Orbital Radiation Therapy in Thyroid Eye Disease.

PURPOSE: To review the current literature summarizing the state of knowledge on the use of orbital radiation therapy (ORT) in thyroid eye disease. METHODS: A systematic review and analysis of the literature were performed. MEDLINE/PubMed, Cochrane Library databases, SCOPUS, and recent relevant journal articles were searched. RESULTS: Thyroid eye disease is an autoimmune disorder that has the propensity to affect multiple orbital tissues and can cause permanent vision loss. In moderate to severe disease, treatment may be warranted and can include multiple therapeutic modalities. Orbital radiation therapy is frequently used in this setting and may act to break the inflammatory cycle of glycosaminoglycan production and deposition. There has been a wealth of data regarding the effectiveness of ORT in thyroid eye disease resulting in the publication of treatment algorithms and management guidelines; however, there continues to be a lack of conformity among experts on the exact role of ORT in thyroid eye disease. CONCLUSION: The multiple different thyroid eye disease classification schemes and the concurrent use of other therapeutic modalities challenge the interpretation of studies evaluating the effectiveness of thyroid eye disease. Despite these limitations, the current literature indicates that ORT is generally safe and well tolerated. Orbital radiation therapy may have a modest effect on motility and proptosis early in the disease process. It is unclear whether ORT leads to improved quality of life. There are some data to support the use of ORT to prevent compressive optic neuropathy.

Safety and efficacy of combined immunosuppression and orbital radiotherapy in thyroid-related restrictive myopathy: two-center experience.

PURPOSE: To evaluate the safety and efficacy of oral steroids when combined with long-term oral azathioprine (AZA) and orbital radiotherapy in patients with active thyroid-related restrictive myopathy. METHODS: A total of 88 patients from adnexal outpatient clinics of Bristol Eye Hospital, UK, and 2nd Department of Ophthalmology at Aristotle University of Thessaloniki, Greece, were enrolled in a retrospective, twin-center study. All patients were diagnosed with active thyroid eye disease and concomitant restrictive myopathy. Treatment included oral AZA, low-dose steroids, and orbital radiotherapy (20 Gy). Clinical activity scores as well as orthoptic assessments were consistently evaluated. Clinical activity scores, improved levels of diplopia, and single muscle excursions were considered major criteria for treatment success. RESULTS: Clinical success was achieved in 54 (61.4%), 57 (64.8%), and 61 (69.3%) patients at 3-, 6-, and 12-month time points, respectively, after the initiation of the combined treatment. At 18 months following initiation of treatment, the percentage of treatment success reached 73.9% (n = 65). Nine patients developed AZA-related side effects. In 4 patients the drug had to be discontinued. CONCLUSIONS: Combined immunosuppression with orbital radiotherapy appears to reduce morbidity in patients with marked restrictive myopathy by improving major motility parameters such as diplopia and duction amplitude.

Reduced risk of compressive optic neuropathy using orbital radiotherapy in patients with active thyroid eye disease.

PURPOSE: To compare the risk of developing compressive optic neuropathy in patients with active thyroid eye disease (TED) treated with corticosteroids with or without orbital radiotherapy. DESIGN: Retrospective single-center case-control study. METHODS: The clinical charts of 351 patients with active TED who received corticosteroids with or without orbital radiotherapy between 1999 and 2010 were reviewed. Patients with compressive optic neuropathy at the time of presentation were excluded. Group 1 received corticosteroids only and Group 2 received corticosteroids as well as orbital radiotherapy. The primary outcome measure was the development of compressive optic neuropathy. Secondary outcome measures were changes in other parameters indicating the activity of TED, including soft tissue inflammation, diplopia, ocular motility restriction, and appearance. RESULTS: There were 144 cases in Group 1 and 105 in Group 2. Both groups were matched for age, sex, and stability of thyroid function. The 2 groups differed only in the modality of treatment for active TED. The main indication for treatment in both groups was soft tissue inflammation. Corticosteroids were initiated an average of 2.6 months following symptom onset in Group 1 and 2.5 months in Group 2. Group 2 received orbital radiotherapy on average 4.2 months following the initiation of corticosteroid therapy and 8% (9/105) were intolerant to corticosteroids. At an average of 3.2 years follow-up, compressive optic neuropathy had developed in 17% (25/144) of Group 1 and 0% of Group 2 (P < .0001), on average 5.5 months following the initiation of corticosteroid therapy. Although both groups experienced a significant reduction in periocular inflammation, the radiotherapy-treated group demonstrated a significantly greater improvement in ocular motility. CONCLUSION: The rate of compressive optic neuropathy was significantly lower and improvement in ocular motility greater in patients receiving orbital radiotherapy in addition to corticosteroids. Patients with active TED appear to have an effective and sustained response to orbital radiotherapy combined with corticosteroids that is protective against disease progression and the development of compressive optic neuropathy.

