Clinical and molecular features associated with cystic visceral lesions in von hippel-lindau disease.

Von Hippel-Lindau (VHL) is an uncommon oncogenic disorder which occurs as a result of genetic mutations on chromosome 3p. Retinal capillary haemangiomas and CNS haemangioblastomas have been well-characterised in genotypic-phenotypic analyses, but cystic visceral lesions are less common and have been less frequently studied. The aim of this study was to perform genotypic and phenotypic analysis of a cohort of VHL patients that developed cystic visceral lesions to determine whether their genotype differs from that seen in other manifestations of VHL and whether the ocular manifestations differ.This study reports a prospective case series of twenty-one patients identified from the Hammersmith Hospital Genetics Service database as having VHL mutations. Patients underwent regular ocular and systemic screening as well as genotypic analysis. The main outcome measures were the development of VHL lesions, either ocular or systemic.Cystic visceral lesions were detected in six of the 21 patients from the clinic (29%). These included renal cysts in four patients, pancreatic cysts in three patients, and an epididymal cystadenoma in one patient. Renal cysts were not associated with any specific genotype. Pancreatic cysts appeared to occur in association with VHL gene deletions and all developed CNS haemangioblastomas. Only one patient developed ocular manifestations, which occurred in this patient in the form of two retinal capillary haemangiomas.VHL gene deletions appeared to be associated with pancreatic cysts and the development of CNS haemangioblastomas. Ocular manifestations are uncommon in this group of patients

Nodular Posterior Scleritis: Clinico-Sonographic Characteristics and Proposed Diagnostic Criteria

Purpose: To report the clinical and ultrasound features and outcomes of a series of nodular posterior scleritis. / Methods: Retrospective medical record review of 11 consecutive patients with nodular posterior scleritis. Patient demographics, ocular and systemic findings, ultrasound features, and final anatomical and visual outcomes were recorded. / Results: There were 9 females and 2 males (11 eyes) with mean age at presentation of 57 years (range, 30-84 years). Underlying systemic inflammatory disease was present in 73%. Symptoms included pain in 73% and blurred vision in 45%. A solitary amelanotic mass without the presence of lipofuscin was found in all cases. Associated ocular features included retinal pigment epithelial changes (67%), intraocular inflammation (55%), subretinal fluid (50%), macular edema (50%), and choroidal folds (30%). B-mode ultrasound showed a sclerochoroidal mass with high internal reflectivity (100%) of mean elevation of 4.1 mm. There was nodular thickening of the sclera (100%) and fluid in Tenon space or "T" sign (36%). A complete regression of the nodule after the treatment was observed only in 1 patient (11%) and partial regression in 4 patients (44%). / Conclusion: Nodular posterior scleritis should be considered in the differential diagnosis of a single amelanotic choroidal mass showing high internal reflectivity on ultrasound B-scan. It can produce intraocular inflammation in 50% of the cases and may be painless in 25%. It has a high association with a systemic underlying disease

Lag time for retinoblastoma in the UK revisited: a retrospective analysis

OBJECTIVES: To explore current delays in diagnosis of retinoblastoma (Rb) and effect on outcome with comparison to a study from the 1990s. SETTING: Primary, secondary, tertiary care: majority from South of England. PARTICIPANTS: A retrospective analysis of 93 new referrals of sporadic (non-familial) Rb to a specialist Rb unit in London, UK from January 2006 to February 2014. PRIMARY AND SECONDARY OUTCOMES: International Intraocular Retinoblastoma Classification, lag times including parental delay and healthcare professional delay, patients requiring enucleation and requirement of adjuvant chemotherapy postenucleation (high-risk Rb). RESULTS: During the study period, 29% presented via accident and emergency (A&E). The median referral time from symptom onset to visiting primary care (PC) was 28 days and PC to ophthalmologist 3 days (range 0-181 days). The median time from local ophthalmologist to the Rb Unit was 6 days (0-33). No significant correlation was found between delay and International Classification of Retinoblastoma grade (p>0.05) or between postenucleation adjuvant chemotherapy and enucleation groups (p>0.05). Less enucleations (60%) are being performed compared with the previous study (81%) (p=0.0015). CONCLUSIONS: Parents are attending A&E more compared with the 1990s and this may reflect the effect of public awareness campaigns. More eyes are being salvaged despite a similar number of children requiring adjuvant chemotherapy. High-risk Rb and Group E eyes do not correlate with increased lag time in the UK. Other determinants such as tumour biology may be more relevant

