Evaluation of the test-retest and inter-mode comparability of the Impact of Vision Impairment questionnaire in people with chronic eye diseases.

PURPOSE: The main objective of this study is to assess the test-retest and inter-administration mode reliability of the Impact of Vision Impairment profile (IVI), a common patient-reported outcome measure (PROM) for people with chronic eye diseases. METHODS: The IVI was administered to adult patients with stable, chronic eye diseases two to four times per participant (average intervals between administrations 12 to 20 days; maximum two phone interviews, paper administration, electronic administration) by two trained interviewers. Rasch models were fit to the data. Intra-class correlation coefficients (ICCs), mean differences and Cronbach's alpha between test-retest administrations (two phone interviews) and inter-mode comparisons were calculated. RESULTS: Two hundred-sixteen patients (mean age 67 ± 12 years, 40% male) were included in the study. The IVI met all psychometric requirements of the Rasch model, and the division into the domains of functional items (IVI_F) and emotional items (IVI_E) corresponded to the German validation study. ICCs (all for IVI_F and IVI_E, respectively) for the retest administrations were 0.938 and 0.912, and 0.853 and 0.893 for inter-mode comparisons phone/paper, 0.939 and 0.930 for phone/electronic, and 0.937 and 0.920 for paper/electronic (all p < 0.01). Mean differences (all for IVI_F and IVI_E, respectively) for the retest administrations were 2.8% and 0.7% and ranged from 2.0% to 6.2% and from 0.4 % to 4.9% between administration modes. Cronbach's alpha ranged from 0.886 to 0.944 for retest and inter-mode comparisons. CONCLUSION: Due to the high test-retest reliability and the almost equally high comparability of different modes of administration of the IVI, the study endorses its use as a robust PROM to capture vision-related quality of life. Our results further support the use of the IVI as an endpoint in clinical trials and may simplify implementing it in both clinical trials or real-world evidence generation by offering multiple administration modes with high reliability.

HYPERREFLECTIVE FOCI NOT SEEN AS HYPERPIGMENTARY ABNORMALITIES ON COLOR FUNDUS PHOTOGRAPHS IN AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To investigate the prognostic value of quantifying optical coherence tomography (OCT)-defined hyperreflective foci (HRF) that do not correspond to hyperpigmentary abnormalities (HPAs) on color fundus photographs (CFPs)-HRF (OCT+/CFP-) -when considered in addition to HPA extent, for predicting late age-related macular degeneration development. This study sought to understand the impact of HRF (OCT+/CFP-) extent on visual sensitivity. METHODS: Two hundred eighty eyes from 140 participants with bilateral large drusen underwent imaging and microperimetry at baseline, and then 6-monthly for 3-years. The extent of HPAs on CFPs and HRF (OCT+/CFP-) on OCT was quantified at baseline. Predictive models for progression to late age-related macular degeneration, accounting for drusen volume and age, were developed using HPA extent, with and without HRF (OCT+/CFP-) extent. The association between HPA and HRF (OCT+/CFP-) extent with sector-based visual sensitivity was also evaluated. RESULTS: Incorporating HRF (OCT+/CFP-) extent did not improve the predictive performance for late age-related macular degeneration development ( P ≥ 0.32). Increasing HPA and HRF (OCT+/CFP-) extent in each sector were independently and significantly associated with reduced sector-based visual sensitivity ( P ≤ 0.004). CONCLUSION: The addition of HRF (OCT+/CFP-) extent to HPA extent did not improve the prediction of late age-related macular degeneration development. HRF (OCT+/CFP-) extent was also independently associated with local reductions in visual sensitivity, after accounting for HPAs.

Knowledge about age-related eye diseases in the general population in Germany.

