Structural and Functional Insights into Human Re-initiation Complexes.

After having translated short upstream open reading frames, ribosomes can re-initiate translation on the same mRNA. This process, referred to as re-initiation, controls the translation of a large fraction of mammalian cellular mRNAs, many of which are important in cancer. Key ribosomal binding proteins involved in re-initiation are the eukaryotic translation initiation factor 2D (eIF2D) or the homologous complex of MCT-1/DENR. We determined the structures of these factors bound to the human 40S ribosomal subunit in complex with initiator tRNA positioned on an mRNA start codon in the P-site using a combination of cryoelectron microscopy and X-ray crystallography. The structures, supported by biochemical experiments, reveal how eIF2D emulates the function of several canonical translation initiation factors by using three independent, flexibly connected RNA binding domains to simultaneously monitor codon-anticodon interactions in the ribosomal P-site and position the initiator tRNA.

Increasing hospitalisation of patients with herpes zoster ophthalmicus-an interdisciplinary retrospective analysis.

BACKGROUND: The occurrence of herpes zoster is rising globally. Future trends will be influenced by changes in population demographics and the growing number of patients at risk. Overall this poses a challenge for healthcare systems. METHODS: In our interdisciplinary, single-centre retrospective analysis, we aimed to assess the burden of the disease within the Department of Dermatology and the Eye Centre from the Medical Centre, University of Freiburg from 2009-2022. We obtained data from 3034 cases coded using the ICD-10 B02.x. Patients were characterised by sex, age, year of treatment, and type of treatment (inpatient vs. outpatient). RESULTS: Overall we observed a 200% increase in the number of herpes zoster patients over the 13-year period. Upon closer analysis, this was mainly due to a rise in inpatient treatment for herpes zoster ophthalmicus. CONCLUSIONS: If the incidence of herpes zoster ophthalmicus continues to increase at the current rate the number of hospitalisations of zoster ophthalmicus would double by 2040, assuming guideline-appropriate treatment. Overall, the results show a growing need for inpatient ophthalmological care.

XEN®-45 implantation for refractory uveitic glaucoma.

PURPOSE: To evaluate the efficacy of XEN®-45 gel stent ab interno implantation for medically uncontrolled uveitic glaucoma. METHODS: Retrospective analysis of 25 eyes receiving XEN® gel stent for medically uncontrolled uveitic glaucoma from February 2019 to February 2023 with recording of intraocular pressure (IOP) values, ocular hypotensive medication, requirement for revision or secondary surgery and complications. Prerequisites for XEN® implantation were a clear cornea, an open iridocorneal angle and an unscarred, mobile conjunctiva at the implantation site. Minimum follow-up required for inclusion was 3 months. The primary outcome measure was IOP compared to baseline. Complete and qualified success were defined as final IOP of ≤ 18 mmHg without or with topical antiglaucomatous treatment, respectively. Failure was defined as IOP > 18 mmHg on two consecutive visits, IOP reduction < 20%, persisting complications from hypotony and open conjunctival bleb revision. Further glaucoma surgical intervention was defined as complete failure. RESULTS: Mean preoperative IOP was 35.3 ± 10.9 mmHg on 2.9 ± 0.9 topical antiglaucomatous agents. 19 of 25 patients (76%) received additional oral acetazolamide. 19 eyes were pseudophakic, 5 eyes phakic and 1 aphakic. Early postoperatively, mean IOP reduced to 7.7 ± 3.0 mmHg (75.8% reduction). At final follow-up (mean 17.7 months) mean IOP was 12.0 ± 3.8 mmHg (62.5% reduction) on 0.2 ± 0.6 medications. Six eyes (24%) required bleb revision at mean 28 weeks and therefore were categorized as failure. One eye failed despite bleb revision and restart of topical ocular hypotensive medication. Three other eyes (12%) had IOP spikes with uveitis flare-ups. Transient hypotony complications occurred in 32%. At final follow-up, 18 eyes (72%) achieved complete success and one eye (4%) qualified success. CONCLUSION: The XEN® gel stent effectively reduced IOP in uncontrolled uveitic glaucoma, with 72% complete success. Bleb revision was required in 24%. IOP spikes occurred in 12% despite functioning blebs. Further follow-up is needed to determine long-term outcomes.

