The Role of Radiotherapy in Orbital Pseudotumor: A Systematic Review of Literature.

PURPOSE: Orbital pseudotumor (or pseudotumor orbitae) is a benign entity, also known as idiopathic orbital inflammatory syndrome (IOIS), which encompasses a wide range of non-tumoral, space occupying lesions of the orbit. In selected cases of refractory disease or presence of side effects or even comorbidities that limit systemic therapies, radiotherapy could play a role in the management because it has been demonstrated that irradiation is effective in suppressing the inflammatory process. METHODS: A systematic review of the literature about the main scientific databases was launched and the time interval included all published articles present in the databases from their inception until September 2020. RESULTS: We were able to identify 19 studies eligible for inclusion in this review from 1978 to 2018. Overall the data of 241 patients were collected and are presented in this systematic review. The response rate varied between 74% and 100% with a median recurrence rate of 10%. The median total dose was 20 Gy whereas the mean total dose was 21 Gy with a range from 4 to 36 Gy. Regarding the fractionation, 2 Gy/fraction daily was the most widely used. CONCLUSIONS: Radiotherapy seemed to achieve good response rates however, in most of the studies, inclusion criteria and outcome parameters are not uniform and therefore the results are difficult to compare. Often important parameters such as chronic pain and permanent functional deficits are not assessed in the outcome. Therefore, prospective studies, with good cohort characteristics and a clear definition of the outcome, are required.

Radiation Therapy for Benign Disease: Keloids, Macular Degeneration, Orbital Pseudotumor, Pterygium, Peyronie Disease, Trigeminal Neuralgia.

Although the use of ionizing radiation on malignant conditions has been well established, its application on benign conditions has not been fully accepted and has been inadequately recognized by health care providers outside of radiation therapy. Most frequently, radiation therapy in these benign conditions is used along with other treatment modalities, such as surgery, when the condition causes significant disability or could even lead to death. Radiation therapy can be helpful for inflammatory/proliferative disorders. This article discusses the present use of radiation therapy for some of the most common benign conditions.

Radiotherapy for Orbital Pseudotumor: The University of Florida Experience.

BACKGROUND: To evaluate outcomes after definitive radiotherapy for orbital pseudotumor. METHODS: We reviewed adult patients treated between 1971 and 2012. RESULTS: 20 patients with 8.0-year median follow-up were analyzed. Symptoms improved in 75% of patients: 40% showed a complete response, 35% partial response, and 20% had stable disease. The disease progressed in 1 and recurred in 8 patients. Local control rates were 63% and 53% at 5 and 10 years, respectively. The most common toxicities were cataracts (10%) and dry eye (10%). CONCLUSIONS: Radiotherapy for orbital pseudotumor is well-tolerated and results in long-term control in most patients, with local control in over half.

Adjunctive Orbital Radiotherapy for Ocular Adnexal IgG4-related Disease: Preliminary Experience in Patients Refractory or Intolerant to Corticosteroid Therapy.

PURPOSE: To present the clinical outcomes of combined orbital radiotherapy and systemic corticosteroid for patients with refractory ocular adnexal IgG4-related disease. METHODS: We retrospectively reviewed 3 patients with histopathologically confirmed ocular adnexal IgG4-related disease who had been refractory or intolerant to corticosteroid therapy and treated with adjunctive orbital radiotherapy (2000 cGy; 10 fractions). Clinical improvement was assessed by monitoring the patient's ability to taper corticosteroid to discontinuation and by follow-up radiologic examination. RESULTS: All 3 patients had a favorable response to adjunctive radiotherapy with improvement of the clinical symptoms and radiologic abnormalities. Systemic corticosteroid was tapered and discontinued in all patients successfully. There were no adverse effects of treatment or recurrence after a mean follow-up of 19 months. CONCLUSION: Adjunctive radiotherapy can help to achieve stable disease and cessation of systemic corticosteroid in patients with refractory ocular adnexal IgG4-related disease.

Review of radiation therapy in benign ocular diseases.

Radiotherapy is a modality used for the treatment of malignant diseases. However it is also used as an effective modality in the treatment of many benign disorders. It is generally not the first choice of therapy in non malignant conditions but usually used when other modalities have failed or may induce more side effects. Benign disorders of the eye can cause severe morbidity in terms of inflammatory symptoms, loss of vision, pain and diplopia. Radiotherapy in such conditions is given in very low doses and the goals are controlling the condition and at the same time minimizing late tissue sequelae, if any. Here we highlight the use of radiotherapy in most common benign conditions of the eye; mainly Pterygium, Haemangioma, Graves' Orbitopathy and Pseudotumour Orbitae.

