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13 pages, 1146 KiB  
Article
Non-Descemet Stripping Automated Endothelial Keratoplasty (nDSAEK) for Late Endothelial Failure After Mushroom Keratoplasty: A Retrospective Analysis of Visual and Anatomical Outcomes
by Antonio Moramarco, Natalie di Geronimo, Marian Sergiu Zimbru, Arianna Grendele, Francesco Biagini, Maurizio Mete, Vito Romano and Luigi Fontana
J. Clin. Med. 2025, 14(15), 5568; https://doi.org/10.3390/jcm14155568 - 7 Aug 2025
Abstract
Background: Mushroom penetrating keratoplasty (MPK) is an alternative to traditional penetrating keratoplasty (PK) that offers improved graft survival and reduced immunological rejection. However, MPK grafts may still experience endothelial failure over time. This study evaluates the outcomes of non-Descemet Stripping Automated Endothelial [...] Read more.
Background: Mushroom penetrating keratoplasty (MPK) is an alternative to traditional penetrating keratoplasty (PK) that offers improved graft survival and reduced immunological rejection. However, MPK grafts may still experience endothelial failure over time. This study evaluates the outcomes of non-Descemet Stripping Automated Endothelial Keratoplasty (nDSAEK) as a surgical approach for endothelial decompensation following MPK. Methods: A monocentric, retrospective study was conducted at the Ophthalmology Department of Sant’Orsola-Malpighi Hospital, including patients who underwent nDSAEK for endothelial failure after MPK between 2022 and 2024. Pre- and postoperative best-corrected visual acuity (BCVA), central corneal thickness (CCT), and endothelial cell density (ECD) were assessed. Results: Eighteen eyes from 18 patients (mean age: 39.94 years) were included. Primary MPK indications were post-keratitis leucoma (77.7%), traumatic scarring (16.7%), and keratoconus (5.6%). At one year, mean BCVA improved significantly from 1.40 ± 0.42 logMAR to 0.46 ± 0.19 logMAR (p < 0.05), and mean CCT decreased from 721 ± 70.12 µm to 616 ± 52.80 µm (p < 0.05). The mean postoperative ECD was 1748 ± 100 cells/mm2, with lower eye values requiring re-bubbling. No immunological rejection or graft failures were reported. Conclusions: nDSAEK is a promising treatment for MPK endothelial failure, demonstrating good visual and anatomical outcomes. Full article
(This article belongs to the Section Ophthalmology)
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24 pages, 1115 KiB  
Review
Stem Cell-Derived Corneal Epithelium: Engineering Barrier Function for Ocular Surface Repair
by Emily Elizabeth Fresenko, Jian-Xing Ma, Matthew Giegengack, Atalie Carina Thompson, Anthony Atala, Andrew J. W. Huang and Yuanyuan Zhang
Int. J. Mol. Sci. 2025, 26(15), 7501; https://doi.org/10.3390/ijms26157501 - 3 Aug 2025
Viewed by 192
Abstract
The cornea, the transparent anterior window of the eye, critically refracts light and protects intraocular structures. Corneal pathologies, including trauma, infection, chemical injury, metabolic diseases, genetic conditions, and age-related degeneration, can lead to significant visual impairment. While penetrating keratoplasty or full-thickness corneal transplantation [...] Read more.
The cornea, the transparent anterior window of the eye, critically refracts light and protects intraocular structures. Corneal pathologies, including trauma, infection, chemical injury, metabolic diseases, genetic conditions, and age-related degeneration, can lead to significant visual impairment. While penetrating keratoplasty or full-thickness corneal transplantation remains a standard and effective intervention for severe corneal dysfunction, limitations in donor tissue availability and the risk of immunogenic graft rejection necessitate alternative therapeutic strategies. Furthermore, for cases of isolated epithelial disfunction, a full-thickness cornea graft may not be required or effective. This review examines the potential of corneal epithelial constructs derived from autologous stem cells with functional barrier properties for corneal reconstruction and in vitro pharmacotoxicity testing. In this review, we delineate the current limitations of corneal transplantation, the advantages of stem cell-based approaches, and recent advances in generating engineered corneal epithelium. Finally, we address remaining technical challenges and propose future research directions aimed at clinical translation. Full article
(This article belongs to the Special Issue Enhancing Stem Cell Grafting in Tissue Regeneration and Repair)
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16 pages, 1291 KiB  
Review
Pellucid Marginal Degeneration: A Comprehensive Review of Pathophysiology, Diagnosis, and Management Strategies
by Michael Tsatsos, Konstantina Koulotsiou, Ioannis Giachos, Ioannis Tsinopoulos and Nikolaos Ziakas
J. Clin. Med. 2025, 14(15), 5178; https://doi.org/10.3390/jcm14155178 - 22 Jul 2025
Viewed by 373
Abstract
Purpose: Pellucid Marginal Degeneration (PMD) is a rare ectatic corneal disorder characterized by inferior peripheral thinning and significant irregular astigmatism. Despite its clinical similarities to keratoconus, PMD presents unique diagnostic and therapeutic challenges. This review aims to provide a comprehensive update on the [...] Read more.
