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PURPOSE: Patients with incurable corneal diseases experience visual impairment (VI) despite having a healthy retina and optic pathway. Low-vision aids (LVAs) can optimize the use of remaining vision through magnification and contrast enhancement, but do not harness the full visual capacity because they rely on the optic media. Therefore, we investigated a novel laser eyewear (LEW) technology that bypasses the anterior segment of the eye. Images captured by an integrated camera are projected directly onto the retina using a low-energy laser. The patient is able to view a full-color video, realized as augmented reality. We aimed to evaluate the efficacy of the LEW to enhance the vision of individuals with corneal diseases. DESIGN: Prospective, randomized, crossover clinical trial. PARTICIPANTS: We examined the retinal projection glasses in 21 patients (25-69 years) with VI (0.7 logarithm of the minimum angle of resolution [logMAR] or worse) resulting from corneal diseases. Patients with comorbidities that impact vision, such as retinal disorders, were excluded. METHODS: Standardized measurements of visual acuity (VA) for near vision (NV) and distance vision (DV) were conducted using ETDRS charts with the respective best correction (BC) and then with LEW. In addition reading speed, vision-related quality of life (QoL) and capacity to carry out daily tasks were assessed at an initial visit and at 2 subsequent visits after a home phase with and without the device. Six weeks after last use of the LEW, an ophthalmologic examination including spectral-domain-OCT or full-field-electroretinography was conducted and compared with baseline findings to evaluate the safety of the device. Four patients participated and completed a subsequent 12-month follow-up phase. MAIN OUTCOME MEASURES: Improvement of VA using the LEW. Secondary objectives included safety, reading speed, QoL, and usability in daily activities. RESULTS: The mean VA in patients with VI was improved by 0.43 logMAR in DV using the LEW compared with BC (P < 0.0001). Using the ×2 magnification mode of the LEW resulted in an average improvement of 0.66 logMAR compared with BC (P < 0.0001). In NV, an increase of 0.47 logMAR was achieved compared with BC (P < 0.0001). Although only 4 of 21 participants were able to read with BC, 17 of 21 participants were able to read with the LEW. Quality of life significantly improved in the 17 participants who completed all visits. CONCLUSIONS: We demonstrated that the retinal projection glasses resulted in enhanced VA for all participants by directly projecting images onto the intact retina. In future, the LEW could represent a new option as an LVA for patients with corneal diseases. No pathological alterations were observed in the safety assessments. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
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Despite recent advancements in the diagnosis and treatment of uveal melanoma (UM), its metastatic rate remains high and is accompanied by a highly dismal prognosis, constituting an unmet need for the development of novel adjuvant therapeutic strategies. We established an in vivo chick chorioallantoic membrane (CAM)-based UM xenograft model from UPMD2 and UPMM3 cell lines to examine its feasibility for the improvement of selection of drug candidates. The efficacy of calcium electroporation (CaEP) with 5 or 10 mM calcium chloride (Ca) and electrochemotherapy (ECT) with 1 or 2.5 µg/mL bleomycin in comparison to monotherapy with the tested drug or electroporation (EP) alone was investigated on the generated UM tumors. CaEP and ECT showed a similar reduction of proliferation and melanocytic expansion with a dose-dependent effect for bleomycin, whereas CaEP induced a significant increase of the apoptosis and a reduction of vascularization with varying sensitivity for the two xenograft types. Our in vivo results suggest that CaEP and ECT may facilitate the adequate local tumor control and contribute to the preservation of the bulbus, potentially opening new horizons in the adjuvant treatment of advanced UM.
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Electroquimioterapia , Melanoma , Neoplasias de la Úvea , Humanos , Animales , Calcio , Bleomicina , Membrana Corioalantoides , Xenoinjertos , Electroporación , Calcio de la Dieta , Adyuvantes Inmunológicos , Adyuvantes Farmacéuticos , Pollos , Modelos Animales de EnfermedadRESUMEN
PURPOSE: The purpose of this study was to analyze tumor-related complications after ruthenium-106 brachytherapy in patients with uveal melanoma, with respect to local tumor control, insufficient radiation response, enucleation, and metastasis rate. PATIENTS/METHODS AND MATERIALS: This retrospective study included 608 patients treated consecutively with ruthenium-106 brachytherapy between January 2008 and December 2010 at the Department of Ophthalmology, University Hospital Essen. The occurrence of radiation-induced results was analyzed by estimating the risk by applying the Kaplan-Meier method, i.e., the "time to event" analysis. The Cox model test was used for the univariate and multivariate risk factor analyses. The median follow-up was 51 months after primary treatment. RESULTS: Tumor recurrence was found in 21 patients (3.5%) and repeated treatment due to insufficient effect after the initial ruthenium-106 brachytherapy was performed in 40 patients (6.6%). The 5-year cumulative risk of recurrence was 4.0% and that of insufficient effect was 7.3%. Thirteen patients (2.1%) underwent a secondary enucleation; 8 because of a local recurrence and 5 because of severe post-brachytherapy complications. The cumulative enucleation risk was 2.3% after 5 years and 2.9% after 10 years, corresponding to eye preservation of 97.7 and 97.1%, respectively. In forty-two patients (7.2%), metastatic disease was diagnosed during the follow-up. The metastatic rate as calculated by the Kaplan-Meier method was 9.0, and 13.1% at 5 and 10 years, respectively. CONCLUSION: Our study demonstrated that ruthenium-106 brachytherapy is an excellent treatment option for achieving local tumor control and eye preservation in well-selected patients. The metastatic rate is in agreement with that of previous studies analyzing small to medium size uveal melanomas.
