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Laura Hoffmann,1,2,&ast; Susanne Müller,1,3,&ast; Lucas M Bachmann,4,5 Daniela Claessens,6 Katja Hatz1,7 1Medical Retina & Research Department, Vista Eye Clinic Binningen, Binningen, Switzerland; 2Department of Ophthalmology, University Hospital Charité - Campus Benjamin Franklin, Berlin, Germany; 3Department for Health Sciences, Donau University Krems, Krems, Austria; 4Oculocare Medical, Medignition AG, Zurich, Switzerland; 5Faculty of Medicine, University of Zurich, Zurich, Switzerland; 6Gemeinschaftspraxis Augenheilkunde Lindenthal, Cologne, Germany; 7Faculty of Medicine, University of Basel, Basel, Switzerland&ast;These authors contributed equally to this workCorrespondence: Katja Hatz, Vista Augenklinik, Hauptstrasse 55, Binningen, 4102, Switzerland, Tel +41 61 426 60 79, Fax +41 61 426 60 01, Email katja.hatz@unibas.ch; katja.hatz@vista.chPurpose: To assess the ability of two self-monitoring digital devices to detect metamorphopsia in myopic choroidal neovascularization (mCNV) and compare their usability.Patients and Methods: This was a 12-month prospective observational study at a tertiary care eye hospital, Switzerland. Twenty-three Caucasian patients with mCNV were recruited, 21 eyes were analyzed. Primary and secondary outcome measures: Primary outcome measures were the metamorphopsia index scores as assessed by the two self-monitoring digital devices (Alleye App and AMD – A-Metamorphopsia-Detector software) at baseline, at 6 and 12 months and individual optional visits in between. Secondary outcome measures included best corrected visual acuity and morphological parameters (including disease activity) as evaluated by spectral-domain optical coherence tomography and fundus autofluorescence imaging. Location of mCNV was graded using the Early Treatment of Diabetic Retinopathy Study grid overlay. A usability questionnaire was administered at 12 months. Bland-Altman plots evaluated the limits of agreement of both devices. Linear regression analysis assessed the correlation between the difference and the average of the two scores.Results: A total of 202 tests were performed. Disease activity of mCNV was observed at least once in 14 eyes. Both scores concordantly detected metamorphopsia exhibiting a displaced scale of measurement yielding a coefficient of determination of 0.99. Concordance rate for pathological scores was 73.3%. Both scores were not significantly different in active and inactive mCNV. Overall, the usability scores were higher for the Alleye App than the AMD – A-Metamorphopsia-Detector software (4.61± 0.56 vs 3.31± 1.20; p< 0.001). In subjects aged > 75 years, scores were slightly lower (4.08± 0.86 vs 2.97± 1.16; p= 0.032).Conclusion: Whilst both self-monitoring devices concordantly identified metamorphopsia, they might act as an adjunct to hospital visits, but due to slight reactivations in mCNV and presence of metamorphopsia also in inactive disease the ability of detecting early mCNV activity might be limited.Keywords: myopic CNV, metamorphopsia, disease activity, self-monitoring, optical coherence tomography

Objective To assess the degree of resilience in patients with CRPS 1, to explore the relationship between resilience and patient-related outcome measurements and to describe a pattern of clinical manifestations associated with low resilience. Methods This study presents a cross-sectional analysis of baseline information collected from patients enrolled in a single center study between February 2019 and June 2021. Participants were recruited from the outpatient clinic of the Department of Physical Medicine & Rheumatology of the Balgrist University Hospital, Zurich, Switzerland. We used linear regression analysis to explore association of resilience with patient reported outcomes at baseline. Further, we explored the impact of significant variables on the low degree resilience using logistic regression analysis. Results Seventy-one patients (females 90.1%, mean age 51.2 ± 12.9 years) were enrolled. There was no association between CRPS severity and the level of resilience. Quality of Life was positively correlated with resilience, as was pain self-efficacy. Pain catastrophizing was inversely correlated with the level of resilience. We observed a significant inverse association between anxiety, depression and fatigue and the level of resilience. The proportion of patients with a low resilience increased with higher level of anxiety, depression and fatigue on the PROMIS-29, without reaching statistical significance. Conclusion Resilience seems to be an independent factor in CRPS 1 and is associated with relevant parameters of the condition. Therefore, caretakers may screen the current resilience status of CRPS 1 patients to offer a supplementary treatment approach. Whether specific resilience training modifies CRPS 1 course, requires further investigations.

The purpose of this study was to assess the diagnostic performance of measurements from a new noninvasive, automated ocular surface analyzer (IDRA) in the diagnosis of dry eye disease (DED).We prospectively identified patients with and without DED using best practice methods. Subsequently, all participants underwent IDRA analysis, consisting of 5 components: noninvasive tear film break-up time, tear meniscus height, lipid layer interferometry, eye blink quality, and infrared meibography. The manufacturer provides cutoff values for a pathologic result for each of these components. Using a stepwise augmentation multivariate logistic regression model, we identified the components with the strongest association for the presence of DED. For the 3 components with the strongest association (interferometry, tear meniscus, and infrared meibography), we calculated the probability of DED.We enrolled 40 patients (80 eyes) with DED (mean age 60.5 years; women 78.3%) and 35 healthy subjects (70 eyes, mean age 31.1 years; women 21.7%). The IDRA had an area under the curve of 0.868 (95% confidence interval: 0.809-0.927) to detect DED. A normal (≥80) interferometry combined with a normal (0.22) tear meniscus and a normal (≤40) infrared meibography was associated with an estimated probability of 18% for the presence of DED, whereas the estimated probability of DED was as high as 96% when all 3 findings were pathologic.The results of IDRA showed a positive concordance with routine clinical diagnostic tests. The new analyzer is an easy-to-access diagnostic tool to rule out the presence of DED in the extramural setting and to guide a timely DED treatment.

