Dilemma of donor testing before corneal retrieval in the COVID-19 era.

Abstract

In the wake of the COVID-19 pandemic, the entire health care system has undergone restructuring to cope with the widespread morbidity and mortality caused by the novel SARS-CoV-2 virus. Elective health care services have temporarily taken a backseat, and eye-banking and keratoplasty services have come to a near-standstill.[1] As we learn to live with the pandemic and move forward, there is a need to revise existing norms and guidelines in order to optimize eye-banking services and effectively tackle the growing backlog of routine keratoplasty procedures. Challenges in Eye Banking and Donor Cornea Retrieval The dual challenge of having to maintain a sufficient supply of donor tissues while ensuring adequate safety in the wake of the pandemic has compelled us to continually adjust and adapt the guidelines pertaining to corneal tissue retrieval, storage, and processing in accordance with the improved understanding of COVID-19 pathophysiology.[2] In addition to the potential threat of viral transmission via donor corneas, there also remains the issue of potential infection transmission to eye-bank technicians involved in donor retrieval and processing. Adequate personal protective equipment, double betadine cleaning of the eyes before tissue retrieval, nasopharyngeal swabs from cadaveric donors for RT-PCR, and quarantining the harvested ocular tissue for 48 hours are some of the measures that have been devised to safeguard technicians and potential recipients. Eye donation counselors face the mammoth task of counseling the next of kin in accord with the COVID-19 norms and eliciting pertinent history to ascertain donor eligibility. Extensive research has been undertaken in the past two years to confirm the presence of coronavirus in the ocular tissues of COVID-19-infected patients as well as to ascertain the plausibility of coronavirus transmission via ocular fluids and tissue. Ocular involvement in COVID-19 is relatively uncommon, with conjunctivitis being the most frequently reported manifestation; however, the presence of SARS-CoV-2 RNA has been reported in the tears and conjunctival secretions of patients both with and without conjunctivitis, raising concerns regarding potential ocular transmission.[34] Post-mortem studies evaluating the presence of viral RNA in the ocular tissue of COVID-19-infected patients are not conclusive, with some studies reporting the presence of viral RNA in cornea, sclera, and retina and other studies reporting the absence of any viral RNA in ocular tissues.[567891011] The variability observed in different studies can be attributed to the extremely low prevalence of the virus in ocular tissues, the relatively small number of samples analyzed, and the lack of a validated diagnostic test for use in post-mortem settings.[911] Currently, there is limited evidence to support direct ocular infection or transmission of SARS-CoV-2 through tissue or cell transplants; however, considering that viral RNA has been detected in tear film and the necessary viral cellular integration machinery exists within ocular surface tissues, the possibility cannot be discounted completely.[49] Moreover, the potential source of viral material in ocular secretions is unlikely to be systemic infection as the virus does not appear to enter the bloodstream, further suggesting that direct ocular infection may be possible.[11] Recent studies reporting the presence of SARS-CoV-2 antigens in the ocular surface of deceased COVID-19 patients with evidence of cadaveric ocular surface cells getting infected on exposure to the virus reinforces this theory.[12] Routine Donor Testing: Weighing the Pros and Cons The utility of universal testing of donor tissue for SARS-CoV-2 remains a matter of debate. Table 1 details the current evidence for universal donor testing for SARS-CoV-2 and post-mortem detection of viral RNA/proteins in ocular tissues of COVID-19-positive donors. Nasopharyngeal RT-PCR test for detecting SARS-CoV-2 RNA is performed most commonly, with antigen testing or donor serum antibody testing performed less frequently. The sensitivity of RT-PCR ranges from 35%–77% for oropharyngeal samples, 59%–94% for nasal samples, and 92%–100% for nasopharyngeal samples. The reported specificity of RT-PCR is high and ranges from 99%–100%.[13]Table 1: Current evidence for universal donor testing for SARS-CoV-2 and post-mortem detection of viral RNA/proteins in ocular tissues of COVID-19 positive donorsInternational eye bank associations such as the Eye Bank Association of America (EBAA) and Global Alliance of Eye Bank Associations (GAEBA) do not prescribe mandatory RT-PCR testing of all potential donors, citing insufficient evidence for ocular transmission of the virus. Other arguments against universal testing include the additional cost of testing, the delay in releasing the tissue to the surgeon, and the limited sensitivity of the test, which may cause false-negative results. The EBAA screening guidelines take into consideration clinical factors such as the presence of signs/symptoms of COVID-19, the presence of an alternative plausible diagnosis if symptomatic, close contact with an infected individual, and the vaccination status of the donor.[14] Recent studies have reported a significant RT-PCR positivity rate of nasopharyngeal swabs obtained from presumed COVID-19-negative potential donors, ranging from 4.8% to as high as 18.64%.[11516] Arora et al.[15] also reported a high viral load (Ct < 25) in 54.54% of the positive cases, suggestive of high risk of disease transmission to the health personnel handling the tissue. These results emphasize that clinical screening measures alone may not be sufficient in capturing all COVID-19-positive donors, and RT-PCR testing is an important supplement to detect asymptomatic carriers (who have a high prevalence) or those who remained positive despite the resolution of undiagnosed COVID-19.