Noninvasive Imaging of Liposomal Delivery of Superparamagnetic Iron Oxide Nanoparticles to Orthotopic Human Breast Tumor in Mice.

PURPOSE: Magnetic resonance imaging (MRI) is widely used for diagnostic imaging in preclinical studies and in clinical settings. Considering the intrinsic low sensitivity and poor specificity of standard MRI contrast agents, the enhanced delivery of MRI tracers into tumors is an important challenge to be addressed. This study was intended to investigate whether delivery of superparamagnetic iron oxide nanoparticles (SPIONs) can be enhanced by liposomal SPION formulations for either "passive" delivery into tumor via the enhanced permeability and retention (EPR) effect or "active" targeted delivery to tumor endothelium via the receptors for vascular endothelial growth factor (VEGFRs). METHODS: In vivo MRI of orthotopic MDA-MB-231 tumors was performed on a preclinical 9.4 T MRI scanner following intravenous administration of either free/non-targeted or targeted liposomal SPIONs. RESULTS: In vivo MRI study revealed that only the non-targeted liposomal formulation provided a statistically significant accumulation of SPIONs in the tumor at four hours post-injection. The EPR effect contributes to improved accumulation of liposomal SPIONs in tumors compared to the presumably more transient retention during the targeting of the tumor vasculature via VEGFRs. CONCLUSIONS: A non-targeted liposomal formulation of SPIONs could be the optimal option for MRI detection of breast tumors and for the development of therapeutic liposomes for MRI-guided therapy.

PREGO (presentation of Graves' orbitopathy) study: changes in referral patterns to European Group On Graves' Orbitopathy (EUGOGO) centres over the period from 2000 to 2012.

BACKGROUND/AIMS: The epidemiology of Graves' orbitopathy (GO) may be changing. The aim of the study was to identify trends in presentation of GO to tertiary centres and initial management over time. METHODS: Prospective observational study of European Group On Graves' Orbitopathy (EUGOGO) centres. All new referrals with a diagnosis of GO over a 4-month period in 2012 were included. Clinical and demographic characteristics, referral timelines and initial decisions about management were recorded. The data were compared with a similar EUGOGO survey performed in 2000. RESULTS: The demographic characteristics of 269 patients studied in 2012 were similar to those collected in the year 2000, including smoking rates (40.0% vs 40.2%). Mild (60.5% vs 41.2%, p<0.01) and inactive GO (63.2% vs 39.9%, p<0.01) were more prevalent in 2012. The times from diagnosis of thyroid disease to being seen in EUGOGO centres (6 vs 16 months) and from first symptoms of GO (9 vs 16 months) or from diagnosis of GO (6 vs 12 months) to first consultation in EUGOGO centres were shorter in 2012 (p<0.01). The initial management plans for GO were no different except surgical treatments for patients with mild inactive disease were more frequently offered in the 2012 cohort than in 2000 (27.3% vs 17%, p<0.05), and selenium supplements were offered only in the 2012 cohort (21.2% vs 0%, p<0.01). CONCLUSIONS: These findings suggest that the clinical manifestations of patients with GO may be changing over time in Europe.

Novel thermal imaging analysis technique for detecting inflammation in thyroid eye disease.