Radiation therapy: orbital tumors.

Orbital tumors are rare overall, comprising 0.1% of all tumors and less than 20% of all orbital diseases. Tumors may be benign, locally aggressive, or malignant. Of the malignant tumors, lymphomas and metastases are the most common and are primarily seen in the elderly population. While surgery and chemotherapeutic agents are often employed in the management of these lesions, not all patients are candidates for these therapies. Radiation therapy offers a noninvasive, well-tolerated primary treatment modality, whereby vision-sparing is feasible in many cases. In this chapter, we review an array of non-neoplastic entities and orbital tumors, for which there exists a role for radiation, and the radiotherapeutic techniques and applications in their management.

Association of clinical response and long-term outcome among patients with biopsied orbital pseudotumor receiving modern radiation therapy.

PURPOSE: To retrospectively evaluate institutional outcomes for patients treated with modern radiation therapy (RT) for biopsied orbital pseudotumor (OP). METHODS AND MATERIALS: Twenty patients (26 affected orbits) with OP were treated with RT between January 2002 and December 2011. All patients underwent biopsy with histopathologic exclusion of other disease processes. Sixteen patients (80%) were treated with intensity modulated RT, 3 (15%) with opposed lateral beams, and 1 (5%) with electrons. Median RT dose was 27 Gy (range 25.2-30.6 Gy). Response to RT was evaluated at 4 months post-RT. Partial response (PR) was defined as improvement in orbital symptoms without an increase in steroid dose. Complete response (CR) 1 and CR 2 were defined as complete resolution of orbital symptoms with reduction in steroid dose (CR 1) or complete tapering of steroids (CR 2). The median follow-up period was 18.6 months (range 4-81.6 months). RESULTS: Seventeen patients (85%) demonstrated response to RT, with 7 (35%), 1 (5%), and 9 (45%) achieving a PR, CR 1, and CR 2, respectively. Of the 17 patients who had ≥ PR at 4 months post-RT, 6 (35%) experienced recurrence of symptoms. Age (>46 years vs ≤ 46 years, P=.04) and clinical response to RT (CR 2 vs CR 1/PR, P=.05) were significantly associated with pseudotumor recurrence. Long-term complications were seen in 7 patients (35%), including 4 with cataract formation, 1 with chronic dry eye, 1 with enophthalmos, and 1 with keratopathy. CONCLUSIONS: RT is an effective treatment for improving symptoms and tapering steroids in patients with a biopsy supported diagnosis of OP. Older age and complete response to RT were associated with a significantly reduced probability of symptom recurrence. The observed late complications may be related to RT, chronic use of steroids/immunosuppressants, medical comorbidities, or combination of factors.

Radiotherapy with or without surgery for patients with idiopathic sclerosing orbital inflammation refractory or intolerant to steroid therapy.

PURPOSE: To evaluate the outcomes of patients with idiopathic sclerosing orbital inflammation (ISOI) treated with radiotherapy with or without surgery. METHODS AND MATERIALS: We retrospectively reviewed 22 patients with histopathologically confirmed ISOI who had been refractory or intolerant to steroid therapy and treated with radiation with or without surgery. The radiation dose ranged from 20 to 40 Gy (median, 20 Gy) at 2 Gy per fraction. Presenting signs and treatment outcomes were assessed. RESULTS: Proptosis was the most common sign at presentation, seen in 19 (86.3%) patients, followed by restriction of extraocular movements in 10 (45.4%) patients. Response to radiotherapy was complete in 15 (68.1%) patients, partial in 3 (13.6%) patients, and none in 4 (18.2%) patients. At the median follow-up of 34 months, 14 (63.6%) patients had progression-free state of symptoms and signs, with the progression-free duration ranging from 3 to 75 months (median, 41.5 months), whereas 8 (36.4%) patients had recurrent or persistent disease although they had received radiotherapy. Of the 14 progression-free patients, 6 underwent a bimodality treatment of debulking surgery of ocular disease and radiotherapy. They had had no recurrent disease. Cataract was the most common late complications, and 2 patients experienced a Grade 3 cataract. CONCLUSION: Our study suggests that for patients with ISOI who are refractory or intolerant to steroid therapy, 20 Gy of radiotherapy appears to be effective for the control of disease with acceptable complications, especially when it is combined with surgery.

