Protective Effect of Amblyopia on Age-Related Macular Degeneration.

PURPOSE: Our aim was to evaluate whether patients with age-related macular degeneration (AMD) and cooccurrent amblyopia are more likely to have diseases diagnosed on both the ipsilateral and the contralateral side in a large Austrian database. DESIGN: Retrospective cross-sectional study. METHODS: Setting: Institutional practice. PATIENT POPULATION: Medical records of all patients who visited the Department of Ophthalmology of the Medical University of Graz between December 1996 and June 2021 were searched for the co-occurrence of AMD and amblyopia. MAIN OUTCOME MEASURES: Data from patients with AMD diagnosed on 1 eye side were used for further analysis. Spectral-domain optical coherence tomography images were analyzed to confirm the lateral asymmetry of AMD. RESULTS: A total of 327,443 patients were screened for the co-occurrence of AMD and amblyopia. Of them, 8742 patients had AMD diagnosed on 1 eye side and 5051 patients had unilateral amblyopia. In total, 163 patients were found to have AMD diagnosed on 1 side and unilateral amblyopia in combination. Of these, 126 patients had AMD and amblyopia on contralateral sides and 37 had AMD and amblyopia on the ipsilateral side (P < .001). CONCLUSIONS: Less amblyopic patients had AMD diagnosed on the amblyopic eye compared with the nonamblyopic eye. In cases of lateral asymmetry, the nonamblyopic eye is more likely to have the more advanced form of AMD.

Progression of PROM1-Associated Retinal Degeneration as Determined by Spectral-Domain Optical Coherence Tomography Over a 24-Month Period.

PURPOSE: To evaluate the progression of atrophy as determined by spectral-domain optical coherence tomography (SD-OCT) in patients with molecularly confirmed PROM1-associated retinal degeneration (RD) over a 24-month period. DESIGN: International, multicenter, prospective case series. METHODS: A total of 13 eyes (13 patients) affected with PROM1-associated RD were enrolled at 5 sites and SD-OCT images were obtained at baseline and after 24 months. Loss of mean thickness (MT) and intact area were estimated after semi-automated segmentation for the following individual retinal layers in the central subfield (CS), inner ring, and outer ring of the ETDRS grid: retinal pigment epithelium (RPE), outer segments (OS), inner segments (IS), outer nuclear layer (ONL), inner retina (IR), and total retina (TR). RESULTS: Statistically significant losses of thickness of RPE and TR were detected in the CS and inner ring and of ONL and IS in the outer ring (all P < .05); a statistically significant decrease in the intact area of RPE and IS was observed in the inner ring, and of ONL in the outer ring (all P < .05); the change in MT and the intact area of the other layers showed a trend of decline over an observational period of 24 months. CONCLUSIONS: Significant thickness losses could be detected in outer retinal layers by SD-OCT over a 24-month period in patients with PROM1-associated retinal degeneration. Loss of thickness and/or intact area of such layers may serve as potential endpoints for clinical trials that aim to slow down the disease progression of PROM1-associated retinal degeneration.

Idebenone Treatment in Patients with OPA1-Dominant Optic Atrophy: A Prospective Phase 2 Trial.

The aim of this study was to evaluate the therapeutic effect of idebenone in patients with OPA1-dominant optic atrophy (DOA). Sixteen patients with genetically confirmed OPA1-DOA were treated with 900 mg idebenone daily for 12 months. The primary endpoint was the best recovery/least deterioration of visual acuity. Secondary endpoints were the changes of visual acuity, colour vision, contrast sensitivity, visual field, peripapillary retinal nerve fibre layer thickness (pRNFLT), and visual-related quality of life. For the primary endpoint, a significant increase was observed for the right eye (p = .0027), for the left eye (p = .0111) and for the better-seeing eye (p = .0152). For visual fields, a significant improvement was observed for the left eye between baseline and 9 months (p = .0038). Regarding pRNFLT, a significant decrease was found for the left eye between baseline and 3 months (p = .0413) and between baseline and 6 months (p = .0448). In the visual function questionnaire, a significant improvement was observed in the subscale general vision (p = .0156) and in the composite score (p = .0256). In conclusion, best recovery of visual acuity improved, even though the amount of improvement was small. Furthermore, a maintenance of visual function after 12 months of idebenone intake could be observed as well as a significant improvement in vision-related quality of life.Whether this effect is due to idebenone treatment, the placebo effect, or is explainable by the natural progression of DOA, remains unclear. Trial registration: EU Clinical Trials Register, EudraCT Number: 2019-001493-28.