PURPOSE: We describe the large-scale self-initiated recruitment of patients to a self-monitoring initiative for macular pathologic features during the coronavirus disease 2019 (COVID-19) pandemic. DESIGN: Observational study with retrospective analysis. PARTICIPANTS: A total of 2272 patients from the Singapore National Eye Centre (SNEC) whose visits were rescheduled over lockdown (April 13-June 1, 2020) were offered participation in a self-monitoring initiative administered by SNEC with the Alleye application (Switzerland) as the testing instrument. METHODS: This was an observational study with retrospective analysis. Demographics and characteristics were compared between those who signed up and those who did not. Similar comparisons were made between patients who complied with the initiative versus those who did not. Outcomes were tracked for 6 months starting from the commencement of lockdown. MAIN OUTCOME MEASURES: Participation and compliance rates and characteristics of patients who were more likely to participate and comply with the initiative. RESULTS: Seven hundred thirty-two patients (32%) participated in this self-monitoring initiative. Those who participated were younger (62 years of age vs. 68 years of age; P < 0.001), men, and living with family. Patients not receiving treatment and those with poorer vision in the worse-seeing eye were more likely to participate. When grouped according to diagnosis, the proportion who participated was highest for diabetic macular edema (52%), nonneovascular age-related macular degeneration (AMD; 42%), diabetic retinopathy (35%), retinal vein occlusions (18%), and neovascular AMD (15%; P < 0.001). Testing compliance rate was 43% (315/732). Patients who complied with the initiative were older, were receiving treatment, and had poorer vision in the worse-seeing eye. Trigger events occurred in 33 patients, with 5 patients having clinically verified disease progression (1.6%). CONCLUSIONS: We provide clinical data on characteristics of patients with stable retinal diseases who were offered, participated in, and complied with a self-monitoring program. The lower participation rate compared with standardized clinical studies reflects the difficulties in implementation for such initiatives in clinical settings. Despite this, self-monitoring continues to show promise in relieving clinic resources, suggesting the feasibility of scaling such programs beyond the COVID-19 pandemic.

Purpose To evaluate the predictive usefulness of quantitative imaging biomarkers, acquired automatically from OCT scans, of cross-sectional and future visual outcomes of patients with neovascular age-related macular degeneration (AMD) starting anti–vascular endothelial growth factor (VEGF) therapy. Design Retrospective cohort study. Participants Treatment-naive, first-treated eyes of patients with neovascular AMD between 2007 and 2017 at Moorfields Eye Hospital (a large, United Kingdom single center) undergoing anti-VEGF therapy. Methods Automatic segmentation was carried out by applying a deep learning segmentation algorithm to 137 379 OCT scans from 6467 eyes of 3261 patients with neovascular AMD. After applying selection criteria, 926 eyes of 926 patients were analyzed. Main Outcome Measures Correlation coefficients (R2 values) and mean absolute error (MAE) between quantitative OCT (qOCT) parameters and cross-sectional visual function, as well as the predictive value of these parameters for short-term visual change, that is, incremental visual acuity (VA) resulting from an individual injection, as well as VA at distant time points (up to 12 months after baseline). Results Visual acuity at distant time points could be predicted: R2 = 0.80 (MAE, 5.0 Early Treatment Diabetic Retinopathy Study [ETDRS] letters) and R2 = 0.7 (MAE, 7.2 ETDRS letters) after injection at 3 and at 12 months after baseline (P Conclusions Automatic segmentation enables rapid acquisition of quantitative and reproducible OCT biomarkers with potential to inform treatment decisions in the care of neovascular AMD. This furthers development of point-of-care decision-aid systems for personalized medicine.

ObjectiveTo investigate whether a video tutorial, highlighting important aspects of keratoconus provided prior to a scheduled follow-up consultation, has a specific effect on patients’ knowledge after the consultation.Methods and AnalysisSingle center, randomized controlled trial registered on ISRCTN registry (number ISCTN75317089, https://doi.org/10.1186/ISRCTN75317089). Consenting eligible keratoconus patients were randomly assigned to either receive a conventional face-to-face consultation (control group) or to an additional video tutorial (interventional group) on definition, risk factors and treatment options provided prior to the consultation. The main outcome measure was the difference of knowledge assessed by a questionnaire after the consultation. Of each participant, clinical characteristics, highest educational level and medical background were obtained. We also performed a meta-analysis of published reports assessing knowledge improvement by video-based patient education.ResultsWe assigned 22 patients to the interventional and 21 patients to the control group. Mean age was 29.0 years (SD 11.6), 8/43 (18.6%) were female and median disease duration was 2.5 years (interquartile range: 2-5years). Compared to the control group, knowledge was 12.0% (95%CI: 5.8%-18.2%; pConclusionThe results suggest that supplementary video information embedded in the clinical management of keratoconus, helps conveying relevant disease knowledge.

Purpose To assess the preoperative objective angle alpha and angle kappa measurements of patients deciding to undergo multifocal refractive lens surgery based on a subjective positive multifocal contact lens test (MCLT). Methods Retrospective, consecutive case series. Alpha and kappa angles were measured using the iTrace aberrometer. All patients also performed a 1-week MCLT. Only patients with a positive MCLT underwent surgery. Visual outcome (UCVA) was obtained in the 1-year follow-up. We assessed the preoperative distribution of angle values within MCLT positive and negative patient groups. Results Two hundred seventeen eyes (111 patients) were included. Mean age was 56.4 years (SD 5.6) and 46.9% were female. In 71 eyes (38 patients), MCLT was positive. Of them, 12 eyes (17%) had an angle alpha and angle kappa ≥ 0.5mm. Of 146 eyes (73 patients) who refrained from surgery due to a negative MCLT, 71 eyes (48.6%) had both angles small (pn=24) with high alpha but low kappa sizes improved less (−0.31 logMAR (SD 0.13; p=0.019)). Conclusion Four out of five patients with a positive MCLT also had correspondingly small angle values. One-half of patients with low preoperative angle values refrained from surgery due to a negative MCLT result. One-year visual acuity improvement was substantial and independent from angle sizes.

