Teprotumumab for Thyroid-Associated Ophthalmopathy.

BACKGROUND: Thyroid-associated ophthalmopathy, a condition commonly associated with Graves' disease, remains inadequately treated. Current medical therapies, which primarily consist of glucocorticoids, have limited efficacy and present safety concerns. Inhibition of the insulin-like growth factor I receptor (IGF-IR) is a new therapeutic strategy to attenuate the underlying autoimmune pathogenesis of ophthalmopathy. METHODS: We conducted a multicenter, double-masked, randomized, placebo-controlled trial to determine the efficacy and safety of teprotumumab, a human monoclonal antibody inhibitor of IGF-IR, in patients with active, moderate-to-severe ophthalmopathy. A total of 88 patients were randomly assigned to receive placebo or active drug administered intravenously once every 3 weeks for a total of eight infusions. The primary end point was the response in the study eye. This response was defined as a reduction of 2 points or more in the Clinical Activity Score (scores range from 0 to 7, with a score of ≥3 indicating active thyroid-associated ophthalmopathy) and a reduction of 2 mm or more in proptosis at week 24. Secondary end points, measured as continuous variables, included proptosis, the Clinical Activity Score, and results on the Graves' ophthalmopathy-specific quality-of-life questionnaire. Adverse events were assessed. RESULTS: In the intention-to-treat population, 29 of 42 patients who received teprotumumab (69%), as compared with 9 of 45 patients who received placebo (20%), had a response at week 24 (P<0.001). Therapeutic effects were rapid; at week 6, a total of 18 of 42 patients in the teprotumumab group (43%) and 2 of 45 patients in the placebo group (4%) had a response (P<0.001). Differences between the groups increased at subsequent time points. The only drug-related adverse event was hyperglycemia in patients with diabetes; this event was controlled by adjusting medication for diabetes. CONCLUSIONS: In patients with active ophthalmopathy, teprotumumab was more effective than placebo in reducing proptosis and the Clinical Activity Score. (Funded by River Vision Development and others; ClinicalTrials.gov number, NCT01868997 .).

Bruch's membrane abnormalities in dome-shaped and mushroom-shaped choroidal melanomas.

INTRODUCTION: Mushroom-shaped choroidal melanoma is known to be associated with breaks in Bruch's membrane and is more likely to develop when Bruch's membrane is diseased. The study's goal is to determine if diseases causing breaks in Bruch's membrane predispose a choroidal melanoma to develop into a mushroom-shaped melanoma. MATERIALS AND METHODS: A retrospective review of cases of choroidal melanoma seen at our institution was carried out to determine if mushroom-shaped melanomas are more common than dome-shaped tumours in patients with macular abnormalities involving a loss of Bruch's membrane integrity. Forty-nine eyes of 48 patients were included in this retrospective study. A dome-shaped or mushroom-shaped configuration was assigned to each tumour. Macular degeneration, macular drusen, retinal pigment epithelial (RPE) stippling, macular oedema, choroidal neovascularisation (CNV), angioid streaks, disciform scars, lacquer cracks, and myopia greater than -3.00 D, were considered to constitute evidence of potential Bruch's membrane breaks and were determined in both eyes. A chi-square evaluation was used to compare the proportion of eyes with macular abnormalities in the 2 tumour configuration groups. RESULTS: The tumour was dome-shaped in 40 eyes (82%) and mushroom-shaped in 9 eyes (18%). Macular abnormalities, indicative of loss of Bruch's membrane integrity, were seen in 21 (53%) of 40 eyes with dome-shaped melanomas and 5 (56%) of 9 eyes with mushroom-shaped melanomas. The proportion of eyes with macular abnormalities was not statistically different between the dome-shaped and mushroom-shaped tumours, as assessed by chi-square analysis (P = 0.87). CONCLUSIONS: Bruch's membrane disease does not influence the differentiation of choroidal melanoma into mushroom-shaped or dome-shaped tumour growth patterns.

Myeloid Sarcoma in the Orbit.

The authors describe a case of myeloid sarcoma of the orbit in a pediatric patient. An 8-month-old male infant presented to the ophthalmology clinic with a left orbital mass, which had been increasing in size over the previous 2 months. The mass was initially diagnosed at another clinic as an infantile hemangioma, and had been treated with a topical formulation of timolol. In the ophthalmology clinic, orbital magnetic resonance imaging showed a solid enhancing mass. A biopsy was performed, and histopathology revealed myeloid sarcoma. The disease responded well to a standard chemotherapy regimen. Myeloid sarcoma is a rare, extra-medullary presentation that can occur as an isolated tumor, concurrently with or at relapse of acute myeloid leukemia. Because few cases of myeloid sarcoma in the orbit have been reported, this case report aids in the management of myeloid sarcoma in pediatric patients. The report describes an 8-month-old male infant, the youngest patient to develop myeloid sarcoma without preexisting acute myeloid leukemia. [J Pediatr Ophthalmol Strabismus. 2016;53:e64-e68.].

Endoscopic transethmoidal decompression of a thrombosed orbital venous malformation.

We describe the case of a 37-year-old woman who experienced a painful thrombosis of an orbital venous malformation. We successfully treated her with surgical decompression via a computer-assisted, endoscopic transethmoidal orbitotomy. Removal of the lamina papyracea and evacuation of the thrombus provided immediate symptomatic relief. Decompression via an endoscopic transethmoidal route provides a more direct and less invasive approach than other techniques.

Tendon sheath fibroma of the medial canthus.

Isolated fibromas of the ocular adnexa are rare. Fibromas of the tendon sheath (FTS) are benign, collagenous, spindle cell neoplasms that typically present as an acquired, painless mass in the adult extremities. They infrequently involve the head and neck. We report a case of FTS presenting as a medial canthal mass. Like most FTS, the lesion in our patient was successfully treated by complete surgical excision. While the differential diagnosis contains a variety of mesenchymal tumors, the clinical and radiographic characteristics should lead to the correct diagnosis. To our knowledge, this is the first case of FTS reported to arise at this site.

The spectrum of orbital Rosai-Dorfman disease.

PURPOSE: To describe the spectrum and treatment of orbital Rosai-Dorfman disease and to review previously documented cases. METHODS: Retrospective, interventional case series of seven patients and literature review. RESULTS: Each patient with Rosai-Dorfman disease had unique disease expression requiring aggressive therapy, such as chemotherapy, radiation, and/or surgical excision. One systemically aggressive case presented with intraocular and choroidal invasion, a previously unreported finding. Response to therapy was variable and unpredictable. CONCLUSIONS: Rosai-Dorfman disease, although historically described as benign and self-limiting, may cause significant morbidity and mortality involving multiple organ systems. Available treatment options may not control the disease. Further research and long-term clinical correlation is necessary.