Teprotumumab-Related Adverse Events in Thyroid Eye Disease: A Multicenter Study.

PURPOSE: To assess the duration, incidence, reversibility, and severity of adverse events (AEs) in patients with thyroid eye disease (TED) treated with teprotumumab. DESIGN: Multicenter, retrospective, observational cohort study. PARTICIPANTS: Patients with TED of all stages and activity levels treated with at least 4 infusions of teprotumumab. METHODS: Patients were treated with teprotumumab between February 2020 and October 2022 at 6 tertiary centers. Adverse event metrics were recorded at each visit. MAIN OUTCOME MEASURES: The primary outcomes measure was AE incidence and onset. Secondary outcome measures included AE severity, AE reversibility, AE duration, proptosis response, clinical activity score (CAS) reduction, and Gorman diplopia score improvement. RESULTS: The study evaluated 131 patients. Proptosis improved by 2 mm or more in 77% of patients (101/131), with average proptosis improvement of 3.0 ± 2.1 mm and average CAS reduction of 3.2 points. Gorman diplopia score improved by at least 1 point for 50% of patients (36/72) with baseline diplopia. Adverse events occurred in 81.7% of patients (107/131). Patients experienced a median of 4 AEs. Most AEs were mild (74.0% [97/131]), 28.2% (37/131) were moderate, and 8.4% (11/131) were severe. Mean interval AE onset was 7.9 weeks after the first infusion. Mean resolved AE duration was 17.6 weeks. Forty-six percent of patients (60/131) demonstrated at least 1 persistent AE at last follow-up. Mean follow-up was 70.2 ± 38.5 weeks after the first infusion. The most common type of AEs was musculoskeletal (58.0% [76/131]), followed by gastrointestinal (38.2% [50/131]), skin (38.2% [50/131]), ear and labyrinth (30.5% [40/131]), nervous system (20.6% [27/131]), metabolic (15.3% [20/131]), and reproductive system (12.2% [16/131]). Sixteen patients (12.2%) discontinued therapy because of AEs, including hearing loss (n = 4), inflammatory bowel disease flare (n = 2), hyperglycemia (n = 1), muscle spasms (n = 1), and multiple AEs (n = 8). CONCLUSIONS: Adverse events are commonly reported while receiving teprotumumab treatment. Most are mild and reversible; however, serious AEs can occur and may warrant treatment cessation. Treating physicians should inform patients about AE risk, properly screen patients before treatment, monitor patients closely throughout therapy, and understand how to manage AEs should they develop. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Automated Perimetry and Visual Dysfunction in Blast-Related Traumatic Brain Injury.

PURPOSE: To evaluate feasibility and results of automated perimetry in veterans with combat blast neurotrauma. DESIGN: Prospective, longitudinal, observational case series. PARTICIPANTS: Sixty-one patients in a Veterans Affairs Polytrauma Center diagnosed with traumatic brain injury (TBI) from combat blast exposure. METHODS: Study participants underwent automated perimetry at baseline (median interval, 2 months after injury) (Humphrey Field Analyzer, Carl Zeiss Meditec, Dublin, CA, Swedish Interactive Threshold Algorithm 30-2 Standard or Fast), and 36 of them were followed up (median interval, 10 months after baseline). Presence of significant mean deviation and pattern standard deviation was determined for testing with reliability indices ≤20% for fixation loss, 15% for false-positives, and 33% for false-negatives. Test-retest stability of global visual field indices was assessed for tests with these cutoffs or with elevated fixation loss. Associations between global visual field defects and predictors were examined. MAIN OUTCOME MEASURES: Global visual field indices (mean deviation and pattern standard deviation). RESULTS: Among 61 study participants (109 study eyes) with baseline testing, a field that met reliability cutoffs was obtained for 48 participants (79%) and 78 eyes (72%). Fixation loss was found in 29% of eyes in initial testing. Nine study participants (15%) demonstrated hemianopia or quadrantanopia, and an additional 36% had an abnormal global visual field index. Global indices were relatively stable at follow-up testing for tests meeting fixation-loss cutoffs and tests that did not. Visual scotomas due to post-chiasmal lesions were associated with moderate to severe TBI or penetrating head injury, but other visual field deficits were prevalent across the range of mild to severe TBI. Ocular injury to the retina or choroid, poorer visual acuity, and pupillary defect were associated with visual field defects. Participants with depressed visual field sensitivity reported lower visual quality of life. CONCLUSIONS: Reliable automated perimetry can be accomplished in most patients with TBI from combat blast exposure and reveals high rates of visual field deficits, indicating that blast forces may significantly affect the eye and visual pathways.