BendaEAM versus BEAM as conditioning regimen for ASCT in patients with relapsed lymphoma (BEB): a multicentre, randomised, phase 2 trial.

Background: Replacement of carmustine (BCNU) in the BEAM regimen (BCNU, etoposide, cytarabine, melphalan) with bendamustine (BendaEAM) before autologous stem cell transplantation (ASCT) is feasible in lymphoma. However, randomised trials are lacking. Here, we present the first trial addressing this topic. Methods: This multicentre, randomised, phase 2 study (BEB-trial) conducted at four haematological centres in Austria and Switzerland compares BEAM with BendaEAM in patients with relapsed lymphoma. Both regimens were administered intravenously before ASCT, in BEAM according to the standard protocol (300 mg/m2 BCNU on day -6), in BendaEAM, BCNU was replaced by 200 mg/m2 bendamustine given on days -7 and -6. Eligible patients were aged 18-75 years and had mantle cell lymphoma, diffuse large B-cell lymphoma, or follicular lymphoma in first or second remission or chemosensitive relapse. The primary endpoint of the study was to evaluate whether replacement of BCNU by bendamustine reduces lung toxicity, defined as a decrease of the diffusion capacity of the lung for carbon monoxide by at least 20% at three months after ASCT. Data analyses were performed on an intention-to-treat basis. This study is registered with ClinicalTrials.gov, number NCT02278796, and is complete. Findings: Between April 20, 2015, and November 28, 2018, 108 patients were enrolled; of whom 53 were randomly assigned to receive BendaEAM (36 male, 17 female) and 55 to receive BEAM (39 male, 16 female). All patients engrafted rapidly. Lung toxicity did not differ between groups (BendaEAM: n = 8, 19.5%; BEAM: n = 11, 25.6%; risk difference = -6.1%: 95% confidence interval: -23.9% to 11.7%). Acute toxicities of at least grade 3 were comparable in both groups (BendaEAM: 35.8%, BEAM: 30.9%). Overall survival (BendaEAM: 92.5%, BEAM: 89.1%) and complete remission (BendaEAM: 76.7%, BEAM: 74.3%) after 1 year (median follow-up: 369 days) were similar. No difference in quality of life was observed. Interpretation: Results were similar for both regimens in terms of survival and response rates. A phase 3 non-inferiority study is required to investigate whether BendaEAM can be considered as an alternative to BEAM. Funding: Mundipharma.

Effects of an online information tool on post-traumatic stress disorder in relatives of intensive care unit patients: a multicenter double-blind, randomized, placebo-controlled trial (ICU-Families-Study).