CONTEXT: The disease phase in thyroid eye disease (TED) is commonly assessed by clinical investigation of cardinal signs of inflammation and using the clinical activity score (CAS). Although CAS is the current gold standard, the clinical assessment would benefit if a more objective tool were available. OBJECTIVE: The aim of this work was to explore the clinical value of a novel thermal imaging analysis technique to objectively quantify the thermal characteristics of the eye and peri-orbital region and determine the disease phase in TED. DESIGN: This was a cross-sectional study comparing consecutive patients with active TED (CAS ≥ 3/7) attending a tertiary center, with a group of consecutive patients with inactive TED (CAS <3). PATIENTS: Thermal images were acquired from 30 TED patients, 17 with active disease and 13 with inactive disease. INTERVENTIONS: Patients underwent standard ophthalmological clinical assessments and thermal imaging. MAIN OUTCOME MEASURES: Five novel thermal eye parameters (TEP) were developed to quantify the thermal characteristics of the eyes in terms of the highest level of inflammation (TEP1), overall level of inflammation (TEP2), right-left asymmetry in the level of inflammation (TEP3), maximum temperature variability across the eyes (TEP4), and right-left asymmetry in the temperature variability (TEP5). RESULTS: All five TEP were increased in active TED. TEP1 gave the largest accuracy (77%) at separating the two groups, with 65% sensitivity and 92% specificity. A statistical model combining all five parameters increased the overall accuracy, compared to using only one parameter, to 93% (94% sensitivity and 92% specificity). All five of the parameters were also found to be increased in patients with chemosis compared to those without. CONCLUSIONS: The potential diagnostic value of this novel thermal imaging analysis technique has been demonstrated. Further investigation on a larger group of patients is necessary to confirm these results.

The effect of B cell depletion therapy on anti-TSH receptor antibodies and clinical outcome in glucocorticoid-refractory Graves' orbitopathy.

OBJECTIVE: This case series documents the response of nine individuals with glucocorticoid-refractory Graves' orbitopathy (GO) to B cell depletion therapy with rituximab (RTX). CONTEXT: Graves' disease (GD) is one of the commonest autoimmune conditions and is frequently associated with inflammatory changes around the eyes (GO). GO frequently results in significant functional visual impairment, and in the most severe cases, it can result in permanent loss of sight. RTX is a therapeutic monoclonal antibody, which targets cell-surface CD-20, resulting in depletion of circulating B lymphocytes. It has been found to be useful for the treatment of a number of autoimmune conditions including, in preliminary studies, GO. DESIGN AND PATIENTS: We have treated nine individuals (1 male, 8 female, age range 37-87 years) with glucocorticoid-resistant GO with RTX since 2008. RTX was administered in divided doses at fortnightly intervals, following 500 mg IV methylprednisolone pretreatment. MEASUREMENTS: Each patient underwent thorough assessment before and after RTX therapy, including thyroid function tests, B cell counts, thyroid autoantibody levels and detailed clinical assessment according to EUGOGO standard protocols. All patients have now been followed up for 16 months or more. RESULTS: There was a significant reduction in thyrotropin receptor binding inhibitory immunoglobulin (TBII) levels in all patients following RTX treatment and a reduction in the clinical activity score (CAS) was seen in all cases. We also report striking improvement in pretibial thyroid dermopathy in one patient following RTX. CONCLUSIONS: This case series adds to the growing literature demonstrating that RTX, administered in our patients with concomitant methylprednisolone, is safe and clinically effective in the treatment of active, moderate to severe and sight-threatening GO. Randomized controlled trials are now needed to confirm the efficacy of RTX for GO.

Delayed Optochiasmal Arachnoiditis following Intervention for a Subarachnoid Haemorrhage.

Visual morbidity following a subarachnoid haemorrhage is common among survivors and it is usually the result of vascular ischaemia at the time of the initial insult. In this report, we present an unusual case of delayed, progressive visual loss following intervention for a ruptured anterior communicating artery aneurysm. We discuss the possible etiological factors and highlight potential diagnostic pitfalls.

Parameters predicting outcomes of strabismus surgery in the management of Graves' ophthalmopathy.