Purpose: Pellucid Marginal Degeneration (PMD) is a rare ectatic corneal disorder characterized by inferior peripheral thinning and significant irregular astigmatism. Despite its clinical similarities to keratoconus, PMD presents unique diagnostic and therapeutic challenges. This review aims to provide a comprehensive update on the pathophysiology, clinical features, diagnostic approaches, and management strategies for PMD, emphasizing the latest advancements in treatment options. Methods: A systematic literature search was performed in MEDLINE (via PubMed), Google Scholar, and Scopus up to February 2025 using the terms: “pellucid marginal degeneration,” “PMD,” “ectatic corneal disorders,” “keratoplasty in PMD,” “corneal cross-linking in PMD,” “ICRS in PMD,” “toric IOL PMD” and their Boolean combinations (AND/OR). The search was restricted to English-language studies involving human subjects, including case reports, case series, retrospective studies, clinical trials, and systematic reviews. A total of 76 studies met the inclusion criteria addressing treatment outcomes in PMD. Results: PMD is characterized by a crescent-shaped band of inferior corneal thinning, leading to high irregular astigmatism and reduced visual acuity. Diagnosis relies on advanced imaging techniques such as Scheimpflug-based corneal tomography, which reveals the characteristic “crab-claw” pattern. Conservative management includes rigid gas-permeable (RGP) lenses and scleral lenses, which provide effective visual rehabilitation in mild to moderate cases. Surgical options, such as CXL, ICRS, and toric IOLs, are reserved for advanced cases, with varying degrees of success. Newer techniques such as CAIRS, employing donor tissue instead of synthetic rings, show promising outcomes in corneal remodeling with potentially improved biocompatibility. Penetrating keratoplasty (PK) and deep anterior lamellar keratoplasty (DALK) remain definitive treatments for severe PMD, though they are associated with significant risks, including graft rejection and postoperative astigmatism. Conclusions: PMD is a complex and progressive corneal disorder that requires a tailored approach to management. Early diagnosis and intervention are critical to optimizing visual outcomes. While conservative measures are effective in mild cases, surgical interventions offer promising results for advanced disease. Further research is needed to refine treatment protocols and improve long-term outcomes for patients with PMD. Full article
(This article belongs to the Special Issue New Insights into Corneal Disease and Transplantation)
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19 pages, 290 KiB  
Review
A Review of Outcomes of Descemet Membrane Endothelial Keratoplasty and Descemet Stripping Automated Endothelial Keratoplasty Interventions in Patients with Pre-Existing Glaucoma
by Keya Jafari, Zahra Ashena and Magdalena Niestrata
J. Clin. Med. 2025, 14(10), 3534; https://doi.org/10.3390/jcm14103534 - 18 May 2025
Viewed by 681
Abstract
Glaucoma is known to impair the function of corneal endothelial cells for various reasons, which increases the likelihood of patients with glaucoma requiring endothelial keratoplasty. Among the techniques available, Descemet membrane endothelial keratoplasty (DMEK) and Descemet stripping automated endothelial keratoplasty (DSAEK) each present [...] Read more.