PURPOSE: Intensive care unit (ICU) hospitalization is challenging for the family members of the patients. Most family members report some level of anxiety and depression, sometimes even resulting in post-traumatic stress disorder (PTSD). An association has been reported between lack of information and PTSD. This study had three aims: to quantify the psychological burden of family members of critically ill patients, to explore whether a website with specific information could reduce PTSD symptoms, and to ascertain whether a website with information about intensive care would be used. METHOD: A multicenter double-blind, randomized, placebo-controlled trial was carried out in Austria and Switzerland. RESULTS: In total, 89 members of families of critically ill patients (mean age 47.3 ± 12.9 years, female n = 59, 66.3%) were included in the study. 46 relatives were allocated to the intervention website and 43 to the control website. Baseline Impact of Event Scale (IES) score was 27.5 ± 12.7. Overall, 50% showed clinically relevant PTSD symptoms at baseline. Mean IES score for the primary endpoint (~ 30 days after inclusion, T1) was 24 ± 15.8 (intervention 23.9 ± 17.9 vs. control 24.1 ± 13.5, p = 0.892). Hospital Anxiety and Depression Scale (HADS - Deutsch (D)) score at T1 was 12.2 ± 6.1 (min. 3, max. 31) and did not differ between groups. Use of the website differed between the groups (intervention min. 1, max. 14 vs. min. 1, max. 3; total 1386 "clicks" on the website, intervention 1021 vs. control 365). Recruitment was prematurely stopped in February 2020 due to coronavirus disease 2019 (COVID-19). CONCLUSION: Family members of critically ill patients often have significant PTSD symptoms and online information on critical illness did not result in reduced PTSD symptoms.

Diagnostic value of two-time point [68Ga]Ga-PSMA-11 PET/CT in the primary staging of untreated prostate cancer.

The emerging PET tracer [68Ga]Ga-PSMA-11 has been established for staging in prostate cancer (PCa). Aim was to determine the value of early static imaging in two-phase PET/CT. 100 men with newly diagnosed histopathologically confirmed untreated PCa who underwent [68Ga]Ga-PSMA-11 PET/CT from January 2017 to October 2019 were included. The two-phase imaging protocol consisted of an early static scan of the pelvis (6 min p.i.) and a late total-body scan (60 min p.i). Associations of semi-quantitative parameters derived via volumes of interest (VOI) with Gleason grade group and PSA were investigated. In 94/100 patients (94%) the primary tumor was detected in both phases. In 29/100 patients (29%) metastases were detected at a median PSA level of 32.2 ng/ml (0.41-503 ng/ml). In 71/100 patients (71%) without metastasis a median PSA level of 10.1 ng/ml (0.57-103 ng/ml) was observed (p = < 0.001). Primary tumors demonstrated a median standard uptake value maximum (SUVmax) of 8.2 (3.1-45.3) in early phase versus 12.2 (3.1-73.4) in late phase and a median standard uptake value mean (SUVmean) of 4.2 (1.6-24.1) in early phase versus 5.8 (1.6-39.9) in late phase, significantly increasing over time (p = < 0.001). Higher SUVmax and SUVmean were associated with higher Gleason grade group (p = 0.004 and p = 0.003, respectively) and higher PSA levels (p = < 0.001). In 13/100 patients the semi-quantitative parameters including SUVmax were declining in the late phase compared to early phase. Two-phase [68Ga]Ga-PSMA-11 PET/CT demonstrates a high detection rate for primary tumor of untreated PCa of 94% and improves diagnostic accuracy. Higher PSA levels and Gleason grade group are associated with higher semi-quantitative parameters in the primary tumor. Early imaging provides additional information in a small sub-group with declining semi-quantitative parameters in the late phase.

Probiotic vs. placebo and metformin: probiotic dietary intervention in polycystic ovary syndrome - A randomized controlled trial.

BACKGROUND: Polycystic Ovary Syndrome (PCOS) is a very common endocrine disorder with a variety of symptoms. Current treatment options include the contraceptive pill as well as metformin, however both treatments are limited to specific symptoms and have common side effects. METHODS: This phase IV study is a monocentric, double blinded randomized clinical trial comparing the effects of six months of probiotic intervention to a placebo, with an additional open-label metformin arm as a positive control in a total of 180 participants with PCOS. The first of three visits is the screening visit, where inclusion/exclusion criteria are assessed. At the first visit, they are randomised into one of the three treatment arms equally and receive their study medication. After six months, all assessments from the first two visits are repeated. The primary endpoint is the change in free testosterone levels after the intervention, while secondary endpoints include changes in hormonal and metabolic parameters associated with PCOS as well as the gut microbial composition and diversity after intervention. DISCUSSION: Based on new insights into the role of the gut microbiome in PCOS development, this study is exploring the potential of using probiotics to treat women with PCOS symptoms. If successful, this new therapy approach could open a new realm of possibilities for treating PCOS. To our knowledge, this is the first study comparing probiotic intervention with not only placebo treatment, but also metformin. This study has been approved by the ethics committee of the Medical University of Graz (EC number 32-230 ex 19/20). REGISTRATION: EudraCT number: 2020-000228-20. CLINICALTRIALS: gov identifier: NCT04593459. PROTOCOL VERSION: Version 1.5 dated 29th November 2021.