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PURPOSE: To analyze the treatment-related complications after ruthenium-106 brachytherapy in patients with uveal melanoma in terms of radiation-induced optic neuropathy, maculopathy and retinopathy, radiation-related vitreous hemorrhage, and retinal detachment, as well as secondary glaucoma and radiogenic cataract. In addition, the course of visual acuity was analyzed. PATIENTS/METHODS AND MATERIALS: This retrospective study included 608 patients treated with ruthenium-106 brachytherapy between January 2008 and December 2010 at the Department of Ophthalmology, University Hospital Essen. The follow-up time was 11 years. The occurrence of the radiation-induced complications was analyzed using the Kaplan-Meier method. Cox regression was used for univariate and multivariate risk factor analyses. Hazard ratios were calculated for each variable. RESULTS: Regarding the complications, 34% (N = 207) of the patients had no reported side effects or complications during follow-up. Radiation optic neuropathy was observed in 18.8% (N = 114) of the patients, with a median time to onset of 16 months (range: 3â-â78 months). Radiation maculopathy occurred in 8.2% (N = 50) after a median time of 17 months (range: 3â-â67 months). Radiation retinopathy was observed in 20.1% (N = 122), with a median time to onset of 21 months (range: 6â-â67 months). Secondary glaucoma developed in 9.7% of the patients (N = 53) and radiogenic cataract in 46.8% (N = 227). Vitreous hemorrhage (11.8%, N = 72) and scleral necrosis (2.1%, N = 13) occurred relatively rarely. CONCLUSION: The observed radiogenic complication rate is comparable with that reported in previous studies.
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Uveal melanoma (UM) is the most common primary cancer of the eye in adults. A new systemic therapy is needed to reduce the high metastasis and mortality rate. As ß-blockers are known to have anti-tumor effects on various cancer entities, this study focuses on investigating the effect of ß1-selective blockers atenolol, celiprolol, bisoprolol, metoprolol, esmolol, betaxolol, and in particular, nebivolol on UM. The study was performed on 3D tumor spheroids as well as 2D cell cultures, testing tumor viability, morphological changes, long-term survival, and apoptosis. Flow cytometry revealed the presence of all three ß-adrenoceptors with a dominance of ß2-receptors on cell surfaces. Among the blockers tested, solely nebivolol concentration-dependently decreased viability and altered 3D tumor spheroid structure. Nebivolol blocked the repopulation of cells spreading from 3D tumor spheroids, indicating a tumor control potential at a concentration of ≥20 µM. Mechanistically, nebivolol induced ATP depletion and caspase-3/7 activity, indicating that mitochondria-dependent signaling is involved. D-nebivolol or nebivolol combined with the ß2-antagonist ICI 118.551 displayed the highest anti-tumor effects, suggesting a contribution of both ß1- and ß2-receptors. Thus, the present study reveals the tumor control potential of nebivolol in UM, which may offer a perspective for co-adjuvant therapy to reduce recurrence or metastasis.
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Etanolaminas , Melanoma , Adulto , Humanos , Nebivolol/farmacología , Etanolaminas/farmacología , Benzopiranos/farmacología , Antagonistas Adrenérgicos beta/farmacología , Melanoma/tratamiento farmacológico , Receptores Adrenérgicos betaRESUMEN
This case illustrates clinical, histopathological, immunohistochemical, and molecular pathological diagnostic testing of smoldering myeloma with atypical ophthalmic manifestations. In our case, the choroidal lesion presented as a solitary manifestation of a systemic disease. Choroidal lesions of monoclonal plasma cells are extremely rare and should be included in the differential diagnosis of amelanotic choroidal lesions, even if the histopathological examination of the primary lesion is not informative. Clinical course, immunohistochemistry, and molecular pathology are essential components of the diagnostic pathway.
