Thyroid-associated Ophthalmopathy Research Articles

Detection of active and inactive phases of thyroid-associated ophthalmopathy using deep convolutional neural network

BackgroundThis study aimed to establish a deep learning system for detecting the active and inactive phases of thyroid-associated ophthalmopathy (TAO) using magnetic resonance imaging (MRI). This system could provide faster, more accurate, and more objective assessments across populations.MethodsA total of 160 MRI images of patients with TAO, who visited the Ophthalmology Clinic of the Ninth People’s Hospital, were retrospectively obtained for this study. Of these, 80% were used for training and validation, and 20% were used for testing. The deep learning system, based on deep convolutional neural network, was established to distinguish patients with active phase from those with inactive phase. The accuracy, precision, sensitivity, specificity, F1 score and area under the receiver operating characteristic curve were analyzed. Besides, visualization method was applied to explain the operation of the networks.ResultsNetwork A inherited from Visual Geometry Group network. The accuracy, specificity and sensitivity were 0.863±0.055, 0.896±0.042 and 0.750±0.136 respectively. Due to the recurring phenomenon of vanishing gradient during the training process of network A, we added parts of Residual Neural Network to build network B. After modification, network B improved the sensitivity (0.821±0.021) while maintaining a good accuracy (0.855±0.018) and a good specificity (0.865±0.021).ConclusionsThe deep convolutional neural network could automatically detect the activity of TAO from MRI images with strong robustness, less subjective judgment, and less measurement error. This system could standardize the diagnostic process and speed up the treatment decision making for TAO.

Proteomics of Tear in Inactive Thyroid-Associated Ophthalmopathy.

Thyroid-associated ophthalmopathy (TAO), one of the most common orbital diseases in adults, seriously reduces patients' quality of life. Although human tear proteomics identified many abnormal expressed proteins and proposed several pathogeneses of TAO, most of these studies focused on the active stage or mixed types in TAO. In this study we identified significantly changed proteins and preliminary revealed the potential signalling pathways and mechanisms of TAO with the late, inactive stage. Tears from TAO patients (n=6) with a CAS score < 3 and 6 control healthy subject were collected. The pooled tears were further fractionated using high pH reversed-phase chromatography, then submitted to LC-MS/MS and subsequent bioinformatic analysis. Proteomic profiling identified 107 significantly changed proteins between the inactive stage of TAO patients and healthy cases. Among these proteins, 62 were upregulated, and 45 were downregulated in TAO cases compared to healthy individuals. Enrichment analysis revealed that the immune system, cell cycle, metabolism (carbohydrate metabolism and metabolism of cofactors and vitamins), protein synthesis and degradation might play a vital role in the progress of inactive TAO. The present investigation represents the first proteomic tear study of TAO patients in the inactive stage. The results shed light on the differences between inactive TAO patients and healthy cases, thus enabling us to understand better the molecular mechanisms and potential targets for the treatment of inactive TAO.

Single-Cell RNA Sequencing Depicts the Local Cell Landscape in Thyroid-Associated Ophthalmopathy

There is a specific reactivity and characteristic remodeling of the periocular tissue in thyroid-associated ophthalmopathy (TAO). However, the cellular components responsible for these changes have not been sufficiently identified. Here, single-cell RNA sequencing was performed to characterize the transcriptional properties of cellular components in the orbital connective tissue in TAO patients. RASD1 expression in orbital fibroblasts defines lipofibroblastic phenotypes. These celltypes specifically expresses adipogenic differentiation associated genes. ACKR1+ Endothelial cells and adipose tissue macrophages are also involved in the disease process. Our study then highlights CD8+CD57+KLRG1+ cytotoxic T lymphoid cells with terminal differentiation phenotype as sources of sustained interferon-γ secretion. Moreover, cell–cell communication analysis revealed evidence of increased activity of the ACKR1/CXCL8 and TNFSF4/TNFRSF4 systems in TAO, which is consistent with stronger inflammatory cell infiltrating and fibrosis response. These cells in the orbital connective tissue constitute an orbital fibroblast-based cell-cell interaction network that regulates the pathogenesis of TAO.

