Orbital Fat Volume Research Articles

Orbital computed tomography imaging characteristics of thyroid-associated ophthalmopathy

This study aims to investigate the distribution characteristics and correlations of orbital soft tissue volume expansion in patients with thyroid-associated ophthalmopathy (TAO) by analyzing orbital computed tomography (CT) data and to determine the most appropriate parameters and corresponding cut-off values for imaging classification. Patients with TAO who met the inclusion and exclusion criteria, along with those with lacrimal duct obstruction requiring orbital CT examination, were included in the study. Raw CT data were imported into Mimics and RadiAnt software for analysis, and measurements of orbital volume, orbital fat volume, extraocular muscle volume, optic nerve volume, and exophthalmos were obtained. The results demonstrated that the combination of Mimics and other softwares for processing orbital CT scans allows for the quantitative analysis of various soft tissue volumes within the orbit. The MV/FV ratio was found to effectively reflect the relative changes in extraocular muscle volume, serving as a valuable indicator for identifying different subtypes of TAO and providing significant clinical reference value.

Evaluation of the Effect of Topical Prostaglandin Analog Treatment on Orbital Structures in Open-Angle Glaucoma with Computed Tomography

Background/Objectives: This study aims to evaluate the computed tomography (CT) scans of glaucoma patients using prostaglandin analogs (PGA) in one eye, investigate findings associated with prostaglandin-associated periorbitopathy (PAP), and compare these findings with those of the contralateral eyes. Methods: Patients with open-angle glaucoma who had CT images of the orbital region taken for another reason at least one month after starting PGA treatment in one eye were included in the study. Enophthalmos measurements from thin-slice CT images, along with 3D volume measurements of orbital fat tissue, periorbital muscles, and the optic nerve, were performed. Ophthalmological examination findings and treatment information were collected. The values were compared with those of the contralateral eyes of the same patients not using PGA. Intraclass correlation coefficients (ICCs) were computed to evaluate measurement repeatability. Results: Forty patients were included in the study. Among them, 29 (72.5%) used latanoprost, 9 (22.5%) used bimatoprost, and 2 (5%) used travoprost. The mean enophthalmos values on the treated side (15.5 ± 2.0 mm) were lower than on the untreated side (16.1 ± 1.4 mm), but this difference was not statistically significant (p = 0.07). In 29 patients (72.5%), enophthalmos measurements were smaller on the treated side, with 7 patients (17.5%) showing a difference of 2 mm or more. No significant correlation was found between the duration of PGA use and enophthalmos measurements (p = 0.768 r = −0.048). Additionally, no significant differences were found in orbital fat volume, total extraocular muscle volume, and optic nerve volume (p > 0.05). ICC values demonstrated excellent reliability (ICC > 0.75) for all measurements. Conclusions: We did not find significant differences in enophthalmos measurements, orbital fat volume, total muscle volume, and optic nerve volume between the PGA-treated and untreated eyes.

Clinical Characteristics and Underlying Pathophysiology in 4 Subtypes of Dysthyroid Optic Neuropathy Patients

