A retrospective study of pediatric thyroid eye disease: the Asian experience.

AIM: To study the clinical presentation, disease characteristics, and management approach for children with thyroid eye disease (TED) over a 10 year period in a multidisciplinary Paediatric Thyroid Eye Disease Clinic at a tertiary care referral center. METHODS: Retrospective case series of patients with TED at Kandang Kerbau Women's and Children's Hospital (KKWCH) Singapore between August 2006 to June 2015. The diagnosis of TED was clinical based on the Bartley criteria. Ophthalmic examination findings, systemic thyroid function and ophthalmological intervention were recorded. RESULTS: Nineteen subjects with pediatric TED were studied. The median age at diagnosis was 12.5 years (range 6-17). The onset of TED was at the same time as their thyroid disease in half of these patients (52.6%) of which all were hyperthyroid except one. The most common signs at TED diagnosis were proptosis (84.2%), lid retraction (63.2%), acquired epiblepharon (63.2%). All patients were inactive and none had evidence of compressive optic neuropathy. TED remained stable in all patients except for one who developed worsening proptosis with exposure keratopathy. No patients were prescribed steroids (oral or intravenous) or had orbital decompression surgery. The most debilitating morbidity was acquired epiblepharon of which out of 12 patients, one had everting sutures and three were offered surgical correction. CONCLUSIONS: Paediatric TED subjects exhibit milder clinical manifestations compared to adults. Acquired epiblepharon causes most significant visual morbidity by compromising the corneal surface. Being cognizant of the subtleties of pediatric TED will permit the discerning clinician to effectively manage such cases accordingly.

Perioperative Prophylactic Antibiotics in 1,250 Orbital Surgeries.

PURPOSE: Intravenous antibiotic prophylaxis is used for many clean-contaminated surgeries or clean surgeries with an implant, but its value for clean orbital surgery has not been determined. This study investigated infection risks and adverse effects related to antibiotics in patients undergoing orbital surgery. METHODS: A prospective, nonrandomized comparative case series of all patients undergoing orbital surgery with participating surgeons between October 1, 2013, and March 1, 2015. Types of surgery, antibiotic regimens, corticosteroid use, antibiotic side effects, and surgical site infections (SSIs) were entered into an electronic database and subsequently analyzed. Cases in which patients received postoperative oral antibiotics were analyzed separately. RESULTS: Of 1,250 consecutive orbital surgeries, 1,225 met inclusion criteria. A total of 1208 patients were included in the primary analysis: 603 received no antibiotic prophylaxis (group A), and 605 received a single dose of intravenous antibiotic (group B). Five patients (0.42%) developed an SSI, 3 in group A and 2 in group B. The difference in SSI rates was not statistically significant between the 2 groups (p = 0.66). Antibiotic prophylaxis, alloplastic implants, paranasal sinus entry, and corticosteroid use were not associated with differences in SSI rates. All SSIs resolved on a single course of oral antibiotics; an implant was removed in 1 case. There were no complications associated with a single dose of intravenous prophylaxis. However, 12% of 17 patients (group C) who received 1 week of oral postoperative prophylactic antibiotics developed antibiotic-related complications (diarrhea, renal injury), yielding a number needed to harm of 8.5. CONCLUSIONS: In this large series, antibiotic prophylaxis does not appear to have reduced the already low incidence of SSI following orbital surgery. Given the detriments of systemic antibiotics, the rarity of infections related to orbital surgery, and the efficacy of treating such infections should they occur, patients undergoing orbital surgery should be educated to the early symptoms of postoperative infection and followed closely, but do not routinely require perioperative antibiotics.

Methotrexate as an Adjuvant in Severe Thyroid Eye Disease: Does It Really Work as a Steroid-Sparing Agent?