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Neoplasias de la Coroides , Mieloma Múltiple Quiescente , Humanos , Coroides/patología , Neoplasias de la Coroides/diagnóstico , Neoplasias de la Coroides/patologíaRESUMEN
OBJECTIVE: Before planned enucleation, local tumor extension in advanced retinoblastoma is routinely assessed preoperatively using high-resolution magnetic resonance imaging (MRI). The aim of our study was to analyse the predictive value of MRI and clinical characteristics for predicting tumor extent, as confirmed by histopathology postoperatively. PATIENTS AND METHODS: All consecutive patients were included who underwent primary enucleation for advanced retinoblastoma after high-resolution MRI examination in our hospital between January 2011 and December 2021. The primary study endpoint was the evaluation of the predictability of histopathological risk factors on preoperative MRI examination. The sensitivity and specificity of the MRI examination with respect to clinically relevant optic nerve infiltration and choroidal infiltration were determined. RESULTS: The mean age of the 209 included patients was 1.6 years (range 1 month to 4.7 years). MRI indicated optic nerve infiltration in 46 (22%) patients, extensive choroidal infiltration in 78 (40.2%) patients, and scleral infiltration in one patient (2.6%). Histopathological examination demonstrated postlaminar optic infiltration in 25 (12%) patients and extensive choroidal infiltration in 17 (8.1%) cases. Scleral infiltration was evident in 8 (3.8%) patients. In the final multivariate analysis, MRI findings of tumor infiltration and a preoperative intraocular pressure ≥ 20 mmHg were independently associated with histopathological evidence of clinically relevant optic nerve (p = 0.033/p = 0.011) and choroidal infiltration (p = 0.005/p = 0.029). The diagnostic accuracy of the prediction models based on the multivariate analysis for the identification of the clinically relevant optic nerve (AUC = 0.755) and choroidal infiltration (AUC = 0.798) was greater than that of purely MRI-based prediction (respectively 0.659 and 0.742). The sensitivity and specificity of MRI examination for determining histopathological risk factors in our cohort were 64% and 65% for clinically relevant optic infiltration and 87% and 64% for clinically relevant choroidal infiltration. CONCLUSION: The local tumor extent of retinoblastoma with infiltration of the optic nerve and choroid can be well estimated based on radiological and clinical characteristics before treatment initiation. The combination of clinical and radiological risk factors supports the possibility of early treatment stratification in retinoblastoma patients.
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PURPOSE: Ocular surface squamous neoplasia (OSSN) has a high recurrence rate if only treated with surgical excision, especially in cases with positive excision margins. To reduce recurrence, we used brachytherapy after surgical excision for limbal and bulbar lesions in addition to chemotherapy/immunotherapy, cryotherapy, or external beam radiotherapy as adjunctive or primary therapies. METHODS: Nine eyes with isolated OSSN lesions were included in the study. Adjunctive brachytherapy with Ruthenium106-plaques was administered. The follow-up included regular biomicroscopic slit-lamp examination and photo-documentation. Additionally, a staging check for metastasis was performed in cases with squamous cell carcinoma (SCC). RESULTS: The average age of patients at the time of presentation was 66 ± 12 years. Follow-up time was 52.8 ± 44.6 months. The maximal tumour base varied between 3 and 28 mm. SCC was confirmed by histology in all cases. No recurrences were recorded during the follow-up, and organ salvage and eye function preservation were achieved. Radiotherapy-induced complications included secondary glaucoma (n = 1) and scleral melting (n = 1). Other complications, such as radiogenic retinopathy, were not observed. CONCLUSION: Brachytherapy with Ruthenium106-plaques offers an additional option for adjunct treatment of limbal and bulbar OSSN presenting with only a focal spread. Organ salvage can be achieved with a low complication rate and recurrence-free survival. This technique offers globe salvage in patients with tumours involving intraocular infiltration.
