Low- vs. high-dose radiotherapy in Graves' ophthalmopathy: a retrospective comparison of long-term results.

PURPOSE: Radiotherapy represents an effective treatment option in Graves' ophthalmopathy (GO), leading to palliation of clinical symptoms. However, there are only a limited number of trials comparing the effectiveness of low- vs. high-dose radiotherapy. METHODS: We analyzed 127 patients treated with radiotherapy for stage 3/4 GO (NOSPECS classification). Patients were treated with single doses of 2.0 Gy (cumulative dose 20 Gy) until 2007, afterwards a single dose of 0.8 Gy (cumulative dose 4.8 Gy) was applied. With a median follow-up-time of 9.0 years, the treatment efficacy (overall improvement, sense of eye pressure, lid edema, ocular motility, exophthalmos, subjective vision, and diplopia) and adverse effects were analyzed by a standardized survey. RESULTS: Overall, 63.8% described improvement of symptoms after radiotherapy. No significant differences in overall treatment response and improvement of main outcome measures between low- or high-dose radiotherapy treatments are detectable, while low-dose radiotherapy leads significantly more often to retreatment (13.1% vs. 1.7%, p = 0.016). The main independent predictor of treatment response is the presence of lid edema (odds ratio, OR, 3.53; p = 0.006). CONCLUSION: At long-term follow-up, the majority of patients reported palliation of symptoms with limited adverse effects, suggesting clinical effectiveness of radiotherapy for amelioration of GO symptoms independent of low- or high-dose radiotherapy.

Metastasis of advanced gastric cancer to the extraocular muscle: a case report.

BACKGROUND: Metastatic tumors in the orbit, especially from gastric cancer, are rare. We present a rare case of extraocular muscle metastasis from gastric cancer and raise consideration of metastasis to extraocular muscle as a differential diagnosis of proptosis/lid swelling in a patient with history of malignancy. CASE PRESENTATION: A 54-year-old Japanese woman presented with proptosis, lid swelling, diplopia, and retro-orbital pain in her left eye, which she had been experiencing for 1 day. She had a medical history of poorly differentiated adenocarcinoma of the stomach, which had metastasized to several organs. A computed tomography scan showed enlargement of the medial rectus muscle in her left eye. She was diagnosed as having gastric cancer metastasis to the medial rectus muscle of her left eye, and received a total of 20 Gy radiation therapy to the orbit, which resulted in resolution of her ocular symptoms. She died 3 months after her initial visit to our ophthalmic department. CONCLUSIONS: Metastasis from malignancy should be considered in the differential diagnosis of a patient presenting with proptosis or lid swelling who has a history of gastric cancer. Radiation therapy of metastases in the orbit may be an effective treatment in such cases.

Natural history of graves' orbitopathy after treatment.

Intravenous glucocorticoids are used for Graves' orbitopathy, alone or associated with/followed by additional treatments (orbital radiotherapy, orbital decompression, palpebral or eye surgery). However, the relation between associated/additional treatments and other variables with Graves' orbitopathy outcome following intravenous glucocorticoids is not clear. Thus, the present study was conducted to investigate retrospectively the impact of associated/additional treatments and other variables on Graves' orbitopathy outcome after intravenous glucocorticoids. We evaluated 226 untreated Graves' orbitopathy patients. Following first observation, patients were given intravenous glucocorticoids and re-examined after a median of 46.5 months. The end-points were the relation between Graves' orbitopathy outcome, outcome of NOSPECS score and of the single Graves' orbitopathy features with several variables, including associated/additional treatments. All Graves' orbitopathy features improved significantly after treatment. Overall, Graves' orbitopathy improved in ~60 % of patients (responders), whereas it was stable or worsened in ~40 % of patients (non-responders). Time between first and last observation and clinical activity score at first observation correlated significantly with Graves' orbitopathy outcome. The outcomes of NOSPECS, eyelid aperture, clinical activity score and diplopia correlated with time between the first and last observation. The NOSPECS outcome correlated with gender. The outcomes of proptosis, eyelid aperture and visual acuity correlated with orbital decompression. The outcome of diplopia correlated with orbital radiotherapy. Taking into account the limitations of retrospective investigations, our findings confirm that time (i.e. the natural history of Graves' orbitopathy) is a key factor in determining the long-term outcome of Graves' orbitopathy, radiotherapy is effective for diplopia, and orbital decompression is followed by an amelioration of several Graves' orbitopathy features.

[Glomus tumor with diplopia]. / Diplopie prin tumora glomica--caz clinic.

This paper highlights the case of a 46-year-old female patient who seeks ophthalmic medical advice for her complaint about double vision on right gaze. Patient's medical history reveals several symptoms like headaches, progressive hearing loss on right side and dysphonia for which all investigations proved irrelevant. Thourough clinical examination, lab exams and imaging techniques revealed the cause for this symptoms i.e. glomic tumour with middle ear extention. We find this case to be exceptional as ocular symptoms led to the diagnose of a non-ocular serious, possible life threatening condition, bearing in mind that previously occured non-ocular symptoms couldn't elucidate the cause.