Ophthalmology faces many challenges in providing effective and meaningful eye care to an ever-increasing group of people. Even health systems that have so far been able to cope with the quantitative patient increase, due to their funding and the availability of highly qualified professionals, and improvements in practice routine efficiency, will be pushed to their limits. Further pressure on care will also be caused by new active substances for the largest group of patients with AMD, the so-called dry form. Treatment availability for this so far untreated group will increase the volume of patients 2-3 times. Without the adaptation of the care structures, this quantitative and qualitative expansion in therapy will inevitably lead to an undersupply.There is increasing scientific evidence that significant efficiency gains in the care of chronic diseases can be achieved through better networking of stakeholders in the healthcare system and greater patient involvement. Digitalization can make an important contribution here. Many technological solutions have been developed in recent years and the time is now ready to exploit this potential. The exceptional setting during the SARS-CoV-2 pandemic has shown many that new technology is available safely, quickly, and effectively. The emergency has catalyzed innovation processes and shown for post-pandemic time after that we are equipped to tackle the challenges in ophthalmic healthcare - ultimately for the benefit of patients and society.

Background/aimsThe objective of this multicentre, multinational, prospective study was to assess the level of basic understanding that individuals with keratoconus possessed about their condition.MethodsWe recruited 200 active keratoconus patients who were under regular review, and cornea specialists established a standard of ‘minimal keratoconus knowledge’ (MKK) that included an understanding of the definition, risk factors, symptoms and treatment options for the condition. We collected data from each participant regarding their clinical characteristics, highest level of education, (para)medical background and experiences with keratoconus within their social circle, and calculated the percentage of MKK attained by each patient.ResultsOur findings revealed that none of the participants met the MKK standard, with the average MKK score being 34.6% and ranging from 0.0% to 94.4%. Furthermore, our study showed that patients with a university degree, previous surgical intervention for keratoconus or affected parents had a higher MKK. However, age, gender, disease severity, paramedical knowledge, disease duration and best-corrected visual acuity did not significantly affect the MKK score.ConclusionsOur study demonstrates a concerning lack of basic disease knowledge among keratoconus patients in three different countries. The level of knowledge exhibited by our sample was only one-third of what cornea specialists would typically anticipate from patients. This highlights the need for greater education and awareness campaigns surrounding keratoconus. Further research is needed to determine the most efficient approaches for enhancing MKK and subsequently improving the management and treatment of keratoconus.

Objectives Systemic lupus erythematosus (SLE) is a systemic autoimmune disease associated with neuro-psychiatric (NP) manifestations. Frequency and patterns of neuro-psychiatric systemic lupus erythematosus (NPSLE) vary substantially between patients. We conducted a systematic review (SR) of the literature and examined prevalence and characteristics of NPSLE in the Swiss SLE cohort study (SSCS). Methods The SR search was performed between January 1999 and January 2020. We included prospective/cross-sectional studies focusing on NPSLE. We secured study characteristics, cohort compositions and frequencies of NP manifestations, assessed heterogeneity across reports and investigated sources of variation using meta-regression models. Regarding the SSCS, we reviewed all patients included and classified NP manifestations. Results The SR searches identified 530 studies. We included 22 studies in our meta-analysis, the mean frequency of NPSLE ranged from 10.6% to 96.4%. The frequency of NPSLE in the SSCS was 28.1%. Severe events including cerebrovascular insults, seizures and psychosis appeared in 7.1%, 5.3% and 6.5% respectively. There was a linear relationship between duration of SLE and cumulative incidence of NPSLE. Conclusions The spectrum of NPSLE is very broad. The diagnostic work-up and rates of reported manifestations varied substantially across studies. We call for concerted efforts and consensus regarding definitions of NPSLE that will facilitate accurate diagnosis and attribution to SLE, particularly with a view to timely intervention and patient outcomes.

For the elderly in nursery homes, a visit to the ophthalmologist is a burden, which might lead to undertreatment. We have recently started offering a novel ophthalmological service combining onsite examination and telemedical interpretation for patients with limited access to ophthalmological care. This study summarises the frequency of findings of treatable eye diseases after the first year of operation in participants who dropped out from regular ophthalmological control.Participants' clinical characteristics, frequency of service utilisation, and findings were extracted from the system and analysed.Of 1946 residents approached, 540 (27.7%; 1080 eyes) signed up for the service. A complete examination was possible in 412 persons (813 eyes) and partially possible in the remaining 128. The mean age of the examined participants mean age was 83.9 years (SD 9.7), and they were predominantly female (69.8%). The majority had a diagnosis of dementia (54.5%) and 20.2% had diabetes mellitus requiring treatment. The median care level (ranging from 0 - 12) was 7 (interquartile range 6 - 9), corresponding to a care need of 121 - 140 min/d. The mean best-corrected decimal visual acuity was 0.55 (SD 0.24). For 164 eyes (15.2%), the current spectacle correction was insufficient. An untreated cataract was present in 145 eyes (13.4%), 89 eyes (8.2%) were receiving glaucoma treatment, and 7 eyes had a decompensated glaucoma. Dry age-related macular degeneration (AMD) appeared in 276 eyes (25.6%), 12 eyes (1.1%) had wet AMD, and 24 eyes (11.0%) among patients with diabetes showed signs of diabetic retinopathy. Other pathologies were uncommon.Residents of nursery homes, who are unable to attend regular ophthalmological control, show various treatable ophthalmological conditions, including cataracts, glaucoma, and retinal pathologies. Screening with a novel telemedicine service allows for the identification of treatable conditions and careful planning and referral of patients to appropriate clinics having the necessary infrastructure for this particular population.Für ältere Menschen in Pflegeheimen ist ein Besuch beim Augenarzt eine Belastung, die zu einer Unterversorgung führen kann. Seit Kurzem bieten wir einen neuartigen augenärztlichen Dienst für Patienten mit eingeschränktem Zugang zur augenärztlichen Versorgung an, der eine Vor-Ort-Untersuchung mit telemedizinischer Interpretation kombiniert. Diese Studie fasst die Häufigkeit von behandelbaren Augenkrankheiten nach dem 1. Betriebsjahr bei Personen zusammen, die sich nicht mehr in regelmäßiger ophthalmologischer Betreuung befanden.Die klinischen Merkmale der Teilnehmer, die Häufigkeit der Inanspruchnahme des Angebotes und die Befunde wurden aus dem System extrahiert und analysiert.Von 1946 kontaktierten Bewohnern meldeten sich 540 (27,7%; 1080 Augen) für die Untersuchung an. Bei 412 Personen (813 Augen) war eine vollständige Untersuchung möglich, bei den übrigen 128 eine teilweise. Das Durchschnittsalter der untersuchten Teilnehmer betrug 83,9 Jahre (SD 9,7) und sie waren überwiegend weiblich (69,8%). Bei der Mehrheit war eine Demenz bekannt (54,5%) und 20,2% hatten einen behandlungsbedürftigen Diabetes mellitus. Die mittlere Pflegestufe (0 – 12) betrug 7 (Interquartilsbereich 6 – 9), was einem Pflegebedarf von 121 – 140 min/d entsprach. Der mittlere bestkorrigierte Dezimalvisus betrug 0,55 (SD 0,24). Bei 164 Augen (15,2%) war die aktuelle Brillenkorrektur unzureichend. Bei 145 Augen (13,4%) lag eine unbehandelte Katarakt vor, 89 Augen (8,2%) befanden sich in Glaukombehandlung und 7 Augen hatten ein dekompensiertes Glaukom. 276 Augen (25,6%) hatten eine trockene AMD, 12 Augen (1,1%) eine feuchte AMD und 24 Augen (11,0%) der Patienten mit Diabetes wiesen Anzeichen einer diabetischen Retinopathie auf. Andere Krankheitsbilder waren selten.Bei Bewohnern von Pflegeheimen, die nicht in der Lage sind, an regelmäßigen augenärztlichen Kontrollen teilzunehmen, treten verschiedene behandelbare Augenkrankheiten auf, darunter Katarakt, Glaukom und Netzhauterkrankungen. Screening mit einem neuartigen telemedizinischen Dienst ermöglicht die Identifizierung behandelbarer Erkrankungen und eine sorgfältige Planung und Überweisung der Patienten an geeignete Kliniken, die über die notwendige Infrastruktur für diese besondere Bevölkerungsgruppe verfügen.

