Bilateral EK Rejection After COVID-19 Vaccine.

ABSTRACT: Owing to its rapid development, short-term and long-term effects of the COVID-19 vaccine are still not well understood. This case report highlights bilateral corneal endothelial graft rejection after administration of the Pfizer COVID-19 vaccine. A 73-year-old woman with bilateral Descemet stripping endothelial keratoplasty presented with bilateral decreased visual acuity, ocular pain, and photophobia after her second dose of the Pfizer-BioNTech COVID-19 vaccine. Two weeks after vaccine administration, the uncorrected visual acuity was 20/70 and 20/40. Central corneal thickness as measured by ultrasound was 809 and 825 µm and by Scheimfplug imaging was 788 and 751 µm at the pupil center. Slit-lamp biomicroscopy revealed quiet conjunctiva and sclera but was significant for thickened corneas with Descemet folds in both eyes. The patient was instructed to use prednisolone acetate 1% every 1 to 2 hours with Muro ointment at bedtime.

Impact of vaccination on keratoplasty.

PURPOSE OF REVIEW: Corneal graft rejection has been reported after coronavirus disease 2019 (COVID-19) vaccination. The purpose of this review is to evaluate the literature regarding corneal graft rejection after vaccination, including rejection rates and risk factors. We aim to create a framework to identify patients who are at higher risk for graft rejection and may warrant consideration of prophylactic interventions. RECENT FINDINGS: Graft rejection has been reported following administration of mRNA, viral vector, and inactivated whole-virion COVID-19 vaccines. Most cases had additional risk factors associated with rejection. Vaccination increases circulation of proinflammatory cytokines, CD4+ and CD8+ T-cell responses, and antispike neutralizing antibody, all of which may contribute to graft rejection. Two prospective studies have found no relationship between recent vaccination and rejection but 20% of cornea specialists report to have seen a vaccine-associated rejection and 22% recommend delaying vaccination in certain circumstances. Many specialists recommend prophylactic topical corticosteroids before and after vaccination to mitigate rejection risk but there is no evidence to support this practice on a wider scale. SUMMARY: Our framework identified 96.8% of penetrating keratoplasty patients with vaccine-associated rejection as higher risk. Further research is needed in order to develop evidence-based guidelines.

Eye banking and keratoplasty trend analysis during the COVID-19 pandemic: A South Indian observational study.

Purpose: To analyze the impact on eye donation and corneal transplantation during the COVID-19 pandemic in a tertiary eye hospital in south India. Methods: A retrospective analysis of the donor and recipient records during the study period from January 2020 to May 2021 was conducted and tabulated in Microsoft Excel 2013. Demographic details of the donor, utility rate, cause of death, culture characteristics, storage methods, wet lab usage, and the surgical donor outcomes were evaluated. Additionally, the postoperative workup of the recipients, diagnosis, graft infection and rejection episodes, development of COVID-19 postoperatively, and outcome in terms of visual acuity at one, three, and six months were also noted. Results: A total of 466 eyes from 249 donors were received during the study period. The mean age of the donor population was 62.43 years (20.9). The corneal transplantation utility rate was 36.4% (n = 170). Fifty-one percent of the total transplant surgeries were for therapeutic purposes. This was followed by penetrating optical keratoplasty (34%), Descemet's stripping endothelial keratoplasty (9%), and patch grafts (3%). Seventeen (10%) graft rejection episodes were noted and nine (53%) had complete resolution after medical treatment. Conclusion: Proper preventive measures are key to carrying out safe and efficient eye banking activities even during a deadly pandemic, as COVID-19 transmission via transplantation is rare.

Corneal Allograft Endothelial Rejection after Sinopharm COVID-19 Vaccination; Report of Six Cases.

AIM: To report the clinical characteristics of six patients with corneal allograft endothelial rejection after COVID-19 vaccination with Sinopharm and to review the literature. METHODS: This is a prospective case series describing corneal allograft rejection among subjects having received Sinopharm (BBIBP-CorV) vaccine, coming to cornea clinic at a university-based hospital (Rassoul Akram Hospital, Tehran, Iran) from September 2021 to March 2022 for regular follow-up examinations. Data on demographics, vaccination (based on vaccine card), and graft condition (based on recent examination and previous medical documents) were recorded. RESULTS: Out of 54 eyes (46 patients), 6 eyes (6 patients) had corneal allograft endothelial rejection after 3 to 117 days, post-vaccination. Three out of six rejections occurred within two weeks following vaccination. All of them were male with the mean age of 53.00 ± 19.66 years. The graft type of all patients was penetrating keratoplasty (PKP). The adverse event developed on average at 40.67 ± 34.33 months after surgery. Four patients were under maintenance treatment by topical steroid at the time of vaccination. One also received systemic immunomodulatory medication. Four grafts ended up with partial or complete graft failure. One case had received two doses of vaccine before undergoing the second corneal graft transplantation. CONCLUSION: COVID-19 vaccination with Sinopharm may trigger corneal allograft endothelial rejection even in individuals with low-risk graft and under maintenance topical and/or systemic immunomodulatory medications.

