Α Case of Severe Thyroid Eye Disease Treated with Tocilizumab.

This is a case report describing a patient with severe thyroid eye disease complicated with dysthyroid optic neuropathy that was unresponsive to intravenous steroids and orbital radiotherapy but responded well to intravenous tocilizumab.

Orbital apex venous cavernous malformation with optic neuropathy: treatment with multisession gamma knife radiosurgery.

PURPOSE: To evaluate the efficacy and safety of multisession gamma knife radiosurgery (GKRS) for orbital apex venous cavernous malformation causing optic neuropathy. METHODS: Retrospective cohort study in a single tertiary institution from January 2007 to December 2016 on patients who underwent multisession GKRS for orbital apex venous cavernous malformations causing optic neuropathy. RESULTS: There were 12 patients included in our study. The mean age was 40.2±14.5 years, and men comprised 66.7% (n=8). Decrease in visual acuity (83.3%) was the most common symptom at presentation. The mean clinical follow-up was 28.5 months. Ten (83.3%) of the 12 patients had improvement in best corrected visual acuity. Of the 10 patients with pre-existing relative afferent pupillary defect (RAPD), 6 (60%) had complete resolution of RAPD. Of the 12 patients with visual field defect, 7 (58.3%) had complete resolution, 3 (25%) had partial improvement, while 2 (16.7%) remained unchanged due to optic atrophy from long-standing compressive optic neuropathy. Mean proptosis reduced from 2.3±1.7 mm pre-GKRS to 0.5±1.3 mm post-GKRS (p=0.005). Tumour shrinkage was observed in all patients. The mean tumour volume at the time of GKRS was 3104 mm3 (range 221-8500 mm3), which reduced to 658 mm3 (range 120-3350 mm3) at last follow-up. None of the patients experienced GKRS-related ocular morbidity during the follow-up period. CONCLUSION: Multisession GKRS has shown to be an effective and safe option for the treatment of orbital apex venous cavernous malformations causing optic neuropathy, with significant improvement in ophthalmic outcomes and reduction in tumour volume.

Orbital Radiotherapy Combined With Corticosteroid Treatment for Thyroid Eye Disease-Compressive Optic Neuropathy.

PURPOSE: To evaluate the effectiveness of orbital radiotherapy (ORT) in the treatment of thyroid eye disease (TED)-compressive optic neuropathy. METHODS: A retrospective review of patients with corticosteroid-responsive compressive optic neuropathy due to TED treated with ORT. Study was conducted in compliance with Health Insurance Portability and Accountability Act. One hundred four patients (163 orbits) with a mean age of 61.7 years met inclusion criteria. Seventy-four percent (77/104) were female, and 32.7% (34/104) were current or previous smokers. A total absorbed dose of 2000 cGy fractionated in 10 treatment doses over the course of 2 weeks was administered to the retroocular tissues according to a standard protocol. The primary end point was failure of ORT, defined as persistent optic neuropathy following completion of radiotherapy that mandated urgent orbital decompression surgery. RESULTS: Ninety-eight of 104 (94%) patients or 152 of 163 (93.3%) orbits did not require orbital decompression surgery during the acute phase. Patients who responded successfully to ORT had similar improvements in visual acuity, color vision, Humphrey threshold visual field testing, and afferent pupillary defects compared with patients who failed ORT and underwent urgent decompression surgery. Only 36.7% of successfully treated patients ultimately underwent elective surgery, including orbital decompression, strabismus, or eyelid surgery, during the inactive phase of TED. CONCLUSIONS: The data from this study, the largest retrospective review reported to date, supports the use of ORT in eyes with corticosteroid-responsive TED-compressive optic neuropathy. ORT may favorably alter the natural history of active-phase TED by preventing recurrent compressive optic neuropathy after withdrawal of corticosteroids.

The effect of orbital radiation therapy on thyroid-associated orbitopathy complicated with dysthyroid optic neuropathy.