BACKGROUND: With a rising prevalence of age-related eye diseases, prevention and early diagnosis of these conditions are key goals of public eye health. Disease-related knowledge in the general public supports these goals but there is little data available. Thus, we have assessed knowledge of cataract, glaucoma, age-related macular degeneration (AMD) and diabetic eye disease in the German adult general population in a cross-sectional study and identified target groups for health education interventions. METHODS: Knowledge assessment content was identified based on a literature review, expert input, and a list of items was generated after a qualitative selection process. The resulting 16-item instrument (4 items per condition) was administered to 1,008 participants from a survey panel, demographically representative of the adult German population. Test properties were evaluated based on a Rasch model and multiple correspondence analysis (MCA). Binary-logistic regression analysis was performed to investigate associations with age, sex, education level, employment status, marital status, income, reported health status, visual difficulties, and recent general practitioner (GP) and ophthalmologist consultations. RESULTS: Replies were correct for a median of 9 out of 16 (range 2 - 16) items, which differed between conditions (p < 0.0001). Most responses were correct for cataract items (median: 3 / 4) and least were correct for AMD items (median: 2 / 4). 27%, 9%, 1% and 19% of respondents replied correctly to all cataract, glaucoma, AMD and diabetic eye disease-related items, respectively. Rasch analysis suggested an adequate targeting of items and in MCA, no evidence of multidimensionality was present. Older age, being retired, decreased general health and recent GP or ophthalmology consultations were significantly associated with more knowledge about common eye conditions (p ≤ 0.005). GP or ophthalmology consultations remained significant in a multivariable model (p ≤ 0.011). CONCLUSIONS: Knowledge gaps regarding eye health are considerable in the German general population and should therefore be addressed in educational interventions targeting the public. Special attention when designing such campaigns needs to be paid to infrequent users of the healthcare system. Knowledge of AMD seems to be poorer compared to other eye conditions.

GABAergic Involvement in Selective Attention.

Animals need to cope with abundant sensory information, and one strategy is to selectively direct attention to only the most relevant part of the environment. Although the cortical networks of selective attention have been studied extensively, its underlying neurotransmitter systems, especially the role of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), remain less well understood. Increased GABAA receptor activity because of administration of benzodiazepines such as lorazepam is known to slow reactions in cognitive tasks. However, there is limited knowledge about GABAergic involvement in selective attention. Particularly, it is unknown whether increased GABAA receptor activity slows the build-up of selectivity or generally widens attentional focus. To address this question, participants (n = 29) received 1 mg lorazepam and placebo (within-subjects, double-blind) and performed an extended version of the flanker task. The spatial distribution of selective attention was studied by systematically manipulating number and position of incongruent flankers; the temporal build-up was characterized using delta plots. An online task version was presented to an independent, unmedicated sample (n = 25) to verify task effects. Under placebo and in the unmedicated sample, only the number of incongruent flankers, but not their position, influenced RTs. Incongruent flankers impaired RTs more strongly under lorazepam than placebo, especially when adjacent to the target. Delta plot analyses of RT showed that this effect persisted even when participants reacted slowly, indicating that lorazepam-induced impairments in selective attention do not result from simply slowed down build-up of selectivity. Instead, our data indicate that increased GABAA receptor activity widens the attentional focus.

Patient-reported vision impairment in low luminance predicts multiple falls.

BACKGROUND: Visual impairment is an independent risk factor for falling. Whether this extends to patient-reported visual difficulties has not been assessed to date. We have evaluated whether patient-reported visual difficulties in low-contrast and low luminance situations are a risk factor for falls and concerns about falling. METHODS: Baseline assessments in outpatients with varying degrees of visual impairment aged ≥ 60 years included the Vision Impairment in Low Luminance (VILL) questionnaire and socio-demographic data; prospective follow-up assessments included falls over 12 months, the Falls Efficacy Scale (FES-I) and the VILL. The VILL was scored using Rasch models, and the FES-I was categorized following published guidelines. Associations were investigated using logistic regression analysis, controlling for age, visual acuity and known risk factors of falling. RESULTS: We included 112 participants (74 women, mean age 70 ± 7 years). Twenty-seven participants recalled any falls and eleven recalled multiple falls at follow-up. Higher VILL reading subscale and mobility subscale scores at baseline were significantly associated with reporting less multiple falls at follow-up (OR 0.559 [0.333-0.936], p = 0.027 and OR 0.595 [0.377-0.940], p = 0.026). VILL scores were significantly associated with concerns about falling (high versus low: p ≤ 0.004, reading, mobility and emotional subscales; high versus moderate: p = 0.004, emotional subscale). CONCLUSIONS: Patient-reported visual difficulties under low illumination and in low-contrast conditions are predictive of multiple falls in the future, have an additional predictive value over established risk scores, and are associated with concerns to fall. Current fall risk assessments may benefit from the inclusion of such assessments, e.g. the VILL questionnaire.

