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In this study we describe peripheral corneal endothelial cell migration in vitro in the absence and presence of a ROCK-inhibitor. For this study, 21 corneal endothelial graft rims, with attached trabecular meshwork (TM), were prepared from Descemet membrane-endothelial cell sheets by 6.5 mm trepanation. For the initial proof-of-concept, 7 outer graft rims were cultured in a thermo-reversible hydrogel matrix for up to 47 days. To assess the effect of a ROCK-inhibitor, 14 paired outer rims were cultured either with or without ROCK-inhibitor for up to 46 days. At the end of culture, tissue was retrieved from the hydrogel matrix and examined for cell viability and expression of different endothelial cell markers (ZO-1, Na+/K+-ATPase, NCAM, glypican, and vimentin). All cultured rims remained viable and displayed either single regions (n = 5/21) or collective areas (n = 16/21) of cell migration, regardless of the presence or absence of ROCK-inhibition. Migration started after 4±2 days and continued for at least 29 days. The presence of ROCK-inhibitor seemed to contribute to a more regular cell morphology of migrating cells. In addition, 7 outer rims demonstrated a phenotypically distinct late-onset but fast-growing cell population emerging from the area close to the limbus. These cells emerged after 3 weeks of culture and appeared less differentiated compared to other areas of migration. Immunostaining showed that migrated cells maintained the expression patterns of endothelial cell markers. In conclusion, we observed 2 morphologically distinct migrating cell populations with the first type being triggered by a broken physical barrier, which disrupted contact inhibition and the second, late-onset type showing a higher proliferative capacity though appearing less differentiated. This cell subpopulation appeared to be mediated by stimuli other than loss of contact inhibition and ROCK-inhibitor presence. Further exploration of the differences between these cell types may assist in optimizing regenerative treatment options for endothelial diseases. [ABSTRACT FROM AUTHOR]

Corneal neurotization is a promising surgical approach for the treatment of moderate to severe neurotrophic keratopathy. This technique aims to restore corneal sensation by transferring healthy nerves, either directly or via a conduit, to the anesthetic cornea. This review provides a report on the current state of development, evidence, and experience in the field. We summarize the data available from clinical reports and case series, placing an emphasis on the diversity of the surgical techniques reported. While these data are encouraging, they also highlight the need for a consensus in reporting outcomes and highlight how the next step will involve validating putative outcome parameters when researching and reporting corneal neurotization surgery. [ABSTRACT FROM AUTHOR]

Chemosis is a common, though typically temporary complication of both upper and lower blepharoplasty surgery, though it is much more common after the latter. It occurs due to extravasation of fluid into the subconjunctival space precipitated by desiccation, inflammation, and manipulation of the conjunctiva and associated lymphatic drainage. Intraoperatively, minimizing surgical exposure and manipulation as well as maintaining a moist ocular surface can reduce the risks. Postoperatively, we propose a stepwise approach, starting with lubricants and escalating to increasingly potent anti-inflammatories with compression bandaging and surgery reserved for persistent cases. [ABSTRACT FROM AUTHOR]

Purpose: To determine the incidence of clinically significant pseudophakic cystoid macular edema (CSPME) after phacoemulsification using the 'bag-in-the-lens' lens (BIL) implantation technique and to examine the influence of associated risk factors for clinically significant pseudophakic macular edema (CSPME), both ocular and systemic. Methods: This retrospective study included 2419 first-operated eyes of 2419 adults who underwent phacoemulsification cataract surgery using the BIL implantation technique between January 2013 and December 2018 in the Antwerp University Hospital, Belgium. The significance of several risk factors (age, gender, previous history, intra- and postoperative complications) was examined by extraction of electronic medical files. Results: The 3-month incidence of CSPME in the subgroup without risk factors was 0.00% (95% CI: 0.00 –NA). The 3-month incidence of CSPME in the subgroup with risk factors was 0.57% (95% CI 0.22–1.29%). The 3-month incidence of CSPME in the total population of 2419 patients was 0.29% (95% CI: 0.11–0.65%). The risk factors most significantly associated with CSPME included renal insufficiency (hazard ration [HR]: 5.42; 95% CI: 1.69–17.44; P =.014), exudative age-related macular degeneration (HR: 74.50, 95% CI: 25.75–215.6; P <.001) and retinal vein occlusion (HR: 22.48, 95% CI: 4.55–111.02; P =.005). Conclusions: In the absence of risk factors, the incidence of CSPME was zero. We can conclude that Primary Posterior Continuous Curvilinear Capsulorhexis (PPCCC) does not increase the risk for CSPME. Non-inferiority of the BIL implantation regarding the development of CSPME, relative to the traditional 'lens-in-the-bag' (LIB) implantation, confirms that BIL is a safe surgical technique. This study also illustrates a previously undescribed risk factor for developing CSPME, namely renal insufficiency. [ABSTRACT FROM AUTHOR]

