[Global ophthalmology : Update]. / Globale Ophthalmologie : Aktueller Stand.

The aim of global ophthalmology is to maximize vision, ocular health and functional ability, thereby contributing to overall health and well-being, social inclusion and quality of life of every individual worldwide. Currently, an estimated 1.1 billion people live with visual impairment, 90% of which can be prevented or cured through largely cost-effective interventions. At the same time, 90% of people affected live in regions with insufficient eye health coverage. This challenge drove the World Health Organization (WHO) and a group of nongovernmental organizations to launch "VISION 2020: the Right to Sight", a global campaign which recently concluded after 20 years. The achievements, challenges and lessons learned were identified and incorporated into the current campaign "2030 IN SIGHT".

Ex Vivo Micro-CT in Ophthalmology: Preparation and Contrasting for Non-invasive 3D-Visualisation. / Ex-vivo-Mikro-CT in der Augenheilkunde: Probenbehandlung und -kontrastierung für die 3D-Darstellung.

X-ray-based micro-computed tomography (micro-CT) is a largely non-destructive imaging method for the visualisation and analysis of internal structures in the ex vivo eye and affords high resolution. In contrast to other high-resolution imaging methods, micro-CT enables spatial recording of larger and more complex tissue structures, such as the anterior chamber of the eye. Special contrasting methods help to enhance the absorption properties of soft tissue, that is otherwise only weakly radiopaque. Critical point drying (CPD), as primarily used in scanning electron microscopy, offers an additional tool for improving differential contrast properties in soft tissue. In the visualisation of intraosseous soft tissue, such as the efferent lacrimal ducts, sample treatment by decalcification with ethylenediaminetetraacetic acid and subsequent CPD provides good results for micro-CT. Micro-CT can be used for a wide range of questions in 1. basic research, 2. application-related studies in ophthalmology (e.g. evaluation of the preclinical application of microstents for glaucoma treatment or analysis of the positioning of intraocular lenses) but also 3. as a supplement to ophthalmological histopathology.

[Chromatic Swept-Source Laser Scanning - Concept for a Cell-Resolving Confocal Laser Slit Lamp?] / Chromatic Swept-Source Laser Scanning ­ Konzept für eine zellauflösende konfokale Laserspaltlampe?

BACKGROUND: The in vivo characterisation of corneal epithelial tissue morphology is of considerable importance for diagnosis, disease prognosis, and the development of a treatment strategy for ocular surface diseases. In contrast to many alternative methods, in vivo corneal confocal microscopy (CCM) not only provides a macroscopic description of the corneal tissue but also allows its visualisation with cellular resolution. However, the translation of CCM from research to clinical practice is significantly limited by the complex and still largely manual operation of available CCM systems. In addition, for cross-sectional images, and analogously to conventional slit lamp microscopy, volume data must be acquired in time-consuming depth scans due to the frontal orientation of the image field in CCM, from which depth slices can subsequently be calculated. The pure acquisition time is already in the range of seconds, and additionally, motion artefacts have to be corrected in a sophisticated way. MATERIALS AND METHODS: This paper presents the concept and optics simulation of a new imaging technique based on a swept-source laser in combination with special chromatic optics. Here, the laser periodically changes its wavelength and is focused at different depths due to the wavelength-dependent aberration of the chromatic optics. RESULTS: The optics simulation results promise good optical resolution at a total imaging depth of 145 µm. CONCLUSION: The long-term goal is cell-resolving in vivo corneal confocal microscopy in real time with differently oriented sectioning directions.

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 drug-elutable 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.

The Antibiotic Kitasamycin-A Potential Agent for Specific Fibrosis Preventing Therapy after Fistulating Glaucoma Surgery?

