neither RT-PCR, antibody testing, nor the newest rapid
antigen testing has been validated for postmortem use in
which setting higher error rates may be observed. If post-
mortem RT-PCR testing is to be performed, the CDC
recommends that NP swabs be used. If a postmortem biopsy
is performed, the collection of swabs from each lung would
also likely increase the diagnostic yield.15
THE ARGUMENT FOR UNIVERSAL TESTING
SARS-CoV-2 Remains Stable and Infectious in
the Nasopharyngeal Mucosa Postmortem
Antemortem and postmortem NP swab samples collected
from individuals who died from COVID-19 have demonstrated
stable levels of recoverable SARS-CoV-2 RNA up to 7 days after
death.16 In addition, replicating virus has been detected in NP
samples collected up to 36 hours after death, indicating that
SARS-CoV-2 infection can be diagnosed using NP samples up to
1 week after death and that eye bank technicians need to use the
appropriate precautions when collecting postmortem samples.16
Fallibility of Screening Recommendations
Although the EBAA is not requiring eye banks to perform
donor RT-PCR testing for SARS-CoV-2, other organizations
such as The American Association of Tissue Banks and
international organizations such as Eye Bank Association of India
are currently advising testing.2,17 Early in the pandemic, the Eye
Bank Association of Australia and New Zealand advised against
routine testing for multiple reasons including test availability, lack
of validation in cadavers, and difficulty in obtaining samples from
deceased patients.18 Because as many as 75% of those infected
with SARS-CoV-2 are asymptomatic at some point during the
course of their infection, a strong argument could be made to test
all donors who were not tested recently before death, taking into
account the high specificity of NP RT-PCR.14,19 In addition,
individuals are most infectious at or before symptom onset and
may pass through other exclusionary criteria that rely on signs,
symptoms, and contact tracing.20
CHALLENGES OF UNIVERSAL TESTING
In considering a SARS-CoV-2 testing mandate for all
donors, there are several logistical components that must also be
considered. Although premortem testing is readily extracted from
the donor chart, postmortem testing will take up to 72 hours, which
could delay tissue placement and further processing. Testing a
large percentage or all the donor pool is not an insignificant
expense to the eye banking system, adding $60 to $200 per test per
donor that will have to be bundled with the tissue processing
charges and ultimately could increase cost to the hospitals, surgery
centers, and payers. Eye bankers, although skilled in collecting
potentially infectious biological samples, have needed to acquire
new skill sets for NP and OP swabs to ensure the safety to the
technician and quality of the testing sample. In addition, the
molecular testing guidelines proposed in the United States and
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EBAA MAB COVID and the Cornea
other countries with developed health care systems may not be
able to be implemented in countries with limited health care
resources where testing modalities are not as available or reliable.
Although donor SARS-CoV-2 testing has a place in current
donor screening paradigms, the uncertainty of test reliability still
creates concerns for accidental transmission of disease and the
disposal of tissue that is actually safe for keratoplasty. A clearer
understanding of host factors facilitating viral infection of ocular
tissue and the persistence of ocular infection are necessary to
understand the risks of disease transmission for corneal transplant
surgery. The emergence of effective vaccinations that confer long-
term immunity may eliminate concerns for large portions of the
donor pool and will likely be incorporated into revised donor
screening paradigms in 2021.
WHAT IS THE RISK OF TRANSMISSION OF SARS-
CoV-2 THROUGH
CORNEAL TRANSPLANTATION?
Because the EBAA established an initial donor screening
protocol in the early phase of the COVID-19 pandemic, a
number of important studies on SARS-CoV-2 have been
performed, which have been informative regarding the poten-
tial risk of viral transmission through corneal transplantation.
Thus far, there has been no documented transmission of SARS-
CoV-2 from donor to recipient in any organ transplant
procedure.1 However, there have been a select number of
cases in the United States in which patients received tissue
from donors who were SARS-CoV-2 positive. This section
will review the current evidence surrounding the possibility of
SARS-CoV-2 transmission through corneal transplantation.