This document is a reply to a survey conducted by the European Board of Ophthalmology on cataract surgical training in Europe. The authors, from various institutions in Australia, provide their perspective on the topic. The document includes contact information for the corresponding author and discloses that the authors have no financial or proprietary interests in the subject matter. The document was published in the Journal of Cataract & Refractive Surgery in August 2024. [Extracted from the article]

Purpose: To present a descriptive system for the elliptic demarcation area seen in keratoconus densitometry maps (obtained with a Scheimpflug tomographer) and to evaluate its suitability for clinical practice. Methods: The subjects were 30 keratoconus patients at different stages and 20 healthy subjects. The averaged densitometry maps ('two‐layers' scan, with fixed layers 120 µm and endothelium) were analysed using a system of four categories (termed 'Brightness', 'Contrast', 'Decentration' and 'Octants surrounded by a dark line') that we created to characterise the demarcation area. Four examiners (three corneal specialists and one junior resident) used the system to classify the maps. The inter‐rater agreement was calculated for two subgroups: (1) clinical keratoconus patients and (2) both healthy patients and forme fruste keratoconus patients. Intra‐rater agreement was also determined. Results: Inter‐rater agreement on classification was higher when analysing clinical keratoconus, reaching levels of substantial agreement. Despite this, only low levels of agreement were found in 'Decentration', penalized due to the skewness in the distribution of this descriptor. Almost perfect intra‐rater agreement was obtained for all descriptors in the first subgroup of clinical keratoconus, whereas the agreement was generally moderate within the second subgroup of normal and forme fruste eyes. Agreement was slightly lower with the less experienced observer. At least three observers agreed on four forme fruste keratoconus eyes presenting abnormalities in the images. The observers reported that the 'Brightness' descriptor was subjective and redundant with 'Contrast'. Conclusions: The description of the area was repeatable and reproducible, and may be a valuable supplement when documenting clinical keratoconus stage and progression in daily practice. However, a minor learning curve was noticed and agreement was higher among the more experienced observers. Since the descriptor 'Brightness' was found to be subjective and redundant, it was excluded from the final proposed classification. [ABSTRACT FROM AUTHOR]

Introduction: To assess the postoperative outcome and patient-reported satisfaction, spectacle independence, and dysphotopsia after implantation with the mutifocal Rayner Sulcoflex supplementary intraocular lens (sIOL). Materials and Methods: We analyzed the outcome of all patients implanted with a multifocal sIOL between 2009 and 2011. In all cases, the sIOL was the Rayner Sulcoflex IOL (type 653F) and the primary IOL was a bag-in-the-lens (BIL) IOL. The data were obtained through a retrospective analysis of the patient records and by means of a questionnaire, 5 years after sIOL implantation. Results: This study included 31 eyes of 20 patients. In 13 eyes, the sIOL needed explantation (n = 13, 41.94%). Dysphotopsia is a frequent complaint (12/15 patients: 80.0%) after sIOL implantation. In 13 out of 31 eyes (41.94%), pigment deposits were found on the sIOL with variable clinical complaints. Five eyes required additional surgery because of clinically significant deposits. Discussion/Conclusion: Patients with a multifocal sIOL in combination with a BIL implantation have a higher incidence of dysphotopsia compared to previously published studies. Dysphotopsia was the main complaint and reason for explantation. We encountered a high incidence of pigmented IOL deposits. The sIOLs can be safely removed even years after implantation. [ABSTRACT FROM AUTHOR]