Transdermal Delivery of Adipocyte Phospholipase A2 siRNA using Microneedles to Treat Thyroid Associated Ophthalmopathy-Related Proptosis

Thyroid associated ophthalmopathy (TAO) is an organ-specific autoimmune disease occurring in patients with thyroid disease. Patients with TAO-related proptosis is largely due to excessive orbital adipose tissue Adipocyte phospholipase A2 (AdPLA) is one of the most important regulatory factors in adipocyte lipolysis, which may be associated with TAO-related proptosis. Thus, silencing AdPLA by RNA interference may be beneficial for the treatment of TAO. In this study, we sought to evaluate the efficiency of two types of microneedles to deliver siRNAs for silencing AdPLA. Our results showed that AdPLA mRNA was up-regulated in the orbit adipose tissues from TAO patients. Silence of AdPLA by siRNA can reduce lipid accumulation in both human and mouse adipocyte cell lines. Moreover, silence effects of silicon microneedle array patch-based and injectable microneedle device-based siRNA administration were examined at the belly site of the mice, and injectable microneedle device showed higher knockdown efficiency than silicon microneedle array patch. This study sets the stage not only for future treatment of TAO-related proptosis using AdPLA siRNA, but also provides the foundation for targeted siRNA delivery by using microneedles.

A Case Report of Kearns-Sayre Syndrome With Thyroid-Associated Ophthalmopathy

A Case Report of Kearns-Sayre Syndrome With Thyroid-Associated Ophthalmopathy

Altered spontaneous brain activity patterns in dysthyroid optic neuropathy: a resting-state fMRI study.

This research investigates the characteristics of spontaneous brain activity in dysthyroid optic neuropathy patients using the regional homogeneity technique. Sixteen patients with dysthyroid optic neuropathy and 16 thyroid-associated ophthalmopathy patients without dysthyroid optic neuropathy were recruited, matched for weight, height, age, sex, and educational level. All participants underwent resting-state functional nuclear resonance imaging, and the characteristics of spontaneous brain activity were evaluated using the regional homogeneity technique. Each participant in the dysthyroid optic neuropathy group also completed the Hospital Anxiety and Depression scale. Receiver operating characteristic curves were used to compare brain activity between the two groups. Pearson correlation analysis evaluated the relationship between regional homogeneity and clinical manifestations in dysthyroid optic neuropathy patients. In addition, we analyzed the correlation between Hospital Anxiety and Depression scale and regional homogeneity. We found that the regional homogeneity values at the corpus callosum/cingulate gyrus and parietal lobe/middle frontal gyrus significantly decreased in dysthyroid optic neuropathy patients. Regional homogeneity values at the corpus callosum/cingulate gyrus and parietal lobe/middle frontal gyrus were negatively correlated with Hospital Anxiety and Depression scale and disease duration. It was found that the regional homogeneity signal values were significantly lower than in thyroid-associated ophthalmopathy without in dysthyroid optic neuropathy, which may indicate a risk of regional brain dysfunction in dysthyroid optic neuropathy. The results show that regional homogeneity has the potential for early diagnosis and prevent dysthyroid optic neuropathy. In addition, the findings suggest possible mechanisms of dysthyroid optic neuropathy optic nerve injury. They may provide a valuable basis for further research on the pathological mechanisms of dysthyroid optic neuropathy.

Assessment of Inflammatory and Morphological Changes in the Conjunctival Cells in Relationship to the Degree of ProptosiS in Thyroid – Associated Ophthalmopathy

Aim: to evaluate the inflammatory and morphological changes in conjunctival cells and the relationship to the degree of proptosis for helping early diagnosis of thyroid -associated eye disease. Subjects and methods: cross sectional observational prospective study that included 40 patients complain from proptosis of thyroid eye disease attended to Ain shams university, Cairo, from May 2019 to November 2020 with control 40 normal person. Exclusion criteria included patients with History of surgical correction of thyroid eye disease, auto immune disease, Previous Lasik surgery, recent Intraocular surgery, diabetic patients and patients under steroid or immune suppressive treatment. All patients were subjected to History taking of thyroid disease with laboratory investigations to assess the thyroid functions, visual acuity measurement, intraocular pressure, Hertel's exophthalmometry for measurement of the degree of proptosis, color vision using Ishihara’s test, Funds examination and Conjunctival impression cytology. Images were taken using an Olympus CX31 microscope fitted with an Olympus E-620 camera. Results: The degree of inflammation in impression cytology showed that most of thyroid eye disease group is in moderate degree (80%) 32 cases, while the rest (20%) is between mild degree of inflammation (15%) 6 cases and severe degree of inflammation (5%) 2 cases. No statistically significant relation found between degree of proptosis and severity of inflammation of right and left eye with p-value = 0.650 and 0.331 respectively. Morphologically, most of thyroid eye disease group showed stage 2 in impression cytology results (65%) 26 cases, while the rest (35%) between stage 4, 3, 1 (5%, 15%, 15%, respectively). Conclusion: Detection of inflammatory and morphological changes occurring in conjunctiva of cases with thyroid –associated Ophthalmopathy by impression cytology can help in early diagnosis of thyroid-associated Ophthalmopathy patients even before appearance of other eye symptoms.

