Acute thyroid eye disease (TED): Principles of medical and surgical management

The active inflammatory phase of thyroid eye disease (TED) is mediated by the innate immune system, and management is aimed at aborting this self-limited period of autoimmune activity. In most patients with TED, ocular and adnexal changes are mild and management involves controlling thyroid dysfunction, cessation of smoking, and addressing ocular surface inflammation and exposure. In patients with acute moderate disease, this being sufficient to impair orbital functions, immunosuppression reduces the long-term sequelae of acute inflammation, and adjunctive fractionated low-dose orbital radiotherapy is used as a steroid-sparing measure. Elective surgery is often required following moderate TED, be it for proptosis, diplopia, lid retraction, or to debulk the eyelid, and this should be delayed until the disease is quiescent, with the patient stable and weaned off all immunosuppression. Thus, surgical intervention during the active phase of moderate disease is rarely indicated, although clinical experience suggests that, where there is significant orbital congestion, early orbital decompression can limit progression to more severe disease. Acute severe TED poses a major risk of irreversible loss of vision due to marked exposure keratopathy, ‘hydraulic'' orbital congestion, or compressive optic neuropathy. If performed promptly, retractor recession with or without a suture tarsorrhaphy protects the ocular surface from severe exposure and, in patients not responding to high-dose corticosteroid treatment, decompression of the deep medial orbital wall and floor can rapidly relieve compressive optic neuropathy, as well as alleviate the inflammatory and congestive features of raised orbital pressure.     

Abducens nerve palsy after orbital decompression

Introduction: Double vision after decompression surgery for Thyroid Eye Disease (TED) is well described in the literature and the incidence ranges from 0 to 64%. The Mechanisms for new onset diplopia after orbital decompression are poorly understood. Common theories include: Fibrosis of muscles, displacement of the muscle cone, and reactivation of the TED.

Aim: We present two cases with Abducens nerve palsy after uncomplicated secondary orbital decompression surgery.

Results: Two patients with inactive TED, who were followed for an average of 2 years prior to uneventful secondary decompression surgery, presented at the first postoperative visit with double vision and limitation of abduction in the recently operated eye. Magnetic resonance imaging(MRI) was done in both cases and revealed no abnormal bleeding or scaring.

Discussion: Our two cases of Abducens palsy following reoperative orbital decompression may be due to ischemic neuropathy caused by postoperative hemorrhage or inflammation.     

Update on thyroid eye disease: Regional variations in prevalence,diagnosis, and management

Thyroid eye disease (TED) is a rare disease that can lead to decreased quality of life, permanent disfigurement, and vision loss. Clinically, TED presents with exophthalmos, periorbital edema, extraocular muscle dysfunction, and eyelid retraction, and can lead to vision-threatening complications such as exposure to keratopathy and dysthyroid optic neuropathy (DON). Over the last several years, significant advancements have been made in the understanding of its pathophysiology as well as optimal management. Ethnic variations in the prevalence, clinical presentation, and risk of vision-threatening complications of TED are summarized, and risk factors associated with TED are discussed. Additionally, significant advances have been made in the management of TED. The management of TED traditionally included anti-inflammatory medications, orbital radiation therapy, orbital surgical decompression, and biologic therapies. Most recently, targeted therapies such as teprotumumab, an insulin-like growth factor-1 receptor antagonist, have been studied in the context of TED, with promising initial data. In this review, updates in the understanding and management of TED are presented with a focus on the international variations in presentation and management.     

Refractive change in thyroid eye disease (a neglected clinical sign)

BACKGROUND/AIMS: The literature on refractive change in thyroid eye disease (TED) is limited. This study documents the refractive change in patients with TED undergoing orbital decompression. The authors propose possible mechanisms for their acquired refractive error. METHODS: This is a retrospective observational case study of five patients with progressive TED. Their detailed eye examinations including refractive state preoperatively and postoperatively are presented. RESULTS: An acquired hypermetropic shift with active TED before orbital decompression of up to 3.75 D spherical equivalent refraction (SER) is reported in one patient. Post-orbital decompression, an induced myopic shift of between 1.00-2.50 D SER for all patients is observed, noted to range from 1 day following surgery to up to 9 months, dependent on the availability of data. Axial length increased in two cases corresponding to postoperative myopic shift. Magnetic resonance imaging findings of one patient demonstrate flattening of the posterior pole as a cause of the acquired preoperative hypermetropia. CONCLUSIONS: TED has a significant effect on the refractive state of patients. The proposed mechanism of acquired hypermetropia relates to increased volume of orbital contents with flattening of the posterior globe. This is reversed with successful orbital decompression. Documentation of refractive error in all cases of progressive TED is recommended. Progressive acquired hypermetropia may be suggestive of TED activity.     