Effect of a flipped classroom course to foster medical students' AI literacy with a focus on medical imaging: a single group pre-and post-test study.

BACKGROUND: The use of artificial intelligence applications in medicine is becoming increasingly common. At the same time, however, there are few initiatives to teach this important and timely topic to medical students. One reason for this is the predetermined medical curriculum, which leaves very little room for new topics that were not included before. We present a flipped classroom course designed to give undergraduate medical students an elaborated first impression of AI and to increase their "AI readiness". METHODS: The course was tested and evaluated at Bonn Medical School in Germany with medical students in semester three or higher and consisted of a mixture of online self-study units and online classroom lessons. While the online content provided the theoretical underpinnings and demonstrated different perspectives on AI in medical imaging, the classroom sessions offered deeper insight into how "human" diagnostic decision-making differs from AI diagnoses. This was achieved through interactive exercises in which students first diagnosed medical image data themselves and then compared their results with the AI diagnoses. We adapted the "Medical Artificial Intelligence Scale for Medical Students" to evaluate differences in "AI readiness" before and after taking part in the course. These differences were measured by calculating the so called "comparative self-assessment gain" (CSA gain) which enables a valid and reliable representation of changes in behaviour, attitudes, or knowledge. RESULTS: We found a statistically significant increase in perceived AI readiness. While values of CSA gain were different across items and factors, the overall CSA gain regarding AI readiness was satisfactory. CONCLUSION: Attending a course developed to increase knowledge about AI in medical imaging can increase self-perceived AI readiness in medical students.

Structural Endpoints and Outcome Measures in Uveitis.

Most uveitis entities are rare diseases but, taken together, are responsible for 5-10% of worldwide visual impairment which largely affects persons of working age. As with many rare diseases, there is a lack of high-level evidence regarding its clinical management, partly due to a dearth of reliable and objective quantitative endpoints for clinical trials. This review provides an overview of available structural outcome measures for uveitis disease activity and damage in an anatomical order from the anterior to the posterior segment of the eye. While there is a multitude of available structural outcome measures, not all might qualify as endpoints for clinical uveitis trials, and thorough testing of applicability is warranted. Furthermore, a consensus on endpoint definition, standardization, and "core outcomes" is required. As stipulated by regulatory agencies, endpoints should be precisely defined, clinically important, internally consistent, reliable, responsive to treatment, and relevant for the respective subtype of uveitis. Out of all modalities used for assessment of the reviewed structural outcome measures, optical coherence tomography, color fundus photography, fundus autofluorescence, and fluorescein/indocyanine green angiography represent current "core modalities" for reliable and objective quantification of uveitis outcome measures, based on their practical availability and the evidence provided so far.

Diabetic Retinopathy Screening Using Smartphone-Based Fundus Imaging in India.