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Braquiterapia , Carcinoma de Células Escamosas , Neoplasias de la Conjuntiva , Neoplasias del Ojo , Rutenio , Humanos , Persona de Mediana Edad , Anciano , Procedimientos Quirúrgicos Oftalmológicos/métodos , Estudios Retrospectivos , Neoplasias de la Conjuntiva/diagnóstico , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/patología , Neoplasias del Ojo/patologíaRESUMEN
We assessed the long-term outcomes and treatment-related adverse effects of patients with Stage I, "orbital-type" lymphomas that were uniformly treated with photons. All consecutive patients diagnosed with low-grade, Ann Arbor Stage IEA orbital lymphoma treated between 1999 and 2020 at our department were retrospectively reviewed. We excluded patients with exclusive conjunctival involvement, typically treated with en face electrons. In order to quantify radiotherapy related side effects we applied the CTCAE criteria, analyzed changes in visual acuity, quantified dry eye symptoms by use of the Ocular Surface Disease Index (OSDI) score and applied the EORTC QLQ-C30 questionnaire for quality of life (QoL) assessment. In total 66 eyes of 62 patients were irradiated with a median dose of 30.6 Gy. The median follow-up was 43.5 months. The predominant histological subtype were MALT lymphomas. No local failure occurred in this cohort. Of nine outfield relapses, six solely occurred in the contralateral eye. The 5- and 10- years distant progression free survival rates (PFS) were 81.4% and 63.5%. The 5- and 10-years overall survival rates were 85.1% and 71.9% without any tumor related death. Of the acute toxicities none was higher than CTCAE grade 1. The predominant late toxicities were dry eyes (21.2%) of CTCAE Grade <2 and radiation induced cataracts (19.7%). During long-term follow up the average visual acuity did not deteriorate. The global QoL was worst before treatment and improved significantly after 24 months (p = 0.007). External beam radiotherapy of "orbital-type" lymphomas with photons is an effective and gentle treatment option with excellent local control rates. From the high control rates the trend to use slightly lower total doses of 24-27 Gy with conventional fractionation is supported. As non-coplanar radiotherapy techniques improved and total doses can slightly be reduced, the current status of radiotherapy as first line therapy is provided.
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Supervivientes de Cáncer , Linfoma , Neoplasias Orbitales , Humanos , Neoplasias Orbitales/radioterapia , Calidad de Vida , Estudios Longitudinales , Estudios de Seguimiento , Estudios Retrospectivos , Linfoma/radioterapiaRESUMEN
OBJECTIVES: As described recently, intravenously injected gadolinium-based contrast agent (GBCA) penetrates into the anterior eye chamber (AC) and is drained from the retina to the distal optic nerve (ON) along perivascular spaces, which serves retinal homeostasis and was termed the orbital glymphatic system (GS). Independently, AC enhancement predicted ON infiltration, a major risk factor for advanced retinoblastoma (RB), in a small RB patient cohort. We aimed to review the supposed imaging biomarker for ON infiltration in a large RB cohort and with respect to the recently described orbital GS. METHODS: This IRB-approved retrospective single-center study encompassed 539 orbital MRIs performed with an orbital coil and with the children under general anesthesia. Differences of signal intensity ratios (∆SIRs) of the AC to the lens were determined between non-contrast and GBCA-enhanced T1-weighted images and were correlated with histopathologic presence of ON infiltration. RESULTS: ∆SIR of the RB eye was an independent, significant predictor for ON invasion in multivariate analysis with adjustment for tumor size (p < 0.05) and increased with infiltration level. CONCLUSIONS: GBCA enhancement of the AC predicts ON infiltration. This might be caused by impairment of the orbital glymphatic system, which is supposed to clear toxic metabolites from the retina to the postlaminar ON. In RB with ON infiltration, this efflux path is likely to be inhibited, which is supposed to result in disturbed retinal homeostasis, release of vascular endothelial growth factor, and iris neovascularization, which increases penetration of GBCA into the AC. KEY POINTS: ⢠Infiltration of the optic nerve can be predicted by anterior chamber enhancement after intravenous MRI contrast agent administration. ⢠Increased anterior chamber enhancement in retinoblastoma with optic nerve infiltration might result from dysfunction of the orbital glymphatic system with disturbance of retinal homeostasis and consecutive iris neovascularization.
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Neoplasias de la Retina , Retinoblastoma , Niño , Humanos , Cámara Anterior/diagnóstico por imagen , Cámara Anterior/metabolismo , Medios de Contraste/farmacología , Imagen por Resonancia Magnética/métodos , Invasividad Neoplásica/patología , Nervio Óptico/metabolismo , Neoplasias de la Retina/diagnóstico por imagen , Neoplasias de la Retina/patología , Retinoblastoma/metabolismo , Estudios Retrospectivos , Factor A de Crecimiento Endotelial VascularRESUMEN
BACKGROUND: Eye-preserving therapy in retinoblastoma comprises systemic chemotherapy, but studies analyzing the efficacy of different chemotherapy regimens are scarce. METHODS: The efficacy and side effects of two different eye-preserving chemotherapy regimens containing either vincristine, etoposide, and carboplatin (VEC) or cyclophosphamide, vincristine, etoposide, and carboplatin (CyVEC) were compared in a prospective non-interventional observational study including children diagnosed with retinoblastoma between 2013 and 2019 in Germany and Austria. Event-free eye survival (EFES) and overall eye survival (OES) of all 164 eyes treated with both regimens and risk factors were investigated. RESULTS: The EFES after VEC (2-year EFES 72.3%) was higher than after CyVEC (2-year EFES 50.4%) (plogrank < .001). The OES did not differ significantly between the two treatment groups (plogrank = .77; 2-year OES VEC: 82.1% vs. CyVEC: 84.8%). Advanced International Classification of Retinoblastoma (ICRB) group was prognostic for a lower EFES (plogrank < .0001; 2-year EFES ICRB A/B/C 71.3% vs. ICRB D/E 43.0%) and OES (plogrank < .0001; 2-year OES ICRB A/B/C 93.1% vs. ICRB D/E 61.5%). The multivariate analysis showed that age at diagnosis older than 12 months and ICRB A/B/C were associated with better EFES. No second malignancies or ototoxicities were reported after a follow-up of median 3.1 years after diagnosis of retinoblastoma (range 0.1-6.9 years). CONCLUSIONS: Despite omitting cyclophosphamide, the EFES was higher after VEC chemotherapy that contains higher doses of carboplatin compared to CyVEC. The major risk factor for enucleation was advanced ICRB tumor grouping. Randomized clinical trials on efficacy and side effects of eye-preserving chemotherapy are required to tailor treatment protocols for retinoblastoma patients.
