Retinal Dystrophies Associated With Peripherin-2: Genetic Spectrum and Novel Clinical Observations in 241 Patients.

Purpose: To describe the clinical, electrophysiological and genetic spectrum of inherited retinal diseases associated with variants in the PRPH2 gene. Methods: A total of 241 patients from 168 families across 15 sites in 9 countries with pathogenic or likely pathogenic variants in PRPH2 were included. Records were reviewed for age at symptom onset, visual acuity, full-field ERG, fundus colour photography, fundus autofluorescence (FAF), and SD-OCT. Images were graded into six phenotypes. Statistical analyses were performed to determine genotype-phenotype correlations. Results: The median age at symptom onset was 40 years (range, 4-78 years). FAF phenotypes included normal (5%), butterfly pattern dystrophy, or vitelliform macular dystrophy (11%), central areolar choroidal dystrophy (28%), pseudo-Stargardt pattern dystrophy (41%), and retinitis pigmentosa (25%). Symptom onset was earlier in retinitis pigmentosa as compared with pseudo-Stargardt pattern dystrophy (34 vs 44 years; P = 0.004). The median visual acuity was 0.18 logMAR (interquartile range, 0-0.54 logMAR) and 0.18 logMAR (interquartile range 0-0.42 logMAR) in the right and left eyes, respectively. ERG showed a significantly reduced amplitude across all components (P < 0.001) and a peak time delay in the light-adapted 30-Hz flicker and single-flash b-wave (P < 0.001). Twenty-two variants were novel. The central areolar choroidal dystrophy phenotype was associated with 13 missense variants. The remaining variants showed marked phenotypic variability. Conclusions: We described six distinct FAF phenotypes associated with variants in the PRPH2 gene. One FAF phenotype may have multiple ERG phenotypes, demonstrating a discordance between structure and function. Given the vast spectrum of PRPH2 disease our findings are useful for future clinical trials.

Development of a robotic cluster for automated and scalable cell therapy manufacturing.

BACKGROUND AIMS: The production of commercial autologous cell therapies such as chimeric antigen receptor T cells requires complex manual manufacturing processes. Skilled labor costs and challenges in manufacturing scale-out have contributed to high prices for these products. METHODS: We present a robotic system that uses industry-standard cell therapy manufacturing equipment to automate the steps involved in cell therapy manufacturing. The robotic cluster consists of a robotic arm and customized modules, allowing the robot to manipulate a variety of standard cell therapy instruments and materials such as incubators, bioreactors, and reagent bags. This system enables existing manual manufacturing processes to be rapidly adapted to robotic manufacturing, without having to adopt a completely new technology platform. Proof-of-concept for the robotic cluster's expansion module was demonstrated by expanding human CD8+ T cells. RESULTS: The robotic cultures showed comparable cell yields, viability, and identity to those manually performed. In addition, the robotic system was able to maintain culture sterility. CONCLUSIONS: Such modular robotic solutions may support scale-up and scale-out of cell therapies that are developed using classical manual methods in academic laboratories and biotechnology companies. This approach offers a pathway for overcoming manufacturing challenges associated with manual processes, ultimately contributing to the broader accessibility and affordability for personalized immunotherapies.

Clinician Awareness of Stickler Syndromes Among Australian Allied Health Care Professionals.