Orbital radiotherapy for thyroid eye disease.

PURPOSE OF REVIEW: Orbital radiotherapy has been used for over 60 years to treat thyroid eye disease (TED) alone or in conjunction with glucocorticoids or orbital decompression surgery. However, numerous observational and randomized controlled trials have yielded conflicting results concerning its efficacy. This review highlights recent systematic reviews concerning the use of radiotherapy for TED. RECENT FINDINGS: Three recent systematic analyses have drawn different conclusions about its efficacy. This relates to the varied nature of the disease, the different selection criteria, and different outcome measures (often focussing on global indices or clinical activity scores rather than subjective quality of life scores and individual disease parameters as specified by the VISA Classification). SUMMARY: Radiotherapy should only be offered in the early active phase, is most effective in combination with glucocorticoids, and may have specific indications for dysthyroid optic neuropathy (DON), inflammatory periocular changes, or progressive motility disturbance. Future research may study its potential benefit in preventing or treating DON and compare the ability of combination radiotherapy/intravenous (i.v.) glucocorticoids versus i.v. glucocorticoids monotherapy for limiting complications from progressive TED.

Novel therapeutic option for orbital atypical lymphoid hyperplasia.

Ocular lymphoid tumours represent a spectrum of lymphoproliferative disease and can be subdivided into benign or reactive lymphoid hyperplasia, indeterminate or atypical lymphoid proliferations and malignant lymphoma. Treatment options include a wait and watch approach, systemic steroids, local radiotherapy or systemic chemotherapy. We describe a case of bilateral atypical lymphoid hyperplasia treated successfully with combination immunotherapy and radiotherapy. A 60-year-old lady presented with proptosis and left supra-orbital mass and was diagnosed to have bilateral atypical lymphoid hyperplasia. She had extensive extraocular facial infiltrates but no other sites of involvement on staging investigations. She was treated with eight doses of rituximab 375 mg/m² at weekly intervals with a good partial response, followed by consolidative radiotherapy. Rituximab may be an effective treatment adjunct/alternative for patients with atypical lymphoid hyperplasia of the orbit, particularly where widespread lesions preclude the use of initial radiotherapy.

Failure of radiation therapy in orbital xanthogranuloma.

PURPOSE: The efficacy of radiation therapy in orbital xanthogranuloma in patients who fail medical therapy is unclear. The purpose of this study was to ascertain its effectiveness. METHODS: The records of 11 cases were reviewed retrospectively for histopathologic findings, age, gender, site of involvement, clinical manifestations, and outcomes of treatment. The case histories of the 4 patients treated with radiation, all of whom had failed medical treatment, were described. RESULTS: Of 11 patients, 5 were female, and all were white. The age range at the time of presentation was 25 to 85 years. Nine patients had bilateral involvement. Five patients, all of whom had bilateral disease, had systemic manifestations or autoimmune disease thought to be related to their orbital disease. In general, patients treated with systemic corticosteroids had at least a partial response of their lesion. However, none of the 4 patients treated with orbital radiation (3 of whom had not responded to steroid treatment and 1 of whom had responded only to high-dose steroids) experienced improvement, and at least 3 experienced exacerbation of their disease. The histologic features before treatment in all cases were similar and consistent with xanthogranuloma. CONCLUSION: Orbital xanthogranuloma may be a unilateral or bilateral condition. Particularly when bilateral, it may be associated with similar lesions elsewhere or with systemic autoimmune disorders. The results of this study suggest that fractionated radiotherapy not only may be ineffective but also may exacerbate the progression of the orbital lesions in patients who do not respond to medical therapy or who are steroid dependent on intolerable doses of medication.

A retrospective study on the efficacy of total absorbed orbital doses of 12, 16 and 20 Gy combined with systemic steroid treatment in patients with Graves' orbitopathy.