Impact of pandemic COVID-19 lockdown on penetrating keratoplasty patients.

Purpose: To study the impact of the COVID-19 lockdown on the regular follow-up of keratoplasty patients. Methods: This retrospective interventional case series included 30 patients who had immunological corneal endothelial rejection out of 190 patients who came for post-PKP follow-up between September 15, 2019, and September 30, 2020. The demographics, primary diagnosis, surgical technique, time of presentation, recovery of graft, associated ocular problems, and visual acuity at 1 month were analyzed. Forward stepwise (likelihood ratio) binary logistic regression was used to find significant variables. Results: The study population had 19 males (63.33%) and 11 females (36.67%). The mean age of the study group was 42.83 ± 18.89 (8-80) years. Of 30 patients, 19 (63.3%) presented before and 11 (36.7%) after the COVID-19 lockdown. Overall, 23 (77%) showed a reversal of graft rejection. Logistic regression showed that preoperative indications, large-sized grafts, and deep corneal vascularization were significant risk factors for non-resolution of graft rejection. It was noted that patients who presented to the hospital late had poor recovery (P = 0.002). The delay in the presentation was a significant risk factor for non-resolution of graft rejection (P < 0.01). Z-test for proportions revealed that the difference in the non-resolution of rejection on immediate or delayed treatment in patients presenting during lockdown (P = 0.002) was significant. Conclusion: This article is to highlight the impact of the COVID-19 lockdown on graft rejection recovery of PKP patients due to delays in follow-up. Early treatment helps in the recovery of graft transparency and the reversal of immunological graft rejection. Also, primary diagnosis, deep vascularization, and large-sized grafts were significant risk factors for non-resolution of graft rejection.

Impact of the COVID-19 Pandemic on Corneal Transplantation and Cornea Procurement.

OBJECTIVES: In this study, we aimed to analyze the effects of the COVID-19 pandemic in its first year on corneal transplant outcomes performed at a tertiary eye care center in Turkey. MATERIALS AND METHODS: Clinical records of patients who underwent corneal transplant between March 2020 and February 2021 (group A) at the Baskent University Faculty of Medicine, Department of Ophthalmology, were analyzed retrospectively. Patient demographics, indications for transplant, type of transplant procedure (lamellar vs penetrating), follow-up duration, and postoperative complications were recorded. The same data were collected for cornea transplant patients who were seen the previous year, between March 2019 and February 2020 (group B). Data from the 2 groups were compared. In related samples, the Wilcoxon signed rank test was used for statistical analysis, and a P value < .05 was considered statistically significant. RESULTS: Six corneal transplants were performed between March 2020 and February 2021 (group A), and 48 corneal transplantations were performed in the previous year (group B). There was an 80% decline in total corneal transplant numbers when compared with the previous year, and lamellar surgeries were not performed at all during the first year of the pandemic. Indications during the pandemic were mainly urgent and limited to tectonic or therapeutic causes. Postoperative follow-up regimens were impaired, and the complication rate was significantly higher during the pandemic period compared with the previous year (67% in group A vs 16% in group B) (P < .001). CONCLUSIONS: There was a steep decline in transplants in 2020, the first year of the pandemic. The prominent increase in complication rates can be attributed to the late diagnosis of corneal rejections due to impaired postoperative follow-up regimens.

COVID-19 Vaccination May Not Increase Rates of Corneal Graft Rejection.