Thyroid-Associated Ophthalmopathy: Preliminary Study Using T2 Mapping to Characterize Intraorbital Optic Nerve Changes Before Dysthyroid Optic Neuropathy

ObjectiveTo evaluate the performance of T2 mapping in detecting intraorbital optic nerve (ON) changes in patients with thyroid-associated ophthalmopathy (TAO) before the onset of dysthyroid optic neuropathy (DON). MethodsThirty-five patients with TAO and without DON (21 active, 14 inactive) and 21 healthy controls (HCs) were enrolled. Magnetic resonance imaging-derived parameters of T2 relaxation time (T2RT) at the intraorbital ON, extraocular muscle (EOM), orbital fat, exophthalmos, summed thickness of EOMs, orbital fat thickness, and clinical variables were compared. Correlations between T2RT at the ON and other variables were assessed. ResultsPatients with TAO showed significantly higher T2RTs at the intraorbital ON than HCs (P < .001). Patients with active TAO had significantly higher T2RTs than those with inactive TAO and HCs (P < .001). Differences between patients with inactive TAO and HCs were insignificant (P > .05/3). T2RT at the intraorbital ON was positively correlated with clinical activity score, modified NOSPECS score, T2RT at EOM, exophthalmos, and summed thickness of EOMs in the TAO group (P ≤ .003) and negatively correlated with visual acuity (P = .033) and visual field indices (P = .030) in patients with active TAO. A T2RT cutoff of 82.9 ms for the intraorbital ON distinguished active TAO and healthy eyes optimally (area under the curve, 0.800; sensitivity, 85.7%; specificity, 64.3%). ConclusionT2RT detects disturbance in the intraorbital ON in patients with TAO, especially active TAO, before DON develops. T2 mapping has a potential for noninvasive evaluation of ON changes in patients with TAO.

Elevated IL-38 inhibits IL-23R expression and IL-17A production in thyroid-associated ophthalmopathy

IL-23/IL-23R and PGE2/EP2+EP4 have been recognized as crucial signals that promote Th17 differentiation in many autoimmune diseases, including thyroid-associated ophthalmopathy (TAO). However, the interactive role of IL-23R in IL-23/Th17 signaling and PGE2/Th17 signaling has not been clarified in TAO. Furthermore, the role of IL-38, a novel anti-inflammatory cytokine, has not been explored in TAO. Thus, we aimed to investigate the roles of IL-23R and IL-38 in the pathogenesis of TAO. Activated peripheral blood mononuclear cells (PBMCs) were cultured with or without IL-23 and PGE2. The results showed that IL-23R and IL-17A were upregulated to different degrees and reached the highest levels with both stimuli, indicating that IL-23 induced PBMCs to secrete PGE2, which further boosted the proportion of IL-23R+CD4+T cells to promote IL-17A secretion. Pretreatment with antagonists aimed at EP2/EP4 receptors diminished PGE2-induced upregulation of IL-23R and IL-17A. IL-38 in TAO patients was increased. Activated orbital fibroblasts (OFs) and PBMCs were pretreated with different concentrations of IL-38. IL-23R and IL-17A expression in circulating PBMCs and IL-6 and IL-8 in resident OFs were suppressed by IL-38 at relatively low concentrations. Our findings suggest that the feedback loop of IL-23/IL-23R/PGE2/EP2+EP4/IL-23R/IL-17A plays a significant role in the pathogenesis of TAO and that IL-23R is one of the key targets. Increased IL-38 in TAO could not only inhibit the expression of IL-23R and IL-17A in PBMCs but also suppress inflammation in OFs. Therapies targeting IL-23R may be effective, and IL-38 could be a potential therapeutic approach for TAO.

