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.

Needs and Satisfaction Analysis of Patients and Referring Physicians in an Outpatient Cataract Service. / Bedarfs- und Zufriedenheitsanalyse von Patienten und Zuweisenden eines ambulanten Kataraktangebots.

BACKGROUND: To ensure efficient use of resources within outpatient services, constant patient flow is vital. This can be achieved by addressing the wishes and needs of all relevant stakeholders. MATERIALS AND METHODS: The present study aims to show how the needs and present satisfaction of patients and referring physicians can be determined in the context of an outpatient cataract service. It presents the conclusions that can be drawn for the design of the service. To assess needs and satisfaction, we developed a patient questionnaire and a referring physician questionnaire. Promoters and detractors for referral were identified following the concept of the net promoter score, a market research instrument. RESULTS: 339 (38%) patients and 26 (45%) referring physicians of the main referring group answered the questionnaires. The most important characteristics for referring physicians were quality of treatment, patient satisfaction, and communication in case of queries as well as speed of sending the doctor's letter. When making their decision on a cataract centre, the patients prioritised professional reputation, previous experience with the clinic, and recommendation of their ophthalmologist as well as customary appointment scheduling. CONCLUSION: The two groups influence each other's recommendation or choice. Simultaneous analysis of patients and referring physicians is therefore essential. Overall, patients and referring physicians are highly satisfied with the cataract service of the university medical centre. Beyond that, however, various potentials for improvement could be identified. In summary, this report describes a comprehensive approach to assess needs and satisfaction of patients and referring physicians in an outpatient clinic trying to sustainably improve patient care.

Corneal Oedema: Aetiology, Diagnostic Testing, and Treatment.

Corneal oedema results from an underlying pathology, which can be diverse in origin, and may be mechanical, dystrophic, or inflammatory, and affect any layer of the cornea. Diagnostic tools such as Scheimpflug imaging and anterior segment optical coherence tomography have standardised quantification of corneal oedema and have become important aids in clinical practice. Timely diagnosis and treatment are key to preventing irreversible damage to the corneal ultrastructure, such as anterior corneal fibrosis or endothelial cell damage. The oedema usually resolves quickly when the underlying cause has been addressed. Symptomatic treatment using hyperosmolar agents has failed to show any benefits in oedema resolution or improvement in visual acuity compared to placebo. In contrast, rho-associated protein kinase (ROCK) inhibitors offer a promising option for medical treatment in cases of endothelial dysfunction, but their safety and efficacy must be further validated in large scale clinical trials. Until then, endothelial or penetrating keratoplasties remain the mainstay treatment where structural changes to the cornea have occurred.

Hyperosmolar Eye Drops for Diurnal Corneal Edema in Fuchs' Endothelial Dystrophy: A Double-Masked, Randomized Controlled Trial.

PURPOSE: The Eye Drops for Early Morning-Associated Swelling (EDEMAS) trial assessed the efficacy of hyperosmolar eye drops on corneal edema resolution. DESIGN: Double-masked, randomized controlled trial of hyperosmolar eye drops. PARTICIPANTS: Participants with Fuchs' dystrophy scheduled for Descemet membrane endothelial keratoplasty. METHODS: One eye was randomized to hyperosmolar eye drops (treatment); the fellow eye was randomized to artificial tears (placebo). After baseline examination in the afternoon, corneas were examined using Scheimpflug tomography after eye opening in the morning. Participants received eye drops twice. Imaging was repeated every 30 minutes up to 4 hours. MAIN OUTCOME MEASURES: Decrease in central corneal thickness 1 hour after eye opening (primary end point), corneal thickness, subjective visual function, glare, visual acuity, and adverse events (AEs) (secondary end points). RESULTS: A total of 68 participants received the allocated intervention (59 eyes received treatment; 55 eyes received placebo). All eyes had stromal edema; none had epithelial edema. Corneal thickness was 626 µm in the treatment arm and 622 µm in the placebo arm after eye opening, indicating an early morning edema compared with baseline of +21 µm and +24 µm, respectively. Decrease in corneal thickness after 1 hour was -10.5 µm in the treatment arm (95% confidence interval [CI], -12.8 to -8.2) and -11.2 µm (95% CI, -13.6 to -8.9) in the placebo arm (between-arm difference, 0.7 µm, 95% CI, -2.0 to 3.5; P = 0.59), indicating no clinically relevant effect of hyperosmolar eye drops on early morning corneal edema. Results were not compatible with a relevant treatment effect on corneal thickness, visual acuity, and glare over the entire course of the study. Increase in subjective visual function was less rapid in the treatment arm than in the placebo arm. Adverse events, most commonly burning after eye drop application, were more common with treatment (30 eyes) than placebo (1 eye; risk difference, 49 percentage points; 95% CI, 36-62). CONCLUSIONS: In this double-masked, randomized controlled trial, resolution of early morning stromal edema was not accelerated by hyperosmolar eye drops, which more frequently caused AEs. These results are not compatible with a clinically relevant effect of hyperosmolar eye drops and do not support their routine use.