Changing indications for keratoplasty: monocentric analysis of the past two decades.

PURPOSE: Over the past two decades, lamellar keratoplasty procedures, such as Descemet's Stripping Automated Endothelial Keratoplasty (DSAEK) and Descemet's Membrane Endothelial Keratoplasty (DMEK) as well as Deep Anterior Lamellar Keratoplasty (DALK), have become an integral part of clinical practice. With advances in contact lens fitting for keratoconus management and the implementation of UVA-Riboflavin Crosslinking (CXL), the landscape of keratoplasty indications is undergoing changes. Procedures and indications in a single tertiary care center over the past two decades are reviewed in this retrospective analysis. METHODS: Retrospective analysis utilized anonymized electronic data from the LIONS cornea bank Baden-Württemberg, Eye Center Freiburg, spanning from beginning of 2004 to end of 2023. The primary focus was on surgical procedures and indications for keratoplasty. RESULTS: The study encompassed a comprehensive analysis of 7130 corneal transplants. Penetrating keratoplasty (PK) exhibited a significant decline from 95% (n = 206, 2004) to 11% (n = 46, 2023), while DMEK increased from 48% (n = 157, 2012) to 82% (n = 347, 2023). Fuchs endothelial dystrophy (FED) emerged as the dominant indication, witnessing a significant increase from 24% (2004, n = 39) to 72% (2023, n = 288). Conversely, keratoconus (KC) showed a reciprocal change from 25% (2004, n = 40) to 4% (2023, n = 17). PK demonstrated a noteworthy indication shift in descending order from Bullous Keratopathy (BK), FED, and KC in 2004 to KC, graft failure, corneal scars, and ulcers in 2023. Repeat keratoplasty following DMEK remained rare, but a discernible upward trend was observed for PK. CONCLUSION: This retrospective analysis highlights significant changes in both keratoplasty indications and techniques over the past two decades. DMEK has emerged as a successful intervention for treating endothelial diseases, while PK retains its qualitative indispensability for a wide range of indications. Modern corneal banks are urged to maintain a robust supply of grafts for all surgical techniques in anticipation of potential increased demand in the future, particularly for repeat keratoplasties. KEY MESSAGES: What is known • Over the past two decades, lamellar keratoplasty procedures such as DSAEK and DMEK have increasingly replaced penetrating keratoplasty (PK) in clinical practice due to their improved outcomes and reduced complications for certain indications. New Findings • Our study reveals a significant shift in keratoplasty indications, with Fuchs endothelial dystrophy (FED) emerging as the predominant indication, increasing from 24% in 2004 to 72% in 2023, while keratoconus (KC) declined from 25 to 4% during the same period. • Penetrating keratoplasty (PK) has shown a marked decline in use, dropping from 95% of keratoplasties in 2004 to 11% in 2023, whereas DMEK has grown to represent 82% of procedures in 2023. • Despite the rise of DMEK, PK remains vital for a broad spectrum of indications, highlighting the necessity for corneal banks to maintain a versatile supply of grafts to meet diverse clinical needs, particularly in cases of repeat keratoplasties.

Analysis of association of bandage contact lens with serious vision-threatening diseases and their management.

BACKGROUND: Bandage contact lenses are important aids for aftercare following ocular surgery and for a wide variety of ocular surface conditions. However, bandage contact lenses also bear the risk of fostering microbial infections of the cornea. We herein report the safety profile of bandage contact lenses from a comprehensive review of medical records in a tertiary care eye hospital in Germany. METHODS: We identified 638 consecutive patients who had been prescribed at least one bandage lens during the past 10 years. For these, we performed a computerized search for the following adverse events: (1) endophthalmitis, (2) emergency keratoplasty and (3) vision loss of at least 2 lines according to the Early Treatment Diabetic Retinopathy Study (ETDRS). We manually assessed the relatedness of each event to the bandage lens. Events later than 100 days following the bandage lens prescription were not considered to be related to bandage contact lenses. RESULTS: We observed 267 adverse events, with 120 occurring within 100 days after bandage lens prescription. This left a total of 18 endophthalmitis events, 21 penetrating keratoplasties and 81 eyes with vision loss of at least 2 ETDRS lines (for individual review of relatedness). Only two episodes of endophthalmitis could be linked to bandage lens wear. All other adverse events were due to causative conditions that had already been present prior to bandage contact lens insertion. CONCLUSIONS: Severe adverse events after bandage contact lens wear are not uncommon because lenses are used in patients suffering from preexisting ocular conditions. However, severe adverse events were almost never caused by the bandage contact lenses directly in our hands. We therefore conclude that bandage contact lenses are safe given proper ophthalmological supervision.