Summary Background Urinary tract infections (UTIs) are among the most prevalent microbial diseases and their financial burden on society is substantial. In the context of increasing antibiotic resistance, finding alternative treatments for UTIs is a top priority. We aimed to determine whether intravesical bacteriophage therapy with a commercial bacteriophage cocktail is effective in treating UTI. Methods We did a randomised, placebo-controlled, clinical trial, at the Alexander Tsulukidze National Centre of Urology, Tbilisi, Georgia. Men older than 18 years of age, who were scheduled for transurethral resection of the prostate (TURP), with complicated UTI or recurrent uncomplicated UTI but no signs of systemic infection, were allocated by block randomisation in a 1:1:1 ratio to receive intravesical Pyo bacteriophage (Pyophage; 20 mL) or intravesical placebo solution (20 mL) in a double-blind manner twice daily for 7 days, or systemically applied antibiotics (according to sensitivities) as an open-label standard-of-care comparator. Urine culture was taken via urinary catheter at the end of treatment (ie, day 7) or at withdrawal from the trial. The primary outcome was microbiological treatment response after 7 days of treatment, measured by urine culture; secondary outcomes included clinical and safety parameters during the treatment period. Analyses were done in a modified intention-to-treat population of patients having received at least one dose of the allocated treatment regimen. This trial is registered with ClinicalTrials.gov , NCT03140085 . Findings Between June 2, 2017, and Dec 14, 2018, 474 patients were screened for eligibility and 113 (24%) patients were randomly assigned to treatment (37 to Pyophage, 38 to placebo, and 38 to antibiotic treatment). 97 patients (28 Pyophage, 32 placebo, 37 antibiotics) received at least one dose of their allocated treatment and were included in the primary analysis. Treatment success rates did not differ between groups. Normalisation of urine culture was achieved in five (18%) of 28 patients in the Pyophage group compared with nine (28%) of 32 patients in the placebo group (odds ratio [OR] 1·60 [95% CI 0·45–5·71]; p=0·47) and 13 (35%) of 37 patients in the antibiotic group (2·66 [0·79–8·82]; p=0·11). Adverse events occurred in six (21%) of 28 patients in the Pyophage group compared with 13 (41%) of 32 patients in the placebo group (OR 0·36 [95% CI 0·11–1·17]; p=0·089) and 11 (30%) of 37 patients in the antibiotic group (0·66 [0·21–2·07]; p=0·47). Interpretation Intravesical bacteriophage therapy was non-inferior to standard-of-care antibiotic treatment, but was not superior to placebo bladder irrigation, in terms of efficacy or safety in treating UTIs in patients undergoing TURP. Moreover, the bacteriophage safety profile seems to be favourable. Although bacteriophages are not yet a recognised or approved treatment option for UTIs, this trial provides new insight to optimise the design of further large-scale clinical studies to define the role of bacteriophages in UTI treatment. Funding Swiss Continence Foundation, the Swiss National Science Foundation, and the Swiss Agency for Development and Cooperation. Translations For the Georgian and German translations of the abstract see Supplementary Materials section.

Background Home monitoring of hyperacuity allows early detection of progression in exudative neovascular age-related macular degeneration (nvAMD) and diabetic macular oedema (DMO). However, false alarms may pose a significant burden to both patients and healthcare professionals alike. Purpose To assess the false alarm rate and positive predictive value of smartphone-based home monitoring of nvAMD and DMO. Methods Patients treated with anti-angiogenic therapy in a pro re nata scheme for nvAMD or DMO at the Medical Retina service (Lucerne, Switzerland) between March and June 2016 were included in this prospective cohort study. The home monitoring test Alleye (Oculocare Ltd, Switzerland) provided a session score from 0–100 in addition to a traffic-light system feedback via the smartphone application. Three consecutive “red” scores were considered as a positive test or alarm signal. Specificity, 1-specificity (false alarm rate) and the predictive value for optical coherence tomography-based disease progression were analysed. Results 73 eyes of 56 patients performed 2258 tests in 222 “follow-up periods”. Progression was observed in 141 periods (63.5%). The specificity of the test was 93.8% (95% CI: 86.2–98.0%), the false alarm rate 6.1% (95% CI: 2.0–13.8%), and the positive predictive value 80.0% (95% CI: 59.3–93.2%) for the detection of progression. Conclusion False alarm rates for the detection of progression in macular disease via home monitoring is low. These findings suggest that home monitoring may be a useful adjunct for remote management of nvAMD and DMO.