Glaucoma is known to impair the function of corneal endothelial cells for various reasons, which increases the likelihood of patients with glaucoma requiring endothelial keratoplasty. Among the techniques available, Descemet membrane endothelial keratoplasty (DMEK) and Descemet stripping automated endothelial keratoplasty (DSAEK) each present unique challenges, particularly for those with a history of glaucoma surgery. We conducted a literature review to evaluate the outcomes of DMEK and DSAEK in glaucoma patients, focusing on factors such as visual prognosis, graft survival, glaucoma exacerbations, and any necessary surgical modifications. The findings indicate that DMEK tends to provide better visual outcomes compared to DSAEK, with a lower rate of steroid responders due to a shorter postoperative steroid regimen. While DMEK has shown a higher incidence of graft detachment and a lower rate of graft rejection, compared to DSAEK, in the general population, the specific data regarding these outcomes in glaucoma patients remain scarce in the existing literature. Overall, the survival rates of both grafting techniques do not show significant differences within the glaucoma patient population. To draw more definitive conclusions about graft survival between the two methods, a greater number of comparative studies with longer follow-up periods is needed. Full article
(This article belongs to the Section Ophthalmology)
9 pages, 731 KiB  
Review
Rho-Kinase Inhibitors in the Management of Fuchs Endothelial Corneal Dystrophy: A Review
by Anđela Jukić, Ana Pupić Bakrač, Biljana Đapic Ivančić, Andrijana Kopić, Ana Meter, Rajka Kasalica Žužul, Josip Pavan and Tomislav Jukić
Medicina 2025, 61(5), 772; https://doi.org/10.3390/medicina61050772 - 22 Apr 2025
Viewed by 1414
Abstract
Fuchs endothelial corneal dystrophy (FECD) is the most common corneal endothelial dystrophy. It is characterized by the progressive loss of corneal endothelial cells (CECs), guttae formation on the Descemet membrane, and corneal edema, leading to visual impairment. Corneal transplantation remains the standard treatment, [...] Read more.
Fuchs endothelial corneal dystrophy (FECD) is the most common corneal endothelial dystrophy. It is characterized by the progressive loss of corneal endothelial cells (CECs), guttae formation on the Descemet membrane, and corneal edema, leading to visual impairment. Corneal transplantation remains the standard treatment, but it has limitations such as donor shortages, infection risk, and graft rejection. Rho-kinase (ROCK) inhibitors have emerged as a promising pharmacological alternative. These agents promote CEC proliferation, migration, and adhesion while inhibiting apoptosis and enhancing corneal endothelial wound healing. Several studies have demonstrated the efficacy of ROCK inhibitors in improving corneal clarity and endothelial function, particularly when used as an adjunct to Descemet Stripping Only (DSO) surgery. Additionally, they show potential in preventing corneal edema in FECD patients undergoing cataract surgery. The methodology involved a literature search through the PubMed and Medline databases using relevant keywords. Only peer-reviewed articles in English were included, with additional references from selected articles reviewed to ensure comprehensive coverage. ROCK inhibitors offer a novel pharmacological approach to managing FECD. They have shown potential in promoting endothelial cell regeneration and improving corneal functIion. Despite promising results, further research is required to determine ROCK inhibitors’ long-term safety, optimal dosing, and efficacy in surgical and non-surgical FECD patients. Their potential to delay or prevent corneal transplantation represents a significant advancement in FECD management. Full article
(This article belongs to the Special Issue Advances in Corneal Management)
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11 pages, 1087 KiB  
Opinion
Ocular Surface Microbiota and Corneal Transplant Outcome: Is There a Link?
by Michele Potenza, Antonio Moramarco, Annalisa Astolfi, Carmen Ciavarella, Luigi Fontana and Piera Versura
Biomedicines 2025, 13(4), 972; https://doi.org/10.3390/biomedicines13040972 - 16 Apr 2025
Viewed by 481
Abstract
Recent research has highlighted the critical role of microbiota in organ transplant outcomes, particularly in the gut. However, the impact of ocular surface microbiota (OSM) on corneal transplantation remains largely unexplored. This piece examines the potential connection between OSM imbalances and corneal graftoutcomes, [...] Read more.
