Evaluating the interreader agreement and intrareader reproducibility of Visual Field Defects in Thyroid Eye Disease- Compressive Optic Neuropathy

PURPOSE To categorize visual field (VF) defects according to Freitag and Tanking's (FT) classification in Thyroid Eye Disease-Compressive Optic Neuropathy (TED-CON) and evaluate the interreader agreement and intrareader reproducibility of the classification. SUBJECTS AND METHODS In this retrospective, observational study we included medical reports of 96 eyes (51 patients), who underwent VF testing with TED-CON in Ludwig-Maximilians-University (2008-2019). Two readers separately examined the VFs at the time of the TED-CON diagnosis, each offering two readings of the same VF in a time interval of 1 month. None of our patients were diagnosed with only VF testing. The visual field testing was only performed when the inclusion criteria for TED-CON were met. RESULTS The most common VF defects upon TED-CON diagnosis were stage 1b defects in FT classification (34.4% for reader 1, 35.4% for reader 2), followed by stage 2b (10.4% for reader 1, 14.6% for reader 2), and stage 3 (10.4% for both readers). The overall interreader agreement between 2 examiners was substantial for the first reading (69.8% agreement, kappa 0.635 (95% CI 0.525-0.745)) and moderate for the second reading (66.7{\%} agreement, kappa 0.598 (95{\%} CI 0.488-0.708)). The intrareader reproducibility ranged from substantial to almost perfect (78.1{\%} agreement) between readings (kappa 0.736 (95{\%}CI 0.638-0.834)) for reader 1 and 90.6{\%} agreement (kappa 0.885 (95{\%}CI 0.814-0.956)) for reader 2. CONCLUSION We found good BCVA (LogMAR $\leq$ 0.2), in nearly half of the cases (44 eyes, 45.8{\%}) and also, strikingly near perfect visual acuity (BCVA LogMAR $\leq$0.1) in 22.9{\%} of the cases (22 eyes) with TED-CON. We conclude that clinicians should be alert to VF defects in the inferior region (stage 1a/1b in the FT classification) even in patients with a good BCVA

A pathological indicator for dysthyroid optic neuropathy: tritan color vision deficiency

PURPOSE To investigate the sensitivity of the color vision test by Arden in patients with dysthyroid optic neuropathy (DON) to improve diagnosis. METHODS In this observational, retrospective study, we included the medical records of 92 eyes (48 patients) with diagnosis of DON between 2008 and 2019 in order to evaluate the full spectrum of findings from the color vision test by Arden, and to determine potential importance of this test. Thirty-five patients were female, and 13 patients were male. The mean age was 58.0~years (range: 34-79) at the time of the DON diagnosis. RESULTS Forty-one eyes displayed relatively good BCVA with ≤ 0.2 LogMAR. We found a protan value exceeding the threshold of ≥ 8% in 57 eyes (30 patients) at the time of the diagnosis. The sensitivity of protan was 61.9% (95% CI 51.2-71.8%), while that of tritan was a striking 98.9% (95% CI 94.1-99.9%). We discovered one pathological sign, tritan deficiency (based on a threshold of ≥ 8%) consistently in all eyes but one at the time of the diagnosis, regardless of the visual field defects or any changes in best-corrected visual acuity (BCVA). CONCLUSION We found blue-yellow (tritan) deficiency, to be a sensitive and reliable indicator of dysthyroid optic neuropathy. We conclude that, in cases with suspected DON, a color vision test that can detect tritan deficiency is an essential tool for the adequate assessment, diagnosis, and treatment of DON

Combined positron emission tomography/computed tomography (PET/CT) for imaging of orbital tumours and tumours extending into the orbit

Objective To assess clinical and radiological performance of combined positron emission tomography/computed tomography (PET/CT) in patients with secondary and primary intraorbital tumours. Methods 14 adults with secondary and 1 child with primary orbital masses underwent combined whole-body PET/CT. Radiopharmaceutical tracers applied were (18F)-fluorodeoxyglucose, (18F)-fluoroethylcholine (FEC) and (68Ga)-DOTATATE. Histopathology and/or all conventional radiographic work-up and clinical course served as standard of reference. Descriptive statistics and Fisher's exact test were used for analysis. Results PET/CT detected all orbital masses. All 15 patients had malignant disease. Local osseous infiltration was correctly identified in 11 patients. Lymph node metastases were present in two of eight patients (25%) with haematogenous orbital metastases and in five of six patients (83%) with infiltrative carcinoma (p=0.05). Further distant metastases were present in all eight patients suffering from orbital metastases, but only one patient with infiltrative carcinoma (17%) presented with disseminated disease (p=0.003). In one metastasis, PET/CT excluded vital orbital tumour tissue after radiation therapy. Local recurrence was detected in another patient suffering from prostate cancer. Conclusion PET/CT is a sensitive tool for the detection and localisation of orbital masses, enabling assessment of both morphology and cell metabolism. Detailed imaging of the head and neck region with a small field-of-view should be performed when suspecting lymphatic metastases. As metastatic disease to the orbit is associated with advanced disease, focus should be laid on whole-body imaging for staging of these patients. Different radiopharmaceutical tracers can be applied to distinguish the origin of orbital metastases