BACKGROUND: Graves' disease (GD) is an autoimmune disease that typically affects the thyroid gland. Thirty to sixty percent of patients also suffer from orbital inflammation. Retrobulbar radiotherapy for Graves' orbitopathy (GO) has been used for decades, though there is no direct evidence for the influence of dose and fractionation schedules on various signs and symptoms. Indeed, optimal fractionation schedules and recommended total irradiation doses are still a matter of discussion. Our aim was to investigate treatment efficacy of retrobulbar irradiation for GO at different total absorbed doses and fractionation schedules. METHODS: A retrospective evaluation of 129 patients who were examined before, as well as 6-8 months after irradiation with different treatment schedules at eight radiotherapeutic departments. Total absorbed doses were 12, 16, or 20 Gy. All patients were additionally treated with systemic application of corticosteroids. Treatment efficacy was evaluated through assessment of proptosis, horizontal and vertical ocular motility and of clinical activity (CAS). Overall group and individual responses were evaluated. Treatment response was defined as inactivation of GO, reduction of proptosis by at least 2 mm, improvement of motility by > or = 8 degrees or unchanged normal parameters. RESULTS: Prior to irradiation, neither age, disease duration, gender distribution, smoking behavior or serologic parameters, nor clinical activity or severity stages varied significantly between groups. Neither did outcome measures, except proptosis, differ significantly. Retrobulbar irradiation led to inactivity of GO in approximately 80% of patients, with no significant group difference. After irradiation with 16 and 20 Gy, vertical motility improved in a significantly higher percentage of patients than after irradiation with 12 Gy. Median improvement of vertical motility in responding patients was excellent in all groups (15 degrees at 12 Gy, 10 degrees at 16 Gy, 10 degrees at 20 Gy). Horizontal motility did not change significantly. CONCLUSION: If the aim of retrobulbar irradiation is primarily to reduce soft-tissue signs, lower doses are sufficient. If a patient also suffers from dysmotility, doses exceeding 12 Gy may be more effective.

Oftalmopatia tireoidea revisitada: [revisão] / Thyroid ophthalmopathy revisited: [review]

A oftalmopatia tireoidea é doença orbitária autoimune intimamente associada com o hipertireoidismo, porém podendo existir separadamente. Pode preceder, coincidir ou suceder o início da disfunção tireoidea, raramente ocorrendo em eutireoideos ou hipotireoideos. Os músculos extraoculares são os principais alvos acometidos e tornam-se aumentados de volume, determinando oftalmoplegia e proptose. Outros sinais importantes incluem retração palpebral, hiperemia conjuntival e edema periorbitário. Perda visual pode ocorrer se há compressão do nervo óptico no ápice orbitário. A oftalmopatia tireoidea é caracterizada por inflamação, congestão, hipertrofia e fibrose da gordura e músculos orbitários. A atividade da doença é dividida em fase aguda ou inflamatória, seguida pela fase inativa associada com alterações fibróticas e infiltração gordurosa. O diagnóstico é clínico, e quando este é difícil ou se suspeita de neuropatia óptica os métodos de imagem são indicados. A tomografia computadorizada e a ressonância magnética podem confirmar o diagnóstico e avaliar a área crítica do ápice orbitário. A ressonância magnética é superior, em virtude da resolução tecidual e da sua capacidade de avaliar a atividade da doença (mediante sequências com TR longo) e detectar alterações inflamatórias, auxiliando o planejamento terapêutico no momento certo, melhorando o prognóstico.

Thyroid ophthalmopathy is an autoimmune orbital disorder closely associated with Graves' disease, although both conditions may also occur isolatedly. Thyroid ophthalmopathy may precede, coincide or follow the thyroid dysfunction onset and may rarely occur in euthyroid and hypothyroid patients. The extraocular muscles are most frequently involved and become enlarged resulting in ophthalmoplegia and proptosis. Other relevant signs include palpebral retraction, conjuctival hyperemia and periorbitary edema. Visual loss may occur in association with compressive optic neuropathy at the orbital apex. Thyroid ophthalmopathy is characterized by inflammation, congestion, hypertrophy and fibrosis involving fat and the orbital muscles. The disease activity is divided into two phases: an acute or inflammatory phase and a second one corresponding to an inactive phase associated with fibrotic changes and fat infiltration of the retrobulbar tissues. The diagnosis is based on clinical findings and imaging methods are indicated in case of doubt or suspicion of optic neuropathy. Computed tomography and magnetic resonance imaging can confirm the diagnosis, allowing the evaluation of the critical region of the orbital apex. Magnetic resonance imaging is the method of choice considering the superior tissue contrast resolution, besides the capacity of evaluating the disease activity by means of long TR sequences and detecting inflammatory changes, with a relevant role in a timely therapeutic planning, which may improve the prognosis.