Ocular Surface Characteristics and Impression Cytology in Patients with Active versus Inactive Thyroid Eye Disease

 PURPOSE:To compare the clinical findings, tear film function and impression cytology between patients with active and inactive Thyroid Eye Disease (TED). METHODS:A total of 56 patients with TED and 30 controls were recruited in this prospective observational cohort study. TED patients were divided into active TED and inactive TED types according to a seven-point modified formulation of the Clinical Activity Score (CAS). All participants underwent full eye examinations including Ocular Surface Disease Index (OSDI) score, tear film break-up time (TBUT), fluorescein staining and Schirmer I test. Thirty nine patients with thyroid-associated orbitopathy (TAO) received Nelson's grade with conjunctival impression cytology. Proptosis, palpebral fissure width and lagophthalmos were assessed. RESULTS:Ocular surface parameters including proptosis, palpebral fissure width and lagophthalmos did not differ between active and inactive TED patients (P>0.05). Both active and inactive TED patients obtained higher fluorescein staining scores, lower TBUT scores and significantly lower Schirmer test scores than those of controls (P<0.001 for all). Additionally, the TBUT score was significantly lower and the OSDI score significantly higher in the active TED group compared with those in the inactive TED group (P<0.001 for both). Impression cytology revealed a higher proportion of grade 2-3 changes in the active TED group compared with the inactive TED group (P<0.001). CONCLUSION:Orbital inflammation in TED patients may lead to decreased tear film stability and ocular surface squamous metaplasia.     

Color Doppler imaging of orbital vasculature before and after orbital decompression in thyroid eye disease

Purpose: To measure alterations in orbital blood flow parameters using color Doppler imaging (CDI) before and after orbital decompression in patients with moderate to severe thyroid eye disease (TED).

Methods: Resistance index (RI) and maximum and minimum velocity of ophthalmic artery (OA), superior ophthalmic vein (SOV), and central retinal artery (CRA) of 24 eyes (14 patients) with TED were measured before and at least 3 months after cosmetic orbital decompression procedure (single or double walls) using CDI. Complete eye examination was performed to define the severity (EUGOGO classification) and activity (clinical activity score) of TED.

Results: Median OA (p = 0.003) and CRA (p = 0.001) resistance indices were significantly reduced postoperatively. Significant differences were found in maximum (p = 0.001) and minimum (p = 0.014) velocity of SOV before and after surgery. While a significant decrease in exophthalmometry was observed after the orbital decompression (p = 0.031), intraocular pressure changes were not significant (p = 0.182).

Conclusion: Orbital decompression procedure led to a significant reduction of RI in both CRA and OA in patients with TED.     

The Management of Patients with Thyroid Eye Disease After Bilateral Orbital 3 Wall Decompression

Introduction: Thyroid eye disease is the most common cause of unilateral and bilateral proptosis in adults. Orbital decompression surgery may cause and/or worsen a pre-existing ocular motility disorder.

Methods: A retrospective review was carried out of all bilateral 3 wall orbital decompressions for severe thyroid eye disease performed between January 2002 and December 2004 by one surgeon. Subsequent surgeries were recorded.

Results: Seventy-four patients were identified, 59 (80%) females and 15 (20%) males. Mean age at the time of decompression was 46 years. Fifteen (20%) patients complained of diplopia due to strabismus prior to decompression surgery and 20 (27%) developed new diplopia postsurgery. Twenty patients (27%) required no further intervention following decompression surgery; the remainder underwent an average of 2.5 procedures. Strabismus surgery was performed in 32 (43%) patients. The mean time from the decompression to first strabismus surgery was 12 months. Forty-three (58%) patients underwent lid surgery. The mean time from decompression to first lid surgery was 16 months.

Conclusion: This study demonstrates how this group of complex patients required multiple surgical procedures within an extended timescale, therefore requiring several in- and outpatient visits.     