Thyroid-associated orbitopathy (TAO) is an inflammatory autoimmune disorder. The most serious complication of TAO is dysthyroid optic neuropathy (DON), which can lead to permanent vision loss because of volume expansion in the orbital apex. Orbital radiation therapy (ORT) is an anti-inflammatory treatment used in the treatment of active TAO. Clinical studies support radiotherapy as having a modest effect on DON, and early radiotherapy may protect against disease progression to DON. Current studies suggest that radiotherapy is generally safe. However, risks still exist in some cases. The possible effects of radiotherapy on TAO, especially complicated with DON, are reviewed. The effects of radiotherapy on DON are not completely known, and evidence from standardized, prospective, and multicenter clinical trials is still lacking.

Comprehensive craniospinal radiation for controlling central nervous system leukemia.

PURPOSE: To determine the benefit of radiation therapy (RT) in resolution of neurologic symptoms and deficits and whether the type of RT fields influences central nervous system (CNS) control in adults with CNS leukemia. METHODS AND MATERIALS: A total of 163 adults from 1996 to 2012 were retrospectively analyzed. Potential associations between use of radiation and outcome were investigated by univariate and multivariate analysis. RESULTS: The median survival time was 3.8 months after RT. Common presenting symptoms were headache in 79 patients (49%), cranial nerve VII deficit in 46 (28%), and cranial nerve II deficit in 44 (27%). RT was delivered to the base of skull in 48 patients (29%), to the whole brain (WB) in 67 (41%), and to the craniospinal axis (CS) in 48 (29%). Among 149 patients with a total of 233 deficits, resolution was observed in 34 deficits (15%), improvement in 126 deficits (54%), stability in 34 deficits (15%), and progression in 39 deficits (17%). The 12-month CNS progression-free survival was 77% among those receiving CS/WB and 51% among those receiving base of skull RT (P=.02). On multivariate analysis, patients who did not undergo stem cell transplantation after RT and base of skull RT were associated with worse CNS progression-free survival. CONCLUSIONS: Improvement or resolution of symptoms occurred in two thirds of deficits after RT. Comprehensive radiation to the WB or CS seems to offer a better outcome, especially in isolated CNS involvement.

Acute dysthyroid optic neuropathy exacerbated by orbital radiotherapy.

A 76-year-old lady presenting with acute dysthyroid optic neuropathy (DON) was stabilised with systemic intravenous methylprednisolone (IVMP). Two separate attempts at a treatment course of orbital radiotherapy (OR) were commenced and subsequently abandoned as there was an acute worsening of her DON during OR, despite cover with oral glucocorticoids and subsequently IVMP. The patient underwent urgent orbital decompression which normalised her vision and optic neuropathy. Our case likely represents worsening of DON due to soft tissue swelling secondary to OR despite cover with IVMP in a patient previously responsive to IVMP alone. Some authors advocate the use of OR in active DON as either a surgery delaying or surgery sparing alternative. This case report illustrates the rare risk of transiently worsening DON with OR. We highlight the need for close monitoring of optic nerve function if OR is utilised in this patient group.

Central nervous system myelomatosis with optic neuropathy and intramedullary spinal cord compression responding to radiation therapy.

Central nervous system (CNS) involvement by multiple myeloma is a rare complication that occurs in less than 1% of cases. The purpose of this report is to highlight the unique presentation and treatment of a patient with CNS myelomatosis. A 58-year-old Caucasian woman with multiple myeloma developed subacute vision loss bilaterally and was found to have plasma cells in her cerebrospinal fluid. Using a helmet field to 25 Gy in 10 fractions, her vision was stabilized with radiotherapy. After developing right upper extremity numbness and weakness, magnetic resonance imaging revealed intramedullary spinal cord lesions from C5 to C7. She received radiotherapy to 25 Gy in 10 fractions from C4 to T1, with improvement in upper extremity strength after 15 Gy. Although CNS involvement by multiple myeloma is a rare complication, increasing awareness is necessary for clinicians to consider meningeal myelomatosis in patients with this neoplasm.