A Peroxygenase from Chaetomium globosum Catalyzes the Selective Oxygenation of Testosterone.

Unspecific peroxygenases (UPO, EC 1.11.2.1) secreted by fungi open an efficient way to selectively oxyfunctionalize diverse organic substrates, including less-activated hydrocarbons, by transferring peroxide-borne oxygen. We investigated a cell-free approach to incorporate epoxy and hydroxyl functionalities directly into the bulky molecule testosterone by a novel unspecific peroxygenase (UPO) that is produced by the ascomycetous fungus Chaetomium globosum in a complex medium rich in carbon and nitrogen. Purification by fast protein liquid chromatography revealed two enzyme fractions with the same molecular mass (36 kDa) and with specific activity of 4.4 to 12 U mg-1 . Although the well-known UPOs of Agrocybe aegerita (AaeUPO) and Marasmius rotula (MroUPO) failed to convert testosterone in a comparative study, the UPO of C. globosum (CglUPO) accepted testosterone as substrate and converted it with total turnover number (TTN) of up to 7000 into two oxygenated products: the 4,5-epoxide of testosterone in ß-configuration and 16α-hydroxytestosterone. The reaction performed on a 100 mg scale resulted in the formation of about 90 % of the epoxide and 10 % of the hydroxylation product, both of which could be isolated with purities above 96 %. Thus, CglUPO is a promising biocatalyst for the oxyfunctionalization of bulky steroids and it will be a useful tool for the synthesis of pharmaceutically relevant steroidal molecules.

Supine Positioning for Graft Attachment After Descemet Membrane Endothelial Keratoplasty: A Randomized Controlled Trial.

PURPOSE: The Supine Positioning for Descemet Membrane Endothelial Keratoplasty Attachment (SUPER-DMEK) trial assessed the efficacy of prolonged supine head positioning on graft attachment. DESIGN: Randomized controlled trial. METHODS: Participants with Fuchs' dystrophy were randomized to 5 days of supine head positioning (intervention) or to 1 day (control). Participants, surgeons, and investigators were masked until the day after surgery. Adherence to the allocated intervention was monitored using a head sensor. Main outcome measures were area and volume of graft detachment (coprimary end points) 2 weeks after surgery quantified using a validated neural network for image segmentation on anterior segment optical coherence tomography images, and repeat air injection (rebubbling), subjective visual function, and adverse events (secondary end points). RESULTS: A total of 86 participants received the allocated intervention (35 eyes intervention and 51 eyes control). In the intention-to-treat analysis, the mean area of graft detachment was 28.6% in the intervention arm and 27.5% in the control arm (adjusted between-arm difference, 1.3; 95% CI, -8.7 to 11.4; P = .80). Results for volume of detachment and as-treated analyses based on head position sensor data indicated no potentially clinically relevant effect of prolonged supine positioning on graft attachment. Results were not compatible with a relevant treatment effect on rebubbling or subjective visual function. Adverse events, most commonly back pain, were more common and more severe with the intervention. CONCLUSIONS: In this randomized controlled trial, graft attachment was not improved with prolonged supine head positioning. Prolonged supine positioning frequently caused back pain. Prolonged supine positioning after Descemet membrane endothelial keratoplasty for Fuchs' dystrophy may not be needed in routine practice.

Draft Genome Sequence of Truncatella angustata (Anamorph) S358.

The ascomycete Truncatella angustata has a worldwide distribution. Commonly, it is associated with plants as an endophyte, pathogen, or saprotroph. The genome assembly comprises 44.9 Mbp, a G+C content of 49.2%, and 12,353 predicted genes, among them 12 unspecific peroxygenases (EC 1.11.2.1).