Recent research has highlighted the critical role of microbiota in organ transplant outcomes, particularly in the gut. However, the impact of ocular surface microbiota (OSM) on corneal transplantation remains largely unexplored. This piece examines the potential connection between OSM imbalances and corneal graftoutcomes, suggesting that microbial shifts could influence immune responses and transplant success. The OSM, though characterized by low microbial density, plays a critical role in local immune modulation and ocular surface homeostasis. Dysbiosis in this microbiota may compromise the immune privilege of the cornea, potentially increasing the risk of graft rejection. Looking at gut microbiota studies, where dysbiosis has been linked to graft failure, it is reasonable to hypothesize that similar mechanisms might be at play on the ocular surface. Disruptions in cornea’s immune tolerance pathways, such as anterior chamber-associated immune deviation (ACAID), may lead to pro-inflammatory responses that threaten graft survival. In addition, ocular surface diseases such as dry eye disease, microbial keratitis, and allergic conjunctivitis, already associated with OSM dysbiosis, may further exacerbate post-transplant complications. Despite the lack of direct studies linking OSM to corneal transplant outcomes, this opinion piece highlights the necessity for future research. Standardizing microbiota analysis methodologies and exploring therapeutic interventions, such as ocular probiotics, could open new roads for improving corneal transplant success and patient prognosis. Full article
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14 pages, 5383 KiB  
Article
Classification of Histologically Proven Inflammation in Clinically Inactive Corneal Scars: Implications for Graft Outcomes After Penetrating Keratoplasty
by Max Schliffka, Helena Siegel, Claudia Auw-Haedrich, Christian van Oterendorp, Daniel Boehringer and Thomas Reinhard
J. Clin. Med. 2025, 14(2), 461; https://doi.org/10.3390/jcm14020461 - 13 Jan 2025
Viewed by 906
Abstract
Background/Objectives: Clinically inactive corneal scars have repeatedly been shown to exhibit histological inflammation. This study aimed to evaluate the degree of histological inflammation in clinically inactive corneal scars of different origins and its correlation with graft rejection and failure following penetrating keratoplasty. [...] Read more.
Background/Objectives: Clinically inactive corneal scars have repeatedly been shown to exhibit histological inflammation. This study aimed to evaluate the degree of histological inflammation in clinically inactive corneal scars of different origins and its correlation with graft rejection and failure following penetrating keratoplasty. Methods: The study included 205 primary corneal explants with clinically inactive central scars resulting from herpes simplex virus keratitis (HSV, n = 55), keratoconus (n = 39), mechanical trauma (n = 27), scrophulosa (n = 22) or other/unknown causes (n = 62). Central histological sections were categorized by the degree of inflammation, and an overall inflammation score (IS) was calculated. Results: HSV-associated scars exhibited a trend towards more graft rejection with higher IS (p = 0.074). Keratoconus-associated scars showed no IS-dependent differences in graft rejection or failure. The rejection rate in this group was 13/39. Scars resulting from mechanical trauma, such as perforating injuries, demonstrated a trend towards higher graft rejection (p = 0.15) and failure rates (p = 0.089) with increasing IS. The rejection rate in this group was 11/27. Scrophulosa-associated scars had significantly higher graft rejection rates (p = 0.041) at a lower cut-off of 0.06 compared to the cut-off of 0.36 for the other groups. Scars of other or unknown causes showed no IS-dependent differences in graft rejection or failure. Conclusions: Histological inflammation in HSV scars and scars resulting from mechanical trauma appeared to contribute to graft rejection. Despite low IS, the rejection rate in keratoconus scars and scars following mechanical trauma was unexpectedly high, indicating the presence of other influencing factors. While some correlations did not reach statistical significance due to small sample sizes in the subgroups, the observed trends should be considered clinically relevant. The study may have been “underpowered”, as histopathologically inflamed specimens with clinically inactive corneal scars are relatively rare. Full article
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8 pages, 1253 KiB  
Case Report
Therapeutic Keratoplasty for Fusarium Keratitis
by David Oliver-Gutierrez, Liliana Gutuleac, Natalia Anglada-Masferrer, Gloria Segura-Duch, Sara Martin, Laia Bisbe, María Teresa Martín-Gómez, Miguel Ángel Zapata and Javier José Puig
J. Clin. Med. 2024, 13(24), 7775; https://doi.org/10.3390/jcm13247775 - 19 Dec 2024
Viewed by 978
Abstract
Purpose: This study evaluates the effectiveness of therapeutic keratoplasty for Fusarium fungal keratitis and explores the diagnosis and management challenges of this infectious corneal disease. Methods: We retrospectively analyzed therapeutic keratoplasty cases at a tertiary hospital for Fusarium keratitis when standard treatments [...] Read more.