Neuroprotective effects of near-infrared light in an in vivo model of mitochondrial optic neuropathy.

Near-infrared light (NIL) promotes a wide range of biological effects including enhancement of energy production, gene expression and prevention of cell death. This is the first report of the in vivo neuroprotective effects of NIL against optic neuropathy induced by mitochondrial complex I inhibition. Subjects were pigmented rats that received single bilateral intravitreal doses of rotenone, a mitochondrial complex I inhibitor, or rotenone plus one of three different doses of NIL. Treatment effects were evaluated at behavioral, structural and neurochemical levels. Rotenone induced a decrease in visual function, as determined by changes in the dark-adapted illuminance sensitivity threshold, escape latency and rate of successful trials in a two-choice visual task, compared with vehicle-treated controls. Behavioral impairment correlated with a decrease in retinal and visual pathway metabolic activity, retinal nerve fiber layer thickness and ganglion cell layer cell density. These changes were prevented by NIL treatments in a dose-dependent manner. Whole-brain cytochrome oxidase and superoxide dismutase activities were also increased in NIL-treated subjects in a dose-dependent manner, suggesting an in vivo transcranial effect of NIL. In whole-brain membrane isolates, NIL prevented the rotenone-induced decrease in cell respiration. The results show that NIL treatment can effectively prevent the neurotoxic effects of rotenone and that it might be used in the treatment of neurodegenerative disorders associated with mitochondrial dysfunction.

Radiation therapy for visual pathway tumors.

The multimodality management of visual pathway tumors frequently involves radiation. Most commonly, photons are delivered via multiple focused beams aimed at the tumor while sparing adjacent tissues. The dose can be delivered in multiple treatments (radiation therapy) or in a single treatment (radiosurgery). Children with visual pathway gliomas should be treated with chemotherapy alone, delaying the use of radiation therapy until progression. Definitive radiation therapy of optic nerve sheath meningiomas results in stable vision in most patients. Radiation therapy or radiosurgery for pituitary tumors can result in control of both tumor growth and hormone hypersecretion. Postoperative radiation therapy or radiosurgery of craniopharyngiomas significantly improves local control rates compared with surgery alone. Radiation therapy is highly effective for eradicating orbital pseudolymphoma and lymphoma. The risk of complications from radiation treatment is dependent on the organ at risk, the cumulative dose it receives, and the dose delivered per fraction.

[Temporopolar epidural transcavernous transpetrous approach. Technique and indications]. / Approche épidurale temporopolaire transcaverneuse transpétreuse. Technique chirurgicale et indications.

BACKGROUND AND PURPOSE: Several selective approaches have been recommended for access to the petroclival region (PCR). However, locoregional extension of the tumor may necessitate more extensive procedures. Dissections from injected specimens allowed us to describe the different osteodural triangles that are exposed to provide an extensive access to the PCR. METHOD: The bony step included a temporopterional flap and exposure of the paraclinoid carotid after removal of the anterior clinoid process. The sphenoid wing was then extensively drilled, exposing the foramen rotundum and ovale. An anterior petrosectomy was subsequently performed. The dura propria of the cavernous sinus was elevated as far as the Meckel cave. The sylvian fissure was also opened. Then, the temporobasal dura and the dura from the posterior surface of the petrous bone were opened and the superior petrosal sinus was coagulated and divided. The tentorium was divided toward its free edge. RESULTS: Via this approach, cranial nerves from the olfactory tract to the acousticofacial bundle are exposed. In the same way, the ventral and lateral surface of the pons is identified. CONCLUSION: The epidural temporopolar transcavernous transpetrous approach is useful to expose during the same procedure, elements of the posterior and middle cranial fossa. It is of particular value when managing tumors simultaneously involving the PCR, the parasellar, and the suprasellar regions.

