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Background and purposeCorneal fluorescein staining is one of the most important diagnostic tests in dry eye disease (DED). Nevertheless, the result of this examination is depending on the grader. So far, there is no method for an automated quantification of corneal staining commercially available. Aim of this study was to develop a software-assisted grading algorithm and to compare it with a group of human graders with variable clinical experience in patients with DED.MethodsFifty images of eyes stained with 2 µl of 2% fluorescein presenting different severity of superficial punctate keratopathy in patients with DED were taken under standardized conditions. An algorithm for detecting and counting superficial punctate keratitis was developed using ImageJ with a training dataset of 20 randomly picked images. Then, the test dataset of 30 images was analyzed (1) by the ImageJ algorithm and (2) by 22 graders, all ophthalmologists with different levels of experience. All graders evaluated the images using the Oxford grading scheme for corneal staining at baseline and after 6–8 weeks. Intrarater agreement was also evaluated by adding a mirrored version of all original images into the set of images during the 2nd grading.ResultsThe count of particles detected by the algorithm correlated significantly (n = 30; p < 0.01) with the estimated true Oxford grade (Sr = 0,91). Overall human graders showed only moderate intrarater agreement (K = 0,426), while software-assisted grading was always the same (K = 1,0). Little difference was found between specialists and non-specialists in terms of intrarater agreement (K = 0,436 specialists; K = 0,417 non-specialists). The highest interrater agreement was seen with 75,6% in the most experienced grader, a cornea specialist with 29 years of experience, and the lowest was seen in a resident with 25,6% who had only 2 years of experience.ConclusionThe variance in human grading of corneal staining - if only small - is likely to have only little impact on clinical management and thus seems to be acceptable. While human graders give results sufficient for clinical application, software-assisted grading of corneal staining ensures higher consistency and thus is preferrable for re-evaluating patients, e.g., in clinical trials.

Until recently, governmental organizations played a dominant and decisive role in natural resource management. However, an increasing number of studies indicate that this dominant role is developing towards a more facilitating role as equal partner to improve efficiency and create a leaner state. This approach is characterized by complex collaborative relationships between various actors and sectors on multiple levels. To understand this complexity in the field of environmental management, we conducted a social network analysis of floodplain management in the Dutch Rhine delta. We charted the current interorganizational relationships between 43 organizations involved in flood protection (blue network) and nature management (green network) and explored the consequences of abolishing the central actor in these networks. The discontinuation of this actor will decrease the connectedness of actors within the blue and green network and may therefore have a large impact on the exchange of ideas and decision-making processes. Furthermore, our research shows the dependence of non-governmental actors on the main governmental organizations. It seems that the Dutch governmental organizations still have a dominant and controlling role in floodplain management. This challenges the alleged shift from a dominant government towards collaborative governance and calls for detailed analysis of actual governance.

Abstract PurposeThe use of face masks has been proposed to cause or exacerbate the symptoms of dry eye disease (DED), which has been widely discussed under the term mask-associated dry eye (MADE). However, no studies have systematically investigated tear film parameters during the use of different face masks. Therefore, the objective of the present study was to investigate clinically relevant parameters of the tear film before and during the short-time use of face masks in dry and normal eyes.MethodsIn a prospective study, the tear film parameters of 42 DED patients and 42 healthy volunteers were examined while wearing different types of face masks in a randomized order. This included measurements of non-invasive tear break-up time (NIBUT), lipid layer thickness, tear meniscus height, and bulbar redness after 30 min of wearing no mask, a surgical face mask or an FFP2/K95 mask. The equivalence of the means was assessed using the two one-sided t-test (TOST) method.ResultsIn healthy volunteers’ lipid layer thickness, NIBUT and tear meniscus height were not significantly altered by 30 min of surgical or FFP2 mask wear (p > 0.016). The use of either type of mask was significantly associated with decreased bulbar redness (p < 0.001) in healthy eyes. In patients with DED, none of the tear film parameters or bulbar redness were significantly altered by 30 min of mask wear (p > 0.016).ConclusionsBased on these results, the short-term wearing of face masks, regardless of type, did not produce a significant difference in tear film parameters of lipid layer thickness, NIBUT, and tear meniscus in healthy or dry eyes, while bulbar redness was reduced after mask wear only in healthy volunteers.

