Corneal transplantation during COVID-19 pandemic: need for special considerations—A live review

Corneal blindness is the fourth leading cause of blindness worldwide, with 10 million people having bilateral corneal blindness, nearly 80% of all corneal blindness cases are avoidable and are reversible. Corneal transplantation (CT) is the most frequently performed type of transplant across the world. This review was conducted with the objective of identifying if it is safe to harvest the cornea from the patients died due to COVID-19 and preventing the chances of transmission from donor to the recipient or healthcare worker handling the harvested cornea. A total of 45 articles were found with the keywords and out of all, only 16 fulfilled the inclusion criteria. RT-PCR is the technique of choice for detection of virus in the corpse and the sample analyzed was a pharyngeal swab. Available literature states unavailability of sufficient evidence-based studies proving presence of virus in the cornea or tear of COVID affected patients There is no proven consensus on presence of Virus in cornea. It is important to follow preferred practice guidelines so as to restart eye banking and do at least the emergency surgeries without having risk of disease transmission and keeping ourselves safe.


Introduction
Corneal blindness is the fourth leading cause of blindness worldwide, with 10 million people having bilateral corneal blindness, nearly 80% of all corneal blindness cases are avoidable and are reversible [1]. and with all personal protective gears except in containment zones. Elective and non-emergency follow ups and surgeries can be deferred [9].
Several aspects of healthcare including eye donation and eye collection require adequate safety precautions in place to keep both the healthcare workers and patients safe [10]. It has made us change our approach to handle and manage the cases and in the aftermath of this pandemic, ophthalmologists will require practical guidelines based on advisories from national health departments on how to restart eye banking and cornea-related healthcare across the country [11].
A significant issue at present is the interaction of the cornea donors with SARS-CoV-2. Even with our currently limited testing capacity, the confirmed cases across globe numbers are significant, and trending towards an unknown peak [12]. The 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 [2].
Majority of the corneal blind patients may be visually rehabilitated by corneal transplantation. An efficient and precise utilization of the donor corneas in developing countries like India is merely possible after an entire knowledge of the collection, storage, and utilization of donor tissues. Thus, this review was conducted with the objective of identifying if it is safe to harvest the cornea from the patients died due to COVID-19 and preventing the chances of transmission from donor to the recipient or healthcare worker handling the harvested cornea.

Methods
A review of Corneal harvesting from COVID-19 positive dead bodies was conducted based on the reports and articles available in PubMed and ScienceDirect.com. Keywords used were-((Corneal Harvesting)) and (COVID patients) OR (eye banking during COVID-19) OR (Corneal Transplant) OR (Keratoplasty).
Articles referring to Mode of Transmission of COVID-19 were also included. Articles were searched in the Third week of November 2020.
Articles were assessed based on the criteria to be included for the review: • Articles/Guidelines/Notes etc. published in last one year.
• Articles related to Harvesting Cornea from COVID-19 affected patients.
• Articles with risk of transmission while harvesting Cornea from COVID affected patients.
• Articles related to eye-banking during COVID times were only included in the study.

Results
A total of 45 articles were found with the keywords and out of all, only 9 fulfilled the inclusion criteria. In addition to that, Four Guidelines/Technical advisories were included which provided the viewpoints pertaining to cornea Harvesting. Three other articles were also included that were obtained from the references of the identified articles.
Out of nine articles, 5 are editorials/commentary/consensus statement on guidelines for cornea and eye banking during COVID-19, 4 articles are literature reviews. Selection criteria is explained in Flowchart. All these articles have been published in 2020.
A total of 16 articles/Guidelines following the inclusion criteria were reviewed. Details of which is attached in Table 1.  • Study recommends post-mortem nasopharyngeal PCR testing and PVP-I disinfection protocol to eliminate any tissue harboring SARS-CoV-2 being used for corneal transplantation.
2. Roy A. et al. [14] Descriptive study of the challenges faced in eye banking during lockdown, and practices adopted to overcome • Immediate drastic reduction of donor retrieval.
• Shift to glycerol preservation.
• Cessation of precut tissues for posterior lamellar surgeries.
• Resumption of donor cornea retrieval guidelines.
• Patient triage for keratoplasty and alternatives to emergency keratoplasty.

Desautels JD et
al. [11] Review of recommendations made by various health agencies/ authorities for retrieving Cornea.

Rodrí guez A et
al. [15] Review of microbiological aspects of COVID-19 infection • No Study reports use of more than one type of sample for microbiological analysis • No specific tests are being recommended to use in corpses.
• Samples to be taken prior to autopsy, more specifically NPS and pharyngeal swab.

Global Alliance of Eye Banking
Association [16].  Review • Study found that although there is a low prevalence of SARS-CoV2 in tears, it is possible to transmit the disease through ocular secretions.

•
The relationship between COVID-19 and the ocular surface as a potential portal of entry and as a transmission mechanism is currently under discussion due to the high transmission rate of the disease.

11.
Chaurasia S et al. [21] Editorial • Donor cornea, however, carries the unknown and unquantifiable risk of transmission of disease to the recipient.