The use of radiotherapy for the treatment of localized orbital amyloidosis.

OBJECTIVE: To describe two patients with localized orbital amyloidosis and the response of their condition to surgical debulking followed by external beam radiotherapy. DESIGN: Retrospective noncomparative interventional case series. OUTCOME MEASURES: Stabilization or regression of orbital signs after treatment. METHODS: Patients with biopsy-proven diagnosis of localized progressive orbital amyloidosis received 34 and 30 Gy fractionated external beam radiotherapy. The clinical case notes and histopathology for the two patients were reviewed. RESULTS: A 69-year-old man with orbital amyloid deposition in association with localized MALT lymphoma had a marked improvement in orbital signs following surgical debulking and radiotherapy, with no recurrence over two years. A 59-year-old woman with localized orbital amyloidosis showed regression of disease after surgical debulking and radiotherapy, with no evidence of recurrence after six years of follow-up. CONCLUSION: External beam radiotherapy following surgical debulking appears to halt the progression of localized orbital amyloidosis. Radiotherapy may be used in conjunction with surgical debulking of disease.

A case of orbital Rosai-Dorfman disease responding to radiotherapy.

Rosai-Dorfman disease (RDD) is a rare histiocytic disorder most often characterized by painless cervical lymphadenopathy, but it may also present with orbital disease. The clinical course of RDD is variable; it can be either relapsing-remitting or progressive, and the outcome relates to clinical location and treatment response. Orbital RDD can have an insidious onset and similar presentation to other ophthalmic conditions; this can result in a delayed diagnosis. Nearly all cases of orbital RDD cause visual disturbances and require treatment. Because orbital RDD is an uncommon presentation, a variety of interventions have been employed, including surgery, immunotherapy, chemotherapy, and radiotherapy. We present a case of salvage radiotherapy for progressive orbital RDD refractory to surgery and chemotherapy in a pediatric patient.

Treatment of benign orbital pseudolymphomas with the monoclonal anti-CD20 antibody rituximab.

OBJECTIVE: To report the results of treating patients with orbital pseudolymphomas with the anti-CD20 monoclonal antibody rituximab. PATIENTS AND METHODS: Patients were included in the study if they had an orbital mass and biopsy-proven orbital pseudolymphomas between January 1, 1998, and December 31, 2005. The study focused on patients treated with rituximab. RESULTS: Ninety-eight patients were evaluated, and the biopsy results revealed malignant non-Hodgkin lymphoma in 72 (73%); the other 26 (27%) had a pseudolymphoma. Eleven (42%) of the 26 patients with a pseudolymphoma were treated with rituximab, 375 mg/m2, intravenously each week for 4 doses, and 10 (91%) of the 11 responded. Seven patients were either treated with maintenance rituximab or successfully retreated with rituximab after relapse. None of the 10 responders has become refractory to rituximab. CONCLUSION: Benign lymphoproliferative tumors are responsive to monoclonal antibody therapy targeted to B lymphocytes. Rituximab should be considered a treatment option for orbital pseudolymphomas.

Palliative treatment of Erdheim-Chester disease with radiotherapy: a Rare Cancer Network study.

A retrospective study of the use of palliative external beam radiotherapy (EBRT) in nine patients with Erdheim-Chester disease was conducted through the Rare Cancer Network. Patients received EBRT for bone pain, brain infiltration, or retro-orbital involvement. EBRT typically provided short-term palliation, with later recurrence of symptoms in most cases.

Retrobulbar irradiation for thyroid-associated orbitopathy: double-blind comparison between 2.4 and 16 Gy.