Slit2 Regulation of Hyaluronan and Cytokine Synthesis in Fibrocytes in Thyroid-associated Ophthalmopathy

Slit2 Regulation of Hyaluronan and Cytokine Synthesis in Fibrocytes in Thyroid-associated Ophthalmopathy

Teprotumumab as a Novel Therapy for Thyroid-Associated Ophthalmopathy

Thyroid-associated ophthalmopathy (TAO) has remained a vexing and poorly managed autoimmune component of Graves’ disease where the tissues surrounding the eye and in the upper face become inflamed and undergo remodeling. This leads to substantial facial disfigurement while in its most severe forms, TAO can threaten eye sight. In this brief paper, I review some of the background investigation that has led to development of teprotumumab as the first and only US FDA approved medical therapy for TAO. This novel treatment was predicated on recognition that the insulin-like growth factor I receptor plays an important role in the pathogenesis of TAO. It is possible that a similar involvement of that receptor in other autoimmune disease may lead to additional indications for this and alternative insulin-like growth factor I receptor-inhibiting strategies.

Comparing isolated-check visual evoked potential, pattern visual evoked potential, and standard automated perimetry in dysthyroid optic neuropathy eyes

ObjectiveTo determine the diagnostic ability of isolated-check visual evoked potential (icVEP), pattern visual evoked potential (pVEP), and standard automated perimetry (SAP) between dysthyroid optic neuropathy (DON) and thyroid-associated ophthalmopathy (TAO) without DON (non-DON).MethodsThis is a case-control study, 49 bilateral patients (26 DON and 23 non-DON) were included. icVEP, pVEP, and SAP were conducted in all the subjects, icVEP parameters compared were signal-to-noise ratios (SNRs) under 8, 16, and 32% depth of modulation (DOM). pVEP parameters compared were amplitude and latency. SAP parameters were mean deviation (MD) and pattern standard deviation (PSD). The area under the receiver operating characteristic (ROC) curve (AUC), net reclassification index (NRI), integrated discrimination index (IDI), and decision curve analysis (DCA) were applied for analysis.ResultsIn icVEP, values of SNR in DON were significantly smaller than non-DON (p < 0.05). In pVEP, P100 latent time in DON was significantly larger than non-DON (p = 0.0026). In SAP, value of PSD in DON was larger than non-DON (p = 0.0006), and value of MD in DON was smaller (p = 0.0007). AUC, NRI, and IDI among the three tests were not significantly different. DCA showed that SNR of icVEP under 8% DOM was the farthest from the two extreme curves.ConclusionsicVEP, pVEP, and SAP have equal diagnostic capabilities to discern between DON and non-DON. In addition, icVEP may represent a significant ancillary diagnostic approach to DON detection, with more clinical benefit.

Peripapillary and macular vessel density in eyes with different phases of thyroid-associated ophthalmopathy

Objective: To analyze the characteristics of vessel density in the optic disc and macular area of patients with different phases of thyroid-associated ophthalmopathy (TAO) and their correlation with visual function. Methods: This case-control study was conducted at the Department of Ophthalmology of Peking Union Medical College Hospital between June 2019 and September 2019. TAO patients and healthy volunteers were included in the study. Patients with a clinical activity score greater than or equal to 3 points were categorized as active TAO. Dysthyroid optic neuropathy (DON) patients with a course less than 6 months were categorized as acute phase of DON, and those more than 6 months were in the chronic group. Healthy volunteers were in the control group. Each group included 12 subjects, with right eyes for analysis. There were 6 males and 6 females in each group. All participants underwent comprehensive ophthalmic examination including best corrected visual acuity and visual field examination for the mean defect (MD). Best corrected visual acuity was subsequently converted to logarithm of minimum angle of resolution (logMAR). Optical coherence tomography was used to measure the thickness of the retinal nerve fiber layer (RNFL) and retinal ganglion cell complex (GCC). Optical coherence tomography angiography was used to the peripapillary and macular vessel density. The differences in the vessel densities in the optic disc and macular area between groups and their correlation with different factors were analyzed. Analysis of variance, non-parametric Mann-Whitney U test and Spearman coefficient were conducted for statistical analysis. Results: There was no significant difference in age among the four groups (P>0.05). The logMAR of the acute DON group was 0.1 (0.0, 0.2), worse than the control group, which was 0.0 (0.0, 0.0) (U=114.000, P<0.05). The overall vessel densities of the optic disc in acute DON and chronic DON were significantly lower than the control group (54.70%±2.31% and 54.31%±3.65% vs. 57.54%±2.17%; t=3.104, 2.636; both P<0.05). The overall superficial vessel densities of the macular area in active TAO, acute DON and chronic DON were significantly lower than the control group (46.07%±3.06% and 42.26%±5.05% and 45.63%±3.87% vs. 49.34%±3.08%), and the differences were statistically significant (t=2.614, 4.147, 2.603; all P<0.05). There was no statistically significant difference in the size of the foveal avascular zone or the density of deep blood vessels in the macular area among the four groups (all P>0.05). In the active TAO period, there was no correlation between the MD value, RNFL thickness, GCC thickness and the vessel densities of the optic disc and macular area (all P>0.05). The vascular density of the whole layer of the optic disc in acute DON was negatively correlated with the MD value (r=-0.591, P<0.05) and positively correlated with the RNFL thickness and GCC thickness (r=0.595, 0.693; both P<0.05). In chronic DON, the overall capillary density of the optic disc was negatively correlated with the MD value (r=-0.673, P<0.05); the superficial overall blood vessel density of the macular area was positively correlated with the thickness of RNFL and GCC (r=0.732, 0.712;both P<0.01). Conclusions: In active TAO, only the blood supply to the superficial layer of the macular area is decreased. In the acute and chronic phases of DON, the blood supply to the superficial layer of the macular area and the optic disc is both reduced; the smaller the blood vessel density, the more severe the visual field defect, and the thinner the RNFL and GCC. (Chin J Ophthalmol, 2020, 56:824-831).