PURPOSE: Early detection and treatment can prevent irreversible blindness from diabetic retinopathy (DR), which is the leading cause of visual impairment among working-aged adults worldwide. Some 80% of affected persons live in low- and middle-income countries, yet lack of resources has largely prevented DR screening implementation in these world regions. Smartphone-based fundus imaging (SBFI) allows for low-cost mobile fundus examination using an adapter on a smartphone; however, key aspects such as image quality, diagnostic accuracy, and comparability of different approaches have not been systematically assessed to date. DESIGN: Evaluation of diagnostic technology. PARTICIPANTS: A total of 381 eyes of 193 patients with diabetes were recruited at outreach eye clinics in South India. METHODS: We compared 4 technically different approaches of SBFI (3 approaches based on direct and 1 approach based on indirect ophthalmoscopy) in terms of image quality and diagnostic accuracy for DR screening. MAIN OUTCOME MEASURES: Image quality (sharpness/focus, reflex artifacts, contrast, and illumination), field-of-view, examination time, and diagnostic accuracy for DR screening were analyzed against conventional fundus photography and clinical examination. RESULTS: Smartphone-based fundus imaging based on indirect ophthalmoscopy yielded the best image quality (P < 0.01), the largest field-of-view, and the longest examination time (111 vs. 68-86 seconds, P < 0.0001). Agreement with the reference standard (Cohen's kappa 0.868) and sensitivity/specificity to detect DR were highest for the indirect SBFI approach (0.79/0.99 for any DR and 1.0/1.0 for severe DR, 0.79/1.0 for diabetic maculopathy). CONCLUSIONS: Smartphone-based fundus imaging can meet DR screening requirements in an outreach setting; however, not all devices are suitable in terms of image quality and diagnostic accuracy. Smartphone-based fundus imaging might aid in alleviating the burden of DR screening in low- and middle-income countries, and these results will allow for a better selection of SBFI devices in field trials for DR screening.

NLRP3 and ASC suppress lupus-like autoimmunity by driving the immunosuppressive effects of TGF-ß receptor signalling.

OBJECTIVES: The NLRP3/ASC inflammasome drives host defence and autoinflammatory disorders by activating caspase-1 to trigger the secretion of mature interleukin (IL)-1ß/IL-18, but its potential role in autoimmunity is speculative. METHODS: We generated and phenotyped Nlrp3-deficient, Asc-deficient, Il-1r-deficient and Il-18-deficient C57BL/6-lpr/lpr mice, the latter being a mild model of spontaneous lupus-like autoimmunity. RESULTS: While lack of IL-1R or IL-18 did not affect the C57BL/6-lpr/lpr phenotype, lack of NLRP3 or ASC triggered massive lymphoproliferation, lung T cell infiltrates and severe proliferative lupus nephritis within 6 months, which were all absent in age-matched C57BL/6-lpr/lpr controls. Lack of NLRP3 or ASC increased dendritic cell and macrophage activation, the expression of numerous proinflammatory mediators, lymphocyte necrosis and the expansion of most T cell and B cell subsets. In contrast, plasma cells and autoantibody production were hardly affected. This unexpected immunosuppressive effect of NLRP3 and ASC may relate to their known role in SMAD2/3 phosphorylation during tumour growth factor (TGF)-ß receptor signalling, for example, Nlrp3-deficiency and Asc-deficiency significantly suppressed the expression of numerous TGF-ß target genes in C57BL/6-lpr/lpr mice and partially recapitulated the known autoimmune phenotype of Tgf-ß1-deficient mice. CONCLUSIONS: These data identify a novel non-canonical immunoregulatory function of NLRP3 and ASC in autoimmunity.

[Digital remote monitoring of chronic retinal conditions-A clinical future tool? : Remote monitoring of chronic retinal conditions]. / Digitale Telemedizin zur Überwachung chronischer Netzhauterkrankungen ­ ein klinisches Werkzeug für die Zukunft? : Fernüberwachung chronischer Netzhauterkrankungen.

BACKGROUND: In view of the predicted increase in incidence and prevalence of chronic retinal diseases and undersupply of care in the population, telemedicine could contribute to reducing access barriers to healthcare and improving the results of treatment. OBJECTIVE: A literature review on remote monitoring of chronic retinal diseases was carried out. MATERIAL AND METHODS: The medical literature was searched for publications on remote monitoring of chronic retinal diseases. The results were compiled in a narrative overview. RESULTS: The four main topics in the literature are: validation studies, implementation strategies, acceptance/target group analyses and health economic analyses. Remote monitoring systems are based on visual function tests, imaging or patient reports and have been particularly investigated in age-related macular degeneration (AMD) and diabetic eye disease (DED). Studies indicate positive effects regarding an optimization of clinical care and a favorable safety profile but randomized controlled trials are lacking for the majority of monitoring tools. CONCLUSION: Remote monitoring could complement existing care structures for patients with chronic retinal diseases, especially AMD and DED. Promising systems are based on hyperacuity or optical coherence tomography, while patient-reported data are not commonly used; however, there is currently insufficient evidence justifying the use of remote monitoring systems in chronic retinal diseases in Europe and more research on the validation of remote monitoring systems is needed.