One major complication after fistulating glaucoma surgeries are fibroblast-mediated scarring processes and their specific prevention is key in the development of novel pharmaceutical concepts. Within this study a possible antifibrotic potential of kitasamycin (KM) in a transforming growth factor (TGF)-ß1-mediated fibroblast model was evaluated in vitro. Primary ocular fibroblasts were isolated, cultivated and a dose-response test including determination of the half maximal effective concentration (EC50) for KM was conducted. Transformation of fibroblasts into myofibroblasts was induced by TGF-ß1and immunofluorescence (IF), and Western blot (WB) analyses were performed with fibroblasts and myofibroblasts. IF analyses were carried out using antibodies against α-smooth muscle actin (α-SMA) and fibronectin, and protein detection of intracellular and extracellular proteins was performed by WB. Using the dose-response test, the viability, cytotoxicity and EC50 of KM after 24 and 48 h were determined. Fibroblasts exposed to various KM concentrations showed no increase in α-SMA and extracellular matrix expression. In TGF-ß1-stimulated myofibroblasts, KM inhibited the expression of α-SMA and fibronectin in a concentration-dependent manner. These findings demonstrate that KM could impair the transformation of fibroblasts into myofibroblasts and the expression of proteins involved in fibrotic processes, representing a potential agent for specific fibrosis prevention in future therapeutic concepts.

Social, Educational and Medical Aspects after Cataract Surgery of Bilaterally Blind Children in Kinshasa-Perception of Parents and Children.

The study investigated the influence of bilateral cataract surgery on the social and educational development of previously bilaterally blind children in Sub-Saharan Africa (SSA), where the prevalence of blindness due to cataract is higher than in high-income countries. The views of both, parents and children, were evaluated with structured interviews based on a newly developed questionnaire related to surgery, follow-up, and family life after surgery. The mean age of the children at interview was 14.4 ± 8.1 years, with 27 females and 26 males. Satisfaction with the outcome of the surgery was reported by 91% of parents. Parents would recommend surgery, because of the children being happy and able to act more independently, with personal, educational and familial factors essentially contributing to the reported satisfaction. The results also showed that 85.0% of children did not wear eyeglasses. Reasons given were mainly cost-related, but also included limited communication between families and health institutions. Providing and maintaining a high-quality and accessible pediatric cataract surgery and healthcare service for follow-up is a major requisite to reduce childhood blindness in SSA. Our study proved the necessity and effectiveness of a community-based rehabilitation program that cares about each individual child, whatever his or her social background.

Assessment of dynamic corneal nerve changes using static landmarks by in vivo large-area confocal microscopy-a longitudinal proof-of-concept study.

Background: The purpose of the present proof-of-concept study was to use large-area in vivo confocal laser scanning microscopy (CLSM) mosaics to determine the migration rates of nerve branching points in the human corneal subbasal nerve plexus (SNP). Methods: Three healthy individuals were examined roughly weekly over a total period of six weeks by large-area in vivo confocal microscopy of the central cornea. An in-house developed prototype system for guided eye movement with an acquisition time of 40 s was used to image and generate large-area mosaics of the SNP. Kobayashi-structures and nerve entry points (EPs) were used as fixed structures to enable precise mosaic registration over time. The migration rate of 10 prominent nerve fiber branching points per participant was tracked and quantified over the longitudinal period. Results: Total investigation times of 10 minutes maximum per participant were used to generate mosaic images with an average size of 3.61 mm2 (range: 3.18-4.42 mm2). Overall mean branching point migration rates of (46.4±14.3), (48.8±15.5), and (50.9±13.9) µm/week were found for the three participants with no statistically significant difference. Longitudinal analyses of nerve branching point migration over time revealed significant time-dependent changes in migration rate only in participant 3 between the last two measurements [(63.7±12.3) and (43.0±12.5) µm/week, P<0.01]. Considering individual branching point dynamics, significant differences in nerve migration rate from the mean were only found in a few exceptions. Conclusions: The results of this proof-of-concept study have demonstrated the feasibility of using in vivo confocal microscopy to study the migration rates of corneal subbasal nerves within large areas of the central human cornea (>1 mm2). The ability to monitor dynamic changes in the SNP opens a window to future studies of corneal nerve health and regenerative capacity in a number of systemic and ocular diseases. Since corneal nerves are considered part of the peripheral nervous system, this technique could also offer an objective diagnostic tool and biomarker for disease- or treatment-induced neuropathic changes.

Micro-CT in ophthalmology: ex vivo preparation and contrasting methods for detailed 3D-visualization of eye anatomy with special emphasis on critical point drying.