Purpose: Stickler Syndromes are multisystem collagenopathies affecting 1 in 7500-9000 individuals and are associated with craniofacial, ocular, auditory, and musculoskeletal complications. Prophylactic retinopexy treatment reduces the risk of retinal detachment, emphasising the need for early detection and multidisciplinary referral. This study evaluated knowledge and awareness of Stickler Syndromes among allied health professionals and their perceived needs for targeted education to improve multidisciplinary care. Methods: A cross-sectional survey was undertaken among audiologists, speech pathologists, optometrists, orthoptists, and physiotherapists in Australia. Survey questions included practitioner demographics, awareness and knowledge of Stickler Syndromes, confidence managing Stickler Syndromes, and perception of multidisciplinary care needs for Stickler Syndromes. Results: Of 180 healthcare professions who participated (79% female; 78% aged between 25 and 44 years), 55% indicated that they had heard of Stickler Syndrome, and 14% had directly worked with patients known to have Stickler Syndromes. Practitioners who had were either optometrists, orthoptists, or audiologists. The most recognised clinical sign of Stickler Syndromes was retinal detachment (selected by 66% of optometrists and orthoptists and 16% of other professions), but only 41% of optometrists and orthoptists (27% all respondents) selected cryopexy as a potential management strategy. Vitreous anomaly was recognised as a clinical feature by 20% of all respondents. Overall, 69% of allied health professionals did not feel confident managing Stickler Syndromes, and a similar number of practitioners (69%) indicated that they were willing to attend professional development courses for complex conditions such as Stickler Syndromes. Conclusion: This study provides meaningful insights on awareness and knowledge of Stickler Syndromes among allied healthcare professionals. Targeted clinician education, enhanced communication between healthcare entities, and multidisciplinary care programs can significantly improve the integrated care of Stickler Syndromes leading to better patient outcomes.

A multinational survey of potential participant perspectives on ocular gene therapy.

Amidst rapid advancements in ocular gene therapy, understanding patient perspectives is crucial for shaping future treatment choices and research directions. This international cross-sectional survey evaluated knowledge, attitudes, and perceptions of ocular genetic therapies among potential recipients with inherited retinal diseases (IRDs). Survey instruments included the Attitudes to Gene Therapy-Eye (AGT-Eye), EQ-5D-5L, National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25), and Patient Attitudes to Clinical Trials (PACT-22) instruments. This study included 496 participant responses (89% adults with IRDs; 11% parents/guardians/carers) from 35 countries, with most from the United States of America (USA; 69%) and the United Kingdom (11%). Most participants (90%) indicated they would likely accept gene therapy if it was available, despite only 45% agreeing that they had good knowledge of gene therapy. The main sources of information were research registries (60% of participants) and the internet (61%). Compared to data from our recently published Australian national survey of people with IRDs (n = 694), USA respondents had higher knowledge of gene therapy outcomes, and Australian respondents indicated a higher perceived value of gene therapy treatments. Addressing knowledge gaps regarding outcomes and financial implications will be central to ensuring informed consent, promoting shared decision-making, and the eventual clinical adoption of genetic therapies.

Biomarker-based human and animal sperm phenotyping: the good, the bad and the ugly.

Conventional, brightfield-microscopic semen analysis provides important baseline information about sperm quality of an individual; however, it falls short of identifying subtle subcellular and molecular defects in cohorts of "bad", defective human and animal spermatozoa with seemingly normal phenotypes. To bridge this gap, it is desirable to increase the precision of andrological evaluation in humans and livestock animals by pursuing advanced biomarker-based imaging methods. This review, spiced up with occasional classic movie references but seriously scholastic at the same time, focuses mainly on the biomarkers of altered male germ cell proteostasis resulting in post-testicular carryovers of proteins associated with ubiquitin-proteasome system. Also addressed are sperm redox homeostasis, epididymal sperm maturation, sperm-seminal plasma interactions and sperm surface glycosylation. Zinc ion homeostasis-associated biomarkers and sperm-borne components, including the elements of neurodegenerative pathways such as Huntington's and Alzheimer's disease, are discussed. Such spectrum of biomarkers, imaged by highly specific vital fluorescent molecular probes, lectins, and antibodies, reveals both obvious and subtle defects of sperm chromatin, DNA and accessory structures of the sperm head and tail. Introduction of next generation image-based flow cytometry into research and clinical andrology will soon enable the incorporation of machine and deep learning algorithms with the end point of developing simple, label-free methods for clinical diagnostics and high throughput phenotyping of spermatozoa in humans and economically important livestock animals.

