Supraorbital Neuralgia Associated With Thyroid Eye Disease.

Thyroid eye disease (TED) is an autoimmune disorder causing inflammation, expansion, and fibrosis of orbital fat, muscle, and lacrimal gland. This article reviews the different methods of grading severity and activity of TED and focuses on the VISA Classification for disease evaluation and planning management. Accurate evaluation of the clinical features of TED is essential for early diagnosis, identification of high-risk disease, planning medical and surgical intervention, and assessing response to therapy. Evaluation of the activity and severity of TED is based on a number of clinical features: appearance and exposure, periorbital tissue inflammation and congestion, restricted ocular motility and strabismus, and dysthyroid optic neuropathy. The authors review these clinical features in relation to disease activity and severity. Several classification systems have been devised to grade severity of these clinical manifestations. These include the NO SPECS Classification, the European Group on Graves Orbitopathy severity scale, the Clinical Activity Score of Mourits, and the VISA Classification as outlined here. The authors compare and contrast these evaluation schemes. An accurate clinical assessment of TED, including grading of disease severity and activity, is necessary for early diagnosis, recognition of those cases likely to develop more serious complications, and appropriate management planning. The VISA Classification grades both disease severity and activity using subjective and objective inputs. It organizes the clinical features of TED into 4 discrete groupings: V (vision, dysthyroid optic neuropathy); I (inflammation, congestion); S (strabismus, motility restriction); A (appearance, exposure). The layout follows the usual sequence of the eye examination and facilitates comparison of measurements between visits and data collation for research.

Background: Thyroid eye disease (TED) is a sight-threatening autoimmune disease with cigarette smoking as one of the key risk factors. Cigarette smoking affects both the severity of TED and the patient's response to medication. However, the underlying pathogenic mechanisms of smoking in TED remain unclear. Methods: Orbital fibroblasts (OFs) were extracted from patients with TED and non-TED controls, and treated with cigarette smoking extract (CSE). Luminex assays and Western blots were employed to examine inflammatory status and pathological phenotypes of OFs. A specific reactive oxygen species (ROS) probe was used to evaluate oxidative stress levels. RNA-sequencing of CSE-treated OFs was used to analyze differentially expressed genes. Immunofluorescence and RNA-sequencing were used to examine the expression of receptor for advanced glycation end products (RAGE) signaling molecules in patients. Small interfering RNA sequences and a RAGE-specific inhibitor were employed to investigate the effects of RAGE blockade on cigarette smoking-related pathological phenotypes. To validate our findings invivo, we generated an adenovirus-induced TED mouse model with exposure to cigarette smoke. Results: Exposure to CSE resulted in an inflammatory phenotype of OFs together with higher levels of oxidative stress. OFs exposed to CSE presented susceptibility to transforming growth factor-β-induced myofibroblast differentiation, and 15-D-PGJ2-induced adipocyte differentiation, indicating pro-fibrotic and pro-adipogenic phenotypes. RNA-sequencing of CSE-treated OFs revealed upregulation of RAGE signaling molecules. TED patients with smoking history also exhibited higher levels of RAGE signaling, both in the orbit and peripheral blood, compared with non-smoking patients. Enhancement of inflammatory status was associated with activation of the ROS-nuclear factor-kappa B pathway downstream of RAGE. RAGE gene interference or administration of RAGE inhibitor effectively mitigated cigarette smoking-related pathological changes in OFs. Disrupting RAGE signaling in TED mice efficiently ameliorated smoking-induced disease progression invivo. Conclusions: Cigarette smoking-relevant TED progression was linked with RAGE signaling activation, leading to the exacerbation of orbital inflammation and tissue-remodeling, including fibrosis and adipogenesis. Our findings demonstrate that cigarette smoke exposure affects the biological characteristics of TED-derived OFs and supports RAGE as a promising therapeutic target for the management of patients with TED and smoking habits.