Histogram analysis of T2 mapping for detecting early involvement of extraocular muscles in patients with thyroid-associated ophthalmopathy

Using histogram analysis of T2 values to detect early involvement of extraocular muscles (EOMs) in patients with thyroid-associated ophthalmopathy (TAO). Five EOMs of each orbit were analyzed for 45 TAO patients and 22 healthy controls (HCs). Patients’ EOMs were grouped into involved or normal-appearing EOMs (NAEOMs). Histogram parameters and signal intensity ratios (SIRs) of EOMs were compared; receiver operating characteristic (ROC) curve analysis was performed to differentiate NAEOMs from EOMs of HCs. 24 patients were reassessed following immunosuppressive treatment. For SIRs, involved muscles showed higher values than those of NAEOMs and HCs (p < 0.05); there were no differences between NAEOMs and HCs (p = 0.26). Parameters of involved muscles showed no different from those of NAEOMs excluding 25th, 50th percentiles, and standard deviation (SD) (p < 0.05). NAEOMs displayed higher values of 90th, 95th percentiles, SD, skewness, inhomogeneity, and entropy than HCs (p < 0.05). ROC curve analysis of entropy yielded the best area under the ROC curve (AUC; 0.816) for differentiating NAEOMs and HCs. After treatment, histogram parameters including 5th, 75th, 90th, and 95th percentiles, SD, kurtosis, inhomogeneity, and entropy were reduced in NAEOMs (p < 0.05). T2 histogram analysis could detect early involvement of EOMs in TAO prior to detection on conventional orbital MRI.

Artificial intelligence CT screening model for thyroid-associated ophthalmopathy and tests under clinical conditions.

Thyroid-associated ophthalmopathy (TAO) might lead to blindness and orbital deformity. The early diagnosis and treatment are conducive to control disease progression, but currently, there is no effective screening method. The present study aimed to introduce an artificial intelligence (AI) model for screening and testing the model with TAO patients under clinical conditions. A total of 1435 computed tomography (CT) scans were obtained from the hospital. These CT scans were preprocessed by resampling and extracting the region of interest. CT from 193 TAO patients and 715 healthy individuals were adopted for three-dimensional (3D)-ResNet model training, and 49 TAO patients and 178 healthy people were adopted for external verification. Data from 150 TAO patients and 150 healthy people were utilized for application tests under clinical conditions, including non-inferiority experiments and diagnostic tests, respectively. In the external verification of the model, the area under the receiver operating characteristic (ROC) curve (AUC) was 0.919, indicating a satisfactory classification effect. The accuracy, sensitivity, and specificity were 0.87, 088, and 0.85, respectively. In non-inferiority experiments: the accuracy was 85.67% in the AI group and 84.33% in the resident group. The model passed both non-inferiority experiments (p = 0.001) and diagnostic test (the AI group sensitivity = 0.87 and specificity = 0.84%). A promising orbital CT-based TAO screening AI model was established and passed application tests under clinical conditions. This may provide a new TAO screening tool with further validation.