A mixed-method systematic review of the perspectives of young people, carers and professionals on psychiatric diagnosis in childhood and adolescence.

PROBLEM: The significance and complexities of a psychiatric diagnosis have been well-documented in existing literature. Despite the reliability and accuracy of such diagnoses, the impact and use of diagnostic labelling on young people remains unclear. METHODS: A systematic review was conducted using six databases, identifying 13 studies that explored psychiatric diagnosis experiences in professionals, caregivers, and young people. FINDINGS: This review focuses on three main themes related to psychiatric diagnosis in young people. The first theme is diagnostic subjectivity, which explores the accuracy, usefulness, potential harm and alternatives (e.g. psychological formulation) to psychiatric diagnosis in this population. The second theme is the utility of psychiatric diagnosis, which considers whether it helps young people access appropriate support and gain a better understanding of themselves and their presenting issues. The third theme is stigma, which examines the negative experiences and discrimination that young people may face due to their psychiatric diagnosis. CONCLUSIONS: There is relatively limited literature which discusses the experience of psychiatric diagnosis in young people, caregivers and professionals. The available literature is difficult to compare due to discrepancies between methodologies and services, and there are several gaps i.e. a limited focus on the experience of young people themselves. Different views and experiences of psychiatric diagnosis among professionals, caregivers, and young people could impact young people's quality of life, access to healthcare, and identity development. The current literature needs to be more comprehensive to draw firm conclusions about young people's experiences with psychiatric diagnosis.

Patient experiences and perceived value of genetic testing in inherited retinal diseases: a cross-sectional survey.

This study evaluated patient experiences with genetic testing for inherited retinal diseases (IRDs) and the association between underlying knowledge, testing outcomes, and the perceived value of the results. An online survey was distributed to adults with IRDs and parents/guardians of dependents with IRDs who had had genetic testing. Data included details of genetic testing, pre- and post- test perceptions, Decision Regret Scale, perceived value of results, and knowledge of gene therapy. Of 135 responses (85% from adults with IRDs), genetic testing was primarily conducted at no charge through public hospitals (49%) or in a research setting (30%). Key motivations for genetic testing were to confirm IRD diagnosis and to contribute towards research. Those who had received a genetic diagnosis (odds ratio: 6.71; p < 0.001) and those self-reported to have good knowledge of gene therapy (odds ratio: 2.69; p = 0.018) were more likely to have gained confidence in managing their clinical care. For over 80% of respondents, knowing the causative gene empowered them to learn more about their IRD and explore opportunities regarding clinical trials. Key genetic counselling information needs include resources for family communications, structured information provision, and ongoing genetic support, particularly in the context of emerging ocular therapies, to enhance consistency in information uptake.

Improper Restraint Use in Fatal Pediatric Motor Vehicle Collisions.

PURPOSE: Motor vehicle collisions (MVC) are the second leading cause of death in children and adolescents, but appropriate restraint use remains inadequate. Our previous work shows that about half of pediatric MVC victims presenting to our trauma center were unrestrained. This study evaluates restraint use among children and adolescents who did not survive after MVC. We hypothesize that restraint use is even lower in this population than in pediatric MVC patients who reached our trauma center. METHODS: We reviewed the local Medical Examiner's public records for fatal MVCs involving decedents <19 years old from 2010 to 2021. When restraint use was not documented, local Fire Rescue public records were cross-referenced. Patients were excluded if restraint use was still unknown. Age, demographics, and restraint use were compared using standard statistical methods. RESULTS: Of 199 reviewed cases, 92 met selection criteria. Improper restraint use was documented in 72 patients (78%). Most decedents were White (72% versus 28% Black) and male (74%), with a median age of 17 years [15-18]. Improper restraint use was more common among Black (92% vs 73% White, p = 0.040) and male occupants (85% vs 58% female, p = 0.006). Improper restraint use was lower in the Hispanic population (73%) compared to non-Hispanic individuals (89%), but this difference was not statistically significant (p = 0.090). CONCLUSION: Most pediatric patients who die from MVCs in our county are improperly restrained. While male and Black patients are especially high-risk, the overall dismal rates of restraint use in our pediatric population present an opportunity to improve injury prevention measures. TYPE OF STUDY: Retrospective Comparative Study. LEVEL OF EVIDENCE: Level III.