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Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Neoplasias de la Retina , Retinoblastoma , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carboplatino , Niño , Ciclofosfamida , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/tratamiento farmacológico , Etopósido , Enucleación del Ojo , Humanos , Estudios Prospectivos , Neoplasias de la Retina/tratamiento farmacológico , Neoplasias de la Retina/patología , Retinoblastoma/tratamiento farmacológico , Retinoblastoma/patología , VincristinaRESUMEN
Non-specific orbital inflammation (NSOI) and IgG4-related orbital disease (IgG4-ROD) are often challenging to differentiate. Furthermore, it is still uncertain how chronic inflammation, such as IgG4-ROD, can lead to mucosa-associated lymphoid tissue (MALT) lymphoma. Therefore, we aimed to evaluate the diagnostic value of gene expression analysis to differentiate orbital autoimmune diseases and elucidate genetic overlaps. First, we established a database of NSOI, relapsing NSOI, IgG4-ROD and MALT lymphoma patients of our orbital center (2000−2019). In a consensus process, three typical patients of the above mentioned three groups (mean age 56.4 ± 17 years) at similar locations were selected. Afterwards, RNA was isolated using the RNeasy FFPE kit (Qiagen) from archived paraffin-embedded tissues. The RNA of these 12 patients were then subjected to gene expression analysis (NanoString nCounter®), including a total of 1364 target genes. The most significantly upregulated and downregulated genes were used for a machine learning algorithm to distinguish entities. This was possible with a high probability (p < 0.0001). Interestingly, gene expression patterns showed a characteristic overlap of lymphoma with IgG4-ROD and NSOI. In contrast, IgG4-ROD shared only altered expression of one gene regarding NSOI. To validate our potential biomarker genes, we isolated the RNA of a further 48 patients (24 NSOI, 11 IgG4-ROD, 13 lymphoma patients). Then, gene expression pattern analysis of the 35 identified target genes was performed using a custom-designed CodeSet to assess the prediction accuracy of the multi-parameter scoring algorithms. They showed high accuracy and good performance (AUC ROC: IgG4-ROD 0.81, MALT 0.82, NSOI 0.67). To conclude, genetic expression analysis has the potential for faster and more secure differentiation between NSOI and IgG4-ROD. MALT-lymphoma and IgG4-ROD showed more genetic similarities, which points towards progression to lymphoma.
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Enfermedad Relacionada con Inmunoglobulina G4 , Linfoma de Células B de la Zona Marginal , Enfermedades Orbitales , Adulto , Anciano , Expresión Génica , Humanos , Inmunoglobulina G , Inflamación/genética , Linfoma de Células B de la Zona Marginal/diagnóstico , Linfoma de Células B de la Zona Marginal/genética , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Enfermedades Orbitales/diagnóstico , ARN , Estudios RetrospectivosRESUMEN
This article is intended to clearly present the basic principles for the use of intraocular tamponades in vitreous/retinal surgery in the event of retinal detachment and other pathologies using additional video footage. It examines the various gases, silicone oils and perfluorocarbon liquids with their indications, administration and in particular intraoperative handling including pitfalls and complications. Characteristic animations show the principles of use in surgery in a comprehensible way. The two lead authors dedicate this article to their teacher Prof. Dr. V.-P. Gabel, who in the early 1990s successfully established the first vitrectomy courses for ophthalmologists at Regensburg University Eye Clinic each year. Many colleagues who still work in retinal surgery today first started learning about this segment on these courses. The other coauthors participated under his supervision in annual vitrectomy wet labs run by the German Academy of Ophthalmology.