Purpose: This study evaluates the effectiveness of therapeutic keratoplasty for Fusarium fungal keratitis and explores the diagnosis and management challenges of this infectious corneal disease. Methods: We retrospectively analyzed therapeutic keratoplasty cases at a tertiary hospital for Fusarium keratitis when standard treatments failed. Results: Five cases of Fusarium keratitis, unresponsive to typical antifungal treatments, required keratoplasty due to fast progression and diagnostic difficulties. Post-surgery, all patients had infection resolution without recurrence, but some complications like anterior chamber leakage, graft rejection, and ocular hypertension were managed effectively. Final visual acuity ranged from 0.9 to finger counting. Conclusions: Fusarium keratitis, often resistant to conventional therapies, may necessitate keratoplasty for resolution. This intervention is crucial for positive outcomes, emphasizing the need for prompt and effective management to prevent severe surgical measures and preserve ocular health. Full article
(This article belongs to the Special Issue New Advances in Keratoplasty)
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13 pages, 851 KiB  
Article
Retrospective Clinical Outcomes of Keratoplasty Using Human Donor Corneas Preserved in Eusol-C Hypothermic Storage Medium
by Rossella Anna Maria Colabelli Gisoldi, Giulio Pocobelli, Umberto Rodella, Laura Giurgola, Claudio Gatto, Gemma Lodato, Giacinta Buffon, Carlo Nucci, Jana D’Amato Tóthová and Augusto Pocobelli
J. Clin. Med. 2024, 13(24), 7606; https://doi.org/10.3390/jcm13247606 - 13 Dec 2024
Cited by 1 | Viewed by 900
Abstract
Objective: To evaluate the clinical outcomes of cornea transplantation (penetrating keratoplasty, Descemet membrane endothelial keratoplasty, Descemet stripping automated endothelial keratoplasty, and deep anterior lamellar keratoplasty) using donor corneas stored in Eusol-C hypothermic storage medium compared to corneas stored in organ-culture. Methods: The [...] Read more.
Objective: To evaluate the clinical outcomes of cornea transplantation (penetrating keratoplasty, Descemet membrane endothelial keratoplasty, Descemet stripping automated endothelial keratoplasty, and deep anterior lamellar keratoplasty) using donor corneas stored in Eusol-C hypothermic storage medium compared to corneas stored in organ-culture. Methods: The clinical outcomes of 92 patients who underwent corneal transplantation with human donor corneas stored in Eusol-C medium at 2–8 °C were retrospectively evaluated. The control group consisted of 169 patients who received corneas organ-cultured at 31 °C. Donor age, sex, death-to-preservation time, and storage time were recorded. Endothelial cell (EC) density (ECD), EC mortality, and EC morphology scores were evaluated during storage in both groups. Complication rates, visual outcomes, and corneal transparency were monitored for up to six months. Results: The mean storage in Eusol-C time was 7.7 ± 2.5 days, while organ-culture time was 14.2 ± 4.0 days. In the Eusol-C group, ECD was 2398 ± 354 cells/mm2, with an average EC morphology score of 3.4 ± 0.7/4. Approximately 28% of the corneas in the Eusol-C group had no EC mortality. In the organ-culture group, ECD was 2256 ± 328 cells/mm2, with an average EC morphology score of 3.5 ± 0.5/4, and 42% were devoid of EC mortality. No complications, such as re-bubbling, were observed in both groups during surgery. Transparent corneas were achieved in 81.3% of the Eusol-C group the day after surgery. Mean corrected distance visual acuity (CDVA) at 3 and 6 months was 4.5 ± 4.0/10 and 5.4 ± 3.7/10 for the Eusol-C group and 5.0 ± 2.9/10 and 5.7 ± 2.8/10 for the organ-culture group, with no statistical differences observed between the groups. No graft failure was observed up to three months. Graft rejection occurred in the Eusol-C group and in the organ-culture group in, respectively, one and two cases at the six-month follow-up. Conclusions: Comparable surgical outcomes were achieved with donor corneas stored in both hypothermic Eusol-C and organ-culture media. Full article
(This article belongs to the Section Ophthalmology)
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15 pages, 2319 KiB  
Article
Analyzing Porcine Corneal Xenograft Compatibility: In Silico Insights on Graft Outcomes
by Patricia Mae De Leon and Heherson Cabrera
Transplantology 2024, 5(3), 193-207; https://doi.org/10.3390/transplantology5030019 - 30 Aug 2024
Cited by 1 | Viewed by 1649
Abstract
Background: Corneal transplantation faces significant challenges due to the shortage in donor corneas. Porcine corneas have emerged as a potential solution due to their similarities in biomechanical properties with pigs, yet xenoimmune rejection poses an obstacle to their efficacy. Methods: In [...] Read more.
