Introduction: Graves orbitopathy (GO) is an autoimmune disease affecting the orbits and the periorbital tissues with an annual incidence of 16 per 100,000 population in women and 2.9 in men. While GO occurs in the spectrum of hyperthyroidism or Graves disease, 7.9% of these patients have a normal thyroid function and only a few are negative for thyroid antibodies. When left untreated, GO may become debilitating and threaten vision. Case Description: A 64-year-old male presented with gross bilateral proptosis and chemosis, which developed over a period of 10 years. Palpitations, hand tremors, heat intolerance, weight loss, and insomnia were notably absent, and the thyroid gland was normal. The bilateral proptosis was left unattended for 10 years until extreme lagophthalmos and chemosis with corneal and mucosal exposure leading to dryness, foreign body sensation, excruciating eye pain, and blurred vision resulted. Thyroid-stimulating hormone (TSH), T3, and T4, were normal. TSH-receptor antibody (TRAb) and thyroid peroxidase antibody were negative. The computed tomography scan with contrast of the orbits showed bilateral proptosis and extraocular muscle enlargement typical for thyroid eye disease. The patient was diagnosed with TRAb- negative euthyroid GO with a European Group on Graves’ Orbitopathy (EUGOGO) clinical score of 7/7, indicating a severe, active disease. Screening prior to administration of GO immunosuppressive therapy revealed chronic hepatitis B infection. The patient was started with tenofovir for 2 weeks before treatment for GO. The patient was given intravenous methylprednisolone with cumulative dose of 4.5 g for 12 weeks, with daily mycophenolate sodium 0.72 g for 12 weeks. Upon completing the 12-week treatment regimen and undergoing an adjunctive lateral canthotomy and partial tarsorrhaphy, the GO signs and symptoms dramatically resolved, and visual acuity markedly improved. Conclusion This case report presents an unusual condition of a euthyroid, TRAb-negative Graves orbitopathy. It provides insights on the diagnosis and treatment of patients with such atypical presentation. Despite the chronicity and severity of this patient’s GO, excellent results were achieved with appropriate and guideline-directed treatment.
Human ; Male ; Middle Aged: 45-64 Yrs Old ; Graves Ophthalmopathy ; Exophthalmos ; Mycophenolic Acid

OBJECTIVES: Graves' ophthalmopathy (GO) is a multifactorial disease, and the mechanism of non coding RNA interactions and inflammatory cell infiltration patterns are not fully understood. This study aims to construct a competing endogenous RNA (ceRNA) network for this disease and clarify the infiltration patterns of inflammatory cells in orbital tissue to further explore the pathogenesis of GO. METHODS: The differentially expressed genes were identified using the GEO2R analysis tool. The Kyoto encyclopedia of genes and genomes (KEGG) and gene ontology analysis were used to analyze differential genes. RNA interaction relationships were extracted from the RNA interactome database. Protein-protein interactions were identified using the STRING database and were visualized using Cytoscape. StarBase, miRcode, and DIANA-LncBase Experimental v.2 were used to construct ceRNA networks together with their interacted non-coding RNA. The CIBERSORT algorithm was used to detect the patterns of infiltrating immune cells in GO using R software. RESULTS: A total of 114 differentially expressed genes for GO and 121 pathways were detected using both the KEGG and gene ontology enrichment analysis. Four hub genes (SRSF6, DDX5, HNRNPC,and HNRNPM) were extracted from protein-protein interaction using cytoHubba in Cytoscape, 104 nodes and 142 edges were extracted, and a ceRNA network was identified (MALAT1-MIR21-DDX5). The results of immune cell analysis showed that in GO, the proportions of CD8⁺ T cells and CD4⁺ memory resting T cells were upregulated and downregulated, respectively. The proportion of CD4 memory resting T cells was positively correlated with the expression of MALAT1, MIR21, and DDX5. CONCLUSIONS This study has constructed a ceRNA regulatory network (MALAT1-MIR21-DDX5) in GO orbital tissue, clarifying the downregulation of the proportion of CD4⁺ stationary memory T cells and their positive regulatory relationship with ceRNA components, further revealing the pathogenesis of GO.
Humans ; CD8-Positive T-Lymphocytes ; RNA, Long Noncoding/genetics* ; Algorithms ; CD4-Positive T-Lymphocytes ; Down-Regulation ; Graves Ophthalmopathy/genetics* ; Gene Regulatory Networks ; MicroRNAs/genetics* ; Serine-Arginine Splicing Factors ; Phosphoproteins