Glucose Metabolism and Metabolomic Changes in Response to Prolonged Fasting in Individuals with Obesity, Type 2 Diabetes and Non-Obese People-A Cohort Trial.

Metabolic regulation of glucose can be altered by fasting periods. We examined glucose metabolism and metabolomics profiles after 12 h and 36 h fasting in non-obese and obese participants and people with type 2 diabetes using oral glucose tolerance (OGTT) and intravenous glucose tolerance testing (IVGTT). Insulin sensitivity was estimated by established indices and mass spectrometric metabolomics was performed on fasting serum samples. Participants had a mean age of 43 ± 16 years (62% women). Fasting levels of glucose, insulin and C-peptide were significantly lower in all cohorts after 36 h compared to 12 h fasting (p < 0.05). In non-obese participants, glucose levels were significantly higher after 36 h compared to 12 h fasting at 120 min of OGTT (109 ± 31 mg/dL vs. 79 ± 18 mg/dL; p = 0.001) but insulin levels were lower after 36 h of fasting at 30 min of OGTT (41.2 ± 34.1 mU/L after 36 h vs. 56.1 ± 29.7 mU/L; p < 0.05). In contrast, no significant differences were observed in obese participants or people with diabetes. Insulin sensitivity improved in all cohorts after 36 h fasting. In line, metabolomics revealed subtle baseline differences and an attenuated metabolic response to fasting in obese participants and people with diabetes. Our data demonstrate an improved insulin sensitivity after 36 h of fasting with higher glucose variations and reduced early insulin response in non-obese people only.

Postoperative Pain after Different Transscleral Laser Cyclophotocoagulation Procedures.

BACKGROUND: As the number of surgical options in glaucoma treatment is continuously rising, evidence regarding distinctive features of these surgeries is becoming more and more important for clinicians to choose the right surgical treatment for each individual patient. METHODS: For this retrospective data analysis, we included glaucoma patients treated with either continuous wave (CW-TSCPC) or micropulse transscleral cyclophotocoagulation (MP-TSCPC) in an inpatient setting. Pain intensity was assessed using a numeric rating scale (NRS) ranging from 0 (no pain) to 10 (worst imaginable pain) during hospitalization. CW-TSCPC was performed using OcuLight® Six (IRIDEX Corporation, Mountain View, CA, USA) and MP-TSCPC was performed using the IRIDEX® Cyclo-G6 System (IRIDEX Corporation, Mountain View, CA, USA). RESULTS: A total of 243 consecutive cases of TSCPC were included. Of these, 144 (59.26%) were treated with CW-TSCPC and 99 (40.74%) with MP-TSCPC. Using the univariable model, the risk for postoperative pain was observed to be lower in MP-TSCPC compared with CW-TSCPC (unadjusted: OR 0.46, 95% CI 0.24-0.84, p = 0.017), but this did not hold using the multivariable model (adjusted: OR 0.52, 95% CI 0.27-1.02, p = 0.056). Simultaneously conducted anterior retinal cryotherapy was associated with a higher risk for postoperative pain (OR 4.41, 95% CI 2.01-9.69, p < 0.001). CONCLUSIONS: We found that the occurrence of postoperative pain was not different in CW-TSCPC compared with MP-TSCPC in a multivariable model. In cases of simultaneous anterior retinal cryotherapy, the risk for postoperative pain was significantly higher.

Risk factors for serious infections in ANCA-associated vasculitis.

