Wundheilungsmodulation im vorderen Augenabschnitt: experimentelle und klinische Betrachtungen

Die vorliegende Arbeit betrachtet Aspekte der Wundheilungsmodulation im vorderen Augenabschnitt. Dabei werden drei ophthalmologische Anwendungsfelder mit hoher klinischer Relevanz betrachtet, welche alle mit fibrotischen Prozessen assoziiert sind. Der erste Themenkomplex beschreibt induzierte Wundheilungsmechanismen nach fistulierender Glaukomchirurgie. Im zweiten Themenbereich der Schrift werden Wundheilungsmechanismen der Kornea und im abschließenden dritten Themenfeld postoperative Wundheilungsprozesse nach durchgeführter Kataraktchirurgie näher betrachtet.The present work considers aspects of wound healing modulation in the anterior segment of the eye. Three ophthalmological fields of application with high clinical relevance are considered, all of which are associated with fibrotic processes. The first topic describes induced wound healing mechanisms after fistulating glaucoma surgery. In the second topic, wound healing mechanisms of the cornea are described, followed by postoperative wound healing mechanisms after cataract surgery in the third topic

Computational analysis on verbal fluency reveals heterogeneity in subjective language interests and brain structure

Language is an essential higher cognitive function in humans and is often affected by psychiatric and neurological disorders. Objective measures like the verbal fluency test are often used to determine language dysfunction. Recent applications of computational approaches broaden insights into language-related functions. In addition, individuals diagnosed with a psychiatric or neurological disorder also often report subjective difficulties in language-related functions. Therefore, we investigated the association between objective and subjective measures of language functioning, on the one hand, and inter-individual structural variations in language- related brain areas, on the other hand. We performed a Latent Semantic analysis (LSA) on a semantic verbal fluency task in 101 healthy adult participants. To investigate if these objective measures are associated with a subjective one, we examined assessed subjective natural tendency of interest in language-related activity with a study-specific questionnaire. Lastly, a voxel-based brain morphometry (VBM) was conducted to reveal associations between objective (LSA) measures and structural changes in language-related brain areas. We found a positive correlation between the LSA measure cosine similarity and the subjective interest in language. Furthermore, we found that higher cosine similarity corresponds to higher gray matter volume in the right cerebellum. The results suggest that people with higher interests in language access semantic knowledge in a more organized way exhibited by higher cosine similarity and have larger gray matter volume in the right cerebellum, when compared to people with lower interests. In conclusion, we demonstrate that there is inter-individual diverseness of accessing the semantic knowledge space and that it is associated with subjective language interests as well as structural differences in the right cerebellum

Atypical cellular elements of unknown origin in the subbasal nerve plexus of a diabetic cornea diagnosed by large-area confocal laser scanning microscopy

In vivo large-area confocal laser scanning microscopy (CLSM) of the human eye using EyeGuidance technology allows a large-scale morphometric assessment of the corneal subbasal nerve plexus (SNP). Here, the SNP of a patient suffering from diabetes and associated late complications was analyzed. The SNP contained multiple clusters of large hyperintense, stellate-shaped, cellular-like structures. Comparable structures were not observed in control corneas from healthy volunteers. Two hypotheses regarding the origin of these atypical structures are proposed. First, these structures might be keratocyte-derived myofibroblasts that entered the epithelium from the underlying stroma through breaks in Bowman’s layer. Second, these structures could be proliferating Schwann cells that entered the epithelium in association with subbasal nerves. The nature and pathophysiological significance of these atypical cellular structures, and whether they are a direct consequence of the patient’s diabetic neuropathy/or a non-specific secondary effect of associated inflammatory processes, are unknown

Morphological characterization of the human corneal epithelium by in vivo confocal laser scanning microscopy