Strabismus as a Presenting Sign in Retinoblastoma

PURPOSE:To report the presenting signs of retinoblastoma in a large cohort of patients who underwent orthoptic assessment at presentation. METHODS:A retrospective medical chart review was conducted on 131 patients with retinoblastoma who presented consecutively to a single institution during a 6-year period. The main outcome measure was the presenting sign(s) of the disease. RESULTS:Of 131 patients with retinoblastoma, 88 presented with unilateral disease and 43 presented with bilateral disease (mean ages: 22.7 and 14.8 months, respectively). Leukocoria was the presenting sign in 56% of patients, leukocoria and strabismus in 18%, strabismus in 13%, inflammation in 8%, and “other” signs in 5%. The fovea was affected by the retinoblastoma tumor or its sequelae in 75% of patients. Patients who presented with strabismus were significantly more likely to have foveal involvement than patients who presented with leukocoria alone (P = .001). Thirty-one percent of patients had strabismus as a component of their presentation; 63% had exotropia, 23% had esotropia, and 14% had variable strabismus. The percentage of patients with strabismus increased to 66% when small angle and variable strabismus were also considered. Patients with inflammation had worse ocular survival (P < .05). CONCLUSIONS:This study assessed the combination of leukocoria and strabismus as presenting features of retinoblastoma. Foveal involvement is common in patients who have strabismus and may influence decision-making regarding globe salvage. The authors confirmed that exotropia is more common than esotropia in retinoblastoma in the largest cohort to have undergone an orthoptic assessment

Retinal Neuronal Ectopia: a new entity in the differential diagnosis of retinoblastoma

BACKGROUND: To present a rare retinal disorder that should be considered in the differential diagnosis of retinoblastoma. METHODS: A 2-year-old boy presented with left ocular discomfort, leukocoria, and a left divergent squint. Examination of the left eye revealed abnormalities in the anterior segment, and fundoscopy showed an irregular white calcified mass with fibrosis and traction toward the lens. As the ocular discomfort worsened, enucleation of the left eye was performed. RESULTS: Histopathological and immunohistochemical assessment of the enucleated eye established the diagnosis of retinal neuronal ectopia. CONCLUSION: We believe that this case is unique in the human retina and highlights the need for specialist differential diagnosis. Although rare, retinal neuronal ectopia should be considered in the differential diagnosis of retinoblastoma

Single capstone or multiple cornerstones? Distributed model of capstone subjects in construction education

Capstone experiences provide critical opportunities for undergraduate students to integrate and apply the skills and knowledge they have previously developed in their degree or program. Commonly, this involves students engaging in learning experiences that involve real-world issues and which in turn enhance the student experience and employability skills. The research on capstone experiences in the construction management education literature indicates a need to develop customized delivery models that addresses the specific requirements of construction industry and education providers. This paper aims to showcase an innovative model of distributed delivery for multiple capstones (cornerstones) in a construction management program. The case study described in this paper realized an improvement in capstone design and practice-based learning by incrementally enhancing a student&#039;s knowledge of construction project management skills. The model of multiple capstones discussed here is applicable to diverse disciplines, including construction engineering and management programs

Online Assessment of Applied Anatomy Knowledge: The Effect of Images on Medical Students' Performance