Quality Control in the Corneal Bank with Artificial Intelligence: Comparison of a New Deep Learning-based Approach with Conventional Endothelial Cell Counting by the "Rhine-Tec Endothelial Analysis System". / Qualitätskontrolle in der Hornhautbank mit künstlicher Intelligenz: Vergleich eines neuen Deep-Learning-basierten Ansatzes mit der konventionellen Endothelzelldichtenbestimmung durch das "Rhine-Tec Endothelial Analysis System".

Endothelial cell density (ECD) is a crucial parameter for the release of corneal grafts for transplantation. The Lions Eye Bank of Baden-Württemberg uses the "Rhine-Tec Endothelial Analysis System" for ECD quantification, which is based on a fixed counting frame method considering only a small sample of 15 to 40 endothelial cells. The measurement result therefore depends on the frame placement and manual correction of the cells counted within the frame. To increase the sample size and create higher objectivity, we developed a new method based on "deep learning" that automatically detects all visible endothelial cells in the image. This study aims to compare this new method with the conventional Rhine-Tec system. 9375 archived phase-contrast microscopic images of consecutive grafts from the Lions Eye Bank were evaluated with the deep learning method and compared with the corresponding archived analyses of the Rhine-Tec system. Means, Bland-Altman and correlation analyses were compared. Comparable results were obtained for both methods. The mean difference between the Rhine-Tec system and the deep learning method was only - 23 cells/mm2 (95% confidence interval - 29 to - 17). There was a statistically significant positive correlation between the two methods, with a correlation coefficient of 0.748. What was striking in the Bland-Altman analysis were clustered deviations in the cell density range between 2000 and 2500 cells/mm2 - with higher values in the Rhine-Tec system. The comparable results for cell density measurement values underline the validity of the deep learning-based method. The deviations around the formal threshold for graft release of 2000 cells/mm2 are most likely explained by the higher objectivity of the deep learning method and the fact that measurement frames and manual corrections were specifically selected to reach the formal threshold of 2000 cells/mm2 when the full area endothelial quality was good. This full area assessment of the graft endothelium cannot currently be replaced by deep learning methods and remains the most important basis for graft release for keratoplasty.

3D Mapping of the DMEK Detachment Area from OCT Scans of the Anterior Segment of the Eye - Clinical Applications. / 3D-Kartierung der DMEK-Abhebungsfläche aus OCT-Scans des vorderen Augensegmentes mit klinischen Anwendungen.

Graft detachment is the most common complication after Descemet membrane endothelial keratoplasty (DMEK). To assess the amount of graft detachment, precision is limited when using slit-lamp biomicroscopy. Detachment of DMEK grafts can be assessed automatically on anterior segment optical coherence tomography (AS OCT) images and allows visualization of the area and volume of detachment using 3D maps. This article provides an overview of its applications such as accurately assessing the course of natural graft attachment, identification of potential risk factors for detachment and evaluation of the long-term effect of graft detachment. The 3D map of DMEK detachment may support researchers and clinicians in precise quantification of the area and volume of graft detachment even in large data sets, and the intuitive, fast and reliable evaluation.

Eye Injury Incidence in Germany from 2008 to 2022: An Analysis of Hospital Quality Reports. / Die Häufigkeit von Augenverletzungen in Deutschland von 2008 bis 2022: eine Analyse der Qualitätsberichte der Krankenhäuser.