OBJECTIVES: Severe infections contribute to morbidity and mortality in antineutrophil cytoplasm antibody-associated vasculitis (AAV). This study aimed to identify risk factors associated with severe infections in participants of the Rituximab versus Cyclophosphamide for ANCA-Associated Vasculitis (RAVE) trial. METHODS: Data on 197 patients recruited into the RAVE trial were analysed. Participants received either rituximab (RTX) or cyclophosphamide (CYC), followed by azathioprine (AZA). Clinical and laboratory data of patients with and without severe infections (≥grade 3, according to the Common Terminology Criteria for Adverse Events version 3.0) were compared. Risk factors for severe infections were investigated using Cox-regression models. RESULTS: Eighteen of 22 (82%) severe infections occurred within 6 months after trial entry, most commonly respiratory tract infections (15/22, 68%). At baseline, lower absolute numbers of CD19+ cells were observed in patients with severe infections either receiving RTX or CYC/AZA at baseline, while CD5+B and CD3+T cells did not differ between groups. In Cox-regression analysis, higher baseline serum immunoglobulin M levels were associated with the risk of severe infections, whereby a higher baseline total CD19+B cell number and prophylaxis against Pneumocystis jirovecii with trimethoprim-sulfamethoxazole (TMP/SMX) with decreased risk of severe infections. Use of TMP/SMX was associated with lower risk of severe infections in both groups, receiving either RTX or CYC/AZA. CONCLUSIONS: The use of low-dose TMP/SMX is associated with reduced risk of severe infections in patients with AAV treated with either RTX or CYC/AZA. Reduced B cell subpopulations at start of treatment might be a useful correlate of reduced immunocompetence.

Neurofilament light chain: a new marker for neuronal decay in the anterior chamber fluid of patients with glaucoma.

BACKGROUND/AIMS: Neurofilament light chain (NfL) levels in cerebrospinal fluid and serum are reliable indicators for neuroaxonal damage in a broad spectrum of neurodegenerative diseases. Herein, we investigate NfL levels in serum and anterior chamber fluid of patients with glaucoma. METHODS: Patients scheduled for routine glaucoma or cataract surgery were recruited for this study. Retinal nerve fibre layer thickness was measured by optical coherence tomography (OCT, Heidelberg Spectralis). NfL levels in serum and in anterior chamber fluid were analysed with Simoa SR-X Analyzer (Quanterix; NFLIGHT, Lexington, Massachusetts, USA). T-test was used for parametric data and Mann-Whitney-U test for nonparametric data. Spearman's rank-order correlation was used to investigate correlations. P values<0.05 were considered as statistically significant. RESULTS: Sixty patients with glaucoma and 58 controls were enrolled. Serum NfL concentration of patients with glaucoma was similar to serum NfL concentration in controls (median (IQR); 22.7 (18.9) pg/mL vs 22.5 (24.0) pg/mL; p=0.763). A positive correlation of serum NfL with age was observed in both patients with glaucoma (r=0.77; p<0.001) and in the control group (r=0.82, p<0.001). In the anterior chamber fluid, the NfL concentration was substantially increased in patients with glaucoma compared with controls (20.7 (101.3) pg/mL vs 3.1 (2.9) pg/mL; p<0.001). Furthermore, we found a positive correlation of anterior chamber fluid NfL with preoperative intraocular pressure (r=0.39, p=0.003) and with retinal nerve fibre layer thickness (r=0.58, p<0.001). CONCLUSION: NfL levels in anterior chamber fluid are elevated in patients with glaucoma and correlate with intraocular pressure and retinal nerve fibre layer thickness. The presented data strongly support anterior chamber fluid NfL as a new marker for glaucoma.

Evaluating a Periapical Lesion Detection CNN on a Clinically Representative CBCT Dataset-A Validation Study.