Background: Micro-computed tomography (micro-CT) provides detailed 3-dimensional (3D) visualization of anatomical structures and encourages morphological reinvestigation of organs with delicate features. The low radiodensity of soft tissues necessitates preceding sample preparation to conduct X-ray imaging with decent contrast between different tissues. In this study, we demonstrate the preparation with three radiopaque agents in combination with elimination of liquids by critical point drying (CPD) introduced for ocular samples. Methods: Enucleated porcine eyes were prepared with ethanolic iodine (EI), aqueous iodine-potassium iodide, or ethanolic phosphotungstic acid (EPTA). Micro-CT scans of the samples were conducted in a moist environment with an isotropic resolution of 9.2-12.5 µm voxel size. Subsequently, samples were chemically dehydrated and critical point (CP) dried to conduct a second scan in a dry environment with a resolution up to 4.7-5.4 µm in voxel size. The visualization effects were qualitatively and semi-quantitatively evaluated with regard to the generated contrast between different ocular tissues. Results: All three contrast agents accumulated well in most of the investigated ocular tissues and lead to an increased X-ray attenuation which allowed for differentiated visualization of ocular structures. Problematic agent penetration into the lens was obvious for iodine-potassium iodide and EPTA. Artificial damages of the lens and thickness reduction for the cornea and sclera due to CPD were noticed. The effects of the different contrasting treatments are described and compared with regard to the effects of CPD. Exclusively CP dried samples that were not treated with contrast agents could also be visualized excellently with a good distinction of different ocular structures from each other. Conclusions: All ocular structures can be visualized by micro-CT. To contrast moist samples, the best results were achieved with iodine potassium iodide (IPI). CPD improved the scan quality in all cases. Even without pretreatment with contrasting agents, the CP dried samples showed a contrast similar to the IPI treated samples.

In Vivo Monitoring of Corneal Dendritic Cells in the Subbasal Nerve Plexus during Trastuzumab and Paclitaxel Breast Cancer Therapy-A One-Year Follow-Up.

Paclitaxel and trastuzumab have been associated with adverse effects including chemotherapy-induced peripheral neuropathy (CIPN) or ocular complications. In vivo confocal laser scanning microscopy (CLSM) of the cornea could be suitable for assessing side effects since the cornea is susceptible to, i.e., neurotoxic stimuli. The study represents a one-year follow-up of a breast cancer patient including large-area in vivo CLSM of the subbasal nerve plexus (SNP), nerve function testing, and questionnaires during paclitaxel and trastuzumab therapy. Six monitoring sessions (one baseline, four during, and one after therapy) over 58 weeks were carried out. Large-area mosaics of the SNP were generated, and identical regions within all sessions were assigned. While corneal nerve morphology did not cause alterations, the number of dendritic cells (DCs) showed dynamic changes with a local burst at 11 weeks after baseline. Simultaneously, paclitaxel treatment was terminated due to side effects, which, together with DCs, returned to normal levels as the therapy progressed. Longitudinal in vivo CLSM of the SNP could complement routine examinations and be helpful to generate a comprehensive clinical picture. The applied techniques, with corneal structures acting as biomarkers could represent a diagnostic tool for the objective assessment of the severity of adverse events and the outcome.

Method for the generation and visualization of cross-sectional images of three-dimensional point spread functions for rotationally symmetric intraocular lenses.

Cross-sectional images of three-dimensional point spread functions of intraocular lenses are used to study their image formation. To obtain those, light sheet-based methods are established. Due to the non-negligible thicknesses of the light sheets, the image quality of the cross-sectional images is constrained. To overcome this hurdle, we present a dedicated evaluation algorithm to increase image quality in the post-processing step. Additionally, we compare the developed- with the light sheet method based on our own investigations of a multifocal diffractive intraocular lens conducted in an in-house designed optical bench. The comparative study showed the clear superiority of the newly developed method in terms of image quality, fine structure visibility, and signal-to-noise ratio compared to the light sheet based method. However, since the algorithm assumes a rotationally symmetrical point spread function, it is only suitable for all rotationally symmetrical lenses.

Progression to severe visual impairment and blindness in POAG patients: pace and risk factors-a cohort study using German health claims data.