Objective: To analyze different subtypes, clinical characteristics, and pathophysiologies of dysthyroid optic neuropathy (DON) based on orbital fat and extraocular muscle (EOM) volume increases on orbital CT images. Methods: The author retrospectively reviewed the medical records of 80 patients (152 eyes) who were diagnosed with DON and treated at Anam, Guro, or Ansan hospitals of the Korea University College of Medicine from February 2006 to December 2023. Clinical features, ophthalmic examination, demographic characteristics, thyroid status, and radiographic findings from computed tomography scans (prevalence of fat or muscle volume increases) were analyzed. Results: Four groups were designated based on EOM volume (MV) and orbital fat volume (FV). Group 1 had no increase in MV or FV (5.3%, 8 eyes), group 2 had increased FV only (8.66%, 13 eyes), group 3 had an increase in MV only (52.6%, 80 eyes), while group 4 had both MV and FV increase (33.6%, 51 eyes). Patients in group 1 were younger and had low diplopia scores than patients in the other groups. Decreases in visual acuity, color vision abnormalities, diplopia score, and apical crowding were less frequent in groups 1 and 2 than groups 3 and 4 (P=0.000). Patients in groups 3 and 4 had significantly more apical crowding and higher diplopia scores and CAS scores than patients in groups 1 and 2 (P=0.000 and 0.013, respectively). The number of patients who underwent decompression surgery was significantly higher in groups 3 and 4 than groups 1 and 2 (P=0.000). Conclusion: Extraocular muscle enlargement occurred in 86% of DON patients and compression of the optic nerve due to enlargement of EOMs at the orbital apex is the main cause of DON. Optic nerve stretch and vascular insufficiency due to increased orbital pressure are other potential mechanisms underlying DON in groups without an increase in FV or MV. Although decreased visual acuity, color vision abnormalities, and diplopia were less frequent in these groups, greater attention should be paid to the timely diagnosis of DON.

Deep-Learning Based Automated Segmentation and Quantitative Volumetric Analysis of Orbital Muscle and Fat for Diagnosis of Thyroid Eye Disease.

Thyroid eye disease (TED) is characterized by proliferation of orbital tissues and complicated by compressive optic neuropathy (CON). This study aims to utilize a deep-learning (DL)-based automated segmentation model to segment orbital muscle and fat volumes on computed tomography (CT) images and provide quantitative volumetric data and a machine learning (ML)-based classifier to distinguish between TED and TED with CON. Subjects with TED who underwent clinical evaluation and orbital CT imaging were included. Patients with clinical features of CON were classified as having severe TED, and those without were classified as having mild TED. Normal subjects were used for controls. A U-Net DL-model was used for automatic segmentation of orbital muscle and fat volumes from orbital CTs, and ensemble of Random Forest Classifiers were used for volumetric analysis of muscle and fat. Two hundred eighty-one subjects were included in this study. Automatic segmentation of orbital tissues was performed. Dice coefficient was recorded to be 0.902 and 0.921 for muscle and fat volumes, respectively. Muscle volumes among normal, mild, and severe TED were found to be statistically different. A classification model utilizing volume data and limited patient data had an accuracy of 0.838 and an area under the curve (AUC) of 0.929 in predicting normal, mild TED, and severe TED. DL-based automated segmentation of orbital images for patients with TED was found to be accurate and efficient. An ML-based classification model using volumetrics and metadata led to high diagnostic accuracy in distinguishing TED and TED with CON. By enabling rapid and precise volumetric assessment, this may be a useful tool in future clinical studies.

Three-dimensional soft tissue reconstruction and volume measurement used for the diagnosis of dysthyroid optic neuropathy.

Dysthyroid optic neuropathy (DON) leads to vision loss. This study aimed to investigate a new method that can directly evaluate the change in muscle cone inner volume (MCIV) and distinguish DON orbits from non-DONs. This study included 54 patients (108 orbits) who were diagnosed with thyroid eye disease and treated at the Beijing Tongren Hospital between December 2019 and September 2021. The extraocular muscle volume (EOMV), orbital fat volume (OFV), and bony orbit volume (BOV) of the patients were measured using three-dimensional reconstruction. MCIV was measured using artificially defined boundaries. The associations between these volumes and clinical indicators were studied, and the diagnostic efficacy of these volumes for DON was described using receiver operating characteristic (ROC) curves. The ROC curve showed that the area under the curve of MCIV/BOV (%) combined with EOMV/BOV (%) reached 0.862 (p < 0.001), with a sensitivity of 85.7% and a specificity of 76.1%. The combination of MCIV/BOV (%) and EOMV/BOV (%) is a good indicator for the diagnosis of DON, which aids in the early detection and intervention of DON.

