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 intraocular pressure (IOP) measured using Goldmann-applanation tonometry (GAT) and Tonopen® tonometry and to evaluate the factors influencing the measurement difference in patients with thyroid-associated ophthalmopathy (TAO)-related restrictive strabismus. METHODS: In 50 eyes of 50 patients who were diagnosed with TAO, IOP measurements were taken using both GAT and a Tonopen® and were subsequently compared between the devices. Factors influencing the measurement difference between the devices were determined, including the restriction of eyeball movement, eyeball deviation, exophthalmometry, central corneal thickness, refractive errors, and blood thyroid hormone levels. RESULTS: In the TAO patients, the GAT-measured IOP was higher than for Tonopen® (16.1 ± 4.7 vs. 13.8 ± 4.5 mmHg, respectively, p < 0.001). As the restriction of vertical eyeball movement increased, the IOP difference between the devices also increased (p = 0.037). The absolute IOP difference between the devices was positively correlated with restrictions in vertical eyeball movement (p = 0.027), degree of vertical strabismus (p = 0.021), and central corneal thickness (p ≤ 0.031). CONCLUSIONS: In patients with TAO accompanying vertical eyeball movement restriction, potential errors in IOP measurements should be considered between the different IOP-measuring devices.
Graves Ophthalmopathy* ; Humans ; Intraocular Pressure* ; Manometry* ; Refractive Errors ; Strabismus* ; Thyroid Gland ; Troleandomycin

Ophthalmic plastic and reconstructive surgery combines the precision of ophthalmic microsurgery with plastic and reconstructive surgical principles, allowing for subspecialized care of the eyelid, orbital, and lacrimal system. A foundation in ophthalmology allows the oculoplastic surgeon's knowledge and skills to safely and successfully protect the globe while achieving good functional and aesthetic results. Oculoplasty emerged following World War II, in which a high rate of ophthalmic and oculoplastic trauma occurred. Following this, more structured and specialized studies dedicated to clinical and surgical management led to the development of a highly specific and rapidly growing sub-specialty dedicated to eyelid, lacrimal, and orbital care. Stem cell treatments in oculoplasty has been spanned a wide array of subfields, ranging from reconstruction of the eyelid to the generation of artificial lacrimal glands and oncological therapeutics. Tissue engineering represents the future of regenerative and reconstructive medicine, with significant potential applications in ophthalmic plastic surgery. Difficulty remains in disease modeling for various disorders, owing to genetic and functional variation across patients as well as the complexity of several diseases. Progressive advances in the understanding of the immunopathogenesis of diseases such as thyroid eye disease and lacrimal gland carcinoma continue to spur clinical trials utilizing targeted therapies to enhance treatment outcomes. Continued investigation of the molecular mechanisms of disease will expand potential treatments. In the future, public awareness and interest in the field of oculoplasty will further grow, and personalized and optimized treatment will become a cornerstone of modern medicine.
Eye Diseases ; Eyelids ; Graves Ophthalmopathy ; History, Modern 1601- ; Humans ; Lacrimal Apparatus ; Microsurgery ; Ophthalmology ; Orbit ; Plastics ; Stem Cells ; Surgery, Plastic ; Thyroid Gland ; Tissue Engineering ; World War II

Radiotherapy is used to treat not only malignant tumors but also benign inflammatory and hypertrophic diseases. Because of concerns about the potential hazards of irradiation, physicians in many countries, especially in North America, ruled radiotherapy out of medical practice for non-malignant diseases. Low-dose radiotherapy modulates the inflammatory response, providing an anti-inflammatory effect. Many researchers have reported low-dose radiotherapy efficacious for degenerative and inflammatory diseases. There are broad potential clinical indications for radiotherapy of non-malignant diseases. The general indications for radiotherapy for non-malignant disorders are acute/chronic painful degenerative diseases, such as chronic or acute painful osteoarthritic diseases of various joints; hypertrophic (hyperproliferative) disorders of soft tissues, such as early stages of Morbus Dupuytren and Ledderhose, keloids and pterygium; functional diseases, such as dysthyroid ophthalmopathy and arteriovenous malformations; and others, such as prophylaxis of heterotopic ossification. Radiotherapy for non-malignant disorders may be safely and effectively used, especially in older patients who suffered from these disorders and those who are reluctant to use other treatment options.
Acute Pain ; Arteriovenous Malformations ; Dupuytren Contracture ; Graves Ophthalmopathy ; Humans ; Joints ; Keloid ; North America ; Ossification, Heterotopic ; Osteoarthritis ; Pterygium ; Radiotherapy* ; Tendinopathy