BACKGROUND: Eye injuries range from minor to severe and may lead to permanent visual impairment. There is still little in the way of epidemiological data on eye injuries in Germany. AIM: The aim of this study was to obtain an objective record of minor and severe eye injuries in Germany by evaluating hospital quality reports. We also investigated the relevance of injuries from fireworks in relation to the total number of eye injuries and the general population. METHODS: This retrospective routine data study entailed analysing hospital quality reports from 2008 to 2022 in XML format. The R programming language was used for data processing and statistical analysis. The number of ICD-coded eye injuries was exported and analysed together with location data. We also included data from a prospective survey study on fireworks-related eye injuries from 2016 to 2023. RESULTS: Eyeball and/or orbital contusions are the most common eye injuries treated in Germany at up to 2,500 cases per year. The most severe injuries comprise traumatic globe rupture with loss of intraocular tissue at up to 990 cases per year. Numbers of eye injuries of any type have been declining since 2020. As a percentage of population, Mecklenburg-Western Pomerania treats the most eye injuries at up to 0.017%; in absolute numbers, North Rhine-Westphalia leads the country at up to 1,600 injuries. Private firework displays are probably responsible for 1.4% of annual globe ruptures and 8.3% of eyeball contusions. CONCLUSION: Our analysis of hospital quality reports has provided the first comprehensive epidemiological record on eye injuries in Germany. Firework-related injuries account for a relevant proportion of total injuries. These results could serve as a basis for preventive measures and health policy decisions.

Addressing bias in manual segmentation of spheroid sprouting assays with U-Net.

Purpose: Angiogenesis research faces the issue of false-positive findings due to the manual analysis pipelines involved in many assays. For example, the spheroid sprouting assay, one of the most prominent in vitro angiogenesis models, is commonly based on manual segmentation of sprouts. In this study, we propose a method for mitigating subconscious or fraudulent bias caused by manual segmentation. This approach involves training a U-Net model on manual segmentations and using the readout of this U-Net model instead of the potentially biased original segmentations. Our hypothesis is that U-Net will mitigate any bias in the manual segmentations because this will impose only random noise during model training. We assessed this idea using a simulation study. Methods: The training data comprised 1531 phase contrast images and manual segmentations from various spheroid sprouting assays. We randomly divided the images 1:1 into two groups: a fictitious intervention group and a control group. Bias was simulated exclusively in the intervention group. We simulated two adversarial scenarios: 1) removal of a single randomly selected sprout and 2) systematic shortening of all sprouts. For both scenarios, we compared the original segmentation, adversarial segmentation, and respective U-Net readouts. In the second step, we assessed the sensitivity of this approach to detect a true positive effect. We sampled multiple treatment and control groups with decreasing treatment effects based on unbiased ground truth segmentation. Results: This approach was able to mitigate bias in both adversarial scenarios. However, in both scenarios, U-Net detected the real treatment effects based on a comparison to the ground truth. Conclusions: This method may prove useful for verifying positive findings in angiogenesis experiments with a manual analysis pipeline when full investigator masking has been neglected or is not feasible.

Developing and validating a questionnaire to assess the symptoms of blepharitis accompanied by dry eye disease.

PURPOSE: To propose additional items for established dry eye disease (DED) instruments that cover blepharitis-specific signs and symptoms and to determine the association between the clinical findings and subjective complaints. METHODS: Thirty-one patients with blepharitis and DED were prospectively included in the pretest period for selecting suitable questions. In the main phase of the study, the selected questions were then tested on 68 patients with blepharitis and DED and 20 controls without blepharitis or DED. Pearson's coefficient of correlation was calculated between the blepharitis-specific questions, tear break-up time (TBUT), the Schirmer test score, and the ocular surface disease index (OSDI) score; and the similarity between the blepharitis-specific questions, OSDI questions, and objective parameters for DED was assessed via hierarchical clustering. Furthermore, the discriminatory power of the blepharitis-specific questions was investigated with the receiver operating characteristic (ROC) curve. RESULTS: The additional question about heavy eyelids revealed a significant correlation with the OSDI score (r = 0.45, p < 0.001) and Schirmer score (r = - 0.32, p = 0.006). Cluster analysis demonstrated the similarity between the question about heavy eyelids and TBUT. In addition, the OSDI questionnaire had the highest discriminatory power in ROC analysis, and the OSDI score significantly correlated with the specific questions about eyelids sticking together (r = 0.47, p < 0.0001) and watery or teary eyes (r = 0.34, p = 0.003). CONCLUSIONS: The blepharitis-specific additional questions were closely associated with objective parameters for DED. The question about heavy eyelids might be well suited for recording the symptoms of hyposecretory and hyperevaporative dry eye with blepharitis.