Revisiting bilateral bony orbital volumes comparison using 3D reconstruction in Korean adults: a reference study for orbital wall reconstruction, 3D printing, and navigation by mirroring

BackgroundOrbital wall fractures can result in changes to the bony orbital volume and soft tissue. Restoring the bony orbital and intraconal fat volumes is crucial to prevent posttraumatic enophthalmos and hypoglobus. We aimed to establish an evidence-based medical reference point for “mirroring” in orbital wall reconstruction, which incorporates three-dimensional (3D)-printing and navigation-assisted surgery, by comparing bilateral bony orbital volumes.MethodsWe retrospectively analyzed the data obtained from 100 Korean adults who did not have orbital wall fractures, categorized by age groups. The AVIEW Research software (Coreline Soft Inc., Seoul, South Korea) was used to generate 3D reformations of the bony orbital cavity, and bony orbital volumes were automatically calculated after selecting the region of interest on consecutive computed tomography slices.ResultsThe mean left and right orbital volume of males in their 20 s was 24.67 ± 2.58 mL and 24.70 ± 2.59 mL, respectively, with no significant difference in size (p = 0.98) and Pearson’s correlation coefficient of 0.977 (p < 0.001). No significant differences were found in orbital volumes in other age groups without fractures or in patients with nasal bone fractures (p = 0.84, Pearson’s correlation coefficient 0.970, p < 0.001). The interclass correlation coefficients (2,1) for inter- and intrarater reliability were 0.97 (p < 0.001) and 0.99 (p < 0.001), respectively.ConclusionsNo significant differences were found in the bilateral bony orbital volumes among males of any age. Thus, the uninjured orbit can be used as a volumetric reference point for the contralateral injured orbit during orbital wall reconstruction.

A clinical study of the effect of 3D reconstruction on exophthalmos after an operation on an old orbital wall fracture.

Orbital blowout fracture is common in ocular trauma. Accurate measurement of orbital volume after fracture is key in improving intraocular correction. This study aims to explore the impact of 3D reconstruction technology in restoring normal exophthalmos in patients with old orbital wall fractures. A total of 31 patients were randomly divided into an experimental group (n= 15) and a control group (n= 16). For orbital wall repair and reconstruction, the conventional group used the conventional surgical scheme, and the 3D group used 3D printing technology. There was no statistical difference between the preoperative mean extraocular muscle volume of the healthy eye and the affected eye. However, the mean orbital volume (24.76 vs 27.11, P= 0.005) and mean retrobulbar fat volume (17.53 vs 16.42, P= 0.006) were significantly different between the healthy eye and the affected eye. After an average follow-up of 16 weeks, the differences in pre- and post-surgery exophthalmos in the two groups were 0.42 ± 0.08 mm and 1.63 ± 0.51 mm, respectively. The difference between the two groups was statistically significant (t= 4.42, P= 0.003). The complications were not statistically different. Using 3D reconstruction technology preoperatively can significantly improve exophthalmos in patients with old orbital wall fractures.

Lower eyelid blepharoplasty combined with ultrasound-guided percutaneous diode laser lipolysis: evaluating effectiveness with long-term outcome.

Laser lipolysis may be considered for selective removal of excess orbital fat via minimally invasive lower blepharoplasty. To control the energy delivery to a precise anatomic location while avoiding complications, ultrasound guidance can be utilized. Under local anesthesia, a diode laser probe (Belody, Minslab, Korea) was introduced percutaneously to the lower eyelid. The tip of the laser device and changes in orbital fat volume were carefully controlled with ultrasound imaging. A 1470-nm wavelength was used for orbital fat reduction (maximal energy 300J), and a 1064-nm wavelength was used to tighten the lower eyelid skin (maximal energy 200J). From March 2015 to December 2019, a total of 261 patients underwent ultrasound-guided diode laser lower blepharoplasty. The procedure took 17min on average. Total energy of 49J-510J (average = 228.31J) was delivered in 1470-nm wavelengths or 45-297J (average = 127.68J) was delivered in 1064-nm wavelengths. Most patients were very satisfied with their results. Fourteen patients experienced complications, including nine cases of transient hypesthesia (3.45%), and three skin thermal burns (1.15%). However, these complications were not observed after strict control of the energy delivery below 500J for each lower lid. Improvement in lower eyelid bags can be achieved using a minimally invasive approach in selected patients with ultrasound-guided laser lipolysis. It is a fast and safe procedure that can be performed in the outpatient setting.