Study Design Simulations using data from a prospective cohort study. Objectives To illustrate how prospective cohort data can be employed in randomized controlled trial (RCT) planning to assess feasibility and operational challenges, using TASCI (Transcutaneous tibial nerve stimulation in patients with Acute Spinal Cord Injury to prevent neurogenic detrusor overactivity: a nationwide randomized, sham-controlled, double-blind clinical trial) as a case study. Setting Spinal cord injury rehabilitation centers in Switzerland. Methods TASCI is nested in the multicenter Swiss Spinal Cord Injury Cohort Study (SwiSCI), which prospectively includes patients with acute spinal cord injury. In simulations, data from 640 patients, collected by SwiSCI, were used to investigate different scenarios of patient eligibility and study consent, as well as the performance of the randomization list. Descriptive analysis was used to describe the population of interest and the simulation results; multivariable logistic regression analysis was performed to identify predictors of discharge within the TASCI intervention time period. Results The recruitment target of 114 patients is obtainable within the originally envisioned three-year time period under the most favorable recruitment scenario examined. The distribution of the primary prognostic factor produced imbalance in the randomization lists and informed further discussion of the cut-off values used in stratification. Influxes of patients resulted in overlapping intervention periods for multiple participants, which guided resource allocation. Early discharge was related to the primary prognostic factor and study center, but is only anticipated in about 8% of participants. Conclusions Prospective cohort data are a very valuable resource for planning RCTs.

Impaired ocular blood flow has been associated with the etiopathogenesis of glaucoma. Topical brimonidine lowers intraocular pressure, a major glaucoma risk factor. However, brimonidine's influence on retinal blood flow remains to be fully elucidated. Our aim was to compare the effect of topical brimonidine and brinzolamide administration on retinal blood flow velocity in second and third order vessels in healthy adults using the retinal function imager.In 10 healthy probands between 23 and 32 years of age, one eye was randomly selected to receive 2 treatment rounds with 3 single doses of brimonidine 2 mg/mL and brinzolamide 10 mg/mL at 12-hour intervals each. The fellow eyes served as intra-individual controls. Immediately before the first drop and 2 hours after the last drop of each treatment round, all subjects were examined, including Goldmann tonometry, Pascal tonometry, assessment of retinal blood flow velocity using the retinal function imager, as well as blood pressure and pulse measurements.Intraocular pressure decreased significantly in treated eyes while remaining stable in control eyes, indicating reliable application of brimonidine and brinzolamide drops. In contrast, retinal blood flow velocities did not demonstrate any significant differences between groups after both treatment rounds.Neither brimonidine nor brinzolamide appear to alter retinal blood flow velocity in a clinically relevant manner. The slight velocity changes detected in our study are likely physiologic fluctuations. Our findings do not support the rationale of a detrimental effect of topical brimonidine on ocular blood flow and hence brimonidine may be further administered for lowering intraocular pressure with the appropriate caution. However, our study is strongly limited by the small sample size and, thus, further research with larger cohorts of healthy volunteers and patients with glaucoma is needed to confirm the results.The study provides information about the effect of the topically administered antiglaucoma medications brimonidine and brinzolamide on the ocular blood flow and its regulation. The findings indicate that beside the lowering of IOP there is no evidence for an additional effect on the development of glaucoma.

BackgroundMany artificial intelligence (AI) studies have focused on development of AI models, novel techniques, and reporting guidelines. However, little is understood about clinicians' perspectives of AI applications in medical fields including ophthalmology, particularly in light of recent regulatory guidelines. The aim for this study was to evaluate the perspectives of ophthalmologists regarding AI in 4 major eye conditions: diabetic retinopathy (DR), glaucoma, age-related macular degeneration (AMD) and cataract.MethodsThis was a multi-national survey of ophthalmologists between March 1st, 2020 to February 29th, 2021 disseminated via the major global ophthalmology societies. The survey was designed based on microsystem, mesosystem and macrosystem questions, and the software as a medical device (SaMD) regulatory framework chaired by the Food and Drug Administration (FDA). Factors associated with AI adoption for ophthalmology analyzed with multivariable logistic regression random forest machine learning.ResultsOne thousand one hundred seventy-six ophthalmologists from 70 countries participated with a response rate ranging from 78.8 to 85.8% per question. Ophthalmologists were more willing to use AI as clinical assistive tools (88.1%, n = 890/1,010) especially those with over 20 years' experience (OR 3.70, 95% CI: 1.10–12.5, p = 0.035), as compared to clinical decision support tools (78.8%, n = 796/1,010) or diagnostic tools (64.5%, n = 651). A majority of Ophthalmologists felt that AI is most relevant to DR (78.2%), followed by glaucoma (70.7%), AMD (66.8%), and cataract (51.4%) detection. Many participants were confident their roles will not be replaced (68.2%, n = 632/927), and felt COVID-19 catalyzed willingness to adopt AI (80.9%, n = 750/927). Common barriers to implementation include medical liability from errors (72.5%, n = 672/927) whereas enablers include improving access (94.5%, n = 876/927). Machine learning modeling predicted acceptance from participant demographics with moderate to high accuracy, and area under the receiver operating curves of 0.63–0.83.ConclusionOphthalmologists are receptive to adopting AI as assistive tools for DR, glaucoma, and AMD. Furthermore, ML is a useful method that can be applied to evaluate predictive factors on clinical qualitative questionnaires. This study outlines actionable insights for future research and facilitation interventions to drive adoption and operationalization of AI tools for Ophthalmology.

