A rare case of severe bilateral Graves' orbitopathy involving an anophthalmic socket.

Summary: This is a report of a rare case of Graves' hyperthyroidism associated with severe bilateral Graves' orbitopathy, in a patient with an anophthalmic eye socket. On clinical review her prosthetic eye (left eye) was tilting upwards, along with worsening of Graves' orbitopathy (GO) in the only seeing eye. As she refused IV glucocorticoids, she was offered rituximab which only caused a transient improvement in the clinical activity score of the eye. She had persistent right upper lid retraction of 6 mm, associated with lagophthalmos. To protect her seeing eye from corneal ulceration, the patient received a botulinum toxin injection to the right upper eyelid to induce blepharoptosis as an interim measure prior to right upper eyelid blepharotomy in April 2021. This patient remains biochemically euthyroid on block and replace therapy and her TRAb level is falling over time. Treatment for active GO is ongoing and the patient required a redo blepharotomy for painful corneal exposure in the right eye. Learning points: Graves' orbitopathy (GO) does not actually primarily affect the eyeball itself but the orbital contents as well. Patients with severe GO in an only seeing-eyed patient should be referred early to a multidisciplinary Joint Thyroid Eye clinic for expert review and management. Patient outcomes including sight loss are likely to be improved by the extended range of medical and surgical treatment modalities available at specialist clinics treating GO, including the use of immunomodulatory drugs like rituximab or teprotumumab.

A non-randomised trial of video and written educational adjuncts in undergraduate ophthalmology.

BACKGROUND: Provision of relevant pre-learning materials has been shown to increase student engagement and improve outcomes in medical education. This non-randomised study attempts to quantify the educational gains, and relative efficacy of video and written pre-learning materials, in ophthalmology undergraduate teaching. METHODS: Ninety-eight final year medical students were contacted prior to their three-day ophthalmology placements at a British tertiary ophthalmology unit. All participants were sent welcome packs prior to arrival requesting they undertake 90 min of work focusing on a list of specified ophthalmic conditions. One cohort (N = 33) were sent written materials, another (N = 32) was provided with video materials and a third cohort (N = 33) were not sent any materials. On arrival participants completed a simple knowledge test, a questionnaire estimating the time they spent preparing for the placement and a self-reported knowledge score. The teaching on placement was the same for all cohorts. At the conclusion of each placement participants completed a challenging knowledge test, a clinical skills test and repeated self-reported knowledge scores. RESULTS: Eighty seven percent of students receiving specified materials claimed to complete pre-placement work compared to 70% of those receiving learning outcomes alone (p = 0.05). Students receiving learning materials scored higher in the post-placement tests of knowledge (p < 0.001), 74.8% (72.4-77.2%) vs 63.6% (95%CI 59.3-67.9%) and skills (p = 0.04), 86.9% (83.9-89.9%) vs 81.3% (77.2-85.4%). Students using video resources outperformed students using written materials in their visual acuity assessment test (p = 0.03), 90.4% (86.6-94.2%) vs 83.6% (80.1-87.1%) whilst those receiving written rather than video material performed better in the end of placement knowledge test (p = 0.03), 77.7% (74.3-81.1%) vs 72.0% (68.9-75.1%). CONCLUSION: This study showed that providing pre-placement learning materials improves undergraduates' commitment and achievement. Written materials better facilitate knowledge acquisition while video materials preferentially promote skill acquisition. This is a novel demonstration within ophthalmology and can help address the imbalance between the expectations placed on undergraduates and the resources committed to ensuring they are met.

Pathogen invasion history elucidates contemporary host pathogen dynamics.

Amphibians, the most threatened group of vertebrates, are seen as indicators of the sixth mass extinction on earth. Thousands of species are threatened with extinction and many have been affected by an emerging infectious disease, chytridiomycosis, caused by the fungal pathogen, Batrachochytrium dendrobatidis (Bd). However, amphibians exhibit different responses to the pathogen, such as survival and population persistence with infection, or mortality of individuals and complete population collapse after pathogen invasion. Multiple factors can affect host pathogen dynamics, yet few studies have provided a temporal view that encompasses both the epizootic phase (i.e. pathogen invasion and host collapse), and the transition to a more stable co-existence (i.e. recovery of infected host populations). In the Sierra Nevada mountains of California, USA, conspecific populations of frogs currently exhibit dramatically different host/ Bd-pathogen dynamics. To provide a temporal context by which present day dynamics may be better understood, we use a Bd qPCR assay to test 1165 amphibian specimens collected between 1900 and 2005. Our historical analyses reveal a pattern of pathogen invasion and eventual spread across the Sierra Nevada over the last century. Although we found a small number of Bd-infections prior to 1970, these showed no sign of spread or increase in infection prevalence over multiple decades. After the late 1970s, when mass die offs were first noted, our data show Bd as much more prevalent and more spatially spread out, suggesting epizootic spread. However, across the ~400km2 area, we found no evidence of a wave-like pattern, but instead discovered multiple, nearly-simultaneous invasions within regions. We found that Bd invaded and spread in the central Sierra Nevada (Yosemite National Park area) about four decades before it invaded and spread in the southern Sierra Nevada (Sequoia and Kings Canyon National Parks area), and suggest that the temporal pattern of pathogen invasion may help explain divergent contemporary host pathogen dynamics.