In this study, we describe a process of preparing, surgically manipulating, and validating a novel "small diameter" 4mm circular Descemet membrane endothelial keratoplasty (DMEK) graft in vitro. Three small diameter DMEK grafts can be prepared from a single donor endothelium and could, therefore, potentially expand the donor pool. Prior to clinical use, however, we aimed to examine each step of the process to determine the effect on the endothelial cell loss and whether or not cells retained their capacity to migrate uniformly. For this study, circular small diameter grafts, obtained from twelve corneas of ten donors deemed ineligible for transplantation, were included. Small diameter DMEK graft preparation was successful in all cases (n = 36). Endothelial cell density (ECD), determined in the eye bank on seventeen grafts, showed an average decrease from 2413 (±189) cells/mm2 before to 2240 (±413) cells/mm2 after preparation. Twenty-four grafts were used to simulate DMEK-surgery in vitro and were successfully stained with 0.06% trypan blue, loaded into a straight DMEK-injector, unfolded, positioned, and centered within the circular ~ 4mm descemetorhexis. The estimated % area populated by viable cells on the grafts decreased from on average 92 (±3) % before to 78 (±10) % (n = 4) after in vitro surgery. Cells displayed a capacity for uniform cell migration from all edges of the graft (n = 4) when embedded in the 3D hydrogel system. Our data show, that by using an in vitro model of DMEK-surgery it was possible to test the 4mm circular DMEK grafts from eye bank preparation to surgical implantation. The cell loss after in vitro surgery was comparable with the in vivo ECD decline early after DMEK and the capacity of the cells to migrate to potentially cover bare stroma indicates that these small diameter grafts may be a viable clinical option to treat central endothelial disease. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the origins of age‐related decreases in axial length in the literature. Methods: A literature review was performed, including all articles regarding axial length changes with age. These data were combined with mean body length and education level for the countries of each study to assess their influence in a multivariate analysis. Furthermore, analyses were performed of how optical path length, used by optical biometers to measure axial length, is affected by the known age‐related changes in the crystalline lens. The influence of other factors mentioned in the literature was also investigated. Results: Seventeen cross‐sectional studies were found that met the search criteria. The decrease in axial length over time was consistent across most of these studies. However, when plotted as a function of year of birth, mean body length and number of years in school, the data indicated an increase in length. Multivariate analysis confirmed the influence of body length (P = 0.005) and birth year (P = 0.017), but not age (P = 0.50). Meanwhile, the lenticular changes due to aging and cataract formation cause a minor bias in the form of increased axial length measurements. Finally, a gradual thinning of the choroidal arteries was reported to cause an increase in axial length. Conclusion: The age‐related decrease in axial length is mainly associated with gradual changes in increased body length and education level, while attenuated by minor biases in measurement procedure and thinning of the choroidal arteries. [ABSTRACT FROM AUTHOR]

Ex vivo grown human corneal endothelial cells (HCEnC) are a new emerging treatment option to treat visually impaired patients aimed at alleviating the current global donor shortage. Expanding HCEnC is still challenging, and obtaining cells in sufficient quantities is a limiting factor. It is already known that conditioned medium obtained from bone marrow mesenchymal stem cells can stimulate the proliferation of endothelial cells. The aim of this study was to take this work a step further to identify some of the underlying factors responsible. We confirmed the stimulatory effect of the mesenchymal stem cell secretome seen previously and separated the exosomes from the soluble proteins using size exclusion chromatography. We demonstrated the presence of exosomes and soluble proteins in the early and late fractions, respectively, with transmission electron microscopy and protein assays. Proliferation studies demonstrated that growth stimulation could be reproduced with the later protein-rich fractions but not with the exosome-rich fraction. Antibody assays revealed the presence of the secreted proteins EGF, IGFBP2, and IGFBP6 in protein-high fractions, but the growth enhancement was not seen with purified protein formulations. In conclusion, we confirmed the stimulatory effect of stem cell-conditioned medium and have determined that the effect was attributable to the proteins rather than to the exosomes. We were not able to reproduce the growth stimulation, however, with the pure recombinant protein candidates tested. Specific identification of the underlying proteins using proteomics could render a bioactive protein that can be used for ex vivo expansion of cells or as an in vivo drug to treat early corneal endothelial damage. [ABSTRACT FROM AUTHOR]