PURPOSE: The aim of the study was to present the rates of rejection from 2018 to 2021 and evaluate the purported association between COVID-19 vaccination and corneal graft rejection. METHODS: Cases of corneal graft rejection diagnosed between January 2018 and December 2021 were reviewed. The conditional Poisson regression model of the self-controlled case series method was used to estimate the incidence risk ratio of graft rejection after COVID-19 vaccination risk period compared with the control period. Based on outcomes of eyes that underwent keratoplasty from January 2018 to December 2020, Cox proportional hazard models were fitted with previous COVID-19 vaccination as a time-varying covariate. RESULTS: Over the past 4 years, the annual tally of diagnosed cases of graft rejection (19 cases in year 2018, 19 cases in year 2019, 21 cases in year 2020, and 18 cases in year 2021) has remained relatively stable. Using the conditional Poisson regression analysis, no significant increase in the incidence rate of rejection in the risk period after COVID-19 vaccination was found (incidence risk ratio = 0.56, 95% confidence interval [CI] = 0.13-2.28, P = 0.70). Fitted as a time-varying covariate, previous COVID-19 vaccination was not associated with graft rejection in both unadjusted (hazard ratio =0.77, 95% CI = 0.29-5.46, P = 0.77) and adjusted Cox models (hazard ratio = 0.75, 95% CI = 0.10-5.52, P = 0.78). CONCLUSIONS: No notable increase in rates of corneal graft rejection was noted in year 2021 when COVID-19 vaccination was broadly implemented. The apparent temporal relationship between COVID vaccination and corneal graft rejection may not represent a causative association.

Lasting Effects: Seven Year Results of the Castrop Nomogram for Femtosecond Laser-Assisted Paired Corneal Arcuate Incisions.

PURPOSE: Long-term results of arcuate incisions are rarely reported. This is unfortunate as long-term stability of astigmatic correction is of great interest to surgeons performing astigmatic correction. This study investigates the 7 year stability of results after application of femtosecond laser-assisted arcuate incisions with the Castrop nomogram. METHODS: Prospective interventional case series at the Augen- und Laserklinik, Castrop-Rauxel, Germany. Single site, single surgeon study. Seven year results of cataract patients with low to moderate corneal astigmatism receiving femtosecond laser-assisted arcuate incisions using a TechnolasVictus SW 2.7 (Bausch & Lomb Inc, Dornach, Germany) were assessed and compared to 1 year results. Outcome evaluation was based on astigmatic vector analysis, manifest refraction, and visual acuity. RESULTS: The study analyzed 19 eyes of 19 patients 7 years after surgery. Ocular residual astigmatism changed from -0.26 to -0.39 D. Preoperative corneal astigmatism was -1.51 D. Correction Index changed from 1.0 to 1.16. The magnitude of difference vector changed from 0.26 to 0.39 D. The index of success changed from 0.20 to 0.29. Spherical equivalent remained stable. A slight tendency to change toward astigmatic overcorrection was mainly observed for patients with preoperative with the rule astigmatism, but not with patients with against the rule astigmatism. CONCLUSIONS: The Castrop nomogram showed stable results 7 years after surgery. Similar to toric IOL surgery, it is advisable to be less aggressive when correcting with the rule astigmatism, to avoid overcorrection over a long period.

A case of acute endothelial corneal transplant rejection following immunization with ChAdOx1 nCoV-19 coronavirus vaccine.

A 28-year-old female who underwent an uneventful femtosecond laser enabled keratoplasty (FLEK) in her left eye presented with pain, redness, and blurring of vision in the operated eye two weeks after getting immunized with COVID-19 vector vaccine (ChAdOx1 nCoV19 Vaccine Recombinant COVISHIELD, AstraZeneca). Slit-lamp examination showed donor stromal edema with Descemet's membrane folds and Khodadoust line (KP's on endothelium) with anterior chamber cells and flare. The patient was diagnosed with acute corneal graft rejection and advised hourly topical steroids with cycloplegics and oral steroids. The patient responded to treatment and there was progressive reversal of graft rejection with the patient achieving best spectacle-corrected visual acuity (BSCVA) of 20/30 after five weeks of treatment. Our case highlights possible immune corneal graft rejection after COVID19 vaccination and the need to step up topical steroids before vaccination.

Tape Splint Tarsorrhaphy for Persistent Corneal Epithelial Defects.