PURPOSE: To compare the efficacy and safety of adjunctive oral methotrexate with intravenous pulsed methylprednisolone against methylprednisolone alone in the treatment of severe thyroid eye disease. METHODS: Retrospective review of clinical data of patients with severe sight-threatening thyroid eye disease with compressive optic neuropathy treated with methylprednisolone with and without methotrexate. Eye disease outcome measures (e.g., VISA inflammatory score and vision) at 0, 3, 6, 12, and 18 months were recorded. RESULTS: There were 72 subjects including 33 who had methylprednisolone alone and 39 with methylprednisolone with methotrexate. There were no statistical differences in demographics and baseline measures of disease activity or vision between the 2 treatment groups. No significant statistical differences in the cumulative dosage of methylprednisolone or occurrence of restrictive myopathy, raised intraocular pressure, proptosis, and exposure keratopathy between the groups at 0, 3, 6, 12, and 18 months were found. However, subjects who received methylprednisolone with methotrexate had better visual acuity of more than 2 lines on Snellen chart (p = 0.026) and VISA inflammatory score (p = 0.034) at 3 months, but no differences at 6, 12, and 18 months. Three patients who received methylprednisolone with methotrexate had transient worsening of liver function. No patient developed severe adverse reaction. CONCLUSIONS: The results demonstrated improved vision and disease activity at 3 months in the combination treatment group. This may suggest that the addition of methotrexate to methylprednisolone is beneficial for accelerating suppression of disease activity and hastens visual recovery. Addition of methotrexate to methylprednisolone did not reduce the requirement for steroids.

Clinical Features and Treatment Outcomes of Orbital Inflammatory Disease in Singapore: A 10-Year Clinicopathologic Review.

PURPOSE: 1) To assess the clinical profile and treatment outcomes of orbital inflammatory disease in the local population, and 2) classify patients using current histopathological criteria. METHODS: Ten-year retrospective clinicopathologic review of patients diagnosed with orbital inflammatory disease who underwent tissue biopsy from January 2001 to December 2011 at a tertiary referral centre in Singapore. Data collection included patient demographics, clinical presentation, investigations, systemic disease, histopathology review, clinical classification, medical and surgical management, response to treatment and recurrence rates. RESULTS: The study comprised 70 patients. Thirty-seven (52.9%) had nonspecific inflammation distributed as follows: lacrimal (n = 23), diffuse (n = 5), anterior (n = 5), myositic (n = 4). Thirty-three (47.1%) had specific inflammation of the following subtypes: idiopathic sclerosing inflammation (n = 9), granulomatous disorders (n = 8), transitional lesions (n = 5), vasculitis (n = 4), and others (n = 7). A total of 76.8% of patients received oral prednisolone, with a median duration of three months. Response to treatment was good in 71.9% of patients. Recurrence occurred in 22 (32.8%) patients at a mean interval of 20 months after completion of treatment, and was higher in myositic and vasculitic subtypes. There was no significant correlation between duration of treatment and recurrence. CONCLUSIONS: This study has re-emphasized the importance and utility of orbital biopsy and histopathologic typing for optimal management of orbital inflammatory disease. It has also improved the knowledge of the rate and response to treatment of its various subtypes.

Axial Globe Position Measurement: A Prospective Multicenter Study by the International Thyroid Eye Disease Society.

PURPOSE: Identify a reproducible measure of axial globe position (AGP) for multicenter studies on patients with thyroid eye disease (TED). METHODS: This is a prospective, international, multicenter, observational study in which 3 types of AGP evaluation were examined: radiologic, clinical, and photographic. In this study, CT was the modality to which all other methods were compared. CT AGP was measured from an orthogonal line between the anterior lateral orbital rims to the cornea. All CT measurements were made at a single institution by 3 individual clinicians. Clinical evaluation was performed with exophthalmometry. Three clinicians from each clinical site assessed AGP with 3 different exophthalmometers and horizontal palpebral width using a ruler. Each physician made 3 separate measurements with each type of exophthalmometer not in succession. All photographic measurements were made at a single institution. AGP was measured from lateral photographs in which a standard marker was placed at the anterior lateral orbital rim. Horizontal and vertical palpebral fissure were measured from frontal photographs. Three trained readers measured 3 separate times not in succession. Exophthalmometry and photography method validity was assessed by agreement with CT (mean differences calculation, intraclass correlation coefficients [ICCs], Bland-Altman figures). Correlation between palpebral fissure and CT AGP was assessed with Pearson correlation. Intraclinician and interclinician reliability was evaluated using ICCs. RESULTS: Sixty-eight patients from 7 centers participated. CT mean AGP was 21.37 mm (15.96-28.90 mm) right and 21.22 mm (15.87-28.70 mm) left (ICC 0.996 and 0.995). Exophthalmometry AGP fell between 18 mm and 25 mm. Intraclinician agreement across exophthalmometers was ideal (ICC 0.948-0.983). Agreement between clinicians was greater than 0.85 for all upright exophthalmometry measurements. Photographic mean AGP was 20.47 mm (10.92-30.88 mm) right and 20.30 mm (8.61-28.72 mm) left. Intrareader and interreader agreement was ideal (ICC 0.991-0.989). All exophthalmometers' mean differences from CT ranged between -0.06 mm (±1.36 mm) and 0.54 mm (±1.61 mm); 95% confidence interval fell within 1 mm. Magnitude of AGP did not affect exophthalmometry validity. Oculus best estimated CT AGP but differences from other exophthalmometers were not clinically meaningful in upright measurements. Photographic AGP (right ICC = 0.575, left ICC = 0.355) and palpebral fissure do not agree with CT. CONCLUSIONS: Upright clinical exophthalmometry accurately estimates CT AGP in TED. AGP measurement was reliably reproduced by the same clinician and between clinicians at multiple institutions using the protocol in this study. These findings allow reliable measurement of AGP that will be of considerable value in future outcome studies.