Endothelial cell migration plays a crucial role in achieving corneal clearance after corneal transplantation when using smaller-sized endothelial grafts to increase the donor pool. In this study we investigated how different strategies of Quarter-Descemet Membrane Endothelial Keratoplasty (Quarter-DMEK) limbal graft edge modification influence peripheral endothelial cell migration in an in vitro culture environment. For this study, 15 Quarter-DMEK grafts, prepared from 7 corneas deemed ineligible for transplantation but with intact and viable endothelial cells, were embedded in a cooled biocompatible, thermoresponsive matrix for culture. The limbal edge of ten Quarter-DMEK grafts were modified, either by using a small diameter punch or by peripheral radial cuts. All Quarter-DMEK grafts showed substantial collective endothelial cell migration from the radial cut graft edges, as observed by light microscopy at standardized time intervals. Grafts were retrieved from the polymer matrix after the two-week culture for immunohistochemistry analyses of the newly formed cell monolayers; this demonstrated the presence of tightly packed and viable cells that showed higher migratory ability at the leading edge. Peripheral endothelial cell migration, however, was not triggered by increasing cell exposure to free space through surgical modifications of the far periphery. Our data suggest that alterations in the far peripheral area of Quarter-DMEK grafts were insufficient to triggering cell migration from the limbal graft edge. This may be due to transient-amplifying cells that reside in the far periphery and which lack cytokinetic directional cues. Understanding the migration capacity of the peripheral endothelium could unlock cells' therapeutic potential which are, at present, routinely discarded from transplantation. Encouraging peripheral cell migration may also improve clinical outcomes from Quarter-DMEK, but a more effective solution is required prior to clinical implementation of modified grafts. [ABSTRACT FROM AUTHOR]

Pterygium is a common eye disease, linked to an increased exposure to UV radiation and dry environments. The associated pathology culminates in visual impairment and, in some rare cases, blindness. However, there remains a lot of uncertainty concerning the pathogenesis of this fibrovascular lesion. As the composition of the tear film provides a reflection into the pathological changes at the ocular surface, tear analysis represents an ideal approach to gain insight in the progression of disease following pterygiectomy. This study enrolled 19 patients and age/gender-matched healthy controls. Tear film levels of interleukin- (IL-) 6, IL-8, and vascular endothelial growth factor (VEGF) were investigated over time, and preoperative concentrations were linked to corneal neovascularization and pterygium size. Diminished tear film levels were found in unilateral patients who show no clinical signs of pterygium recurrence over a period of one year. Hence, our results highlight the potential of using the course of IL-6, IL-8, and VEGF levels in tears as biomarkers for recovery. In addition, when focusing on the affected eyes (i.e., primary and recurrent pterygium), we detected fold changes in preoperative cytokine concentrations to correspond with disease severity. As our proposed biomarkers did not reveal a linear relationship with corneal neovascularization nor the invasive behaviour of pterygium, no exact role in the pterygium pathology could be established. Hence, our data point to these factors being contributors rather than decisive players in the pathological processes. [ABSTRACT FROM AUTHOR]