Background: Regarding the growing interest and importance of understanding the cellular changes of the cornea in diseases, a quantitative cellular characterization of the epithelium is becoming increasingly important. Towards this, the latest research offers considerable improvements in imaging of the cornea by confocal laser scanning microscopy (CLSM). This study presents a pipeline to generate normative morphological data of epithelial cell layers of healthy human corneas. Methods: 3D in vivo CLSM was performed on the eyes of volunteers (n=25) with a Heidelberg Retina Tomograph II equipped with an in-house modified version of the Rostock Cornea Module implementing two dedicated piezo actuators and a concave contact cap. Image data were acquired with nearly isotropic voxel resolution. After image registration, stacks of en-face sections were used to generate full-thickness volume data sets of the epithelium. Beyond that, an image analysis algorithm quantified en-face sections of epithelial cells regarding the depth-dependent mean of cell density, area, diameter, aggregation (Clark and Evans index of aggregation), neighbor count and polygonality. Results: Imaging and cell segmentation were successfully performed in all subjects. Thereby intermediated cells were efficiently recognized by the segmentation algorithm while efficiency for superficial and basal cells was reduced. Morphological parameters showed an increased mean cell density, decreased mean cell area and mean diameter from anterior to posterior (5,197.02 to 8,190.39 cells/mm²; 160.51 to 90.29 µm²; 15.9 to 12.3 µm respectively). Aggregation gradually increased from anterior to posterior ranging from 1.45 to 1.53. Average neighbor count increased from 5.50 to a maximum of 5.66 followed by a gradual decrease to 5.45 within the normalized depth from anterior to posterior. Polygonality gradually decreased ranging from 4.93 to 4.64 sides of cells. The neighbor count and polygonality parameters exhibited profound depth-dependent changes. Conclusions: This in vivo study demonstrates the successful implementation of a CLSM-based imaging pipeline for cellular characterization of the human corneal epithelium. The dedicated hardware in combination with an adapted image registration method to correct the remaining motion-induced image distortions followed by a dedicated algorithm to calculate characteristic quantities of different epithelial cell layers enabled the generation of normative data. Further significant effort is necessary to improve the algorithm for superficial and basal cell segmentation

Development of a Novel Valve-Controlled Drug-Elutable Microstent for Microinvasive Glaucoma Surgery: In Vitro and Preclinical In Vivo Studies

Purpose: Microinvasive glaucoma surgery (MIGS) has become an important treatment approach for primary open-angle glaucoma, although the safe and long-term effective lowering of intraocular pressure with currently available implants for MIGS is not yet achieved to a satisfactory extent. The study focusses on the development and in vitro and in vivo testing of a novel microstent for MIGS. Methods: A silicone elastomer-based microstent was developed. Implants were manufactured using dip coating, fs-laser cutting, and spray coating. Within the current study no antifibrotic drug was loaded into the device. Sterilized microstents were analyzed in vitro regarding pressure–flow characteristics and biocompatibility. Six New Zealand white rabbits were implanted with a microstent draining the aqueous humor from the anterior chamber into the subconjunctival space. Drainage efficacy was evaluated using oculopressure tonometry as a transient glaucoma model. Noninvasive imaging was performed. Results: Microstents were manufactured successfully and characterized in vitro. Implantation in vivo was successful for four animals with additional device fixation. Without additional fixation, dislocation of microstents was found in two animals. Safe and effective intraocular pressure reduction was observed for the four eyes with correctly implanted microstent during the 6-month trial period. Conclusions: The described microstent represents an innovative treatment approach for MIGS. The incorporation of a selectively antifibrotic drug into the microstent drugelutable coating will be addressed in future investigations. Translational Relevance: The current preclinical study successfully provided proof of concept for our microstent for MIGS which is suitable for safe and effective intraocular pressure reduction and offers promising perspectives for the clinical management of glaucoma

Bilateral paediatric cataract surgery - outcomes of 298 children from Kinshasa, the Democratic Republic of the Congo

