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AIM: To describe volumes of orbital fat (FV) and extraocular muscles (MV) in Graves' orbitopathy (GO) as a function of the duration of GO. PATIENTS: i) Cross-sectional survey among 95 consecutive patients with untreated GO who had been referred to the combined thyroid-eye clinics of our university hospital. ii) Longitudinal survey among 39 of the 95 patients who did not receive any therapeutic intervention and were followed for 1 year. METHODS: A computed tomography (CT)-based and well-validated method for calculating orbital soft tissues. In order to neutralize sex differences, results are expressed as ratios of FV:orbital volume (OV) and MV:OV. RESULTS: i) Patients with GO duration of >1 year had greater FV:OV (0.65 vs 0.55, P=0.004), similar MV:OV (0.22 vs 0.21, not significant (NS)), and more proptosis (22 mm vs 21 mm, P=0.03) as compared to those with shorter duration. ii) As compared to baseline, after 1 year, FV:OV had increased (0.56 vs 0.63, P=0.000), MV:OV had not changed (0.19 vs 0.19, NS), proptosis was higher (20 mm vs 21 mm, P=0.003), and clinical activity scores had become lower (2 vs 1, P=0.02) (median values). CONCLUSION: CT images show that a longer duration of GO is associated with a higher orbital FV. Extraocular MV, however, is not associated with GO duration; rather, it is related to the severity of GO.

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Graves' ophthalmopathy (GO) is characterized by swelling of orbital fat and extraocular muscles, but little attention has been given to differential involvement of fat and muscles. Advancements in imaging allow rather accurate measurements of orbital bony cavity volume (OV), fat volume (FV) and muscle volume (MV), and are the topics of this review. Ratios of FV/OV and MV/OV neutralize gender differences. In adult Caucasian controls, mean values ± SD of FV/OV are 0.56 ± 0.11 and of MV/OV are 0.15 ± 0.02. FV increases substantially and MV decreases slightly with advancing age, requiring age-specific reference ranges. In 95 consecutive untreated Caucasian GO patients, both FV and MV were within normal limits in 25%, increased FV but normal MV was present in 5%, normal FV but increased MV was detected in 61%, and both increased FV and MV was evident in 9%. Increased FV was associated with more proptosis and longer GO duration. Increased MV was associated with older age, more severe GO (more proptosis and diplopia, worse eye muscle ductions), higher TBII and current smoking. At the cellular and molecular level differential involvement of fat and muscles might be related to differences between fibroblast phenotypes and cytokine profiles in each compartment, to different orbital T cell subsets during the course of the disease and to peroxisome proliferator activator receptor-γ polymorphisms and modulation of 11ß-hydroxysteroid dehydrogenase-1. Enlarged muscles are apparently a rather early phenomenon in GO, whereas increases in fat mass occur relatively late. Why a minor subset of GO patients presents with an increase of only fat remains poorly understood.

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PURPOSE: To investigate CT densities of orbital soft tissue volumes in patients with Graves orbitopathy (GO) and to compare these with the densities of controls. METHODS: Observational case series. Of 95 patients with GO and 150 controls, soft tissue volumes, mean densities, and ratios of fat volume to orbital volume and muscle volume to orbital volume were calculated with software. The 95% confidence intervals of the controls were used as reference values. The densities were plotted against age and volume ratios. For statistical analysis SPSS 16.00.2 was used. p values were calculated with the following tests: analysis of variance, Pearson correlation, Kruskal-Wallis, Mann-Whitney, and linear regression. RESULTS: The main outcome measurements were differences in orbital soft tissue densities. In GO patients the mean orbital fat density was significantly higher than in controls (p ≤ 0.001) and independent of age (p = 0.23). The mean extraocular muscle density of GO patients was within the range of controls and did not decrease with age (p = 0.16) as it did in controls (p ≤ 0.001). Mean fat density increased with decreasing fat volume (p = 0.001). Mean extraocular muscle density increased slightly with increasing muscle volume (p = 0.09). Muscle density correlated with fat density in both controls and GO patients. CONCLUSIONS: Orbital fat density in GO patients is significantly higher than in controls and negatively correlated to fat volume but positively correlated to muscle volume and muscle density.

