Additional measures of macular function beyond visual acuity.

PURPOSE: Visual function is a complex process in which external visual stimuli are interpreted. Patients with retinal diseases and prolonged follow-up times may experience changes in their visual function that are not detected by the standard visual acuity measure, as they are a result of other alterations in visual function. With the advancement of different methods to evaluate visual function, additional measurements have become available, and further standardization suggests that some methods may be promising for use in clinical trials or routine clinical practice. The objectives of this article are to review these additional measurements and to provide guidance on their application. METHODS: The Vision Academy's membership of international retinal disease experts reviewed the literature and developed consensus recommendations for the application of additional measures of visual function in routine clinical practice or clinical trials. RESULTS: Measures such as low-luminance visual acuity, contrast sensitivity, retinal fixation and microperimetry, and reading performance are measures which can complement visual acuity measurements to provide an assessment of overall visual function, including impact on patients' quality of life. Measures such as dark adaptation, color vision testing, binocular vision testing, visual recognition testing, and shape discrimination require further optimization and validation before they can be implemented in everyday clinical practice. CONCLUSION: Additional measurements of visual function may help identify patients who could benefit from earlier diagnosis, detection of disease progression, and therapeutic intervention. New and additional functional clinical trial endpoints are required to fully understand the early stages of macular disease, its progression, and the response to treatment.

Usher syndrome type IV: clinically and molecularly confirmed by novel ARSG variants.

Usher syndrome (USH) is an autosomal recessively inherited disease characterized by sensorineural hearing loss (SNHL) and retinitis pigmentosa (RP) with or without vestibular dysfunction. It is highly heterogeneous both clinically and genetically. Recently, variants in the arylsulfatase G (ARSG) gene have been reported to underlie USH type IV. This distinct type of USH is characterized by late-onset RP with predominantly pericentral and macular changes, and late onset SNHL without vestibular dysfunction. In this study, we describe the USH type IV phenotype in three unrelated subjects. We identified three novel pathogenic variants, two novel likely pathogenic variants, and one previously described pathogenic variant in ARSG. Functional experiments indicated a loss of sulfatase activity of the mutant proteins. Our findings confirm that ARSG variants cause the newly defined USH type IV and support the proposed extension of the phenotypic USH classification.

Context, coping, and mental health in refugees living in protracted displacement.

There is currently an unprecedented number of forcibly displaced people worldwide. Little is known, however, about how external stressors and internal coping strategies intersect to influence mental health in displaced refugees, particularly whether specific types of coping strategies are more or less effective across different levels of external stress. This study aimed to understand whether positive and negative internal coping strategies were differentially associated with mental health across high and low levels of external stressors in displaced refugees. Participants were 1,216 refugees living in Indonesia who completed an online survey indexing demographic characteristics, exposure to ongoing stressors, positive psychological coping strategies (i.e., cognitive flexibility, self-efficacy, and hope), negative psychological coping strategies (i.e., rumination and intolerance of uncertainty), psychological symptoms (i.e., posttraumatic stress disorder, depression, and anxiety) and mental health-related quality of life. Participants (27.3% female, Mage = 30.52 years) were from Arabic-, Farsi-, Tamil-, Somali-, Dari-, and English-speaking backgrounds. Results of latent moderated structural equation modeling indicated that the association between negative psychological coping strategies and poorer mental health was stronger at higher levels of stress, whereas the association between positive psychological coping strategies and better quality of life was stronger at lower levels of stress. These findings provide evidence in support of tailored approaches that integrate interventions addressing external stressors and internal coping strategies to support positive mental health and enhanced quality of life in displaced refugees.

Clinical and Genetic Re-Evaluation of Inherited Retinal Degeneration Pedigrees following Initial Negative Findings on Panel-Based Next Generation Sequencing.