Background Retinopathy of Prematurity (ROP) can progress despite standard treatments such as laser coagulation and VEGF inhibitors. Scleral buckle surgery (SBS) is a surgical option in stage 4 ROP, though anatomical success in stage 5 is rare. We present a unique case of spontaneous retinal reattachment after SBS in stage 5 ROP without further intervention. Case presentation A female infant, born at 24 + 2 weeks and weighing 440 g, developed stage III ROP with plus disease in the left eye. Despite laser treatment, the disease progressed to stage 4B, prompting SBS at 39 weeks PMA. Within three weeks, the eye advanced to stage 5 ROP. Surprisingly, complete retinal re-attachment occurred spontaneously within four months. Although the anatomical outcome was favorable, the left eye developed high myopia and amblyopia. Conclusions This case highlights the potential for spontaneous improvement after SBS in advanced ROP. While anatomical success is possible, functional outcomes may remain poor. Individualized follow-up and further research on subretinal fluid dynamics are needed to optimize treatment strategies.

PurposeThe study aims to evaluate visual outcome, central corneal thickness, and rebubbling rate in a cohort with oversized DMEK grafts after failed penetrating keratoplasty (PK). The unique feature of the study is a descemetorhexis diameter larger than the full-thickness graft, i.e., peripheral to the PK interface.MethodsA monocentric, retrospective evaluation of all patients with endothelial graft failure after PK treated with an oversized DMEK graft and descemetorhexis outside of the PK interface (i.e., in host tissue) between January 2015 and July 2019 at the Department of Ophthalmology at the University of Düsseldorf (Germany) was performed.ResultsEleven eyes of 10 patients were identified. Mean age was 69 years. On average (arithmetic mean ± standard deviation), 1.7 ± 1.0 previous PKs have been performed per eye in this cohort. The mean time between last PK and DMEK was 10.1 ± 7.3 years (range 2 to 23 years). In all cases, the graft diameter exceeded the diameter of the previous PK and descemetorhexis was performed in host tissue, that is, peripheral to the graft-host interface. Rebubbling was performed in 18.2% of the patients (n = 2 eyes) because of central graft detachment. Mean central corneal thickness showed a statistically significant improvement at 5.3 ± 3.5 months after surgery from 688.23 ± 151.01 to 527.75 ± 88 µm (p = 0.002).Visual acuity increased significantly by 5 lines from 1.24 ± 0.5 logMAR (range from 0.5 to 2) to 0.73 ± 0.76 logMAR (range from 0.1 to 2) within 3 months (p = 0.006). Excluding patients without visual potential and transplant failure, visual acuity improved significantly by 8 lines (p < 0.001), and stayed stable until the last follow-up at 15.1 ± 11.4 months (range 6 to 39 months, p < 0.001, n = 8) after surgery.ConclusionDMEK can be successfully used to treat endothelial cell failure after PK, and can provide good postoperative results with regards to visual acuity. This study shows that stripping of Descemet’s membrane (DM) peripheral to the PK interface is surgically feasible. Overlapping, larger DMEK grafts with more endothelial cells can be used without increasing rebubbling rates and may potentially improve long-term graft survival.