Medical management of thyroid eye disease

Thyroid eye disease (TED) is the most common cause of orbital disease in adults. The immunologic pathogenesis of TED has been an area of active research and considerable progress has resulted in an expansion of therapeutic options. Although surgical intervention may be required, a majority of TED patients can be managed with medical therapies. Of medical therapies, glucocorticoids remain the agent of choice in the control of TED activity. The objective of this review is to discuss the paradigm and options in medical management of TED.     

Orbital decompression for thyroid eye disease

The literature regarding orbital decompression for thyroid eye disease is vast, spanning multiple specialty areas including neurosurgery, head and neck, maxillofacial, and ophthalmic plastic surgery. Although techniques have advanced considerably over the more than 100 years during which this procedure has been performed, the 4 major approaches remain: transorbital, transcranial, transantral, and transnasal. The explosion in literature related to orbital decompression has mostly involved minor technical variations on broader surgical themes. The purpose of this review is to organize the major approaches in terms of bony anatomy and to contextualize variation in transdisciplinary techniques within a common conceptualization.     

Sensitivity and responsiveness of the patient-reported TED-QOL to rehabilitative surgery in thyroid eye disease

We tested the sensitivity and responsiveness of the TED-QOL to rehabilitative surgery in thyroid eye disease (TED). The 3-item TED-QOL and 16-item GO-QOL, which assess quality of life (QoL) in TED, were administered to consecutive patients undergoing rehabilitative surgery. The questionnaires were completed pre-and post-operatively to assess sensitivity (ability to discriminate between different surgical groups) and responsiveness (ability to detect within patient changes over time).56 patients underwent 69 procedures for TED (29 orbital decompressions, 15 strabismus operations, 25 eyelid procedures).

The differences in scores between the three types of surgery (a measure of sensitivity) were statistically significant at the 5% level pre-operatively and post-operatively for all 3 TED-QOL scales and for both GO-QOL scales, but much more so for the TED-QOL scales in each case.

The within-patient changes between the pre- and post-operative scores for the same subjects (a measure of responsiveness) were statistically very highly significant for the TED-QOL overall and appearance scales for each of the surgeries. The pre- and post-operative difference for the TED-QOL functioning scale was highly statistically significant for strabismus surgery but not for decompression or lid surgery. The change between the pre- and post-operative scores for the GO-QOL was significant for the functioning scale with strabismus and lid surgery, and was highly significant for the appearance scale with lid surgery but not for strabismus surgery or decompression.

The 3-item TED-QOL is sensitive and responsive to rehabilitative surgery in TED and compares favorably with the lengthier GO-QOL for these parameters.     

IgG4-related orbital disease masquerading as thyroid eye disease,vice versa,or both?

A 40 year-old male presented after one year of unilateral, progressive, steroid-responsive, orbital inflammatory disease causing proptosis, extraocular muscle (EOM) restriction, and compressive optic neuropathy. The development of anti-thyroidal antibodies prompted the diagnosis of thyroid eye disease (TED); however, the prolonged active phase, remarkable reversibility of ophthalmic features with high-dose corticosteroids, unilaterally of disease, uncharacteristic EOM involvement (including both obliques), and the absence of autoimmune thyroid disease provoked consideration of alternative diagnoses. Inferior oblique biopsy stained positive for IgG4 with histologic features atypical of TED. The patient received rituximab for presumed IgG4-related orbital disease (IgG4-ROD) with subsequent reversal of compressive optic neuropathy, near complete resolution of EOM restriction, and improved proptosis, the latter two of which are not routinely anticipated in advanced TED. The possible role for B-cell depletion in both TED and IgG4-ROD suggests a degree of overlap in the underlying immune-related pathophysiology that is yet to be defined.     

Current trends in orbital decompression

A questionnaire was sent to members of the American Society of Ophthalmic Plastic and Reconstructive Surgery (ASOPRS) and the Orbital Society in regard to indications, surgical techniques and results of orbital decompression for Graves' disease. It was found that more than 60% of orbital decompressions were performed for mild to severe exophthalmos to correct corneal exposure or disfigurement. A total of 3.9% of these procedures were performed to relieve visual loss in compressive neuropathy. The large majority of decompressions were performed using antral-ethmoidal decompression via a translid or fornix approach. The amount of retrodisplacement was greatest with Kennerdell-Maroon or four-wall decompression and the least with lateral wall decompression. The antral-ethmoidal and three-wall decompression techniques gave an average of 4 to 6 mm of retrodisplacement. It was determined from the survey that antral-ethmoidal decompressions performed through the transantral approach were more likely to relieve the pressure in compressive neuropathy and also more likely to induce a worsening of muscle balance. In contrast, antral-ethmoidal decompressions performed via the translid approach were not as effective in relieving compressive neuropathy but had a much lower incidence of worsened muscle balance, and in fact, resulted in a higher incidence of improved muscle balance. The same trends were confirmed in the author's surgical practice, and an anatomic explanation is offered. The importance of creating nasoantral windows following decompression is emphasized. The risks of cerebrospinal fluid leakage and changes in eyelid positioning following decompression are described.     