EVIDENCE SUPPORTING a RISK OF SARS-CoV-
2 TRANSMISSION
Presence of SARS-CoV-2 in the Tear Film
Although a number of viruses can cause corneal and
ocular surface disease, confirmed viral transmission through
corneal transplantation is rare. Theoretical pathways by which
SARS-CoV-2 may be transmitted through corneal trans-
plantation include viral presence in the tear film and viral
binding and/or replication on the ocular surface and within
the cornea. SARS-CoV-2 has been detected in the tear film of
patients using RT-PCR testing, establishing the possibility of
the virus being present on the ocular surface of donors.21
Presence of SARS-CoV-2 Receptors on the
Ocular Surface and in the Cornea
Recent reports have established the presence of SARS-
CoV-2 viral entry factors on the ocular surface and within the
cornea.22,23 These include angiotensin converting enzyme-2
(ACE2), which is thought to be the major receptor to which
the virus binds within the respiratory tract to establish
infection. ACE2 and transmembrane serine protease 2 have
been detected on the conjunctiva and within the corneal
epithelium, stroma, and endothelium.23 A study of 5 donor
corneas revealed variable expression of dendritic cell-specific
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Aldave et al Cornea  Volume 40, Number 7, July 2021

TABLE 1. Summary of Cases of Corneal Transplantation Using Tissue From Donors Testing Positive for SARS-CoV-2
Testing Method Date of Eye Bank Type of Recipient Outcome/Analysis of
Case Donor Date of Death (Location) Notification Eye Date of Surgery Surgery Untransplanted Donor Cornea
1 51 M May 16, 2020 Postmortem, NP PCR May 20, 2020 OD None — Donor cornea—IHC and RT-PCR
(tissue agency) for SARS-CoV-2 negative (CDC)
OS May 20, 2020 PK Recipient—graft successful, no
signs or symptoms of COVID-19
2 59 M May 20, 2020 Postmortem, NP PCR August 3, 2020* OD May 26, 2020 DMEK Recipient—graft successful;
(tissue agency) developed COVID-19 around July
18, 2020 after family members
grew ill (community-acquired)
OS May 25, 2020 DMEK Recipient—graft successful, no
signs or symptoms of COVID-19
3 30 M June 10, 2020 Postmortem, NP PCR June 14, 2020 OD June 13, 2020 PK Recipient—graft successful, no
(tissue agency) signs or symptoms of COVID-19
OS None — Donor cornea—IHC and RT-PCR
for SARS-CoV-2 negative (CDC)
4 47 W October 6, 2020 Postmortem, NP PCR November 24, 2020 OD None† — Donor cornea—RT-PCR testing
(tissue agency) not performed
OS October 12, 2020 DALK Recipient—graft successful, no
signs or symptoms of COVID-19
5 39 M December 6, 2020 Postmortem, NP PCR December 10, 2020 OD December 10, 2020 PK Recipient—graft successful, no
(tissue agency) signs or symptoms of COVID-19
OS December 10, 2020 PK Recipient—graft successful, no
signs or symptoms of COVID-19
6 42 M December 24, 2020 Postmortem, NP PCR January 14, 2021 OD None — Cornea not recovered
(tissue agency) OS January 05, 2021 PK Recipient—graft successful, no
signs or symptoms of COVID-19
*Extremely late notice by tissue agency related to that agency’s quality decision to determine ineligible previously preserved, irradiated tissues from stock.
†Cornea deemed ineligible for transplantation because of leaking viewing chamber before obtaining positive donor SARS-CoV-2 result.
DALK, deep anterior lamellar keratoplasty; DMEK, Descemet membrane endothelial keratoplasty; IHC, immunohistochemistry; M, man; W, woman; PK, penetrating
keratoplasty.

intracellular adhesion molecule 3-grabbing nonintegrin (DC-
SIGN) and DC-SIGN–related protein, which may serve as
alternative entry receptors.22 In the same study, ACE2,
transmembrane serine protease 2, DC-SIGN, and DC-SIGN–
related protein were also detected in cultured corneal, limbal,
and conjunctival epithelial cells.
SARS-CoV-2 Can Infect Ocular Tissue In Vitro
and In Vivo
Recently reported data indicate that SARS-CoV-2 can
infect cultured corneal, limbal, conjunctival, and endothelial
cells in vitro and remains viable in storage media for 14 days
(Joshua Hou, Can SARS-CoV-2 be Transmitted through
Donor Corneal Tissue? An in vitro Infection Study. Cornea
and Eye Banking Forum, November 7, 2020). In addition, a
study examining intentional ocular (conjunctival) infection of
rhesus macaques demonstrated subsequent pulmonary infec-
tion and a sustained weak viral load in the lacrimal gland,
conjunctiva, and optic nerve after autopsy.24
Presence of SARS-CoV-2 in Human
Postmortem Ocular Tissues
Evidence for the presence of SARS-CoV-2 in the human
cornea is provided by 2 recently published studies. In a
postmortem study of 132 ocular tissues from 33 potential
donors who were screened out for surgical use, which included
conjunctiva, corneal epithelium, anterior cornea, posterior
cornea, and vitreous samples, 17 were positive for SARS-
CoV-2 RNA.25 Another study that examined corneas from 11
individuals who died of COVID-19 infection demonstrated the
presence of SARS-CoV-2 RNA in 6 of the 11, although the
investigators were not able to detect viral structural proteins or
isolate infectious virus from the corneas.26
EVIDENCE AGAINST a RISK OF SARS-CoV-
2 TRANSMISSION
In Vitro Virucidal Activity of Povidone-Iodine
Against Coronaviruses
Current EBAA Medical Standard E1.100 Recovery
requires a double exposure of povidone-iodine to the ocular
surface before ocular tissue recovery from the donor. Because
in vitro studies have demonstrated a rapid virucidal effect of
povidone-iodine on SARS-CoV and SARS-CoV-2, it would
likely inactivate all infectious virus on the ocular surface.27,28
However, it is not known if infectious virus that is
intracellular or within deeper layers of the ocular tissue
would be eliminated by povidone-iodine application to the
ocular surface.