A Novel Bioresorbable Implant for Repair of Orbital Floor Fractures.

PURPOSE: To describe clinical, radiologic, and safety outcomes of orbital floor fracture repair using a novel bioresorbable polycaprolactone (PCL) mesh implant (Osteomesh™, Osteopore International, Singapore). METHODS: This is a prospective interventional case series of orbital floor fractures repaired using a novel PCL mesh implant. Clinical evaluation was conducted at presentation and postoperatively at 1, 4, 12, 24 and 48 weeks. Computed tomography (CT) of the orbits was performed 1 year postoperatively. RESULTS: A total of 20 patients were recruited. Mean follow up was 50.4 ± 31.88 weeks. The majority of the patients were male (60%) and of Chinese ethnicity (75%), and the mean age was 39.35 (range 13-69) years. The most common mechanism of injury was assault. The average fracture size was 21.9 mm (range 12-32 mm) in the anteroposterior meridian and 18.65 mm (range 6-27 mm) in the horizontal meridian. Fifty percent of the patients were classified as having a large orbital defect (horizontal width ≥20 mm). The binocular single vision (BSV) score improved from 72.1% preoperatively to 90.8% postoperatively (P < 0.05) for 17 patients who had pre and postoperative charts. BSV improvement did not differ significantly between those with large and small orbital fracture sizes. There were features of neobone formation on CT scan performed 1.5 years after implantation. CONCLUSION: This bioresorbable implant is a promising material for the repair of both small and large orbital floor fractures, giving good functional and aesthetic outcomes.

A combined transcriptomics and proteomics approach reveals S100A4 as a potential biomarker for Graves' orbitopathy.

Background: There are no reliable biomarkers to identify Graves' disease patients who will develop severe Graves' orbitopathy (GO). We hypothesize that integrating various omics platforms can enhance our understanding of disease mechanisms and uncover potential biomarkers. This study aimed to (1) elucidate the differential gene expression profile of orbital fibroblasts in GO during early adipogenesis to better understand disease mechanisms and (2) compare tear protein profiles from our earlier study and the transcriptome profiles of orbital fibroblasts (OFs) to identify possible biomarkers of the disease. Methods: OFs were grown from orbital adipose tissue obtained from nine GO patients (three for discovery and six for validation experiments). Total RNA was extracted from OFs on day 0 as the baseline for each sample and from differentiated OFs on days 4 and 8. Protein-protein interaction (PPI) analysis and functional enrichment analysis were also carried out. The differentially expressed genes (DEGs) from the RNA sequencing experiments were then compared to the full tear proteome profile from the author's previous study, which examined the tear protein changes of GO patients based on fold change > 1.6 or < -1.6. FDR < 0.05 was applied within all datasets. Further validation of S100 calcium-binding protein A4 (S100A4) downregulation in GO was performed via quantitative real-time PCR (qPCR). Results: The whole transcriptomic analysis revealed 9 upregulated genes and 15 downregulated genes in common between the discovery and validation experiments. From the PPI network analysis, an interaction network containing six identified DEGs (ALDH2, MAP2K6, MT2A, SOCS3, S100A4, and THBD) was observed. The functional enrichment network analysis identified a set of genes related to oxysterol production. S100A4 was found to be consistently downregulated in both our transcriptome studies and the full-tear proteome profile from the author's previous study. Conclusion: Our study identified several DEGs and potential gene pathways in GO patients, which concurred with the results of other studies. Tear S100A4 may serve as a biomarker for the propensity to develop thyroid eye disease (TED) in patients with autoimmune thyroid disease (AITD) before clinical manifestation and should be confirmed in future studies.