ObjectiveCardiovascular autonomic neuropathy is a common but underestimated diabetes-related disorder. Associations between cardiovascular autonomic dysfunction and subclinical inflammation, both risk factors of diabetic comorbidities and mortality, have been proposed in non-diabetic populations, while data for type 1 and type 2 diabetes are conflicting. Our aim was to investigate associations between inflammation-related biomarkers and cardiac autonomic dysfunction in patients with diabetes.MethodsWe characterised the associations between seven biomarkers of subclinical inflammation and cardiac autonomic dysfunction based on heart rate variability and cardiovascular autonomic reflex tests (CARTs) in 161 individuals with type 1 and 352 individuals with type 2 diabetes (time since diagnosis of diabetes <1 year). Analyses were adjusted for age, sex, anthropometric, metabolic and lifestyle factors, medication and cardiovascular comorbidities.ResultsIn individuals with type 2 diabetes, higher serum interleukin (IL)-18 was associated with lower vagal activity (p≤0.015 for association with CARTs), whereas higher levels of total and high-molecular-weight adiponectin showed associations with very low frequency power, an indicator of reduced sympathetic activity (p≤0.014). Higher levels of soluble intercellular adhesion molecule-1 were associated with indicators of both lower vagal (p=0.025) and sympathetic (p=0.008) tone, soluble E-selectin with one indicator of lower vagal activity (p=0.047). Serum C-reactive protein and IL-6 were also related to cardiac autonomic dysfunction, but these associations were explained by confounding factors. No consistent associations were found in individuals with type 1 diabetes.ConclusionsBiomarkers of inflammation were differentially associated with diminished cardiac autonomic dysfunction in recent-onset type 2 diabetes.

Abstract Context/Objective Impaired adipose tissue (AT) function might induce recent-onset type 2 diabetes (T2D). Understanding AT energy metabolism could yield novel targets for the treatment of T2D. Design/Patients Male patients with recently-diagnosed T2D and healthy male controls (CON) of similar abdominal subcutaneous AT (SAT)-thickness, fat mass, and age (n = 14 each), underwent hyperinsulinemic-euglycemic clamps with [6,6-2H2]glucose and indirect calorimetry. We assessed mitochondrial efficiency (coupling: state 3/4o; proton leak: state 4o/u) via high-resolution respirometry in superficial (SSAT) and deep (DSAT) SAT-biopsies, hepatocellular lipids (HCL) and fat mass by proton-magnetic-resonance-spectroscopy and -imaging. Results T2D patients (known diabetes duration: 2.5 [0.1; 5.0] years) had 43%, 44%, and 63% lower muscle insulin sensitivity (IS), metabolic flexibility (P < 0.01) and AT IS (P < 0.05), 73% and 31% higher HCL (P < 0.05), and DSAT-thickness (P < 0.001), but similar hepatic IS compared with CON. Mitochondrial efficiency was ~22% lower in SSAT and DSAT of T2D patients (P < 0.001) and ~8% lower in SSAT vs DSAT (P < 0.05). In both fat depots, mitochondrial coupling correlated positively with muscle IS and metabolic flexibility (r ≥ 0.40; P < 0.05), proton leak correlated positively (r ≥ 0.51; P < 0.01) and oxidative capacity negatively (r ≤ −0.47; P < 0.05) with fasting free fatty acids (FFA). Metabolic flexibility correlated positively with SAT-oxidative capacity (r ≥ 0.48; P < 0.05) and negatively with DSAT-thickness (r = −0.48; P < 0.05). DSAT-thickness correlated negatively with mitochondrial coupling in both depots (r ≤ −0.50; P < 0.01) and muscle IS (r = −0.59; P < 0.01), positively with FFA during clamp (r = 0.63; P < 0.001) and HCL (r = 0.49; P < 0.01). Conclusions Impaired mitochondrial function, insulin resistance, and DSAT expansion are AT abnormalities in recent-onset T2D that might promote whole-body insulin resistance and increased substrate flux to the liver.