Although rare, inherited retinal degenerations (IRDs) are the most common reason for blind registration in the working age population. They are highly genetically heterogeneous (>300 known genetic loci), and confirmation of a molecular diagnosis is a prerequisite for many therapeutic clinical trials and approved treatments. First-tier genetic testing of IRDs with panel-based next-generation sequencing (pNGS) has a diagnostic yield of ≈70-80%, leaving the remaining more challenging cases to be resolved by second-tier testing methods. This study describes the phenotypic reassessment of patients with a negative result from first-tier pNGS and the rationale, outcomes, and cost of second-tier genetic testing approaches. Removing non-IRD cases from consideration and utilizing case-appropriate second-tier genetic testing techniques, we genetically resolved 56% of previously unresolved pedigrees, bringing the overall resolve rate to 92% (388/423). At present, pNGS remains the most cost-effective first-tier approach for the molecular assessment of diverse IRD populations Second-tier genetic testing should be guided by clinical (i.e., reassessment, multimodal imaging, electrophysiology), and genetic (i.e., single alleles in autosomal recessive disease) indications to achieve a genetic diagnosis in the most cost-effective manner.

An Interaction Model of Environmental and Psychological Factors Influencing Refugee Mental Health.

In this paper, we draw on empirical research and theoretical models of refugee and posttrauma mental health to propose the "Psychological Interaction with Environment (PIE) Matrix Model" of refugee mental health. This model focuses on the mental health of adult refugees and proposes that psychological factors and the external environment interact to influence mental health outcomes and functioning for individuals with refugee backgrounds. Environmental factors include adversity faced before, during, and after the migration journey, including adversity faced in a resettlement or postdisplacement environment. Psychological factors refer to psychological (i.e., cognitive and emotional) mechanisms that individuals may use to cope with adversity. We posit that individuals from refugee backgrounds are likely to show individual differences in psychological processes that may protect against or underpin the development and maintenance of psychopathology following exposure to trauma and displacement. The PIE Matrix Model proposes a framework to guide intervention by identifying key pathways by which psychological and environmental factors impact one another. We suggest that psychological interventions can be targeted according to the kind and level of support different individuals may require, based on individualized and context-driven assessments of the interaction between environmental and psychological factors at any given point in time. This model draws on existing models of refugee adaptation and highlights the need for longitudinal and experimental research to explain the interaction between these factors and their causal impact on refugee mental health.

Viewing faculty development through an organizational lens: Sharing lessons learned.

INTRODUCTION: Faculty Development (FD) plays a key role in supporting education, especially during times of change. The effectiveness of FD often depends upon organizational factors, indicating a need for a deeper appreciation of the role of institutional context. How do organizational factors constrain or enhance the capacity of faculty developers to fulfil their mandates? METHODS: Using survey research methodology, data from a survey of FD leaders at Canadian medical schools were analyzed using Bolman and Deal's four frames: Symbolic, Political, Structural, and Human Resource (HR). RESULTS: In the Symbolic frame, FD leaders reported lack of identity as a FD unit, which was seen as a constraining factor. Within the Political frame, developing visibility was seen as an enhancing factor, though it did not always ensure being valued. In the Structural frame, expanding scope of practice was seen as an enhancing factor, though it could also be a constraining factor if not accompanied by increased resources. In the HR frame, a sense of instability due to changing leadership and uncertainty about human resources was seen as a constraining factor. CONCLUSION: While broadening the mandate of FD can generally be considered as positive, it is imperative that it is appropriately resourced and accompanied by recognition of FD as a valued contributor to the educational mission.

Differential Circulating MicroRNA Expression in Age-Related Macular Degeneration.