The Thyrotropin receptor antibody (TRAb) is the main driver of Graves' disease (GD) and its most common extra-thyroidal manifestation: thyroid eye disease (TED). Though key to diagnosis, it has not been used routinely as a marker of disease activity or to guide treatment. Here we demonstrate, through a retrospective review of 105 patients with TED, that serial TRAb levels vary with time, correlate with disease activity and are affected by smoking and endocrine control. Such serial measurements can guide the modern management of thyroid eye disease, helping to prevent the more serious manifestations. We show that surgical thyroidectomy is associated with a reduction in antibody levels and a reduced rate of TED reactivation when compared to radio-iodine ablation where the stimulating antigen is not removed. This provides a molecular explanation for epidemiological studies showing radio-ablation being associated with an increased risk of orbitopathy. To demonstrate the effect of our clinical approach on a patient population, we then compared the incidence and severity of TED in a clinic in a period before and after the introduction of serial TRAb measurements. Despite an increase in disease incidence and severity at presentation over the two-decade study period, our approach saw a significant reduction in the need for surgical intervention for this orbital disorder.

Orbital decompression is an established procedure for the management of exophthalmos and visual rehabilitation from optic neuropathy in cases of thyroid eye disease. Numerous procedures for removal of orbital bony wall, fat or a combination of these for a variety of indications in different stages of the disease have been well reported in the medical literature. However, the relative effectiveness and safety of these procedures in relation to the various indications remains unclear. To review current published evidence for the effectiveness of surgical orbital decompression for disfiguring proptosis in adult thyroid eye disease and summa rise information on possible complications and the quality of life from the studies identified. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2011, Issue 10), MEDLINE (January 1950 to October 2011), EMBASE (January 1980 to October 2011), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com) and ClinicalTrials.gov (http://clinicaltrials.gov). There were no date or language restrictions in the electronic searches for trials. The electronic databases were last searched on 6 October 2011. We searched oculoplastic textbooks, conference proceedings from the European and American Society of Ophthalmic Plastic and Reconstructive Surgery (ESOPRS, ASOPRS), European Ophthalmological Society (SOE), the Association for Research in Vision and Ophthalmology (ARVO) and American Academy of Ophthalmology (AAO) for the years 2000 to 2009 to identify relevant data. We attempted to contact researchers who are active in this field for information about further published or unpublished studies. We included randomised controlled trials (RCTs) with no restriction on date or language comparing two or more surgical methods for orbital decompression with removal of bony wall, orbital fat or a combination of both for disfiguring proptosis or comparison of surgical techniques with any form of medical decompression. Each review author independently assessed study abstracts identified from the electronic and manual searches. Author analysis was then compared and full papers for appropriate studies were obtained according to the inclusion criteria. Disagreements between the authors were resolved by discussion. We identified two randomised trials eligible for inclusion in the review. There was significant variability between the trials for interventions, methodology and outcome measures and therefore meta-analysis was not performed. One study suggested that the transantral approach and endoscopic transnasal technique had similar effects in reducing exophthalmos but that the endoscopic approach may be safer, relating to fewer complications. This study had short-term follow-up and lacked information on our primary outcome (success or failure of treatment). The second study provided evidence that intravenous steroids may be superior to primary surgical decompression in the management of compressive optic neuropathy requiring less secondary surgical procedures, although it relates more frequently to transient side effects. This study was weakened by a small sample size. Until more credible evidence is available recommendations as to best treatment cannot be reliably made. A single study showed that the transantral approach for orbital decompression was related to more complications than the endoscopic transnasal technique which is preferred by Ear, Nose and Throat (ENT) surgeons, usually as an adjunctive procedure. Intravenous steroids were reported in a single trial to be the most efficient intervention for dysthyroid optic neuropathy. The majority of published literature on orbital decompression for thyroid eye disease consists of retrospective, cohort, or case series studies. Although these provide useful descriptive information, clarification is required to show the relative effectiveness of each intervention for various indications.The two RCTs reviewed are not robust enough to provide credible evidence to our understanding of current decompressive surgery and to support recommendations for clinical practice. There is evidence from currently available uncontrolled studies that removal of the medial and lateral wall (balanced decompression) with or without fat removal may be the most effective surgical method related to only a few complications.There is a clear need for randomised studies evaluating the balanced two-wall, three-wall and orbital fat decompression techniques. Comparison with other surgical techniques for orbital decompression or with immunosuppression in cases of compressive optic neuropathy would also be important. These studies should primarily address the reduction of exophthalmos, disease severity, complication rates, quality of life and cost of the intervention.