Artificial Intelligence in Cataract Surgery: A Systematic Review.

Purpose: The purpose of this study was to assess the current use and reliability of artificial intelligence (AI)-based algorithms for analyzing cataract surgery videos. Methods: A systematic review of the literature about intra-operative analysis of cataract surgery videos with machine learning techniques was performed. Cataract diagnosis and detection algorithms were excluded. Resulting algorithms were compared, descriptively analyzed, and metrics summarized or visually reported. The reproducibility and reliability of the methods and results were assessed using a modified version of the Medical Image Computing and Computer-Assisted (MICCAI) checklist. Results: Thirty-eight of the 550 screened studies were included, 20 addressed the challenge of instrument detection or tracking, 9 focused on phase discrimination, and 8 predicted skill and complications. Instrument detection achieves an area under the receiver operator characteristic curve (ROC AUC) between 0.976 and 0.998, instrument tracking an mAP between 0.685 and 0.929, phase recognition an ROC AUC between 0.773 and 0.990, and complications or surgical skill performs with an ROC AUC between 0.570 and 0.970. Conclusions: The studies showed a wide variation in quality and pose a challenge regarding replication due to a small number of public datasets (none for manual small incision cataract surgery) and seldom published source code. There is no standard for reported outcome metrics and validation of the models on external datasets is rare making comparisons difficult. The data suggests that tracking of instruments and phase detection work well but surgical skill and complication recognition remains a challenge for deep learning. Translational Relevance: This overview of cataract surgery analysis with AI models provides translational value for improving training of the clinician by identifying successes and challenges.

Skeleton density and ellipsoid zone loss are prognostic for progression in Macular Telangiectasia Type 2.

Macular Telangiectasia Type 2 (MacTel) is a chronic, progressive disease of the central retina characterized by vascular and neurodegenerative changes. As there is currently no treatment for non-neovascular MacTel, there is a dearth for biomarkers identifying eyes with an increased risk for disease progression for patient counseling and clinical trial recruitment. Eyes were classified to be stable or progressive, defined by the fundus photography-based grading system by Gass and Blodi. First, structural differences between these two groups were assessed, employing optical coherence tomography (OCT) and OCT-angiography. Univariate regression analyses revealed evidence towards a lower superficial retinal layer (SRL) vessel density (VD), skeleton density (SD) and deep retinal layer (DRL) SD in progressing compared to stable eyes (p = 0.05, p = 0.05, p = 0.07). Second, a multivariable predictive model was employed to examine the predictive value of structural and functional parameters for disease progression. Baseline best corrected visual acuity (BCVA) and SRL SD are prognostic for disease progression (p < 0.001, p = 0.05). The presence of ellipsoid zone (EZ) loss is prognostic for future central retinal thickness (p < 0.01). We propose SRL SD, BCVA, and EZ loss as prognostic biomarkers and as possible outcome measures in future interventional studies in MacTel.

Piloting Rasch model scoring of the National Eye Institute Visual Function Questionnaire in uveitis.