Introduction: The leading cause of childhood blindness globally is paediatric cataract. Bilateral cataract surgery can help to improve visual performance and to diminish the burden of childhood blindness. Objective: To report in a retrospective observational cohort study the long-term outcomes of 298 children who had bilateral cataract surgery with IOL implantation from 2001-2016 in Kinshasa. Methods: A standardized surgical treatment of paediatric cataract was practiced on 298 children. Patient\u2019s follow-up, complications, and visual outcomes were recorded and analysed. Results: The mean age was 5.7 \ub1 4.3 years and males were predominant (64.9%). Most of children were living mainly in urban poorest areas (96.3%). Strabismus, nystagmus and microcornea were encountered in 20.1%, 25.1% and 8.7% of children, respectively. Using WHO criteria most of patients were classified as blind preoperatively and 81.9% of them had improved visual outcomes after surgery. Main reasons for reduced vision during follow-up were secondary cataract (5.7%), IOL decentration (1.2%), retinal detachment (1.2%), and secondary glaucoma (1.5%). Conclusion: In spite of the post conflict challenges, elimination of cataract blindness in children remains a priority. Children present at a late age for surgery and long term follow-up is poor. There is need for program strengthening in these areas

Presbyopia:Effectiveness of correction strategies

Presbyopia is a global problem affecting over a billion people worldwide. The prevalence of unmanaged presbyopia is as high as 50% of those over 50 years of age in developing world populations due to a lack of awareness and accessibility to affordable treatment, and is even as high as 34% in developed countries. Definitions of presbyopia are inconsistent and varied, so we propose a redefinition that states “presbyopia occurs when the physiologically normal age-related reduction in the eye's focusing range reaches a point, when optimally corrected for distance vision, that the clarity of vision at near is insufficient to satisfy an individual's requirements”. Presbyopia is inevitable if one lives long enough, but intrinsic and extrinsic risk factors including cigarette smoking, pregnancy history, hyperopic or astigmatic refractive error, ultraviolet radiation, female sex (although accommodation is similar to males), hotter climates and some medical conditions such as diabetes can accelerate the onset of presbyopic symptoms. Whilst clinicians can ameliorate the symptoms of presbyopia with near vision spectacle correction, bifocal and progressive spectacle lenses, monovision, translating or multifocal contact lenses, monovision, extended depth of focus, multifocal (refractive, diffractive and asymmetric designs) or ‘accommodating’ intraocular lenses, corneal inlays, scleral expansion, laser refractive surgery (corneal monovision, corneal shrinkage, corneal multifocal profiles and lenticular softening), pharmacologic agents, and electro-stimulation of the ciliary muscle, none fully overcome presbyopia in all patients. While the restoration of natural accommodation or an equivalent remains elusive, guidance is gives on presbyopic correction evaluation techniques

Endocrinologic, neurologic, and visual morbidity after treatment for craniopharyngioma

Craniopharyngiomas are locally aggressive tumors which typically are focused in the sellar and suprasellar region near a number of critical neural and vascular structures mediating endocrinologic, behavioral, and visual functions. The present study aims to summarize and compare the published literature regarding morbidity resulting from treatment of craniopharyngioma. We performed a comprehensive search of the published English language literature to identify studies publishing outcome data of patients undergoing surgery for craniopharyngioma. Comparisons of the rates of endocrine, vascular, neurological, and visual complications were performed using Pearson’s chi-squared test, and covariates of interest were fitted into a multivariate logistic regression model. In our data set, 540 patients underwent surgical resection of their tumor. 138 patients received biopsy alone followed by some form of radiotherapy. Mean overall follow-up for all patients in these studies was 54 ± 1.8 months. The overall rate of new endocrinopathy for all patients undergoing surgical resection of their mass was 37% (95% CI = 33–41). Patients receiving GTR had over 2.5 times the rate of developing at least one endocrinopathy compared to patients receiving STR alone or STR + XRT (52 vs. 19 vs. 20%, χ2P < 0.00001). On multivariate analysis, GTR conferred a significant increase in the risk of endocrinopathy compared to STR + XRT (OR = 3.45, 95% CI = 2.05–5.81, P < 0.00001), after controlling for study size and the presence of significant hypothalamic involvement. There was a statistical trend towards worse visual outcomes in patients receiving XRT after STR compared to GTR or STR alone (GTR = 3.5% vs. STR 2.1% vs. STR + XRT 6.4%, P = 0.11). Given the difficulty in obtaining class 1 data regarding the treatment of this tumor, this study can serve as an estimate of expected outcomes for these patients, and guide decision making until these data are available