Prospective audit of ptosis surgery at the Singapore National Eye Centre: two-year results.

PURPOSE: To evaluate the demographics, presentation, and surgical outcomes of patients undergoing ptosis surgery in an Asian population in a prospective manner. METHODS: A prospective ptosis audit was conducted over a 2-year period from January 2010 to December 2011 in a tertiary eye hospital in Singapore. All patients undergoing ptosis surgery by, or under the supervision of, an oculoplastic-trained consultant in the institution were included. Institutional Review Board approval was obtained for the study. RESULTS: This study comprises 302 patients, of which 236 were acquired and 66 were congenital ptosis cases. Levator repair (77.2%) was the most commonly performed procedure, followed by levator resection (13.9%) and brow suspension (8.9%). Forty-seven (10.1%) eyes had readjustment within 2 weeks, the reasons for readjustment being eyelid height undercorrection (n = 35), eyelid height overcorrection (n = 9), and unsatisfactory eyelid contour (n = 4). Postoperatively, 93.8% of patients showed an increase in marginal reflex distance-1 (MRD1), 91.3% achieved symmetry or <1 mm of asymmetry in MRD1, 98.5% had good eyelid contour, and 74.3% had symmetric eyelid crease. On a scale of 1 to 10, 83.1% of patients gave a subjective grade of 7 or better. CONCLUSIONS: This study is the first prospective ptosis surgery audit in an Asian population and takes a leading step in assessing both subjective and objective surgical outcomes in a prospective manner. With the continuation of this audit in years to come, it will allow us to generate clinical outcomes in a robust manner and allow for more reliable benchmarking with major centers elsewhere.

Combined radiological intervention and surgical excision of a periorbital arteriovenous fistula.

OBJECTIVE: To describe a case of periorbital arteriovenous fistula (AVF) treated with a combined approach of endovascular intervention and surgical excision. CASE REPORT: A 21-year-old lady presented with a vascular lump followed blunt trauma above the left medial brow area. Computed Tomography Angiogram (CTA) and Angiography of the internal and external carotid arteries showed presence of an AVF with main feeder vessel from a hypoplastic left ophthalmic artery. Pre-operative radiological embolization was performed but the patient defaulted planned surgery. She returned 4 months later complaining of pain and increased swelling of the lesion. Repeat CTA demonstrated residual shunt located below the supra-orbital rim medially supplied by the left supratrochlear artery. Excision was later performed without repeat embolization and was uncomplicated. Histological reported chronic inflammation with granulomatous foreign body giant cell reaction confirming pre-operative diagnosis of tissue reaction to glue cast. CONCLUSION: Treatments of Orbital AVFs are challenging and require multidisciplinary team management involving interventional radiologists and orbital surgeons. A foreign body reaction can develop followed embolization with tissue glue alone. Prompt surgical excision is therefore recommended to minimize post operation morbidity.

A survey of the histopathology of lacrimal gland lesions in a tertiary referral centre.

PURPOSE: To describe the histopathological distribution of biopsied lacrimal gland lesions in a tertiary referral centre in Singapore. METHODS: This was a retrospective chart review. Clinical records of patients who underwent lacrimal gland biopsy at a tertiary referral centre in Singapore between 2000 to 2010, were reviewed. Data collated included patient demographics, clinical presentation, association with systemic disease and histopathological diagnosis. RESULTS: Sixty-nine patients were studied. Median age of presentation was 50 years. Forty patients (58%) were female and the majority (84%, n = 29) were Chinese. The mean follow-up duration was 35.0 ± 34.5 months. 30.4% (n = 21) of the patients had bilateral disease. Chronic dacryoadenitis (46%, n = 32) was the most common histopathological diagnosis, followed by lymphoproliferative disorders (38%, n = 26) and pleomorphic adenoma (10%, n = 7). The diagnoses in four other patients included adenoid cystic carcinoma, lacrimal gland hypertrophy, lacrimal duct cyst and orbital vascular malformation. CONCLUSION: Chronic dacryoadenitis and lymphoproliferative disorders are the two commonest causes of lacrimal gland lesions in our series. Although many cases remain non-specific, about 60% have a specific inflammation that may be associated with a systemic disease. As one third of our patients with lymphoproliferative disease of the lacrimal gland had an associated systemic lymphoma, patients with such lesions should be referred for investigation of possible systemic lymphoma. The results of our study can aid in providing a more targeted approach to patient management.