Closed-globe injuries of the ocular surface associated with combat blast exposure.

PURPOSE: To describe closed-globe conjunctival and corneal injuries and endothelial cell abnormalities associated with blast exposure and their relationships to other closed-globe injuries and blast-event characteristics. DESIGN: Observational cross-sectional study. PARTICIPANTS: Veterans with a history of blast-related traumatic brain injury (TBI). METHODS: History and ocular examination, including slit-lamp biomicroscopy, gonioscopy, specular microscopy. MAIN OUTCOME MEASURES: Type and location of blast injuries to the conjunctiva and cornea. RESULTS: Ocular surface injuries were present in 25% (16 of 65) of blast-exposed veterans with TBI. Injuries included partial-thickness anterior stromal corneal scars (15 eyes), Descemet membrane ruptures (6 eyes), and conjunctival or corneal foreign bodies (7 eyes). Based on normative information from an age-matched comparison group, endothelial cell abnormalities were identified in 37% of participants. Eyes with ocular surface injury were more likely to have lower endothelial cell density, higher coefficient of variation of cell area, and lower percentage of hexagonal cells compared with eyes without injury. Presence of ocular surface injury or endothelial cell abnormalities was associated with elevated rates of other anterior and posterior segment injuries, as well as impairment of visual acuity. We found no relationship between ballistic eyewear use or severity level of TBI and presence of ocular surface injuries from blast. CONCLUSIONS: Independent of TBI severity or use of protective eyewear, ocular surface injuries and endothelial cell abnormalities were found in significant numbers of veterans with blast-related brain injury. Descemet membrane ruptures from blast exposure were described. Ocular surface trauma was associated with other ocular injuries throughout the globe. Potential mechanisms for the types and locations of ocular injuries seen were discussed. Any corneal or conjunctival injury in a blast survivor should prompt a thorough ocular trauma examination, including gonioscopy and specular microscopy, with appropriate follow-up for associated injuries. Longitudinal studies are required to determine long-term visual outcomes after blast exposure.

Visual performance and the ocular surface in traumatic brain injury.

The pathophysiology of neurotrauma is reviewed and an original study investigating the prevalence of dry eye disease in a sample of veterans with traumatic brain injury (TBI) is presented. Fifty-three veterans with TBI were evaluated by history of injury, past ocular history, and medication use. Ocular Disease Surface Index (OSDI), ocular examination, cranial nerve evaluation, tear osmolarity, tear film break-up time (TFBUT), ocular surface staining and tear production testing were performed. A matched comparison group underwent similar testing. TBI causes were blast (44) or non-blast (9). TBI subjects scored significantly worse on the OSDI (P<.001), and ocular surface staining by Oxford scale (P<.001) than non-TBI subjects. Scores for tear film breakup (P=.6), basal tear production less than 3 mm (P=.13), and tear osmolarity greater than 314 mOsm/L (P=.15) were all higher in TBI subjects; significantly more TBI subjects had at least one abnormal dry eye measure than comparisons (P<.001). The OSDI related to presence of dry eye symptoms (P<.01). These effects were present in both blast and non-blast TBI. Seventy percent of TBI subjects were taking at least one medication in the following classes: antidepressant, atypical antipsychotic, anticonvulsant, or h1-antihistamine. There was no association between any medication class and the OSDI or dry eye measures. Reduced corneal sensation in 21 TBI subjects was not associated with OSDI, tear production, or TFBUT, but did correlate with reduced tear osmolarity (P=.05). History of refractive surgery, previous contact lens wear, facial nerve weakness, or meibomian gland dysfunction was not associated with DED. In summary, we found a higher prevalence of DED in subjects with TBI, both subjectively and objectively. This effect is unrelated to medication use, and it may persist for months to years. We recommend that patients with TBI from any cause be evaluated for DED using a battery of standard testing methods described in a protocol presented in this article. Further research into the pathophysiology and outcomes of DED in neurotrauma is needed.

Bridging the Gap between Ophthalmology and Emergency Medicine in Community-Based Emergency Departments (EDs): A Neuro-Ophthalmology Guide for ED Practitioners.