Clinical Course of Different Types of Immune Reactions following Keratoplasty.

BACKGROUND: Immune-mediated corneal graft rejection (IR) is a leading cause of corneal graft failure. The endothelium, stroma, epithelium, or a combination can be affected. Little is known about the long-term outcomes of different types of IR. METHODS: We reviewed the medical records of all keratoplasties that had been performed at our eye centre between 2003 and 2016 (n = 3934) for any kind of IR that occurred between the surgery and 2019. All patients with a definite diagnosis of IR and sufficient clinical data were included in the analysis. IRs were grouped according to the affected part of the graft (endothelial, stromal, epithelial, and mixed). We analysed the dynamics of recovery and the clinical outcomes. RESULTS: We identified a total of 319 patients with IR. Twenty-seven of those were lost to follow-up and were excluded from further analysis. Of the IRs, 89% affected the endothelium. Endothelial IR resulted more frequently in a considerable loss of endothelial cell density than other forms of IR. Stromal IR showed a lower relapse rate and a better visual recovery than other types of IR and resulted less often in a failure of the graft. CONCLUSIONS: We herein report comprehensive data about the prognosis regarding functional recovery after different types of IR following keratoplasty. Our data underline that timely recognition and correct classification of IR are important because they determine the clinical course and prognosis.

[The 2021 Activity Report of the Tissue Transplantation and Biotechnology Section of the German Ophthalmological Society]. / Aktivitäten der Sektion Gewebetransplantation und Biotechnologie der Deutschen Ophthalmologischen Gesellschaft: Leistungsbericht 2021.

The Section on Tissue Transplantation and Biotechnology of the German Ophthalmologic Society presented its 11th annual report for the year 2021. The number of corneal samples has still risen in comparison to former years. Nevertheless, there is still a need for import of transplants from abroad. Therefore, the transplant bottleneck has not yet been eliminated.

Glaucoma Treatment in German Hospitals in 2019. / Glaukombehandlung in deutschen Krankenhäusern 2019.

BACKGROUND: Surgical procedures in ophthalmology are subject to fluctuations in their application and are dependent on new developments, availability, and success rates. In the field of glaucoma surgery in particular, numerous new procedures have been introduced over the last few years. So far, hardly any analyses have been done on the current application of these newer procedures. In this paper, we present the extent to which different glaucoma surgery procedures were used in German hospitals in 2019. METHODS: The quality reports of German hospitals from 2019 were evaluated regarding all glaucoma-specific procedure codes. In particular, laser procedures, "classic" glaucoma procedures, and "modern" procedures such as MIGS (minimally invasive glaucoma surgery) are compared below. RESULTS: In 2019, 49,031 glaucoma procedures were performed in German hospitals. Numerically, cyclodestructive procedures were used most frequently. MIGS accounted for approximately 10% of procedures according to the available data. Among filtering procedures, about 40% were implant-assisted. DISCUSSION AND CONCLUSION: On the one hand, the data analyzed show a mixed expansion of the spectrum with newer procedures such as the MIGS and implants; on the other hand, classic procedures such as cyclodestruction are still used. It can be assumed that further shifts in surgical methods will be seen in the coming years.

[Keratoconus: biomechanics ex vivo]. / Keratokonus: Biomechanik ex vivo.