LBSAT238 Teprotumumab Reduces Orbital Fat And Muscle Volume In Patients With Thyroid Eye Disease

Abstract Teprotumumab, a novel IGF-1R antibody has been shown to reduce proptosis in patients with thyroid eye disease (TED) in 2 randomized controlled trials. At present, it is unclear whether the reduction in proptosis is related to a decrease in extraocular muscle or orbital fat tissue. In this prospective longitudinal study, we reviewed the changes to orbital fat and muscle, and compared them, in consecutive patients with TED, who had completed treatment with teprotumumab (8 infusions). The primary outcome was change in orbital fat and muscle volume within 6 weeks of starting and completing therapy. Secondary outcome measures included change in proptosis and the clinical activity score (CAS). All patients had either CT or MRI with ≤ 1 mm slice thickness. Three-dimensional volumetric analysis of the orbital fat and muscle volume was performed using the previously validated 3D image analysis software, MIMICS (Materialise, Leuven, Belgium). Hounsfield units of fat and muscle were defined manually. All extraocular muscle tissue and fat between the orbital septum (eyelid) and the orbital outlet of the optic canal was included. A 3D model created by voxel addition was expressed in millimeters cubed. Segmentation and measurements were performed independently by two graders to review repeatability and observer variability. In line with previous clinical trials, the orbit with the most proptosis was defined as the study orbit and the contralateral orbit was designated the fellow orbit. Twenty-one patients (15 females and 6 males) met the inclusion criteria. Mean (SD) age was 55 (16), while mean (SD) duration of TED was 71 (46) months. There was a reduction of 3 mm in both; study and fellow orbits following treatment (p &amp;lt; 0. 01 for both). Compared to baseline, there was a mean (SD) CAS reduction of 4 (1) in the study orbit and 2.4 (1.1) in the fellow orbit (p &amp;lt; 0. 01 for both). Following therapy, mean (SD) reduction in muscle tissue was 1691 mm3 (1358) in the study orbit and 1714 mm3 (1927) in the fellow orbit (p &amp;lt; 0. 01 when compared to baseline for each). The mean (SD) reduction of fat volume was 1382 mm3 (1318) in the study orbit and 933 mm3 (1699) in the fellow orbit (p &amp;lt; 0. 01 when compared to baseline for each). There was no difference between fat and muscle reduction for the study orbit (p = 0.4) or fellow orbit (p = 0.2). There was a significant correlation between a reduction in proptosis and reduction in orbital soft tissue (fat and muscle) volume. The results of this study suggest that following treatment with teprotumumab, there is a significant decrease in orbital fat and muscle volume. This reduction in soft tissue volume likely drives the reduction in proptosis. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Orbital Aging: A Computed Tomography-Based Study of 240 Orbits.