Graft Detachment after Descemet Membrane Endothelial Keratoplasty with and without Cataract Surgery.

Purpose: To evaluate graft detachment after Descemet membrane endothelial keratoplasty (DMEK) in pseudophakic eyes and DMEK combined with cataract surgery (triple DMEK). Design: Analysis of 3 single-center prospective cohort studies and 1 randomized controlled trial. Participants: Participants with Fuchs' endothelial corneal dystrophy. Methods: A validated neural network for image segmentation quantified graft detachment on anterior segment OCT (AS-OCT) images 3 days after DMEK and at the 2-week postoperative visit. Area and volume of graft detachment were compared between DMEK only and triple DMEK using generalized estimating equation models and adjusting for participant age and the size of the air bubble. Main Outcome Measures: Area and volume of DMEK graft detachment. Results: Among 207 participants with 270 eyes included, 75 pseudophakic eyes had DMEK only and 195 eyes had triple DMEK. A total of 147 eyes had less than one third of detachment at day 3. In 139 of these eyes (95%), detachment was still less than one third at the 2-week scan, indicating that postoperative graft detachment at 2 weeks occurred mainly in eyes with early detachment. When superimposing all 3-dimensional maps from 2 weeks after surgery, the central graft was mainly attached and detachment was located at the graft margin. The mean area of graft detachment decreased from 28% in DMEK only and 38% in triple DMEK to 16% in DMEK only and 25% in triple DMEK at the 2-week postoperative visit. At 2 weeks, the mean area of detachment was 1.85-fold higher (95% confidence interval [CI], 1.34-2.56) and the mean volume was 2.41-fold higher (95% CI, 1.51-3.86) in triple DMEK compared with DMEK. A total of 46 eyes received rebubbling procedures, with 7 eyes (9%) in the DMEK group and 39 eyes (20%) in the triple DMEK group (adjusted risk ratio, 3.1; 95% CI, 1.3-7.1), indicating that rebubbling was more common in eyes undergoing triple DMEK. Conclusions: Automated segmentation of AS-OCT images allowed precise quantification of graft detachment over time and identified DMEK combined with cataract surgery as a risk factor. Frequency of operative follow-up might be guided by extent of detachment in the first postoperative days after DMEK.

Predicting Edema Resolution After Descemet Membrane Endothelial Keratoplasty for Fuchs Dystrophy Using Scheimpflug Tomography.

IMPORTANCE: Predicting the extent of corneal edema resolution after Descemet membrane endothelial keratoplasty (DMEK) may help in preoperative decision-making by identifying patients who may benefit from restoring endothelial function. OBJECTIVE: To develop and validate a predictive model for edema resolution after DMEK using Scheimpflug tomographic imaging. DESIGN, SETTING, AND PARTICIPANTS: Two prospective studies recruited participants with advanced Fuchs dystrophy at a university-based tertiary referral center between July 1, 2017, and August 31, 2019. Analyses were designed in November 2019 and completed on June 30, 2020. Development of a predictive model using linear least absolute shrinkage and selection operator regression was conducted in a derivation cohort (100 eyes). Overall performance, discrimination, and calibration were tested in the separate validation cohort (32 eyes). EXPOSURES: Preoperative Scheimpflug parameters and patient-reported visual disability were considered as potential predictors of edema resolution: (1) tomographic features (irregularity of lines of equal corneal thickness, displacement of the thinnest point of corneal thickness from the inferior-temporal quadrant, and absolute amount of focal posterior corneal depression), (2) standardized anterior and posterior corneal backscatter, (3) preoperative central corneal thickness, and (4) Fuchs dystrophy-specific visual disability. MAIN OUTCOMES AND MEASURES: Decrease in central corneal thickness after DMEK indicative of edema resolution. RESULTS: Of the 88 patients included in the analysis, 54 were women (61%); median age was 68 years (interquartile range [IQR], 59-76 years). A median of 13 months after DMEK (IQR, 9-16 months), median corneal thickness was 77 µm lower (IQR, 51-94 µm) in the derivation cohort and 75 µm lower in the validation cohort (IQR, 54-96 µm) than before surgery. Per 10-µm edema resolution, eyes gained 0.66 Early Treatment Diabetic Retinopathy Study letters (95% CI, 0.09-1.23) in best-corrected visual acuity. Three tomographic features were present in 68 of 100 eyes (68%) in the derivation cohort and in 18 of 32 eyes (56%) in the validation cohort before DMEK and in only 1 of 132 eyes (1%) after DMEK. To predict edema resolution after DMEK based on preoperative assessment, 5 variables were selected by the statistical learning algorithm: nonparallel isopachs, focal posterior depression, anterior and posterior corneal backscatter, and central corneal thickness. In the separate validation cohort, the model showed high overall performance, discrimination, and calibration. CONCLUSIONS AND RELEVANCE: These post hoc analyses of prospective cohorts support a model for use in the prediction of edema resolution after DMEK using Scheimpflug measurement to identify patients benefitting most from DMEK.