An unusual causative agent for an orbital abscess: Granulicatella Adiacens.

We present a patient who developed an orbital abscess secondary to a retained organic (wooden) foreign body after a fall. Clinically, he had a right sub brow fistula exuding purulent discharge, four millimetres of proptosis, limitation of ocular motility in all directions of gaze, but no signs of optic neuropathy. Preoperative computed tomography and magnetic resonance imaging of the orbits was performed to localise the abscess and to facilitate surgical planning. He underwent exploration, drainage of the abscess and removal of the wooden foreign body with good postoperative recovery. Cultures isolated Ganulicatella Adiacens, a nutritionally variant streptococcus. This is an unusual causative organism and to our knowledge, this is the first reported case of a posttraumatic orbital abscess associated with Granulicatella Adiacens. Clinical suspicion, isolation of the organism and appropriate microbial treatment requires a multidisciplinary approach, with input from the ophthalmologist, microbiologist and infectious disease team. This will ensure a good outcome in patient management.

Neuroendocrine tumors of the orbit--clinicopathological findings in 3 more cases of this rare entity and review of the literature.

INTRODUCTION: Neuroendocrine orbital tumors are rare occurrences. They are poorly characterized histologically and a spectrum of different cell types exists. This short case series studies the various tumor morphologies as well as the patients' clinical profiles. METHODS AND MATERIALS: Patients treated and followed up at the Singapore National Eye Centre over a period of 8 years from 1(st) January 2002 to 31(st) December 2009 were identified from the orbital tumor board results. The case notes of patients with the diagnosis of neuroendocrine tumors were analysed, and a review of the literature performed. RESULTS: Three patients are described in this series. The history, clinical examination findings, imaging findings as well as tumor histology were described. The mean age was 63 years, and 2 patients were male. All presented with proptosis. Only one patient had systemic symptoms on presentation. All patients had surgical excision of the tumor and two had adjuvant radiotherapy of the orbit. Median follow-up period was 3.5 years. DISCUSSION: Patients with a biopsy-proven diagnosis of orbital neuroendocrine tumors should be monitored even when systemic examination fails to identify peripheral disease. Such examination should always include a full endoscopic gastrointestinal review.

De Novo Extra-Thyroidal Manifestations of Graves' Disease presenting 16 Years after Total Thyroidectomy for Thyroid Cancer.

We present a 61-year-old Chinese female who had a history of angioinvasive follicular thyroid cancer (FTC) treated with total thyroidectomy 16 years ago, without radioactive iodine (RAI) treatment who now presents with de novo pretibial myxedema (PTM) followed by active severe Graves' ophthalmopathy (GO) requiring pulse steroids and radiotherapy.

The incidence of ptosis following extracapsular and phacoemulsification surgery: comparison of two prospective studies and review of the literature.

We prospectively compared 120 patients who underwent either phacoemulsification or extracapsular cataract (ECCE) surgery to establish the incidence of postoperative ptosis between the two techniques. Of the 120 patients, 60 underwent ECCE (unpublished data 1989) and 60 had phacoemulsification. Data was collected prospectively on upper and lower margin reflex distance, upper lid skin crease and levator function, preoperatively and 6 weeks postoperatively. Photographs were taken pre and postoperatively and examined by a blinded observer. At 6 weeks, ptosis was present in 18% of ECCE patients compared with 0% in the phacoemulsification group. By changing from ECCE to phacoemulsification the incidence of postoperative ptosis has reduced. The possibility to induce postoperative ptosis remains, potential mechanisms are discussed.

Visual outcomes in patients with paranasal mucoceles.