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Cornea  Volume 40, Number 7, July 2021
SARS-CoV-2 Does Not Replicate in Human
Corneal Explants
In an ex vivo human corneal culture model, investiga-
tors studying the ability of HSV-1, Zika virus, and SARS-
CoV-2 to cause infection and replicate found that unlike
HSV-1 and Zika virus, SARS-CoV-2 was not able to infect
and replicate within human corneal explants, as demonstrated
by quantitative RT-PCR.29 The authors postulated that there
may be a local pathway that prevents efficient SARS-CoV-2
infection of the ocular surface, despite the presence of viral
entry factors.
Absence of SARS-CoV-2 in Human
Postmortem Ocular Tissues
Two publications have reported the results of quantita-
tive RT-PCR testing for SARS-CoV-2 RNA in a variety of
ocular tissues, including corneal epithelium, stroma and
endothelium, bulbar conjunctiva, and aqueous aspirates from
individuals with confirmed COVID-19 infection before death.
The investigators failed to identify SARS-CoV-2 RNA in any
of the 20 corneas from 10 donors or in any of the extracorneal
ocular tissues from the 12 eyes from 6 donors who were
tested.30,31
Absence of SARS-CoV-2 Transmission
Through Corneal Transplantation From
Infected Donors
The data above highlight the importance of maintaining an
evidence-based tissue screening protocol while continuing to
investigate potential pathways by which SARS-CoV-2 may be
transmitted through corneal transplantation. Despite the efforts of
the EBAA and local eye banks to screen out tissue from donors
with COVID-19, we are aware of 8 cases in which corneal tissue
from infected donors was transplanted in the United States (Table
1). Fortunately, only one of the 8 recipients developed COVID-
19, attributed to community acquisition rather than via corneal
transplantation. In each of these cases, a delay in communication
of postmortem SARS-CoV-2 testing results by the tissue agency
performing the testing to the eye bank, combined with the eye
bank not being aware of the performance of postmortem testing
by the tissue agency, led to the release of corneas from donors
testing positive for SARS-CoV-2.
CONCLUSIONS AND FUTURE DIRECTIONS
The detection of SARS-CoV-2 in the tear film of some
patients with COVID-19, the presence of viral portals of
entry on the ocular surface and within the cornea, the
demonstrated ability of SARS-CoV-2 to infect ocular tissue
in vitro and in vivo, and the detection of SARS-CoV-2 RNA
in postmortem ocular tissue samples suggest that trans-
mission of SARS-CoV-2 from an infected corneal transplant
donor to recipient is possible. Thus, despite the demon-
strated virucidal activity of povidone-iodine against corona-
viruses, the failure of SARS-CoV-2 to replicate in ex vivo
human corneal culture models, the absence of SARS-CoV-2
in a small number of human postmortem ocular tissues, and
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EBAA MAB COVID and the Cornea
the absence of SARS-CoV-2 transmission through corneal
transplantation from a handful of infected donors, it is
incumbent on eye banks to continue to follow the EBAA
COVID-19 eligibility criteria for ocular tissue donation
(Fig. 1). However, as highlighted in the 8 cases in which
corneal tissue from infected donors was transplanted, it is
also essential for eye banks to establish a protocol to ensure
timely communication with testing agencies about testing
notification and results.
The EBAA, eye bank staff, and corneal surgeons all
have important roles to play in ensuring the safety of corneal
transplantation during the COVID-19 pandemic. In addition
to updating and implementing tissue screening protocols as
new information is gathered and improving communication
regarding SARS-CoV-2 testing results, well-designed
research studies are needed. These may include in vitro,
ex vivo, and/or in vivo investigations to determine the
following: 1) the ability of and pathway(s) by which SARS-
CoV-2 may bind to and/or infect the ocular surface, cornea,
and deeper structures within the eye; 2) the ability of
povidone-iodine and/or other agents to inactivate the virus
on the ocular surface and/or within the cornea; and 3) the
ability to determine which, if any, donor characteristics may
be predictive for the presence of SARS-CoV-2 within
ocular tissue.
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