PURPOSE: To report outcomes of tape splint tarsorrhaphy (TST) for persistent corneal epithelial defects (PCED). DESIGN: Retrospective, interventional case series. METHODS: The study population was consecutive patients with a PCED (14 days or longer) treated at a tertiary cornea clinic with TST. Patients with a corneal epithelial defect that did not respond to treatment with a bandage contact lens were included. Patients with a follow-up time of less than 3 months were excluded. Time to PCED resolution was the main outcome measure. RESULTS: Thirty-four eyes of 33 patients (mean age 62.9 ± 17.8 years; range, 27-90 years) were included in this study. The main etiologies of the PCED were post keratoplasty (n = 15), herpes simplex virus (n = 4), superficial keratectomy (n = 3), neurotrophic cornea (n = 4), fungal keratitis (n = 2), exposure keratopathy (n = 2), failed graft (n = 1), peripheral ulcerative keratitis (n = 1), rosacea (n = 1), and stitch abscess (n = 1). Mean ± SD time from PCED presentation to TST was 58.9 ± 106.3 days (range, 14-390 days). The mean ± SD area of the PCED was 25.1 ± 15.7 mm2 (range, 0.50-42.0 mm2). After TST, resolution of the PCED was achieved in 29/34 eyes (85.3%) without the need for additional interventions within 22.5 ± 24.3 days (range, 2-105 days). The mean ± SD logMAR best-corrected visual acuity improved significantly from 1.11 ± 0.41 to 0.83 ± 0.70 (P = .02). There were no complications attributed to TST and 2 patients elected to discontinue due to discomfort. CONCLUSIONS: TST achieved resolution of PCEDs secondary to various etiologies in 85.3% of eyes, with significant improvement in vision demonstrated. This simple, inexpensive, noninvasive technique may be considered for patients with PCEDs.

Five Cases of Corneal Graft Rejection After Recent COVID-19 Vaccinations and a Review of the Literature.

PURPOSE: The purpose of this study was to report 5 cases of acute corneal graft rejection after COVID-19 vaccination and perform a review of the literature. METHODS: This was a case series and review of literature dated on the October 10, 2021. RESULTS: We describe 5 cases-2 patients with Descemet stripping automated endothelial keratoplasty (for Fuchs endothelial dystrophy) who presented with acute corneal graft rejection after their first dose of mRNA (BNT162) vaccine. The other 3 patients who had penetrating keratoplasty performed more than 10 years ago for keratoconus presented with acute graft rejection-2 patients after their second dose of adenovirus vector (AZD1222) vaccine and 1 patient after first dose of mRNA (BNT162) vaccine. Three patients were not using any topical steroid treatment at the time of diagnosis of graft rejection. The mean duration between vaccination and onset of symptoms was 16.86 ± 6.96 days for the mRNA vaccine and 17 ± 11.89 days for the adenovirus vector vaccine. CONCLUSIONS: Corneal graft rejection has recently been reported after COVID-19 vaccination. Patients with keratoplasty need to be advised regarding the risk of corneal graft rejection and warning symptoms of rejection after COVID-19 vaccination. Seeking early referral to the emergency department and increasing topical steroids pre-COVID-19 and post-COVID-19 vaccination may reduce the risk of rejection.

"Smoldering" Rejection of Keratolimbal Allograft.

PURPOSE: The purpose of this study was to report a case of "smoldering" keratolimbal allograft (KLAL) rejection in a patient with subtherapeutic levels of systemic immunosuppression in temporal association with BNT162b2 messenger RNA vaccination for severe acute respiratory syndrome coronavirus 2. METHODS: This was a case report. OBSERVATIONS: A 72-year-old man presented with circumferential perilimbal engorgement, stagnation, and tortuosity of vessels with mild chemosis in his right eye KLAL segments 1 month after receiving the BNT162b2 messenger RNA vaccine while his tacrolimus trough blood levels were subtherapeutic measuring <2 ng/mL. He had undergone KLAL 6.5 years before for total limbal stem cell deficiency from a chemical injury and had been stable without any history of rejection. The donor was blood type O, and the patient had no systemic comorbidities. The patient was treated with hourly difluprednate 0.05% and increasing of his oral tacrolimus dose to 2 mg twice a day with improvement of rejection signs. CONCLUSIONS: There may be a temporal association between KLAL rejection after immunization against severe acute respiratory syndrome coronavirus 2 in patients with subtherapeutic levels of systemic immunosuppression. Patients should be on alert for any ocular signs or symptoms postimmunization and present for treatment immediately.

Exploration of the ocular surface infection by SARS-CoV-2 and implications for corneal donation: An ex vivo study.

