The mechanism of intraocular pressure rise after keratoplasty

Purpose: To determine the pathomechanism of increased intraocular pressure after penetrating and lamellar keratoplasty based on clinical observation and literature data. Materials and methods: Morphometric analysis of the anterior segment of the eye using spectroscopic optical coherence tomography, gonioscopy and biomicroscopy. Results: Pre- and postoperative spectroscopic optical coherence tomography scans in patients after keratoplasty reveal deformation of the peripheral cornea, narrowing of the iridocorneal angle, presence of anterior synechiae and various types of pupillary block. Conclusions: The mechanism of elevated intraocular pressure after corneal grafting is complex and depends on pre-, intra- and postoperative factors, such as anatomy changes of the iridocorneal angle, presence of anterior synechiae, as well as anterior and posterior pupillary block. Spectroscopic optical coherence tomography plays an important role in diagnosis and further treatment management.

Use of biomaterials in corneal endothelial repair

Human corneal endothelium (HCE) is a single layer of hexagonal cells that lines the posterior surface of the cornea. It forms the barrier that separates the aqueous humor from the rest of the corneal layers (stroma and epithelium layer). This layer plays a fundamental role in maintaining the hydration and transparency of the cornea, which in turn ensures a clear vision. In vivo, human corneal endothelial cells (HCECs) are generally believed to be nonproliferating. In many cases, due to their nonproliferative nature, any damage to these cells can lead to further issues with Descemet’s membrane (DM), stroma and epithelium which may ultimately lead to hazy vision and blindness. Endothelial keratoplasties such as Descemet’s stripping automated endothelial keratoplasty (DSAEK) and Descemet’s membrane endothelial keratoplasty (DEK) are the standard surgeries routinely used to restore vision following endothelial failure. Basically, these two similar surgical techniques involve the replacement of the diseased endothelial layer in the center of the cornea by a healthy layer taken from a donor cornea. Globally, eye banks are facing an increased demand to provide corneas that have suitable features for transplantation. Consequently, it can be stated that there is a significant shortage of corneal grafting tissue; for every 70 corneas required, only 1 is available. Nowadays, eye banks face long waiting lists due to shortage of donors, seriously aggravated when compared with previous years, due to the global COVID-19 pandemic. Thus, there is an urgent need to find alternative and more sustainable sources for treating endothelial diseases, such as utilizing bioengineering to use of biomaterials as a remedy. The current review focuses on the use of biomaterials to repair the corneal endothelium. A range of biomaterials have been considered based on their promising results and outstanding features, including previous studies and their key findings in the context of each biomaterial.

Five Years Pathological Evaluation of Corneal Regrafts: A Study from Southern Iran

Purpose. Corneal regrafts sometimes needed to restore the transparency after graft failure. The aim of the study is five years epidemiologic and histopathological evaluation of corneal regrafts. Methods. In this cross-sectional study, all corneal regrafts during 5 years (2012–2016) were assessed in the Khalili Ophthalmology Center at Shiraz city. Demographic data including age, area of residence, primary disease, type of graft, cause of regraft, interval between primary and subsequent grafts (IPSG), associated eye diseases or surgeries, and systemic diseases were recorded. Also, microscopic findings of corneas were reviewed. Results. Among a total of 1190 corneal grafts, 76 of them (6.38%) were regrafts. The most common type of grafting was penetrating keratoplasty (PK). The shortest IPSG was observed in fungal keratitis. Main causes of graft failure were endothelial dysfunction, infection, immunologic rejection, technical problems, and recurrence of primary disease, respectively. The most common histopathological finding in failed grafts was severe endothelial cell loss (89.8%). Also, more than half and one-third of cases had Descemet membrane changes and stromal ingrowth, respectively. Conclusion. Endothelial cell loss was the major cause of failure in our study. Also, recurrence rate in infective cases, especially fungal keratitis, was very high. Considerable presence of histopathological changes such as doubling of Descemet membrane and retrocorneal fibrous ingrowth need further investigations. Perhaps, modification in techniques of corneal grafting and assessment of donor tissue and recipient bed along with any need for longer medical treatment are the basis for future studies in order to increase graft survival.

