Background The purpose of this retrospective follow-up study is to evaluate the prevalence of patients with thyroid eye disease presenting with apparent unilateral proptosis and determine the occurrence of exophthalmos in contralateral non-proptotic eye over the time. Associated features with this event were evaluated. Methods A cohort of 655 consecutive patients affected by thyroid eye disease with a minimum follow-up of 10 years was reviewed. Exophthalmos was assessed by using both Hertel exophthalmometer and computed tomography (CT). The influence of age, gender, hormonal status and of different therapies such as corticosteroids, radiotherapy and surgical decompression on this disease progression was evaluated. Results A total of 89 patients (13.5%) (95% confidence interval [CI] 15%-10%) had clinical evidence of unilateral exophthalmos at the first visit. Among these, 13 patients (14%) (95% CI 22%-7%) developed subsequent contralateral exophthalmos. The increase of protrusion ranged from 2 to 7 mm (mean of 4.2). The time of onset varied from 6 months to 7 years (mean time: 29 months). Smoking status, young age and surgical decompression are significantly associated with development of contralateral proptosis (p< .05). Conclusions Asymmetric thyroid eye disease with the appearance of unilateral exophthalmos at the initial examination is a fairly frequent event, while subsequent contralateral proptosis occurs less commonly. However, physicians should be aware that young patients, particularly if smokers, undergoing orbital decompression in one eye may need further surgery on contralateral side over time.

Purpose: Identify a reproducible measure of axial globe position (AGP) for multicenter studies on patients with thyroid eye disease (TED). Methods: This is a prospective, international, multicenter, observational study in which 3 types of AGP evaluation were examined: radiologic, clinical, and photographic. In this study, CT was the modality to which all other methods were compared. CT AGP was measured from an orthogonal line between the anterior lateral orbital rims to the cornea. All CT measurements were made at a single institution by 3 individual clinicians. Clinical evaluation was performed with exophthalmometry. Three clinicians from each clinical site assessed AGP with 3 different exophthalmometers and horizontal palpebral width using a ruler. Each physician made 3 separate measurements with each type of exophthalmometer not in succession. All photographic measurements were made at a single institution. AGP was measured from lateral photographs in which a standard marker was placed at the anterior lateral orbital rim. Horizontal and vertical palpebral fissure were measured from frontal photographs. Three trained readers measured 3 separate times not in succession. Exophthalmometry and photography method validity was assessed by agreement with CT (mean differences calculation, intraclass correlation coefficients [ICCs], Bland-Altman figures). Correlation between palpebral fissure and CT AGP was assessed with Pearson correlation. Intraclinician and interclinician reliability was evaluated using ICCs. Results: Sixty-eight patients from 7 centers participated. CT mean AGP was 21.37 mm (15.96–28.90 mm) right and 21.22 mm (15.87–28.70 mm) left (ICC 0.996 and 0.995). Exophthalmometry AGP fell between 18 mm and 25 mm. Intraclinician agreement across exophthalmometers was ideal (ICC 0.948–0.983). Agreement between clinicians was greater than 0.85 for all upright exophthalmometry measurements. Photographic mean AGP was 20.47 mm (10.92–30.88 mm) right and 20.30 mm (8.61–28.72 mm) left. Intrareader and interreader agreement was ideal (ICC 0.991–0.989). All exophthalmometers’ mean differences from CT ranged between −0.06 mm (±1.36 mm) and 0.54 mm (±1.61 mm); 95% confidence interval fell within 1 mm. Magnitude of AGP did not affect exophthalmometry validity. Oculus best estimated CT AGP but differences from other exophthalmometers were not clinically meaningful in upright measurements. Photographic AGP (right ICC = 0.575, left ICC = 0.355) and palpebral fissure do not agree with CT. Conclusions: Upright clinical exophthalmometry accurately estimates CT AGP in TED. AGP measurement was reliably reproduced by the same clinician and between clinicians at multiple institutions using the protocol in this study. These findings allow reliable measurement of AGP that will be of considerable value in future outcome studies.