Coordination of care for patients with neuro-ophthalmic disorders can be very challenging in the community emergency department (ED) setting. Unlike university- or tertiary hospital-based EDs, the general ophthalmologist is often not as familiar with neuro-ophthalmology and the examination of neuro-ophthalmology patients in the acute ED setting. Embracing image capturing of the fundus, using a non-mydriatic camera, may be a game-changer for communication between ED physicians, ophthalmologists, and tele-neurologists. Patient care decisions can now be made with photographic documentation that is then conveyed through HIPAA-compliant messaging with accurate and useful information with both ease and convenience. Likewise, external photos of the anterior segment and motility are also helpful. Finally, establishing clinical and imaging guidelines for common neuro-ophthalmic disorders can help facilitate complete and appropriate evaluation and treatment.

Quality of Life in Patients with Chronic Thyroid Eye Disease in the United States.

INTRODUCTION: Thyroid eye disease (TED) is an autoimmune condition producing ocular pain, dysmotility, and ocular structure and function changes. As disease activity changes, redness, swelling, and pain can improve, but eye comfort, appearance, and motility alterations often persist. There are limited data on chronic TED patient-reported outcomes. This study examined chronic US TED patient-reported symptoms and quality of life (QOL). METHODS: Existing data from an online survey regarding chronic TED signs/symptoms and patient QOL were retrospectively examined. The Graves' Ophthalmopathy QOL instrument (GO-QOL; 0-100, 100 = highest QOL) evaluated overall, appearance, and vision-related QOL. Influencing factors were examined by stratifying patients into low (overall QOL ≤ 50), moderate (> 50 and < 75), and high (≥ 75) QOL categories. RESULTS: One hundred patients (47 women, 81 Caucasian, 45.2 ± 7.6 years) were included. The duration of inactive TED was 3.0 ± 4.6 years and total duration of TED was 5.8 ± 5.9 years. Patients reported an average of 20 doctor visits/year and high prevalence of anxiety (34%) and depression (28%). Prior TED treatments for the polled population included systemic corticosteroids during active TED (25%), orbital radiation (5%), and surgery (25%). The overall GO-QOL score was 60.5 ± 21.8 (vision-related: 58.6 ± 24.0, appearance-related: 62.3 ± 25.1). Patients with low QOL more frequently reported hypothyroidism, anxiety, and a larger number of chronic TED signs/symptoms (average: 4.2). Compared to high QOL patients, low QOL patients had more pain (39% vs. 13%), blurry vision (30% vs. 17%), and diplopia (27% vs. 3%, all p ≤ 0.025). Additionally, the low QOL group more often had TED-specific surgical history (45% vs. 10%, p = 0.002), more often reported disability/unemployment (21% vs. 3%, p = 0.055), and had a higher number of doctor visits (40 vs. 5 visits/person/year, p < 0.001). CONCLUSION: TED severely impacts patient QOL, despite becoming stable and chronic. Patients reported vision and appearance impairment and psychosocial impact long after acute TED had subsided.

Thyroid eye disease (TED) occurs when loss of immune tolerance results in orbital and retro-orbital inflammation. Fat and muscle tissue can swell severely, causing debilitating symptoms, including pain around/behind the eyes, eye movement abnormalities, bulging eyes (proptosis), and double vision (diplopia), manifesting in appearance and vision quality of life (QOL) changes. Some improvement can occur as inflammation quiets and TED becomes chronic/inactive. However, appearance and visual changes often remain due to persistent proptosis and eye muscle and eyelid changes. This study examined TED symptoms and QOL in 100 chronic TED patients. They answered questions about symptoms, how TED affected them, and their medical care. The average duration of TED was 6 years (3 years inactive), patients had an average of 20 TED-related doctor visits/year, and nearly one-half (42%) of patients reported having anxiety and/or depression. Prior TED treatments included steroids (25% when TED-related inflammation was present), orbital radiation (5%), and surgery (25%). Disease-specific QOL scores (average score: 60.5 of 100) indicated that these chronic patients reported similar QOL impact as those with moderate-to-severe, active disease. Compared with the least impacted group, the most impacted patients reported higher rates of hypothyroidism (18% vs. 0%), anxiety (48% vs. 17%), disability/unemployment (21% vs.3%), number of doctor visits (40 vs. 5 visits/person/year), pain (39% vs. 13%), blurry vision (30% vs. 17%), diplopia (27% vs. 3%), and surgical treatment for TED (45% vs. 10%). This study demonstrates that QOL continues to be severely impacted by TED long after TED-related inflammation has quieted.