Background: The presence of a space between the posterior capsule and the anterior vitreous was first reported in 1887, but difficulties inherent in examining this structure made it impossible to visualize this area in vivo until now. Estimation of the size of this space was considered to be impossible. Materials and Methods: We utilized an optical coherence tomography (OCT) system attached to the Zeiss Opmi Lumera 700/Rescan microscope (Zeiss Ltd., Jena, Germany) to provide real-time images of the Berger space, the anterior hyaloid and the ligament of Wieger. Results: Imaging in 3 patients provided beautiful, real-time OCT images of the Berger space and of the ligament of Wieger. In one highly myopic eye, there was even evidence of anterior vitreous detachment. Conclusion: Previously unseen transparent structures of the eye can now be imaged intraoperatively using realtime OCT. This new technology seems very promising in achieving a better understanding of the anterior vitreous interface, more specifically of the anterior hyaloid and its posterior capsule attachment by the ligament of Wieger. Changes in the anterior hyaloid and its capsular attachment may contribute to a better understanding of the posterior segment complications after cataract surgery. [ABSTRACT FROM AUTHOR]

Severe ocular surface disease can result in limbal stem cell deficiency (LSCD), a condition leading to decreased visual acuity, photophobia, and ocular pain. To restore the ocular surface in advanced stem cell deficient corneas, an autologous or allogenic limbal stem cell transplantation is performed. In recent years, the risk of secondary LSCD due to removal of large limbal grafts has been significantly reduced by the optimization of cultivated limbal epithelial transplantation (CLET). Despite the great successes of CLET, there still is room for improvement as overall success rate is 70% and visual acuity often remains suboptimal after successful transplantation. Simple limbal epithelial transplantation reports higher success rates but has not been performed in as many patients yet. This review focuses on limbal epithelial stem cells and the pathophysiology of LSCD. State-of-the-art therapeutic management of LSCD is described, and new and evolving techniques in ocular surface regeneration are being discussed, in particular, advantages and disadvantages of alternative cell scaffolds and cell sources for cell based ocular surface reconstruction. [ABSTRACT FROM AUTHOR]

The article describes the case of a slowly progressive keratouveitis in a 38-year-old West-African patient with known systemic leishmaniasis and human-immunodeficiency virus (HIV) disease. Topics discussed include the laboratory examinations conducted on the patient including direct microscopic evaluation of a conjunctival biopsy and polymerase chain reaction (PCR) and the cutaneous manifestations of keratouveitis such as multiple small nonulcerating nodules on hands, arms and face.

Cataract is a common condition observed in patients with diabetes mellitus frequently requiring surgical intervention. The bag-in-the-lens (BIL) intraocular implant is an alternative approach to standard lens-in-the-bag cataract surgery. The lens is supported by anterior and posterior capsulorhexes, which confers a number of advantages in terms of lens centration, rotational stability and prevention of posterior capsular opacity. The purpose of this report is to describe the results of BIL cataract surgery in a retrospective cohort of diabetic patients. Fifty-four cases of BIL surgery are included with a follow-up period of 1 year. Visual acuity outcomes were comparable to previously published standard lens-in-the-bag procedures. There were no reports of posterior capsular opacification and the grade of diabetic retinopathy remained stable. Three cases of clinically significant macular edema were detected over the follow-up period. We conclude that the BIL implantation technique is an advantageous approach to treating cataract in the diabetic population. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Purpose Methods Results Conclusions To report national practices and recent progress in competency‐based medical education (CBME) implementation in ophthalmology across European countries.A 30‐question online survey was emailed to European Union of Medical Specialists (UEMS) ophthalmology section delegates, European Board of Ophthalmology Diploma (EBOD) examiners and presidents of ophthalmology societies affiliated with UEMS/EBO.A total of 230 ophthalmologists with an average age of 54.7 years [30–77] and from 28 countries completed the survey. Half of them had been involved as medical educators for more than 10 years. The majority (74%) exercised their educational role in a University Hospital. Ninety six percent of them dedicated less than 50% of their activity to teaching. A third dedicated more than a half of their activity to patient care. The teaching of skills reported (medical, surgical, research, attitudinal and theoretical knowledge) was significantly better applied than their assessment. While 91% of the respondents found it necessary to harmonize European Training Requirements (ETR) in ophthalmology, competency‐based education concepts were rarely implemented in their country (for instance, 8% for CBME; 6% for entrustable professional activities (EPAs) and 3% for ETR).Despite considerable diversity in European residency programmes, post‐graduate medical education leaders in ophthalmology agree on the need to find a platform for equivalence in the content of the basic training requirements that constitute the professional identity of a practicing ophthalmologist. [ABSTRACT FROM AUTHOR]