Characterizing acute and postsurgical pain management in patients receiving buprenorphine or buprenorphine/naloxone.

BACKGROUND: There is currently a clinical dilemma in treating acute pain in patients receiving long-term buprenorphine products. METHODS: This is a retrospective cohort review involving patients receiving long-term buprenorphine therapy who either underwent a surgical procedure or presented to an emergency department (ED) for acute pain between January 1, 2012 and January 1, 2022. Patients were excluded if opioids were prescribed 30 days before the index date. Chart reviews were conducted to characterize buprenorphine treatment strategies and the addition of new pain medications. Chart review revealed (1) incidence of opioid use disorder (OUD) relapse, (2) hospital re-presentation for pain or OUD, (3) fatal and non-fatal overdose, and (4) all-cause mortality and suicidality. Descriptive statistics were used to analyze results. RESULTS: A total of 70 of 259 screened patients met inclusion criteria. The mean (±SD) age was 50.3 ± 13 years, 92.9% male, 64.3% White, and 78.6% had an OUD diagnosis. While 84.3% presented to the ED, 15.7% underwent surgical procedures. For the primary endpoint, the total daily dose of buprenorphine or buprenorphine/naloxone from index date to discharge was continued in 90.0%, increased in 2.9%, decreased in 1.4%, and discontinued in 5.7% of cases. At discharge, 46.2% were prescribed an additional pain medication. A total of 7.1% re-presented for pain or OUD relapse, 15.7% experienced an OUD relapse, 1.4% experienced new-onset suicidality, and 1.4% experience all-cause mortality within 90 days of the index date. No fatal or non-fatal opioid overdoses were observed. CONCLUSION: The most commonly observed practice was continuing buprenorphine doses in patients with acute or postsurgical pain, which was effective and safe. Although further data is necessary to fully elucidate these findings, the data herein may suggest that clinicians can safely continue buprenorphine doses in the acute pain setting in patients receiving these products chronically.

EQ-5D-5L health utility scores in Australian adults with inherited retinal diseases: A cross-sectional survey.

PURPOSE: Economic evaluations of interventions for ocular disease require utility scores that accurately represent quality of life in the target population. This study aimed to describe the distribution of EQ-5D-5L utility values among Australian adults with symptomatic inherited retinal diseases (IRDs) and to assess the relationship between these scores and vision-related quality of life. METHODS: A survey was administered predominantly online in 2021. Participants completed the EQ-5D-5L general health utility instrument, the EQ vertical visual analogue scale (EQ-VAS) and the National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25). Self-reported IRD diagnoses were classified as being associated with central or widespread retinal involvement. RESULTS: Responses from 647 participants aged 18-93 years were included, 50.1% were men and 77.6% had an IRD associated with widespread retinal involvement. The majority reported no problems with self-care and no pain/discomfort but did report anxiety/depression and problems with work, study, housework, or family/leisure activities. Most people with widespread involvement reported problems with mobility. Median EQ-5D-5L utility was 0.88 and 0.91 among people with widespread and central involvement, respectively (age and sex-adjusted p = 0.029); and median EQ-VAS was 75 and 80, respectively (adjusted p = 0.003). A moderate curvilinear correlation was observed between EQ-5D-5L and NEI-VFQ-25 composite score (Spearman's ρ 0.69), but not all people with poor vision-related quality of life had low EQ-5D-5L utility values. CONCLUSIONS: EQ-5D-5L health utility values are correlated with vision-related quality of life among adults with IRDs. However, the EQ-5D-5L may not be sensitive to the full impact of vision impairment on quality of life.

