Histomorphological view of the cornea investigated by laser confocal microscopy in keratoplasty

Introduction. Corneal transplantation is the most successful and commonly performed allotransplantation procedure as compared with other organs and tissues. Over 100,000 corneal transplantations are performed worldwide every year.Purpose. This study investigated whether in vivo confocal microscopy (IVCM) can aid in the diagnosis of a graft rejection reaction by detecting changes in cellular structures and density of immune cells after penetrating keratoplasty.Materials and methods. The study included thirty-four eyes of 34 patients who underwent penetrating keratoplasty (7 eyes with corneal graft rejection, 27 without rejection). The average age of patients is 51.1 ± 13.6 years (from 23 to 76 years). The follow-up period ranged from 12 to 36 months (24.5 ± 4.84 months). Follow-up was performed at 1, 3, 6, 12 months and annually after PKP. To study the morphology of the cornea all patients underwent IVCM to assess the basal epithelium, subbasal layer, stroma and endothelium. Immune cells were identified and evaluated for the shape, length of the processes and their density.Results. Patients with corneal graft rejection demonstrated significant accumulation of corneal dendritic-like immune cells compared to patients with non-rejected grafts. In addition, the cells acquired a more mature morphology (grade 2–3). The density of dendritic cells (DC) was 809.17 ± 342.19 (p < 0.001). A positive correlation was found between DC density and graft rejection (p < 0.001). As well the patients showed signs of endothelial failure with low endothelial cell density and pleomorphism, increased light scattering and hyperreflectivity of the stroma.Conclusions. In a complex of diagnostic measures, confocal microscopy may provide a valuable clinical adjunctive tool in diagnosis and management of early corneal graft rejection.

Correction of postkeratoplastic astigmatism by intrastromal corneal segments implantation using a femtosecond laser

Background. After penetrating keratoplasty, mild to high induced corneal astigmatism was observed in each case. The existing choice of correction of postkeratoplastic astigmatism is aimed at fi nding an individual approach in order to compensate for it and not weaken the biomechanical properties of the corneal graft.The aim: to analyze the clinical, functional, and morphological results of postkeratoplastic astigmatism correction by implantation of intrastromal corneal segments using a femtosecond laser.Methods. 22 patients were examined before and 1 year after surgery. The operation was performed under local anesthesia: stage I – an intrastromal tunnel was formed using a femtosecond laser “Femto Visum” 1 MHz (Optosystems, Russia); stage II – the intrastromal corneal segments were implanted. The results were assessed using standard and special research methods using optical coherence tomography Visante OCT (Zeiss, Germany), keratotopography (Tomey-5, Japan), optical corneal analyzer ORA (Reichert, USA), laser tindalemetry FC-2000 (Kowa, Japan) and confocal microscope Confoscan-4 (Nidek, Japan).Results. Before the operation, uncorrected visual acuity averaged 0.09 ± 0.05, after a year – 0.50 ± 0.16; best corrected visual acuity – 0.30 ± 0.12 and 0.60 ± 0.05 respectively; cylindrical component of refraction – –10.29 ± 3.12 and –2.20 ± 0.64 D respectively; mean keratometry value – 43.59 ± 2.14 and 38.56 ± 1.75 D respectively; corneal hysteresis – 7.92 ± 1.22 and 8.95 ± 1.05 mm Hg respectively; corneal resistance factor – 7.01 ± 1.81 and 8.44 ± 1.44 mm Hg respectively; protein fl ux in the moisture of the anterior chamber – 2.97 ± 0.28 and 3.04 ± 0.24 f/ms respectively; endothelial cell density – 1521 ± 327 and 1475 ± 419 cells/mm2 respectively.Conclusion. Intrastromal corneal segments implantation into a corneal graft using a femtosecond laser has efficiency and safety method in correcting postkeratoplastic astigmatism.

Acute corneal graft rejection after anti-severe acute respiratory syndrome-coronavirus-2 vaccination: A report of four cases

Purpose This study intends to add to previous reports on acute corneal graft rejection following anti-severe acute respiratory syndrome-coronavirus-2 vaccination, providing data to corroborate a possible causative relationship between anti-COVID-19 immunization and corneal graft rejection, regardless of vaccine or graft type. Methods and Results This report describes 4 cases of acute-onset rejection as early as 5 days following the first dose of anti-severe acute respiratory syndrome-coronavirus-2 vaccine types not yet referred for corneal allograft. Patients were individually given the Moderna messenger RNA-1273 COVID-19 vaccine (2 patients) and the AstraZeneca COVID-19 vaccine, Vaxzevria, AZD1222 (2 patients). Conclusions Even though a direct causative effect is hard to prove, temporal proximity between anti-severe acute respiratory syndrome-coronavirus-2 vaccines of different types and consecutive reports of corneal graft rejection indicates the need for further investigation. Consistent advice must be given to corneal transplant patients regarding such risk.