OBJECTIVES: Dysthyroid optic neuropathy (DON) is a class of diseases that makes seriously endanger to the vision of patients with thyroid-associated ophthalmopathy. This study aims to observe the visual function changes in patients with DON, and to evaluate the diagnostic value of indicators diagnosing DON. METHODS: A retrospective study was conducted on 98 eyes of 49 patients with dysthyroid optic neuropathy (DON) who were treated in Xiangya Hospital of Central South University from January 2017 to December 2019. All patients were received the examination of best corrected visual acuity (BCVA), Humphrey visual field, visual evoked potential (VEP), and contrast sensitivity. Ninety-eight eyes were divided into a DON group (45 eyes) and a non-DON group (53 eyes). T-test was used to compare the related indicators between the 2 groups. The sensitivity and specificity of each indicator were analyzed by receiver operating characteristic (ROC) curve. RESULTS: The BCVA and visual field index (VFI) of the DON group were significantly lower than those of the non-DON group (all P<0.05). The mean deviation (MD) and pattern standard deviation (PSD) of the DON group were significantly higher than those of the non-DON group (all P<0.05). The low frequency contrast sensitivity (CSL), medium frequency contrast sensitivity (CSM), and high frequency contrast sensitivity (CSH) of the DON group were significantly lower than those of the non-DON group (all P<0.05), with CSH being particularly prominent. Compared with the non-DON group, at spatial frequencies of 15°, 30°, and 60°, the amplitude of N135 wave was significantly reduced, and the latency of N75 wave, P100 wave, and N135 wave was significantly prolonged in the DON group (all P<0.05); at spatial frequencies of 15° and 30°, the amplitude of P100 wave was significantly reduced in the DON group (P<0.05). The ROC curve analysis results showed that the area under the curve (AUC) of VFI, CSL, CSM, CSH and 15° P100 amplitude diagnosing DON were 0.812, 0.841, 0.880, 0.784, and 0.791, respectively, with CSM possessing the highest sensitivity and specificity. CONCLUSIONS The visual function of patients with DON is decreased. VFI, contrast sensitivity of low, medium, and high frequency, and 15° P100 wave amplitude might be effective indicators for early diagnosis of DON.
Humans ; ROC Curve ; Optic Nerve Diseases/complications* ; Retrospective Studies ; Evoked Potentials, Visual ; Graves Ophthalmopathy

Graves' ophthalmopathy is the most common clinical orbital disease, and T helper (Th) cells play an important role in the development of Graves' ophthalmopathy. Th17 cells are a major subpopulation of Th cells and abnormally highly expressed in patients with Graves' ophthalmopathy. Th17 cells and the related cytokines interleukin (IL)-17A, IL-21 and IL-23 are involved in regulating the inflammatory response, fibrosis and adipogenesis. Th17 cells are unstable and exhibit a degree of plasticity, and they can differentiate into IL-17A and interferon (IFN)-γ dual-producing Th17.1 cells, which exacerbate the pathogenicity of Th17 cells. In addition, Th17 cells and the relevant factors are strongly associated with disease activity and severity in Graves' ophthalmopathy.
Humans ; Cytokines ; Th17 Cells ; Graves Ophthalmopathy ; Adipogenesis