BACKGROUND: Ocular dysmotility is a common feature of Graves' ophthalmopathy and frequently requires strabismus surgery. We reviewed the short-term results of strabismus surgery for Graves' ophthalmopathy to determine pre- and perioperative parameters predictive of postoperative outcome. METHODS: A retrospective review of Graves' ophthalmopathy patients who underwent strabismus surgery. Outcomes were correlated with preoperative and operative characteristics. The main outcome measure was field of binocular single vision score. Residual postoperative strabismus was considered a secondary outcome. Preoperative characteristics examined included age and laterality at onset, sex, disease activity, smoking status, and treatment for Graves' ophthalmopathy. Good outcome was defined as field of binocular single vision >50% and heterophoria in the primary position. Moderate outcome was defined as a field of binocular single vision 1% to 50% with heterotropia but with correctable diplopia in the primary position using prisms or head tilt. Poor outcome was defined as no measurable field of binocular single vision and intractable diplopia. RESULTS: Fifty patients were identified: 28 women, 22 men; mean age, 54 years (SD +/- 12.8). Thirty-seven (74%) had good and 13 (26%) had moderate or poor outcomes. Preoperative characteristics that were associated with good outcomes were symmetry of orbitopathy at Graves' ophthalmopathy onset (chi(2) = 7.5, p = 0.001) and earlier timing of surgery (t = -2.9, p = 0.003). CONCLUSION: Relative symmetry of orbitopathy at onset and a shorter time interval between onset of orbitopathy and surgery, while allowing for disease stability, are predictive of a good outcome following strabismus surgery for Graves' ophthalmopathy.

Clinical features of dysthyroid optic neuropathy: a European Group on Graves' Orbitopathy (EUGOGO) survey.

BACKGROUND: This study was performed to determine clinical features of dysthyroid optic neuropathy (DON) across Europe. METHODS: Forty seven patients with DON presented to seven European centres during one year. Local protocols for thyroid status, ophthalmic examination and further investigation were used. Each eye was classified as having definite, equivocal, or no DON. RESULTS: Graves' hyperthyroidism occurred in the majority; 20% had received radioiodine. Of 94 eyes, 55 had definite and 17 equivocal DON. Median Clinical Activity Score was 4/7 but 25% scored 3 or less, indicating severe inflammation was not essential. Best corrected visual acuity was 6/9 (Snellen) or worse in 75% of DON eyes. Colour vision was reduced in 33 eyes, of which all but one had DON. Half of the DON eyes had normal optic disc appearance. In DON eyes proptosis was > 21 mm (significant) in 66% and visual fields abnormal in 71%. Orbital imaging showed apical muscle crowding in 88% of DON patients. Optic nerve stretch and fat prolapse were infrequently reported. CONCLUSION: Patients with DON may not have severe proptosis and orbital inflammation. Optic disc swelling, impaired colour vision and radiological evidence of apical optic nerve compression are the most useful clinical features in this series.

Imaging of metastatic orbital leiomyosarcoma.

A 74-year-old man with a previous history of lower leg soft tissues leiomyosarcoma and multiple metastasis presented with a progressive painless proptosis of the left eye. Orbital ultrasound, CT, and MRI revealed a large mass in the left medial orbit. The mass was surgically removed and pathologic examination confirmed the diagnosis of a metastatic orbital leiomyosarcoma. The imaging characteristics of this rare tumor are comprehensively detailed, using complementary ultrasound, CT, and MRI, the combination of which allowed planning of total excision of the lesion.

Clinical outcome of endonasal KTP laser assisted dacryocystorhinostomy.

BACKGROUND: To evaluate the clinical outcome of primary endonasal laser assisted dacryocystorhinostomy (ENL-DCR) using the potassium-titanyl-phosphate laser. METHODS: We retrospectively reviewed all primary ENL-DCRs performed within a period of twelve months by the same combined Ophthalmology and Otorhinolaringology team in Freeman Hospital, Newcastle upon Tyne, UK. The main outcome measure for success was resolution or significant improvement of epiphora. Details of surgery, intraoperative and postoperative complications, as well as pathology associated with failure were also studied. Patients were followed up for at least 12 months. RESULTS: A total of 41 consecutive ENL-DCRs on 29 patients (22 females, 7 males, mean age 75 years) were analysed. All patients had bicanalicular silicone intubation for at least 4 months. The success rate at 12 months postoperatively was 78.1%. Pathology associated with failure included: intranasal pathology (12.2%), mucocele (7.3%), and systemic sarcoidosis (2.4%). No significant intra-operative complications were recorded. CONCLUSION: The ENL-DCR with potassium-titanyl-phosphate laser can be considered as a safe and efficient primary procedure for the treatment of nasolacrimal duct obstruction.