Aim The objective of the study was to evaluate the long-term results of allogenic penetrating limbo-keratoplasy. This method allows simultaneous transplantation of a corneal graft and limbal stem cells of the donor by means of eccentric trephination of the donor button. Method The data of 192 consecutive cases of allogenic penetrating limbo-keratoplasty from 1995 to 2015 were reviewed. These had been performed exclusively in eyes with complete failure of the limbal stem cells, in combination with deep corneal scarring. Indications were predominantly eye burns, inflammatory conditions, and congenital aniridia. Graft survival and rejection rates were assessed using Kaplan–Meier analysis. Results Follow-up averaged 2.1±2.2 years. Median graft survival was 3.4 years in eye burns, 3.9 years in inflammatory disease, and 3.2 years in congenital aniridia. Median survival was 3.9 years in the heterogenous group of other indications. Conclusion Allogenic limbo-keratoplasty is a suitable option used to treat patients with bilateral complete failure of the limbal stem cells and deep opacification of the central cornea. The main reasons for graft failure are the loss of graft-limbal stem cell functioning and endothelial graft rejection.

Background Assess the intake of carbohydrate quality and their association with cardiovascular risk factors among diabetes subtypes. Methods Participants of the German Diabetes Study (GDS) (recent-onset diabetes (n = 487) and 5-years thereafter (n = 209)) were allocated into severe autoimmune diabetes (SAID, 35%), severe insulin-deficient diabetes (SIDD, 3%), severe insulin-resistant diabetes (SIRD, 5%), mild obesity-related diabetes (MOD, 28%), and mild age-related diabetes (MARD, 29%). Dietary glycemic index (GI), glycemic load (GL), and intake of higher- (≥ 55) and low-GI (< 55) foods, dietary fiber, and total sugar were derived from a validated food frequency questionnaire and cross-sectionally associated with cardiovascular risk factors (blood lipids, subclinical inflammation, blood pressure, fatty liver index) using multivariable linear regression analysis for subtypes with prevalences ≥ 10%. Results Intake of carbohydrate quality parameters was broadly comparable between the subtypes. Among SAID higher total sugar intake was associated with lower HDL-cholesterol (ß (95% CI) relative change per 1 SD increment: − 3.4% (− 6.7; − 0.1)). No clear associations were seen among MOD. Among MARD, a higher dietary GL and higher-GI carbohydrate intake were associated with higher serum triglycerides (10.9% (2.4; 20.1), 12.4% (3.9; 21.5)) and fatty liver index (absolute change: 0.18 (0.06; 0.31), 0.17 (0.05; 0.28)) and lower HDL-cholesterol (− 4.1% (− 7.6; − 0.4), − 4.4% (− 7.8; − 0.8)), whilst higher intake of low-GI carbohydrates and dietary fiber were associated with lower high-sensitivity C-reactive protein (− 16.0% (− 25.7; − 5.1), − 13.9% (− 24.2; − 2.2)). Conclusions Associations of carbohydrate quality parameters with blood lipids, subclinical inflammation, and fatty liver index differed between diabetes subtypes. However, evidence is too preliminary to derive subtype-specific recommendations. Trial registration Clinicaltrials.gov: NCT01055093.

IntroductionThe study aimed to assess the effect of COVID-19 on hepatic lipid (HL) content, fibrosis risk, and adiposity in persons with type 2 diabetes.Research design and methodsParticipants with type 2 diabetes with a history of mild COVID-19 (n=15, age 58±12 years, body mass index 30.9±5.2 kg/m2) were examined before (baseline) and 1 year (12±2 months) after (follow-up) recovery from COVID-19. Investigations for changes in metabolic risk comprised clinical examination, fasting blood sampling and MR-based measurements. Potential changes were corrected with the time course of the respective parameters in a group of participants who did not contract COVID-19 over the same time course (n=14, 61±6 years, 30.0±4.6 kg/m2).ResultsCOVID-19 resulted in a relative increase in HL content of 56% (95% CI 18%, 106%; p=0.04) measured as proton density fat fraction (HL-PDFF), corrected for the time course in the absence of COVID-19. While no changes in hepatic stiffness and volume, intramyocellular lipids, whole-body, subcutaneous and visceral adipose tissue volumes as well as homeostatic model assessment of insulin resistance and beta-cell function were observed.ConclusionsHistory of COVID-19 in persons with type 2 diabetes is associated with higher HL-PDFF after 1 year following recovery from infection.Trial registration numberNCT01055093.