To investigate the values of orbital single photon emission computed tomography/computerized tomography (SPECT/CT) with 99mTc-diethylene triamine pentaacetic acid (99mTc-DTPA) on the evaluation of lacrimal gland inflammation in patients with thyroid associated ophthalmopathy (TAO).
 Methods: A total of 58 TAO patients were retrospectively recruited for this study, all of whom were categorized into all active group and all inactive group based on the clinical active score (CAS). Another 12 patients with the negative images on SPECT/CT served as a normal control group (NC). All patients were undergone the 99mTc-DTPA orbit SPECT/CT. Quantitative parameters of lacrimal gland including width, length, volume, and the count ratio of region of interest (ROI) drawn on lacrimal gland to the region of occipital brain (target/non-target ratio, T/NT), were measured on axial and coronal slices, respectively. Quantitative parameters were compared among the 3 groups, and the diagnostic value on discrimination of TAO patients from inactive to active ones was evaluated.
 Results: All parameters in TAO patients (except the length on coronal slices and the mean radioactive counts of axial T/NT in the TAO inactive group) were much greater than those in the NC group (P<0.05). All parameters in the TAO active group (except the length on axial and coronal slices) were much greater than those in the TAO inactive group (P<0.05). There were significant lineal positive correlations between the parameters in all TAO patients (except the length on coronal slices ) and CAS. The best diagnostic value was detected by the max radioactive counts of axial T/NT (area under the curve=0.82, P<0.01).
 Conclusion: As an invasive imaging modality, 99mTc-DTPA orbital SPECT/CT is helpful to estimate the lacrimal gland inflammation and to assess the disease activity in TAO patients.
Graves Ophthalmopathy ; Humans ; Inflammation ; Lacrimal Apparatus ; Orbit ; Retrospective Studies ; Tomography, Emission-Computed, Single-Photon ; Tomography, X-Ray Computed

PURPOSE: We sought to investigate the effects of Graves' orbitopathy (GO) and orbital decompression on lamina cribrosa depth (LCD) using spectral-domain optical coherence tomography. METHODS: Forty eyes that underwent orbital decompression to relieve compressive optic neuropathy or correct disfiguring exophthalmos in the context of GO were included. Subjects were imaged with spectral-domain optical coherence tomography before surgery and at 1 and 3 months after surgery, at which the examiner measured the LCD (distance from the anterior surface of the lamina cribrosa to the Bruch membrane opening line) and peripapillary retinal nerve fiber layer thickness. Subjects were divided into two groups—a muscle-dominant group composed of patients who had extraocular muscle enlargement on preoperative orbital computed tomography scan and a fat-dominant group composed of patients who did not show extraocular muscle enlargement on preoperative orbital computed tomography scan—and subgroup analysis was performed. Preoperative and postoperative intraocular pressure, exophthalmos, LCD, and retinal nerve fiber layer thickness were evaluated. RESULTS: At baseline, LCD was remarkably shallower in the muscle-dominant group than in the fat-dominant group (95% confidence interval, p = 0.007). In the muscle-dominant group, LCD showed no definite change after surgery. However, the fat-dominant group showed temporary posterior displacement of the lamina cribrosa at 1-month postoperation that was reversed to baseline at 3 months postoperation (95% confidence interval, p < 0.01). CONCLUSIONS: The lamina cribrosa was anteriorly displaced preoperatively, and its position was nearly unchanged after the surgery, especially in association with extraocular muscle enlargement. An enlarged extraocular muscle could reduce the pressure-relieving effect of orbital decompression around the scleral canal in patients with GO.
Bruch Membrane ; Decompression ; Exophthalmos ; Graves Ophthalmopathy ; Humans ; Intraocular Pressure ; Nerve Fibers ; Optic Nerve ; Optic Nerve Diseases ; Orbit ; Retinaldehyde ; Tomography, Optical Coherence