Background/Aim. To evaluate the efficacy of methotrexate for the treatment of thyroid eye disease (TED).Methods. 36 consecutive patients with active TED, previously treated with corticosteroids but stopped due to the occurrence of side effects, were commenced on methotrexate therapy. Two different weekly doses were administered depending on the weight of the patient (7.5 mg or 10 mg). Clinical activity score (7-CAS), visual acuity (VA), ocular motility, exophthalmos, and eyelid position were retrospectively evaluated at 3, 6, and 12 months and compared with baseline data.Results. There was a statistically significant improvement in 7-CAS at 3, 6, and 12 months after treatment (P<0.0001). There was no significant change in visual acuity. Ocular motility disturbances improved at 6 and 12 months (P<0.001). There was no significant change in exophthalmos (mean 24 mm, SD 3 mm) or eyelid position (marginal reflex distance mean 6 mm, SD 1.5 mm) during the follow-up period. No side effects were registered.Conclusions. Methotrexate therapy is effective in reducing CAS and ocular motility disturbances. No significant improvement in proptosis or eyelid retraction should be expected from this treatment. Eventually, it might be considered a suitable alternative treatment in TED for patients who cannot tolerate steroids.

Purpose: To present an update on the efficacy and safety of immunosuppressive therapy for thyroid eye disease (TED) and to offer a general recommendation for management of TED, in light of these reports.Methods: Data were retrieved from a literature search on PubMed, using the following words: thyroid eye disease, immunosuppressant, corticosteroid, methotrexate, azathioprine, cyclosporine, cyclophosphamide, rituximab, etanercept, adalimumab, tocilizumab, teprotumumab, adverse effects, side effects, and complications.Results: Corticosteroids continue to be the primary medical therapy for TED. Recent research has offered insight into potential differences between oral corticosteroid and intravenous corticosteroid treatment regimens in terms of efficacy and side-effect profiles, which proved more favorable for the latter. The use of some traditional immunosuppressive agents, such as methotrexate and mycophenolate, seems suitable as steroid-sparing medications. In recent years, many scientific reports demonstrated the effectiveness of biologic immunosuppressive agents in the management of TED. Etanercept, adalimumab, and tocilizumab have been shown to be effective in reduction of the inflammatory signs with the possible added advantage of preventing relapse of the disease. Teprotumumab may control the disease activity, and it seems to be very effective in preventing disease progression. Infliximab might be useful in severe TED resistant to steroids and orbital decompression.Conclusions: Steroid therapy remains the first-line therapy for moderate/severe and severe vision-threatening TED. The biological agents may provide a deep and long-standing block of inflammatory activity in TED, with the hope to lower the risk of recurrences and to reduce the need of surgical intervention in moderate-to-severe disease. Indeed, the actual incidence of adverse effects is not yet well assessed because of the paucity of studies. Therefore, their use should be limited to those cases that really need an alternative therapy to steroids, handled by expert physician in this field.

Background: Primary orbital lymphoma is a rare disease that accounts for 10% of all orbital tumors. Radiotherapy on the orbital cavity is the treatment of choice for this unusual presentation of localized non-Hodgkin's lymphoma (NHL). The aim of this study is to retrospectively evaluate the effectiveness and the toxicity of radiation treatment in patients with primary orbital lymphoma. Methods: Forty-seven consecutive patients having primary orbital lymphoma treated in our department between May 1983 and September 2006 were investigated in a retrospective study. Either ⁶⁰Co γ rays or 6 MV X rays were used to deliver daily fractions of 1.8 or 2.0 Gy, 5 times/week, with total doses ranging from 34.2 to 50 Gy. Forty-three patients had stage IE, three had stage II and one stage IV disease. Thirty-eight patients had marginal zone B-cell lymphoma, 5 diffuse large B cell lymphoma, 3 mantle cell lymphoma and 1 Burkitt lymphoma. Local control (LC), disease free survival (DFS), overall survival (OS) and late side effects were evaluated in all patients. Results: With a median follow up of 45 months, LC was obtained in 100% of patients. The estimated 5- and 7-year DFS rates were 75.8% and 55.3%, and the 5- and 7-year OS rates were 88.7% and 79.9% respectively. Acute toxicity was minimal. Late toxicity such as cataract, keratitis, retinopathy and xerophthalmia occurred respectively in 12 (25.5%), 5 (10.6%), 1 (2.1%), and 9 (19.1%) patients. Conclusion: Radiotherapy is an effective and at the same time well tolerated treatment for primary orbital lymphoma.