Quantitative retinal microvasculature in children using swept-source optical coherence tomography: the Hong Kong Children Eye Study.

AIMS: To evaluate the distributions of quantitative optical coherence tomography angiography (OCT-A) metrics and its associated factors in children. METHODS: 1059 children aged 6-8 years were recruited from the Hong Kong Children Eye Study. All the participants underwent OCT-A with a swept-source OCT. Retinal microvasculature on superficial capillary plexus was assessed and quantified by a customised automated image analysis programme. Univariable and multiple linear regression analyses were performed to determine systemic (body mass index (BMI), waist circumference, head circumference and blood pressure), demographic and ocular (axial length (AL), macular thickness and volume, retinal nerve fibre layer (RNFL) thickness and visual acuity) variables (independent variables) associated with OCT-A metrics (dependent variables). RESULTS: In multiple linear regression analyses, enlarged foveal avascular zone area was associated with female gender (ß=0.110, p<0.001), decreased AL (ß=-0.097, p<0.001) and decreased central macular thickness (ß=-0.008, p<0.001). Decreased vessel density was associated with increased BMI (ß=-4.12×10-4, p=0.006), decreased AL (ß=0.003, p<0.001) and decreased central macular thickness (ß=7.87×10-5, p=0.001). Increased vessel diameter index was associated with female gender (ß=0.020, p=0.007) and decreased AL (ß=-0.020, p<0.001). Decreased fractal dimension was associated with older age (ß=-0.001, p=0.008). There were no significant correlations between OCT-A metrics with visual acuity, RNFL thickness, central corneal thickness, waist circumference, head circumference and blood pressure (all p>0.05). CONCLUSION: Our findings provides new information on baseline morphology of retinal microvasculature and its associated factors in school children, which will be useful for interpreting OCT-A metrics and for identifying and characterising pathological changes in retinal microvasculature.

A case series of anophthalmic socket cysts excised utilising fibrin sealant.

Anophthalmic socket cysts are challenging to remove and incomplete excision has been shown to increase the risk of recurrence. This case series describes a novel technique utilising the fibrin sealant Tisseel (Baxter AG, Vienna, Austria) to retain the socket cyst integrity during surgical removal to facilitate its complete excision. Five patients were included and followed up for a minimum of 1 year, and there were no signs of recurrence in any of the cases. The surgical technique is described and illustrated. This technique is a safe way of simplifying challenging socket cyst surgery.

Dermatologist and Patient Preferences in Choosing Treatments for Moderate to Severe Psoriasis.

INTRODUCTION: The objective of the study was to determine the relative importance (RI) of treatment attributes psoriasis patients and physicians consider when choosing between biologic therapies based on psoriasis severity. METHODS: A discrete choice experiment (DCE) weighting preference for eight sets of hypothetical treatments for moderate or severe psoriasis was conducted. DCE hypothetical treatments were defined and varied on combinations of efficacy, safety, and dosing attributes [frequency/setting/route of administration (ROA)]. RESULTS: When assuming moderate psoriasis in the patient DCE, ROA (RI 29%) and efficacy (RI 27%) drive treatment choices. When assuming severe disease in the DCE, patients preferred treatments with higher efficacy (RI 36%); ROA was relatively less important (RI 15%). From the physician perspective, ROA (RI 32%) and efficacy (RI 26%) were most important for moderate psoriasis patients. In the physician model for severe psoriasis, efficacy (RI 42%) was the predominant driver followed by ROA (RI 22%). Regardless of severity, probability of loss of response within 1 year was the least important factor. CONCLUSIONS: The severity of disease is a critical element in psoriasis treatment selection. There are high levels of alignment between physician- and patient-derived preferences in biologic treatment choice selection for psoriasis. FUNDING: Janssen Pharmaceuticals.

The Urgency of Neuroimaging Among UK Neuro-Ophthalmologists: Consensus and Disagreement.

The timing of imaging in neuro-ophthalmology is critical. There are few published studies, however, that address the question of how urgently to request imaging for neuro-ophthalmic clinical scenarios. We therefore conducted a national survey of expert opinion on the urgency of neuroimaging in neuro-ophthalmology. We devised a list of 40 clinical scenarios, reflecting a wide range of neuro-ophthalmic presentations. For each scenario, respondents were asked to state how urgently they would obtain neuroimaging in day-to-day NHS (National Health Service) practice. There were five response options: "Emergency" (i.e., within 1 d), "Urgent" (i.e., within 1 week), "Semi-urgent" (i.e., within 1 month), "Observation" (only if not resolving after a period of observation [greater than 1 month]), and "Not normally scanned unless new features appear." Respondents were recruited by e-mailing individuals who were on the UKNOSIG (UK Neuro-Ophthalmology Special Interest Group) mailing list. All were Consultant Ophthalmologists or Neurologists specialising in neuro-ophthalmology. Consensus was set at an a priori level of 80% agreement. Only 17 out of 40 scenarios met the criterion for consensus. Nine of these were for emergency/urgent imaging, three were for not imaging, and five were for semi-urgent imaging. For the remaining 23 scenarios, consensus was not reached. Unanimity (100% agreement) was not reached for any scenario. Agreement between neuro-ophthalmologists on the urgency of neuroimaging is patchy, with consensus for some clinical scenarios and disagreement for many. There is a need for a prospective study of neuroimaging in neuro-ophthalmology to determine whether timing of imaging influences outcomes.