There are a variety of protocols for manufacturing autologous serum (AS) eye drops. The Lucerne protocol for the production of AS eye drops uses a slightly reduced gravitational (g)-force and time for the centrifugation process (2500 × g for 10 minutes), compared to previously published optimised protocols, to obtain high levels of epitheliotropic growth factors (3000 × g for 15 minutes). The goal of this study was to compare the concentrations of growth factors, albumin and lysozyme in autologous serum eye drops manufactured with these protocols.Blood from 5 healthy volunteers was placed in plastic tubes without an anticoagulant. Tubes from each donor were left in a vertical position for 2 hours at room temperature to facilitate coagulation, followed by centrifugation at either 2500 × g for 10 minutes or at 3000 × g for 15 minutes at room temperature. The serum levels of beta nerve growth factor (β-NGF), transforming growth factor β1 (TGF-β1), epidermal growth factor (EGF), hepatocyte growth factor (HGF), platelet-derived growth factor BB (PDGF-BB) and vascular endothelial growth factor A (VEGF-A) were measured in triplicate with a multi-analyte Simple Plex platform. The Simple Plex cartridge allows each sample to be run in triplicate for each analyte and prevents any interaction between the antibody components for each biomarker. The serum level of albumin was measured by turbidimetric immunoassay Tina-quant and of lysozyme by single radial immunodiffusion assay.For all analytes, the reduced g-force and centrifugation time did not result in a significant difference in serum levels.The Lucerne protocol for the production of autologous serum eye drops with reduced g-force and a shorter centrifugation time does not affect the concentrations of the main epitheliotropic growth factors, albumin and lysozyme, in AS eye drops.Es gibt verschiedene Protokolle zur Herstellung von Eigenserum-Augentropfen. Das Luzerner Protokoll zur Herstellung von Eigenserum-Augentropfen benutzt eine leicht reduzierte Zentrifugierungskraft und eine kürzere Zeitspanne (2500 × g, 10 Minuten) im Vergleich zu den früher publizierten optimierten Protokollen (3000 × g, 15 Minuten), um epitheliotrope Wachstumsfaktoren zu erhalten. Ziel dieser Studie war es, die Konzentrationen von Wachstumsfaktoren, Albumin und Lysozym in mit diesen Protokollen hergestellten Eigenserum-Augentropfen zu vergleichen.Es wurden Plastikröhrchen mit Blutproben von 5 gesunden, freiwilligen Spendern ohne Beigabe eines Antikoagulans gefüllt. Die Röhrchen wurden 2 Stunden lang senkrecht bei Zimmertemperatur gehalten, um die Koagulation anzuregen. Danach wurden die Röhrchen entweder 10 Minuten lang mit 2500 × g oder 15 Minuten lang mit 3000 × g bei Zimmertemperatur zentrifugiert. Die Serumspiegel der Wachstumsfaktoren β-NGF, TGF-β1, EGF, HGF, PDGF-BB und VEGF-A wurden mithilfe eines Simple-Plex-Systems für mehrere Analyten gemessen. Mit der Simple-Plex-Patrone wird jede Blutprobe 3 × für jeden Analyten getestet, und es kommt zu keiner Interaktion zwischen den Antikörperkomponenten der jeweiligen Biomarkern. Der Albuminserumspiegel wurde mit dem Tina-quant-Immunoassay und der Lysozymserumspiegel mit einem radialen Einfachimmundiffusionstest gemessen.Die Reduzierung der Zentrifugierungskraft und -zeit führte zu keinem signifikanten Unterschied der Konzentrationen der Analyten im Serumspiegel.Die Konzentration der wichtigsten epitheliotropen Wachstumsfaktoren sowie von Albumin und Lysozym in den mit Luzerner Protokoll hergestellten Eigenserum-Augentropfen bleibt unverändert hoch.

Background Urodynamic investigations have a pivotal role in the diagnosis of lower urinary tract symptoms. Despite expert statements and guidelines supporting their usefulness for clinical decision making in various clinical domains, the academic debate remains controversial. Objective To provide a metaepidemiological inventory of studies assessing the diagnostic properties of urodynamic investigations. Design, setting, and participants Systematic searches without language restrictions were performed in (Pre-)Medline, EMBASE, and the Cochrane Library from inception until August 31, 2018. Checking of reference lists of included studies and reviews complemented searches. Records were compiled and screened for possible inclusion by reading title and abstracts by two teams of two research fellows. Inclusion criteria were as follows: prospective data collection and urodynamic investigations performed either as a diagnostic test or using a therapy monitoring instrument. No a priori selection on clinical domain was done. Double reading was performed on records marked “included.” Extraction into a developed and piloted matrix was performed in duplicate and checked by a third research fellow. Outcome measurements and statistical analysis Of each included article, study specifics, objective, study design, type of data collection, clinical domain, type and description of test used, and type of outcome were extracted and attributed to a framework. Results and limitations Electronic searches retrieved 20 841 records. After screening, 299 abstracts were considered relevant. The main reasons for exclusion were as follows: animal studies, no primary data, editorial/opinion based on published data or reviews, primary objective of the study being not the assessment of urodynamic investigations, and post hoc (opportunistic) correlation studies. Conclusions To our knowledge, this is the first comprehensive collection of studies assessing the clinical usefulness of urodynamic investigations. The collection is the starting point for a series of systematic reviews assessing the diagnostic properties of urodynamic investigations. Patient summary The usefulness of urodynamic investigations for clinical decision making is under debate. We established an inventory of diagnostic studies on urodynamics to assess the value of urodynamics in various clinical applications.

Background There are no reliable signs or symptoms that differentiate Mycoplasma pneumoniae (Mp) infection in community-acquired pneumonia (CAP) from other etiologies. Additionally, current diagnostic tests do not reliably distinguish between Mp infection and carriage. We previously determined that the measurement of Mp-specific immunoglobulin M antibody-secreting cells (ASCs) by enzyme-linked immunospot assay allowed for differentiation between infection and carriage. Using this new diagnostic test, we aimed to identify clinical and laboratory features associated with Mp infection. Methods This is a prospective cohort study of children, 3–18 years of age, with CAP from 2016 to 2017. Clinical features and biomarkers were compared between Mp-positive and -negative groups by Mann-Whitney U test or Fisher exact test, as appropriate. Area under the receiver operating characteristic curve (AUC) differences and optimal thresholds were determined by using the DeLong test and Youden J statistic, respectively. Results Of 63 CAP patients, 29 were Mp-positive (46%). Mp positivity was statistically associated with older age (median, 8.6 vs 4.7 years), no underlying disease, family with respiratory symptoms, prior antibiotic treatment, prolonged prodromal respiratory symptoms and fever, and extrapulmonary (skin) manifestations. Lower levels of C-reactive protein, white blood cell count, absolute neutrophil count, and procalcitonin (PCT), specifically PCT 5 years (AUC = 0.77), prodromal fever and respiratory symptoms >6 days (AUC = 0.79), and PCT, Community-acquired pneumonia (CAP) caused by Mycoplasma pneumoniae (Mp) is difficult to diagnose. A combination of clinical features and biomarkers may aid physicians in identifying patients at high risk for Mp CAP.