BACKGROUND: Keratoconus is associated with an impairment in corneal biomechanics. Using nanoindentation, spatially resolved measurement of biomechanical properties can be performed on corneal tissue. The aim of this study is to assess the biomechanical properties of corneas with keratoconus in comparison to healthy controls. METHODS: 17 corneas with keratoconus and 10 healthy corneas unsuitable for transplantation were included in the study. After explantation, corneas were kept in culture medium containing 15% dextran for at least 24 h. Nanoindentation was then performed to a depth of 25 µm at a force increase of 300 µN/min. RESULTS: A total of 2328 individual indentations were performed for this study. In the keratoconus group; the mean modulus of elasticity was 23.2 kPa (± 15.0 kPa) for a total of 1802 indentations. In the control group, the mean modulus of elasticity was 48.7 kPa (± 20.5 kPa) with a total of 526 indentations. The Wilcoxon test showed that the differences were statistically significant. CONCLUSION: Using nanoindentation, a significantly lower elastic modulus was found in corneas with keratoconus compared to corneas without keratoconus. Further studies are needed to gain a better understanding of how keratoconus affects corneal biomechanics.

Long-Term Outcomes of Excimer Laser-Assisted Penetrating Keratoplasty Using a Commercially Available Laser System - A Retrospective Case Series.

BACKGROUND: Favorable functional outcomes have been reported after excimer laser-assisted penetrating keratoplasty (EXL PKP). But this technique has not been widely adopted, and there are reports on EXL PKP from only a very limited number of institutions. Some of these results refer to operations carried out with laser systems that are not commercially available. In this retrospective case series, we report the long-term outcome of EXL PKP using the Schwind Amaris 500E laser system. MATERIAL AND METHODS: This retrospective consecutive case series included 30 eyes of 29 patients who had undergone EXL PKP between 2010 and 2013. Primary outcome measures were topographic astigmatism and visual acuity. Secondary outcome measures were the rates of graft rejection and graft failure, and the rate of grafts with an endothelial cell density below 500 cells/mm2. Survival analyses were carried out for the following endpoints: visual acuity, rate of graft rejection, and rate of grafts with endothelial cell densities higher than 500 cells/mm2. RESULTS: The median interquartile range (IQR) duration of follow-up was 45 (36) months. The indications for PKP were keratoconus (n = 21), corneal scarring (n = 6), Fuchs endothelial dystrophy (n = 1), and corneal dystrophy other than Fuchs endothelial dystrophy (n = 2). The median (IQR) topographic astigmatism at the end of the follow-up period was 5.3 (2.9) D. Forty-five months after surgery, 73% of all eyes had a visual acuity better than 0.3 LogMAR. The rate of graft rejection after 45 months of follow-up was 32%. All eyes maintained endothelial cell densities higher than 500 cells/mm2. There was no graft failure. CONCLUSIONS: EXL PKP is a safe and effective surgical procedure. No general conclusions can be drawn on the refractive outcome of EXL PKP. Potential advantages, such as a higher degree of graft-host congruity, that could possibly improve the refractive outcome should be weighed against the higher costs of EXL PKP.

Culturing Limbal Epithelial Cells of Long-term Stored Corneal Donors (Organ Culture) In Vitro - A Stepwise Linear Regression Algorithm.

PURPOSE: To assess various potential factors on human limbal epithelial cell (LEC) outgrowth in vitro using corneal donor tissue following long-term storage (organ culture) and a stepwise linear regression algorithm. METHODS: Of 215 donors, 304 corneoscleral rings were used for our experiments. For digestion of the limbal tissue and isolation of the limbal epithelial cells, the tissue pieces were incubated with 4.0 mg/mL collagenase A at 37 °C with 95% relative humidity and a 5% CO2 atmosphere overnight. Thereafter, limbal epithelial cells were separated from limbal keratocytes using a 20-µm CellTricks filter. The separated human LECs were cultured in keratinocyte serum-free medium medium, 1% penicillin/streptomycin (P/S), 0.02% epidermal growth factor (EGF), and 0.3% bovine pituitary extract (BPE). The potential effect of donor age (covariate), postmortem time (covariate), medium time (covariate), size of the used corneoscleral ring (360°, 270°180°, 120°, 90°, less than 90°) (covariate), endothelial cell density (ECD) (covariate), gender (factor), number of culture medium changes during organ culture (factor), and origin of the donor (donating institution and storing institution, factor) on the limbal epithelial cell outgrowth was analyzed with a stepwise linear regression algorithm. RESULTS: The rate of successful human LEC outgrowth was 37.5%. From the stepwise linear regression algorithm, we found out that the relevant influencing parameters on the LEC growth were intercept (p < 0.001), donor age (p = 0.002), number of culture medium changes during organ culture (p < 0.001), total medium time (p = 0.181), and size of the used corneoscleral ring (p = 0.007), as well as medium time × size of the corneoscleral ring (p = 0.007). CONCLUSIONS: The success of LEC outgrowth increases with lower donor age, lower number of organ culture medium changes during storage, shorter medium time in organ culture, and smaller corneoscleral ring size. Our stepwise linear regression algorithm may help us in optimizing LEC cultures in vitro.