This study explored the expression of several miRNAs reported to be deregulated in age-related macular degeneration (AMD). Total RNA was isolated from sera from patients with dry AMD (n = 12), wet AMD (n = 14), and controls (n = 10). Forty-two previously investigated miRNAs were selected based on published data and their role in AMD pathogenesis, such as angiogenic and inflammatory effects, and were co-analysed using a miRCURY LNA miRNA SYBR® Green PCR kit via quantitative real-time polymerase chain reaction (qRT-PCR) to validate their presence. Unsupervised hierarchical clustering indicated that AMD serum specimens have a different miRNA profile to healthy controls. We successfully validated the differentially regulated miRNAs in serum from AMD patients versus controls. Eight miRNAs (hsa-let-7a-5p, hsa-let-7d-5p, hsa-miR-23a-3p, hsa-miR-301a-3p, hsa-miR-361-5p, hsa-miR-27b-3p, hsa-miR-874-3p, hsa-miR-19b-1-5p) showed higher expression in the serum of dry AMD patients than wet AMD patients and compared with healthy controls. Increased quantities of certain miRNAs in the serum of AMD patients indicate that these miRNAs could potentially serve as diagnostic AMD biomarkers and might be used as future AMD treatment targets. The discovery of significant serum miRNA biomarkers in AMD patients would provide an easy screening tool for at-risk populations.

Longitudinal association between trust, psychological symptoms and community engagement in resettled refugees.

BACKGROUND: The mental health and social functioning of millions of forcibly displaced individuals worldwide represents a key public health priority for host governments. This is the first longitudinal study with a representative sample to examine the impact of interpersonal trust and psychological symptoms on community engagement in refugees. METHODS: Participants were 1894 resettled refugees, assessed within 6 months of receiving a permanent visa in Australia, and again 2-3 years later. Variables measured included post-traumatic stress disorder symptoms, depression/anxiety symptoms, interpersonal trust and engagement with refugees' own and other communities. RESULTS: A multilevel path analysis was conducted, with the final model evidencing good fit (Comparative Fit Index = 0.97, Tucker-Lewis Index = 0.89, Root Mean Square Error of Approximation = 0.05, Standardized Root-Mean-Square-Residual = 0.05). Findings revealed that high levels of depression symptoms were associated with lower subsequent engagement with refugees' own communities. In contrast, low levels of interpersonal trust were associated with lower engagement with the host community over the same timeframe. CONCLUSIONS: Findings point to differential pathways to social engagement in the medium-term post-resettlement. Results indicate that depression symptoms are linked to reduced engagement with one's own community, while interpersonal trust is implicated in engagement with the broader community in the host country. These findings have potentially important implications for policy and clinical practice, suggesting that clinical and support services should target psychological symptoms and interpersonal processes when fostering positive adaptation in resettled refugees.

A Novel FLVCR1 Variant Implicated in Retinitis Pigmentosa.

Here we describe the identification and evaluation of a rare novel autosomal recessive mutation in FLVCR1 which is implicated solely in RP, with no evidence of posterior column ataxia in a number of affected patients. The mutation was detected as part of an ongoing target capture NGS study (Target 5000), aimed at identifying candidate variants in pedigrees with inherited retinal degenerations (IRDs) in Ireland. The mutation, FLVCR1 p.Tyr341Cys, was observed homozygously in seven affected patients across four pedigrees. FLVCR1 p.Tyr341Cys is a very rare mutation, with no previous reports of pathogenicity and no homozygous cases reported in online allele frequency databases. Our sequencing study identified seven homozygotes across multiple pedigrees, all with similar clinical presentations of RP without ataxia, a scenario extremely unlikely to occur by chance for a benign allele, particularly given the low population frequency of p.Tyr341Cys.

Multimodal imaging in a pedigree of X-linked Retinoschisis with a novel RS1 variant.

BACKGROUND: To describe the clinical phenotype and genetic cause underlying the disease pathology in a pedigree (affected n = 9) with X-linked retinoschisis (XLRS1) due to a novel RS1 mutation and to assess suitability for novel therapies using multimodal imaging. METHODS: The Irish National Registry for Inherited Retinal Degenerations (Target 5000) is a program including clinical history and examination with multimodal retinal imaging, electrophysiology, visual field testing and genetic analysis. Nine affected patients were identified across 3 generations of an XLRS1 pedigree. DNA sequencing was performed for each patient, one carrier female and one unaffected relative. Pedigree mapping revealed a further 4 affected males. RESULTS: All affected patients had a history of reduced visual acuity and dyschromatopsia; however, the severity of phenotype varied widely between the nine affected subjects. The stage of disease was classified as previously described. Phenotypic severity was not linearly correlated with age. A novel RS1 (Xp22.2) mutation was detected (NM_000330: c.413C > A) resulting in a p.Thr138Asn substitution. Protein modelling demonstrated a change in higher order protein folding that is likely pathogenic. CONCLUSIONS: This family has a novel gene mutation in RS1 with clinical evidence of XLRS1. A proportion of the older generation has developed end-stage macular atrophy; however, the severity is variable. Confirmation of genotype in the affected grandsons of this pedigree in principle may enable them to avail of upcoming gene therapies, provided there is anatomical evidence (from multimodal imaging) of potentially reversible early stage disease.