One key element to the health of the ocular surface encompasses the presence of gel-forming mucins in the pre-ocular tear film. Conjunctival goblet cells are specialized epithelial cells that secrete mucins necessary for tear film stability and general homeostasis. Their dysfunction can be linked to a range of ocular surface inflammation disorders and chronic injuries. To obtain new perspectives and angles to tackle mucin deficiency, the need for an accurate evaluation of their presence and corresponding mucin secretion in ex vivo conjunctival cultures has become a requisite. In vitro, goblet cells show a significant decrease in the production and secretion of gel-forming mucins, accompanied by signs of dedifferentiation or transdifferentiation. Explant cultures on laminin-treated CLP-PEG hydrogels can, however, support the production of gel-forming mucins. Together, we challenge the current paradigm to evaluate the presence of cultured goblet cells solely based on their general mucin (MUC) content through imaging analyses, showing the need for additional techniques to assess the functionality of goblet cells. In addition, we broadened the gel-forming mucin profile of in vivo goblet cells with MUC5B and MUC6, while MUC2 and MUC6 is added to the profile of cultured goblet cells. [ABSTRACT FROM AUTHOR]

Early and accurate detection of keratoconus progression is particularly important for the prudent, cost-effective use of corneal cross-linking and judicious timing of clinical follow-up visits. The aim of this study was to verify whether a progression could be predicted based on two prior tomography measurements and to verify the accuracy of the system when labelling the eye as stable or suspect progressive. Data from 743 patients measured by Pentacam (Oculus, Wetzlar, Germany) were available, and they were filtered and preprocessed to data quality needs. The time delay neural network received six features as input, measured in two consecutive examinations, predicted the future values, and determined the classification (stable or suspect progressive) based on the significance of the change from the baseline. The system showed a sensitivity of 70.8% and a specificity of 80.6%. On average, the positive and negative predictive values were 71.4% and 80.2%. Including data of less quality (as defined by the software) did not significantly worsen the results. This predictive system constitutes another step towards a personalized management of keratoconus. While the results obtained were modest and perhaps insufficient to decide on a surgical procedure, such as cross-linking, they may be useful to customize the timing for the patient's next follow-up. [ABSTRACT FROM AUTHOR]

Pterygium is a multifaceted pathology that displays apparent conflicting characteristics: benign (e.g., self-limiting and superficial), bad (e.g., proliferative and potentially recurrent) and ugly (e.g., signs of preneoplastic transformation). The natural successive question is: why are we lacking reports showing that pterygium lesions become life-threatening through metastasis, especially since pterygium has considerable similarities with UV-related malignancies on the molecular level? In this review, we consider how our pathophysiological understanding of the benign pterygium pathology overlaps with ocular surface squamous neoplasia and skin cancer. The three UV-related disorders share the same initial insult (i.e., UV radiation) and responsive repair mechanisms to the ensuing (in)direct DNA damage. Their downstream apoptotic regulators and other cellular adaptations are remarkably alike. However, a complicating factor in understanding the fine line between the self-limiting nature of pterygium and the malignant transformation in other UV-related diseases is the prominent ambiguity in the pathological evaluation of pterygium biopsies. Features of preneoplastic transformation (i.e., dysplasia) are used to define normal cellular reactions (i.e., atypia and metaplasia) and vice versa. A uniform grading system could help in unraveling the true nature of this ancient disease and potentially help in identifying the earliest intervention point possible regarding the cellular switch that drives a cell's fate towards cancer. [ABSTRACT FROM AUTHOR]