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Abstract Background About 90% of blind children come from low- and middle-income countries. The main cause of childhood blindness is cataract. Cataract surgery can improve vision, but regular follow-up is necessary. Low attendance at follow-up is a medical and statistical challenge, as missing information can lead to biased results. Two research questions arise: what social factors influence attendance at first follow-up? What social factors influence a poor outcome of visual acuity at first follow-up? Methods An observational cohort study was conducted, and the total base population was analysed. The study includes children who received cataract surgery at Saint Joseph Hospital (Kinshasa, Democratic Republic of the Congo) from 2001 to 2021. Cox regression was used to examine attendance at the first follow-up (n = 1100 operated eyes), ordinal logistic regression to analyse visual acuity at the first follow-up (n = 699 operated eyes), both clustered by patient identification number. Due to the high number of missing values, multiple imputation was performed as a sensitivity analysis. Results Female sex, young age, very good visual acuity after surgery, and disease in both eyes led to lower attendance at follow-up. Poor visual acuity outcome at follow-up was associated with female sex, young age, poor financial situation, blindness after surgery and nystagmus. Conclusions As regular follow-up is crucial for an improved visual acuity outcome, it is recommended that special attention needs to be paid to the groups identified in our analysis to better integrate them into follow-up. In particular, the higher risk of poor outcome in younger children is surprising and requires further analysis.

Elevated intraocular pressure is the main risk factor for glaucoma and its adjustment to physiological levels can prevent progression of the disease. If conventional drop-based glaucoma therapy fails, surgical interventions such as trabeculectomy or the application of implants, which drain aqueous humour from the eye and thus reduce intraocular pressure, are used as final therapeutic procedures. These interventions are becoming increasingly minimally invasive and the drainage implants are getting steadily smaller, which is why these interventions are now called microinvasive glaucoma surgery (MIGS). Both, surgery and drainage implant-based glaucoma therapy are limited by wound healing processes and fibrosis that occlude the newly created drainage pathways for the aqueous humour. To suppress unwanted postoperative fibrosis coupled with an increased extracellular matrix production, cytostatics like mitomycin c or 5- fluorouracil are currently used, which are associated with side effects. Therefore, more specific antifibrotic agents are key for a durable functionality of the interventions in glaucoma therapy. In this study a specific active substance (pirfenidone, PFD) was added in a polymer matrix for controlled release. Previous studies have shown that the release of pirfenidone from a thermoplastic silicone polycarbonate elastomer, which could be used as a material for a glaucoma drainage implant, has been relatively fast. To decelerate the release the influence of the alternate polymers Poly-L-Lactide (PLLA) and Poly-D,LLactide (PDLLA) as alternative drug carriers was investigated. Furthermore, a reduction of the pirfenidone content was used to delay the release.

Since the start of the COVID-19 pandemic in 2020, wastewater surveillance programs were established, or upscaled, in many countries around the world and have proven to be a cost-effective way of monitoring infectious disease pathogens. Many of these programs use RT-qPCR, and quantify the viral concentrations in samples based on standard curves, by including preparations of a reference material with known nucleic acid or virus concentrations in the RT-qPCR analyses. In high-throughput monitoring programs it is possible to combine data from multiple previous runs, circumventing the need for duplication and resulting in decreased costs and prolonged periods during which the reference material is obtained from the same batch. However, over time, systematic shifts in standard curves are likely to occur. This would affect the reliability and usefulness of wastewater surveillance as a whole. We aim to find an optimal combination of standard curve data to compensate for run-to-run measurement variance while ensuring enough flexibility to capture systematic longitudinal shifts. Based on more than 4000 observations obtained with the CDC N1 and N2 assays, taken as a part of the National Sewage Surveillance program at the Dutch National Institute for Public Health and the Environment, we show that seasonal and long-term shifts in RT-qPCR efficiency and sensitivity occur. We find that in our setting, using five days of standard-curve data to quantify, results in the least error prone curve or best approximation. This results in differences up to 100% in quantified viral loads when averaged out over a nationwide program of >300 treatment plants. Results show that combining standard curves from a limited set of runs can be a valid approach to quantification without obscuring the trends in the viral load of interest.

Abstract 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.

The development of strategies for fibrosis prevention is a perpetual cutting the edge challenge, especially in ophthalmologic fistulating surgery. Stenosis of liquid draining implants but also fibrotic activation of implant-associated tissues are major clinical examples for fibrosis induced implant failure. Implant coating or incorporation of antifibrotic agents offer a promising approach to minimise failure rates. Nintendanib is a drug that has been successfully used for the treatment of ideopathic pulmonary fibrosis since 2015. In this study, we evaluated the suitability of Nintedanib for ophthalmic therapeutic treatment. Therefore, the antifibrotic potential of the active substance was tested with a fibrotic cell culture model on primary fibroblasts of the Tenon (hTF) in vitro. The concentration of 10μM Nintedanib demonstrated a marginal effect on cell viability but coincidently diminished cell proliferation remarkably. Both, immunocytochemical and Western blot analyses revealed a significant inhibitory effect of Nintedanib on the TGF-β1 induced expression of the extracellular matrix (ECM) components fibronectin and collagen. Moreover it supressed the expression and formation of stress fibres of the fibrotic marker protein alpha smooth muscle actin (α-SMA).

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, p0.05).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.

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)-β1-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-β1and 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.

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.

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.