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Fluorocarburos , Desprendimiento de Retina , Humanos , Vitrectomía/efectos adversos , Aceites de Silicona/uso terapéutico , Desprendimiento de Retina/cirugía , Desprendimiento de Retina/etiología , Cuerpo VítreoRESUMEN
The aim of the study was to investigate the use of serial measurements of TSH-receptor autoantibodies (TRAb) with the newest available assay technology to predict the course of Graves' Orbitopathy (GO) during the first 24 months from disease onset. Serial serum samples from patients with GO (103 mild/135 severe) were collected between 2007 and 2017 and retrospectively analyzed. The course of GO were classified into mild/severe 12 months after manifestation (severe: NOSPECS≥5; mild<5). TRAb were measured with automated binding immunoassays (IU/l): TRAb Elecsys (Cobas, Roche), TRAb bridge assay (IMMULITE, Siemens), and a cell-based bioassay (percent of specimen to reference ratio - SRR%) (Thyretain, Quidel). Variable cut off levels of measured TRAb were calculated at specificity of 90% from receiver operator curve (ROC) analysis for several timepoints during the course of GO. To select one: 5-8 months after first GO symptoms, which is the timepoint for usual referals for treatment mild course could be predicted at cut offs of 1.5 IU/l (Elecsys), 0.8 IU/l (Immulite) and 402% SRR (Thyretain) and the risc of severe course has to be anticipated if TRAb are above 11.6 IU/l (Elecsys), 6.5 IU/l (Thyretain), and 714% SRR (Thyretain). The Thyretain bioassay showed the highest diagnostic sensitivity (using the commercial cut off's) over the entire follow up period. TRAb measurements during the 24-month follow up of GO provide added value to the GO clinical activity and severity scores and should be used especially in the event of an unclear decision-taking situation with regard to therapy.
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Autoanticuerpos/sangre , Biomarcadores/sangre , Oftalmopatía de Graves/patología , Inmunoensayo/métodos , Receptores de Tirotropina/inmunología , Adulto , Anciano , Autoanticuerpos/inmunología , Femenino , Estudios de Seguimiento , Oftalmopatía de Graves/sangre , Oftalmopatía de Graves/inmunología , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Adulto JovenRESUMEN
The aim of this study was to investigate the potential of the new TSH-receptor antibody (TRAb) assays to predict remission or relapse of hyperthyroidism in patients with Graves' disease (GD) and Graves' orbitopathy (GO). TRAbs were measured retrospectively in sera from a cohort of GD patients with GO (n=117; remission n=38 and relapse n=79-Essen GO biobank) with automated binding immunoassays: TRAb Elecsys (Cobas Roche) and TRAb bridge assay (IMMULITE, Siemens), and the TSAb (thyroid stimulating Ab) cell-based bioassay (Thyretain, Quidel Corp.). To identify relapse risk/remission of hyperthyroidism patients were followed up at least 10 months after the end of antithyroid drug therapy (ATD) therapy. ROC plot analysis was performed to calculate cut-off levels of TRAb and TSAb for prediction of relapse and remission of hyperthyroidism. Cut-off serum levels are provided for timepoints around 3, 6, 10, and 15 months after the beginning of ATD. Repeated measurements of TRAb increase the rate of relapses predictions to 60% (Elecsys), 70% (IMMULITE), and 55% (Thyretain). Patients with remission have consistently TRAb levels below the cut off for relapse in repeated measurements. The cell-based bioassay was the most sensitive - and continued to be positive during follow up [at 15 months: 90% vs. 70% (IMMULITE) and 65% (Elecsys)]. Identification of relapsing hyperthyroidism is possible with automated immunoassays and cell-based bioassay especially with serial TRAb measurements during the course of ATD therapy. Patient who need eye surgery may profit from an early decision towards definitive treatment.
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Antitiroideos/uso terapéutico , Autoanticuerpos/sangre , Oftalmopatía de Graves/tratamiento farmacológico , Receptores de Tirotropina/inmunología , Adulto , Anciano , Oftalmopatía de Graves/sangre , Oftalmopatía de Graves/inmunología , Oftalmopatía de Graves/patología , Humanos , Masculino , Persona de Mediana Edad , Receptores de Tirotropina/genética , Recurrencia , Estudios Retrospectivos , Adulto JovenRESUMEN
INTRODUCTION: Advanced intraocular retinoblastoma can be cured by enucleation, but spread of retinoblastoma cells beyond the natural limits of the eye is related to a high mortality. Adjuvant therapy after enucleation has been shown to prevent metastasis in children with risk factors for extraocular retinoblastoma. However, histological criteria and adjuvant treatment regimens vary and there is no unifying consensus on the optimal choice of treatment. METHOD: Data on guidelines for adjuvant treatment in European retinoblastoma referral centres were collected in an online survey among all members of the European Retinoblastoma Group (EURbG) network. Extended information was gathered via personal email communication. RESULTS: Data were collected from 26 centres in 17 countries. Guidelines for adjuvant treatment were in place at 92.3% of retinoblastoma centres. There was a consensus on indication for and intensity of adjuvant treatment among more than 80% of all centres. The majority of centres use no adjuvant treatment for isolated focal choroidal invasion or prelaminar optic nerve invasion. Patients with massive choroidal invasion or postlaminar optic nerve invasion receive adjuvant chemotherapy, while microscopic invasion of the resection margin of the optic nerve or extension through the sclera are treated with combined chemo- and radiotherapy. CONCLUSION: Indications and adjuvant treatment regimens in European retinoblastoma referral centres are similar but not uniform. Further biomarkers in addition to histopathological risk factors could improve treatment stratification. The high consensus in European centres is an excellent foundation for a common European study with prospective validation of new biomarkers.
