Comparative effectiveness of different treatment modalities for active, moderate-to-severe Graves' orbitopathy: a systematic review and network meta-analysis.

To compare the effects of different treatment modalities on active, moderate-to-severe Graves' orbitopathy (GO). We searched PubMed and Embase for randomized controlled trials published up to 30 Nov 2020, of different modalities for the treatment of active, moderate-to-severe GO. We performed Bayesian network meta-analyses. This study is registered with PROSPERO (CRD42020166287). Fifteen RCTs were identified. Network meta-analysis showed that in comparison with placebo, teprotumumab, mycophenolate plus intravenous glucocorticoids (IVGCs), mycophenolate, rituximab, azathioprine, IVGCs, orbital radiotherapy, oral glucocorticoids (OGCs) were effective treatments (ordered from most effective to least effective). Teprotumumab was more efficacious in reducing proptosis than IVGCs. No significant difference in changes in diplopia grade was recorded between teprotumumab, rituximab, orbital radiotherapy and IVGCs. Low (4.5-5 g), middle (6 g) and high (7-8 g) cumulative doses of IVGCs were shown to be more effective than OGC in improving the overall response rate, but the very low-group (<3 g) seemed to have a lower risk of adverse events. We found that teprotumumab offered the highest level of efficacy in terms of the overall response rate and was more efficacious in reducing proptosis than IVGCs. With regard to different dosages of IVGCs, the cumulative dose of 4.5-5 g of IVGCs seems to be the most appropriate schedule in terms of efficacy and safety outcomes. Due to the limited number of patients treated with teprotumumab and the lack of comparison with other effective therapeutics, teprotumumab might not become the standard first-line therapy for active, moderate-to-severe GO.

Acute Orbital Compromise after Intra-Arterial Chemotherapy in a Complex Retinoblastoma Associated with 13q Deletion Syndrome.

INTRODUCTION: The intra-arterial chemotherapy (IAC) is increasingly used as a first-line therapy for retinoblastoma. The IAC has proved to be relatively safe. However, many local side effects of IAC have been described. CASE PRESENTATION: This case report describes a local side effect presenting as proptosis and myositis with vascular access difficulty of the middle meningeal artery, in a 2-year-old male with left eye diffuse multifocal stage Vb retinoblastoma complicated with retinal detachment. DISCUSSION/CONCLUSION: IAC is assured to provide as efficient results in eliminating the tumor as the systemic chemotherapy, without causing the systemic side effects. It has become an alternative to systemic chemotherapy. A better understanding of the local side effects is required.

A Rare Case of Mixed Adenoneuroendocrine Carcinoma (MANEC) of the Gastroesophageal Junction with HER2/neu Overexpression and Distinct Orbital and Optic Nerve Toxicity after Intravenous Administration of Cisplatin.

BACKGROUND: Mixed adenoneuroendocrine carcinomas (MANECs) are rare malignancies with both neuroendocrine and non-neuroendocrine components. To date, the prognosis of gastroenteropancreatic MANECs remains dismal, and treatment options are mainly based on guidelines for the treatment of pure neuroendocrine carcinomas or small cell lung cancer. Established first-line therapy in the metastatic situation is cisplatin and etoposide. Platinum derivatives are known to cause a variety of side effects also involving the visual system. Severe orbital and optic nerve toxicities have been described mainly after intracarotid infusion of cisplatin. CASE REPORT: Herein we report a rare case of a 60-year-old male patient suffering from MANEC of the gastroesophageal junction with HER2/neu overexpression who developed severe orbital and ocular neurotoxicity (grade 3 according to CTCAE v4.03) after intravenous cisplatin. CONCLUSION: We discuss diagnostic approaches and differential diagnoses in this clinical situation. Before starting treatment with intravenous and topical steroids, it is crucial to rule out meningeal and cerebral spread as well as paraneoplastic and endocrine syndromes.

Hyaluronidase hypersensitivity: A rare complication of peribulbar block.

Peribulbar block, though safe, can cause serious complications such as globe perforation and peribulbar hemorrhage. Hyaluronidase is an enzyme that is used as an adjuvant in peribulbar anesthesia, and it helps in rapid penetration of the anesthetic agent. Hypersensitivity to hyaluronidase is a rare but potentially sight-threatening complication. We report a case of hyaluronidase hypersensitivity following peribulbar injection for cataract surgery mimicking as peribulbar hematoma in the immediate postinjection phase and as orbital cellulitis 48 h later.

Adverse health effects and histological changes in white sturgeon (Acipenser transmontanus) exposed to dietary selenomethionine.