C. elegans agrin is expressed in pharynx, IL1 neurons and distal tip cells and does not genetically interact with genes involved in synaptogenesis or muscle function.

Agrin is a basement membrane protein crucial for development and maintenance of the neuromuscular junction in vertebrates. The C. elegans genome harbors a putative agrin gene agr-1. We have cloned the corresponding cDNA to determine the primary structure of the protein and expressed its recombinant fragments to raise specific antibodies. The domain organization of AGR-1 is very similar to the vertebrate orthologues. C. elegans agrin contains a signal sequence for secretion, seven follistatin domains, three EGF-like repeats and two laminin G domains. AGR-1 loss of function mutants did not exhibit any overt phenotypes and did not acquire resistance to the acetylcholine receptor agonist levamisole. Furthermore, crossing them with various mutants for components of the dystrophin-glycoprotein complex with impaired muscle function did not lead to an aggravation of the phenotypes. Promoter-GFP translational fusion as well as immunostaining of worms revealed expression of agrin in buccal epithelium and the protein deposition in the basal lamina of the pharynx. Furthermore, dorsal and ventral IL1 head neurons and distal tip cells of the gonad arms are sources of agrin production, but no expression was detectable in body muscles or in the motoneurons innervating them. Recombinant worm AGR-1 fragment is able to cluster vertebrate dystroglycan in cultured cells, implying a conservation of this interaction, but since neither of these proteins is expressed in muscle of C. elegans, this interaction may be required in different tissues. The connections between muscle cells and the basement membrane, as well as neuromuscular junctions, are structurally distinct between vertebrates and nematodes.

Manual application of controlled forces to thoracic and lumbar spine with a device: rated comfort for the receiver's back and the applier's hands.

PURPOSE: High volumes of manual therapy work can lead to overuse hand and wrist injuries. This study evaluated hand and back comfort in asymptomatic volunteers during spinal mobilization carried out with an instrumented manual therapy tool. METHODS: This crossover design study examined 36 asymptomatic physiotherapy students that were tested in pairs. One participant assumed the role of the simulated therapist and the other the simulated patient, before reversing roles. Posteroanterior mobilization conditions formed by using 2 spinal segments (thoracic/lumbar), 2 force application methods (hands/device), and 3 grades of mobilization were applied in a random order. After each combination, both participants in each pair rated hand or back comfort, respectively, on a 100-mm visual analogue scale. Data were analyzed by analysis of variance. RESULTS: Rated back comfort was greater for hands than for the device and decreased with greater applied force. When the original hard rubber device tip was changed to one of soft molded rubber, both back and hand comfort improved significantly. Although tool mobilization was still rated as significantly less comfortable than mobilization with hands only, this difference was approximately half the discomfort experienced as the grade of mobilization increased from grade I to grade III. For hand comfort when using the softer device tip, the method of force application was no longer a significant determinant of comfort. CONCLUSIONS: The mobilizing tool with a molded rubber tip was acceptably comfortable in use with asymptomatic backs and hands. Further research is indicated in manual therapy settings with therapists who have experienced hand pain.

Optic disk size and optic disk-to-fovea distance in preterm and full-term infants.

PURPOSE: Few studies have assessed optic disk and retinal morphology in infants. Here the optic disk and optic disk-to-fovea distance were measured in preterm and full-term infants in vivo. METHODS: Optic disk (OD) dimensions and the center-to-center distance between the OD and the macula were measured using digital imaging in infants undergoing routine ophthalmic examinations. Postmenstrual age of the mother at the time of examination ranged from 32 to 50 weeks. From each image, the OD-to-fovea distance (ODF) and the OD height (ODH) and OD width (ODW) were measured. RESULTS: In 51 retinal images from 51 infants, mean +/- SD values obtained were 4.4 +/- 0.4 mm (ODF), 1.41 +/- 0.1 9 mm (ODH), and 1.05 +/- 0.13 mm (ODW). These dimensions did not change significantly over the age range studied. The mean value for the ratio between ODF and mean OD diameter (ODF/DD) was 3.76. CONCLUSIONS: Results of this in vivo study suggest that though the optic nerve head diameter increases by more than 50%, only limited growth occurs at the highly organized area of the posterior pole from birth to adulthood. This study discusses the finding of a large-angle kappa in infants and the use of a disk macula/disk diameter ratio in the diagnosis of optic nerve hypoplasia.