Purpose To investigate descriptions and inclusion criteria of keratoconus used in randomized trials assessing the efficacy of surgical and nonsurgical interventions. Methods Systematic review: we searched (Pre-)Medline and the Cochrane Library from inception until December 2018 and checked the reference lists of included articles and reviews. We included randomized trials assessing the efficacy of any kind of keratoconus treatment. No language restrictions were imposed. We assessed articles against the inclusion criteria, extracted relevant data including any kind of keratoconus description, and examined the methodological quality. Results Searches retrieved 459 nonduplicate records, and we included 57 randomized controlled trials investigating 9 different surgical interventions with the most used primary outcome measure being maximum keratometry. Only 15 (26.3%) described eligibility parameters regarding keratoconus staging/classification, of which 12 studies used the Amsler-Krumeich classification. Eleven studies were published before 1997 (before publication of the Consolidated Standards of Reporting Trials statement), and none of these described the use of a classification. From 1997 onward, 15 of 46 studies (32.6%) described the incorporation of a classification system (P = 0.051). The average methodological quality of included trails was modest. Conclusions The evidence from randomized trials, even after introduction of the Consolidated Standards of Reporting Trials statement, remains ill-formed regarding a careful definition of keratoconus. This is unfortunate because imprecisions regarding the specification of included patients preclude clinicians to assess applicability, that is, the extent to which they can use inferences drawn from study participants regarding efficacy and adverse events in the care of individual patients.

Mycoplasma pneumoniae (Mp) is reported to be the most common bacterial cause of community-acquired pneumonia (CAP) in hospitalized U.S. children (1). However, current diagnostic tests, including PCR of upper respiratory tract (URT) specimens and serology, do not differentiate between Mp infection and carriage (2). Mp carriage in the URT is found in up to 56% of healthy children (2, 3). A ≥4-fold increase in IgG levels is still used in most centers to confirm Mp infection but has low sensitivity (4) and is not helpful in acute clinical management (3). In the absence of an accurate diagnostic test, it is not surprising that studies and meta-analyses on the efficacy of antibiotics are inconclusive for Mp CAP in children (5, 6). Circulating antibody-secreting cell (ASC) responses have been demonstrated to be more rapid and shorter-lived than antibody responses (7). We hypothesized that Mp-IgM-ASCs circulate in peripheral blood only for a few days or weeks after Mp infection, whereas Mp-DNA in the URT and serum antibodies persist for months. We aimed to evaluate the measurement of Mp-IgM-ASCs by enzyme-linked immunospot (ELISpot) assay as a new test for diagnosing Mp CAP. Methods Pediatric patients with CAP (n = 152) and control subjects (n = 156) were enrolled from May 2016 to April 2017 after written informed consent. Inclusion criteria for patients with CAP were clinical diagnosis of pneumonia (fever >38.5°C and tachypnea [8]) in previously healthy children aged 3–18 years. Children 4 h after sampling) or reduced ASC recovery (after a freeze–thaw cycle) (10). Samples and clinical data (using a standardized questionnaire) were collected at follow-up visits at

ObjectiveWe compared patients with neovascular age-related macular degeneration (nvAMD), diabetic macular oedema (DMO) and other macular pathologies testing their vision with the hyperacuity home-monitoring app Alleye to patients not performing home-monitoring regarding clinical outcomes and clinical management.DesignMatched-pair analysis.SettingRetina Referral Centre, Switzerland.ParticipantsFor each eye using Alleye, we matched 2–4 controls not using home-monitoring based on age, gender, number of previous intravitreal injections (IVI), best corrected visual acuity (BCVA) (Early Treatment Diabetic Retinopathy Study letters), central macular thickness (CRT) and time point of enrolment, using the Mahalanobis distance matching algorithm. We included 514 eyes (288 patients); 107 eyes with nvAMD using home monitoring and 218 controls not using home monitoring, 25 eyes with DMO (n=52 controls) and 40 eyes with miscellaneous conditions (n=72 controls). 173 eyes (33.7%) received no IVI during follow-up.Main outcome measuresImprovement of ≥5 letters, number of injection visits and treatment retention after correcting for differences in baseline characteristics with multivariate analyses.ResultsThe mean follow-up duration was 809 days (range 147–1353) and the mean number of IVI/year among treated eyes was 6.7 (SD 3.1). Mean age at baseline was 70.4 years (SD 10.9), BCVA was 77.6 letters (SD 11.6) and CRT was 263.6 µm (SD 86.7) and was similar between patients using and not using home monitoring. In multivariate analyses, patients using home monitoring had a higher chance to improve visual acuity by ≥5 letters (OR 1.67 (95% CI 1.01 to 2.76; p=0.044)) than controls. Treated eyes using home monitoring had less injection visits/year (−0.99 (95% CI −1.59 to −0.40; p=0.001)) and a longer treatment retention +69.2 days (95% CI 2.4 to 136.0; p=0.042). These effects were similar across retinal pathologies.ConclusionsThis data suggest that patients capable of performing mobile hyperacuity home monitoring benefit in terms of visual acuity and discontinue treatment less often than patients not using home monitoring.