Color Doppler imaging in thyroid eye disease and its correlation to disease activity

Purpose: To evaluate alterations in orbital color Doppler imaging (CDI) parameters and their correlation to disease activity and severity in patients with thyroid eye disease (TED).

Methods: Seventy-six orbits of 45 TED patients and 40 orbits of 40 normal controls were enrolled in this cross-sectional study. According to clinical activity score (CAS), patients were categorized to active (CAS ≥ 3) or inactive disease (CAS < 3). Patients were also classified as having mild, moderate or severe disease. Peak systolic velocity (PSV), end diastolic velocity (EDV), and resistance index (RI) in ophthalmic artery and central retinal artery, and maximum and minimum velocity in superior ophthalmic vein and central retinal vein were determined in all subjects.

Results: There was a significant difference in maximum velocity of superior ophthalmic vein and EDV and RI of ophthalmic artery between patients with TED and normal subjects. Superior ophthalmic vein maximum and minimum velocity and ophthalmic artery RI were significantly higher in patients with active disease than inactive cases. Disease severity did not affect the blood flow parameters independently. A cutoff point of 3.99 cm/s in superior ophthalmic vein maximum velocity yielded a sensitivity of 91.2% and specificity of 81.2% in detecting active disease.

Conclusion: Retrobulbar blood flow is altered in TED and is related to disease activity. Superior ophthalmic vein maximum velocity could be helpful in differentiation of active and inactive cases.     

Hyperthyroid vs hypothyroid eye disease: the same severity and activity

Purpose

To compare demographics, severity, and activity of thyroid eye disease (TED) in patients with hyperthyroidism (Hr-TED) vs primary hypothyroidism (Ho-TED).

Patients and Methods

In a cross-sectional study, demographics, complete eye examination, severity score (NOSPECS, total hundred eye score), clinical activity score, and Rundle grading were recorded for patients with TED and different thyroid disorders referred from an endocrinology clinic from 2003 to 2006.

Results

TED was clinically found in 303 patients (303/851, 35.6%). The majority of them (280/303, 92.4%) had Graves'' hyperthyroidism and 23 (23/303, 7.5%) had primary hypothyroidism. Mean age, gender, mean severity score, mean activity score, Rundle grade, unilateral presentation of TED, smoking habit, mean duration of eye disease, and mean interval time of thyroid to TED were not significantly different between the two groups (0.06<P<0.9). Mean duration of thyroid disease was significantly (P=0.02) longer in the Hr-TED group (49.6 months) than in the Ho-TED group (22.7 months). Most of the patients in both groups (63.2% of Hr-TED and 73.9% of Ho-TED) developed the eye disease within 18 months before or after the thyroid disease.

Conclusion

The same demographics, clinical characteristics, and severity and activity scores for Hr-TED and Ho-TED imply that both groups present the same category of eye disease.     

Low Dose Orbital Radiotherapy for Thyroid Eye Disease

Purpose: The use of low dose orbital radiotherapy for thyroid eye disease (TED) remains controversial. This is a review of patients with TED treated with radiotherapy in our department over the last twelve years.

Methods and Materials: Fifty-nine consecutive patients received low dose orbital radiotherapy of 20 Gray (Gy) for active TED at the Beatson Oncology Centre. Their records were retrospectively reviewed and data including duration of symptoms, clinical activity score (CAS) pre- and post-orbital radiotherapy, immunosuppression requirement, subjective assessment and range of rehabilitative surgery was collected.