ObjectiveThis study aims to estimate the incidence of severe binocular vision impairment and blindness (SVI/B) and to identify eye diseases and regional risk factors of persons with SVI/B at ages 50 years and older.MethodsWe designed an observational cohort study based on longitudinal, multifactorial, and administrative information of a random sample of 250,000 persons at ages 50+. All individuals were included in the process-produced health claims register of the Allgemeine Ortskrankenkasse in 2004, and were followed until 2015. We analyzed ten selected eye diseases and regional characteristics as risk factors for SVI/B using Cox models, adjusting for demographic characteristics and multi-morbidity.ResultsThe age-standardized incidence was 79 new diagnoses of SVI/B per 100,000 person-years (95%-CI: 76-82); 77 for males (72-82) and 81 for females (77-85). By adjusting for multiple factors, the model revealed and confirmed that individuals who were very old (Hazard ratio90+: 6.67; 3.59-12.71), male (1.18; 1.01-1.38), had multi-morbidities (three+ diseases: 3.36; 2.51-4.49), or had diabetes (1.26; 1.07-1.49) had an increased risk of SVI/B. Compared to persons without the particular eye disease (all pConclusionThe study revealed and confirmed some profound risk factors of SVI/B at both the individual and the macro level. The sizes of the effects of the characteristics of the living context were smaller than those of the individual characteristics, especially for some severe eye diseases. While urbanity and access to health services had no effect, regional economic wealth was a risk factor for SVI/B. Future health care measures and advice by physicians should take these dimensions of inequalities in SVI/B into account.

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.

This paper analyzes the relationship between culture and financial development in Europe, with culture defined as informal constraints on human interactions. We assert that various national characteristics such as people’s trust and trustworthiness, and the level of control they feel they have over their lives can modify transaction costs, which in turn leads to different levels of financial development. Furthermore, we consider communism as an exogenous shock to the cultural values existent in Central and Eastern Europe. This exogenous component of culture is negatively related to present financial development, even after controlling for other historical variables such as religion and formal institutions at the beginning of the 20th century. Via 2SLS regression analysis, we show that communism has shaped cultural values, which in turn affect financial development.

Abstract The purposes of this study were (1) to characterize embryonic eye development during incubation in ovo and (2) to analyze the putative influence of repetitive ultrahigh-field MRI (UHF-MRI) measurements on this development. A population of 38 fertilized chicken eggs was divided into two sub-groups: two eggs (Group A) were examined repeatedly during the developmental period from embryonic day 1 (E1) to embryonic day 20 (E20) to evaluate the influence of daily MRI scanning. A second larger group of 36 eggs was examined pairwise on one day only, from E3 to E20, and the embryos were sacrificed immediately after MR imaging (Group B). Fast T2-weighted MR sequences provided biometric data on the eye with an in-plane resolution of 74 μm. The data show rapid growth of the eye with a steep increase in intraocular dimensions in all axis directions and in eyeball volume during initial development up to E10, followed by a phase of reduced growth rate in later developmental stages. Comparison of the two groups revealed no differences in ocular development.

During breast cancer therapy, paclitaxel and trastuzumab are both associated with adverse effects such as chemotherapy-induced peripheral neuropathy and other systemic side effects including ocular complications. Corneal nerves are considered part of the peripheral nervous system and can be imaged non-invasively by confocal laser scanning microscopy (CLSM) on the cellular level. Thus, in vivo CLSM imaging of structures of the corneal subbasal nerve plexus (SNP) such as sensory nerves or dendritic cells (DCs) can be a powerful tool for the assessment of corneal complications during cancer treatment. During the present study, the SNP of a breast cancer patient was analyzed over time by using large-scale in vivo CLSM in the course of paclitaxel and trastuzumab therapy. The same corneal regions could be re-identified over time. While the subbasal nerve morphology did not alter significantly, a change in dendritic cell density and an additional local burst within the first 11 weeks of therapy was detected, indicating treatment-mediated corneal inflammatory processes. Ocular structures such as nerves and dendritic cells could represent useful biomarkers for the assessment of ocular adverse effects during cancer therapy and their management, leading to a better visual prognosis.

Background and Objectives: Thus far, tumor control for choroidal melanoma after teletherapeutic radiation is clinically difficult. In contrast to brachytherapy, the tumor height does not necessarily have to shrink as a result of teletherapy. Therefore, the objective of this study was to evaluate tumor vascularization determined by color Doppler flow imaging (CDFI) as a possible approach for monitoring the therapy response after teletherapy of choroidal melanoma. Materials and Methods: A single-center retrospective pilot study of 24 patients was conducted, all of whom had been diagnosed with choroidal neoplasm, treated and followed up. Besides tumor vascularization, the following parameters were collected: age, gender, tumor entity, location, radiation dose, knowledge of relapse, tumor height, radiation-related complications, occurrence of metastases, visual acuity in logMAR. Results: The level of choroidal melanoma vascularization markedly decreased in all included subjects after treatment with the CyberKnife® technology. Initially, the level of vascularization was 2.1 (SD: 0.76 for n = 10); post-therapeutically, it averaged 0.14 (SD: 0.4). Regarding the tumor apex, CDFI sonography also demonstrated a significant tumor regression (mean value pre-therapeutically: 8.35 mm—SD: 3.92 for n = 10; mean value post-therapeutically: 4.86 mm—SD: 3.21). The level of choroidal melanoma vascularization declined in the patient collective treated with ruthenium-106 brachytherapy. The pre-therapeutic level of vascularization of 2 (SD: 0 for n = 2) decreased significantly to a level of 0 (mean: 0—SD: 0). The tumor height determined by CDFI did not allow any valid statement regarding local tumor control. In contrast to these findings, the patient population of the control group without any radiation therapy did not show any alterations in vascularization. Conclusions: Our data suggest that the determination of the tumor vascularization level using CDFI might be a useful and supplementary course parameter in the follow-up care of choroidal melanoma to monitor the success of treatment. This especially applies to robot-assisted radiotherapy using CyberKnife®. Further studies are necessary to validate the first results of this assessment.