This article summarizes the results of research on the morphological and functional features of different types of orbital bone decompression in thyroid eye disease (TED) and presents an analysis of surgical anatomy of the lateral orbital wall in the context of performing deep lateral bone decompression of the orbit was carried out. The study includes an analysis of the results of orbital bone decompression with resection of the greater wing of the sphenoid bone using ultrasound osteodestructor in comparison with osteodestruction using a high-speed drill, description of transethmoidal orbital decompression with endonasal access both as a single method of surgical treatment of TED and in combination with lateral bone decompression of the orbit, including the advantages and disadvantages of the method, and presents a morphological description of the pathological changes in the medial orbital wall bone fragments obtained during endonasal transethmoidal orbital decompression in patients with TED.

Purpose To report the clinical features, ultrasound biomicroscopic features, and management outcome in patients presenting with thyroid eye disease (TED) and lower eyelid entropion. Methods Retrospective interventional case review of patients with TED presenting with lower eyelid entropion over a 12-year period. Results Five patients (eight eyes) of a total of 1211 presented with lower eyelid entropion as one of the presenting signs of TED (0.41%). The average age was 28.8 years (18–39 years), and three patients were males. Three had systemic hyperthyroidism, and two were euthyroid. Four (80%) had bilateral TED, three had inactive disease, and two were active. The average Hertel exophthalmometry reading was 24.6 mm. All patients had upper lid retraction. Four (80%) had concomitant lower eyelid retraction. Entropion was medial in five and complete in three eyes. Symptomatic corneal epitheliopathy was noted in four eyes. UBM was performed in four eyes which showed a thickened middle lamella. In four eyes (three patients), the entropion was managed conservatively as the patient was not contemplating surgery for proptosis. In the remaining four eyes (two patients) orbital decompression was performed and the lower eyelid retractor release corrected the symptomatic entropion. The average follow-up was 11.6 months (range 1–30). Conclusion Lower eyelid entropion is a rare presenting sign in TED. The mechanism is multifactorial and could be caused by the thickened and fibrosed lower lid retractors, as demonstrated by UBM. Young age and globe projection may play a role. Decompression approaches that involve lower lid retractor release correct the entropion.

To review and summarize a comprehensive synopsis of surgery of the eyelid in thyroid eye disease (TED). A PubMed search for specific eyelid manifestations of TED was performed. Studies reporting surgical management of these were reviewed, along with the author's own experience. The most common eyelid manifestations of TED include eyelid retraction, blepharoptosis, entropion, and epiblepharon, with most of them requiring surgical intervention. The correction of eyelid retraction has received maximum attention, with several surgical techniques that have stood the test of time. Blepharoptosis in TED that requires surgical intervention is usually aponeurotic. Entropion and Epiblepharon are rare in TED, and may resolve spontaneously, or following orbital decompression. Retraction is the commonest eyelid manifestation of TED, with multiple surgical options available for its correction. Blepharoptosis, entropion, and epiblepharon are rare eyelid findings in TED, that may occasionally require surgical correction.

Thyroid eye disease (TED) is the most common orbital disorder in adults and significantly affects patient health. Orbital decompression surgery is an important treatment option. Central retinal artery occlusion (CRAO) after orbital medial wall decompression is rare in patients with TED. Therefore, the earlier the identification and treatment, the more likely it is to reduce visual impairment. This paper examines a case of CRAO occurring postoperatively in a patient who underwent medial wall orbital decompression for TED. Central retinal artery occlusion. During the operation, the pupil was dilated, and eye massage and peribulbal injection of atropine were performed immediately. Fundus fluorescein angiography suggested the possibility of CRAO. Intravenous methylprednisolone 1000 mg, mannitol 50 g, ginkgo biloba extract 20 mL, nimodipine 20 mg tid, cobamamide 0.5 mg tid, and oral citicoline 0.2 g tid, along with periocular injection of atropine and hyperbaric oxygen therapy were also administered. Fifteen days after onset, the patient's retinal edema and retinal blood perfusion greatly improved. The patient's visual acuity recovered from counting fingers to 0.6. Retinal vascular obstruction is a serious threat to vision; therefore, early detection and treatment are very important.