Not just trust: factors influencing learners' attempts to perform technical skills on real patients.

CONTEXT: As part of their training, physicians are required to learn how to perform technical skills on patients. The previous literature reveals that this learning is complex and that many opportunities to perform these skills are not converted into attempts to do so by learners. This study sought to explore and understand this phenomenon better. METHODS: A multi-phased qualitative study including ethnographic observations, interviews and focus groups was conducted to explore the factors that influence technical skill learning. In a tertiary paediatric emergency department, staff physician preceptors, residents, nurses and respiratory therapists were observed in the delivery and teaching of technical skills over a 3-month period. A constant comparison methodology was used to analyse the data and to develop a constructivist grounded theory. RESULTS: We conducted 419 hours of observation, 18 interviews and four focus groups. We observed 287 instances of technical skills, of which 27.5% were attempted by residents. Thematic analysis identified 14 factors, grouped into three categories, which influenced whether residents attempted technical skills on real patients. Learner factors included resident initiative, perceived need for skill acquisition and competing priorities. Teacher factors consisted of competing priorities, interest in teaching, perceived need for residents to acquire skills, attributions about learners, assessments of competency, and trust. Environmental factors were competition from other learners, judgement that the patient was appropriate, buy-in from team members, consent from patient or caregivers, and physical environment constraints. CONCLUSIONS: Our findings suggest that neither the presence of a learner in a clinical environment nor the trust of the supervisor is sufficient to ensure the learner will attempt a technical skill. We characterise this phenomenon as representing a pool of opportunities to conduct technical skills on live patients that shrinks to a much smaller pool of technical skill attempts. Learners, teachers and educators can use this knowledge to maximise the number of attempts learners make to perform technical skills on real patients.

Shared Canadian Curriculum in Family Medicine (SHARC-FM): Creating a national consensus on relevant and practical training for medical students.

PROBLEM ADDRESSED: In 2006, leaders of undergraduate family medicine education programs faced a series of increasing curriculum mandates in the context of limited time and financial resources. Additionally, it became apparent that a hidden curriculum against family medicine as a career choice was active in medical schools. OBJECTIVE OF PROGRAM: The Shared Canadian Curriculum in Family Medicine was developed by the Canadian Undergraduate Family Medicine Education Directors and supported by the College of Family Physicians of Canada as a national collaborative project to support medical student training in family medicine clerkship. Its key objective is to enable education leaders to meet their educational mandates, while at the same time countering the hidden curriculum and providing a route to scholarship. PROGRAM DESCRIPTION: The Shared Canadian Curriculum in Family Medicine is an open-access, shared, national curriculum (www.sharcfm.ca). It contains 23 core clinical topics (determined through a modified Delphi process) with demonstrable objectives for each. It also includes low- and medium-fidelity virtual patient cases, point-of-care learning resources (clinical cards), and assessment tools, all aligned with the core topics. French translation of the resources is ongoing. CONCLUSION: The core topics, objectives, and educational resources have been adopted by medical schools across Canada, according to their needs. The lessons learned from mounting this multi-institutional collaborative project will help others develop their own collaborative curricula.

Bullous Variant of Central Serous Chorioretinopathy: Expansion of Phenotypic Features Using Multimethod Imaging.