Growth of a presumed orbital venous anomaly during pregnancy with spontaneous resolution postpartum.

A 27-year-old pregnant woman in her second trimester presented with a 3-month history of gradual proptosis, decreased vision, and choroidal folds in her right eye. MRI revealed an intraconal mass with inhomogeneous enhancement consistent with a vascular lesion. The patient was followed clinically and the lesion remained stable for the remainder of her pregnancy and delivery by Cesarean section. Three months postpartum, the proptosis, choroidal folds, and decreased vision had resolved. Repeat scanning revealed complete resolution of the lesion. Pregnant patients with orbital vascular lesions need to be followed carefully during their pregnancy and after delivery. These lesions can worsen during pregnancy and may resolve spontaneously in the postpartum period.

Disseminated silicone granulomatosis in the face and orbit.

PURPOSE: To report a case of disseminated silicone granulomatosis presenting with ptosis, proptosis and vision loss. OBSERVATIONS: A 56-year-old female presented with ptosis, proptosis, and vision loss and was noted to have palpable, erythematous masses involving the orbit, face, trunk, and body. She had a history of bilateral silicone breast implants and cosmetic facial filler injections. Orbital biopsy demonstrated non-caseating granulomas with foreign-body giant cells and vacuoles containing material consistent with silicone. Removal of the patient's breast implants and systemic immunosuppression led to dramatic granuloma regression. CONCLUSIONS: Silicone can induce a severe, systemic inflammatory response and should be considered in the differential for facial and periorbital granulomas in patients with a history of silicone breast implants. Management of disseminated silicone granulomatosis is challenging and requires multimodal treatment with silicone removal and systemic immunomodulation.

Ophthalmic manifestations of infections caused by the USA300 clone of community-associated methicillin-resistant Staphylococcus aureus.

PURPOSE: To report the microbiological, clinical, and pathological characteristics of community-associated methicillin-resistant Staphylococcus aureus (CAMRSA) infections of the eye and orbit. DESIGN: Prospective case series. PARTICIPANTS: Nine patients with CAMRSA infections of the eye and orbit were identified during a 6-month period at 2 tertiary care hospitals in San Francisco. METHODS: Case identification was by prospective case selection and retrospective laboratory review of 549 MRSA cultures collected in the 2 hospitals. Ophthalmic microbial isolates were analyzed by pulsed-field gel electrophoresis and compared with a control CAMRSA clone (USA300). Clinical characteristics of patients infected with CAMRSA were reviewed, and all surgical specimens underwent pathological examination. MAIN OUTCOME MEASURES: Pulsed-field gel electrophoresis banding patterns of MRSA isolates, antibiotic sensitivity profiles, patient demographics, systemic and ocular complications of infection, and posttreatment visual acuities. RESULTS: Nine ophthalmic isolates were CAMRSA clone USA300. The infections included orbital cellulitis, endogenous endophthalmitis, panophthalmitis, lid abscesses, and septic venous thrombosis. Patients were treated with trimethoprim-sulfamethoxazole, rifampin, clindamycin, or vancomycin based on microbial sensitivity studies and severity of infection. Eight of the 9 patients had no history of hospitalization. Seven patients required hospitalization, 3 required surgery, and an additional 4 required invasive procedures. Eight patients had good visual outcomes, but 1 deteriorated to no light perception. Pathological analyses showed extensive necrosis in eyelid and orbital specimens, and disorganized atrophy bulbi in an enucleated eye. CONCLUSION: The USA300 CAMRSA clone, which carries Panton-Valentine leukocidin genes, can cause aggressive infections of the eye and orbit in hospital-naive patients. Treatment of infections often required debridement of necrotic tissues in addition to non-beta-lactam class antibiotics. In communities where CAMRSA is prevalent, ophthalmologists should obtain microbial cultures and sensitivity studies to help guide antibiotic therapy for severe ophthalmic infections.

Periorbital zygomycosis (mucormycosis) treated with posaconazole.