Clinical features and clinical course of thyroid-associated ophthalmopathy: a case series of 3620 Chinese cases.

To determine the clinical features and course of thyroid-associated ophthalmopathy (TAO) in a large sample of Chinese patients. We retrospectively identified a cohort of consecutive patients diagnosed with TAO at the West China Hospital from October 1, 2009 to October 1, 2019. We analysed clinical data from 3620 patients, including demographic data, clinical manifestations, ophthalmology examinations, and prognosis. TAO most frequently occurred with hyperthyroidism, with most patients developing TAO after thyroid disease (TD). The TAO phenotype was asymmetric in 375 (50.7%) euthyroid patients, 25 (27.8%) hypothyroid patients, and 314 (12.1%) hyperthyroid patients (p < 0.0001). The most frequent symptom was lid lag and the most commonly involved extraocular muscle was the inferior rectus. Severity assessment (NOSPECS score) and clinical activity assessment (Clinical Activity Scores, CAS) differed significantly between male and female patients (P < 0.000). The majority (88.8%) of patients had clinically inactive TAO, and only 3.2% of cases were sight-threatening. Regarding the clinical process, 75.5% of patients had an active phase time less than 12 months and 2.1% showed complete remission. TAO most commonly develops in females and is closely related to hyperthyroidism. Euthyroid TAO often has an asymmetric clinical phenotype. CAS combined with magnetic resonance imaging can improve the detection of TAO. NOSPECS scores should be slightly refined regarding the criteria for corneal involvement. Clinical management of TAO should be individualized according to CAS or NOSPECS assessments and a multidisciplinary approach is paramount. A minority of patients showed complete remission.

PDK2-enhanced glycolysis promotes fibroblast proliferation in thyroid-associated ophthalmopathy.

The study aimed to investigate the role of pyruvate dehydrogenase kinase (PDK) in regulating glycolysis and proliferation of perimysial orbital fibroblasts (pOFs) during the pathogenesis of thyroid-associated ophthalmopathy (TAO). EdU and BrdU incorporation assays were performed to examine cell proliferation. Lactate production and oxygen consumption assays were conducted to evaluate glycolysis. Real-time PCR was adapted to quantify PDK mRNA levels. Capillary Western immunoassay was adapted to quantify PDK2, Akt, pAkt308 and GAPDH in protein samples. The TAO pOFs exhibited stronger proliferation activity, higher intracellular lactate concentration, and lower oxygen consumption rate than the control pOFs. The PDK inhibitor dichloroacetic acid (DCA) dose-dependently suppressed the proliferation of both TAO and control pOFs. DCA reduced lactate production and promoted oxygen consumption in the TAO pOFs but showed no significant effects on glycolysis in the control pOFs. Among four PDK isotypes, PDK2 was overexpressed in the TAO pOFs. The potential PDK signaling mediator, cytoplasmic Akt, was more abundant in TAO pOFs than control pOFs. Knockdown of PDK2 resulted in lower lactate production, stronger oxygen consumption, weaker proliferation activity, and less cytoplasmic Akt in the TAO pOFs but showed no significant effects in the control pOFs. The Akt inhibitor MK2206 suppressed proliferation in both TAO and control pOFs, and lactate production was inhibited by MK2206 in the TAO OFs but not the control pOFs. To conclude, PDK2 overexpression enhances glycolysis and promotes proliferation via Akt signaling in the TAO pOFs. These findings yield insights that PDK2 is a potential therapeutic target for TAO treatment.

Tear proteomics of orbital decompression for disfiguring exophthalmos in inactive thyroid‑associated ophthalmopathy