INTRODUCTION: The National Eye Institute Visual Function Questionnaire (NEI VFQ) is a common patient-reported outcome measure (PROM) in uveitis trials. Its psychometric properties using state-of-the-art scoring based on Rasch models, a latent trait model that improves accuracy of PROMs assessment, has not yet been investigated. METHODS: The study participants were recruited online from uveitis patient organizations, where individuals self-reported their uveitis diagnosis and visual acuity level. These participants then completed the NEI VFQ-25. The visual function (VF) and socioemotional (SE) subscales were psychometrically analysed in terms of item fit, targeting, internal consistency, dimensionality, and differential item functioning (DIF), using Rasch models. Criterion validity was examined based on associations between NEI VFQ person measures and recent visual acuity (VA) levels. RESULTS: Ninety-nine participants recruited online from uveitis patient organizations (68 women, 31 men; mean age 50 ± 15 years; 46.5% self-reported receiving systematic therapy for uveitis, 0.6% NEI VFQ-25 missing data) were included. The mean difficulty of items was lower than the average person ability. None of the items demonstrated misfit to an extent that would induce noise into the measurement. The consistency metrics person reliability and person separation index of the subscales were 0.85 and 2.34 (NEI VFQ-VF), 0.86 and 2.52 (NEI VFQ-SE), respectively. There was no evidence of multidimensionality and none of the items showed DIF by gender. The differences between item and person measures were 1.44 (NEI VFQ-VF) and 1.03 (NEI VFQ-SE). NEI VFQ-25 person measures were significantly lower in participants with visual impairment (all p values ≤ 0.007). CONCLUSION: Rasch model-based scoring of the re-engineered NEI VFQ-25 demonstrates acceptable internal consistency, item fit and construct validity for assessing two key domains of quality of life in individuals self-reporting uveitis. The PROM was targeted at a higher level of difficulty than present in our heterogeneous sample.

Vessel density on optical coherence tomography angiography is prognostic for future disease course in intermediate uveitis.

As most rare diseases, intermediate uveitis lacks reliable endpoints necessary for randomized clinical trials. Therefore, we investigated longitudinal changes of retinal and choriocapillaris perfusion on optical coherence tomography angiography (OCT-A) in intermediate uveitis and their prognostic value for future best corrected visual acuity (BCVA) and central retinal thickness (CRT). In this retrospective, longitudinal cohort study eyes of patients with intermediate uveitis were imaged by swept-source OCT-A (macula-centered 3 × 3 mm; PLEX Elite 9000, Zeiss) and stratified into clinically stable, worsened and improved based on changes in clinical parameters. Superficial (SRL) and deep retinal layers (DRL) were automatically analyzed for vessel density (VD) and choriocapillaris layer for non-perfused area (CCNPA) using ImageJ. Mixed-effects regression analysis controlling for age, sex, and OCT-A signal strength index (SSI) was used to evaluate the prognostic value of OCT-A parameters. 91 eyes (62 stable, 12 worsened, and 17 improved) were included in the analysis and mean follow-up time was 296 days. Longitudinal changes of VD were different between all three groups (p = 0.002 for SRL and p = 0.017 for DRL). Clinically worsened eyes showed a decrease in VD (- 0.032 ± 0.055 for SRL and - 0.027 ± 0.025 for DRL), whereas clinically improved eyes showed an increase in VD (0.037 ± 0.039 for SRL and 0.001 ± 0.023 for DRL). No difference was found for CCNPA. When controlling for age, sex, and SSI, observed differences held true in clinically worsened eyes for DRL (p = 0.011) and in clinically improved eyes for SRL (p = 0.002). An increase of CCNPA in clinically worsened eyes (p = 0.03) compared to clinically stable and improved eyes was evident. Predictive analysis revealed an association of VD in SRL and DRL at baseline with BCVA at follow-up (p = 0.039 and p = 0.047, respectively) and of VD in SRL at baseline with CRT at follow-up (p = 0.046). Alterations in retinal perfusion on OCT-A in intermediate uveitis are partly reversible and OCT-A VD may serve to predict future BCVA and CRT. Thus, perfusion parameters on OCT-A might aid monitoring and serve as prognostic imaging-biomarker.

Effects of lorazepam on saccadic eye movements - evidence from prosaccade and free viewing tasks.