BackgroundOrbital decompression is an essential tool for reducing proptosis in thyroid eye disease (TED), yet the impact of surgical approach and preoperative factors on outcomes remains uncertain.ObjectiveTo compare proptosis reduction following different orbital decompression techniques, identify additional risk factors that may play a role in surgical orbital decompression outcomes, and develop clinical decision-making recommendations based on these results.MethodsA retrospective analysis was performed on TED patients who underwent endoscopic medial wall, orbital floor, and/or open lateral wall decompression. We evaluated the influence of preoperative comorbidities, anatomic and laboratory values, and surgical approach on postdecompression Hertel exophthalmometry outcomes.ResultsAnalysis encompassed 130 orbits from 80 patients, 83% female, 48 with preoperative diplopia, and mean age of 54.4 years. Preoperative Hertel measurement was predictive of extent of proptosis reduction (P < .0001), indicating that higher initial Hertel measurement predicts greater absolute reduction following surgical intervention. Surgical technique correlated with outcome on univariate analysis (P = .04), but not multivariate (P = .13) analyses. When categorized into preoperative Hertel ranges, combined endoscopic medial and open lateral wall decompression resulted in mean proptosis reduction of 3.13 mm for range 20.01 to 24 mm and 3.85 mm for range 24.01 to 28 mm. Three-wall decompression resulted in mean proptosis reduction of 2.49 mm for and 3.84 mm for these ranges, respectively. Variables such as smoking, body mass index, orbital wall height, and TRAb level, did not affect outcomes. Nine patients had new onset diplopia.ConclusionsPreoperative Hertel exophthalmometry is the strongest predictor of proptosis reduction following orbital decompression in TED. Surgical technique appears to be less impactful on outcome than expected. Surgical decision making should be individualized based on patient goals; these findings can be used to achieve proptosis reduction and limit the risk of new onset diplopia.

To evaluate progressive changes in retinal nerve fibre layer (RNFL), ganglion cell layer/inner plexiform layer (GCL/IPL) and visual function in thyroid eye disease (TED) patients with and without orbital decompression. Sixty TED patients (105 eyes) were included. All patients were divided into mild, moderate-to-severe and dysthyroid optic neuropathy (DON) groups. Orbital decompression was performed in the moderate-to-severe and DON groups. Optic coherence tomography (OCT), visual field (VF) and best-corrected visual acuity (BCVA) were performed pre- and postoperatively. Preoperative follow-up was performed in the mild group and in part of the moderate-to-severe and DON groups. After decompression, the thickness of GCL/IPL and RNFL significantly decreased in DON group (p < 0.05), with varying degrees of decrease in eyes with optic disc swelling, atrophy and normal appearance. The mean GCL/IPL thickness significantly decreased in moderate-to-severe group (p < 0.05), the mean RNFL thickness slightly decreased with no statistical significance (p = 0.07). During the preoperative follow-ups, the mean GCL/IPL thickness significantly decreased (p = 0.04), whereas the mean RNFL thickness tended to increase (p = 0.13) in DON group. The thickness of GCL/IPL and RNFL did not change significantly in the mild and moderate-to-severe groups (p > 0.05). BCVA and VF did not change significantly in any group (p > 0.05) preoperatively. Swelling and degeneration of retinal ganglion cells (RGCs) may coexist in DON eyes, leading to continuous changes in the RNFL and GCL/IPL thickness either before or after decompression. Slight swelling and degeneration of RGCs may exist in moderate-to-severe TED eyes, although OCT measurements and visual functions remain stable before surgery.

Rituximab in the Treatment of Thyroid Eye Disease: A Review

The advent of endoscopic sinus surgery has created an exciting interface between rhinology and ophthalmology in the area of orbital and optic nerve decompression Objectives: (1) To study the utilization of open versus endoscopic medial orbital decompression based on geography and indication, (2) to describe the demographics of the patient populations who underwent these different techniques, and (3) to compare outcomes, including mean charges and operating room (OR) times Methods: Cases identified by Current Procedural and Terminology codes were extracted from the California, Florida, Maryland, and New York State Ambulatory Surgery Databases from 2009 to 2011. Patient demographics, diagnoses, mean charge, and OR time were compared. A total of 1009 patients underwent orbital decompression; 93.0% of cases involved the medial wall only; 22.9% of medial decompressions were performed endoscopically, 74.5% were open, and 2.6% were via combined approach. Eighty percent of patients had thyroid eye disease. Analyses adjusted for sex, age, race, state, and diagnosis found that surgeries for infection (N = 47) were more likely to be performed endoscopically compared with procedures for other diagnoses (N = 962) (odds ratio 5.27 [2.67-10.40], p < 0.001). Patients in Florida were more likely to undergo endoscopic decompression compared with patients in California (odds ratio 2.35 [1.42-3.62]). The difference in median charge for endoscopic ($13,119) versus open ($11,291; p = 0.085) procedures was not significant on bivariate analysis but was significant on multivariate analysis (p = 0.04). The median OR time for open procedures was, on average, 33 minutes shorter (endoscopic, 132 minutes; open, 98 minutes; p ≤ 0.001) on bivariate analysis but was not significantly different when controlling for covariables (p = 0.08). In the study sample, endoscopic orbital decompression was performed in 22.9% of patients, with significant variation in surgical technique based on geography and indication. Procedures that used endoscopic compared with open decompression techniques had no significant difference in charge on bivariate analysis. The OR time for open procedures was shorter on bivariate but not on multivariate analysis. Further research is required regarding the relative effectiveness of open versus endoscopic surgical techniques for various indications.