Results: Before orbital radiotherapy, all fifty-nine patients had an initial response to glucocorticoids and therefore presumed to have active phase thyroid eye disease. They received retro-orbital radiotherapy of 20 Gy in 12 fractions over 2 weeks. After treatment, only five patients remained on steroids and only one patient had CAS ≥ 3 at last follow up. Response (change in CAS) to orbital radiotherapy was statistically significant from 3.17?±?1.75 standard deviation (SD) to 0.73?±?0.92 SD (P?<?0.001) at mean follow up of 6.5 months. There was a reduction in CAS at each subsequent follow up for all subgroups when the patients were grouped according to disease severity i.e. mild TED(CAS 1–2), moderate (CAS 3–4), severe CAS (5–7) and optic neuropathy.

Conclusions: We believe orbital radiotherapy has a definite role to play in the treatment of active thyroid eye disease. The majority of our patients experienced a reduction in their clinical activity scores after orbital radiotherapy and this was irrespective of the severity of thyroid eye disease.     

Orbital and ocular perfusion in thyroid eye disease

Thyroid eye disease (TED) is characterized by enlargement of extraocular muscles, an increase in retrobulbar fat, orbital fibrosis, and fluctuations in plasma thyroid hormone levels in most patients, often associated with raised autoantibody titers. The occurrence of orbital space conflict compromises the orbital perfusion, unchecked progression of which results in irreversible loss of visual acuity and visual fields. The quantitative assessment of orbital perfusion can be done by measurement of blood flow velocities in the superior ophthalmic vein (SOV), ophthalmic artery (OA), central retinal artery (CRA), and posterior ciliary artery by color Doppler imaging. The retinal and choroidal microvasculature is studied by optical coherence tomography and optical coherence tomography angiography. The orbital and ocular perfusion fluctuates during the course of TED. Orbital congestion is reflected by the reduction or reversal of SOV flow and an increase in subfoveal choroidal thickness. The active phase is characterized by high blood flow velocities of the OA and CRA. The onset of dysthyroid optic neuropathy is associated with reduced arterial perfusion and reduction in parafoveal and peripapillary vascular density. Orbital decompression improves the SOV flow and decreases the resistivity index of CRA. Sequential evaluation of orbital hemodynamic changes can thus supplement the clinical scoring systems for monitoring and planning intervention in TED.     

Graves' orbitopathy

Graves' orbitopathy (GO) is part of an autoimmune systemic disease (prevalence of 0.5 - 2%) which is composed of hyperthyroidism, orbitopathy, dermopathy and acropachy. Stimulating antibodies against the TSH receptor plays the central pathogenetic role and high levels indicate the risk of a severe course of the disease. The main symproms of GO comprise soft tissue inflammation, proptosis impairment of ocular motility and lid retraction. Inflammatory reactions of orbital fibroblasts are responsible for the symptoms. To restrict damage, anti-inflammatory therapy (mainly i. v. systemic steroids, orbital irradiation) is indicated in moderate to severe active disease stages, and surgical orbital decompression is indicated in sight-threatening states. In mild GO selenium administration and otherwise a wait and see strategy is sufficient. In inactive disease stages surgery (orbital decompression, eye muscle surgery and lid surgery) is performed to improve appearance and function. Smoking increases the prevalence and severity of GO and reduces the efficiency of therapy. Restoring euthyroidism leads to an improvement of GO in about 60% of the patients.     

Review of 345 eye amputations carried out in the period 1996–2003, at Rigshospitalet,Denmark

Purpose: The aim of this study was to identify the number of eye amputations, and the causative diagnoses, indications for surgery and surgical techniques applied, and to evaluate a possible change in surgical technique in a tertiary referral centre in Denmark. Methods: The hospital database was screened using surgery codes for patients who had undergone bulbar evisceration, enucleation or orbital exenteration in the period 1996–2003. Patient records were reviewed for gender, age, time since surgery, causative diagnosis (the disease process leading to the indication for amputation), indication for eye amputation, type of surgery and whether an implant was applied. Results: A total of 345 patients were identified as having undergone eye amputation during the 8‐year period. Indications for eye amputation were: painful blind eye (127); neoplasm (119); infection (42); recent injury (25); disfiguring blind eye (25); prevention of sympathetic ophthalmia (5), and other reasons (2). Surgical procedures included 174 eviscerations, 154 enucleations and 17 orbital exenterations. The mean number of surgeries per year was 43.1. An orbital implant was applied in 168 patients. Conclusions: The most frequent indications for eye amputation were painful blind eye (37%) and neoplasm (34%). During the study period, the annual number of eye amputations was stable, but an increase in bulbar eviscerations was noticed. Orbital implants were used in 33% of patients in 1996 and 67% in 2003.