To compare diagnostic value of 4 kinds of target-to-nontarget ratio (T/NT), and to choose a better one to assess thyroid associated ophthalmopathy (TAO) activity.
 Methods: The clinical data were collected for 29 newly-diagnosed patients (58 eyes) with TAO who underwent orbital 99mTc-DTPA single photon emission computed tomography/computed tomography (SPECT/CT) fusion images according to the clinical activity score (CAS). They were divided into an active group (18 cases, 36 eyes), an inactive group (11 cases, 22 eyes), and a control group (9 cases, 18 eyes). Diagnostic value of orbital/occipital lobe radioactive uptake count ratio (T/NT1), orbital/occipital radioactive uptake count ratio (T/NT2), orbital/thalamus radioactive uptake count ratio (T/NT3), and orbital/cerebellar radioactivity uptake count ratio (T/NT4) were calculated, and the CAS of Spearman rank correlation and receiver operating characteristic (ROC) curve were analyzed.
 Results: T/NT1, T/NT2 and CAS were correlated (r1=0.873, r2=0.527; P<0.001), with the better correlation between T/NT1 and CAS and there was no correlation between T/NT3, T/NT4 and CAS (r3=0.039, r4=0.090; P>0.05). Area under the ROC curve of T/NT1 was 0.860, area under the ROC curve of T/NT2 was 0.581, and the accuracy for T/NT1 on TAO activity was good. T/NT1=9.74 could be used as active threshold for judge of TAO in patients.
 Conclusion: There is a good correlation between T/NT1 and CAS. TAO activity assessment possesses high diagnostic value, and SPECT/CT together with imaging anatomical location is more accurate.
Case-Control Studies ; Graves Ophthalmopathy ; diagnostic imaging ; Humans ; Orbit ; diagnostic imaging ; ROC Curve ; Radiopharmaceuticals ; Statistics, Nonparametric ; Technetium Tc 99m Pentetate ; Tomography, Emission-Computed, Single-Photon ; methods

PURPOSE: To evaluate the therapeutic results of the patients wearing the prism glasses due to strabismus with diplopia unrelated to strabismus surgery. METHODS: Between May 2002 and October 2016, this retrospective study evaluated medical records of 23 patients who were wearing prism glasses due to strabismus with diplopia unrelated to strabismus surgery. The patients failed to adjust to the prism glasses and stopped within 3 months were defined as the adaptation failure group. The patients wearing prism glasses for 3 months or more was defined as adaptation success group. In the prism adaptation success group, he patients who underwent strabismus surgery during follow up were defined as treatment failure. Data were collected the types and causes of strabismus, the deviation angle at starting treatment of prism glasses and last visits, best corrected visual acuity, Titmus stereo test and Worth 4 dot test. RESULTS: Of the total 23 patients, 18 patients had horizontal strabismus, four patients had vertical strabismus and one had horizontal and vertical strabismus. The causes of strabismus were acute acquired comitant esotropia (12 patients), paralytic strabismus (9 patients), and thyroid associated ophthalmopathy (two patients). There was no significant changes in deviation angle as well as the prism diopter of prism glasses after prism glasses treatmet. The prism glasses-adaptation group was 70%, and 31% of them were performed strabismus surgery. There was no reduction in visual acuity in all patients. Among the prism glasses adaptation group, 33% of the prism glasses-adaptation group had poor binocular function. CONCLUSIONS: In the strabismus patients with diplopia unrelated to strabismus surgery 70% of the patients adapted prism glasses more than 3 months and 31% of them required strabismus surgery. Therefore, prism glasses treatment may be one of the non-surgical approaches in the strabismus patients with diplopia unrelated to strabismus surgery.
Diplopia ; Esotropia ; Eyeglasses ; Follow-Up Studies ; Glass ; Graves Ophthalmopathy ; Humans ; Medical Records ; Retrospective Studies ; Strabismus ; Telescopes ; Treatment Failure ; Visual Acuity