Previous studies have attempted to explain age-related changes to the orbit in isolation, often producing conflicting results. The authors used highly accurate imaging software to analyze computed tomographic scans to characterize changes related to age objectively. In this case-control study, patients seen in an ear, nose, and throat clinic were screened for study entry. Male and female participants were divided into two age groups (20 to 30 years and 60 to 75 years). Primary outcomes included measurement of bony orbital dimensions, volume of soft tissues (muscle and fat volume), and anterior globe position. Three-dimensional reconstructions were created of each orbit allowing these measurements. The generalized estimating equation was used so that both orbits from each patient could be included without any bias. The final sample included 240 orbits from 120 patients. There were 30 patients in each age group. Among female participants, the bony orbital volume ( p < 0.05), fat volume ( p < 0.01), and central width ( p < 0.001) of the bony orbit increased with age. The anterior globe position was significantly greater in older female participants ( p < 0.01). For male participants, the fat volume ( p < 0.0001) and central height ( p < 0.03) increased with age; the lateral rim moved posteriorly with age ( p < 0.007). The anterior globe position was not different between the age groups in male participants ( p = 0.56). The female bony orbit expands with age and is associated with a more anterior position of the globe; the male bony orbital volume remains the same and the lateral rim moves posteriorly.

A Paradigm Shift in the Management of Thyroid Eye Disease How Teprotumumab Has Changed the Therapeutic Interface.

Teprotumumab, a monoclonal antibody that blocks the insulin-like growth factor-1 receptor, has recently been approved by the US Food and Drug Administration (FDA) for the treatment of thyroid eye disease (TED). Since its approval, aside from data on the safety and clinical efficacy of teprotumumab from Phase-2 and Phase-3 trials, only a handful of reports have been published regarding its use in the wider population. In this review, we briefly describe the mechanism of action of teprotumumab and review the literature to provide an overview of published clinical experience. This information was used to provide recommendations for patient selection, management of patient expectations, infusion details and site options, tips to optimize the authorization process, and how to monitor and mitigate side effects. A systemic review of the literature was performed regarding teprotumumab, focusing on its mechanisms of action and published reports on its use on patients with TED. A review of Embase, Medline (PubMed), Web of Science, and Google Scholar was conducted. Clinical experience following the approval of teprotumumab has confirmed its efficacy in reducing inflammation and proptosis in patients with acute TED (<2 years). The reduction in proptosis occurs due to a reduction in orbital fat and muscle volume. Furthermore, there is evidence for its use in patients with compressive optic neuropathy. There are also reports that show its efficacy in reducing proptosis, inflammation, and diplopia in patients with chronic TED (>2 years). Teprotumumab was associated with side effects, such as muscle spasm, hearing loss, and hyperglycemia. To date, 2 case reports have shown a possible association with flares of inflammatory bowel disease. Teprotumumab is a powerful therapeutic option for the treatment of TED. Clinical experience following FDA approval has demonstrated efficacy in treating patients with acute and chronic TED. It is the only therapeutic option that has been shown to reduce orbital soft tissue expansion in TED. However, it is expensive, and sometimes, obtaining insurance authorization can be time consuming and difficult. Further work will reveal its full side effect profile and help to establish its role in the armamentarium used to treat TED.

The method of the exophthalmos value predicted calculation when planning the orbital decompression procedure in patients with endocrine ophthalmopathy

BACKGROUND: The most effective method of surgical treatment of lipogenic and mixed forms of edematous exophthalmos is currently the internal orbital decompression. During this surgical procedure, the excessive pathologically altered adipose tissue is removed from the external and the internal surgical spaces of the orbit. Many scientists are developing methods for calculating the volume of orbital fat, but the question on developing a method for predicted exophthalmos after internal orbital decompression, which could be used without attracting additional equipment and software, is easy to learn and does not require a long calculation time, remains actual. This method has to take into account the individual features of the patients orbital structure and be used for calculations in the bilateral proptosis correction.&#x0D; AIM: To develop and evaluate the effectiveness of a new method for calculating the eyeball position after orbital decompression.&#x0D; MATERIALS AND METHODS: 64 patients (126 orbits) with lipogenic and mixed forms of endocrine ophthalmopathy were examined. All patients underwent internal orbital decompression, during which the orbital fat was removed, the volume of which was calculated according to the developed original method. Patients underwent ophthalmological examination and MSCT before surgery and 6 months after it. .&#x0D; RESULTS: As a result of orbital decompression in the examined group, a decrease in proptosis was observed in all patients, and the exophthalmos calculated by the method corresponded to the eyeball position in patients in 6 months after surgery. The level of statistical significance of the planned postoperative eyeball position in relation to the actual postoperative exophthalmos calculated according to the Students t-test was 0.98 (p 0.05), that is, it can be argued that the groups do not differ, and no statistically significant differences were found.&#x0D; CONCLUSIONS: The developed method for calculating the estimated postoperative exophthalmos is effective without using additional software. This technique allows you to achieve a symmetrical eyeball position in the postoperative period and to reduce the risk of complications.