OBJECTIVE: Glaucoma is a leading cause of severe visual impairment and blindness (SVI/B) worldwide. Hence, it is of utmost importance to explore relevant risk factors and study the pace of progression to SVI/B. METHODS AND ANALYSIS: We used a random sample of 250 000 persons from administrative individual-level health records of the Allgemeine Ortskrankenkassen between 2004 and 2015. We identified 3535 primary open-angle glaucoma (POAG) patients aged 55 and older and followed them for up to 10 years. Monocular and binocular SVI/B were defined by the ICD-10 classifications H54.0 and H54.4. Ophthalmological and chronic disease risk factors were analysed by applying a multivariable Cox proportional hazard model. RESULTS: The risk of SVI/B in POAG patients was significantly increased by the presence of specific additional eye diseases such as secondary glaucoma (HR: 3.08, p<0.001), retinal vascular occlusion (HR: 3.00, p<0.001) or age-related macular degeneration (AMD) (HR: 2.26, p<0.001). The risk was highest in the first 2 years after the POAG diagnosis and significantly decreased after the fifth year (HR: 0.36, p=0.002). Ocular injuries, other ocular diseases, non-ophthalmological comorbidities, and age and sex had no significant influence (p>0.05). CONCLUSION: Although progression to SVI/B is relatively rare in POAG patients in Germany, one must be aware of additional risk factors, such as secondary glaucoma, retinal vascular occlusion and AMD. Regular ophthalmological examinations help prevent the progression of SVI/B, especially in the first years after the POAG diagnosis. Specific, targeted, and timely treatments for the other eye diseases could help prevent or delay SVI/B.

Therapeutic Strategies in 103 Children with Congenital Microphthalmos. / Therapiestrategien bei 103 Kindern mit kongenitalem Mikrophthalmus.

INTRODUCTION: Congenital microphthalmos can either occur alone (simple microphthalmos) or be associated with other ocular malformations, such as sclerocornea or cataract (complex microphthalmos). As this is a rare condition, there are no uniform recommendations for treatment. MATERIAL AND METHODS: Retrospective case series of 103 patients or a total of 114 eyes with congenital microphthalmos, with reporting of age, sex, visual acuity, pupil reaction, axial length, horizontal width of the palpebral fissure, type of therapy performed and complications. RESULTS: All patients would have been able to be fitted with a prosthesis primarily. The size of the palpebral fissure depended on the underlying findings: "bilateral microphthalmos" < "microphthalmos and healthy fellow eye" < "microphthalmos and fellow anophthalmos". In order to assess visual (residual) function in an infant in the first weeks or months of life, the pupillary response is of the upmost importance in deciding on therapy, especially in unilateral disease, and as assessed with the indirect light response of the healthy eye. In about half of the cases, conservative prosthetic treatment was sufficient. After the successful initial fitting of a prosthesis, the prosthesis was enlarged according to the ocularist's instructions. If the eye length difference was so large that symmetry could not be achieved even with a double-walled prosthesis, volume filling with retrobulbar implanted self-swelling pellet expanders (osmed GmbH, Ilmenau) was offered. In almost one third of the patients, no surgical therapy or prosthetic treatment was performed. The reason for this was usually the presence of minimal visual function of the microphthalmos - ranging from light perception to hand movements. CONCLUSIONS: In the case of visual function of the microphthalmos, surgical measures should not be indicated or only with extreme caution, since the preservation of the existing visual acuity must be regarded as having priority over the cosmetic findings. In cases of asymmetry or underdeveloped palpebral fissure, therapy can be started early in the first year of life without fear of resulting complications.

Real-time large-area imaging of the corneal subbasal nerve plexus.

The morphometric assessment of the corneal subbasal nerve plexus (SNP) by confocal microscopy holds great potential as a sensitive biomarker for various ocular and systemic conditions and diseases. Automated wide-field montages (or large-area mosaic images) of the SNP provide an opportunity to overcome the limited field of view of the available imaging systems without the need for manual, subjective image selection for morphometric characterization. However, current wide-field montaging solutions usually calculate the mosaic image after the examination session, without a reliable means for the clinician to predict or estimate the resulting mosaic image quality during the examination. This contribution describes a novel approach for a real-time creation and visualization of a mosaic image of the SNP that facilitates an informed evaluation of the quality of the acquired image data immediately at the time of recording. In cases of insufficient data quality, the examination can be aborted and repeated immediately, while the patient is still at the microscope. Online mosaicking also offers the chance to identify an overlap of the imaged tissue region with previous SNP mosaic images, which can be particularly advantageous for follow-up examinations.