RATIONALE: Peak velocities of saccadic eye movements are reduced after benzodiazepine administration. Even though this is an established effect, past research has only examined it in horizontal prosaccade tasks. OBJECTIVES: The spectrum of saccadic eye movements, however, is much larger. Therefore, we aimed to make a first attempt at filling this research gap by testing benzodiazepine effects on saccades under different experimental task conditions. METHODS: 1 mg lorazepam or placebo was administered (within-subjects, double-blind, in randomised order) to n = 30 healthy adults. Participants performed an extended version of the prosaccade task, including vertical saccade directions and different stimulus eccentricities, as well as a free viewing task. RESULTS: Results from the prosaccade task confirmed established effects of benzodiazepines as well as saccade direction on saccadic parameters but additionally showed that the drug effect on peak velocity was independent of saccade direction. Remarkably, in the free viewing task peak velocities as well as other saccade parameters were unaffected by lorazepam. Furthermore, exploration patterns during free viewing did not change under lorazepam. CONCLUSIONS: Overall, our findings further consolidate the peak velocity of prosaccades as a biomarker of sedation. Additionally, we suggest that sedative effects of low doses of benzodiazepines may be compensated in tasks that more closely resemble natural eye movement behaviour, possibly due to the lack of time constraints or via neurophysiological processes related to volition.

Retinal Vascular Changes in Heart Failure with Preserved Ejection Fraction Using Optical Coherence Tomography Angiography.

Background: Systemic microvascular regression and dysfunction are considered important underlying mechanisms in heart failure with preserved ejection fraction (HFpEF), but retinal changes are unknown. Methods: This prospective study aimed to investigate whether retinal microvascular and structural parameters assessed using optical coherence tomography angiography (OCT-A) differ between patients with HFpEF and control individuals (i.e., capillary vessel density, thickness of retina layers). We also aimed to assess the associations of retinal parameters with clinical and echocardiographic parameters in HFpEF. HFpEF patients, but not controls, underwent echocardiography. Macula-centered 6 × 6 mm volume scans were computed of both eyes. Results: Twenty-two HFpEF patients and 24 controls without known HFpEF were evaluated, with an age of 74 [68-80] vs. 68 [58-77] years (p = 0.027), and 73% vs. 42% females (p = 0.034), respectively. HFpEF patients showed vascular degeneration compared to controls, depicted by lower macular vessel density (p < 0.001) and macular ganglion cell-inner plexiform layer thickness (p = 0.025), and a trend towards lower total retinal volume (p = 0.050) on OCT-A. In HFpEF, a lower total retinal volume was associated with markers of diastolic dysfunction (septal e', septal and average E/e': R2 = 0.38, 0.36, 0.25, respectively; all p < 0.05), even after adjustment for age, sex, diabetes mellitus, or atrial fibrillation. Conclusions: Patients with HFpEF showed clear levels of retinal vascular changes compared to control individuals, and retinal alterations appeared to be associated with markers of more severe diastolic dysfunction in HFpEF. OCT-A may therefore be a promising technique for monitoring systemic microvascular regression and cardiac diastolic dysfunction.

Fundus Autofluorescence in Posterior and Panuveitis-An Under-Estimated Imaging Technique: A Review and Case Series.

Fundus autofluorescence (FAF) is a prompt and non-invasive imaging modality helpful in detecting pathological abnormalities within the retina and the choroid. This narrative review and case series provides an overview on the current application of FAF in posterior and panuveitis. The literature was reviewed for articles on lesion characteristics on FAF of specific posterior and panuveitis entities as well as benefits and limitations of FAF for diagnosing and monitoring disease. FAF characteristics are described for non-infectious and infectious uveitis forms as well as masquerade syndromes. Dependent on the uveitis entity, FAF is of diagnostic value in detecting disease and following the clinical course. Currently available FAF modalities which differ in excitation wavelengths can provide different pathological insights depending on disease entity and activity. Further studies on the comparison of FAF modalities and their individual value for uveitis diagnosis and monitoring are warranted.

Autofluorescence-based tissue characterization enhances clinical prospects of light-sheet-microscopy.

