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.

Transcranial orbital decompression for progressive compressive optic neuropathy after 3-wall decompression in severe graves' orbitopathy.

PURPOSE: To determine surgical outcomes after transcranial decompression of the superior orbit in patients with progressive compressive optic neuropathy (CON) secondary to Graves' orbitopathy (GO) who had previously been treated with 3-wall decompression. METHODS: Approval from the West Virginia University Institution Review Board was obtained. A retrospective review of 4 patients with GO who received bilateral transcranial decompression of the orbits for progressive compressive optic neuropathy after bilateral maximal extracranial 3-wall decompression was performed. The patients were treated by the Multidisciplinary Orbit and Skull Base Services at West Virginia University and the University of Michigan. RESULTS: Bilateral transcranial decompression of the orbit for GO was performed on 8 orbits in 4 patients. All 8 orbits had radiographic evidence of compression of the orbital apex, and all patients had been treated with steroids, orbital radiation, and bilateral 3-wall decompression. Preoperative vision ranged from 20/25 to 20/100, which improved to 20/25 or better in all eyes. The visual field mean deviation improved from a mean of -13.05 to -1.67 dB. Hertel measurements improved from a mean of 19.25 to 15.25 mm. Extraocular motility was essentially unchanged. Two patients were noted to have asymptomatic ocular pulsations. There were no other complications, and all patients remained stable during a follow-up period of 5 years (range 2-8 years). CONCLUSIONS: Transcranial decompression is an effective and safe method of salvaging vision when standard treatments fail. This is only the second report of transcranial decompression for refractory compressive optic neuropathy after decompression from a standard approach.

Calculated computed tomography volumes of lacrimal glands and comparison to clinical findings in patients with thyroid eye disease.

PURPOSE: To describe the range of lacrimal gland volumes on CT in Caucasian patients with thyroid eye disease (TED) and to correlate with clinical findings. METHODS: With institutional review board approval, 125 orbital CT scans for TED were reviewed. OsiriX software was used to calculate the volume of the lacrimal gland. Comparison of the volumes was made with previously published results of the normal population. Patient race, gender, smoking status, diplopia, tearing, exophthalmometry, superficial punctate keratitis (SPK), lagophthalmos, restriction in motility, and VISA score were collected. RESULTS: The mean volume of the lacrimal gland in patients with TED was 0.890 cm in right orbits (standard deviation [SD] 0.348), 0.851 cm in left orbits (SD 0.350), with no significant difference between right and left (p = 0.311). The mean volume was 0.811 cm in right male orbits (SD 0.386) and 0.911 cm in right female orbits (SD 0.335), with no significant difference between men and women (p = 0.774). These findings were confirmed in an analysis of left orbits. The volume of right and left orbits correlated well (r = 0.777, p < 0.0001). The lacrimal gland volume in patients with TED was greater compared with the normal population using a 2-sample t test (p < 0.0001). Exophthalmometry (right: r = 0.225, p = 0.0115; left: r = 0.267, p = 0.0026) and subjective tearing (right: r = 0.226, p = 0.0138; left: r = 0.197, p = 0.0322) correlated with lacrimal gland volume. CONCLUSIONS: This study is the first to report the volume of the lacrimal gland calculated on CT scan for patients with TED. The lacrimal gland is larger in patients with TED and correlates with subjective tearing and exophthalmometry.

Calculated CT volumes of lacrimal glands in normal Caucasian orbits.

INTRODUCTION: The objective was to describe the range of normal volumes for the lacrimal gland calculated from CT. METHODS: A retrospective review with institutional review board approval of 293 CT scans of 586 orbits was performed. Patients were included if they were Caucasian and aged 18 years or older. Orbits were excluded if there was a disease or trauma. OsiriX software was used to outline the lacrimal gland in consecutive axial slices and to calculate the volume. Inter-rater agreement was assessed in a subset of 30 randomly selected orbits by observers of different levels of training using the intraclass correlation coefficient (ICC). RESULTS: Two hundred sixty orbits of 187 patients were included. The mean volume of the lacrimal gland was 0.696 cm2 in right orbits (SD = 0.261) and 0.649 cm2 in left orbits (SD = 0.231), with no significant difference between right and left (p= 0.125). The mean volume was 0.680 cm2 in men (SD = 0.241) and 0.662 cm2 in women (SD = 0.260), with no significant difference between men and women (p = 0.564). There was an inverse relationship between gland volume and age (Pearson r= -0.428 right orbits and -0.469 left orbits). Of the 73 bilateral patients, right and left orbits correlated well (Pearson r = 0.712). Agreement was good among the observers (ICC = 0.727). CONCLUSIONS: This is the first study to report the range of normal volume for Caucasian lacrimal glands measured on CT scans. The volume of the lacrimal gland decreases with age, and there is no gender or laterality difference.

S14 protein in breast cancer cells: direct evidence of regulation by SREBP-1c, superinduction with progestin, and effects on cell growth.

Most breast cancers exhibit brisk lipogenesis, and require it for growth. S14 is a lipogenesis-related nuclear protein that is overexpressed in most breast cancers. Sterol response element-binding protein-1c (SREBP-1c) is required for induction of lipogenesis-related genes, including S14 and fatty acid synthase (FAS), in hepatocytes, and correlation of SREBP-1c and FAS expression suggested that SREBP-1c drives lipogenesis in tumors as well. We directly tested the hypothesis that SREBP-1c drives S14 expression and mediates lipogenic effects of progestin in T47D breast cancer cells. Dominant-negative SREBP-1c inhibited induction of S14 and FAS mRNAs by progestin, while active SREBP-1c induced without hormone and superinduced in its presence. Changes in S14 mRNA were reflected in protein levels. A lag time and lack of progestin response elements indicated that S14 and FAS gene activation by progestin is indirect. Knockdown of S14 reduced, whereas overexpression stimulated, T47D cell growth, while nonlipogenic MCF10a mammary epithelial cells were not growth-inhibited. These data directly demonstrate that SREBP-1c drives S14 gene expression in breast cancer cells, and progestin magnifies that effect via an indirect mechanism. This supports the prediction, based on S14 gene amplification and overexpression in breast tumors, that S14 augments breast cancer cell growth and survival.