Deep Anterior Lamellar Keratoplasty Following Epikeratophakia: A Novel Two-Stage One-Graft Method To Treat Acute Corneal Hydrops

Purpose To evaluate the clinical effects of deep anterior lamellar keratoplasty (DALK) using a single graft after epikeratophakia for the treatment of acute corneal hydrops. Methods This novel surgical procedure was performed on seven eyes of seven patients between 2019 and 2020. The procedure combines a first-stage surgery of epikeratophakia with intracameral sterile air injection and a second-stage surgery of DALK using the same corneal graft for both procedures. Main outcome measures included pre- and postoperative best-corrected visual acuity (BCVA) and anterior segment optical coherence tomography (AS-OCT) parameters. Corneal transparency, neovascularization and epithelization were observed at the 1-year follow-up. Results Corneal edema resolved rapidly in six of the seven cases. The group mean central corneal thickness was significantly reduced from baseline at 1 day, 1 week, 1 month, and 2 months after the first-stage surgery, respectively (P < 0.0001). At a mean of 2.1±0.7 months after the first-stage surgery, DALK was successfully performed in all cases. Six months later, the central corneal thickness was 611±31 µm and the thickness of the recipient’s residual stroma bed was 20±6 µm at the central corneal area. LogMAR BCVA was improved from 1.74±0.34 at baseline to 0.20±0.11 after DALK (P < 0.0001). No postoperative complications appeared in our case series during one years of observation. Conclusion A novel curative effect was found in the treatment of acute corneal hydrops with epikeratophakia followed by DALK using the same corneal graft.

Immunology and Donor-Specific Antibodies in Corneal Transplantation

The first human corneal transplantation was performed in 1905 by Eduard Zirm in the Olomouc Eye Clinic, now Czech Republic. However, despite great advancements in microsurgical eye procedures, penetrating keratoplasty in high-risk patients (e.g., vascularized or inflamed corneal tissue, consecutive transplants) remains a challenge. The difficulty is mainly due to the risk of irreversible allograft rejection, as an ocular immune privilege in these patients is abolished and graft rejection is the main cause of corneal graft failure. Therefore, tailored immunosuppressive treatment based on immunological monitoring [e.g., donor-specific antibodies (DSA)] is considered one of the best strategies to prevent rejection in transplant recipients. Although there is indirect evidence on the mechanisms underlying antibody-mediated rejection, the impact of DSA on cornea transplantation remains unknown. Determining the role of pre-existing and/or de novo DSA could advance our understanding of corneal graft rejection mechanisms. This may help stratify the immunological risk of rejection, ultimately leading to personalized treatment for this group of transplant recipients.

Dual Corneal-Graft Rejection after mRNA Vaccine (BNT162b2) for COVID-19 during the First Six Months of Follow-Up: Case Report, State of the Art and Ethical Concerns

Present mass vaccination against Coronavirus Disease-19 (COVID-19) is the most widely used health policy and the most promising approach to curb the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic globally. However, new side effects are emerging from the mass vaccination not described during the experimental stages. In the present study, we discuss a case of acute corneal graft rejection, which has occurred 25 years after transplantation and 13 days after the administration of the BNT162b2 vaccine (Comirnaty, BioNTech/Pfizer), which was followed-up for a period of six months. In this period, the corneal inflammation appeared twice but was successfully managed with topical therapy and supplementation of Vitamin D. A risk of corneal graft rejection must be included in the list of potential vaccine complications, in order to inform the transplanted patient to undergo a preliminary and a follow-up ocular examination, and eventually to include corneal graft in the list of contraindications to vaccination.

Role of Immune Cell Diversity and Heterogeneity in Corneal Graft Survival: A Systematic Review and Meta-Analysis

Corneal transplantation is one of the most successful forms of solid organ transplantation; however, immune rejection is still a major cause of corneal graft failure. Both innate and adaptive immunity play a significant role in allograft tolerance. Therefore, immune cells, cytokines, and signal-transduction pathways are critical therapeutic targets. In this analysis, we aimed to review the current literature on various immunotherapeutic approaches for corneal-allograft rejection using the PubMed, EMBASE, Web of Science, Cochrane, and China National Knowledge Infrastructure. Retrievable data for meta-analysis were screened and assessed. The review, which evaluated multiple immunotherapeutic approaches to prevent corneal allograft rejection, showed extensive involvement of innate and adaptive immunity components. Understanding the contribution of this immune diversity to the ocular surface is critical for ensuring corneal allograft survival.