Light sheet fluorescence microscopy (LSFM) is a transformative imaging method that enables the visualization of non-dissected specimen in real-time 3D. Optical clearing of tissues is essential for LSFM, typically employing toxic solvents. Here, we test the applicability of a non-hazardous alternative, ethyl cinnamate (ECi). We comprehensively characterized autofluorescence (AF) spectra in diverse murine tissues-ocular globe, knee, and liver-employing LSFM under various excitation wavelengths (405-785 nm) to test the feasibility of unstained samples for diagnostic purposes, in particular regarding percutaneous biopsies, as they constitute to most harvested type of tissue sample in clinical routine. Ocular globe structures were best discerned with 640 nm excitation. Knee tissue showed complex variation in AF spectra variation influenced by tissue depth and structure. Liver exhibited a unique AF pattern, likely linked to vasculature. Hepatic tissue samples were used to demonstrate the compatibility of our protocol for antibody staining. Furthermore, we employed machine learning to augment raw images and segment liver structures based on AF spectra. Radiologists rated representative samples transferred to the clinical assessment software. Learning-generated images scored highest in quality. Additionally, we investigated an actual murine biopsy. Our study pioneers the application of AF spectra for tissue characterization and diagnostic potential of optically cleared unstained percutaneous biopsies, contributing to the clinical translation of LSFM.

Treatment exit options for non-infectious uveitis registry: participant characteristics at 3 years.

PURPOSE: The Treatment exit Options For non-infectious Uveitis (TOFU) registry documents disease courses for non-anterior non-infectious uveitis entities with and without treatment to generate more evidence for clinical management recommendations including treatment exit strategies. In this article, we present the participants' baseline characteristics after the first 3 years. METHODS: TOFU is an observational, prospective registry and recruits patients ≥18 years of age with non-anterior non-infectious uveitis with or without a history of previous disease-modifying antirheumatic drugs (DMARDs) treatment. The data are collected in the electronic data capture software REDCap and include ophthalmological and general medical history as well as clinical findings. RESULTS: Between 24.10.2019 and 27.12.2022, 628 patients were enrolled at 25 clinical sites in Germany and Austria. Patients with intermediate uveitis were most frequently included (n=252; 40.1%) followed by posterior uveitis (181; 28.8%), panuveitis (n=154; 24.5%) and retinal vasculitis (n=41, 6.5%). At baseline, 39.6% were treated with systemic corticosteroids, 22.3% with conventional synthetic (cs) DMARDs, 20.5% with biological (b) DMARDs and 3.6% with other systemic treatments. Average best corrected visual acuity (BCVA) was 0.69 decimal. Patients with panuveitis had the worst BCVA with 0.63 decimal. Overall, only 8 patients (1.3%) suffered from severe visual impairment. CONCLUSIONS: Less than half of participants required DMARD treatment at baseline, with csDMARDs used more frequently than bDMARDs. The presence of severe visual impairment was low, mostly affecting patients with panuveitis. These findings are in line with comparable monocentric cross-sectional studies of tertiary uveitis centres in Germany and will allow us to generate generalisable evidence in TOFU.

Accurate drusen segmentation in optical coherence tomography via order-constrained regression of retinal layer heights.

Drusen are an important biomarker for age-related macular degeneration (AMD). Their accurate segmentation based on optical coherence tomography (OCT) is therefore relevant to the detection, staging, and treatment of disease. Since manual OCT segmentation is resource-consuming and has low reproducibility, automatic techniques are required. In this work, we introduce a novel deep learning based architecture that directly predicts the position of layers in OCT and guarantees their correct order, achieving state-of-the-art results for retinal layer segmentation. In particular, the average absolute distance between our model's prediction and the ground truth layer segmentation in an AMD dataset is 0.63, 0.85, and 0.44 pixel for Bruch's membrane (BM), retinal pigment epithelium (RPE) and ellipsoid zone (EZ), respectively. Based on layer positions, we further quantify drusen load with excellent accuracy, achieving 0.994 and 0.988 Pearson correlation between drusen volumes estimated by our method and two human readers, and increasing the Dice score to 0.71 ± 0.16 (from 0.60 ± 0.23) and 0.62 ± 0.23 (from 0.53 ± 0.25), respectively, compared to a previous state-of-the-art method. Given its reproducible, accurate, and scalable results, our method can be used for the large-scale analysis of OCT data.