Mechanisms of immune regulation and transplantation immunity in corneal transplants

At the present time, corneal transplantation (keratoplasty) is one of the most frequent modes of solid tissue transplants in the world. Unlike other kinds of transplants, corneal grafting is often performed without tissue typing and systemic immunosuppression.High frequency of transparent corneal engraftment (up to 90% of cases) in the absence of risk factors is due to special immunoprivileged area in the anterior eye segment (functionally, a structural aggregation of the cornea and anterior chamber, AC) accomplished by local and systemic immunoregulatory mechanisms, i.e., phenomenon of immune deviation associated with anterior chamber of the eye (ACAID), components of the internal liquid medium, a watery moisture with immunosuppressive properties, e.g., IL-1ra, TSP-1,TGF-β2, regulatory complement proteins, α-MSH (alpha-melanocyte stimulating hormone), VIP (vasoactive intestinal peptide), indolamine 2,3-dioxygenase (IDO), calcitonin-gene-bound peptide (CGRP), somatostatin, etc.In addition to ACAID and liquid AC components, a contribution to the maintenance of immune privilege which is extremely important for a successful outcome of keratoplasty, is provided by other mechanisms, in particular, immunologically active membrane-associated molecules of corneal endothelium, i.e., PDL-1 (Programmed death ligand 1), and sVEGFR-1, sVEGFR-2, sVEGFR-3 involved in maintaining avascularity of the corneal tissue. Disturbances of the immune privilege of the cornea promotes activation of immune recognition with switching the effector mechanisms of transplantation immunity, thus leading to subsequent development of the tissue incompatibility reaction and clouding of transplanted cornea. Graft rejection can be localized in any of the corneal cell layers, including epithelium, stroma, and endothelium. Endothelial rejection causes the most severe affection of visual functions, due to the inability of local endothelial recovery, and water accumulation due to the endothelial dysfunction.Graft rejection is clinically characterized by edema and the presence of inflammatory cells, either circulating in the anterior chamber, or forming precipitates on the graft endothelial cells.A number of factors are associated with an increased risk of corneal graft rejection, including the degree of inflammation and/or vascularization of the transplant bed i.e., location of the donor cornea, repeated keratoplasty, allosensitization due to other cellular transplants, including bone marrow, blood transfusions, pregnancy, etc., as well as allergic and systemic diseases.This review article considers and systematizes the data from the literature concerning studies of the factors determining the immune privileged state of cornea, and the ACAID phenomenon, their role in development of allotolerance in corneal transplantation, highlights the main conditions required for triggering the tissue incompatibility reactions, discusses the mechanisms of allogeneic recognition and effector stage of the immune response, destruction of corneal allografts.

Comparative evaluation of decellularized bovine omentum alone and in combination with mitomycin-C in the management of corneal injuries in dogs

Background and Aim: Ulcerative corneal lesions are common ocular affections encountered in veterinary ophthalmology, having a higher incidence in dogs with brachycephalic conformation. Prompt and effective diagnosis and repair are necessary to avoid corneal perforation and restore vision. Corneal wound healing is a complex phenomenon often resulting in vision impairment as a consequence of corneal fibrosis and pigmentation. The present study investigated the efficacy of decellularized and gamma-irradiated bovine omentum as an extracellular matrix scaffold in the reconstruction of extensive and full-thickness corneal defects, and the cytotoxic effects of mitomycin-C (MMC) to prevent corneal fibrosis and pigmentation. Materials and Methods: Twelve injured corneas of eleven dogs irrespective of breed, age, and sex were randomly divided into Groups I and II, consisting of six corneas each. Under general anesthesia, corneal grafting with decellularized and gamma-irradiated bovine omentum was carried out in Group I, whereas Group II corneas underwent single time intra-operative application of topical MMC for 2 min before corneal grafting with the same material. Epithelialization of cornea and observations including corneal edema, neovascularization, the extent of pigmentation, corneal clarity, and scarring was recorded on days 7, 14, 21, and 60 postoperatively. Results: All corneas in Group I showed early epithelialization by day 7 compared to Group II where the MMC delayed epithelialization in 50% of the corneas. Visual function scores improved greatly from 0.17±0.17 in Group II on the day of presentation to 1.0±00 by the end of the observation period compared to Group I (from 0.33±0.15 to 0.88±0.11). Although epithelialization and corneal healing were delayed, 50% of the corneas recovered with undetectable corneal scar and melanosis at the end of the observation period in Group II due to the anti-fibrotic effect of MMC. Conclusion: From the present study, it was concluded that re-epithelialization of the cornea was enhanced by corneal grafting with decellularized bovine omentum, and application of MMC was effective in delaying corneal fibrosis and pigmentation.

