The Risk and Impact of SARS-CoV-2 Infection on Corneal Transplantation: A Case-Control Study

Abstract

Purpose:

To evaluate the risk of symptomatic SARS-CoV-2 infection after corneal transplantation surgery, with cataract surgeries as controls. Secondarily, to evaluate the impact of the COVID-19 pandemic in the clinical and surgical complications of corneal transplantation and cataract surgeries.

Methods:

Retrospective matched case-control study of 480 consecutive individuals that underwent surgery at the Bascom Palmer Eye Institute between May 2020 and November 2020. A total of 240 patients that underwent corneal transplantation with tissue obtained from the Florida Lions Eye Bank were age-, race-, ethnicity-, and sex- matched with 240 patients that underwent cataract surgery during the same day and by the same surgical team. Only the first corneal transplant or cataract surgery during this period was considered for each individual. All donors and recipients were SARS-CoV-2 negative by nasopharyngeal PCR test before surgery. Post-operative SARS-CoV2 infections were defined as previously SARS-CoV2(−) individuals that developed symptoms or had a positive-SARS-CoV2 PCR-test during the first post-operative month.

Results:

Mean age, sex, race, and ethnicity were similar between groups. There were no differences in SARS-CoV-2 infections prior to surgery between transplant and cataract groups (5.8% vs 7.5%, p=0.6), or in post-operative SARS-CoV-2 infections (2.9% vs 2.9%, p=1). The rates of post-operative complications did not increase during the pandemic, compared to previously reported ranges.

Conclusions:

In this study, post-operative SARS-CoV-2 infection was similar for individuals undergoing corneal transplantation or cataract surgery. Further research is required to evaluate the transmission of SARS-CoV-2 through corneal tissue.

INTRODUCTION

The novel coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been striking due to its rapid emergence and spread since December 2019. It is not only a public health emergency, but also a significant socio-economic burden¹. While the main mode of transmission of SARS-CoV2 is through respiratory droplets, other modes of transmission have not been fully evaluated, including the ocular route. Cornea transplantation remains the most common type of solid transplant performed worldwide². Despite taking appropriate measures with corneal tissue preparation and transplantation, there is a potential risk of infectious diseases and viral particles transmission from the donor to the recipient.^{3, 4}

The risk of SARS-CoV2 through ocular tissue is low, but it remains a biological possibility. There have been multiple studies evaluating the presence of SARS-CoV2 in ocular secretions of infected patients, with levels varying depending on the infection state of the patient.^5–9 It is possible that the proximity of the nasolacrimal system with respiratory tissues could serve as a bridge for infections such as SARS-CoV-2 to invade respiratory and lung epithelium,^{5, 10, 11} The ocular transmission of SARS-CoV2 has been reported in animal models,^12–14 as well as in vitro studies of human embryonic stem cells derived ocular tissue and corneal epithelial cells.^{15, 16} It has been shown that human corneal and conjunctival tissues from healthy individuals have expression of receptors such as ACE2^17–19, TMPRSS2,^19–21 and CD147²² which are necessary for SARS-CoV-2 cell entry.²³ Moreover, SARS-CoV-2 RNA and viral proteins have been identified in post-mortem corneal tissue from both COVID-19 positive individuals^{24, 25} and symptomatic negative donors.²⁴

Despite protocols for corneal donation and procurement implemented during the pandemic by organizations like the Eye Bank Association of America and the Global Alliance of Eye Bank Associations,²⁶ there is a possibility of transplanting tissue with SARS-CoV2 viral components from individuals who tested negative for COVID-19 at the time of corneal recovery, and had symptoms that were unreported at the time of death.^{24, 27} It is unclear at this time if the presence of this virus in human corneal tissue could lead to the systemic spread of the infection if transplanted. Thus, the purpose of this study was to evaluate the risk of developing SARS-CoV-2 infection after receiving a corneal transplant during the height of the COVID-19, by comparing individuals that underwent corneal transplantation with individuals that underwent cataract surgery performed during the same day and by the same surgical team. Secondarily, to evaluate the impact of the pandemic in the clinical and surgical outcomes of these patients. Thus, this study could serve as a guidance of the ophthalmic considerations regarding safety related to cornea surgery during the COVID-19 pandemic.