Current Practice in the Treatment of Epithelial and Melanocytic Tumours with Interferon-α2b: A Survey of Tertiary Eye Centres in Germany.

PURPOSE: To evaluate the standard of care, in particular the use of topical or subconjunctival interferon-α2b, in treating ocular surface squamous neoplasia or melanocytic tumours in tertiary eye centres in Germany. METHODS: A survey containing 14 questions was sent to 43 tertiary eye centres in Germany. The questions addressed the surgical and medical management of ocular surface squamous neoplasia and melanocytic tumours (primary acquired melanosis and malignant melanoma), as well as the clinical experiences and difficulties in prescribing off-label interferon-α2b eye drops and subconjunctival injections. RESULTS: Twenty-four tertiary eye centres responded to the survey. Eighty-three percent of centres had used interferon-α2b in their clinical practice and 25% prescribed it as the first-line cytostatic agent following surgical excision of ocular surface squamous neoplasia, while 10% would do so for melanocytic tumours. Correspondingly, the majority of respondents selected mitomycin C as their first-line agent. Side effects were uncommon with topical interferon-α2b eye drops but were more frequently reported after subconjunctival interferon-α2b injections. In total, eight centres had experience with interferon-α2b injections. The most significant obstacles perceived by ophthalmologists when prescribing interferon-α2b were its high cost and the reimbursement thereof. CONCLUSION: Off-label mitomycin C was the preferred adjuvant therapy for epithelial and melanocytic tumours, with interferon-α2b being the standard second-line option. Interferon-α2b has predominantly been used to treat ocular surface squamous neoplasia and, to a lesser extent, melanocytic tumours at German tertiary eye centres. Following its market withdrawal, supply shortages of interferon-α2b are likely to have a profound impact on patient care and their quality of life.

Structure of a eukaryotic cytoplasmic pre-40S ribosomal subunit.

Final maturation of eukaryotic ribosomes occurs in the cytoplasm and requires the sequential removal of associated assembly factors and processing of the immature 20S pre-RNA Using cryo-electron microscopy (cryo-EM), we have determined the structure of a yeast cytoplasmic pre-40S particle in complex with Enp1, Ltv1, Rio2, Tsr1, and Pno1 assembly factors poised to initiate final maturation. The structure reveals that the pre-rRNA adopts a highly distorted conformation of its 3' major and 3' minor domains stabilized by the binding of the assembly factors. This observation is consistent with a mechanism that involves concerted release of the assembly factors orchestrated by the folding of the rRNA in the head of the pre-40S subunit during the final stages of maturation. Our results provide a structural framework for the coordination of the final maturation events that drive a pre-40S particle toward the mature form capable of engaging in translation.

Pediatric Cataract Surgery: Rate of Secondary Visual Axis Opacification Depending on Intraocular Lens Type.

