Grave's Ophthalmopathy Research Articles

Genetic proxied IL-12 p40 inhibition and risk of Grave's ophthalmopathy: a mendelian randomization study

Genetic proxied IL-12 p40 inhibition and risk of Grave's ophthalmopathy: a mendelian randomization study

Non-coding RNA-mediated epigenetic alterations in Grave's ophthalmopathy: A scoping systematic review.

It is becoming more and more apparent that Grave's Ophthalmopathy (GO) pathogenesis may be aided by epigenetic processes such as DNA methylation modifications, histone tail covalent modifications, and non-coding RNA (ncRNA)-based epigenetic processes. In the present study, we aimed to focus more on the miRNAs rather than lncRNAs due to lack of investigations on these non-coding RNAs and their role in GO's pathogenesis. A six-stage methodology framework and the PRISMA recommendation were used to conduct this scoping review. A comprehensive search was conducted across seven databases to discover relevant papers published until February 2022. The data extraction separately, and quantitative and qualitative analyses were conducted. A total of 20 articles were found to meet inclusion criteria. According to the results, ncRNA were involved in the regulation of inflammation (miR-146a, LPAL2/miR-1287-5p axis, LINC01820:13/hsa miR-27b-3p axis, and ENST00000499452/hsa-miR-27a-3p axis), regulation of T cell functions (miR-146a/miR-183/miR-96), regulation of glycosaminoglycan aggregation and fibrosis (miR-146a/miR-21), glucocorticoid sensitivity (miR-224-5p), lipid accumulation and adipogenesis (miR-27a/miR-27b/miR-130a), oxidative stress and angiogenesis (miR-199a), and orbital fibroblast proliferation (miR-21/miR-146a/miR-155). Eleven miRNAs (miR-146a/miR-224-5p/miR-Let7d-5p/miR-96-5p/miR-301a-3p/miR-21-5p) were also indicated to have the capacity to be used as biomarkers. Regardless of the fact that there is significant documentation of ncRNA-mediated epigenetic dysfunction in GO, additional study is needed to thoroughly comprehend the epigenetic connections concerned in disease pathogenesis, paving the way for novel diagnostic and prognostic tools for epigenetic therapies among the patients.

ODP506 Posterior Staphyloma misdiagnosed as unilateral Grave's ophthalmopathy

Abstract 21 year old female presented to our clinic for management of "grave's disease" She was given diagnosis of Graves’ disease three years before presentation to our institution She was treated with PTU for 2-3 months then it was stopped On physical exam On physical exam she has a small diffused goiter Left eye was prominent without chemosis or lid lag Right eye was normal Decreased vision in the left eye, counting fingers only Thyroid function was normal Thyroid receptor antibody was negative Because of decline of vision and unilateral protrusion of Left eye she was referred to ophthalmology for further evaluation. MRI of the Orbits was ordered MRI revealed findings consistent with Staphyloma Staphyloma is a chronic eye condition which results from poor vision if left untreated and causes increase in AP diameter of eye which results in protrusion of eye which might be confused with grave's ophthalmopathy This diagnosis should be considered when patients present with unilateral ophthalmopathy, especially if there is significant decline in vision in the effected eye. Since she presented late in adulthood there is no treatment to improve her vision at this point From the thyroid standpoint she had negative thyroid antibodies and normal thyroid function Ultrasound of thyroid showed thyroid to be diffusely enlarged with homogenous texture Complete eye exam by ophthalmology is indicated in evaluation of ophthalmopathy especially in case of red flags like decreased vison or unilateral presentation With unilateral Ophthalmopathy MRI of the orbits should be part of the workup to exclude other etiologies such as retro-orbital tumors which may be confused with grave's ophthalmopathy. As evident in this case MRI revealed different diagnosis. Presentation: No date and time listed

ODP590 Combined Orbital Irradiation and Systemic Steroids in the Management of Progressive Thyroid Eye Disease