Background: Corneal transplantation faces significant challenges due to the shortage in donor corneas. Porcine corneas have emerged as a potential solution due to their similarities in biomechanical properties with pigs, yet xenoimmune rejection poses an obstacle to their efficacy. Methods: In this study, in silico methods were employed to analyze the compatibility of porcine corneal xenografts, focusing on two key aspects: the comparison of corneal matrix proteins and investigation of the immunological mediators and pathways involved in corneal graft rejection. The amino acid sequences of the fourteen (14) most abundant proteins in the corneal matrix were compared to determine their structural and functional differences. The primary amino acid structures and compositions, theoretical pI, and grand average of hydropathicity were determined and compared between the two species. Results: In graft performance, similarities and differences between the donor and recipient tissues influence the success of transplantation. When the proteins closely resemble each other, in terms of structural characteristics and biochemical properties, the host’s immune system is less likely to recognize the tissue as foreign. The immunological mediators and pathways involved in corneal graft rejection were investigated, elucidating the mechanisms underlying xenograft incompatibility. Based on the results generated from STRING, the specific groups of molecules that are involved in the immune-mediated rejection process are costimulatory molecules, cytokines, immune checkpoint molecules, apoptosis regulators, cell adhesion molecules, growth factors, neuropeptides and hormones, certain receptors, the cytotoxic molecule GZMA, and the chemokine CCL5. Conclusions: The results of this study establish that the porcine cornea has a high suitability for corneal xenotransplantation into humans but requires immune-based therapeutic interventions to increase graft acceptance. Full article
(This article belongs to the Section Transplant Immunology and Immunosuppressive Drugs)
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12 pages, 2655 KiB  
Article
Assessment of Corneal Graft Outcomes in a Murine Model of Endothelial Keratoplasty
by Akitomo Narimatsu, Rohan Bir Singh, Pier Luigi Surico, Seokjoo Lee, Katayoon Forouzanfar, Francesca Kahale, Aytan Musayeva, Thomas H. Dohlman, Tomas Blanco and Reza Dana
J. Clin. Med. 2024, 13(17), 5010; https://doi.org/10.3390/jcm13175010 - 24 Aug 2024
Viewed by 1786
Abstract
Objectives: In this study, we establish a protocol for evaluating the outcomes of endothelial keratoplasty, including graft survival, rejection, or failure. Additionally, we also evaluate the alloimmune response in graft recipients. Methods: We performed EK using C57BL/6 (allogeneic) and BALB/c (syngeneic) [...] Read more.
Objectives: In this study, we establish a protocol for evaluating the outcomes of endothelial keratoplasty, including graft survival, rejection, or failure. Additionally, we also evaluate the alloimmune response in graft recipients. Methods: We performed EK using C57BL/6 (allogeneic) and BALB/c (syngeneic) as donors and BALB/c mice as recipients. Slit-lamp examination and optical coherence tomography were performed for clinical evaluations for 16 weeks post-procedure. Criteria for the assessment of corneal opacity were established and the animals were graded weekly. Additionally, we assessed corneal endothelial cell density by harvesting the corneas and staining with zonula occludens-1 (ZO-1). Lastly, lymph nodes were collected, and CD4+ T cells were MACS-sorted and co-cultured with syngeneic or allogeneic antigen-presenting cells (APCs) to assess the IFN-γ expression levels by alloreactive Th1 cells (ELISPOT) in response to the direct (donor) or indirect (host) pathways of sensitization. Results: We observed graft failure in four animals, including irreversible corneal opacity, graft detachment, and anterior synechiae in the first four weeks. The remaining animals were graded between 0 and 5 as per the established criteria. The total and graft corneal thickness and endothelial cell density progressively worsened with a higher grade of corneal opacity. The direct allosensitization of Th1 cells was significantly higher in mice with a higher grade of corneal opacity. At 16 weeks follow-up, the grafts remained stable with low opacity scores in syngeneic EK recipients; however, the opacity scores were higher and variable in allogeneic EK recipients. Conclusions: These findings establish a standardized protocol to assess the graft outcomes in a murine model of EK. Furthermore, we delineate the underlying immunological pathway that contributes to the immune-mediated rejection of grafts in this model. Full article
(This article belongs to the Special Issue New Insights into Corneal Regeneration and Transplantation)
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11 pages, 1062 KiB  
Article
Selective, Temporary Postoperative Inhibition of Lymphangiogenesis by Integrin α5β1 Blockade Improves Allograft Survival in a Murine Model of High-Risk Corneal Transplantation
by Tina Dietrich-Ntoukas, Felix Bock, Jasmine Onderka, Deniz Hos, Bjoern O. Bachmann, Grit Zahn and Claus Cursiefen
J. Clin. Med. 2024, 13(15), 4418; https://doi.org/10.3390/jcm13154418 - 28 Jul 2024
Cited by 1 | Viewed by 1394
Abstract
Background: Corneal inflammatory hem- and lymphangiogenesis significantly increase the risk for immune rejection after subsequent allogeneic corneal transplantation. The purpose of this study was to analyze the impact of temporary selective inhibition of lymphangiogenesis after transplantation on graft survival. Methods: Allogeneic transplantation from [...] Read more.