PURPOSE: To assess the time course of secondary visual axis opacification (VAO) leading to additional surgery after primary intraocular lens (IOL) implantation in children and to describe further surgical outcomes. Comparison of lens types. DESIGN: Single-center, retrospective analysis of children aged 1 to 14 years who underwent cataract surgery with primary IOL implantation. The surgical technique was either in-bag IOL placement with primary posterior capsulotomy and anterior vitrectomy or bag-in-lens IOL placement. We excluded eyes with visually significant ocular comorbidities. PARTICIPANTS: Total of 135 eyes of 95 children. Of these, 64 had received an acrylic 3-piece IOL, 51 had an acrylic single-piece IOL, and 20 had an acrylic single-piece bag-in-lens IOL. The median ages at surgery were 53 months (interquartile range [IQR], 35-75), 52 months (27-65), and 60 months (40-84) in the 3-piece, 1-piece, and bag-in-lens groups, respectively. METHODS: Analysis of medical records. We used the Kaplan-Meier method and a Cox proportional hazards model with predefined adjustments for age at surgery, year of surgery, and the German Index of Socioeconomic Deprivation (score by postal code) to analyze VAO-free survival by lens type. Patients were invited to attend a clinical visit to achieve longer follow-ups. MAIN OUTCOME MEASURES: The rate of survival without VAO that required clearing of the visual axis after cataract surgery with primary IOL implantation. Any other surgical complications. RESULTS: The overall median follow-up was 19 months (IQR, 3-58). There were 13 cases of VAO, occurring at a median of 10 months (IQR, 10-12) after surgery. Of these, 1 eye had a 3-piece in-bag IOL, 10 eyes had 1-piece in-bag IOLs, and 2 eyes had bag-in-lens IOLs. The adjusted hazard ratio was 32.8 (95% confidence interval [CI], 3.3-327, P = 0.003) for 1-piece acrylic IOLs and 19.6 (CI, 1.22-316, P = 0.036) for bag-in-lens IOLs, compared with 3-piece acrylic in-bag IOLs. Two eyes with bag-in-lens surgery (10%) had an iris capture. There was 1 case of endophthalmitis. We found no cases of postoperative retinal detachment or new glaucoma. CONCLUSIONS: Children with secondary VAO who required a procedure to clear the visual axis generally presented within 15 months. Opacification rates were lowest when a 3-piece acrylic IOL was used.

A comparison of long-term results after Baerveldt 250 implantation in advanced uveitic vs. other forms of glaucoma.

INTRODUCTION: Uveitic glaucoma remains challenging despite medical and surgical advancements and can potentially lead to blindness if left uncontrolled. Conservative alternatives as well as microinvasive surgeries can postpone the necessity of a highly invasive intervention. However, such procedures are still necessary to treat some refractive glaucoma cases. Since previous studies have reported excellent results following the primary implantation of glaucoma drainage devices, it was our study's aim to evaluate long-term results following a Baerveldt 250 implantation in highly complex and surgically burdened uveitic glaucoma eyes (UG) and compare these to a similar population suffering from other forms of glaucoma (OFG). MATERIAL AND METHODS: We performed a retrospective analysis of all eyes (UG vs. OFG) following a Baerveldt 250 implant between 2013 and 2019. Efficacy parameters as well as post-operative complication data were extracted from our electronic data system for statistical analysis. RESULTS: A total of 62 eyes were included in our study (24 UG and 38 OFG). UG baseline mean IOP was 35.04 mmHg (± 11.85 mmHg) with 3.08 (± 1.13) topical agents, and OFG was 32.63 mmHg (± 7.74 mmHg) with 2.68 (± 1.28) topical agents. A majority of eyes also required systemic acetazolamide (UG: 79% OFG: 87%) and had undergone at least one glaucoma-related operation prior to the Baerveldt 250 implant ((UG: 1.21 (± 0.66)), OFG: 1.74 (± 1.33)). At the median follow-up period (UG 592, OFG 764 days), 52.5%/32.5% of UG/OFG cases showed qualified success (IOP below 21 mmHg with either topical or/and systemic medication), 15%/30% no longer required topical medication, and 47.5% /47.5% were free of acetazolamide systemically. Moreover, 75%/72.5% of eyes experienced no further pressure-related surgical event. Although sight-threatening complications such as corneal and macular edema were reported in both groups, most either maintained or improved their visual acuity at the last follow-up (58.33%/57.89%). CONCLUSION: The Baerveldt 250 implant is shown to be both effective and safe for advanced glaucoma cases in uveitis and other forms. No further glaucoma-related surgery is required in the majority of eyes in either group within a follow-up period of almost 2 years. Despite sight-threatening complications such as macular and corneal edema, visual acuity can be either maintained or improved in most eyes.