МРТ диагностика объема ретробульбарной клетчатки у пациентов с эндокринной офтальмопатией

МРТ диагностика объема ретробульбарной клетчатки у пациентов с эндокринной офтальмопатией

Teprotumumab reduces extraocular muscle and orbital fat volume in thyroid eye disease

PurposeThyroid eye disease (TED) is a progressive, debilitating and potentially vision-threatening autoimmune disease. Teprotumumab, a novel human monoclonal antibody, has been shown to reverse the clinical manifestations of TED. Patients...

Semi-automatic magnetic resonance imaging based orbital fat volumetry: reliability and correlation with computed tomography

Post-processing analysis can provide valuable information for diagnosis and planning of orbital disorders. This cross-sectional study aims to evaluate the reliability of semi-automatic, orbital fat volumetry using magnetic resonance imaging (MRI). Two observers assessed the orbital fat volume using a standard MRI protocol (3T, T1w sequence) in 12 orbits diagnosed with Graves’ orbitopathy (GO) and 10 healthy control orbits. MRI and computed tomography (CT) based analysis were compared. Intra-observer variability was good (intraclass correlation coefficient (ICC) 0.88; 95% confidence interval (CI) [0.70, 0.95]) and interobserver agreement was moderate (ICC 0.55; 95% CI [−0.09, 0.81]), which corresponds to a mean percentage difference of 1.3% and 17.9% of the total orbital fat volume. Mean differences between MRI and CT measurements were, respectively, 1.1 cm3 (P= 0.064, 95% CI [−0.20, 2.43]) and 1.4 cm3 (P=0.016, 95% CI [0.21, 2.56]) for the control and the GO group. MRI volumetry was strongly correlated with CT (Pearson’s r= 0.7, P<0.001). We conclude that orbital fat volumetry is feasible with a semi-automatic segmentation procedure and standard MRI protocol. Correlation with CT volumetry is good, but considerable bias may derive from observer variability and these errors should be taken into account for the purpose of volumetric analysis. Better definition of error sources may increase measurement accuracy.

Optic neuropathy and exophthalmos edematous: symptom or complication?

The article is concentrated on the mechanism of the development of optic neuropathy in patients with edematous proptosis one of the clinical forms of endocrine ophthalmopathy. All probable options for the pathogenesis of optic neuropathy are reviewed in detail: increased intraorbital pressure, compression of the optic nerve by enlarged extraocular muscles, the formation of the apical syndrome with compression of the optic nerve in the zone of the Zinns ring, an increase in the volume of orbital fat, tension of the optic nerve by an anteriorly shifted eye (exophthalmos), and arterial blood flow impairment in the ophthalmic artery, impaired venous blood flow in the orbit. Based on 103 follow-ups of patients with edematous proptosis and optic neuropathy (68 of them had initial optical neuropathy), the author offers her concept of the pathogenesis of optic neuropathy in patients with sub- and decompensated edematous proptosis, considering optic neuropathy as a complication of endocrine ophthalmopathy. The signs of optical neuropathy in the initial stage of its development are conceived.

Orbital Fat Volume After Treatment with Topical Prostaglandin Agonists.

