Large ciliary body melanocytoma with pseudocysts: a case report.

BACKGROUND: To describe the correlation between standardized A-scan echography and histopathology in a ciliary body melanocytoma. CASE PRESENTATION: We present a case of a large ciliary body melanocytoma with significant growth, vision loss, and elevated intraocular pressure that was diagnosed clinically as a melanoma, but the standardized A-scan findings correlated to the histopathological description of a melanocytoma with multiple pseudocysts. CONCLUSIONS: The reflectivity of this melanocytoma by standardized A-scan was consistent with multiple pseudocysts on pathological evaluation. This echographic pattern guided the differential diagnosis. Standardized A-scan is an important diagnostic tool in the differentiation of ciliary body melanocytomas from melanomas.

LADD syndrome with glaucoma is caused by a novel gene.

PURPOSE: Lacrimo-auriculo-dento-digital (LADD) syndrome is an autosomal dominant disorder displaying variable expression of multiple congenital anomalies including hypoplasia or aplasia of the lacrimal and salivary systems causing abnormal tearing and dry mouth. Mutations in the FGF10, FGFR2, and FGFR3 genes were found to cause some cases of LADD syndrome in prior genetic studies. The goal of this study is to identify the genetic basis of a case of LADD syndrome with glaucoma and thin central corneal thickness (CCT). METHODS: Whole exome sequencing was performed, and previously described disease-causing genes (FGF10, FGFR2, and FGFR3) were first evaluated for mutations. Fifty-eight additional prioritized candidate genes were identified by searching gene annotations for features of LADD syndrome. The potential pathogenicity of the identified mutations was assessed by determining their frequency in large public exome databases; through sequence analysis using the Blosum62 matrix, PolyPhen2, and SIFT algorithms; and through homology analyses. A structural analysis of the effects of the top candidate mutation in tumor protein 63 (TP63) was also conducted by superimposing the mutation over the solved crystal structure. RESULTS: No mutations were detected in FGF10, FGFR2, or FGFR3. The LADD syndrome patient's exome data was searched for mutations in the 58 candidate genes and only one mutation was detected, an Arg343Trp mutation in the tumor protein 63 (TP63) gene. This TP63 mutation is absent from the gnomAD sequence database. Analysis of the Arg343Trp mutation with Blosum62, PolyPhen2, and SIFT all suggest it is pathogenic. This arginine residue is highly conserved in orthologous genes. Finally, crystal structure analysis showed that the Arg343Trp mutation causes a significant alteration in the structure of TP63's DNA binding domain. CONCLUSIONS: We report a patient with no mutations in known LADD syndrome genes (FGF10, FGFR2, and FGFR3). Our analysis provides strong evidence that the Arg343Trp mutation in TP63 caused LADD syndrome in our patient and that TP63 is a fourth gene contributing to this condition. TP63 encodes a transcription factor involved in the development and differentiation of tissues affected by LADD syndrome. These data suggest that TP63 is a novel LADD syndrome gene and may also influence corneal thickness and risk for open-angle glaucoma.

Prevalence of Open-angle Glaucoma in the Faroese Population.

PURPOSE: The Faroe Islands are home to 50,000 genetically isolated people in the North Atlantic. The prevalence of open-angle glaucoma (OAG) in the Faroese population is unknown. Consequently, we conducted a survey to determine the prevalence of OAG in the Faroese population. We also investigated the role of known glaucoma-causing genes in Faroese OAG. MATERIALS AND METHODS: We conducted a prospective survey of known and newly diagnosed glaucoma patients at the Faroese National Hospital, Landssjukrahusid, Tórshavn between October 1, 2015 to December 31, 2017. In addition we reviewed the only eye care provider in the Faroese Islands by scrutinizing electronic medical records between 2009 and June 15, 2014, October 1, 2015 and the partly overlapping prescriptions for ocular hypotensive medications in 2016 to identify patients with either a diagnosis of glaucoma, a diagnosis of ocular hypertension or a prescription for ocular hypotensive medications. Next, we prospectively confirmed diagnoses with complete eye examinations. Patient DNA samples were tested for variations in known glaucoma-causing genes [myocilin (MYOC), optineurin (OPTN), and TANK binding kinase 1 (TBK1)]. RESULTS: We determined the age-related prevalence of OAG January 1, 2017 in individuals 40 years or older to be 10.7/1000 (1.07%) and highly age-related. A diagnosis of OAG was present in 264 patients, of whom 211 (79.9%) had primary OAG (including normal tension glaucoma), 49 (18.6%) had pseudoexfoliation glaucoma, and 4 (1.5%) had pigmentary glaucoma. Among patients receiving medications for glaucoma, nearly 50% had primary OAG, while the majority of the rest had ocular hypertension or secondary glaucoma. No disease-causing variants were detected in MYOC, OPTN, or TBK1. CONCLUSIONS: The calculated prevalence of OAG in the Faroe Islands was 1.07%. The absence of MYOC, OPTN, or TBK1 disease-causing variants in Faroese primary OAG patients suggests that a different, potentially unique set of genes may be contributing to the pathogenesis of glaucoma in this population.

Research to Translation: The Healthy Schools Toolkit and New Approaches to the Whole School, Whole Community, Whole Child Model.

BACKGROUND: The Whole School, Whole Community, Whole Child (WSCC) model is an evidence-based comprehensive framework to address health in schools. WSCC model use improves health and educational outcomes, but implementation remains a challenge. METHODS: Working with 6 schools in 2 districts in the Midwest, we used a mixed-methods approach to determine the people, systems, and messages needed to activate WSCC implementation. We report on social network analysis and message testing findings and research translation to develop the Healthy Schools Toolkit. RESULTS: Social networks for both districts included more than 150 individuals. Both demonstrated network densities less than half of the desirable threshold, with evidence of clustering by role and minimal cross-school relationships, posing challenges for WSCC implementation. Across stakeholder groups, messages that emphasize empathy, teamwork, and action were well-received, especially when shared by trusted individuals through communication channels that align with stakeholder needs. CONCLUSIONS: The Healthy Schools Toolkit provides an example of a translational product that helps to bridge research with practice. With features that highlight 6 design principles, the toolkit provides complementary activities that schools and districts can use as they plan for integration of the WSCC model.