BACKGROUND: The risk of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) transmission through corneal graft is an ongoing debate and leads to strict restrictions in corneas procurement, leading to a major decrease in eye banking activity. The aims of this study are to specifically assess the capacity of human cornea to be infected by SARS-CoV-2 and promote its replication ex vivo, and to evaluate the real-life risk of corneal contamination by detecting SARS-CoV-2 RNA in corneas retrieved in donors diagnosed with Coronavirus Disease 2019 (COVID-19) and nonaffected donors. METHODS AND FINDINGS: To assess the capacity of human cornea to be infected by SARS-CoV-2, the expression pattern of SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE-2) and activators TMPRSS2 and Cathepsins B and L in ocular surface tissues from nonaffected donors was explored by immunohistochemistry (n = 10 corneas, 78 ± 11 years, 40% female) and qPCR (n = 5 corneas, 80 ± 12 years, 40% female). Additionally, 5 freshly excised corneas (80 ± 12 years, 40% female) were infected ex vivo with highly concentrated SARS-CoV-2 solution (106 median tissue culture infectious dose (TCID50)/mL). Viral RNA was extracted from tissues and culture media and quantified by reverse transcription quantitative PCR (RT-qPCR) (viral RNA copies) 30 minutes (H0) and 24 hours (H24) after infection. To assess the risk of corneal contamination by SARS-CoV-2, viral RNA was tested by RT-qPCR (Ct value) in both corneas and organ culture media from 14 donors diagnosed with COVID-19 (74 ± 10 years, 29% female) and 26 healthy donors (79 ± 13 years, 57% female), and in organ culture media only from 133 consecutive nonaffected donors from 2 eye banks (73 ± 13 years, 29% female). The expression of receptor and activators was variable among samples at both protein and mRNA level. Based on immunohistochemistry findings, ACE-2 was localized mainly in the most superficial epithelial cells of peripheral cornea, limbus, and conjunctiva, whereas TMPRSS2 was mostly expressed in all layers of bulbar conjunctiva. A significant increase in total and positive strands of IP4 RNA sequence (RdRp viral gene) was observed from 30 minutes to 24 hours postinfection in central cornea (1.1 × 108 [95% CI: 6.4 × 107 to 2.4 × 108] to 3.0 × 109 [1.4 × 109 to 5.3 × 109], p = 0.0039 and 2.2 × 107 [1.4 × 107 to 3.6 × 107] to 5.1 × 107 [2.9 × 107 to 7.5 × 107], p = 0.0117, respectively) and in corneoscleral rim (4.5 × 109 [2.7 × 109 to 9.6 × 109] to 3.9 × 1010 [2.6 × 1010 to 4.4 × 1010], p = 0.0039 and 3.1 × 108 [1.2 × 108 to 5.3 × 108] to 7.8 × 108 [3.9 × 108 to 9.9 × 108], p = 0.0391, respectively). Viral RNA copies in ex vivo corneas were highly variable from one donor to another. Finally, viral RNA was detected in 3 out of 28 corneas (11%) from donors diagnosed with COVID-19. All samples from the 159 nonaffected donors were negative for SARS-CoV-2 RNA. The main limitation of this study relates to the limited sample size, due to limited access to donors diagnosed with COVID-19 and concomitant decrease in the procurement corneas from nonaffected donors. CONCLUSIONS: In this study, we observed the expression of SARS-CoV-2 receptors and activators at the human ocular surface and a variable increase in viral RNA copies 24 hours after experimental infection of freshly excised human corneas. We also found viral RNA only in a very limited percentage of donors with positive nasopharyngeal PCR. The low rate of positivity in donors diagnosed with COVID-19 calls into question the utility of donor selection algorithms. TRIAL REGISTRATION: Agence de la Biomédecine, PFS-20-011 https://www.agence-biomedecine.fr/.

Acute graft rejection in a high-risk corneal transplant following COVID-19 vaccination: A case report.

As COVID-19 vaccination is being undertaken all over the world, its side effects are materializing slowly. One such emerging side effect is acute graft rejection in corneal transplant (CT) cases post COVID-19 vaccination. We report a case of left eye (LE) repeat penetrating keratoplasty presenting with diminished vision in LE within 2 days of COVID-19 vaccination (ChAdOx1 nCoV-19 Corona Virus Vaccine Recombinant, COVISHIELD™). The patient was diagnosed with acute graft rejection post vaccination and was treated with topical and systemic immunosuppression therapy with successful outcome in terms improvement of visual acuity and corneal graft clarity. Timely presentation, diagnosis, and management may help to survive acute rejection episodes post vaccination.