METHODS:

Study population

The study population included 240 individuals that underwent corneal transplant, and 240 that underwent cataract surgery at the Bascom Palmer Eye Institute in Miami, FL between May 2020 and November 2020. These individuals were age-, sex-, race-, ethnicity- matched with 240 individuals that received cataract surgery during the same day and by the same surgical team, as controls. Patients were excluded from the study if they had less than one-month post-operative follow-up. Only the first surgery during the study period was considered for each individual.

Data Collection

A retrospective chart review was conducted and data regarding demographic information, systemic and ocular co-morbidities, history of recent hospitalizations, ocular surgical procedures, and laboratory tests results were collected. Data regarding SARS-CoV-2 prior and post-operatively were collected from the electronic medical records, including history of hospitalization due to SARS-CoV-2 infection and SARS-CoV-2 tests, and routinely administered screening questionnaires given to all individuals per hospital pandemic protocols^{28, 29}. These questionnaires were standardized and included questions regarding self-reported symptoms (fever, conjunctivitis, cough, sore throat, difficulty breathing, diarrhea, body aches and/or lack of smell or taste in past 10 days) and self-reported positive SARS-Cov-2 tests. Post-operative cases of SARS-CoV-2 infection were considered if they occurred during the first post-operative month; SARS-CoV-2 infections were defined as having either self-reported symptoms or a positive SARS-CoV-2 test. A period of one month after surgery was deemed appropriate, in order to include individuals who could have received delayed medical care or presented with late-onset symptoms.^30–32

Donor corneal tissues were obtained through the Florida Lions Eye Bank, Miami, FL. All corneal tissue donors were screened for SARS-CoV-2 with nasopharyngeal PCR immediately prior to procurement, and corneal tissue was processed with standard technique. All corneal transplants and cataract surgeries were performed with standard techniques and in a sterile environment. All individuals were deemed SARS-CoV-2 negative by nasopharyngeal PCR within 48 hours prior to surgery. Additional surgical interventions were performed at the discretion of the surgeon as indicated, based on the clinical presentation of individuals.

Telemedicine visits

Due to the COVID-19 pandemic, protocols for the implementation of telemedicine visits were established to minimize exposure and contact between patients and clinical staff. Virtual visits were utilized moderately as part of the routine evaluation of patients, due to the limited ophthalmic examination that can be performed and were conducted in-conjunction with in-person visits as necessary and after the appropriate screening for SARS-CoV2 infection. All telemedicine visits were conducted utilizing the Zoom platform (Zoom Video Communications Inc, San Jose, CA) linked with the Epic electronic medical records system (Epic Systems Corporation, Madison, WI), and all interactions and associated clinical notes were documented in the electronic medical record. Some telemedicine visits were conducted in hybrid format, in which patients were seen in-person by technicians for clinical photographs, and then the results were discussed virtually with the ophthalmologist.

Statistical analysis

Descriptive statistics were used to summarize the data. Independent t-tests were utilized for continuous variables and Chi-square or Fisher’s exact tests for categorical variables, as appropriate. A forward stepwise binomial logistic regression analysis was subsequently conducted to evaluate the contribution of demographics, number of in-person visits during the first post-operative month, type of surgery and medical history (comorbidities and prior SARS-CoV-2 infection) in the risk of developing SARS-CoV2 infection during the first pre-operative month. All statistical analyses were performed with SPSS version 26.0 (IBM Corp, Armonk, NY). A p-level of 0.05 was considered statistically significant.

Ethical Statement

This study was approved by the Institutional Review Board (IRB) at the University of Miami Miller School of Medicine (IRB#20201471) and was conducted in accordance with the principles of the Declaration of Helsinki and the United States Health Insurance Portability and Accountability Act.