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Neoplasias de la Retina/terapia , Retinoblastoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioterapia Adyuvante/métodos , Niño , Preescolar , Terapia Combinada/métodos , Europa (Continente) , Enucleación del Ojo , Humanos , Pronóstico , Radioterapia Adyuvante/métodos , Neoplasias de la Retina/patología , Retinoblastoma/patología , Factores de Riesgo , Encuestas y CuestionariosRESUMEN
PURPOSE: This study aims to determine local diagnostic reference levels (LDRLs) of intra-arterial chemotherapy (IAC) procedures of pediatric patients with retinoblastoma (RB) to provide data for establishing diagnostic reference levels (DRLs) in pediatric interventional radiology (IR). METHODS: In a retrospective study design, LDRLs and achievable dose (AD) were assessed for children undergoing superselective IAC for RB treatment. All procedures were performed at the flat-panel angiography systems (I) ArtisQ biplane (Siemens Healthineers) and (II) Allura Xper (Philips Healthcare). Patients were differentiated according to age (A1: 1-3 months; A2: 4-12 months; A3: 13-72 months; A4: 73 months-10 years; A5: > 10 years), sex, conducted or not-conducted chemotherapy. RESULTS: 248 neurointerventional procedures of 130 pediatric patients (median age 14.5 months, range 5-127 months) with RB (68 unilateral, 62 bilateral) could be included between January 2010 and March 2020. The following diagnostic reference values, AD, and mean values could be determined: (A2) DRL 3.9 Gy cm2, AD 2.9 Gy cm2, mean 3.5 Gy cm2; (A3) DRL 7.0 Gy cm2, AD 4.3 Gy cm2, mean 6.0 Gy cm2; (A4) DRL 14.5 Gy cm2, AD 10.7 Gy cm2, mean 10.8 Gy cm2; (A5) AD 8.8 Gy cm2, mean 8.8 Gy cm2. Kruskal-Wallis-test confirmed a significant dose difference between the examined age groups (A2-A5) (p < 0.001). There was no statistical difference considering sex (p = 0.076) and conducted or not-conducted chemotherapy (p = 0.627). A successful procedure was achieved in 207/248 cases. CONCLUSION: We report on radiation exposure during superselective IAC of a pediatric cohort at the German Retinoblastoma Referral Centre. Although an IAC formally represents a therapeutic procedure, our results confirm that radiation exposure lies within the exposure of a diagnostic interventional procedure. DRLs for superselective IAC are substantially lower compared with DRLs of more complex endovascular interventions.
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Exposición a la Radiación , Neoplasias de la Retina , Retinoblastoma , Niño , Preescolar , Niveles de Referencia para Diagnóstico , Humanos , Lactante , Recién Nacido , Infusiones Intraarteriales , Neoplasias de la Retina/diagnóstico por imagen , Neoplasias de la Retina/tratamiento farmacológico , Retinoblastoma/diagnóstico por imagen , Retinoblastoma/tratamiento farmacológico , Estudios RetrospectivosRESUMEN
PURPOSE: Currently, therapeutic management of patients with Graves' orbitopathy (GO) relies on clinical assessments and MRI. However, monitoring of inflammation remains difficult since external inflammatory signs do not necessarily represent the orbital disease activity. Therefore, we aimed to evaluate the diagnostic value of 18F-FDG-PET/MRI to assess the inflammation of GO patients. METHODS: Enrolled patients with new onset of GO underwent ophthalmological examinations to evaluate the activity (CAS) and severity of GO (NOSPECS), as well as an 18F-FDG-PET/MRI (Siemens Biograph mMR) with dual time point imaging (immediately post-injection and 60 min p.i.). A subset of PET parameters including maximum standardized uptake value (SUVmax), metabolic target volume (MTV), and total lesion glycolysis (TLG) were obtained separately per eye and per extraocular eye muscle (EOM). EOM thickness was measured on the co-registered MRI. RESULTS: Of 14 enrolled patients, three showed mild, seven moderate-to-severe, and four sight-threatening GO. Patients with severe GO showed statistically significant higher TLG than patients with mild GO (p = 0.02) and higher MTV than patients with mild (p = 0.03) and moderate (p = 0.04) GO. Correlation between NOSPECS on one hand and MTV and TLG on the other was significant (R2 = 0.49-0.61). CONCLUSION: TLG and MTV derived from FDG-PET appear to be good discriminators for severe vs. mild-to-moderate GO and show a significant correlation with NOSPECS. As expected, PET parameters of individual eye muscles were not correlated with associated eye motility, since fibrosis, and not inflammation, is mainly responsible for restricted motility. In conclusion, 18F-FDG-PET/MRI can be used for assessment of GO inflammation.