The aim of this validation study was to comprehensively evaluate the performance and generalization capability of a deep learning-based periapical lesion detection algorithm on a clinically representative cone-beam computed tomography (CBCT) dataset and test for non-inferiority. The evaluation involved 195 CBCT images of adult upper and lower jaws, where sensitivity and specificity metrics were calculated for all teeth, stratified by jaw, and stratified by tooth type. Furthermore, each lesion was assigned a periapical index score based on its size to enable a score-based evaluation. Non-inferiority tests were conducted with proportions of 90% for sensitivity and 82% for specificity. The algorithm achieved an overall sensitivity of 86.7% and a specificity of 84.3%. The non-inferiority test indicated the rejection of the null hypothesis for specificity but not for sensitivity. However, when excluding lesions with a periapical index score of one (i.e., very small lesions), the sensitivity improved to 90.4%. Despite the challenges posed by the dataset, the algorithm demonstrated promising results. Nevertheless, further improvements are needed to enhance the algorithm's robustness, particularly in detecting very small lesions and the handling of artifacts and outliers commonly encountered in real-world clinical scenarios.

Disease Management Program in patients with type 2 diabetes mellitus, long-term results of the early and established program cohort: A population-based retrospective cohort study.

BACKGROUND: The aim of this study was to evaluate the long-term follow up of the early and the effectiveness of the established program of the Austrian Disease Management Program (DMP) 'Therapie aktiv-Diabetes im Griff' for patients with type 2 diabetes mellitus concerning mortality, major macrovascular complications, costs and process quality of care parameters. METHODS: We conducted a propensity score matched cohort study based on routine health insurance data for type 2 diabetic patients. The observational period from the matched early program cohort starts from January 1, 2009 to December 31, 2017 and includes 7181 DMP participants and 21543 non-participants. In the established matched program cohort, 3087 DMP participants and 9261 non-participants were observed within January 1, 2014 to December 31, 2017. RESULTS: In the early program cohort, 22.1% of the patients in the DMP-group and 29.7% in the control-group died after 8 years follow-up (HR = 0.70; 95% CI: 0.66-0.73). A difference of € 1070 (95% bootstrap-T interval: € 723 - € 1412) in mean total costs per year was observed. In the established program cohort, 10.4% DMP participants died 4 years after enrollment, whereas in the control-group 11.9% of the patients died (HR = 0.88, 95% CI: 0.78-0.99). Healthcare utilization is higher in the DMP-group (75%-96%) compared to the control-group (63%-90%). CONCLUSIONS: The 8-year long-term follow up of the DMP program showed a relevant improvement of survival and healthcare costs of patients with type 2 diabetes. The established program cohort had improved survival and quality of care. Our findings indicate that the DMP "Therapie aktiv" provides a long-term advantage for type 2 diabetes patients.

The impact of surgeon's experience and sex on the incidence of cystoid macular edema after uneventful cataract surgery.

PURPOSE: To assess the rate of pseudophakic cystoid macular edema (pCME) in uneventful cataract surgery in surgeons in training vs experienced surgeons and to analyze the rate of pCME according to surgeon's sex. METHODS: Medical reports post phacoemulsification between 2010 and 2018 at the Department of Ophthalmology, Medical University of Graz, Austria, were reviewed for pCME. A running lifetime number of preceding cataract surgeries was used to express hands-on experience. A cut-off number of 300 surgeries was defined to distinguish between surgeons in training and experienced surgeons. Outcome parameters were incidence of pCME, patient's sex and age, laterality of eye, coexistence of pseudoexfoliation syndrome (PEX), duration of surgery and surgeon's sex. RESULTS: 25.422 surgeries on 18.266 patients were included. The majority was performed by experienced surgeons (23.139, 91.0%) vs 2.283 (9.0%) by surgeons in training (25 surgeons, 9 (36%) female and 16 (64%) male). pCME occurred in 32 eyes (1.4%) following surgery by surgeons in training and in 152 eyes (0.7%) following surgery by experienced surgeons. Chance for pCME was 1.57 higher in training surgeries (95% CI 1.03-2.41, p = 0.034) and longer duration (OR = 1.04; 95% CI 1.02-1.07, p = 0.001). After excluding the first 100 surgeries for every surgeon in training similar results were observed. No difference in risk for pCME was found between female and male surgeons in both groups (training and experienced surgeons). CONCLUSION: In conclusion, the rate for pCME after uneventful cataract surgery is significantly higher for surgeons in training but steadily decreasing and associated to surgical time. No difference in the risk for pCME was found between female and male surgeons.