Purpose. To evaluate the influence of the thickness of the lateral orbital wall on the technique of access performance during lateral orbital wall decompression. Material and methods. A comparative analysis of the thickness of the lateral orbital wall in the projection of the sphenozygomatic suture (527 orbits, 350 patients) who underwent lateral wall rim-sparing orbital decompression by ab externo access was performed. 1st group included 469 orbits (83% of patients) with one-stage primary bone window formation. The 2nd group included 58 orbits (11% of patients) in which the outer part of the bone fragment was broken off during the bone window formation. The distance between the sphenozygomatic suture and the orbital rim in both groups was measured. The parameters of the lateral orbital wall bone fragment extracted «en bloc» at the stage of bone window formation were determined. Results. The reliable correlation between the thickness of lateral orbital wall in the projection of the speno-zygomatic suture and the risk of complicated bone window formation was revealed. In both groups there was no significant correlation between the bone window formation and the presence of the spheno-zygomatic suture displaced in the caudal direction, determined by the distance between the spheno-zygomatic suture and the orbital rim in the central part of the lateral orbital wall. No direct correlation between the parameters of the removed bone fragment and the lateral orbital wall thickness was revealed. Conclusion. The thickness of the lateral orbital wall of 6.02±1.45 mm in the region of the spheno-zygomatic suture directly correlates with a high risk of complicated formation of the primary bone window at lateral orbital wall decompression. Key words: thyroid eye disease, bony orbital decompression, lateral orbital wall, sphenoid bone, computed tomogr aphy.

Teprotumumab, a monoclonal antibody targeting the insulin-like growth factor-1 receptor, has demonstrated significant efficacy in treating thyroid eye disease. While its ophthalmic benefits are well established, limited data exist regarding its effects on thyroid hormone regulation. To characterize changes in thyroid function associated with teprotumumab therapy in thyroid eye disease patients. We performed a retrospective comparative study of 46 thyroid eye disease patients treated with teprotumumab and 46 thyroid eye disease patients treated with orbital decompression at a tertiary care facility between January 2020 and December 2023. Thyroid function tests (thyroid-stimulating hormone and free thyroxine) were analyzed at pretreatment and posttreatment. Subgroup analysis was conducted based on prior thyroidectomy or radioactive iodine therapy. Clinical outcomes, including proptosis and Clinical Activity Score, were also evaluated. The teprotumumab cohort had a mean age of 55.9 years, with 80.5% female and 65.2% hyperthyroid at presentation. The orbital decompression cohort mean age was 49.8 years, with 89.1% female and 80.4% hyperthyroid. Both groups showed significant improvements in Clinical Activity Score and proptosis. In the teprotumumab group, free thyroxine levels significantly declined posttreatment (1.7 ± 1.2 to 1.3 ± 0.4, p = 0.049), particularly in patients without prior thyroidectomy/radioactive iodine (1.8 ± 1.4 to 1.2 ± 0.3, p = 0.041). The orbital decompression group showed no significant change in free thyroxine levels (p = 0.63). Over half (52.2%) of teprotumumab patients required medication adjustments during therapy, compared with 12.5% in the orbital decompression group (p < 0.001). Teprotumumab may impact thyroid hormone homeostasis, especially in patients with functioning thyroid tissue, suggesting a need for endocrine monitoring with treatment.

Association of orbital decompression and the characteristics of subsequent strabismus surgery in thyroid eye disease