PURPOSE: To describe the ophthalmic complications and visual outcome of patients with paranasal mucoceles. METHODS: This is a retrospective case series of patients with a diagnosis of paranasal mucocele. Their medical records were examined with particular emphasis on the location of the paranasal mucoceles, presence of inflammation (mucocele vs. pyelocele), presence of optic neuropathy, and final visual outcome. RESULTS: Ten patients with an average age of 57.6 years (range, 30-71 years) were studied. Seven mucoceles were in the frontal or fronto-ethmoidal sinuses, one was in the sphenoidal sinus, one was within an Onodi cell, and one was in the maxillary sinus. Four patients developed optic neuropathy, of which 2 cases were related to fronto-ethmoidal mucoceles. Four patients had pyeloceles. Two of these 4 patients had resultant loss of light perception: one case was associated with a fronto-ethmoid sinus and the other with an Onodi cell). CONCLUSIONS: Our series highlights the greater risk of optic neuropathy and poor visual outcome with sphenoid sinus and Onodi cell mucoceles because of their proximity to the optic nerve. However, fronto-ethmoidal mucoceles are not benign and may compromise vision, especially if a posterior ethmoid component is present, or if treatment is delayed and secondary infection has ensued to form a pyelocele. Management of paranasal mucoceles should be prompt, particularly when signs of inflammation are present.

Orbital cellulitis in children-medical treatment versus surgical management.

INTRODUCTION: Ophthalmologists differ in their threshold for surgical management in paediatric patients with orbital cellulitis. We studied the management choices and outcome of children admitted with this disorder. MATERIAL AND METHODS: A retrospective review was performed on patients with orbital cellulitis admitted between January 2001 and December 2004 to a tertiary paediatric referral centre in Singapore. The patients were studied for age, associated systemic disease, medical treatment, drainage procedure undertaken, organism isolated and outcome. Statistical methods were applied for comparing medical treatment with surgical treatment with respect to recovery time, recurrence, and time between the presentation of patient and initiation of treatment. RESULTS: Twenty patients were studied. Average age was 5.5 years. 5/20 (25%) had a preceding history of upper respiratory tract infection. From CT findings, we came to know that 3/20 (15%) were due to isolated ethmoiditis, 5/20 (25%) had obstruction of the osteomeatal complex of the paranasal sinuses, 2/10 (10%) had intracranial abscesses due to frontal sinusitis. 4/20 (20%) had all 4 ipsilateral paranasal sinuses infected. 2/20 (10%) had preseptal cellulitis with posterior extension into the orbit. 2/20 (10%) had orbital cellulitis related to dacryoadenitis and 2/20 (10%) had pansinusitis with orbital soft tissue stranding. 13/20 (65%) had orbital and /or endoscopic drainage. The remainder of the patients had good immediate response to sole medical treatment and did not require surgery. The most commonly isolated organism was Staphylococcus aureus 5/20 (25%). All patients recovered within a mean of 9.6 days with no complications or functional deficit. CONCLUSIONS: Paediatric orbital cellulitis can be treated conservatively or with surgical drainage. Indications for surgery include pansinusitis, large abscesses with significant mass effect, concurrent intracranial involvement, poor response to initial medical treatment and the presence of an orbital abscess and gas. Sole medical treatment worked well in children with no orbital abscess, small or medial abscesses as they tend to have a single organism infection. This is also of particular significance in young children below the age of one where endoscopic surgery can be technically difficult. Intracranial involvement occurred in association with frontal sinusitis and affected patients had the longest duration of hospitalization.

The tear cytokine profile in patients with active Graves' orbitopathy.

PURPOSE: The primary aim of this study is to isolate cytokines specific for active Graves' orbitopathy (GO) in the tears of affected patients. The secondary aim is to identify other cytokines of interest and to look at the profile of their levels over time. METHODS: This is a prospective pilot study conducted at the Singapore National Eye Centre. A total of 10 patients with active GO and 10 patients from each of 3 control groups were recruited. The 3 control groups were the following: age-matched normal female patients, patients with GO who were clinically inactive and patients with bilateral viral conjunctivitis. Tears from patients from the control groups were collected on a single visit. For patients with active GO, tears were collected on presentation, at 6 months, 12 months and 18 months. RESULTS: Of all the cytokines examined, only IL-7 yielded a difference when the concentration in patients with active GO was compared with concentrations in all the control groups. This difference was most significant at the 18-month follow-up visit. CONCLUSIONS: Low concentrations of IL-7 in tears exhibit specificity for active GO in patients nearly 2 years from the clinical onset of activity. Although using IL-7 in tears as a biomarker for disease activity may be limited due to its late manifestation, targeting immune restitution using IL-7 may have disease modifying effects.

Development and Validation of the Singapore Thyroid Eye Disease Quality of Life Questionnaire.