PURPOSE: To define the phenotypic characteristics of the bullous variant of central serous chorioretinopathy (CSC) using multimethod imaging. DESIGN: Retrospective, observational case series. PARTICIPANTS: Twenty-one eyes of 14 patients with bullous retinal detachment resulting from CSC (bullous CSC group) and 122 eyes of 84 patients with chronic CSC without bullous retinal detachment (nonbullous CSC group). METHODS: We performed a retrospective review of clinical and multimethod imaging data of patients who sought treatment from the authors with bullous retinal detachment resulting from CSC between January 2010 and November 2015. Multimethod imaging comprised color photography, fluorescein angiography, fundus autofluorescence, and high-resolution optical coherence tomography. Consecutive cases of chronic CSC without bullous retinal detachment, seen during the same period, comprised a comparative group. MAIN OUTCOME MEASURES: Qualitative and quantitative characteristics of the choroid, retinal pigment epithelium, and retina were compared between the 2 groups. RESULTS: Mean age of the bullous CSC group was 53.8 years. There was no difference in age, visual acuity, corticosteroid use, or the proportion of white patients and men between the 2 groups (all P > 0.132). Peripheral nonperfusion occurred only in eyes with bullous retinal detachment (38% of cases). Retinal pigment epithelial tears were seen in 95% of eyes in the bullous group and none of the eyes in the nonbullous CSC group. The bullous CSC group demonstrated a greater number of pigment epithelial detachments (PEDs) and more eyes demonstrated PEDs with internal hyperreflectivity (both P < 0.016). Mean subfoveal choroidal thickness in the bullous CSC group (463.1±83.1 µm) was not different compared with that of the nonbullous CSC group (400.6±100.6 µm; P = 0.993). More eyes in the bullous CSC group demonstrated hyperreflectivity around large choroidal vessels and at the level of the choriocapillaris on OCT (P < 0.001). Retinal folds and subretinal fibrin were identified in a greater proportion of eyes in the bullous CSC group (both P < 0.001). CONCLUSIONS: Bullous retinal detachment is a rare manifestation of chronic CSC and is characterized by a unique constellation of phenotypic and multimethod imaging features.

Objective assessment of symptomatic vitreous floaters using optical coherence tomography: a case report.

BACKGROUND: Vitrectomy for symptomatic vitreous floaters carries significant risks. Justification of surgery is difficult, particularly in healthy eyes with normal visual acuity and without a posterior vitreous detachment. This is the first reported case of optical coherence tomography being utilized to objectively assess the impact of a vitreous opacity on the macula. CASE PRESENTATION: A 37-year-old Caucasian female complained of the sudden onset of a ring-like floater in the central visual field of her left eye. Visual acuity was 20/20, there was no intraocular inflammation and the posterior vitreous was not detached. Complete blood count with differential, serology screen (including cysticercosis and echinococcus), chest x-ray and abdominal ultrasound found no evidence of systemic infective or cystic disease. A color photograph and B-scan ultrasound confirmed a 4.31 mm free-floating semi-translucent vitreous cyst with a hyperechogenic, pigmented surface and faint internal strands suspended in the mid-vitreous cavity, in the visual axis. The cyst moved with ocular movements, but only within the vitreous lacuna it resided in. Humphrey and Goldmann visual fields were normal. However, spectral domain optical coherence tomography (OCT) demonstrated shadowing on either side of the fovea, consistent with the ring-like scotoma described by the patient. Removing the retinal layers from the 3D-reconstructed macular cube OCT revealed a circular shadow on the macula. The patient elected for conservative management and at 3-month follow-up her symptoms had almost fully resolved as the cyst migrated to the inferior vitreous cavity, no longer casting a shadow on the macula. CONCLUSION: To our knowledge, this is the first description of using OCT as an objective, qualitative assessment of symptoms caused by large vitreous opacities and may provide a simple yet useful adjunctive tool in evaluating the risk-benefit ratio of vitrectomy in patients with large symptomatic vitreous floaters.

Addressing Technical Failures in a Diabetic Retinopathy Screening Program.