Background: Corneal inflammatory hem- and lymphangiogenesis significantly increase the risk for immune rejection after subsequent allogeneic corneal transplantation. The purpose of this study was to analyze the impact of temporary selective inhibition of lymphangiogenesis after transplantation on graft survival. Methods: Allogeneic transplantation from C57BL/6 mice to BalbC mice was performed as “high-risk” keratoplasty in a prevascularized corneal host bed (suture-induced inflammatory corneal neovascularization). The treatment group received integrin α5β1-blocking small molecules (JSM6427) at the time of transplantation and for two weeks afterwards. Control mice received a vehicle solution. Grafts were evaluated weekly for graft rejection using an opacity score. At the end of the follow-up, immunohistochemical staining of corneal wholemounts for lymphatic vessels as well as CD11b+ immune cells was performed. Results: Temporary postoperative inhibition of lymphangiogenesis by JSM6427 improved the corneal graft survival significantly. At the end of the follow-up, no significant reduction in CD11b+ immunoreactive cells within the graft compared to controls was found. Conclusions: The significant improvement of corneal graft survival by the selective, temporary postoperative inhibition of lymphangiogenesis after keratoplasty using integrin antagonists shows the impact of lymphatic vessels in the early postoperative phase. Retarding lymphatic vessel ingrowth into the graft might be sufficient for the shift to immunological tolerance in the postoperative period, even after high-risk keratoplasty. Full article
(This article belongs to the Special Issue New Insights into Corneal Regeneration and Transplantation)
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18 pages, 1307 KiB  
Review
Ocular Implications of COVID-19 Infection and Vaccine-Related Adverse Events
by Uday Pratap Singh Parmar, Pier Luigi Surico, Rohan Bir Singh, Mutali Musa, Anna Scarabosio, Giorgio Surico, Antonino Maniaci, Salvatore Lavalle, Fabiana D’Esposito, Antonio Longo, Andrea Russo, Caterina Gagliano and Marco Zeppieri
J. Pers. Med. 2024, 14(8), 780; https://doi.org/10.3390/jpm14080780 - 23 Jul 2024
Cited by 4 | Viewed by 2964
Abstract
The COVID-19 pandemic, caused by SARS-CoV-2, has significantly impacted various organ systems, including the eyes. Initially considered a primarily respiratory disease, it is now evident that COVID-19 can induce a range of ocular symptoms. Recognizing these ocular manifestations is crucial for eye care [...] Read more.
The COVID-19 pandemic, caused by SARS-CoV-2, has significantly impacted various organ systems, including the eyes. Initially considered a primarily respiratory disease, it is now evident that COVID-19 can induce a range of ocular symptoms. Recognizing these ocular manifestations is crucial for eye care practitioners as they can serve as early indicators of the disease. This review consolidates current evidence on the ocular effects of COVID-19, identifying manifestations such as conjunctivitis, scleritis, uveitis, and retinopathy. The increasing prevalence of these symptoms highlights the importance of thorough eye examinations and detailed patient histories in COVID-19 cases. Potential routes of viral entry into ocular tissues and the underlying mechanisms, including direct infection, immune responses, and vascular involvement, are explored. Additionally, this review addresses ocular side effects associated with COVID-19 vaccines, such as corneal graft rejection, uveitis, and retinal issues. These findings emphasize the need for ongoing surveillance and research to ensure vaccine safety. Full article
(This article belongs to the Section Mechanisms of Diseases)
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10 pages, 3878 KiB  
Article
Simultaneous Muraine Sutures and Excimer Laser-Assisted Penetrating Keratoplasty for Acute Keratoconus
by Marie Elisabeth Burghardt, Joana Heinzelmann, Marlene Stein, Anja Viestenz and Arne Viestenz
J. Clin. Med. 2024, 13(13), 3792; https://doi.org/10.3390/jcm13133792 - 28 Jun 2024
Cited by 1 | Viewed by 1232
Abstract
Background: Acute keratoconus (acute KC), which affects approximately 1.6–2.8% of keratoconus (KC) patients, is a pathological condition of the cornea characterized by stromal edema due to entry of aqueous humor through a tear in Descemet’s membrane. Methods: We present a novel combination [...] Read more.