Three-Dimensional Map of Descemet Membrane Endothelial Keratoplasty Detachment: Development and Application of a Deep Learning Model.

Purpose: To develop and apply a neural network for quantification of endothelial corneal graft detachment using anterior segment (AS) OCT. Design: Training and validation of a neural network and application within a prospective cohort. Participants: Patients two weeks after Descemet membrane endothelial keratoplasty. Methods: Investigators manually labeled the posterior cornea and the graft in cross-sectional images of rotational AS OCT scans. Neural networks for image segmentation were trained to identify the area of graft detachment on cross-sectional images. The best-performing neural network with the lowest misclassification (Youden index) and highest spatial overlap with the ground truth (Dice coefficient) was selected and evaluated in a separate dataset. Three-dimensional maps of the area and volume of graft detachment were calculated. For application, the neural network's rating on the detachment was compared with slit-lamp-based ratings of cornea specialists on the same day as the AS OCT imaging took place. Main Outcome Measures: Youden index and Dice coefficient. Results: Neural networks were trained on 27 AS OCT scans with 6912 labeled images. Among 48 combinations of probability thresholds and epoch states, the best-performing neural network showed a Youden index of 0.99 and a Dice coefficient of 0.77, indicating low misclassification and good spatial overlap on individual image segmentation. In the validation set unknown to the neural network with 20 scans (5120 images), the Youden index was 0.85 and the Dice coefficient was 0.73, and a high overall performance compared with the manually labeled ground truth (R 2 = 0.90). In the application set with 107 eyes, the neural network estimated the mean percent detachment larger than the cornea specialist (mean difference, 8.2 percentage points; 95% confidence interval, 6.2-10.2). Masked review of 42 AS OCTs with more than ±10 percentage points difference in ratings showed that clinicians underestimated the true detachment in cases with significant detachment requiring intervention. Conclusions: Deep learning-based segmentation of AS OCT images quantified the percent and the volume of DMEK graft detachment with high precision. Fully automated 3-dimensional quantification of graft detachment is highly sensitive, particularly in corneas with a significant amount of detachment, and may support decision making.

Rotational alignment of corneal endothelial grafts and risk of graft detachment after Descemet membrane endothelial keratoplasty: a double-masked pseudo-randomized study.

PURPOSE: The posterior cornea is rotationally asymmetric, and Descemet membrane endothelial keratoplasty (DMEK) grafts preferentially scroll vertically. This prospective study assessed whether graft attachment after DMEK differed depending on the rotational alignment of the donor graft in the recipient eye. METHODS: Pseudo-randomization and blinding of the graft orientation in the recipient's eye were possible by procedural separation: (1) The eye bank recorded the position of an orientation marker in the donor cornea; (2) the surgeon preparing the DMEK graft recorded an upside-down marker relative to the eye bank marker; and (3) the surgeon assessed the position of the upside-down marker in the recipient after DMEK. Surgeons were masked towards the eye bank marker. Using mixed-effects models, we assessed graft attachment relative to the rotational alignment of the donor graft. RESULTS: Postoperatively, the graft was not fully attached in 59 of 179 eyes (33%). A second air fill (rebubbling) was performed in 11%. The graft axis was in line with the recipient cornea axis in 40%, oblique in 28% and orthogonal in 32%. We did not detect an elevated risk of incomplete attachment (odds ratio [OR], 1.16; 95% CI, 0.61-2.20), risk of rebubbling (OR, 1.25; 95% CI, 0.47-3.31) or larger areas of graft detachment in non-aligned grafts compared to aligned grafts. CONCLUSION: Rotational alignment was not strongly associated with the risk of incomplete graft attachment, although modestly elevated risks cannot be ruled out. Efforts are needed to reduce the need for rebubbling after DMEK and to identify modifiable risk factors for graft detachment.