Introduction:MRI of extra-ocular muscles (EOM) in patients with myasthenia gravis (MG) could aid in diagnosis and provide insights in therapy-resistant ophthalmoplegia. We used quantitative MRI to... Show moreIntroduction:MRI of extra-ocular muscles (EOM) in patients with myasthenia gravis (MG) could aid in diagnosis and provide insights in therapy-resistant ophthalmoplegia. We used quantitative MRI to study the EOM in MG, healthy and disease controls, including Graves’ ophthalmopathy (GO), oculopharyngeal muscular dystrophy (OPMD) and chronic progressive external ophthalmoplegia (CPEO).Methods:Twenty recently diagnosed MG (59±19yrs), nineteen chronic MG (51±16yrs), fourteen seronegative MG (57±9yrs) and sixteen healthy controls (54±13yrs) were included. Six CPEO (49±14yrs), OPMD (62±10yrs) and GO patients (44±12yrs) served as disease controls. We quantified muscle fat fraction (FF), T2water and volume. Eye ductions and gaze deviations were assessed by synoptophore and Hess-charting.Results:Chronic, but not recent onset, MG patients showed volume increases (e.g. superior rectus and levator palpebrae [SR+LPS] 985±155 mm3 compared to 884±269 mm3 for healthy controls, p < 0.05). As expected, in CPEO volume was decreased (e.g. SR+LPS 602±193 mm3, p < 0.0001), and in GO volume was increased (e.g. SR+LPS 1419±457 mm3, p < 0.0001). FF was increased in chronic MG (e.g. medial rectus increased 0.017, p < 0.05). In CPEO and OPMD the FF was more severely increased. The severity of ophthalmoplegia did not correlate with EOM volume in MG, but did in CPEO and OPMD. No differences in T2water were found.Interpretation:We observed small increases in EOM volume and FF in chronic MG compared to healthy controls. Surprisingly, we found no atrophy in MG, even in patients with long-term ophthalmoplegia. This implies that even long-term ophthalmoplegia in MG does not lead to secondary structural myopathic changes precluding functional recovery. Show less
Background: Adult orbital xanthogranulomatous disease (AOXGD) is a group of rare disorders. Four subtypes are identified: adult-onset xanthogranuloma (AOX), adult-onset asthma and periocular... Show moreBackground: Adult orbital xanthogranulomatous disease (AOXGD) is a group of rare disorders. Four subtypes are identified: adult-onset xanthogranuloma (AOX), adult-onset asthma and periocular xanthogranuloma (AAPOX), necrobiotic xanthogranuloma (NBX), and Erdheim-Chester disease (ECD). Therapy options vary and little is known about the long-term effect of the treatment. In this study, we will describe the clinical behaviour, effect of treatment, and long-term outcome in a consecutive series of patients with AOXGD. Methods: This is a descriptive, retrospective study with a long follow-up term of 21 patients with histologically proven AOXGD, treated between 1989 and 2021 in the Rotterdam Eye Hospital and Erasmus MC University Medical Center. Results: Twenty-one patients with histologically proven AOXGD were included. The follow-up ranged from 2-260 months (median of 67 months). Six of the nine patients with AOX were treated with surgery alone, with recurrence in two. Three received systemic therapy, with recurrence in one. All four patients with AAPOX received systemic treatment, the disease recurred in two. Two patients with NBX were treated with surgery alone, with recurrence in one. Four required additional therapy with recurrence in two. Both patients with ECD required systemic therapy. Conclusions: Recognition of AOXGD is important, in particular, because of the potential severe systemic locations in the different subtypes. Surgical excision might be a sufficient therapy for patients with AOX. Patients with AAPOX, NBX, and ECD warrant systemic therapy. Currently, there is no conclusive evidence for a superior treatment strategy, but further studies are necessary to investigate treatment options. Show less
Uveal melanoma (UM) is the second most frequent type of melanoma. Therapeutic options for UM favor minimally invasive techniques such as irradiation for vision preservation. As a consequence, no... Show moreUveal melanoma (UM) is the second most frequent type of melanoma. Therapeutic options for UM favor minimally invasive techniques such as irradiation for vision preservation. As a consequence, no tumor material is obtained. Without available tissue, molecular analyses for gene expression, mutation or copy number analysis cannot be performed. Thus, proper patient stratification is impossible and patients' uncertainty about their prognosis rises. Minimally invasive techniques have been studied for prognostication in UM. Blood-based biomarker analysis has become more common in recent years; however, no clinically standardized protocol exists. This review summarizes insights in biomarker analysis, addressing new insights in circulating tumor cells, circulating tumor DNA, extracellular vesicles, proteomics, and metabolomics. Additionally, medical imaging can play a significant role in staging, surveillance, and prognostication of UM and is addressed in this review. We propose that combining multiple minimally invasive modalities using tumor biomarkers should be the way forward and warrant more attention in the coming years. Show less
PURPOSE. Uveal melanoma (UM) is characterized by multiple chromosomal rearrangements and recurrent mutated genes. The aim of this study was to investigate if copy number variations (CNV) alone and... Show morePURPOSE. Uveal melanoma (UM) is characterized by multiple chromosomal rearrangements and recurrent mutated genes. The aim of this study was to investigate if copy number variations (CNV) alone and in combination with other genetic and clinico-histopathological variables can be used to stratify for disease-free survival (DFS) in enucleated patients with UM.METHODS. We analyzed single nucleotide polymorphisms (SNP) array data of primary tumors and other clinical variables of 214 UM patients from the Rotterdam Ocular Melanoma Study (ROMS) cohort. Nonweighted hierarchical clustering of SNP array data was used to identify molecular subclasses with distinct CNV patterns. The subclasses associate with mutational status of BAP1, SF3B1, or EIF1AX. Cox proportional hazard models were then used to study the predictive performance of SNP array cluster-, mutation-, and clinico-histopathological data, and their combination for study endpoint risk.RESULTS. Five clusters with distinct CNV patterns and concomitant mutations in BAP1, SF3B1, or EIF1AX were identified. The sample's cluster allocation contributed significantly to mutational status of samples in predicting the incidence of metastasis during a median of 45.6 (interquartile range [IQR]: 24.7-81.8) months of follow-up (P < 0.05) and vice versa. Furthermore, incorporating all data sources in one model yielded a 0.797 C-score during 100 months of follow-up.CONCLUSIONS. UM has distinct CNV patterns that correspond to different mutated driver genes. Incorporating clinico-histopathological, cluster and mutation data in the analysis results in good performance for UM-related DFS prediction. Show less
