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.

ZEISS PLEX Elite 9000 Widefield Optical Coherence Tomography Angiography as Screening Method for Early Detection of Retinal Hemangioblastomas in von Hippel-Lindau Disease.

Purpose: To evaluate early detection of retinal hemangioblastomas (RHs) in von Hippel-Lindau disease (VHLD) with widefield optical coherence tomography angiography (wOCTA) compared to the standard of care in ophthalmologic VHLD screening in a routine clinical setting. Methods: We conducted prospective comparisons of three screening methods: wOCTA, standard ophthalmoscopy, and fluorescein angiography (FA), which was performed only in uncertain cases. The numbers of detected RHs were compared among the three screening methods. The underlying causes for the lack of detection were investigated. Results: In 91 eyes (48 patients), 67 RHs were observed (mean, 0.74 ± 1.59 RH per eye). FA was performed in eight eyes. Ophthalmoscopy overlooked 25 of the 35 RHs detected by wOCTA (71.4%) due to the background color of the choroid (n = 5), small tumor size (n = 13), masking by a bright fundus reflex (n = 2), and masking by surrounding retinal scars (n = 5). However, wOCTA missed 29 RHs due to peripheral location (43.3%). The overall detection rates were up to 37% on the basis of ophthalmoscopy alone, up to 52% for wOCTA, and 89% for FA. Within the retinal area covered by wOCTA, the detection rates were up to 46.7% for ophthalmoscopy alone, up to 92.1% for wOCTA, and 73.3% for FA. Conclusions: The overall low detection rate of RHs using wOCTA is almost exclusively caused by its inability to visualize the entire peripheral retina. Therefore, in unclear cases, FA is necessary after ophthalmoscopy. Translational Relevance: Within the imageable retinal area, wOCTA shows a high detection rate of RHs and therefore may be suitable to improve screening for RHs in VHLD.

Vertical Scrolling Axis of Corneal Endothelial Grafts for Descemet Membrane Endothelial Keratoplasty.

PURPOSE: Heterogeneity in scrolling behavior of Descemet membrane endothelial keratoplasty (DMEK) grafts complicates DMEK surgery. This prospective observational study assessed scrolling axes of DMEK grafts relative to the donor's eye. METHODS: The eye bank randomly marked the rim of corneoscleral donor buttons during trephination and recorded the position relative to the donor's axis. Surgeons were masked to the absolute position of the eye bank marking and recorded the scrolling axis relative to the eye bank marking and DMEK upside-down orientation. The scrolling axis was categorized as vertical (0 to 30 degrees and 150 to 180 degrees), oblique (>30 to 60 degrees and 120 to <150 degrees), and horizontal (>60 to <120 degrees). Scrolling patterns of corneas from the same donor were assessed. RESULTS: Scrolling patterns of 202 donor corneas from 149 donors were determined. The donor graft scrolled predominantly vertically to the donor's cornea [75%; 95% confidence interval (CI), 68%-80%]. Horizontal axes (11%) and oblique axes (14%) were less common. The median deviation in scrolling axes after unfolding the grafts was 0 degrees from the original scrolling axis (interquartile range, 0-15), indicating that scrolling axes were stable. Fellow eyes of 46 donors had 3.55 times higher odds of a nonvertical scrolling pattern if the first eye had a nonvertical scrolling pattern (95% CI, 1.37-9.20), suggesting that donor factors influencing both eyes could contribute to scrolling patterns. CONCLUSIONS: DMEK grafts have a natural and stable scrolling tendency at vertical axis of donor's cornea. Anticipating scrolling axes might help improve preparation techniques for DMEK grafts and outcomes.

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.

Morphological and Optical Determinants of Visual Disability in Fuchs Endothelial Corneal Dystrophy.