Abstract We present a case of a 62-year-old female with Multinodular Toxic Goiter who later developed Grave's Ophthalmopathy. She had an elevated baseline TRAb with an orbital MRI that showed bilateral proptosis with enlarged bilateral medial and lateral recti and extraocular muscles of the superior complex. She was initially treated with oral steroids which led to resolution of her visual complaints. However, due to recurrence of an active ophthalmopathy, she was subsequently given pulsing corticosteroid therapy. This was followed by radiotherapy due to minimal improvement in double vision. After completion of treatment, inflammatory ophthalmologic signs and symptoms were significantly improved. Radiotherapy in combination with glucocorticoids, particularly in the presence of diplopia or restriction of extraocular motility, should be considered in the management of active thyroid associated orbitopathy. Presentation: No date and time listed

Monitoring and Predicting Treatment Response of Extraocular Muscles in Grave's Orbitopathy by 99mTc-DTPA SPECT/CT.

Objective: To investigate single-photon emission computed tomography/computed tomography (SPECT/CT) for assessing inflammation in the extraocular muscles (EOMs) and predicting the therapeutic efficacy of periocular glucocorticoid therapy (PGT) for Grave's ophthalmopathy (GO).Materials and Methods: A total of 412 eyes from 206 patients with GO referred for 99mTc-DTPA orbital SPECT/CT were enrolled. Fourteen age- and gender-matched healthy controls (28 eyes) were included. The thickness and uptake ratio (UR) of four EOMs were derived from SPECT/CT. Eighty-six eyes from patients with GO patients received PGT. Changes in SPECT/CT parameters were evaluated between the pre- and post-treatment.Results: 195 eyes and 217 eyes were classified as active and inactive stages by clinical activity score (CAS). Values of the thickness and UR of each EOM, Tmax, and Umax were all significantly higher in the active GO than in the inactive GO and controls (p < 0.01). Among the 86 eyes (48 GO patients) included in the efficacy analysis, 56 eyes and 30 eyes were classified as responders and non-responders. Values of thicknesses and UR of each EOM, the maximum thickness (Tmax), and the maximum UR (Umax) all dropped following PGT in the responders (p < 0.01). Logistic regression analysis identified the Umax as an independent predictor for the responders (p < 0.01). Moreover, the Umax demonstrated incremental predictive value over clinical characters and CAS, as evidenced by the improved area under the curve (0.85 vs. 0.78) and global chi-square (34.12 vs. 18.1).Conclusion: 99mTc-DTPA SPECT/CT has the potential to assess inflammatory activity by detecting the involvement of EOMs in GO. Pre-treatment UR provides independent and incremental values for the prediction of PGT treatment response.

MicroRNAs and Autoimmune-Mediated Eye Diseases.

MicroRNAs (miRNAs) are evolutionarily conserved short non-coding RNAs that act at post-transcriptional regulation of gene expression by destroying target messenger RNA or inhibiting its translation. Recently, miRNAs have been identified as important regulators in autoimmunity. Aberrant expression and function of miRNAs can lead to dysfunction of immune system and mediate autoimmune disorders. Here, we summarize the roles of miRNAs that have been implicated in three representative ocular autoimmune disorders, including autoimmune uveitis, Grave’s ophthalmopathy, and Sjögren’s syndrome dry eye, and discuss the potential of miRNAs as biomarkers and therapeutic targets for the diagnosis and treatment of these diseases.

Surgical Outcomes of Endoscopic Medial Orbital Wall Decompression.