Blindness and visual impairment in Central Europe.

PURPOSE: To assess the prevalence and causes of visual impairment and blindness in a Central European country. The findings may have implications for the planning of further research and development of therapies in order to prevent blindness. SETTING: Department of Ophthalmology, Medical University of Graz, Austria. DESIGN: Retrospective, epidemiological study. METHODS: The database of the Main Confederation of Austrian Social Insurances was searched for patients with visual impairment, legal blindness or deaf-blindness. This database gathers data from patients of all insurance providers in the country who receive care due to visual impairment and blindness. To determine the prevalence of these conditions, the number of all entries recorded in February 2019 was evaluated. Additionally, all new entries between (January 1st,) 2017, and (December 31st,) 2018, were analysed for distinct characteristics, such as sex, the cause of blindness/visual impairment, and age. Since health care allowances can provide a considerable source of income (459.90€-936.90€ per month), good coverage of practically all patients who are blind and visually impaired in the country can be assumed. RESULTS: On February 2nd, 2019, 17,730 patients with visual impairments, blindness or deaf-blindness were registered in Austria, resulting in a prevalence of these diagnoses of 0.2% in the country. During the observational period from 2017 to 2018, 4040 persons met the inclusion criteria. Of these, 2877 were female (65.3%), and 1527 were male (34.7%). The mean age was 75.7 ± 18.0 years (median 82). Most patients (n = 3675, 83.4%) were of retirement age, while 729 (16.6%) were working-age adults or minors. In total, an incidence of 25.0 (95% confidence limit (CL) 24.3-25.8) per 100,000 person-years was observed from 2017 to 2018. A higher incidence was observed for females (32.2, 95% CL 31.0-33.3) than for males (17.7, 95% CL 16.8-18.5). Incidences where higher for males in lower age groups (e.g. 10-14 years: rate ratio RR = 2.7, 95% CL 1.1-6.8), and higher for females in higher age groups (e.g. 70-74 years: RR = 0.6, 95% CL 0.5-0.8). In total, the most frequent diagnoses were macular degeneration (1075 persons, 24.4%), other retinal disorders (493 persons, 11.2%) and inherited retinal and choroidal diseases (IRDs) (186 persons, 4.2%). Persons with IRDs were significantly younger compared to persons with macular degeneration or retinal disorders (IRDs: median 57, range 2-96 vs 83, 5-98 and 82, 1-98 years, p<0.001). For persons of retirement age, macular degeneration, other retinal disorders and glaucoma were the three most frequent diagnoses. In contrast, among working-aged adults and children, IRDs were the leading cause of visual impairment and blindness (103 persons, 14.1%). CONCLUSION: These data show that IRDs are the leading cause of blindness and visual impairment in working-aged persons and children in Austria. Thus, these findings suggest to draw attention to enhance further research in the fields of emerging therapies for IRDs.

The Risk of Severe Infections Following Rituximab Administration in Patients With Autoimmune Kidney Diseases: Austrian ABCDE Registry Analysis.