PURPOSE: To report on the successful treatment of periorbital zygomycosis (mucormycosis) with posaconazole, a broad-spectrum oral antifungal available for compassionate use. DESIGN: Interventional case report. METHODS: Review of a medical record. RESULTS: A 22-year-old male undergoing induction chemotherapy for acute lymphoblastic leukemia presented with periorbital cellulitis attributable to Rhizopus. The patient was initially treated with liposomal amphotericin B, surgical debridement, and reversal of immune compromise. The patient was switched to posaconazole because of amphotericin side effects and lack of improvement. He took posaconazole for five months while undergoing additional cycles of chemotherapy. Despite recurrent profound neutropenia, the periorbital infection resolved, he tolerated reconstructive procedures, and he did not develop orbital invasion. His Rhizopus isolate was highly susceptible to posaconazole in vitro. CONCLUSIONS: Drug toxicities can limit the use of amphotericin in some patients with zygomycosis. Posaconazole shows promise as an alternative antifungal agent in the treatment of periorbital zygomycosis.

Bilateral blindness from orbital cellulitis caused by community-acquired methicillin-resistant Staphylococcus aureus.

PURPOSE: To describe bilateral blindness resulting from infection with community-acquired methicillin-resistant Staphylococcus aureus (MRSA). DESIGN: Observational case report. METHODS: A 44-year-old man developed proptosis, ptosis, ophthalmoplegia, and no light perception vision after attempting to lance a nasal pustule. A nasal culture grew MRSA. Imaging showed bilateral orbital cellulitis, pansinusitis, and cavernous sinus thrombosis. The right fundus showed severe ischemia, but the left fundus was essentially normal. RESULTS: Despite initiation of appropriate antibiotics early in the course of infection, the patient lost sight in both eyes. Surgical drainage of the paranasal sinuses and use of intravenous corticosteroids and heparin led to the resolution of orbital cellulitis. CONCLUSIONS: MRSA orbital cellulitis can progress to irreversible blindness despite antibiotic treatment. A new, community-acquired clone of this organism has exhibited increased potential for tissue invasion.

Visual field deficit caused by vascular compression from a suprasellar meningioma: case report.

OBJECTIVE AND IMPORTANCE: Suprasellar meningiomas typically cause bitemporal hemianopsia by direct compression of the chiasm, its blood supply, or both. We report another mechanism for visual loss in suprasellar meningiomas, whereby compression by the suprajacent vascular complex is the offending agent. CLINICAL PRESENTATION: A 78-year-old woman with a suprasellar meningioma was diagnosed incidentally. During the follow-up period, she developed an inferior homonymous wedge defect consistent with superior compression, without any detectable radiological progression. It was decided to resect her tumor. INTERVENTION: The patient underwent a fronto-orbital approach for tumoral excision. Intraoperatively, a groove by the anterior cerebral artery complex was found along the superior surface of the chiasm. Postoperatively, the patient's visual deficit resolved. CONCLUSION: This case illustrates an unusual visual field deficit associated with a suprasellar meningioma. It also emphasizes the importance of frequent and careful visual field monitoring, which can precede radiological and symptomatic progression.

Visual quality of life in veterans with blast-induced traumatic brain injury.

IMPORTANCE: Traumatic brain injury (TBI) is an important cause of morbidity worldwide, with increasing awareness of the role of blast exposure in military and civilian casualties. Visual problems have been reported in TBI and may affect functioning and quality of life. OBJECTIVE: To evaluate the 25-item National Eye Institute Visual Functioning Questionnaire and Neuro-Ophthalmic Supplement for utility in assessing the effect of blast exposure on perceived visual functioning among veterans with TBI. DESIGN, SETTING, AND PARTICIPANTS: Observational cohort study from a tertiary care Veterans Health Administration hospital. Reported visual quality of life was compared with existing norms, and relationships between perceived visual quality and ocular injury, diplopia, visual performance, and blast exposure characteristics were examined. Participants included inpatients with blast-induced TBI who underwent baseline examination between December 7, 2006, and January 11, 2012, at a multiple-trauma rehabilitation center and who had at least 1 intact eye and were able to undergo psychometric testing and ocular examination. Among 64 sequentially eligible patients, 60 completed visual quality testing, 1 declined study participation, and 3 were evaluated prior to inclusion of visual quality testing in the protocol. Thirty-nine patients returned for outpatient follow-up, with a median test-retest interval of 11 months. EXPOSURE: Combat blast exposure with documented TBI. MAIN OUTCOMES AND MEASURES: Composite and subscale scores on the 25-item National Eye Institute Visual Functioning Questionnaire and Neuro-Ophthalmic Supplement. RESULTS: Both tests had high test-retest reliability. Blast-exposed veterans reported significantly poorer visual quality compared with healthy samples and some patient samples with known eye disease. Scores tended to be worse for participants with identified visual performance deficits (poorer visual acuity or spatial contrast sensitivity, visual field depression or defects). Scores were not related to the extent of ocular injury or to blast exposure characteristics such as use of protective eyewear or TBI severity level. CONCLUSIONS AND RELEVANCE: Individuals with blast-induced TBI reliably completed both tests and reported significant decrements in their subjective visual experiences. Measures of subjective visual quality may be useful to identify patients needing additional visual or neurologic evaluation and to monitor the effect of visual rehabilitation on patients with blast-related visual disabilities.