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BACKGROUND: Smoking adversely affects the course and severity of Graves' orbitopathy (GO). Cigarette smoke enhances adipogenesis in cultured human orbital fibroblasts. The present study tested our hypothesis that smoking is associated with increased orbital fat in GO patients. METHODS: This was an observational case series study. In 95 consecutive patients with untreated GO, the ratios of fat volume/orbital volume (FV/OV) and muscle volume/OV (MV/OV) were calculated with validated software. The most affected orbit of each patient was chosen for analysis. Patients were divided into two groups based on smoking behavior. One group was current smokers (Sm+) and the other were those who never smoked or those who had not smoked for at least 1 year (Sm-). Patients were grouped in tertiles of FV/OV and MV/OV and contrast in OVs between the Sm+ and Sm- group. The main characteristics of GO were analyzed using Jonckheere-Terpstra trend analysis and Mann-Whitney U-test. RESULTS: The proportion of current smokers was not different in GO patients when divided in tertiles according to their FV/OV. In contrast, analysis of MV/OV tertiles showed a trend to a higher prevalence of current smokers in patients with larger MVs. Smoking did not influence FV, but the Sm+ group had significantly larger MVs than the Sm- group. CONCLUSION: Smoking is associated with an increase in extraocular MV in untreated patients with GO and not with an increase in FV.

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BACKGROUND: To investigate the natural history and the growth rate of spheno-orbital meningiomas (SOMs). METHODS: Ninety patients with a diagnosis of SOM were included, and patient charts and imaging were evaluated. In a subset of 32 patients, volumetric studies were performed. RESULTS: The median follow-up for the entire group was 4 years (range, 1-15); the mean age was 47.8 (range, 26-93) years; 94% of the patients were female. The most common clinical signs and symptoms were proptosis (93%), visual deterioration (65%), retro-bulbar pain (23%) and diplopia (6%). In 35% of patients in this series, no visual deterioration occurred, and in 30% only mild proptosis was present. The median annual growth rate of the SOMs in the subset of 32 patients was 0.3 cm³/year (range, 0.03-1.8 cm³/year). We assessed a trend for more rapid tumour growth in younger patients and found the initial volume of the tumour (rho = 0.63) and of the soft tissue component (rho = 074) to be significantly related to the growth rate. CONCLUSION: SOMs are slow-growing tumours that cause primarily proptosis and visual deterioration. In a significant number of patients, these tumours cause minimal discomfort and symptomatology. Therefore, in the absence of risk factors, we advocate a "wait and see" policy. For patients with large SOMs or with a large soft tissue component at first visit or with fast growing SOMs (>1cm³/year), a follow-up examination every 6 months is indicated.

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PURPOSE: To describe the prevalence of fat and muscle volume (MV) increase in Graves' orbitopathy (GO) patients, calculated from computed tomography scans, and the associated ophthalmic and endocrine characteristics. DESIGN: Consecutive, observational case series. PARTICIPANTS: Ninety-five consecutive Caucasian GO patients attending the thyroid eye clinic. METHODS: Volumetry using age-specific reference values in untreated GO patients who had been rendered euthyroid. MAIN OUTCOME MEASURES: Subgroups in GO and main characteristics. RESULTS: Four subgroups could be distinguished: Group 1, no fat volume (FV) or MV increase (n = 24); group 2, only FV increase (n = 5); group 3, only MV increase (n = 58); and group 4, both FV and MV increase (n = 8). Patients with an increase of MV were older and had higher thyroid-stimulating hormone-binding inhibitory immunoglobulin TBII, more proptosis, and more impaired ductions than those without MV increase. Patients with an increase of FV differed from those without FV increase only in having more proptosis. The clinical activity score did not differ between the 4 groups. CONCLUSIONS: Of these GO patients, 25% have orbital fat and MVs within an age-specific reference range. An increase of the FV is seen in only 14% of GO patients and characterized by proptosis. Muscle enlargement occurs in 70% of patients and is associated with older age, higher TBII values, more proptosis, and impaired motility.