Hertel-exophthalmometry-like multi-detector-row-CT-exophthalmometry: inter-disciplinary inter-observer reproducibility of measurements

Objectives: To investigate the interdisciplinary interobserver reproducibility of Hertel-exophthalmometry-like protrusion measurements on multidetector-row-computed-tomography- (MDCT-) images of the orbit to facilitate structured evaluation of the orbit and mid-face. Methods: Respective reproducibility of base-length along the interfronto-zygomatic line, right and left ocular protrusion, and deriving interocular difference was measured in this retrospective (04/2009-03/2020) single-centre observational study. MDCT-series and slice-positions were selected independently, using picture-archiving-and-communication-system- (PACS-) tools on tilt-corrected axial MDCT-images (slice-thickness 0.6–3.0 mm, window/centre 350/50 HU) in 37 selected adult patients (24 female, age 57 ± 13 years, average±standard-deviation) with clinical indication for Hertel-exophthalmometry, by one radiology-attending, two ophthalmology-attendings, one critical-care-attending, and one ear-nose-throat-surgery resident, respectively. Bland-Altman plots and Wilcoxon-matched-pairs-signed-rank-tests compared interobserver results. Results: Mean and median interobserver and intraobserver (radiology-attending) deviations were within 1 mm of respective averages of base-length (98 ± 4 mm), right and left ocular protrusion (21 ± 4 mm) and interocular difference (2 ± 1 mm). Relative interobserver deviations were within 2.0% of average (all patients) for base-length, and 5.0% (>80% of patients) for ocular protrusion. Pairwise interobserver comparison showed no significant differences between interocular differences of protrusion. Conclusions: Respective measurements of base-length, ocular protrusion, and deriving interocular difference show high interdisciplinary interobserver reproducibility in tilt-corrected axial MDCT-images of the orbit or mid-face. Advances in knowledge: Hertel-exophthalmometry-like protrusion measurements did not depend on the years of experience or the medical subspecialty of the observer. Measurements are objective, well reproducible and important for multiple medical disciplines and should thus be included in pertinent radiology reports

Expression of pH-Sensitive TRPC4 in Common Skin Tumors

TRPCs (transient receptor potential classical or cation channels) play a crucial role in tumor biology, especially in the Ca2+ homeostasis in cancer cells. TRPC4 is a pH-sensitive member of this family of proteins. As solid tumors exhibit an inversed pH-gradient with lowered extracellular and increased intracellular pH, both contributing to tumor progression, TRPC4 might be a signaling molecule in the altered tumor microenvironment. This is the first study to investigate the expression profiles of TRPC4 in common skin cancers such as basal cell carcinoma (BCC), squamous cell carcinoma (SCC), malignant melanoma (MM) and nevus cell nevi (NCN). We found that all SCCs, NCNs, and MMs show positive TRPC4-expression, while BCCs do only in about half of the analyzed samples. These data render TRPC4 an immunohistochemical marker to distinguish SCC and BCC, and this also gives rise to future studies investigating the role of TRPC4 in tumor progression, and especially metastasis as BCCs very rarely spread and are mostly negative for TRPC4

Presentation of Graves' orbitopathy within European Group On Graves' Orbitopathy (EUGOGO) centres from 2012 to 2019 (PREGO III)