Diagnosis and investigation of suspected haemophagocytic lymphohistiocytosis in adults: 2023 Hyperinflammation and HLH Across Speciality Collaboration (HiHASC) consensus guideline.

Haemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory syndrome characterised by persistently activated cytotoxic lymphocytes and macrophages, which, if untreated, leads to multiorgan dysfunction and death. HLH should be considered in any acutely unwell patient not responding to treatment as expected, with prompt assessment to look for what we term the three Fs-fever, falling blood counts, and raised ferritin. Worldwide, awareness of HLH and access to expert management remain inequitable. Terminology is not standardised, classification criteria are validated in specific patient groups only, and some guidelines rely on specialised and somewhat inaccessible tests. The consensus guideline described in this Health Policy was produced by a self-nominated working group from the UK network Hyperinflammation and HLH Across Speciality Collaboration (HiHASC), a multidisciplinary group of clinicians experienced in managing people with HLH. Combining literature review and experience gained from looking after patients with HLH, it provides a practical, structured approach for all health-care teams managing adult (>16 years) patients with possible HLH. The focus is on early recognition and diagnosis of HLH and parallel identification of the underlying cause. To ensure wide applicability, the use of inexpensive, readily available tests is prioritised, but the role of specialist investigations and their interpretation is also addressed.

Technology Access and Perceptions of Telehealth Services Among Young Adults Involved in the Court System.

PURPOSE: This study examined access to technology and telehealth among young adults (ages 18-24) who were court-involved and were recruited from an alternative sentencing program in New York City. METHODS: Using sequential mixed methods design, we examined demographic factors linked with access to technology and perceived usefulness of the Internet among n = 321 young adults who were court-involved (75% male, 65% African American, 35% Latinx). We then conducted in-depth interviews with 27 young adults to elicit first-person account of their access to, interest in, and experience with technology and telehealth. RESULTS: Although most participants had access to a phone with a data plan, a substantial proportion reported inconsistent access to the technology critical to telehealth. Certain young adults were more likely to lack consistent access to the technology needed for telehealth, including Black young adults, males, those with less than a high school diploma, those with a history of homelessness, and those who had difficulties paying for basic necessities. Qualitative interviews revealed that most had a strong self-efficacy using technology, while distrust of technology, inexperience with and skepticism of telehealth, low perceived need for care, and medical mistrust were common significant barriers in this underserved population. DISCUSSION: Findings underscored the critical need to address medical mistrust and increase access to and utilization of care among young adults who are court-involved. Results can inform the development and implementation of interventions designed to improve accessibility and acceptability of telehealth.

Immediate Versus Delayed Surgical Management of Infant Cryptorchidism With Inguinal Hernia.

INTRODUCTION: Cryptorchidism is commonly treated with orchiopexy at 6-12 months of age, often allowing time for undescended testicle(s) (UT) to descend spontaneously. However, when an inguinal hernia (IH) is also present, some surgeons perform orchiopexy and inguinal hernia repair (IHR) immediately rather than delaying surgery. We hypothesize that early surgical intervention provides no benefit for newborns with both IH and UT. METHODS: The Nationwide Readmissions Database was used to identify newborns with diagnoses of both IH and UT from 2010 to 2014. Patients were stratified by management: IHR performed on initial admission (Repair) or not (Deferral). Demographics, outcomes, and complications were compared. Results were weighted for national estimates. RESULTS: We analyzed 1306 newborns (64% premature) diagnosed with both IH and UT. IHR was performed at index admission in 30%. Repair was more common in premature babies (43% vs. 8% full-term, p < 0.001) and patients with congenital anomalies (33% vs. 27% without congenital anomaly, p = 0.012). There was no difference in readmission rates. Repair patients had higher rates of orchiectomy than did Deferral. No Deferral patients were readmitted for bowel resection, and <1% were readmitted for orchiectomy or hernia incarceration. CONCLUSION: In newborns with UT and IH, immediate repair is not associated with improved outcomes. Even with incarceration on initial presentation, rates of readmission with incarceration or bowel compromise for patients who undergo Deferral of surgery are minimal. Moreover, Repair newborns have higher rates of orchiectomy. We found no benefit to early operative intervention; thus, we recommend waiting until 6-12 months of age to reassess for surgery. LEVEL OF EVIDENCE: Level III TYPE OF STUDY: Retrospective Comparative Study.