Retrospective chart review. The aim of this study was to evaluate the surgical outcomes and complications after endoscopic medial orbital wall decompression. From November 2016 to July 2017, we retrospectively reviewed 40 eyes of 20 patients who had undergone orbital decompression because of thyroid ophthalmopathy and other causes of proptosis.The eyes were classified into 2 groups: orbits which received only endoscopic medial wall decompression, and orbits which received both endoscopic medial wall decompression and transconjunctival inferior wall decompression. Statistical analysis was performed for all data generated. The preoperative and 3-month postoperative follow-up examinations for all patients were assessed by Hertel ophthalmometry, interpalpebral fissure, marginal reflex distance 1, Goldmann applanation tonometry, diplopia test, and Grave ophthalmopathy specific quality of life survey. Endoscopic medial wall decompression was performed in 17 of the total 40 eyes, and endoscopic medial wall decompression and transconjunctival inferior wall decompression was performed in the remaining 23 eyes. Proptosis improved from 20.4 ± 1.16 mm preoperatively to 16.8 ± 1.02 mm postoperatively in the endoscopic medial wall approach group, and from 20.8 ± 1.75 mm preoperatively to 14.8 ± 1.79 mm postoperatively in the endoscopic medial wall and transconjunctival inferior wall approach group. Postoperative complications occurred in 2 patients who displayed periphery diplopia, in the endoscopic medial wall and transconjunctival inferior wall approach group. A survey to assess the level of cosmetic satisfaction was significantly improved in both groups after surgery. Endoscopic medial wall decompression is an approach that achieves sufficient orbital decompression while minimizing complications.

Diffusion-weighted magnetic resonance imaging of extraocular muscles in patients with Grave's ophthalmopathy using turbo field echo with diffusion-sensitized driven-equilibrium preparation.

The purpose of this study was to correlate diffusivity of extraocular muscles, measured by three-dimensional turbo field echo (3DTFE) magnetic resonance (MR) imaging using diffusion-sensitized driven-equilibrium preparation, with their size and activity in patients with Grave's ophthalmopathy. Twenty-three patients with Grave's ophthalmopathy were included. There were 17 women and 6 men with a mean age of 55.8±12.6 (SD) years (range: 26-83 years). 3DTFE with diffusion-sensitized driven-equilibrium MR images were obtained with b-values of 0 and 500s/mm2. The apparent diffusion coefficient (ADC) of extraocular muscles was measured on coronal reformatted MR images. Signal intensities of extraocular muscles on conventional MR images were compared to those of normal-appearing white matter, and cross-sectional areas of the muscles were also measured. The clinical activity score was also evaluated. Statistical analyses were performed with Pearson correlation and Mann-Whitney U tests. On 3DTFE with diffusion-sensitized driven-equilibrium preparation, the mean ADC of the extraocular muscles was 2.23±0.37 (SD)×10-3mm2/s (range: 1.70×10-3-3.11×10-3mm2/s). There was a statistically significant moderate correlation between ADC and the size of the muscles (r=0.61). There were no statistically significant correlations between ADC and signal intensity on conventional MR and the clinical activity score. 3DTFE with diffusion-sensitized driven-equilibrium preparation technique allows quantifying diffusivity of extraocular muscles in patients with Grave's ophthalmopathy. The diffusivity of the extraocular muscles on 3DTFE with diffusion-sensitized driven-equilibrium preparation MR images moderately correlates with their size.

A multidisciplinary approach in the management of a challenging Grave's ophthalmopathy case

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Matrix expansion and syncytial aggregation of syndecan-1+ cells underpin villous atrophy in coeliac disease.

BackgroundWe studied the expression of sulphated glycosaminoglycans (GAGs) in coeliac disease (CD) mucosa, as they are critical determinants of tissue volume, which increases in active disease. We also examined mucosal expression of IL-6, which stimulates excess GAG synthesis in disorders such as Grave's ophthalmopathy.MethodsWe stained archival jejunal biopsies from 5 children with CD at diagnosis, on gluten-free diet and challenge for sulphated GAGs. We then examined duodenal biopsies from 9 children with CD compared to 9 histological normal controls, staining for sulphated GAGs, heparan sulphate proteoglycans (HSPG), short-chain HSPG (Δ-HSPG) and the proteoglycan syndecan-1 (CD138), which is expressed on epithelium and plasma cells. We confirmed findings with a second monoclonal in another 12 coeliac children. We determined mucosal IL-6 expression by immunohistochemistry and PCR in 9 further cases and controls, and used quantitative real time PCR for other Th17 pathway cytokines in an additional 10 cases and controls.ResultsIn CD, HSPG expression was lost in the epithelial compartment but contrastingly maintained within an expanded lamina propria. Within the upper lamina propria, clusters of syndecan-1+ plasma cells formed extensive syncytial sheets, comprising adherent plasma cells, lysed cells with punctate cytoplasmic staining and shed syndecan ectodomains. A dense infiltrate of IL-6+ mononuclear cells was detected in active coeliac disease, also localised to the upper lamina propria, with significantly increased mRNA expression of IL-6 and IL-17A but not IL-23 p19.ConclusionsMatrix expansion, through syndecan-1+ cell recruitment and lamina propria GAG increase, underpins villous atrophy in coeliac disease. The syndecan-1+ cell syncytia and excess GAG production recapitulate elements of the invertebrate encapsulation reaction, itself dependent on insect transglutaminase and glutaminated early response proteins. As in other matrix expansion disorders, IL-6 is upregulated and represents a logical target for immunotherapy in patients with coeliac disease refractory to gluten-free diet.