The efficacy of radiotherapy in the treatment of orbital pseudotumor.

PURPOSE: To review institutional outcomes for patients treated with external-beam radiotherapy (EBRT) for orbital pseudotumor. METHODS AND MATERIALS: This is a single-institution retrospective review of 20 orbits in 16 patients diagnosed with orbital pseudotumor that received EBRT at the University of Oklahoma, Department of Radiation Oncology. Treated patients had a median follow-up of 16.5 months. RESULTS: Fifteen patients (93.7%) were initially treated with corticosteroids. Eight had recurrence after steroid cessation, six were unable to taper corticosteroids completely or partially, and one experienced progression of symptoms despite corticosteroid therapy. Fourteen patients (87.5%) initially responded to radiotherapy indicated by clinical improvement of preradiation symptoms and/or tapering of corticosteroid dose. Mean EBRT dose was 20 Gy (range, 14-30 Gy). Thirteen patients (81.2%) continued to improve after radiation therapy. Patient outcomes were complete cessation of corticosteroid therapy in nine patients (56.3%) and reduced corticosteroid dose in four patients (25%). Radiotherapy did not achieve long-term control for three patients (18.7%), who still required preradiation corticosteroid dosages. Three patients received retreatment(s) of four orbits, of which two patients achieved long-term symptom control without corticosteroid dependence. One patient received retreatment to an orbit three times, achieving long-term control without corticosteroid dependence. No significant late effects have been observed in retreated patients. CONCLUSIONS: Radiotherapy is an effective treatment for acute symptomatic improvement and long-term control of orbital pseudotumor. Orbital retreatment can be of clinical benefit, without apparent increase in morbidity, when initial irradiation fails to achieve complete response.

Orbital pseudotumor.

Orbital pseudotumor is a benign condition that accounts for approximately 10% of all orbital mass lesions. Any part of the orbit may be involved. The etiology is unknown. The presentation may be either acute or subacute. Patients may present with a palpable mass, a swollen eyelid, congestion, pain, diminished ocular motility, and/or decreased visual acuity. Approximately, 25% of patients present with bilateral disease. A modest proportion of patients experience resolution of their symptoms without treatment. Biopsy is indicated for those who do not respond to, or relapse after, first-line therapy. Oral corticosteroids are the initial treatment and approximately 80% of patients respond. Roughly half of those who respond to corticosteroids relapse. Second-line therapy consists of either low-dose radiotherapy (20-30 Gy at 2 Gy per fraction), cytotoxic chemotherapy, or immunosuppressive agents. Radiotherapy results in long-term local control rates of 50% or higher. Limited lesions may be successfully resected. A small subset of patients may experience inexorable progression to a fixed, painful, sightless eye and require orbital exenteration.

[Idiopathic orbital inflammation with extraorbital extension: case report]. / Inflamação idiopática da órbita com extensão extra-orbital: relato de caso.

The authors report a case of a patient with idiopathic orbital inflammation with extension beyond the orbit. Biopsy was performed to confirm the diagnosis of idiopathic orbital inflammation and computed tomography demonstrated the extraorbital extension. Treatment with methotrexate and radiotherapy was used.

Idiopathic sclerosing orbital inflammation.

OBJECTIVE: To perform a multicenter review of the clinical features and treatment of 31 patients with idiopathic sclerosing orbital inflammation. METHODS: We included all patients with histologically confirmed idiopathic sclerosing orbital inflammation from 5 regional orbital centers. We reviewed the case notes to determine the clinical presentation, diagnostic features, and response to treatment. The main outcome measures were duration and nature of symptoms, anatomical location of disease, histopathological findings, treatment modalities, treatment efficacy and adverse effects, and final clinical status. RESULTS: We included 13 male and 18 female patients ranging in age from 7 to 83 years. The average duration of symptoms at presentation was 13.4 months. There was a predilection for the lateral and superior quadrants. Thirteen patients had apical disease, and 4 had extraorbital involvement. Histopathological findings invariably showed sclerosis associated with a sparse mixed cellular infiltrate. Twenty-seven patients were treated with oral prednisolone, response to which was good in 9 patients, partial in 11, and poor in 7. Six patients were treated with a second-line immunosuppressive agent, and 6 received radiotherapy. The response to radiotherapy was generally poor. CONCLUSIONS: Idiopathic sclerosing orbital inflammation is a rare condition that can be difficult to diagnose and manage. Early intervention with immunosuppression in the form of corticosteroids combined with second-line agents can result in control and even regression of the disease.