PURPOSE: To identify determinants of visual disability in patients with advanced Fuchs endothelial corneal dystrophy. METHODS: This prospectively sampled cross-sectional study at a tertiary referral center included participants with clinically advanced Fuchs dystrophy requiring endothelial keratoplasty and no other vision-limiting pathologies. We quantified visual disability using the Fuchs dystrophy-specific Visual Function and Corneal Health Status (V-FUCHS) visual disability instrument. We calculated Fuchs dystrophy-specific glare and diurnal variation (Glare Factor) scores and visual acuity-related disability (Visual Acuity Factor) scores. To assess corneal morphology and optics, all participants underwent standardized Scheimpflug imaging and tests for disability glare and best-corrected visual acuity on Early Treatment Diabetic Retinopathy Study charts after subjective refraction. Associations of morphological and optical parameters with V-FUCHS scores were assessed adjusting for age, sex, and lenticular status. RESULTS: Participants with more posterior corneal backscatter had more visual disability (higher scores), with participants in the highest quartile of backscatter (median, 1409 scatter units) having 0.57 higher Glare Factor scores (95% confidence interval, 0.14-1.00) and 0.61 higher Visual Acuity Factor scores (95% confidence interval, 0.15-1.06) compared with participants in the lowest quartile of backscatter (median, 812 scatter units). Other morphological and optical factors such as anterior corneal backscatter, higher-order aberrations, or edematous surface changes were not empirical contributors to visual disability, especially when accounting for posterior corneal backscatter. CONCLUSIONS: Corneal backscatter is a driver of characteristic visual disability in Fuchs dystrophy. Comprehensive assessments of morphology and direct quantification of disease-related disability may help identify the best candidates for endothelial keratoplasty.

[The German version of the Visual Function and Corneal Health Status (V­FUCHS): a Fuchs dystrophy-specific visual disability instrument]. / Visual Function and Corneal Health Status (V-FUCHS) auf Deutsch: Ein Fragebogen spezifisch für Fuchs-Endotheldystrophie.

BACKGROUND: In Fuchs' endothelial corneal dystrophy (FECD), the timing and expectation of interventions has changed in recent years because of improved therapeutic options. To assess outcomes and compare interventions, a patient-reported quantification of visual disability is important. OBJECTIVE: To develop the German version of the Visual Function and Corneal Health Status (V­FUCHS), an instrument specifically for patients with FECD, and to assess its retest reliability and validity. MATERIAL AND METHODS: The V­FUCHS was translated to German by certified forward and backward translators. Patients tested the translated questions regarding content areas, language and problem questions. After the pretest, V­FUCHS was assessed for retest reliability and validity in FECD patients. Patients were also asked to complete a cataract-specific questionnaire (Catquest-9SF) and to complete V­FUCHS again after 6 weeks to assess retest reliability. RESULTS: After successful pretesting in 30 patients, V­FUCHS was completed by another 52 FECD patients before endothelial keratoplasty. Participants (median age 69 years) were (self-)employed or homemakers (42%), 49% were active vehicle drivers. The retest reliability confirmed agreement and consistency of response (intraclass correlation coefficient, > 0.60, both factors). The V­FUCHS Visual Acuity score correlated with the Catquest-9SF score (r = 0.77; 95% CI, 0.67-0.85), whereas correlation of the Glare Factor specific for Fuchs' endothelial dystrophy with Catquest-9SF was weaker (r = 0.65; 95% CI, 0.50-0.76). CONCLUSION: V­FUCHS allows for standardized quantification of visual disability in patients with FECD. The German version of V­FUCHS is a valid and reliable visual disability instrument. It may serve as a patient-reported outcome measure and needs to be studied further in clinical practice, research and trials.

Avoiding Hyperopic Surprises After Descemet Membrane Endothelial Keratoplasty in Fuchs Dystrophy Eyes by Assessing Corneal Shape.

PURPOSE: It is unclear which patients unexpectedly have a hyperopic refractive outcome after combined Descemet membrane endothelial keratoplasty and cataract surgery (triple DMEK). We assessed how corneal shape predicts hyperopia after triple DMEK. DESIGN: Retrospective cohort study. METHODS: Patients with Fuchs endothelial corneal dystrophy (FECD) with Scheimpflug examinations before uncomplicated triple DMEK at a tertiary referral center were included. The arithmetic error was calculated (stable postoperative refraction minus predicted refraction). Using multinomial logistic regression, risk ratios of > +0.5 diopter (D) hyperopic and > 0.5 D myopic arithmetic errors were calculated. RESULTS: In 112 eyes, the median predicted refraction was -0.43 D (interquartile range [IQR], -0.47 to -0.17) with an achieved refraction of -0.63 to 0.56 (IQR). The arithmetic error was 0.34 D (IQR, -0.22 to 0.81). A hyperopic arithmetic error was present in 46% of eyes. FECD eyes with an oblate posterior cornea (Q value >0) had a 3.0 times higher risk of hyperopic shift after triple DMEK (95% confidence interval [CI], 1.3-7.0; P = .011), compared to spherical or prolate corneas (Q value ≤ 0). In eyes with posterior Q > 0, the mean prediction error was +0.50 D higher than in eyes with negative Q values (95% CI, 0.19-0.82; P = .002), independent of corneal thickness. CONCLUSIONS: Hyperopic surprises after triple DMEK particularly occur in corneas that are flatter centrally than the periphery because of edematous changes (oblate posterior profile). Eyes with a positive Q value on Scheimpflug imaging should be considered for additional power at the intraocular lens level.