RESULTS:

Study population:

A total of 240 consecutive cataract transplant cases were included in this study. They were age-, sex-, race-, ethnicity- matched with 240 individuals who underwent cataract surgery during the same day and by the same surgical team, as controls. The demographics of the study population, by group (corneal transplant versus cataract surgery) are presented in Table 1. There were no differences in sex, race, and ethnicity between the two groups. The age of individuals that underwent cataract surgery was slightly, albeit statistically significantly higher (68.9±9.9 years) than those who underwent corneal transplant surgery (66.3±15.0 years; p-0.03). As expected, the average follow-up time was significantly higher among individuals who underwent transplant surgery compared those who underwent cataract surgery (5.8±2.5 vs 3.5±2.7 months, p<0.01).

Table 1.

Demographics of the study population

Demographics	Transplant (n=240)	Cataract (n=240)	P-value
Age (years), mean ± SD	66.3± 15.0	68.9± 9.9	0.03
Biological Sex			0.07
Male	45.0%	53.8%
Female	54.3%	45.5%
Race/Ethnicity			0.18
Non-Hispanic White	35.4%	42.1%
Non-Hispanic Black or African American	15.8%	10.4%
Hispanic, of any race	40.8%	41.7%
Other	7.9%	5.8%
Current smoker	15.5%	22.1%	0.08
Follow up time (months), mean ± SD	5.8±2.5	3.5±2.7	<0.01

SD: Standard Deviation

Systemic and ocular comorbidities

The systemic and ocular comorbidities of individuals that underwent corneal transplant and those that underwent cataract surgery are presented in Table 2. There were no differences in the presence of systemic comorbidities in patients that underwent transplant surgery compared to those that underwent cataract surgery. Patients within the corneal transplant group were significantly more likely to present with ocular comorbidities such as history of infectious keratitis, ocular trauma, prior corneal transplant, glaucoma, and history of prior glaucoma and retinal surgeries.

Table 2.

Systemic and ocular comorbidities of study population

Parameter	Transplant (n=240)	Cataract (n=240)	P-Value
Systemic Comorbidities
Hypertension	61.7%	60.8%	0.93
Cardiovascular disease	17.9%	16.3%	0.72
Cardiac Arrythmia	15.0%	14.2%	0.90
Lipid disorder	51.2%	57.9%	0.17
Obesity (BMI ≥30)	32.9%	32.1%	0.92
Diabetes Mellitus	25.8%	23.8%	0.67
Thyroid disease	20.4%	19.6%	0.91
Autoimmune disease*	7.1%	8.0%	0.73
Lung disease (e.g., COPD, Asthma, Obstructive Sleep Apnea)	25.0%	25.4%	1.00
Chronic Kidney Disease	10.4%	10.5%	1.00
Malignant neoplasm	11.3%	13.8%	0.49
Arthritis	35.4%	42.1%	0.16
Cerebrovascular Disease	5.0%	4.2%	0.83
Dementia	3.3%	2.1%	0.58
Psychiatric comorbidities (e.g., anxiety, depression)	27.9%	26.7%	0.84
Ocular comorbidities
Dry Eye Syndrome	51.7%	51.2%	1.00
Meibomian Gland Dysfunction	58.3%	60.4%	0.71
History of refractive surgery (RK, LASIK, PRK, ICL)	4.6%	7.9%	0.19
Pterygium or pinguecula	2.9%	2.5%	1.00
History of Bacterial or fungal keratitis	15.4%	0.8%	<0.01
History of Herpetic Keratitis	11.3%	2.9%	<0.01
Ocular trauma history	12.5%	3.3%	<0.01
Prior corneal transplant	40.4%	2.1%	<0.01
Uveitis	9.6%	5.0%	0.08
Glaucoma	44.6%	12.5%	<0.01
Glaucoma surgery**	30.4%	2.9%	<0.01
Age-Related Macular Degeneration	7.5%	7.5%	1.00
Cystoid Macular Edema	15.0%	5.0%	<0.01
Retinal detachment	9.6%	7.9%	0.63
Other retinal disease	26.7%	32.1%	0.23
Retina surgery	15.8%	6.7%	<0.01

BMI: Body Mass Index; COPD: Chronic Obstructive Pulmonary Disease; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; RK: Radial Keratotomy; LASIK: Laser assisted in-situ keratomileusis; PRK: Photorefractive keratectomy; ICL: Implantable Collamer Lens.