Anatomical examinations have been designed to assess topographical and/or applied knowledge of anatomy with or without the inclusion of visual resources such as cadaveric specimens or images, radiological images, and/or clinical photographs. Multimedia learning theories have advanced the understanding of how words and images are processed during learning. However, the evidence of the impact of including anatomical and radiological images within written assessments is sparse. This study investigates the impact of including images within clinically oriented single‐best‐answer questions on students' scores in a tailored online tool. Second‐year medical students (n = 174) from six schools in the United Kingdom participated voluntarily in the examination, and 55 students provided free‐text comments which were thematically analyzed. All questions were categorized as to whether their stimulus format was purely textual or included an associated image. The type (anatomical and radiological image) and deep structure of images (question referring to a bone or soft tissue on the image) were taken into consideration. Students scored significantly better on questions with images compared to questions without images (P < 0.001), and on questions referring to bones than to soft tissue (P < 0.001), but no difference was found in their performance on anatomical and radiological image questions. The coding highlighted areas of “test applicability” and “challenges faced by the students.” In conclusion, images are critical in medical practice for investigating a patient's anatomy, and this study sets out a way to understand the effects of images on students' performance and their views in commonly employed written assessments

Prognostic Information for Known Genetic Carriers of RB1 Pathogenic Variants (Germline and Mosaic)

OBJECTIVE: To compare the number of tumors per eye for mosaic carriers of RB1 pathogenic variants with full germline variants and the conversion from unilateral to bilateral disease. DESIGN: Retrospective cohort study comparing patients with retinoblastoma and different genetic subtypes (HP: high penetrant, LP: low penetrant & mosaicism). SUBJECTS: Data were analysed between 1992 and 2018 at the Retinoblastoma Unit, Royal London Hospital, London UK. All familial patients had a parent with a known pathogenic variant even if the parent did not manifest the disease. MAIN OUTCOME MEASURES: Number of tumors per eye in children who developed retinoblastoma in that eye. Other outcomes included total number of tumors per patient, age at diagnosis, laterality at presentation and later, sex and stage according to International Intraocular Retinoblastoma Classification RESULTS: 111 patients were included: 64 full germline, familial patients (53 HP and 11 LP) & 47 were mosaic patients. 12 (23%) of HP patients were unilateral and 8 of 12 (67%) developed tumors in their previously unaffected eye. 34 (72%) of mosaic patients were unilateral and only 2 (6%) developed tumors in their unaffected eye. Age at diagnosis was higher in mosaic patients (median 22 months) than HP patients (median 7) (p<0.00002). Number of tumors per eye was fewer in patients with mosaic alleles (median 1.0 range 1-6) compared to patients with HP alleles (median 3.0 range 1-8) (p<0.0003). All three children (4 eyes) with mosaicism and more than 2 tumors per eye had high levels of mosaicism. CONCLUSIONS: Children with mosaic alleles have fewer tumors per eye compared to those with known high penetrant pathogenic variants and are more likely to remain unilateral. The level of mosaicism has an impact on laterality and number of tumors

Repeatability of swept-source optical coherence tomography retinal and choroidal thickness measurements in neovascular age-related macular degeneration

BACKGROUND: The aim was to determine the intrasession repeatability of swept-source optical coherence tomography (SS-OCT)-derived retinal and choroidal thickness measurements in eyes with neovascular age-related macular degeneration (nAMD). METHODS: A prospective study consisting of patients with active nAMD enrolled in the Distance of Choroid Study at Moorfields Eye Hospital, London. Patients underwent three 12×9 mm macular raster scans using the deep range imaging (DRI) OCT-1 SS-OCT (Topcon) device in a single imaging session. Retinal and choroidal thicknesses were calculated for the ETDRS macular subfields. Repeatability was calculated according to methods described by Bland and Altman. RESULTS: 39 eyes of 39 patients with nAMD were included with a mean (±SD) age of 73.9 (±7.2) years. The mean (±SD) retinal thickness of the central macular subfield was 225.7 μm (±12.4 μm). The repeatability this subfield, expressed as a percentage of the mean central macular subfield thickness, was 23.2%. The percentage repeatability of the other macular subfields ranged from 13.2% to 28.7%. The intrasession coefficient of repeatability of choroidal thickness of the central macular subfield was 57.2 μm with a mean choroidal thickness (±SD) of 181 μm (±15.8 μm). CONCLUSIONS: This study suggests that a change >23.2% of retinal thickness and 57.2 μm choroidal thickness in the central macular subfield is required to distinguish true clinical change from measurement variability when using the DRI OCT-1 device to manage patients with nAMD