From DMEK to Corneal Endothelial Cell Therapy: Technical and Biological Aspects

The main treatment available for restoration of the corneal endothelium is keratoplasty and DMEK provides faster visual recovery and better postoperative visual acuity when compared to DSAEK. However, the technical challenges related to this technique and the steep technical learning curve seem to prevent the overcoming of DSAEK in favor of DMEK. Furthermore, the outcome of lamellar keratoplasty techniques is influenced by problems related to corneal grafting tissue availability, management, and quality. On the other hand, improvements in the field of cell engineering have opened the way for the use of stem cells-derived corneal endothelial cells with regenerative intent. In this overview, latest findings in endothelial cell engineering are reported, and perspectives of clinical application of mesenchymal stem cells for corneal endothelial replacement and regeneration are evaluated.

mTOR complex 1 pathway activation in severe keratoconus; the functional implications of GWAS identified loci

PurposeKeratoconus (KC) is an eye condition that can lead to a severe vision loss and may warrant a corneal grafting procedure. Meta-analyses of genome wide association studies have identified several genes that confer risks for differences in corneal curvature, corneal thickness, and developing keratoconus. Currently, there is limited evidence of a functional role for the identified loci in the affected corneal tissues.MethodsWe investigated the gene expression profiles of 4 GWAS confirmed risk loci and several related pathways that function in cellular ageing and cell cycle control in corneal tissue of a discovery and replication cohort comprising in total 27 keratoconus patients, 16 healthy controls, and 21 diseased controls (failed corneal grafts).ResultsWe confirmed the MTOR gene locus as differentially expressed in KC corneas in a discovery cohort Next, we replicated these results in a second cohort and found evidence of increased expression of various mTORC1 pathway signature genes, namely MTOR itself (P=0.040), AKT1 (P=0.028), IGF1R (P=0.022) and RAPTOR (P=0.007).ConclusionsGene expression profiling in cornea tissues revealed robust up-regulation of the mTORC1 pathway in KC and substantiates a potential role for this pathway in its pathogenesis. Functional implications should be further studied since biomarkers for disease activity are needed and selective targeting of the mTOR pathway is a promising treatment concept.

Use of the Femtosecond Lasers in Ophthalmology

Femtosecond laser (FSL) is an infrared laser with a wavelength of 1053 nm. FS laser works producing photodisruption or photoionization of the optically transparent tissue such as cornea. Currently FS lasers have a wide range of applications in ophthalmic surgery. They are used above all in corneal surgery in refractive procedures and keratoplasty, and recently in cataract surgery. The use of the FSL in corneal refractive surgery includes LASIK flap creation, astigmatic keratotomy, Femtosecond Lenticule Extraction (FLEx), Small Incision Lenticule Extraction (SMILE) and channels creation for implantation of the intrastromal corneal rings. As to the corneal grafting, the FS lasers are used in laser-assisted anterior and posterior lamellar keratoplasty and customized trephination in the penetrating keratoplasty. FS Laser Assisted Cataract Surgery (FLACS) includes capsulorrhexis and nuclear fragmentation that enhance safety and efficacy of the procedure.