PURPOSE: To compare the macular choroidal thickness in patients with thyroid-associated ophthalmopathy (TAO) with those with normal tension glaucoma (NTG). METHODS: A total of 70 normal eyes, 74 eyes with TAO and 60 eyes with NTG were enrolled in this study. All patients underwent spectral-domain optical coherence tomography (SD-OCT) (Cirrus HD-OCT, Carl Zeiss Meditec Inc., Dublin, CA, USA). Macular choroidal thickness was assessed using enhanced depth imaging. The average macular choroidal thickness was defined as the average value of three measurements: at the fovea and at the points located 1.5 mm in the nasal and temporal directions from the fovea. Generalized estimating equations were used to uncover factors affecting the average macular choroidal thickness. RESULTS: The average, superior and inferior quadrant retinal nerve fiber layer thicknesses were significantly thinner in the NTG group compared with the TAO and control groups (p < 0.001). The average macular choroidal thickness of the TAO group, NTG group and controls was 281.01 ± 60.06 µm, 241.66 ± 55.00 µm and 252.07 ± 55.05 µm, respectively, which were significantly different (p = 0.013). The subfoveal, nasal and temporal side choroidal thicknesses were significantly thinner in the NTG group compared with the TAO group (p = 0.014, 0.012 and 0.034, respectively). Subjects with TAO were associated with a thicker average macular choroidal thickness compared with the NTG group after adjusting for age, sex, spherical equivalent and intraocular pressure (β = 32.61, p = 0.017). CONCLUSIONS: Macular choroidal thickness was significantly thicker in patients with TAO compared with those with NTG. Further evaluation is required to determine if a thick choroid in subjects with TAO has any role in glaucomatous optic neuropathy.
Choroid* ; Graves Ophthalmopathy* ; Humans ; Intraocular Pressure ; Low Tension Glaucoma* ; Nerve Fibers ; Optic Nerve Diseases ; Retinaldehyde ; Tomography, Optical Coherence* ; Troleandomycin

PURPOSE: This study was conducted to identify and to functionally characterize genetic variants in ST3GAL5 and ST8SIA1 in Korean patients with thyroid-associated ophthalmopathy (TAO). MATERIALS AND METHODS: Genetic analyses were conducted using DNA samples from TAO patients (n=50) and healthy subjects (n=48) to identify TAO-specific genetic variants of ST3GAL5 or ST8SIA1. The effect of each genetic variant on the transcription or expression of these genes was examined. Additionally, correlations between functional haplotypes of ST3GAL5 or ST8SIA1 and clinical characteristics of the patients were investigated. RESULTS: Six promoter variants and one nonsynonymous variant of ST3GAL5 were identified, and four major promoter haplotypes were assembled. Additionally, three promoter variants and two major haplotypes of ST8SIA1 were identified. All ST3GAL5 and ST8SIA1 variants identified in TAO patients were also found in healthy controls. Promoter activity was significantly decreased in three promoter haplotypes of ST3GAL5 and increased in one promoter haplotype of ST8SIA1. Transcription factors activating protein-1, NKX3.1, and specificity protein 1 were revealed as having roles in transcriptional regulation of these haplotypes. The nonsynonymous variant of ST3GAL5, H104R, did not alter the expression of ST3GAL5. While no differences in clinical characteristics were detected in patients possessing the functional promoter haplotypes of ST3GAL5, exophthalmic values were significantly lower in patients with the ST8SIA1 haplotype, which showed a significant increase in promoter activity. CONCLUSION: These results from genotype-phenotype analysis might suggest a possible link between the ST8SIA1 functional promoter haplotype and the clinical severity of TAO. However, further studies with larger sample sizes are warranted.
DNA ; Exophthalmos ; Graves Ophthalmopathy* ; Haplotypes ; Healthy Volunteers ; Humans ; Korea ; Polymorphism, Single Nucleotide ; Sample Size ; Sensitivity and Specificity ; Sialyltransferases ; Transcription Factors ; Troleandomycin