Background: Differentiating between dysthyroid optic neuropathy (DON), which requires urgent therapy to prevent blindness, and moderate-to-severe Graves orbitopathy (GO) remains challenging. There is no pathognomonic feature of DON in either ophthalmological or radiological examinations. Objectives: Our aim was to investigate the prevalence of radiological signs of DON in magnetic resonance imaging (MRI) in patients with moderate-to-severe and very severe GO. Methods: Two researchers reassessed MRI scans of 23 consecutive patients (46 eyes) with active, moderate-to-severe GO and 14 patients (23 eyes) with very severe GO. Typical signs of DON in MRI include apical crowding and optic nerve stretching. These were evaluated in the eyes of both groups of patients. Lack of cerebrospinal fluid in the optic nerve sheath as well as muscle index values were also studied. These clinical evaluations and laboratory results were then compared between groups. Results: At least one of the typical radiological features of DON was found in 22 (96%) and 16 (35%) eyes with very severe and moderate-to-severe GO, respectively. Each occurred statistically more often in patients with very severe GO. There were no ophthalmological signs of very severe GO observed in the group of patients with moderate-to-severe GO during the study or its subsequent follow-up (234 weeks). Conclusions: MRI is a useful tool in evaluating very severe GO. However, features typical for DON are also found in up to 35% of eyes in patients with active, moderate-to-severe GO. Therefore, ophthalmological evaluation seems to be most important in the recognition of very severe GO.

To evaluate the effectiveness of methylprednisolone (MP) and surgical treatment in achieving complete reversal of dysthyroid optic neuropathy (DON) and predictive factors of this therapy. The group consisted of 10 patients (18 eyes) with DON. The diagnosis of DON was based on at least two criteria from the following: (i) deterioration of visual acuity (VA< 1.0), (ii) loss of colour vision, (iii) optic disc swelling, and/or (iv) signs of DON in magnetic resonance imaging (presence of apical crowding and/or optic nerve stretching). A complete recovery of DON was defined as the normalisation of VA (VA = 1.0), normal colour vision, and reversal of optic disc swelling. A significant improvement was defined as improvement of VA of at least 0.2. The consecutive steps of treatment of DON consisted of: (i) first-line treatment - intravenous MP pulse therapy (3 × 1 g); (ii) second-line treatment - endoscopic intranasal orbital decompression of medial wall; (iii) additional treatment - additional MP therapy and/or surgical decompression. A significant improvement in VA could be achieved in the majority of patients; a complete recovery was noted in 22.2%, 33.3%, and 66.7% of eyes after first-line, second-line, and additional treatment, respectively. Positive predictive factors were: younger age (p = 0.049), shorter duration of DON (p = 0.035), and a higher Graves' orbitopathy clinical activity score (p = 0.035). By using combination therapy (intravenous MP pulse therapy and surgical decompression), a complete recovery can be achieved in the majority of patients with DON.

We aimed to study the spatiotemporal pattern of lymphatic system formation in the embryonic and early postnatal mouse hearts. The first sign of the development of lymphatics are Lyve‐1–positive cells located on the subepicardial area. Strands of Lyve‐1–positive cells occur first along the atrioventricular sulcus of the diaphragmatic surface and then along the great arteries. Lumenized tubules appear, arranged in rows or in a lattice. They are more conspicuous in dorsal atrioventricular junction, along the major venous and coronary artery branches and at the base of the aorta and the pulmonary trunk extending toward the heart apex. At later stages, some segments of the lymphatic vessels are partially surrounded by smooth muscle cells. Possible mechanisms of lymphangiogenesis are: addition of Lyve‐1–positive cells to the existing tubules, elongation of the lymphatic lattice, sprouting and coalescence of tubules. We discuss the existence of various subpopulations of endothelial cells among the Lyve‐1–positive cells. Developmental Dynamics 237:2973–2986, 2008.

Graves’ ophthalmopathy (GO) is a chronic autoimmune inflammatory disorder involving orbital tissues. A receptor for advanced glycation end products (RAGE) and its ligand high mobility group box 1 (HMGB1) protein trigger inflammation and cell proliferation and are involved in the pathogenesis of various chronic inflammatory diseases. This study was aimed to evaluate RAGE and HMGB1 expression in GO to determine its potential clinical significance. To the best of our knowledge, this is the first study showing RAGE and HMGB1 expression in orbital tissue using immunohistochemistry. Sections of orbital adipose tissue obtained from patients diagnosed with GO (23 patients; 36 orbits) and normal controls (NC) (15 patients; 15 orbits) were analyzed by immunohistochemistry for RAGE and HMGB1 expression. Expression profiles were then correlated with clinical data of the study group. RAGE and HMGB1 expression were elevated in GO patients in comparison with NC (p = 0.001 and p = 0.02, respectively). We observed a correlation between RAGE expression and occurrence of dysthyroid optic neuropathy (DON) (p = 0.05) and levels of TSH Receptor Antibodies (TRAb) (p = 0.01). Overexpression of RAGE and HMGB1 might be associated with GO pathogenesis. In addition, RAGE and HMGB1 proteins may be considered as promising therapeutic targets, but this requires further research.