^*Includes psoriasis, psoriatic arthritis, rheumatoid arthritis, sarcoidosis, systemic lupus erythematosus, scleroderma, systemic vasculitides (giant cell arteritis, polyarteritis nodosa, granulomatosis with polyangiitis, microscopic polyangiitis, Henoch-Schönlein purpura, Behcet’s disease, Cogan syndrome)

^**except laser iridotomy

SARS-CoV-2 infection rate before and after surgery

The number of pre- and post-operative SARS-CoV-2 infections by group are presented in Table 3. There were no significant differences in the rates of SARS-CoV-2 infection or hospitalization due to SARS-CoV-2 before surgery between individuals that underwent corneal transplant compared to individuals that underwent cataract surgery (5.8% vs 7.5%, p-0.58). Furthermore, there was no difference in the number of post-operative SARS-CoV-2 infections during the first month after surgery (2.9% vs 2.9%, p-1.0).

Table 3.

Pre- and post-operative SARS-CoV-2 infection rates by surgical group

	Transplant group (n=240)	Cataract group (n=240)	P-value
Prior SARS-Cov2 infection	5.8%	7.5%	0.58
Prior hospitalization due to SARS-Cov2 infection	0.8%	0.4%	1.00
SARS-Cov2 infection during postoperative month 1	2.9%	2.9%	1.00
SARS-Cov2 infection after postoperative month 1	2.9%	1.3%	0.34

SARS-CoV-2= severe acute respiratory syndrome coronavirus 2

Individuals that underwent corneal transplant had 3.2±1.4 in-person evaluations during the first month after surgery, compared to 2.2±1.1 visits among individuals who underwent cataract surgery (p<0.01). Two individuals in the transplant group and one in the cataract group had to reschedule their post-operative appointments within the first month due to a positive SARS-CoV2 test.

A binomial logistic regression analysis with forwards stepwise analysis was performed to evaluate the contribution of demographics, comorbidities, type of surgery received, number of visits within the first post-operative month, and history of prior SARS-CoV-2 infection in the risk of developing SARS-CoV-2 infection within the first post-operative month. A concomitant diagnosis of cardiovascular disease (OR: 6.63, 95% CI: 1.43–30.81, p=0.016) remained a significant predictor of developing SARS-CoV2 infection during the first post-operative month, which accounted for approximately 10% of the variance in the model (R= 0.32, p=0.018).

Telemedicine pre- and post-operative evaluations

Among the study population, 5.8% of individuals that underwent corneal transplantation had at least one telemedicine visit within 14 days before surgery as part of their pre-operative evaluation compared to 7.1% of those that underwent cataract surgery (P=0.71).

Post-operatively, 4.6% of individuals that underwent corneal transplantation received at least one telemedicine visit compared to 1.3% in the cataract group (p=0.05). The telemedicine visits for the individuals that underwent cataract surgery occurred mostly within the early post-operative period (8.0±5.1 days after surgery; range: 3–15 days) while the telemedicine visits for the transplant group occurred throughout the post-operative period with an average time of 78.7±66.1 days after surgery (range:10–237 days; p=0.09). Among those in the transplant group, 36.4% (4/11) of visits occurred within the first post-operative month, 36.4% (4/11) within the second post-operative month, and 27.3% (3/11) after the third post-operative month.