The progress and achievements that have been made in tear proteomics in thyroid-associated ophthalmopathy (TAO) are critical for exploring the pathogenesis of TAO and investigating potential therapeutic targets. However, the tear proteomics of orbital decompression for disfiguring exophthalmos in inactive TAO have yet to be properly investigated. In the present study, orbital decompression was performed to repair disfiguring exophthalmos in patients with inactive TAO. Tears were collected before and after orbital decompression in patients with inactive TAO. Liquid chromatography with tandem mass spectrometry (LC-MS/MS) was performed to explore the changes in tear proteomics. Bioinformatics analyses were then employed to analyze the functions of the differentially expressed proteins (DEPs) identified by LC-MS/MS. The palpebral fissure height and exophthalmia area were significantly restored after 1 month of orbital decompression such that they approached the normal levels identified in healthy eyeballs. Among the 669 proteins identified by LC-MS/MS, 83 proteins were changed significantly between the preoperative and postoperative stages in inactive TAO patients and healthy control individuals. The DEPs were predicted to be involved in numerous signaling pathways. Bioinformatics analyses revealed that pathways associated with the immune system, metabolism, programmed cell death, vesicle-mediated transport, neuronal system and extracellular matrix organization may fulfill significant roles in orbital decompression in patients with inactive TAO. Taken together, these results provided a preliminary understanding of the mechanism of orbital decompression for disfiguring exophthalmos in inactive TAO patients.

Radiological Staging of Thyroid-Associated Ophthalmopathy: Comparison of T1 Mapping with Conventional MRI.

Background Accurate staging of patients with thyroid-associated ophthalmopathy (TAO) is crucial for clinical decision. Full cognition of pathologic changes and staging TAO using conventional T2-weighted imaging is still limited. Purpose To investigate the feasibility of using T1 mapping to evaluate changes of extraocular muscles (EOMs) in TAO patients, as well as to compare T1 mapping and conventional T2-weighted imaging in staging TAO. Materials and Methods Forty TAO patients were retrospectively enrolled. “Hot spot” and “cold spot” T1 relaxation times (T1RTHS and T1RTCS) of EOMs, as well as conventionally applied highest signal intensity ratio (SIR) of EOMs, were measured and compared between active and inactive groups. Results T1RTCS and SIR were significantly higher in active TAOs than in the inactive ones (P < 0.001), while T1RTHS was not (P=0.093). Meanwhile, T1RTCS and SIR were positively correlated with clinical activity score (r = 0.489, 0.540; P < 0.001). TIRTCS and SIR showed no significant area under curve for staging TAO (0.830 vs. 0.852; P=0.748). T1RTCS ≥ 1000 alone showed optimal staging specificity (90.0%), while integration of T1RTCS ≥ 1000 and SIR ≥ 2.9 demonstrated optimal staging efficiency and sensitivity (area under curve, 0.900; sensitivity, 86.0%). Conclusions Our findings suggest that the T1-mapping technique holds the potency to be utilized in TAO. The derived T1RTCS of EOMs, which may be associated with fat infiltration, could be a useful biomarker to stage the disease, serving added efficiency, sensitivity, and specificity to single usage of conventional SIR.

Evaluation of retinal and choroidal variations in thyroid-associated ophthalmopathy using optical coherence tomography angiography

BackgroundTo investigate the difference in retinal nerve fiber layer (RNFL) thickness, choroidal thickness (CT) and superficial retinal vessels between thyroid-associated ophthalmopathy (TAO) patients and healthy controls. To identify the potential influencing factors for these parameters and evaluate their diagnostic abilities in TAO.MethodsTwenty active TAO patients, 33 inactive TAO patients and 29 healthy participants were enrolled. TAO patients were divided according to the clinical activity score (CAS). RNFL thickness and CT were measured by HD-OCT, while foveal avascular zone (FAZ), vascular density and perfusion density were measured by optical coherence tomography angiography (OCTA). SPSS software was used for statistical analysis.ResultsActive TAO patients had thinner RNFL thickness than the other two groups (P < 0.001, P < 0.001). Both active and inactive TAO patients had significantly higher CT in the macular region (all P < 0.05). The FAZ area in the active TAO group was significantly larger than the other two groups (P = 0.045, P = 0.001). The inactive TAO group had significantly higher vascular density than the other two groups (all P < 0.05). With regard to the perfusion density, significant differences were observed in the temporal and inferior areas (P = 0.045, P = 0.001), as well as the average values (P = 0.032). The FAZ area was positively correlated with intraocular pressure (r = 0.274, P = 0.013), while it was negatively correlated with axial length (r = − 0.344, P = 0.002). The vascular density and perfusion density were not significantly correlated with different clinical variables (all P > 0.05). The AUC analysis indicated these parameters also exhibited a significant discriminatory power in TAO diagnosis.ConclusionsTAO patients had significant variations in RNFL thickness, choroidal thickness, FAZ area and superficial retinal vessels. These parameters appeared to be potential adjuncts in the evaluation of TAO patients.