Diurnal Variation in Corneal Edema in Fuchs Endothelial Corneal Dystrophy.

PURPOSE: The extent of diurnal variation in corneal edema in Fuchs dystrophy is unknown. We measured corneal thickness and posterior profile over the course of the day using Scheimpflug imaging. DESIGN: Prospective cohort study. METHODS: Participants with clinically advanced Fuchs dystrophy eyes undergoing endothelial keratoplasty and participants with healthy corneas were assessed around noon the day before surgery and late afternoon, in presumed steady state. After controlled overnight patching to standardize eyelid closure, participants were assessed immediately upon eye opening in hospital the morning of surgery. RESULTS: Directly upon awakening, patients had mean corneal thickness of 663 µm (interquartile range [IQR], 625-707) in Fuchs dystrophy (n = 44) and controls (n = 11) had thickness of 557 µm (IQR, 527-601). In control corneas, there were no systematic changes with time. In Fuchs dystrophy eyes, corneal thickness decreased after awakening. Ninety-five percent of patients can be expected to have a decrease in corneal thickness over the first 4 hours after awakening between 31 µm and 58 µm (95% prediction interval). Posterior Q decreased on average by 0.15 (95% confidence interval [CI], 0.07-0.23) and posterior radius of curvature decreased by 0.20 mm (95% CI, 0.14-0.27) over the first 4 hours, indicating that edema resolution steepened the central posterior cornea. Beyond 4 hours after awakening, corneas no longer changed considerably in Fuchs dystrophy. CONCLUSION: Impaired hydration control in clinically advanced Fuchs dystrophy makes measurements of key corneal parameters unreliable directly after eye opening. Beyond the first hours after eye opening, corneal thickness measurements are unlikely to vary more in Fuchs dystrophy eyes than in normal eyes.

Complications after pancreaticoduodenectomy are associated with higher amounts of intra- and postoperative fluid therapy: A single center retrospective cohort study.

BACKGROUND: Perioperative mortality after pancreaticoduodenectomy has decreased significantly in high-volume centers, but morbidity remains high. Restrictive perioperative fluid management may contribute to reduced complication rates after various surgical procedures. The aim of this study was to determine whether there is a correlation between the amount of fluid administered and postoperative complications. We hypothesized that higher amounts of intra- and total fluid is associated with greater postoperative morbidity. MATERIALS AND METHODS: We retrospectively examined data of 553 patients who underwent pancreaticoduodenectomy at University of Freiburg Medical Center between 2001 and 2013. Data on intra - and postoperative fluid administration (until postoperative day 5) were obtained from anesthesiological and surgical records. Data on complications were retrieved from our institutional pancreatic database. RESULTS: The median values for intra- and total fluid administered were 6000 ml (range 400-15,000 ml) and 13,600 ml (range 5000-57,700 ml), respectively. The overall in-hospital mortality was 1.9% (no correlation with fluid administration). Patients who received more than 6000 ml intraoperative fluid had more wound infections (P = 0.049), intra-abdominal abscesses (P = 0.020) and postoperative interventions (P = 0.007). In patients who received more than 14000 ml fluid until postoperative day 5 all evaluated types of postoperative complications (infectious, fistula, delayed gastric emptying, bleeding) and re-interventions occurred significantly more frequently than in patients who received less than 14,000 ml (P < 0.05-0.001). CONCLUSIONS: Higher amounts of fluids may contribute to postoperative complications. More studies are needed to adequately assess the use of intra/postop fluid therapy.