IgG4-positive sclerosing orbital inflammation involving the conjunctiva: a case report.

PURPOSE: To describe IgG4-positive sclerosing orbital inflammation with prominent conjunctival and scleral involvement. DESIGN: Case report. METHODS: Clinical, radiologic, and pathologic correlation. RESULTS: A 66-year-old man presented with right eye redness and irritation. Examination revealed unilateral scleritis and nongranulomatous anterior uveitis with elevated p-ANCA and CRP. Orbital CT scan showed inferotemporal scleral thickening. Biopsy revealed sclerosis and IgG4-positive plasma cells in the conjunctiva and inferior rectus. CONCLUSIONS: IgG4-mediated sclerosing inflammation is well-recognized in the orbit and adnexa, particularly the lacrimal gland. Scleritis with anterior uveitis should be recognized as a possible presentation for this entity, which has important systemic associations.

Increased expression of TSH receptor by fibrocytes in thyroid-associated ophthalmopathy leads to chemokine production.

CONTEXT: The molecular basis for anatomically dispersed clinical manifestations in Graves' disease (GD) eludes our understanding. Bone marrow-derived, pluripotent fibrocytes represent a subset of peripheral blood mononuclear cells and infiltrate the orbital and thyroid tissues in GD. These cells may be involved in the pathogenesis of thyroid-associated ophthalmopathy (TAO). OBJECTIVE: The objective of the study was to quantify fibrocyte display of functional cell surface TSH receptor (TSHR), identify the profile of chemokines they express after TSHR activation, and determine whether circulating TSHR(+) peripheral blood fibrocytes are more frequent in situ in patients with TAO. DESIGN/SETTING/PARTICIPANTS: Using a newly developed technique, fibrocytes were directly identified in peripheral blood from 31 patients with TAO and 19 healthy subjects receiving care at a multidisciplinary academic center. MAIN OUTCOME MEASURES: The frequency in situ of fibrocytes (collagen 1(+), CD45(+), CD34(+), CD14(+), CD86(+) peripheral blood mononuclear cells) was assessed by multiparameter flow cytometry and correlated to clinical disease activity and smoking status. Levels of TSHR-displaying fibrocytes and their response to TSH and TSHR-activating antibody, M22, were measured by flow cytometry, Luminex, and real-time PCR. RESULTS: The levels of TSHR expression by fibrocytes are substantially higher than those found in orbital fibroblasts. Moreover, the frequency of TSHR(+) fibrocytes in patients with TAO was greater than that in healthy subjects in situ. Their abundance is not influenced by disease activity or smoking history. These cells produce high levels of several cytokines and chemokines including IL-8, regulated upon activation, normal T cell expressed and secreted, and monocyte chemoattractant protein-1 when treated with TSH or M22. TSH induces IL-8 production at the pretranslational level. This induced cytokine can be detected in intact fibrocytes ex vivo. CONCLUSIONS: Frequency of circulating TSHR(+) fibrocytes is markedly increased in patients with TAO, and they express proinflammatory chemokines in response to TSH. Because they infiltrate both orbit and thyroid in GD, they may represent the link between systemic immunoreactivity and organ-specific autoimmunity.

Thyroid eye disease.

Thyroid eye disease (TED) is the most common cause of proptosis in adults, and should always be a consideration in patients with unexplained diplopia, pain, or optic nerve dysfunction. At least 80% of TED is associated with Graves disease (GD), and at least 50% of patients with GD develop clinically evident symptomatic TED. The most confusing patients for doctors of all subspecialties are the patients with eye symptoms and signs that precede serum evidence of a thyroid imbalance. Management of TED may include immunosuppressive medications, radiation, or surgery. Although the prognosis for optic nerve function is excellent, the restrictive dysmotility can result in permanent disability. Orbit and eyelid reconstruction are reserved for stable, inactive patients and are the final steps in minimizing facial alterations and enhancing the patient's daily functioning.