[Radiation therapy for thyroid-associated ophthalmopathy].

OBJECTIVE: To observe indication and effectiveness of radiation therapy (RT) in the treatment of the patients with thyroid-associated ophthalmopathy (TAO). METHODS: 23 patients of TAO who received RT in Sichuan University were collected from 1992 to 2004. Among those patients, 9 cases of infiltrative exophthalmos and 14 cases of compressive optic neuropathy were ineffectively with glucocorticoid treatment or could not treated with glucocorticoid, or could not perform orbital decompression due to severe diabetic mellitus or hypertension, or feared to receive the operation, all of patients were active ophthalmopathy and with short duration. Outer orbital radiation was applied using linear accelerator with Donaldson's method, radiation treatment fields was 4 cm x 5 cm, exposure energy was 2 GY fractions with total of 20 GY. In 11 cases with severe inflammation prednisone was administered during radiotherapy. Photos and CT scan were taken for each patient before and after RT. RESULTS: Visual acuity (VA) of the patients was improved from before RT 0.04 - 0.2 to after RT 0.1 - 0.8 in 14 cases of compressive optic neuropathy. Extraocular muscle of patients decreased in size confirmed by CT scan. VA improvement was correlated with the degree of extraocular muscle decreased in size. Eyelid and conjunctive swelling, eyelid incompletely closure, exposure keratitis, limitation of motion and proptosis were improved after RT in 9 patients with infiltrative exophthalmos. Following up the patients for 1 - 3 years, it was found that VA decreased in 3 cases and inflammation recurred in 4 cases, eyelids could not closed in 2 cases after RT. CONCLUSIONS: RT could be used in severe, active cases of TAO. If there is severe inflammation, steroids could be combined with RT therapy.

Metastatic pituitary tumor from renal cell carcinoma treated by fractionated stereotactic radiotherapy--case report.

A 63-year-old man presented with rapidly progressive visual field deficit and hypopituitarism including diabetes insipidus, 8 years after treatment for a renal cell carcinoma. Neuroimaging studies revealed a dumbbell-shaped pituitary mass that had destroyed the sellar floor and abutted against the optic apparatus. Fractionated stereotactic radiotherapy (SRT), employing computer-image integration techniques and a frame that could be relocated to facilitate a fractionated dosing scheme, was carried out under a plan for reducing the treatment risk to the optic apparatus. Three months later, the patient exhibited marked improvement in the visual field deficit and visual acuity concomitant with a reduction in tumor volume. Magnetic resonance imaging of the sellar region confirmed striking shrinkage of the metastasis. His neurological status remained stable at 12 months after the SRT with no complications. Fractionated SRT appears to be effective for preserving or improving the residual vision in patients with visual loss secondary to metastatic tumor of the pituitary gland, and may result in a longer and better quality of life.

Radiotherapy for moderate-to-severe Graves' ophthalmopathy: improved outcomes with early treatment.

PURPOSE: The purpose of this review is to quantify the response to radiotherapy delivered early in the active inflammatory phase of moderate-to-severe Graves' ophthalmopathy. MATERIALS AND METHODS: A retrospective review of radiotherapy delivered early in the active phase of Graves' ophthalmopathy was performed. All 47 cases had moderate-to-severe ophthalmopathy, and 30 cases had optic neuropathy. Variables examined included exophthalmos, color vision, and resistance to retropulsion. Statistical analyses comparing these variables at presentation and at 3 and 6 months after radiotherapy were performed. Subset analyses comparing responses of patients with symptoms lasting longer or less than 6 months were also performed. RESULTS: At 6 months after radiotherapy, there was improvement in exophthalmos in 74.5% of cases and improvement in retropulsion in 83.0%, and all cases of previous color deficiency improved. The mean improvement in exophthalmos was 1.38 mm, color vision was two plates, and retropulsion was 1 grade. On subset analyses, there was a trend toward greater improvement in patients treated earlier in the course of their symptoms. CONCLUSIONS: Radiotherapy may play an important role in the treatment of Graves' ophthalmopathy, especially for patients with optic neuropathy. Early intervention (symptoms < 6 months) with radiotherapy may be the optimal timing for this treatment.