Genetic testing and gene therapy in retinal diseases: Knowledge and perceptions of optometrists in Australia and New Zealand.

With advances in gene-based therapies for heritable retinal diseases, primary eye care clinicians should be informed on ocular genetics topics. This cross-sectional survey evaluated knowledge, attitudes, and concerns regarding genetic testing and gene therapy for retinal diseases among optometrists in Australia and New Zealand. Survey data included practitioner background, attitudes and practices towards genetic testing for monogenic inherited retinal disease (IRDs) and age-related macular degeneration, and knowledge of ocular genetics and gene therapy. Responses were received from 516 optometrists between 1 April and 31 December 2022. Key perceived barriers to accessing genetic testing were lack of clarity on referral pathways (81%), cost (65%), and lack of treatment options if a genetic cause is identified (50%). Almost all respondents (98%) believed that ophthalmologists should initiate genetic testing for IRDs and fewer understood the role of genetic counsellors and clinical geneticists. This study found that optometrists in Australia and New Zealand have a high level of interest in ocular genetics topics. However, knowledge gaps include referral pathways and awareness of genetic testing and gene therapy outcomes. Addressing perceived barriers to access and promoting sharing of knowledge between interdisciplinary networks can set the foundation for genetic education agendas in primary eye care.

Adaptive optics imaging in inherited retinal diseases: A scoping review of the clinical literature.

Adaptive optics (AO) imaging enables direct, objective assessments of retinal cells. Applications of AO show great promise in advancing our understanding of the etiology of inherited retinal disease (IRDs) and discovering new imaging biomarkers. This scoping review systematically identifies and summarizes clinical studies evaluating AO imaging in IRDs. Ovid MEDLINE and EMBASE were searched on February 6, 2023. Studies describing AO imaging in monogenic IRDs were included. Study screening and data extraction were performed by 2 reviewers independently. This review presents (1) a broad overview of the dominant areas of research; (2) a summary of IRD characteristics revealed by AO imaging; and (3) a discussion of methodological considerations relating to AO imaging in IRDs. From 140 studies with AO outcomes, including 2 following subretinal gene therapy treatments, 75% included fewer than 10 participants with AO imaging data. Of 100 studies that included participants' genetic diagnoses, the most common IRD genes with AO outcomes are CNGA3, CNGB3, CHM, USH2A, and ABCA4. Confocal reflectance AO scanning laser ophthalmoscopy was the most reported imaging modality, followed by flood-illuminated AO and split-detector AO. The most common outcome was cone density, reported quantitatively in 56% of studies. Future research areas include guidelines to reduce variability in the reporting of AO methodology and a focus on functional AO techniques to guide the development of therapeutic interventions.

Characterization of a FourU RNA Thermometer in the 5' Untranslated Region of Autolysin Gene blyA in the Bacillus subtilis 168 Prophage SPß.

RNA thermometers are noncoding RNA structures located in the 5' untranslated regions (UTRs) of genes that regulate gene expression through temperature-dependent conformational changes. The fourU class of RNA thermometers contains a specific motif in which four consecutive uracil nucleotides are predicted to base pair with the Shine-Dalgarno (SD) sequence in a stem. We employed a bioinformatic search to discover a fourU RNA thermometer in the 5'-UTR of the blyA gene of the Bacillus subtilis phage SPßc2, a bacteriophage that infects B. subtilis 168. blyA encodes an autolysin enzyme, N-acetylmuramoyl-l-alanine amidase, which is involved in the lytic life cycle of the SPß prophage. We have biochemically validated the predicted RNA thermometer in the 5'-UTR of the blyA gene. Our study suggests that RNA thermometers may play an underappreciated yet critical role in the lytic life cycle of bacteriophages.