It has been shown that selenium (Se) released to the aquatic environment can have devastating effects on local wildlife. White sturgeon (Acipenser transmontanus) have a life history particularly susceptible to contaminants, and their protection is of interest as they are culturally and economically important, and many populations are classified as endangered. During the present 72-d dietary study, multiple signs of decreased health and Se lethality were observed. Juvenile white sturgeon were given diets containing 1.4 µg, 5.6 µg, 22.4 µg, or 104.4 µg selenomethionine/g food (dry mass). Selenium accumulated in muscle and liver tissue in a dose-dependent manner. Edema causing exophthalmos developed within 15 d and 23 d, and lethal effects occurred in 54% and 22% of fish in the high- and medium-dose groups, respectively. Growth and hepatosomatic index were significantly lower in the high-dose group, which also had a high incidence of food avoidance. Histology of the liver revealed a dose-dependent increase in melanomacrophage aggregates and decrease of energy stores, which indicated toxicity. These results indicate that white sturgeon are susceptible to the effects of Se accumulation over relatively short time periods. This stresses the need for continued sturgeon research and studies looking into the environmental fate and regulation of released Se. Environ Toxicol Chem 2016;35:1741-1750. © 2015 SETAC.

[Isolated superior ophthalmic vein thrombosis due to tamoxifen]. / Thrombose isolée de la veine ophtalmique supérieure secondaire au tamoxifène.

Superior ophthalmic vein thrombosis is a rare entity, which may lead to serious vision complications. We report the unusual observation of a 78-year-old patient who developed exophtalmos, chemosis, and blurred vision due to isolated superior ophthalmic vein thrombosis. This rare complication is likely due to tamoxifen therapy. In contrast with published data, in the present case, cessation of tamoxifen therapy did not improve ocular symptoms.

Thyroid-like ophthalmopathy in a euthyroid patient receiving Ipilimumab.

A 68-year-old lady with metastatic malignant melanoma was treated with Ipilimumab. She presented to Eye Casualty unable to move her eyes. Physical examination confirmed ophthalmoplegia and identified proptosis bilaterally. Radiological imaging showed bilateral enlargement of all the extra-ocular muscles suggestive of thyroid eye disease. Laboratory investigations found this patient to be euthyroid. A diagnosis of thyroid-like orbitopathy secondary to Ipilimumab therapy was made. Thyroid function tests should be performed for all patients prior to their commencement of Ipilimumab. Thyroid-like eye disease may develop in patients treated with Ipilimumab even if they remain euthyroid.

Drug-induced graves disease from CTLA-4 receptor suppression.

Monoclonal antibody, ipilimumab, useful for treatment of metastatic melanoma, blocks CTLA-4 mediated T-cell suppression and can also cause a Graves ophthalmopathy like syndrome. Epidemiologic study has linked variant polymorphisms of CTLA-4 receptor gene to the presence of thyroid eye disease. The combination of these observations suggests CTLA-4 mediated T-cell functions are important to the pathogenesis of thyroid-associated eye disease.

Orbital steroid injection versus oral steroid therapy in management of thyroid-related ophthalmopathy.

BACKGROUND: The aim of this study was to evaluate the efficacy, safety and complications of orbital steroid injection versus oral steroid therapy in the management of thyroid-related ophthalmopathy. METHODS: A total of 29 patients suffering from thyroid ophthalmopathy were included in this study. Patients were randomized into two groups: group I included 15 patients treated with oral prednisolone and group II included 14 patients treated with peribulbar triamcinolone orbital injection. Only 12 patients in both groups (16 female and 8 male) completed the study. RESULTS: Both groups showed improvement in symptoms and in clinical evidence of inflammation with improvement of eye movement and proptosis in most cases. Mean exophthalmometry value before treatment was 22.6 ± 1.98 mm that decreased to 18.6 ± 0.996 mm in group I, compared with 23 ± 1.86 mm that decreased to 19.08 ± 1.16 mm in group II. Mean initial clinical activity score was 4.75 ± 1.2 and 5 ± 1.3 for group I and group II before treatment, respectively, which dropped to 0.83 ± 1.2 and 0.83 ± 1.02, 6 months after treatment, respectively. There was no change in the best-corrected visual acuity in both groups. There was an increase in body weight, blood sugar, blood pressure and gastritis in group I in 66.7%, 33.3%, 50% and 75%, respectively, compared with 0%, 0%, 8.3% and 8.3% in group II. No adverse local side effects were observed in group II. CONCLUSION: Orbital steroid injection for thyroid-related ophthalmopathy is effective and safe. It eliminates the adverse reactions associated with oral corticosteroid use.

Marrow suppression with myelodysplastic features, hypoerythropoetinemia, and lipotrophic proptosis due to rosiglitazone.