PurposeTopical prostaglandin analogs (PGAs) are common treatment for primary open-angle glaucoma (POAG) but reportedly may cause adnexal fat atrophy. We asked if patients with POAG treated with PGAs have abnormalities in orbital fat volume (OFV).MethodsWe studied 23 subjects with POAG who had never experienced intraocular pressure (IOP) exceeding 21 mm Hg and were treated long term with PGAs, in comparison with 21 age-matched controls. Orbital volume, non-fat orbital tissue volume, and OFV were measured using high-resolution magnetic resonance imaging.ResultsSubjects with POAG had been treated with PGAs for 39 ± 19 months (SD) and were all treated within the 4 months preceding study. In the region from trochlea to orbital apex, OFV in POAG was significantly less at 9.8 ± 1.9 mL than in the control subjects at 11.1 ± 1.3 mL (P = 0.019). However, between the globe-optic nerve junction (GONJ) and trochlea, OFV was similar in both groups. Width and cross sectional area of the bony orbit were significantly smaller in POAG than in controls (P < 0.0001). Posterior to the GONJ, the average orbital cross-sectional area was 68.2 mm2 smaller, and the orbital width averaged 1.5 mm smaller throughout the orbit, in patients with POAG than in controls.ConclusionsPatients with POAG who have been treated with PGAs have lower overall OFV than controls, but OFV in the anterior orbit is similar in both groups. Lower overall OFV in POAG may be a primary association of this disorder with a horizontally narrower bony orbit, which may be a risk factor for POAG at nonelevated IOPs.

Teprotumumab for the Treatment of Active Thyroid Eye Disease

BackgroundThyroid eye disease is a debilitating, disfiguring, and potentially blinding periocular condition for which no Food and Drug Administration–approved medical therapy is available. Strong evidence has implicated the insulin-like growth factor I receptor (IGF-IR) in the pathogenesis of this disease.MethodsIn a randomized, double-masked, placebo-controlled, phase 3 multicenter trial, we assigned patients with active thyroid eye disease in a 1:1 ratio to receive intravenous infusions of the IGF-IR inhibitor teprotumumab (10 mg per kilogram of body weight for the first infusion and 20 mg per kilogram for subsequent infusions) or placebo once every 3 weeks for 21 weeks; the last trial visit for this analysis was at week 24. The primary outcome was a proptosis response (a reduction in proptosis of ≥2 mm) at week 24. Prespecified secondary outcomes at week 24 were an overall response (a reduction of ≥2 points in the Clinical Activity Score plus a reduction in proptosis of ≥2 mm), a Clinical Activity Score of 0 or 1 (indicating no or minimal inflammation), the mean change in proptosis across trial visits (from baseline through week 24), a diplopia response (a reduction in diplopia of ≥1 grade), and the mean change in overall score on the Graves’ ophthalmopathy-specific quality-of-life (GO-QOL) questionnaire across trial visits (from baseline through week 24; a mean change of ≥6 points is considered clinically meaningful).ResultsA total of 41 patients were assigned to the teprotumumab group and 42 to the placebo group. At week 24, the percentage of patients with a proptosis response was higher with teprotumumab than with placebo (83% [34 patients] vs. 10% [4 patients], P<0.001), with a number needed to treat of 1.36. All secondary outcomes were significantly better with teprotumumab than with placebo, including overall response (78% of patients [32] vs. 7% [3]), Clinical Activity Score of 0 or 1 (59% [24] vs. 21% [9]), the mean change in proptosis (−2.82 mm vs. −0.54 mm), diplopia response (68% [19 of 28] vs. 29% [8 of 28]), and the mean change in GO-QOL overall score (13.79 points vs. 4.43 points) (P≤0.001 for all). Reductions in extraocular muscle, orbital fat volume, or both were observed in 6 patients in the teprotumumab group who underwent orbital imaging. Most adverse events were mild or moderate in severity; two serious events occurred in the teprotumumab group, of which one (an infusion reaction) led to treatment discontinuation.ConclusionsAmong patients with active thyroid eye disease, teprotumumab resulted in better outcomes with respect to proptosis, Clinical Activity Score, diplopia, and quality of life than placebo; serious adverse events were uncommon. (Funded by Horizon Therapeutics; OPTIC ClinicalTrials.gov number, NCT03298867, and EudraCT number, 2017-002763-18.)