PURPOSE: Current instruments to assess thyroid eye disease (TED) quality of life (QoL) were not developed using modern psychometric theory and may not be applicable to Asian populations. Therefore, we developed a psychometrically robust questionnaire, the Singapore Thyroid Eye Disease Quality of Life questionnaire (STED-QoL), for assessing QoL in Asian patients. METHODS: This cross-sectional study was conducted at the Singapore National Eye Centre between 2012 and 2015. In Phase 1, content for the questionnaire was developed using qualitative methods. A total of 20 patients participated in three different focus groups. Thematic analysis was conducted to identify relevant themes from which 12 items, rated on a 5-point Likert-type scale, were generated. In Phase 2, the pilot instrument was administered to 59 TED patients and psychometric assessment of the STED-QoL was conducted using Rasch analysis. RESULTS: After collapsing categories from five to four and deleting two misfitting items, we generated a 10-item STED-QoL befitting the Rasch model. The scale showed good criterion validity, with scores decreasing as severity of TED worsened: mild (1.78 logits), moderate (0.27 logits), and severe (0.92 logits). A 'Psychosocial' subscale also had adequate psychometric properties and psychosocial scores were significantly worse in those who underwent surgery for TED compared to those who had not (0.41 vs. 1.82 logits, P = 0.021). CONCLUSIONS: The STED-QoL is a robust 10-item questionnaire specifically developed to measure the impact of TED on QoL and psychosocial well-being in an Asian population. TRANSLATIONAL RELEVANCE: QoL assessment is important for holistic management of TED patients.

Tear Proteins Calcium binding protein A4 (S100A4) and Prolactin Induced Protein (PIP) are Potential Biomarkers for Thyroid Eye Disease.

There are no reliable biomarkers to predict thyroid eye disease (TED) in patients with autoimmune thyroid disease (AITD) currently. Several evidences support the involvement of the lacrimal gland in TED. The aim of our study was to quantitatively correlate the changes in tear protein profile with increasing severity of TED. Tear samples were collected from four groups of patients; AITD without TED (AITD), AITD with mild TED (mild TED), AITD with severe TED (severe TED) and normal controls. A total of 72 patients were recruited for the study. In discovery phase, isobaric tags for relative and absolute quantification (iTRAQ) 4-plex was used for quantitative proteomics analysis. For verification of results from discovery phase, sequential window acquisition of all theoretical fragment ion spectra (SWATH) was used to analyze an independent cohort from normal controls, AITD, mild TED and severe TED. Two proteins, S100A4 and PIP showed consistent dysregulation trends in the discovery and validation phase experiments. Our study demonstrated the differences in tear proteome across the spectrum of different severity and activity of TED in patients with AITD. Two tear proteins, S100A4 and PIP may serve as potential biomarkers to predict progression to severe TED in patients with AITD.

Detection of thyroid peroxidase mRNA and protein in orbital tissue.

OBJECTIVE: We have previously reported that the absence of thyroid peroxidase antibodies (TPOAb) in Graves' disease (GD) was associated with an increased risk of Graves' ophthalmopathy (GO). This observation raised the possibility that TPOAb could act as a protective factor. However, the presence of thyroid peroxidase (TPO) in the orbit has not been previously reported. The aim of this study was to confirm or exclude the presence of orbital TPO. METHODS AND DESIGN: Relative TPO mRNA expression from GO (n=6) and normal (n=5) orbital fat tissue was determined using real-time PCR technique. Orbital fat in the normal group from blepharoplasty represents extraconal (anterior) fat. mRNA expression in fibroblasts grown from these tissues before and after adipocyte differentiation was also documented. Finally, Western blotting was carried out to verify translation of TPO mRNA transcripts. RESULTS AND DISCUSSION: TPO transcripts were detected in the orbital fat tissue obtained from normal and GO subjects using the real-time PCR technique. TPO expression was increased in GO compared to normal (N) tissues. However, TPO expression in cultured fibroblasts was similar in both groups and adipogenesis did not appear to alter TPO expression. Protein was detected by Western blot analysis using the TPO MAB 47 (mAb 47). The predicted 110-kDa band was detected in orbital fat as well as in orbital fibroblasts. Our results suggest the presence of TPO in GO and N orbital tissues. We hypothesise that immune responses directed against orbital TPO might play a role in modulating the clinical expression of GO.