What do patients with diabetes and providers think of an innovative Australian model of remote diabetic retinopathy screening? A qualitative study

Background: Diabetic retinopathy (DR) is the commonest cause of preventable blindness in working age populations, but up to 98% of visual loss secondary to DR can be prevented with early detection and treatment. In 2012, an innovative outreach DR screening model was implemented in remote communities in a state of Australia. The aim of this study was to explore the acceptability of this unique DR screening model to patients, health professionals and other key stakeholders. Methods: This descriptive qualitative study used semi-structured interviews with patients opportunistically recruited whilst attending DR screening, and purposefully selected health care professionals either working within or impacted by the programme. Interviews were audiotaped, transcribed and analysed using NVIVO. An iterative process of thematic analysis was used following the principles of grounded theory. Results: Interviews were conducted with fourteen patients with diabetes living in three remote communities and nine health professionals or key stakeholders. Nine key themes emerged during interviews with health professionals, key stakeholders and patients: i) improved patient access to DR screening; ii) efficiency, financial implications and sustainability; iii) quality and safety; iv) multi-disciplinary diabetes care; v) training and education; vi) operational elements of service delivery; vii) communication, information sharing and linkages; viii) coordination and integration of the service and ix) suggested improvements to service delivery. Conclusions: The Remote Outreach DR Screening Service is highly acceptable to patients and health professionals. Challenges have primarily been encountered in communication and coordination of the service and further development in these areas could improve the programme's impact and sustainability in remote communities. The service is applicable to other remote communities nationally and potentially internationally

Whole genome landscapes of uveal melanoma show an ultraviolet radiation signature in iris tumours

Uveal melanoma (UM) is the most common intraocular tumour in adults and despite surgical or radiation treatment of primary tumours, ~50% of patients progress to metastatic disease. Therapeutic options for metastatic UM are limited, with clinical trials having little impact. Here we perform whole-genome sequencing (WGS) of 103 UM from all sites of the uveal tract (choroid, ciliary body, iris). While most UM have low tumour mutation burden (TMB), two subsets with high TMB are seen; one driven by germline MBD4 mutation, and another by ultraviolet radiation (UVR) exposure, which is restricted to iris UM. All but one tumour have a known UM driver gene mutation (GNAQ, GNA11, BAP1, PLCB4, CYSLTR2, SF3B1, EIF1AX). We identify three other significantly mutated genes (TP53, RPL5 and CENPE)

Whole genome landscapes of uveal melanoma show an ultraviolet radiation signature in iris tumours

Uveal melanoma (UM) is the most common intraocular tumour in adults and despite surgical or radiation treatment of primary tumours, ~50% of patients progress to metastatic disease. Therapeutic options for metastatic UM are limited, with clinical trials having little impact. Here we perform whole-genome sequencing (WGS) of 103 UM from all sites of the uveal tract (choroid, ciliary body, iris). While most UM have low tumour mutation burden (TMB), two subsets with high TMB are seen; one driven by germline MBD4 mutation, and another by ultraviolet radiation (UVR) exposure, which is restricted to iris UM. All but one tumour have a known UM driver gene mutation (GNAQ, GNA11, BAP1, PLCB4, CYSLTR2, SF3B1, EIF1AX). We identify three other significantly mutated genes (TP53, RPL5 and CENPE).This project was funded by the National Health and Medical Research Council (NHMRC; 1093017), the Walking On Sunshine Foundation, Anne Stanton, Nicola Laws and Lloyd Owen in Memorial and Civic Solutions. This study was also funded by Fight for Sight, Denmark. A.L.P. is supported by Highland Island Enterprise (HMS9353763). This work was supported by an NHMRC Program Grant (G.V.L., G.J.M., R.A.S. and N.K.H.). G.V.L. is supported by an NHMRC Practitioner Fellowship and The University of Sydney, Medical Foundation. R.A.S. is supported by an NHMRC Practitioner Fellowship. Support from Melanoma Institute Australia and The Ainsworth Foundation is also gratefully acknowledged. J.S.W. is supported by a NHMRC early career fellowship (1111678). N.W. is supported by an NHMRC Senior Research Fellowship (1139071). N.K.H. is supported by an NHMRC Senior Principal Research Fellowship (1117663)

An innovative Australian outreach model of diabetic retinopathy screening in remote communities

Background: Up to 98% of visual loss secondary to diabetic retinopathy (DR) can be prevented with early detection and treatment. Despite this, less than 50% of Australian and American diabetics receive appropriate screening. Diabetic patients living in rural and remote communities are further disadvantaged by limited access to ophthalmology services.\ud \ud Research Design and Methods: DR screening using a nonmydriatic fundal camera was performed as part of amultidisciplinary diabetes service already visiting remote communities. Images were onforwarded to a distant general practitioner who identified and graded retinopathy, with screenpositive patients referred to ophthalmology. This retrospective, descriptive study aims to compare the proportion of remote diabetic patients receiving appropriate DR screening prior to and following implementation of the service. \ud \ud Results: Of the 141 patients in 11 communities who underwent DR screening, 16.3% had received appropriate DR screening prior to the implementation of the service. In addition, 36.2% of patients had never been screened. Following the introduction of the service, 66.3% of patients underwent appropriate DR screening (p=0.00025). \ud \ud Conclusion: This innovative model has greatly improved accessibility to DR screening in remote communities, thereby reducing preventable blindness. It provides a holistic, locally appropriate diabetes service and utilises existing infrastructure and health workforce more efficiently

Comprehensive Study of the Clinical Phenotype of Germline BAP1 Variant-Carrying Families Worldwide

Background: The BRCA1-associated protein-1 (BAP1) tumor predisposition syndrome (BAP1-TPDS) is a hereditary tumor syndrome caused by germline pathogenic variants in BAP1 encoding a tumor suppressor associated with uveal melanoma, mesothelioma, cutaneous melanoma, renal cell carcinoma, and cutaneous BAP1-inactivated melanocytic tumors. However, the full spectrum of tumors associated with the syndrome is yet to be determined. Improved understanding of the BAP1-TPDS is crucial for appropriate clinical management of BAP1 germline variant carriers and their families, including genetic counseling and surveillance for new tumors. Methods: We collated germline variant status, tumor diagnoses, and information on BAP1 immunohistochemistry or loss of somatic heterozygosity on 106 published and 75 unpublished BAP1 germline variant-positive families worldwide to better characterize the genotypes and phenotypes associated with the BAP1-TPDS. Tumor spectrum and ages of onset were compared between missense and null variants. All statistical tests were two-sided. Results: The 181 families carried 140 unique BAP1 germline variants. The collated data confirmed the core tumor spectrum associated with the BAP1-TPDS and showed that some families carrying missense variants can exhibit this phenotype. A variety of noncore BAP1-TPDS -associated tumors were found in families of variant carriers. Median ages of onset of core tumor types were lower in null than missense variant carriers for all tumors combined (P < .001), mesothelioma (P < .001), cutaneous melanoma (P < .001), and nonmelanoma skin cancer (P < .001). Conclusions: This analysis substantially increases the number of pathogenic BAP1 germline variants and refines the phenotype. It highlights the need for a curated registry of germline variant carriers for proper assessment of the clinical phenotype of the BAP1-TPDS and pathogenicity of new variants, thus guiding management of patients and informing areas requiring further research