Analysis of Periorbital Soft Tissue in Thyroid Eye Disease

To investigate periorbital tissue enlargement in thyroid eye disease (TED) by 3-dimensional CT volumetric analysis. Twenty-four adult subjects, 16 with TED and 8 controls, were studied. Three-dimensional volumetric calculations were performed on CT imaging of the orbit and face, focusing on the retroorbicularis oculi fat, suborbicularis oculi fat, facial muscles in periorbital region, orbital fat, extraocular muscles, and orbital volume. Analysis was performed using JMP version 12 software. Each measure was compared between the TED and control groups using Wilcoxon rank sum test. Correlations were investigated between periorbital and orbital tissue using the Spearman's correlation coefficient method. A statistically significant increase in volume was measured in TED patients in the superior and inferior periorbital fat tissue (p = 0.0044, p = 0.047), including the retroorbicularis oculi fat (p = 0.0011), suborbicularis oculi fat (p = 0.0093), and a decrease in facial muscle of superior periorbital region (p = 0.035). Strong positive correlation was noted between the muscles of superior and inferior periorbital region (rs = 0.65; p = 0.0006), and between the suborbicularis oculi fat and retroorbicularis oculi fat (rs = 0.50; p = 0.013). No correlation was observed between orbital and periorbital tissue, except between the orbital fat and the inferior periorbital fat tissue (p = 0.047). Facial fat in the periorbital region is enlarged in TED, with the superior component correlating with orbital fat tissue expansion. These findings may assist in the clinical evaluation and management of disfigurement in TED patients.Superior and inferior periorbital fat is enlarged in thyroid eye disease with the superior periorbital fat expansion correlating with orbital fat expansion.

Post-traumatic enophthalmos secondary to orbital fat atrophy: a volumetric analysis

ABSTRACT Purpose To investigate via volumetric analysis whether orbital fat atrophy occurs in late post-traumatic enophthalmos. Methods An IRB-approved retrospective cohort study identified patients with diagnoses of both orbital fracture and enophthalmos with a CT orbits >3 months after injury. Exclusion criteria were surgical repair, other orbital disease or surgery, adjacent sinus disease, and an abnormal contralateral orbit. Images were analyzed using OsiriX imaging software (v.9.0.2, Pixmeo, Switzerland). Total orbital volume and orbital fat volume for the fractured and normal contralateral orbits were measured via three-dimensional volume rendering assisted region-of-interest computation. Enophthalmos was measured radiographically. Paired samples t-tests were used to compare orbital fat and total orbital volumes between the fractured and normal contralateral orbits. Results Thirteen patients met the inclusion criteria. The numbers of patients with each fracture pattern were floor (4), medial wall (4), floor/medial wall (3), zygomaticomaxillary complex (floor+lateral wall) (1), zygomaticomaxillary complex+medial (inferior/medial/lateral walls) (1). Mean time from injury to CT scan was 21.8 ± 16.3 months. Comparing the fractured and normal contralateral orbits, there was a statistically significant decrease in orbital fat volume (mean difference 0.9 ml (14.2%), p = .0002) and increase in total orbital volume (mean difference 2.0 ml (7.0%), p = .0001). One ml orbital volume change was responsible for 0.83 mm enophthalmos. Conclusions In addition to an increase in total orbital volume, orbital fat loss occurs with late post-traumatic enophthalmos due to unrepaired fractures. This suggests correction of bony change alone may be insufficient in some cases, and the use of custom implants may compensate for fat atrophy.