Thiazolidinediones (TZDs) are frequently used pharmacotherapeutics for type II diabetes mellitus, which exert their effect through peroxisomal proliferator agonist receptor (PPAR) mediated increased insulin sensitivity. TZDs are known to cause marrow suppression and to stimulate adipogenesis. Case and cohort studies show TZDs worsen thyroid-associated orbitopathy. We present a case consistent with earlier reports of marrow suppressive pancytopenia manifesting as myelodysplastic syndrome, a new implication of hypoerythropoetinemia, and non-Graves'-associated proliferative proptosis.

Exacerbation of Graves ophthalmopathy with interferon-alpha therapy.

Thyroid dysfunction, particularly hypothyroidism, following interferon-alpha therapy is not uncommon. To our knowledge, this is the first case report of exacerbation of Graves ophthalmopathy during treatment with interferon-alpha for chronic hepatitis C virus.

Thiazolidinedione induced thyroid associated orbitopathy.

BACKGROUND: To describe an episode of thyroid associated orbitopathy (TAO) following the initiation of thiazolidinedione (TZD). CASE PRESENTATION: We report a female patient with a history of Graves' disease and stabilised thyroid associated orbitopathy for 2.5 years, who experienced rapid progression of TAO after the initiation of thiazolidinedione for glycemic control. Following the discontinuation of TZD, the patient experienced subsequent stabilisation of disease and normalization of vision. The medical history, ophthalmic findings, and clinical course are discussed. CONCLUSION: Thiazolidinediones may exacerbate TAO, and this should be taken into consideration when selecting treatment for diabetic patients with a history of autoimmune thyroid disorders.

Periocular inflammation after retrobulbar chlorpromazine (thorazine) injection.

PURPOSE: Retrobulbar chlorpromazine injection is a relatively recently described method of pain control in nonseeing eyes. This report illustrates severe sterile inflammation as a potential complication. METHODS: In this university-based, retrospective, small case series, we reviewed the records of 2 female patients and 1 male patient (ages, 13 to 89 years) who developed severe inflammation after retrobulbar chlorpromazine injection. RESULTS: Three patients had development of severe periocular edema after retrobulbar chlorpromazine injection. Two had development of chemosis, limited extraocular motility, proptosis, and incomplete eyelid closure, necessitating temporary tarsorrhaphy. The third patient had development of facial edema involving the ipsilateral eyelids, forehead, and cheek. Strikingly, it extended to the contralateral face. All 3 patients denied discomfort. In each case, swelling was first noted the day after injection and progressed for 1 week. All were treated with topical lubrication and two with temporary tarsorrhaphy. Resolution occurred within 3 weeks in each case. CONCLUSIONS: Severe periocular inflammation can result from retrobulbar chlorpromazine injection and may manifest as chemosis, proptosis, limited ocular motility, and facial swelling that may extend well beyond the eyelids. Awareness of this potential adverse reaction is important both for patient counseling before injection and subsequent treatment. Specifically, a sterile inflammatory response should be differentiated from infection to avoid inappropriate therapy.

Treatment with a thiazolidinedione increases eye protrusion in a subgroup of patients with type 2 diabetes.

OBJECTIVE: Changes in eye protrusion in patients treated with pioglitazone. DESIGN: Open-label prospective. PATIENTS: Thirty-six patients with type 2 diabetes and HbA1c >or= 6.5% were included in a study where pioglitazone was added to current therapy with metformin and sulphonylurea. MEASUREMENTS: The degree of eye protrusion before and 26 weeks after treatment with pioglitazone was measured using Krahn's exophthalmometer. RESULTS: Thirteen patients (group A) exhibited an increase of >or= 2 mm and 23 patients (group B) exhibited an increase of < 2 mm (P (between groups) = 0.036). Patients of group A vs. group B had the same BMI, HbA1c and mean doses of pioglitazone, but had lower levels (mean +/- SD) of adiponectin in microg/ml at the start (4.9 +/- 2.1) vs. (7.1 +/- 2.5), P = 0.017 and at the end of study (10.2 +/- 4) vs. (14.9 +/- 5), P = 0.007. Patients with thyroid disturbance were more frequent in group A (five vs. one), P = 0.02. In a logistic regression analysis, thyroid disturbance, low adiponectin levels and pioglitazone dose predicted a significant change in eye protrusion. CONCLUSIONS: A subgroup of patients with type 2 diabetes treated with pioglitazone responded with increased eye protrusion. This subgroup showed decreased plasma concentration of adiponectin and more frequent thyroid disturbance, and was treated with higher doses of pioglitazone. The relationship between insulin resistance, thyroid disturbance and thiazolidinedione-induced eye protrusion should be further studied.