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AIM: To provide age and gender-specific reference values for orbital fat and muscle volumes (MV) in Caucasian adults. PATIENTS AND METHODS: Computed tomographic scans of 160 orbits from 52 men and 55 women, aged 20-80 years, not affected by orbital disease were evaluated. Orbital bony cavity volume (OV), fat volume (FV) and MV were calculated by a previously validated method using the software program Mimics. Ratios of FV to OV and of MV to OV were determined. RESULTS: OV, FV and MV were all significantly larger in men than in women (p<0.001), but FV/OV and MV/OV were similar in both sexes. OV and MV did not change with age, but FV increased with advancing age in both women (p<0.001) and men (p<0.001). Linear regression analysis with FV/OV and MV/OV ratios as dependent variables and age and gender as independent variables showed a significant correlation between age and FV/OV (r=0.52, p<0.0001) and age and MV/OV (r=-0.26, p=0.001). CONCLUSIONS: Advancing age is associated with an increase of FV/OV and a minor decrease of MV/OV. Gender-specific differences in orbital FV and MV disappear once FV and MV are related to OV, by calculating the ratios FV/OV and MV/OV. Age-specific gender-neutral reference ranges (2.5 and 97.5 percentiles) of FV/OV and MV/OV are presented.

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PURPOSE: To present and discuss the occurrence of a traumatic neuroma subsequent to inferomedial orbital decompression surgery in Graves' orbitopathy. METHODS: Case report. RESULTS: Approximately 1 month after surgery, a patient who underwent bilateral rehabilitative inferomedial orbital decompression developed a mass with clinical and radiologic characteristics compatible with a traumatic neuroma of the left infraorbital nerve. The lesion, which was thought to be the result of unnoticed nerve trauma at the time of surgical dissection of the infraorbital canal, remained stable in shape and other imaging characteristics during the 39-month follow-up period. Symptoms of trigeminal neuralgia could be only partially controlled with medical therapy (oral pregabalin 75 mg 3 times daily). CONCLUSIONS: The second branch of the trigeminal nerve may be damaged in the course of orbital floor removal decompression for Graves' orbitopathy. This may potentially induce the formation of traumatic or amputation neuromas. Such lesions should be included in the potential complications of decompressions when counseling patients about to undergo this type of surgery, as they are difficult to treat and may cause persistent and disabling pain.

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PURPOSE: There is no consensus as how to calculate orbital soft tissue volume based on CT or MRI scans. The authors sought to validate their technique and to assess the intraobserver and interobserver variability of their calculations of bony orbital volume (OV), orbital fat volume (FV), and extraocular muscle volume (MV) on CT scans of humans. METHODS: The authors calculated these volumes with the use of a manual segmentation technique on CT scans with commercially available software. Two observers (one of them masked) calculated the orbital soft tissue volumes in a CT scan of a phantom constructed of dry skull, butter, and chicken muscle. These calculations were compared with previously taken standard volume measurements of these materials. Repetitive calculations on one CT scan by the same observer were compared. Soft tissue volumes taken from 10 orbital CT scans were calculated by two observers and compared. From the data acquired, intraobserver and interobserver variability was calculated. RESULTS: Outcomes of these calculations using this software approximated the volumes of the phantom measured with standardized techniques. Accuracy of the phantom calculations between the two observers varied from +0.7% to -0.7% for FV and between -1.5% and -2.2% for MV. Mean differences between the repeated calculations were smaller than 5%. The intraclass correlation coefficient varied from 0.961 to 0.999. CONCLUSIONS: Calculating orbital soft tissue volume using a manual segmentation technique for CT scans is a reliable and accurate tool.

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