Surgical complications

The surgical complications of individuals that underwent corneal transplantation (grouped by type of graft) or cataract surgery are presented in Table 4. Surgical complications for endothelial transplants included graft detachment in 31.6% of DMEK and 12.1% of DSAEK cases; graft failure in 42.1% of DMEKs and 13.1% of DSAEKs; and CME in 5.3% of DMEK surgeries. Among full thickness transplants, 6% had persistently elevated IOP and 10.7% developed graft failure. In the case of anterior lamellar grafts, 11.1% of grafts had a persistent corneal epithelial defect and 11.1% of grafts failed. One individual (25%) that underwent K-pro developed a retro-prosthetic membrane, and another one developed a Dellen which required reassembly of the implant. Among patients that underwent cataract surgery, there were three cases (1.3%) of intra-operative floppy iris syndrome and one case of intraoperative posterior capsular tear. Moreover, there was one case (0.4%) of postoperative intraocular toric lens rotation.

Table 4.

Surgical complications of individuals after corneal transplantation or cataract surgery during the height of the COVID-19 pandemic.

Complications	PKP (n=84)	DSAEK (n=107)	DMEK (n=38)	ALK (n=7)	K-Pro (n=4)	All transplants (n=240)	Cataract surgery (n=240)
Graft detachment***	-	12.1%	31.6%	-	-	10.4%	-
Graft failure***	10.7%	13.1%	42.1%	11.1%	0%	16.3%	-
Pupillary block	-	0%	2.6%	0%	-	0.4%	-
CME*	0%	0.9%	5.3%	0%	0%	1.3%	0%
Wound dehiscence*	3.6%	0%	0%	0	0%	1.3%	0%
Intraocular Infection	2.4%	0.9%	0%	0%	0%	1.3%	0%
Retro-prosthetic membrane	-	-	-	-	25%	0.4%	-
Dellen*	0%	0%	0%	0%	25%	0.4%	0%
Persistent KED	2.4%	0.9%	0%	11.1%	0%	1.3%	0%
Persistently elevated IOP	6.0%	0%	2.6%	0%	0%	2.5%	0%
Intra-operative Choroidal hemorrhage	1.2%	0%	0%	0%	0%	0.4%	0%
IFIS	0%	0%	0%	0%	-	0%	1.3%
IOL rotation	0%	0%	0%	0%	0%	0%	0.4%
Intraoperative posterior capsule tear	-	-	-	-	-	-	0.4%

PKP=penetrating keratoplasty, DSAEK=Descemet Stripping Automated Keratoplasty, DMEK= Descemet membrane endothelial keratoplasty, ALK=Anterior Lamellar keratoplasty, K-pro= keratoprosthesis, KED=Corneal epithelial defect, CME=Cystoid macular edema, IOP=intraocular pressure, IFIS= intra-operative floppy iris syndrome.

^*Statistically significant at p<0.05 level

^***Statistically significant at p<0.01 level

Two individuals had graft failure after developing SARS-CoV2 infection. The first case occurred in a 40-year-old male with history of herpetic keratitis and 2 prior corneal transplants due to Pseudophakic bullous keratopathy. He received an uneventful DSAEK that cleared initially. After 8 months, he developed SARS-CoV2 infection, and within one week his graft failed, despite use of topical corticosteroids. The other case was in a 36-year-old female with history of keratoconus and no history of prior transplants. She received an uneventful full thickness corneal transplant that was clear for 4.5 months, until she developed a rejection episode within 3 weeks of a COVID-19 infection. Despite a high dose topical corticosteroids course, the graft failed during the 6^th post-operative month.