Measuring response to treatment in axial spondyloarthritis using quantitative imaging biomarkers: a prospective observational cohort study.

OBJECTIVE: Objective assessments of disease activity and response to treatment in axial spondyloarthritis (axSpA) remain a challenge; quantitative imaging biomarkers (QIBs) of inflammation could enhance assessments of disease activity and therapeutic response. We aimed to determine the responsiveness of QIBs obtained from diffusion-weighted imaging (DW-MRI) and chemical shift-encoded MRI (CSE-MRI) using the partially automated Bone Edema and Adiposity Characterisation with Histograms (BEACH) software tool in axSpA patients undergoing biologic therapy. METHODS: We conducted a prospective longitudinal cohort study, including 30 patients with axSpA undergoing biologic therapy. Patients were scanned before and after biologic therapy using conventional MRI, DWI and CSE-MRI at 3T. Apparent diffusion coefficient (ADC) and proton density fat fraction (PDFF) were assessed using the BEACH tool (https://github.com/TJPBray/BEACH), and conventional MR images were assessed using established visual scoring methods by expert radiologists. Responsiveness - the ability of the MRI measurements to capture changes in disease occurring as a result of biologic therapy - was assessed using the standardized response mean (SRM). Inter-reader reliability of the ADC and PDFF maps was assessed using Bland-Altman limits of agreement analysis and the intraclass correlation coefficient. RESULTS: Responsiveness to therapy was moderate for ADC-based parameters (SRM 0.50) and comparable to established visual scoring methods for bone marrow oedema (SRM 0.53). Interobserver variability was lower for QIBs compared with conventional visual scores methods. CONCLUSIONS: QIBs measured using the BEACH tool are sensitive to changes in inflammation in axSpA following biologic therapy, with similar responsiveness and lower interobserver variability to visual scoring by expert radiologists. ADVANCES IN KNOWLEDGE: QIBs measured using the partially automated BEACH tool offer an objective measure of response to biologic therapy in axSpA.

Characterising the diagnosis of genetic maculopathies in a real-world private tertiary retinal practice in Australia: protocol for a retrospective clinical audit.

PURPOSE: Accurate diagnosis of macular atrophy is paramount to enable appropriate treatment when novel treatments for geographic atrophy and macular dystrophies become available. Genetic testing is useful in distinguishing between the two conditions but is not feasible for the majority of patients in real-world clinical practice. Therefore, we aimed to investigate the potential misdiagnosis of inherited macular dystrophy as age-related macular degeneration (AMD) in real-world ophthalmic practice to assist in the development of guidelines to improve diagnostic accuracy while minimizing genetic testing for targeted patients. METHODS: Retrospective review of the medical records of patients diagnosed with AMD, which included imaging, between 1995 and 2023 from a large multidisciplinary private ophthalmic practice in Australia. We will use a stepwise method to screen for probable cases of macular dystrophy, followed by a consensus review by an expert panel. The outcomes are (1) to determine the potential misdiagnosis rate of macular dystrophy as atrophic AMD by retinal specialists and general ophthalmologists; (2) to identify clinical imaging modalities that are most useful for differentiating macular dystrophy from atrophic AMD; and (3) to establish preliminary guidance for clinicians to improve the diagnosis of macular atrophy from AMD in practice, and thereby target cost-efficient genetic testing. DISCUSSION: Improving the diagnostic accuracy of both AMD and macular dystrophy, while ensuring cost-efficient genetic testing, will improve the targeted treatment of macular diseases when emerging treatments become available.