[Radiotherapy for Graves' ophthalmopathy]. / Radiotherapie der endokrinen Orbitopathie.

Graves' ophthalmopathy (GO) is the most frequent extrathyroidal manifestation of Graves' disease, an autoimmune disorder of the thyroid, whereas the precise pathogenesis still remains unclear. In Hashimoto's thyroiditis the occurrence of proptosis is an extremely rare event. The therapy for middle and severe courses of GO shows in partly disappointing results, although several therapy modalities are possible (glucocorticoid therapy, radiotherapy, antithyroid drug treatment, surgery). All these therapies lead in only 40 - 70 % to an improvement of the pathogenic symptoms. An intensive interdisciplinary cooperation is necessary to satisfy the requirements for the treatment of Graves' ophthalmopathy. As a consequence of the very different results of the few of clinical studies that were accomplished with reference to this topic, treatment by radiotherapy in the management of the disease is presently controversially discussed. In the German-speaking countries the radiotherapy is, however, firmly established as a therapy option in the treatment of the moderate disease classes (class 2-5 according to NO SPECS), especially if diplopia is present. This article describes the sequences, dosages and fractionation schemes as well as the risks and side effects of the radiotherapy. Altogether, radiotherapy is assessed as an effective and sure method. The administration of glucocorticoids can take place before the beginning of or during the radiotherapy. For the success of treatment the correct selection of patients who may possibly profit from a radiotherapy is absolutely essential. By realising that GO proceeds normally over a period of 2-5 years, which is followed by a period of fibrotic alteration, the application of the radiotherapy in the early, active phase is indispensable. A precise explanation for the effects of radiotherapy in treatment of the GO does not exist at present. The determination of the most effective irradiation doses was made from retrospectively evaluated collectives. Recently the results of a national survey of all German RT departments were published, initiated by the working group of the DEGRO (German Society of Radiooncology). In the most of the German radiooncology departments irradiation with 8 to 10 x 1.8-2.0 Gy 5 x weekly to 16 or 20 Gy is standard. Two recently published prospective German studies pointed out the equivalence of the effectiveness of a short therapy in low dose ranges up to 2.4 Gy as well as of a low proportioned irradiation during a longer period in relation to a standard therapy with 20 Gy. That is why at the moment it is not possible to give a definite recommendation with reference to dosages or the fractionation schemes. In 2003 the first European group (European Group on Graves ' Orbitopathy Experience -- EUGOGO) was founded for pursuing investigations of GO in multi-centric studies, mainly to improve therapy results.

Management of thyroid eye disease.

Thyroid eye disease (TED) is the most frequent extrathyroidal manifestation of Graves' disease. In most instances it is mild and non-progressive, but in 3%-5% of cases it is severe. Non-severe TED requires only supportive measures, such as eye ointments, sunglasses and prisms. By contrast, severe TED requires aggressive treatment, either medical (high-dose glucocorticoids, orbital radiotherapy) or surgical (orbital decompression). The choice of treatment relies on the assessment of both TED severity and activity. Removal of controllable risk factors, especially cigarette smoking, is important to improve the course and the therapeutic outcome. A coordinated approach to the treatment of hyperthyroidism and TED is also required. Novel promising treatments, to be verified in large series of patients, include somatostatin analogues and cytokine antagonists.

Radiotherapy in thyroid eye disease: the effect on the field of binocular single vision.

PURPOSE: Thyroid eye disease (TED) can be a functionally disabling condition if ocular muscle involvement causes diplopia. The extraocular muscle restriction creates a reduced or eccentric field of binocular single vision (BSV). Orbital radiotherapy is now widely used in the treatment of TED, and although it has been reported as improving ocular motility, there have been few quantitative studies of the effect of treatment on ocular motor function. METHODS: Retrospective case note review of patients undergoing orbital radiotherapy for TED between 1992-1998 identified 79 case records. A total of 27 patients had diplopia in primary position or a significantly reduced binocular field before undergoing radiotherapy. The fields of BSV were analyzed pretreatment and at 3, 12, and 24 months after therapy to assess any improvement in function. We used the field of BSV as an outcome measure because it can be quantified and is a good indicator of functional ability. RESULTS: None of the 12 patients with double vision in primary position pretreatment regained a central binocular field with radiotherapy alone. Of the 15 patients with a central but reduced binocular field, 8 (53%) remained unchanged with treatment. In 4 patients (26.6%), there was an improvement in the field, while in 3 (20%) the field deteriorated. In all, 12 patients (44%) went on to require strabismus surgery. CONCLUSIONS: Orbital radiotherapy alone is ineffective in treating restrictive thyroid myopathy and improving binocular function.

Radiotherapy for thyroid orbitopathy. Effects on extraocular muscle balance.