DISCUSSION

In the current study of individuals undergoing cornea transplant compared to individuals undergoing cataract surgery during the height of the COVID-19 pandemic, there was no difference in the risk of developing SARS-CoV2 infection. Thus, these surgeries can be considered safe if the appropriate protocols are followed.^{33, 34} The rate of developing SARS-CoV-2 within the first month after surgery in our study (2.9%) is comparable to that reported after elective surgery in other centers (0.5–3.2%).^35–38 Among the individuals that had a SARS-CoV-2 infection, 35.7% (5/14), occurred during the month of July 2020 coinciding with the peak of cases in Miami-Dade county, which had an incidence of 6.89% (187,259 positive tests/2,716,940 individuals) and a positivity rate of 15.34% (187,259 positive tests/1,220,657 total tests) during that month.^{39, 40} In this study, individuals with history of cardiovascular disease were at a significantly increased risk of developing SARS-CoV-2 infection during the first post-operative month, independently of the procedure received. This is in accordance with other studies suggesting that individuals with cardiovascular disease may be disproportionately affected by SARS-CoV2 infection and have a higher likelihood of developing severe disease.^{35, 41, 42} In the current study population, the prevalence of SARS-CoV2 infection prior to surgery (5.8–7.5%) was considerably higher than that reported by others (0.6%–3.7%).^{28, 33, 43, 44} This could be attributed to the high number of cases in Miami during that time.^{28, 39} There were no associations between having a prior SARS-CoV2 infection and intra- or post-operative complications. However, the number of individuals who had a prior positive test in this study was relatively small and thus, further research is still needed to fully evaluate the impact of prior SARS-CoV2 infection in surgical outcomes. It has been shown that there is a risk of infection imposed by the generation of aerosolized microdroplets with surgical techniques such as phacoemulsification.^{45, 46} This risk can be mitigated with the continued use of personnel-protective equipment as well as with the application of topical Povidone-Iodine immediately before surgery, which is effective against coronaviruses similar to SARS-CoV2.^47–49 It is imperative to conduct a thorough medical evaluation prior to surgery, including SARS-CoV-2 screening during the perioperative period, to ensure the safety of both patients and medical personnel during the COVID-19 pandemic.

In this cohort of individuals, the incidence of surgical complications after corneal transplantation or cataract surgery during the height of the pandemic did not increase considerably compared to prior studies, despite minimizing in-person visits to avoid unnecessary exposures.⁵⁰ Complications requiring immediate attention and prompt management during the post-operative period, such as infections were minimal across the surgeries performed. Among those that received cataract surgery, complications included intra-operative floppy iris syndrome in 1.3% of cases, which is comparable to previously reported incidence of 2.0–9.1%;^51–53 one case of intraoperative posterior capsule perforation and one case of intraocular lens dislocation. For patients that received a full thickness transplant, the most common complication was graft failure in 10.7% of cases, which is similar to 6–31% reported by others, depending on the optical or therapeutic indications for transplantation.^{54, 55} Patients with anterior lamellar grafts had a failure rate of 11% (compared to 0–7.0%),^{56, 57} however, this could be related to our relatively small sample. The rate of endothelial graft detachment was 12.1% for DSAEKs and 31.6% for DMEKs, which is similar to the previously reported incidences of 1.3–23.0%^{58, 59} and 6.8–40.0%^60–62 respectively. Graft failure was observed in 13.1% of DSAEKs, comparable to 18–19.1% of previously reported incidence.⁵⁸ In the case of DMEK surgeries, 42.1% of cases required subsequent re-transplantation due to graft failure, which is higher than the average rate reported by others (5.2–16%)^{63, 64} The early graft failure among DMEK recipients could be explained by our relative complexity of cases and high prevalence of ocular-comorbidities, such as anterior and posterior synechia, glaucoma draining devices, and partial aniridia. It has been reported that high risk DMEKs, such as those in individuals with complicated anterior segments and re-DMEK have failure rates of 30–50%.⁶⁵ Furthermore, during this period three surgeons made the transition from performing DMEK in uncomplicated cases of Fuchs endothelial dystrophy or pseudophakic bullous keratopathy and started performing DMEK in eyes with corneal edema and significant anterior segment pathology.