Objective: To characterize the incidence, type, and risk factors of severe infections (SI) in patients with autoimmune kidney diseases treated with rituximab (RTX). Methods: We conducted a multicenter retrospective cohort study of adult patients with immune-related kidney diseases treated with at least one course of RTX between 2015 and 2019. As a part of the ABCDE Registry, detailed data on RTX application and SI were collected. SI were defined by Common Terminology Criteria for Adverse Events v5.0 as infectious complications grade 3 and above. Patients were dichotomized between "nephrotic" and "nephritic" indications. The primary outcome was the incidence of SI within 12 months after the first RTX application. Results: A total of 144 patients were included. Twenty-five patients (17.4%) presented with SI, mostly within the first 3 months after RTX administration. Most patients in the nephritic group had ANCA-associated vasculitis, while membranous nephropathy was the leading entity in the nephrotic group. Respiratory infections were the leading SI (n= 10, 40%), followed by urinary tract (n=3, 12%) and gastrointestinal infections (n=2, 8%). On multivariable analysis, body mass index (BMI, 24.6 kg/m2versus 26.9 kg/m2, HR: 0.88; 95%CI: 0.79-0.99; p=0.039) and baseline creatinine (HR: 1.25; 95%CI: 1.04-1.49; p=0.017) were significantly associated with SI. All patients in the nephritic group (n=19; 100%) who experienced a SI received oral glucocorticoid (GC) treatment at the time of infection. Hypogammaglobulinemia was frequent (58.5%) but not associated with SI. Conclusions: After RTX administration, impaired kidney function and lower BMI are independent risk factors for SI. Patients with nephritic glomerular diseases having concomitant GC treatment might be at higher risk of developing SI.

Cotinine and cytokine levels in the vitreous body and blood serum of smokers and non-smokers - A pilot study.

Tobacco smoking is a risk factor for many ocular diseases. Of the multiple tobacco smoke compounds nicotine and its main metabolite cotinine are likely agents in disease modulation. The interaction of these compounds with exposed tissue is complex and ranges from proinflammatory to potentially neuroprotective properties. We aimed to determine cotinine and cytokines in the vitreous in smokers and non-smokers in this prospective, cross-sectional study at the Department of Ophthalmology, Medical University Graz, Austria. We included 10 smokers and 10 non-smokers. Vitreous and serum samples were analyzed for cotinine and cytokines. The cytokine analysis was performed with multiplex assay and cotinine was quantified with enzyme-linked immunosorbent assay. Cotinine was detectable in smokers only with a mean of 154.0 ng/ml ± 107.3 ng/ml in the vitreous and of 194.1 ng/ml ± 121.3 ng/ml in the serum. The difference between intraocular and systemic levels was statistically significant. There were no statistically significant differences between the cytokine levels of smokers and non-smokers. However, intravitreal VEGF-A was by trend elevated in smokers and correlated positively with intravitreal cotinine (r = 0.59, p = 0.073). In conclusion cotinine is detectable in the vitreous of smokers and is lower than the serum. There is a trend towards elevation of VEGF-A in the vitreous of smokers.

The Impact of Tape Sealing Face Masks on Visual Field Scores in the Era of COVID-19: A Randomized Cross-over Study.

PRECIS: Tape sealing of the face mask can prevent fogging artifacts of visual field testing. Here, we demonstrate that tape sealing can improve visual field scores even when fogging artifacts are not obvious. PURPOSE: The purpose of this study was to demonstrate that visual field scores improve when the face masks are taped to prevent fogging artifacts. METHODS: A Single-center, randomized 2×2 cross-over study. Twenty-six visual fields of 13 patients of the glaucoma outpatient clinic were included. Patients were randomized in either sequence 1 (Octopus visual field examination without tape sealing, followed by examination with tape sealing) or sequence 2 (examination with, followed by without tape sealing). RESULTS: The results for mean defect and square root of loss variance differ significantly in the examination with and without tape sealing [mean difference (without-with) 0.39 dB, 95% confidence interval: 0.07-0.70 dB, P=0.018 and 0.49 dB, 95% confidence interval: 0.19-0.79 dB, P=0.003, respectively]. There was no sequence effect (P=0.967) for mean defect nor the square root of loss variance (P=0.779). A significant effect for period (P=0.023) for mean defect was yielded. CONCLUSION: Tape sealing of face masks during visual field testing prevented fogging artifacts and improved visual field scores even when fogging artifacts were not obvious and should be considered in clinical practice.