Background: Graves' orbitopathy (GO) is subject to epidemiological and care-related changes. Aim of the survey was to identify trends in presentation of GO to the European Group On Graves' Orbitopathy (EUGOGO) tertiary referral centres and initial management over time. Methods: Prospective observational multicentre study. All new referrals with diagnosis of GO within September-December 2019 were included. Clinical and demographic characteristics, referral timelines and initial therapeutic decisions were recorded. Data were compared with a similar EUGOGO survey performed in 2012. Results: Besides age (mean age: 50.5±13 years vs 47.7±14 years; p 0.007), demographic characteristics of 432 patients studied in 2019 were similar to those in 2012. In 2019, there was a decrease of severe cases (9.8% vs 14.9; p<0.001), but no significant change in proportion of active cases (41.3% vs 36.6%; p 0.217). After first diagnosis of GO, median referral time to an EUGOGO tertiary centre was shorter (2 (0-350) vs 6 (0-552) months; p<0.001) in 2019. At the time of first visit, more patients were already on antithyroid medications (80.2% vs 45.0%; p<0.001) or selenium (22.3% vs 3.0%; p<0.001). In 2019, the initial management plans for GO were similar to 2012, except for lid surgery (2.4% vs 13.9%; p<0.001) and prescription of selenium (28.5% vs 21.0%; p 0.027). Conclusion: GO patients are referred to tertiary EUGOGO centres in a less severe stage of the disease than before. We speculate that this might be linked to a broader awareness of the disease and faster and adequate delivered treatment

Potential Delay of Diagnosing Infraorbital Skin Tumors Due to Coverage by Face Masks During the COVID-19 Pandemic: An Observational Study

Aim: To assess the potential danger of belated diagnosis or underdiagnosis of cutaneous infraorbital pathologies that are partially or fully covered by face masks worn due to the COVID-19 pandemic.Methods: We evaluated data of 257 patients with infraorbital pathologies presenting at a large tertiary German university center between 04/2020 and 06/2021. This mono-centric, retrospective analysis included descriptive statistics and non-parametric tests.Results: Out of 257 cutaneous infraorbital pathologies, 32 (12.5%) were partially and 20 (7.8%) fully covered by the required face mask. Significantly more patients with lesions that were partially or fully covered came from a single household (p=0.003, Fisher's exact test) with 125 (48.6%) patients reportedly living alone. In patients with multiple periocular pathologies (n = 51, 19.8%), the risk of at least one periocular lesion being covered by the face mask was significantly elevated (p=0.009, Fisher's exact test). As expected, malignant tumors were significantly larger than benign pathologies (largest diameter, malignant median 9.0mm, range 1.3-34.0mm, mean 10.5mm, and benign median 3.0mm, range 1.0-7.0mm, mean 4.3mm, respectively;p<0.001, Mann-Whitney-Utest) and patients presenting with malignant lesions were significantly older (median age 78.4, range 33-93, mean 73.7 years versus median age 57.9, range 18-90, mean 59.8 years, respectively; p<0.001, Mann-Whitney-U test). Additionally, in subgroup analysis, patients with malignant lesions coming from single households were significantly older (p=0.041, Mann-Whitney-U test).Conclusion: For adequate and timely treatment of infraorbital lesions, patients should be examined without their face mask. This is of utmost importance for the elderly (being at greater risk for malignant pathologies) and patients coming from single households. The presence of multiple pathologies must always be excluded. Trial Registration Number: Not applicable

The length of unsutured mucosal margins in external dacryocystorhinostomy

PURPOSE: To compare the extent of mucosal margins remaining unsutured at the end of external dacryocys, torhinostomy (DCR) using single or double flap techniques and to evaluate the influence on outcome. DESIGN: Prospective, consecutive case series. METHODS: The number and length of mucosal Mar. gins remaining unsutured at the end of external DCR were evaluated in 64 patients. Mucosal anastomosis was performed using either a conservative (group 1) or extended (group 2) double flap, or a single flap (group 3) dissection. Patients were selected for group 1 if the regional anatomy permitted the desired dissection. All other patients were randomized to group 2 or 3. The mean length of unsutured mucosal margins was calculated for each group. Subjects were followed up to 12 months, with final success rate recorded. RESULTS: In groups 1, 2, and 3 respectively: 11, 24 and 29 patients were recruited; four, 12, and 10 mucosal margins remained unsutured; and the mean length of unsutured mucosal margins was 16.36 mm (SD = 2.8), 70.66 mm (SD = 9.3), and 62.00 mm (SD = 6.0). The mean length of unsutured mucosal margins was significantly different, although groups 1 and 2 collectively did not have a significantly different mean length of unsutured mucosal margin from group 3. Mean follow,up was 11 months (SD = 2.2), 63 patients (98-43%) had a successful outcome with no significant difference among groups (P =.429). CONCLUSION: Different patterns of mucosal dissection in external DCR create a different number and extent of unsutured mucosal margins which do not appear to adversely affect the success rate of external DCR. (C) 2004 by Elsevier Inc. All rights reserve