Interestingly, in the current study population, there were two individuals who developed graft failure coinciding with SARS-CoV2 infection. Due to the small number of individuals developing SARS-CoV2 infection in our sample, the natural history of this infection or its impact in corneal graft survival remains uncertain. Given the quick development of the COVID-19 pandemic, there is limited evidence in the literature regarding the possibility of graft failure secondary to SARS-CoV2 infection. Nevertheless, there have been reports of acute graft rejection in the setting of COVID-19 infection^66–68 as well as cases of graft rejection in patients that received the SARS-CoV2 mRNA vaccine,^69–71 which were thought to be secondary to the increased immune response to viral proteins.^{69, 70, 72, 73} It has been demonstrated that a NF-κβ-mediated inflammatory response is elicited in human corneal, limbal and scleral cells after inoculation with SARS-CoV2, with a more prominent pro-inflammatory chemokine response in limbal cells.^{15, 16, 19} This pro-inflammatory state is coupled with the suppression of the IFN-I and IFN-III response and partial inhibition of the antiviral immune system,^{16, 19, 74, 75} thus, enabling sustained viral replication and a prolonged inflammatory micro-environment within the ocular surface.^{75, 76} Given the biological possibility of SARS-CoV2 infection leading to acute graft failure or rejection due to increased inflammatory state, further research with larger samples of individuals with SARS-CoV2 infection in the setting of prior corneal transplantation would be needed to conclusively evaluate the impact of this infection in the corneal graft survival.

During the height of the COVID-19 pandemic, there has been a noticeable increase in telemedicine visits for ophthalmological triage and evaluation of patients across ophthalmological centers.^77–80 In our institution, telemedicine visits increased across all specialties, in order to minimize in-person visits, when feasible. Most of the telemedicine visits in the current study occurred as an adjunct to the pre-operative evaluation. They were conducted to tele-triage and gather clinical history of patients and were followed by in-person visits allowing for a complete ophthalmic examination prior to surgery. Moreover, in some cases telemedicine visits were utilized to complement post-operative follow up of individuals, as appropriate, based on the individual clinical picture and situation. In this study, the reason for telemedicine visits within the first-post-operative month were primarily for clarification of post-operative medications and recommendations; and evaluation of alarm symptoms (such as redness, loss of vision, pain, increased light sensitivity) requiring expedited in-person examination. Visits occurring after the first-operative month focused primarily on medicine regimen optimization, tele-triaging, evaluation of patients in rural or inaccessible areas, and coordination of care with local ophthalmologists. While telemedicine and remote ophthalmological evaluations have been deemed appropriate for the screening of certain conditions, such as glaucoma⁸¹ or diabetic retinopathy⁸², they are not routinely utilized for the diagnosis and management of anterior segment pathologies. Currently, remote teleophthalmology approaches include the use of smartphones with or without external lenses and/or lighting devices attached. While the sensitivity for anterior segment pathologies with these approaches is not yet optimal for wide-spread clinical implementation,^{83, 84} the use of telemedicine can be highly sensitive for the identification and referral of urgent ophthalmological conditions.⁸⁵ The use of telemedicine for anterior segment pathology and follow-up of patients after surgery still needs refinement, but could be a useful resource in the setting of social isolation for the preoperative surgical evaluation, identification of urgent early surgical complications and improvement of compliance with medications.

There are several limitations that should be noted when interpreting the results of this study. First, this study evaluated a population of older individuals seeking care at a tertiary level hospital and may not be generalizable to other populations. Second, the number of SARS-CoV-2 infections was assessed with self-reported data and medical chart review, and thus, the number of cases may not include asymptomatic infections and could be affected by recall bias. Third, only individuals that underwent corneal transplantation during days when cataract surgeries were performed by the same surgical team were included. However, we chose this approach intentionally in order to control for unaccounted iatrogenic SARS-CoV-2 exposures.

Despite these limitations, data from the current study suggest that there is no increased risk of developing SARS-CoV-2 infection after corneal transplantation when compared to patients that underwent cataract surgery during the same time. Based on the current study data, corneal transplantation and cataract surgeries can be performed safely, with the protocols in place to accommodate for social isolation and minimize unnecessary exposure. Further longitudinal studies evaluating the SARS-CoV-2 infection of corneal cells, transmission of SARS-CoV-2 through corneal tissue, and impact of SARS-CoV2 infection in graft survival are still needed.