Background: Acute keratoconus (acute KC), which affects approximately 1.6–2.8% of keratoconus (KC) patients, is a pathological condition of the cornea characterized by stromal edema due to entry of aqueous humor through a tear in Descemet’s membrane. Methods: We present a novel combination of surgical procedures that allows swifter visual recovery in a consecutive, retrospective case series. The new surgical procedure for acute KC consists of a combination of Muraine corneal sutures to smooth the corneal curvature and Excimer laser-assisted penetrating keratoplasty and was performed in six acute KC patients from 2019 to 2022 at the Department of Ophthalmology, University Hospital of Martin-Luther-University Halle-Wittenberg (UMH), Germany. We monitored data on preoperative status, operative details, intraoperative and postoperative complications and visual outcomes were analyzed. Results: The mean age was 41.5 ± 13.5 years (3 OD, 3 OS). Neurodermatitis was present in 3 patients (50%). All patients received significant visual benefits from the procedure. Preoperative BCVA was hand motion (logMAR 3.0) in all patients; postoperatively, BCVA improved significantly logMAR 0.03 ± 0.09 [range: 0.2–0.4; p < 0.001, FUP 20+/−10 months). Visual acuity remained stable throughout the roughly biannual follow-ups. One patient developed endothelial graft rejection after 2 years. During the last examination, all eyes had clear grafts and stable curvatures, K1 and K2 being 42.43 ± 4.17 D and 44.95 ± 4.07 D, respectively, and mean corneal astigmatism was 2.61 ± 1.74 D. The thinnest corneal thickness was 519 ± 31 µm. A graft size of 8.0 × 8.1 mm was the most beneficial. Conclusions: in patients with acute KC and hydrops, a penetrating keratoplasty with Muraine corneal sutures is successful in terms of graft clarity and visual outcome. Combining the procedures allows quicker visual recovery. Patients with a history of neurodermatitis should have preoperative and postoperative dermatologic treatment and close follow-up for possible complications. Full article
(This article belongs to the Special Issue Clinical Advances in Corneal and Refractive Surgery for Keratoconus)
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33 pages, 2733 KiB  
Review
Regenerative Therapy for Corneal Scarring Disorders
by Christine Chandran, Mithun Santra, Elizabeth Rubin, Moira L. Geary and Gary Hin-Fai Yam
Biomedicines 2024, 12(3), 649; https://doi.org/10.3390/biomedicines12030649 - 14 Mar 2024
Cited by 9 | Viewed by 6917
Abstract
The cornea is a transparent and vitally multifaceted component of the eye, playing a pivotal role in vision and ocular health. It has primary refractive and protective functions. Typical corneal dysfunctions include opacities and deformities that result from injuries, infections, or other medical [...] Read more.
The cornea is a transparent and vitally multifaceted component of the eye, playing a pivotal role in vision and ocular health. It has primary refractive and protective functions. Typical corneal dysfunctions include opacities and deformities that result from injuries, infections, or other medical conditions. These can significantly impair vision. The conventional challenges in managing corneal ailments include the limited regenerative capacity (except corneal epithelium), immune response after donor tissue transplantation, a risk of long-term graft rejection, and the global shortage of transplantable donor materials. This review delves into the intricate composition of the cornea, the landscape of corneal regeneration, and the multifaceted repercussions of scar-related pathologies. It will elucidate the etiology and types of dysfunctions, assess current treatments and their limitations, and explore the potential of regenerative therapy that has emerged in both in vivo and clinical trials. This review will shed light on existing gaps in corneal disorder management and discuss the feasibility and challenges of advancing regenerative therapies for corneal stromal scarring. Full article
(This article belongs to the Collection Feature Papers in Gene and Cell Therapy)
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