The role of radiation therapy in benign diseases.

Although adequate prospective data are lacking, radiation therapy seems to be effective for many benign diseases and remains one of the treatment modalities in the armamentarium of medical professionals. Just as medication has potential adverse effects, and surgery has attendant morbidity, irradiation sometimes can be associated with acute and chronic sequelae. In selecting the mode of treatment, most radiation oncologists consider the particular problem to be addressed and the goal of therapy in the individual patient. It is the careful and judicial use of any therapy that identifies the professional. With an understanding of the current clinical data, treatment techniques, cost, and potential detriment, the goal is to provide long-term control of the disease while minimizing unnecessary treatment and potential risks of side effects. The art lies in balancing benefits against risks.

Radiation therapy for idiopathic orbital myositis: two case reports and literature review.

We report two cases of idiopathic orbital myositis treated with radiation therapy (RT). Both patients visited our hospital with complaints of orbital pain on eye movement and eyelid swelling. There was no history of thyroid disease or trauma, and no signs of infection, neoplasm, or collagen disease. The laboratory investigations, including a thyroid function test, showed no abnormalities in either woman. They were initially treated with a combination of corticosteroids (CS) and nonsteroidal anti-inflammatory drugs (NSAIDs), however, they became dependent on or refractory to oral CS therapy, and received 20 Gy in 10 fractions of RT to the orbit. Their symptoms decreased immediately, and both patients were able to reduce the dosage of oral CS after RT. One patient could completely withdraw oral CS thereafter. However, they both experienced recurrence at eight months after RT, and have been receiving oral CS to control their symptoms. RT at doses of 20 Gy in 10 fractions for patients with idiopathic orbital myositis appears to be effective in palliating symptoms, but long-term control is not satisfactory.

Diagnosis and management of orbital pseudotumor.

Orbital pseudotumor, also known as idiopathic orbital inflammatory syndrome (IOIS), may have protean clinical manifestations. Some presentations of IOIS may mimic common conditions such as orbital cellulitis and optic neuritis. IOIS should be considered a diagnosis of exclusion, with evaluation directed toward eliminating other causes of orbital disease. Orbital magnetic resonance imaging is the single most important diagnostic test, but serologic studies are necessary to exclude a systemic cause. Biopsy is usually not performed at presentation, as the risk of producing damage to vital structures within the orbit outweighs the benefits. Patients with multiple recurrences, or those unresponsive to therapy, should have biopsy samples taken. Corticosteroids are the mainstay of therapy and are administered for several months to ensure remission. Radiotherapy may be used in patients who fail to respond to steroids or who have a rapidly progressive course. For those patients who are refractory to both corticosteroids and radiotherapy, anecdotal reports have suggested the use of chemotherapeutic agents such as cyclophosphamide, methotrexate, and cyclosporine.

A clinical analysis of idiopathic orbital inflammatory pseudotumor.

PURPOSE: To observe the clinical findings and response to treatment in patients with a diagnosis of idiopathic orbital inflammatory pseudotumor. METHODS: 209 idiopathic orbital inflammatory pseudotumor cases seen between Jan 1, 1978 and Dec 31, 1999 in our hospital were evaluated retrospectively. RESULTS: Of the 209 cases, 118 were male and 91 were female; there were 90 in the right eye, 81 left eye and 38 both eyes. Patients age ranged from 4 to 80 years (mean 44.4). Proptosis (66%), palpable mass (65%), swollen eyelid (55%), increased orbital pressure (55%) and motility restriction (48%) were the five most common presenting signs. According to radiologic and surgical findings, focal mass within orbit was the most frequent subtype (43%), followed by lacrimal inflammatory pseudotumor (32%), diffuse orbital inflammation (10%), myositis (8%). Perineuritis (2%), periscleritis (2%), acute inflammation (2%) and eyelid pseudotumor (1%) were rare clinical findings. The response to treatment (with a mean follow-up of 1.5 years) showed that the cure rate was 40% and the effective rate 97% after combined management of surgical resection, systemic steroid and local low dose radiotherapy. CONCLUSIONS: Although recurrence of IOIP is common, the success rate of treatment for this group of patients is high.