Rituximab therapy in steroid-resistant severe hypothyroid Grave′s ophthalmopathy

Association of Grave's ophthalmopathy with hyperthyroidism is well known, and it has also been reported in euthyroid or hypothyroid autoimmune thyroiditis, which rarely requires treatment. Here, we report a case of bilaterally symmetrical severe corticosteroid-resistant hypothyroid Grave's ophthalmopathy successfully treated with rituximab.

Assessing Graves’ ophthalmopathy-specific quality of life in Korean patients

To investigate the clinical significance of Grave's ophthalmopathy-specific quality of life (GO-QOL) in Korean patients. A cross-sectional study was conducted at the Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Korea, on 98 consecutive Grave's ophthalmopathy (GO) patients. The GO-QOL survey provided by Terwee and colleagues and suggested by the European group on Graves' orbitopathy (EUGOGO) was translated into Korean language and distributed to study participants. Clinical severity was judged by scores of the modified NOSPECS classification, and inflammatory activity was measured by a seven-point scale of clinical activity score (CAS). The mean GO-QOL scores were 73.7 (standard deviation (SD), 26) for visual functioning, 61.9 (SD 26) for appearance, and 67.8 for total quality of life (QOL; SD 22). The worse QOL scores for each part were significantly associated with the higher modified NOSPECS score and CAS after adjusting for confounders such as age and sex (P<0.05, respectively). In particular, decreased QOL scores for visual function were significantly correlated with a higher grade of extraocular muscle involvement (P<0.05). Lower QOL scores for appearance were associated with more severe soft-tissue involvement and proptosis (P<0.05, respectively). GO-QOL suggested by EUGOGO showed correlation with objective clinical parameters. GO-QOL can be a simple and effective tool in the evaluation of the clinical and psychological illness of GO patients.

Long-term Result of Fat Orbital Decompression

Purpose: To evaluate the long-term results of orbital fat decompression with or without lateral wall decompression in Grave's ophthalmopathy. Methods: The authors studied retrospectively the 24 thyroid-related orbitopathy patients (32 eyes) who had undergone fat removal decompression or combined orbital decompression (lateral wall decompression with fat removal) based on average exophthalmometric values for Koreans. The patients were followed for over six months postoperatively, from December 2000 to December 2008. Results: The average amount of exophthalmos reduction was 4.132.60 mm in the fat removal decompression group and 5.792.02 mm in the combined orbital decompression group, respectively (p

Reversal of optic neuropathy secondary to voluntary globe luxation

Luxation of the globe is rare in the general population and may be spontaneous, voluntary, or traumatic. Spontaneous or voluntary globe luxation results from shallow orbit, floppy eyelids, lax orbital ligaments, backward displacement of orbital septum, or proptotic eyes due to orbital tumors or infiltrative processes, as in Grave's ophthalmopathy. The authors report a case with unilateral voluntary globe luxation presented with unilateral progressive visual loss.

Environmental tobacco smoke exposure and eye disease

Aim:To undertake a systematic review of the literature on the effect of environmental tobacco smoke (ETS) and eye disease.Methods:Medline (1950–January Week 2 2007), EMBASE (1980 to 2007 Week 07), SCOPUS...