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Fluorodesoxiglucosa F18 , Oftalmopatía de Graves , Oftalmopatía de Graves/diagnóstico , Humanos , Tomografía de Emisión de Positrones , Pronóstico , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , Carga TumoralRESUMEN
PURPOSE: A central diagnostic tool in adult glaucoma is the peripapillary retinal nerve fibre layer (pRNFL) thickness. It can be assessed by scanning laser polarimetry (SLP) or optical coherence tomography (OCT). However, studies investigating the relevance of pRNFL measurements in children are rare. This study aims to compare the glaucoma diagnosing ability of SLP and OCT pRNFL thickness measurements in a paediatric population. METHODS: This retrospective study included 105 children (glaucoma: 22 (21.0%); healthy glaucoma suspects: 83 (79.0%)) aged 4-18 years, examined with SLP (GDxPro/ECC, Carl Zeiss Meditec) and spectral-domain OCT (SPECTRALIS®, Heidelberg Engineering). The thickness of pRNFL sectors was compared between diseased and healthy participants. Areas under the receiver-operating characteristic curves (AUC) and logistic regression results were used to compare the glaucoma discriminative capacity between SLP and OCT measurements. RESULTS: Using OCT, pRNFL thickness was decreased in the superior, nasal, and inferior quadrants of glaucoma patients compared to healthy controls (P < 0.001, each). With SLP, such a difference was only observed in the inferior quadrant (P = 0.011). A correlation between glaucoma diagnosis and OCT-measured pRNFL thickness was found in all quadrants (P < 0.001) other than the temporal. With SLP, a correlation was found for the total average thickness (P = 0.037) and inferior quadrant (P = 0.0019). Finally, the AUCs of OCT measurements were markedly higher than those of SLP (e.g., inferior quadrant: OCT 0.83, SLP 0.68). CONCLUSION: pRNFL thickness measurements using both OCT and SLP, correlate notably with the presence of glaucoma. In general, the diagnostic performance of pRNFL thickness measurements seems higher for OCT than for SLP. Thus, pRNFL thickness measurements could provide important information, complementing conventional clinical and functional parameters in the diagnostic process of paediatric glaucoma.
Asunto(s)
Glaucoma , Tomografía de Coherencia Óptica , Adulto , Niño , Glaucoma/diagnóstico , Humanos , Fibras Nerviosas , Células Ganglionares de la Retina , Estudios Retrospectivos , Polarimetría de Barrido por LaserRESUMEN
BACKGROUND: We investigated effects of submacular fluid volume (SMFV) on visual outcomes following surgery for macula-off primary rhegmatogenous retinal detachment (RRD) using automated fluid volumetric quantification with optical coherence tomography (OCT). METHODS: We analysed 127 eyes that were surgically treated for macula-off RRDs. We obtained preoperative images following the spectral domain (SD)-OCT dense volume protocol, applied automated retinal segmentation and used an automated algorithm to quantify each eye's SMFV. We used multivariate models to identify various risk factors for impaired visual outcome. RESULTS: Linear regression showed that preoperative SMFV (ß = 0.013; P = .005) was significantly associated with a reduced visual outcome 12 months after the treatment of macula-off RRDs. SMFV was negatively correlated with 12-month postoperative (r = .311; P = .001) visual acuity (VA). The group with low preoperative SMFV (≤9.0 mm3 ) showed an increasing VA up to 12 months postoperatively (P < .001), while the VA did not increase in the group with high SMFV (>9.0 mm3 ) beyond 3 months of follow-up. Patients with a high SMFV were 8.0 times more likely to have worse visual outcomes after 12 months of follow-up (P = .018). CONCLUSIONS: SMFV was negatively correlated with visual outcomes after the surgical treatment of macula-off RRDs. Patients with SMFV <9.0 mm3 12 months after surgery had an 8.0 times greater chance for better visual recovery than patients with high preoperative SMFV. Our findings highlight the efficacy of automated SMFV quantification in predicting surgical outcomes in patients with RRDs, which could be useful in future clinical practice and the development of research models.