OBJECTIVE: To investigate the effects of radiotherapy on the restrictive ophthalmopathy and strabismus that occur with Graves' orbitopathy. DESIGN: A prospective study of patients with motility disturbances due to thyroid orbitopathy, followed by serial quantitative measurements of ocular restrictions and deviations, both before and at 1 and 6 months after treatment with high-energy radiotherapy. SETTING: Urban subspecialty private practice. PATIENTS: Thirty-three consecutive patients with restricted extraocular movements and diplopia secondary to thyroid orbitopathy who were treated with radiotherapy were seen during an 8-year period. MEASURES: Maximal horizontal and vertical ductions, plus ocular deviations in primary and reading positions of gaze, were quantitatively evaluated by one clinical investigator to ensure consistency. RESULTS: Statistically significant improvement in gaze restriction on supraduction and improvement of vertical and horizontal strabismus were demonstrated at follow-up visits after treatment. CONCLUSIONS: Although statistically significant improvement of motility disturbances were demonstrated after radiotherapy, there was less than desirable functional improvement of restrictive ophthalmopathy and strabismus; thus the usefulness of radiotherapy was limited when it was used alone to treat diplopia.

Graves ophthalmopathy: MR evaluation of 10-Gy versus 24-Gy irradiation combined with systemic corticosteroids.

PURPOSE: To establish the most effective radiation dose for treatment of Graves ophthalmopathy (GO). MATERIALS AND METHODS: A combination of 10 Gy (n = 15) or 24 Gy (n = 16) of radiation and corticosteroids was used to treat 31 patients with GO. Magnetic resonance (MR) images obtained before treatment showed swollen extraocular muscles with prolonged T2 relaxation times in all patients. RESULTS: Before therapy, T2 relaxation time of extraocular muscle was 79.6 msec (95% confidence interval, 76.3, 82.9) in the 24-Gy group and 77.4 msec (95% confidence interval, 74.6, 80.1) in the 10-Gy group (P = .32). After therapy, T2 relaxation time was 62.8 msec (95% confidence interval, 61.2, 64.4) in the 24-Gy group and 68.9 msec (95% confidence interval, 66.8, 71.1) in the 10-Gy group. In the 24-Gy group, there was a significant decrease in T2 relaxation times (P = .001) and clinical response to initial treatment was better. At 1- and 3-month follow-up, the resistance rate was lower in the 24-Gy group. CONCLUSION: In treatment of GO, 24 Gy of radiation is a more effective dose than 10 Gy when combined with systemic corticosteroids.

Therapy of Graves' ophthalmopathy with intravenous high-dose steroid followed by orbital irradiation.

We investigated the effects of intravenous high-dose steroid therapy followed by orbital irradiation for Graves' ophthalmopathy in eight patients. All patients presented with diplopia or fixed globes. Extraocular muscle dysfunction showed excellent improvement after the combined therapy; diplopia disappeared completely in five of them, and one patient with fixed globes showed normal eye movement. Two other patients also exhibited great improvement, although their diplopia persisted. Their ophthalmopathy index was decreased from (mean +/- SD) 4.25 +/- 0.82 to 0.75 +/- 1.48. Extraocular muscle enlargement, assessed by magnetic resonance imaging study after the radiotherapy, was also reduced after the combined therapy, although two patients did not show remarkable enlarged extraocular muscles. There was no change in extraocular muscle thickness 6-9 months after the therapy, and the ophthalmopathy index did not show change in a long follow-up (maximum 37 months after the therapy). These results suggest that high-dose methylprednisolone followed by orbital radiotherapy is a good therapeutic design for Graves' ophthalmopathy and justify a prospective randomized trial.

Clinical evaluation of radiotherapy for Graves' ophthalmopathy.

Seventeen patients with moderately severe ophthalmopathy due to Graves' disease were treated by cobalt or supervoltage radiotherapy. All patients complained of diplopia. The mean proptosis value was 21.4 mm. Three patients (18%) showed good response, 7 (41%) moderate and 7 minimal or no response. Improvement was noted mainly in soft tissue changes and diplopia, while proptosis decreased in only 5 patients. All except one patient who had marked extraocular muscle involvement revealed by computed tomography responded to treatment. These data indicate that radiotherapy may be indicated in patients with progressive ophthalmopathy, especially in those who are associated with extraocular muscle enlargement.

Radiotherapy of severe ophthalmic Graves' disease.

The effects of orbital irradiation on Ophthalmic Graves' Disease (OGD) were evaluated in 24 patients. All patients were irradiated after a median duration of eye symptoms of 12 months (range 3-36 months). Irradiation therapy was performed for loss of visual acuity, progressive diplopia and/or keratitis due to recent progression of eye symptoms. During a follow up period of 2-4.5 years, in 11 patients after irradiation, a mean decrease in proptosis oculi of 5.1 mm was found while 8 of these patients showed a mean increase in visual acuity of 0.26. Apparently, a decrease of activity of the inflammatory process in retrobulbar tissues can be achieved after irradiation, over a longer period of time in many patients. Furthermore concomitantly administered corticosteroids could be tapered off completely in all patients. Treatment of severe OGD of recent onset with irradiation, in combination with a short course of prednisone is very effective. This study also shows that prednisone treatment alone is not very successful because of the high recurrence rate of eye sings after decrease of the dose and the many side effects of the drug.