Purpose: Diabetic retinopathy (DR) is a preventable cause of blindness detectable through screening using retinal digital photography. The Irish National Diabetic Retina Screening (DRS) programme, Diabetic RetinaScreen, provides free screening services to patients with diabetes from aged 12 years and older. A technical failure (TF) occurs when digital retinal imaging is ungradable, resulting in delays in the diagnosis and treatment of sight-threatening disease. Despite their impact, the causes of TFs, and indeed the utility of interventions to prevent them, have not been extensively examined. Aim: Primary analysis aimed to identify factors associated with TF. Secondary analysis examined a subset of cases, assessing patient data from five time points between 2019 and 2021 to identify photographer/patient factors associated with TF. Methods: Patient data from the DRS database for one provider were extracted for analysis between 2018 and 2022. Information on patient demographics, screening results, and other factors previously associated with TF were analyzed. Primary analysis involved using mixed-effects logistic regression models with nested patient-eye random effects. Secondary analysis reviewed a subset of cases in detail, checking for causes of TF. Results: The primary analysis included a total of 366,528 appointments from 104,407 patients over 5 years. Most patients had Type 2 diabetes (89.2%), and the overall TF rate was 4.9%. Diabetes type and duration, dilate pupil status, and the presence of lens artefacts on the camera were significantly associated with TF. The Secondary analysis identified the primary cause of TF was found to be optically dense cataracts, accounting for over half of the TFs. Conclusion: This study provides insight into the causes of TF within the Irish DRS program, highlighting cataracts as the primary contributing factor. The identification of patient-level factors associated with TF facilitates appropriate interventions that can be put in place to improve patient outcomes and minimize delays in treatment and diagnosis.

The Role of the Ophthalmic Genetics Multidisciplinary Team in the Management of Inherited Retinal Degenerations-A Case-Based Review.

(1) Background: Inherited retinal degenertions are rare conditions which may have a dramatic impact on the daily life of those affected and how they interact with their environment. Coordination of clinical services via an ophthalmic genetics multidisciplinary team (OG-MDT) allows better efficiency of time and resources to reach diagnoses and facilitate patient needs. (2) Methods: This clinical case series was conducted by a retrospective review of patient records for patients enrolled in the Target 5000 programme and managed by the OG-MDT, at the Mater Hospital Dublin, Ireland (n = 865) (3) Results: Herein we describe clinical cases and how the use of the OG-MDT optimizes care for isolated and syndromic IRD pedigrees. (4) Conclusions: this paper demonstrates the benefits of an OG-MDT to patients with IRDs resulting in the holistic resolution of complex and syndromic cases. Furthermore, we demonstrate that this format can be adopted/developed by similar centres around the world, bringing with it the myriad benefits.

DFPE, partially fluorinated ether: a novel approach for experimental intravitreal tamponade.

PURPOSE: To evaluate decafluoro-di-n-pentyl ether (DFPE) as a vitreous tamponade by examining ocular tolerance in rabbits' eyes. METHODS: Thirteen rabbits were divided into 4 groups after mechanical vitrectomy and were followed up to 12 months. The tamponade remained in the eye for 6 months in group 1 (DFPE) and Group 3 (DFPE and silicone oil) and for 12 months in group 2 (DFPE). Group 4 served as control. RESULTS: In groups 1, 2, and 3, dispersion of the fluid appeared 2 weeks postoperatively. Posterior subcapsular cataracts appeared in rabbits' eyes with large fills of DFPE (>50%). Histologic findings in groups 1 and 2 showed no detectable change in outer nuclear layer thickness. Except for some vacuolations, the inner retina was well preserved in all injected rabbits' eyes. On the electroretinography of injected rabbits' eyes, there was no effect on the a wave amplitude and b wave implicit time, but the b wave amplitude was elevated with statistical significance (P < 0.001) at 1, 3, and 6 months postoperatively but with no statistical significance (P > 0.05) after that period when compared with group 4 and unoperated fellow rabbits' eyes of each group. CONCLUSION: Decafluoro-di-n-pentyl ether demonstrated minimum adverse effects in retinal rabbits; further studies are needed before clinical use as short-term tamponade.