[Illustration Techniques in Ophthalmic Textbooks 200 Years Ago - a Platform for the Rostock Glass Eye Collection of Anterior Segment Pathologies from 1860]. / Ophthalmologische Abbildungstechnik vor 200 Jahren ­ der Atlas von Antoine Pierre Demours als Grundlage der Rostocker Kunstaugensammlung.

Very recent research results have demonstrated that the "Rostock Artificial Eye Collection" - assembled 150 years ago with 132 glass modelled exhibits of anterior segment pathologies - is mainly based on the figures of the Atlas of Ophthalmology published by Antoine Pierre Demours in 1818. This article focusses on the analyses of the imaging techniques of this atlas. Present knowledge implies that the author used different colour etching concepts which were partially re-coloured individually. In the opinion of contemporaries, the figures of Demours' atlas represent the climax of scientific imaging techniques. In the academic literature, it is still described as a "recent remarkable masterpiece", even 100 years later.

Clinical Congenital Anophthalmos and Microphthalmos-Experiences of Patients and Their Parents after More than 10 Years of Treatment.

Congenital clinical anophthalmos and blind microphthalmos describe the absence of an eye or the presence of a small eye in the orbit. Between 1999 and 2013, 97 children with anophthalmos or microphthalmos were treated with self-inflating, hydrophilic gel expanders at the Rostock Eye Clinic. More than a decade later, this study investigated the perspective of patients and parents regarding the treatment, the surgical outcome, and the emotional and social well-being of the patients. A total of 22 families with 16 patients sighted in the other eye and six patients blind in both eyes participated. Questionnaires were developed, including items on physical, emotional, social, and medical aspects. The patients felt emotionally stable and integrated into their social environment, with no major limitations reported by the majority. These statements were confirmed by most of the parents. Parents (67%) indicated that the success of the operation was already apparent after the first intervention and that the current situation did not play a role in the patients' social environment. The study provided new insights into the therapy results, the postoperative care, and the social and emotional stability of the prosthesis-wearing patients, indicating the chosen expander methods as promising in terms of positive postoperative care.

Optical Technologies, Digitally Assisted: Surgical Microscope - quo vadis? / Optische Technologien, digital unterstützt: Operationsmikroskop ­ quo vadis?

Adequate magnification and proper illumination are crucial for success in microsurgical interventions. Thus, surgical microscopes have long been an integral part of modern eye surgery and are at the heart of modern operating theatres. This paper first briefly reviews the history microscopes in ophthalmic surgery - from the initial developments in the mid 19th century to the current state of the art systems with powerful coaxial illumination and fibre-guided xenon or LED light sources. The discussion then turns to current developments, particularly in the area of workflow support and integration of complementary technologies such as intraoperative OCT, "augmented reality", and visual data feeds useful to the surgeon. The last part presents an outlook on future developments, with a particular focus on the digital image chain and intelligent automated assistance.

Ocular Morbidity-A Critical Analysis to Improve Outpatient Services in an Eye Department in a Sub-Saharan Megacity.

The aim of this study was to analyse outpatient services in an ophthalmic clinic of a church-run hospital providing secondary level care in an African megacity, paying special attention to the poorest users of the services. The range of examination was reviewed from 500 patient records of all ages consecutively chosen on random days attending the outpatient department for the first time in order to optimize workflow and to analyse the offered treatment modalities. Mean age was 41.9 ± 21.9 years, and 53.6% of the patients were female. Of the patients, 74.8% presented with visual impairment. The most frequent findings were refractive errors (35.8%), presbyopia (21.2%), allergic conjunctivitis (14.0%), cataract (13.2%) and glaucoma (6.4%). Patient management consisted of optical treatment (49.6%), surgery (11.4%) and medical treatment (39.0%). These results show the importance of the demand in refractive services and the need to train specific service providers. Knowing the frequencies of common conditions enables more appropriate diagnostic and treatment strategies, e.g., the importance of refractive errors, and should lead to improvements in training, staffing, therapeutics and patient outcomes. This approach can be applied to many other outpatient services and should be evaluated in light of the city's impoverished health outreach and educational situation.