To evaluate the usability and long-term adherence to the mobile hyperacuity app Alleye in patients with retinal pathology.We enroled 72 patients (95 eyes) mainly treated for wet AMD (48/95; 50.5%). We calculated changes of clinical characteristics and the System Usability Score (SUS), and personal ratings of usefulness and number of tests performed per month at a follow-up visit of eighteen months.At baseline, mean best corrected visual acuity (BCVA) was 74.9 letters (SD 14.8), mean age was 69.9 (SD 11.4) and 39/72 (54.2%) were female. Of included patients, 47/72 (65.2%) reported to use mobile devices daily. The retention rate until last follow-up was 73.6 % (53/72). The median SUS score at baseline was 90 (interquartile range (IQR) 82.5-95) and 92.5 (IQR 82.5-95) in the follow-up. No association between changes of SUS and clinical characteristics was seen. At baseline, 76.4% (55/72) stated that they would recommend the app to a friend, 83.3% (60/72) were very satisfied with the app and 58/72 (80.6%) of respondents said they trusted the app. These assessments remained similar among patients remaining on the program until the follow-up. Patients who dropped out of the study (n = 19) did not differ in age, gender, BCVA, and SUS at baseline, but stated that they did not use the mobile device daily (Odds Ratio 7.40 (95%CI: 2.32-23.65); p = 0.001).The majority of users willing to perform home monitoring with the Alleye app are satisfied with the usability and have a positive attitude towards its trustworthiness and usefulness.

Background To assess whether Swiss general ophthalmologists have the minimal keratoconus knowledge that corneal specialists would expect them to have. Methods Corneal specialists defined “minimal keratoconus knowledge” (MKK) with respect to definition, risk factors, symptoms and possible treatment options of keratoconus. A telephone interview survey was conducted among one hundred ophthalmologists (mean age 51.9 years (SD 9.5), 60 % male) from the German-speaking part of Switzerland. For each participant, years of work experience, number of keratoconus patients seen per year and access to a topography device were obtained. We calculated the proportion of MKK and examined in multivariate analyses whether ophthalmologists with access to topography and with greater work experience performed better than other groups. Results No single ophthalmologist had MKK. The mean MKK was 52.0 %, and the range was 28.6–81.0 %. Per 10 years of working in private practice, the MKK decreased by 8.1 % points (95 % CI: -14.2, -2.00; p = 0.01). Only 24 % of participants correctly recalled the definition of keratoconus, 9 % all risk factors, 5 % all symptoms and 20 % all treatment modalities. The MKK values were not associated with the number of keratoconus patients seen per year and the availability of topography to diagnose keratoconus. Conclusions There is a substantial mismatch between corneal specialist’ expectations and general ophthalmologists’ knowledge about keratoconus. The low recall of symptoms and risk factors may explain why ophthalmologists diagnose relatively few cases of keratoconus, resulting in inefficient care delivery and delayed intervention.

Summary Background Deep learning has the potential to transform health care; however, substantial expertise is required to train such models. We sought to evaluate the utility of automated deep learning software to develop medical image diagnostic classifiers by health-care professionals with no coding—and no deep learning—expertise. Methods We used five publicly available open-source datasets: retinal fundus images (MESSIDOR); optical coherence tomography (OCT) images (Guangzhou Medical University and Shiley Eye Institute, version 3); images of skin lesions (Human Against Machine [HAM] 10000), and both paediatric and adult chest x-ray (CXR) images (Guangzhou Medical University and Shiley Eye Institute, version 3 and the National Institute of Health [NIH] dataset, respectively) to separately feed into a neural architecture search framework, hosted through Google Cloud AutoML, that automatically developed a deep learning architecture to classify common diseases. Sensitivity (recall), specificity, and positive predictive value (precision) were used to evaluate the diagnostic properties of the models. The discriminative performance was assessed using the area under the precision recall curve (AUPRC). In the case of the deep learning model developed on a subset of the HAM10000 dataset, we did external validation using the Edinburgh Dermofit Library dataset. Findings Diagnostic properties and discriminative performance from internal validations were high in the binary classification tasks (sensitivity 73·3–97·0%; specificity 67–100%; AUPRC 0·87–1·00). In the multiple classification tasks, the diagnostic properties ranged from 38% to 100% for sensitivity and from 67% to 100% for specificity. The discriminative performance in terms of AUPRC ranged from 0·57 to 1·00 in the five automated deep learning models. In an external validation using the Edinburgh Dermofit Library dataset, the automated deep learning model showed an AUPRC of 0·47, with a sensitivity of 49% and a positive predictive value of 52%. Interpretation All models, except the automated deep learning model trained on the multilabel classification task of the NIH CXR14 dataset, showed comparable discriminative performance and diagnostic properties to state-of-the-art performing deep learning algorithms. The performance in the external validation study was low. The quality of the open-access datasets (including insufficient information about patient flow and demographics) and the absence of measurement for precision, such as confidence intervals, constituted the major limitations of this study. The availability of automated deep learning platforms provide an opportunity for the medical community to enhance their understanding in model development and evaluation. Although the derivation of classification models without requiring a deep understanding of the mathematical, statistical, and programming principles is attractive, comparable performance to expertly designed models is limited to more elementary classification tasks. Furthermore, care should be placed in adhering to ethical principles when using these automated models to avoid discrimination and causing harm. Future studies should compare several application programming interfaces on thoroughly curated datasets. Funding National Institute for Health Research and Moorfields Eye Charity.

We aimed to systematically assess the evidence on the efficacy and safety of alpha-blockers in patients with multiple sclerosis (MS) suffering from neurogenic lower urinary tract dysfunction (NLUTD).The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was used to perform this systematic review. An electronic search of Cochrane register, Embase, Medline, Scopus (last search 3 March 2018) and screening of reference lists as well as reviews were used to identify the studies. Articles were included if they reported on efficacy/safety of alpha-blockers for the treatment of NLUTD in patients with MS.After screening of 7'015 abstracts, three studies enrolling a total of 50 patients were included: one randomized, placebo-controlled, single-blind trial and two prospective cohort studies. Alpha-blocker treatment was successful in 50% to 96% of the patients. Pooling data from the three included studies, the relative risk for successful alpha-blocker treatment was 3.89 (95% confidence interval 2.7-7.0). The general safety profile of alpha-blockers was favorable with 8% of the patients reporting adverse events.Alpha-blockers may be effective and safe for treating NLUTD in female and male patients with MS but the studies were small and the overall quality of evidence was low. To make definitive conclusions, well designed randomized controlled trials are highly warranted.