PURPOSE: Retrobulbar irradiation is used as a standard therapy for thyroid-associated orbitopathy. The evidence of its effectiveness is, however, scarce. Doses from 2.5 to 20 Gy have been recommended. METHODS: Forty-three patients with active thyroid-associated orbitopathy were irradiated with 2.4 Gy and 43 with 16 Gy. Five measures of outcome were used: (1) appearance of the eye region, documented with photographs; (2) Hertel exophthalmometry; (3) range of vertical eye movements; (4) eye muscle thickness (sum of three MRI sections across the eight rectus eye muscles); and (5) complaints, indicated on a visual analog scale. RESULTS: At 3 and 6 months after irradiation, no difference between 2.4 and 16 Gy was found in any of the five outcome measures (p between 0.099 and 0.993; Kruskal-Wallis test, Holm correction). Most outcome measures were slightly, but not significantly, improved in both the 2.4 and the 16 Gy groups. Patient complaints had improved significantly in both groups and the eye muscle thickness was significantly reduced in the 2.4 Gy group after 6 months. CONCLUSION: The lack of a difference between 2.4 and 16 Gy is compatible with four different interpretations: (1) the irradiation could be ineffective; (2) the maximal effect could be already reached at 2.4 Gy; (3) the maximal effect could lie between 2.4 and 16 Gy; and (4) the effect could increase beyond a threshold of >or=16 Gy. From general experience with inflammatory disease, the last two possibilities are unlikely; only the first two interpretations carry some probability. Although the design of the study did not allow a distinction between these two possibilities, we conclude that retrobulbar irradiation for thyroid-associated orbitopathy should not exceed 2.4 Gy.

Eosinophilic granuloma of the orbit: a paradox of aggressive destruction responsive to minimal intervention.

PURPOSE: To describe the findings and outcomes in eosinophilic granuloma (unifocal Langerhans cell histiocytosis [LCH]) of the orbit, and to explain the paradox of aggressive bone destruction responsive to minimal intervention. METHODS: Retrospective, consecutive, interventional case series of patients treated from 1985 through 2001. Minimum inclusion criteria were demonstration of CD1a positivity or Birbeck granules, treatment by a single surgeon, systemic evaluation by a pediatric oncologist, and follow-up of 12 months. A pathogenetic construct was assembled from general LCH concepts and the specific orbital findings. RESULTS: Seven patients met study criteria. All were male, 2 to 16 years of age. All had eyelid or forehead swelling and osteolytic defects, with symptoms of 2 to 6 weeks' duration. All underwent incisional biopsy, with frozen-section examination suggestive of LCH in 6 of 7 cases. The 2 earliest patients received low-dose irradiation after simple biopsy. The 5 most recent patients had subtotal curettage at the time of biopsy; 4 of 5 received simultaneous intralesional corticosteroid injection. In all cases, systemic evaluation showed no other focus of LCH, reossification was timely, and no local recurrence or additional focus was noted in follow-up of 1 to 17 years. CONCLUSIONS: Transient immune dysfunction may provoke the cytokine-mediated proliferation of pathologic Langerhans cells within the hematopoietic marrow of the anterolateral frontal bone. These cells cause osteolysis through elaboration of interleukin-1 and prostaglandin E2. Corticosteroids can inhibit the mediators. We recommend incisional biopsy, frozen-section provisional diagnosis, subtotal curettage, intralesional corticosteroid instillation, postoperative systemic evaluation, and long-term follow-up.

Orbital presentation of posttransplantation lymphoproliferative disorder: a small case series.

OBJECTIVE: To describe a small series of patients with orbital presentation of posttransplantation lymphoproliferative disorder (PTLD). DESIGN: Retrospective, interventional case series. PARTICIPANTS: Three patients with orbital presentation of histologically diagnosed PTLD. METHODS: Review of medical records. MAIN OUTCOME MEASURES: Measured parameters included vision, proptosis, and tumor extent. RESULTS: Three cases of orbital PTLD are described. In two of the cases, the tumor initially demonstrated orbital signs and symptoms, whereas in the third case, orbital and systemic signs were synchronous. Two of three patients had disseminated disease discovered at the time of presentation. One adult patient had synchronous presentation of PTLD in the orbit and prostate. One pediatric patient had tumor dissemination to the liver at the time of presentation. The PTLD tumors were classified histologically as diffuse large cell lymphoma of monomorphic or immunoblastic type in all three cases. Treatment included local irradiation, decreased immunosuppression, and antilymphocyte monoclonal antibodies. CONCLUSIONS: Orbital presentation is a rare manifestation of PTLD. However, ophthalmologists must consider this diagnosis carefully in organ transplant recipients with subtle orbital signs and symptoms at presentation. Early detection may alter prognosis. In each case presented, the diagnosis was established via lesion biopsy and subsequent histologic or flow cytometric evaluation, or both.