•
Harvesting eyes from donors with conditions potentially hazardous to eye bank personnel should be strictly avoided. Therefore, death due to COVID-19 will fall into this category. Ballouz et al. [22] Review • There is evidence that transmission through blood donation and organ or tissue transplantation is possible. SARS-CoV-2 has been detected in conjunctival swabs of infected patients, and the ocular surface may play an important role in viral entry.
• The risk of SARS-CoV-2 transmission through corneal transplantation is likely low.
• However, tissue screening guidelines need to be re-evaluated regularly as knowledge regarding the SARS-CoV-2 virus evolves 13 Kates OS et al. [23] Review • Study found that the current data provide little evidence to suggest the presence of intact transmissible SARS-CoV in organs that can potentially be transplanted. 14 Mukhra R et al. [24] Review • Till date, there is a single report of conjunctivitis along with the viral RNA in the tear body fluid. However, an absence of the virus in the patients' conjunctival sac implicated an unusual route of transmission of SARS-CoV-2.
• Study recommends more research to develop a detailed understanding of the transmission mechanism through tear secretions and ocular surfaces. 15 Sharma N et al. [25] None • Paper highlights the consensus-based guidelines by an expert panel comprising of representatives from the All-India.

Ophthalmological Society (AIOS), Eye Bank Association of India (EBAI), Indian Society of Cornea and Kerato refractive surgeons
(ISKRS), Cornea society of India (CSI) and major governmental and private ophthalmological institutions in India. 16 Siedlecki J et al. [26] Review (n = 21) • The novel coronavirus SARS-CoV 2, currently causing the COVID-19 pandemic, has severe implications for ophthalmology-be it because the eyes represent an important route of infection, most probably through lacrimal drainage into the nasal mucosa, or because of ocular manifestations, which, even if rather rare, can represent the first symptoms of this novel disease.

Discussion
The COVID -19 pandemic has had an enormous impact on healthcare both by the direct mortality and morbidity associated and therefore the indirect effects of lockdown and social distancing measures to regulate. The death toll around the world has risen steadily and the challenges faced by the healthcare systems is manifold [12]. Due to the close contact with patients, procedures which generate aerosols and potential risk of presence of virus in tears there was a fear that ophthalmologists and eye-related HCWs are at a slightly higher risk of developing the infection.
Various infection control measures are evolved within the previous couple of months to attenuate the spread of infection to both patients and health care workers. Hospitals have adopted a triage system to attenuate cross-infection. Eye Banking is an integral component of eye care services. Eye-banking activities would need strategic planning for the longer term when things normalizes. The pandemic has made the eye bankers reflect and introspect crisis that can occur and help devise a plan to handle a similar situation if it arises in the future [21].
Some of the available literature states unavailability of sufficient evidence based studies proving availability of virus in the cornea or tear of COVID affected patients [3,19,20,22]. It is too early to possess evidence that SARS-CoV-2 are often transmitted by transfusion or tissue transplantation. Maybe a rapid screening test for all donors can help to rule out in the future [21].
An article by Sharma et all on Procurement and Utilization trends of eye banks in India states the precautionary measures that needs to be taken before harvesting the cornea. The harvesting can be planned after following a triage system that is used in clinics. The detailed history may be elicited from family members before collection. The collection can be restricted only to the death cases due to completely nonrelated causes like a road traffic accident, hanging, poisoning, etc., Those on ventilators of any time duration should be avoided [27].
Literature by Toro et.al and Joran D.D. et al. have stated that there is no evidence to substantiate that harvested corneal grafts from COVID-19 patients can contain SARS-CoV-2 virus and lead to a systemic infection. Although risk of transmission through corneal stromal tissue is low, it potentially exists [3]. While other literature states that we currently lack sufficient evidence to suggest that a sizable viral load presenting a significant risk to donor recipients is harbored within the corneal stroma [11].
A literature available by Amesty MA et al. on COVID-19 Disease and Ophthalmology highlights that there is need to plan a well-designed trial to rule out other ocular manifestations that may result from COVID-19 infection and to understand the transmission of the virus through the eyes [20], similar findings have also been mentioned in an editorial by Ang M, Moriyama A et.al states that more research is needed to examine the risk of ocular transmission of SARSCoV-2, both from an eye banking and healthcare provider perspective [19].
An article by Ferná ndez-Rodrí guez A et al. reviews the microbiological aspects of the COVID-19 infection and recommends that the RT-PCR is the technique of choice for detection of virus in the corpus and the sample analyzed was a pharyngeal swab, and only a few cases used samples taken from the lower airways, such as lung parenchyma swabs or lung necropsies fixed in paraffin. Study has also stated that there are very few papers that are available on the results of autopsies in cases of COVID-19 are restricted to certain organs and/or tissues, or they use minimally invasive techniques [15].
Another technical Advisory by Welsh Government states that, if COVID-19 testing on postmortem swab specimens is being considered for a suspected COVID-19 case, SARS-CoV-2 RNA may still be detected up to 3 days postmortem and possibly longer; however, sensitivity may be reduced with a longer postmortem interval, and duration of illness may need to be considered in interpreting a negative result. Advisory have also recommended that Post-mortem testing policy should be kept under review and may evolve in the response to new evidence, similar findings have also been reported in an advisory by Health department of The Republic of South Africa [17,18].

MOHFW has published a Standard Guidelines on Safe Ophthalmology Practices in COVID-19
Scenario which outlines the preventive and response measures to be observed to minimize and avoid the spread of COVID-19 in eye care facilities. In-spite of all a general understanding was kept that the Cornea can be harvested from the COVID affected dead bodies with due precaution [28].

Conclusions
There is no proven consensus on presence of Virus in cornea. It is important to use preferred practice guidelines so that we can exert extra care to restart eye banking and do at least the emergency surgeries without facilitating disease transmission and keeping ourselves safe.