Stereotactic Radiotherapy for Unilateral Orbital Lymphoma and Orbital Pseudo-Tumors: A Planning Study

Orbital lymphoma and Grave's ophthalmopathy (GO) are successfully treated with radiation therapy. The lenses are blocked to prevent cataract formation. However, blocking of the lens by traditional methods can be difficult for tumors located anteriorly and extending into the retrobulbar space. We present a series of 3 patients with orbital lymphoma and 1 with GO treated with stereotactic intensity modulated radiation therapy (IMRT) to spare normal structures, including the lens. Three patients with orbital lymphomas and 1 with unilateral GO were treated with IMRT using a linac with stereotactic capabilities. Avoidance structures included the ipsilateral lens and globe, the contralateral lens and globe, the chiasm, and the brainstem. Two patients with orbital lymphoma were treated with 24 Gy in 12 fractions, and 1 patient was treated with 30.6 Gy in 17 fractions. The patient with GO was treated with 20 Gy in 10 fractions. The dosimetry was analyzed to determine the dose to normal tissues. Patient follow-up varies between 8 and 24 months. The mean minimal dose to the ipsilateral lens was 13.6% of the total dose, the mean maximal dose was 33.5%, and the mean median dose was 19.3%. The mean median dose to the contralateral eye was 1.1% of the total dose. The mean median dose to the chiasm was 14.9% of the total dose. The mean median dose to the brainstem was 1.9% of the total dose. No cataracts or other complications were noted in the 4 patients treated with this technique so far. IMRT gives a more conformal treatment to the orbital contents while sparing normal tissues such as the ipsilateral lens and adjacent critical structures. This should result in fewer complications such as cataracts.

Grave's Eye Disease Developing Following Radioiodine Treatment for Toxic Nodular Goitre

The development of Grave's ophthalmopathy (GO) following radioiodine (RI) treatment for Grave's thyrotoxicosis, though controversial, is well described. The development of ophthalmopathy following RI treatment for toxic nodular goitre is much less recognised. We report a 49 year-old female patient who developed thyrotoxicosis and GO after receiving RI treatment for toxic nodular goitre and we also review the relevant literature.

O.226 Computer assisted orbital decompression for Grave's ophthalmopathy

O.226 Computer assisted orbital decompression for Grave's ophthalmopathy

Die Behandlung der Oberlidretraktion bei endokriner Orbitopathie durch die Rücklagerung des Levatorkomplexes

The chronic stage in Grave's orbitopathy is characterised by fibrotic changes within the orbital soft tissues, especially the extraocular muscles. Retraction of the eyelids is a common clinical feature of this phenomenon. To solve this problem several techniques for lengthening the upper eyelid have been described with variable rates of success. In this report we describe our modified Harvey's technique for the correction of upper eyelid retraction which includes a complete recession of the Muller's muscle/levator complex from the tarsal plate without the interposition of a spacer. Finally only the skin and the superficial orbicularis muscle are sutured. We also report about our results with this procedure. 8 patients (1 male, 7 female) with lid retraction in Grave's ophthalmopathy were recorded who had undergone the modified lengthening technique by an external approach between 2001 and 2004. Four patients underwent a bilateral procedure and 1 patient showed a significant under-correction, necessitating reoperation. So a total of 13 procedures were included in this follow-up study. Beside the common ophthalmological examination, special interest was put in the difference of the two eyelid apertures in primary position pre- and postoperatively. Within a follow-up period of at least 3 months we recorded an averaged lengthening of the upper eyelid of 3.1 mm. The difference of the two eyelid apertures in primary position improved from 2.2 mm preoperatively to 1.0 mm postoperatively. Only 1 patient needed reoperation because of a significant under-correction. There were no late over-corrections observed. The modified Harvey's technique to lengthen the upper eyelid is a safe and effective method to reduce upper eyelid retraction in Grave's disease. An eventually required orbital decompression or extraocular muscle surgery has to be done before the lid surgery.

Grave's ophthalmopathy long-term results efficiency in 33 patients

Grave's ophthalmopathy long-term results efficiency in 33 patients