[15] These observations are in agreement with our own, which reinforces the inadequacy of relying on symptoms and history alone for screening potential donors.[17] The infectivity of SARS-CoV-2 in tissues of deceased RT-PCR-positive COVID-19 patients has been reported to be maintained up to 7 days post mortem, which underlines the need for careful and conscious handling of tissues by health personnel, especially in settings where universal testing is not being practiced.[18] Universal precautions, including the proper use of personal protective equipment, should be adhered to while retrieving donor tissues. The role of povidone-iodine for disinfection of donor ocular surface prior to retrieval was substantiated in a recent study wherein no viral antigens were detected in corneas treated with the solution.[7] Our Perspective Eye-banking services, including donor cornea retrieval and elective keratoplasty, were temporarily ceased at the National Eye Bank, RP Centre for Ophthalmic Sciences, AIIMS, New Delhi during the nationwide and later state-imposed lockdown during 2020–21. Donor retrieval was gradually restarted in accord with global norms, and potential COVID-19-positive individuals and high-risk suspects were excluded from the pool of potential donors. Donor corneas were retrieved from only presumed non-COVID-19 deceased donors, and mandatory RT-PCR testing of the deceased was performed at the time of retrieval. The donor tissues were quarantined following retrieval and used only subsequent to a confirmed negative RT-PCR report. A total of 432 donor corneas were collected in the period of July 2020–July 2021; of these, 24 donor corneas (5.55%) were not used for keratoplasty as the RT-PCR test of the deceased donor was positive. This figure assumes even more importance when we consider the fact that all these donors were presumed to be COVID-19 negative based on the guidelines established by various global and national eye banks. In addition, one donor had previously recovered from a COVID-19 infection with a documented negative RT-PCR two months prior to death, thus highlighting the need to account for re-infection even in recently recovered donors. The evidence regarding the presence of viable viral particles in these donor tissues capable of transmitting disease remains inconclusive; however, in the absence of adequate knowledge, utilization of these tissues for keratoplasty should not be recommended. Vaccination and Eye-Banking Internationally, various nations are slowly easing the COVID-19 restrictions with an increase in the proportion of the vaccinated population. As the vaccination coverage further increases, the question will soon arise regarding the need for routine RT-PCR testing of vaccinated individuals for a variety of activities, including elective surgeries and organ donation. This is one aspect that needs to be addressed in the coming future, keeping in mind that no vaccine at present guarantees 100% safety from COVID-19 infection. Conclusion The COVID-19 pandemic is unlikely to end in the near future, and the disease may in fact become integrated in the communities with variable morbidity and mortality. The peaks of the COVID-19 wave will be associated with the pooling of all health care resources and cessation of nonemergent procedures, and the intervening quiescent phases will witness a significant backlog of elective cases, which needs to be tackled efficiently. Eye banking and corneal transplantation need to be restored, and in fact, boosted in accordance with the new norms, to help restore sight to corneal blind patients while maintaining the safety standards. Further, the existing eye-banking and keratoplasty guidelines need to continually evolve with the emerging information and changing nature of the novel SARS-CoV-2 virus. Mandatory donor RT-PCR testing acts as a second line of defense to help exclude asymptomatic carriers who have been overlooked despite the stringent screening guidelines. Considering the high prevalence of asymptomatic infection, significant RT-PCR positivity rate reported among presumed COVID-19-negative asymptomatic donors and the recent evidence supporting the presence of virus in corneal tissue and the possibility of ocular transmission of disease, the merits of universal donor testing appear to outweigh its demerits. About the author Prof. Jeewan S Titiyal Professor Jeewan S Titiyal is the Chief and Professor at RP Centre, AIIMS, New Delhi. He is the Chairman of the National Eye Bank, and his field of expertise comprises of cornea, cataract and refractive surgery. He has been conferred with the Padma Shri for his outstanding contribution in the field of Medicine (Ophthalmology) by President of India in 2014. He has been honored with the ‘Distinguished Service Award’ by the Asia-Pacific Academy of Ophthalmology, the AAO Senior Achievement Award, APAO Achievement Award, APACRS Certified Educator Award, P Siva Reddy Award and RP Dhanda Award by AIOS amongst numerous other awards, over 30 orations and keynote addresses. He has been the ‘Teacher of Teachers’ and performed over 100 live surgical demonstrations and delivered over 1000 lectures and talks. He is the 1st Indian to perform live surgery in ASCRS, USA. He has been regularly conducting instruction courses at AAO, ASCRS, ESCRS, APAO, APACRS and AIOS. He has two patents to his credit for his innovations. He has to his credit more than 300 Indexed Publications with over 3365 citations. He has co-authored 5 text books in his field of expertise and written over 52 book chapters. He has completed over 30 funded international and national research projects