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.

Intraocular pressure changes after treatment for Graves' orbitopathy.

OBJECTIVE: To evaluate the change in intraocular pressure (IOP) in subjects with Graves' orbitopathy (GO) after orbital decompression, strabismus surgery, and orbital radiation. DESIGN: Retrospective case review. METHODS: The charts of 172 consecutive subjects from the Neuro-ophthalmology Service at Wills Eye Hospital (Philadelphia, PA) with GO who underwent either orbital decompression, strabismus surgery, or orbital radiation between 1994 and 1999 were analyzed. Subject age, gender, diagnosis of glaucoma in either eye, use of systemic steroids or topical glaucoma medications, procedure performed, and the preoperative and postoperative IOP (in primary position and upgaze) were evaluated. RESULTS: Of 116 eyes that underwent orbital decompression, the mean preoperative IOP was 21.6+/-4.6 mmHg (standard deviation) in primary position and 27.9+/-6.8 mmHg in upgaze. The postoperative IOP was 17.5 mmHg +/- 3.0 mmHg in primary position and 20.1+/-4.7 mmHg in upgaze, a decrease in IOP of 18.9% in primary position and 27.9% in upgaze (P<0.001). Subjects taking glaucoma medication or who had IOP greater than 21 mmHg demonstrated a significantly (P<0.001) greater reduction in IOP postoperatively. The mean preoperative IOP in the 32 subjects who had strabismus surgery was 18.5+/-2.8 mmHg (primary position), and 24.7+/-4.3 mmHg (upgaze). Postoperative IOP was 16.1 mmHg (primary position) and 16.9 mmHg (upgaze), a decrease of 2.4 mmHg (13.3%, P<0.01 in primary position) and 7.8 mmHg (31.2%, P<0.01 in upgaze). There was no statistically significant reduction in IOP after orbital radiation. CONCLUSIONS: In the selected subgroup of subjects with GO who required intervention, orbital decompression and strabismus surgery resulted in a significant reduction in IOP in the early postoperative period, especially in subjects with preoperative IOP greater than 21 mmHg.

Objective evaluation of improvement in optic neuropathy following radiation therapy for thyroid eye disease.

PURPOSE: While the literature supports the use of radiation therapy for thyroid eye disease, it does not sufficiently describe in detail the results of radiation therapy for optic neuropathy associated with thyroid eye disease. The objective of this study is to quantify the changes in parameters of optic neuropathy after orbital irradiation for thyroid eye disease. METHODS AND MATERIALS: Twelve consecutive patients with optic neuropathy from thyroid eye disease were followed by a single neuro-ophthalmology practice and treated by one radiation oncologist with radiation therapy from 1991 through 1995. All cases were prospectively followed for visual acuity, color vision, mean deviation, and/or foveal sensitivity and afferent pupillary defect. All patients received 2000 cGy in 10 fractions with megavoltage irradiation to the orbits. RESULTS: Ten of 12 patients were evaluated for follow-up (one moved out of this country and one had a stroke, which confounded interpretation of examination results). An analysis was performed retrospectively while treatment and evaluation remained uniform. Five men and five women formed the basis of this study with a median age of 60 years (35-76 years). Nineteen eyes were evaluated for thyroid optic neuropathy. Improvement in optic nerve function occurred in eight of ten patients. Improvement was seen either during radiotherapy or within 2 weeks of completion. No long-term adverse effects were noted. CONCLUSION: This study objectively demonstrates improvement in optic neuropathy from radiation therapy for thyroid eye disease.

Visual pathway glioma: an erratic tumour with therapeutic dilemmas.

OBJECTIVE: Our experience in children with visual pathway glioma (VPG) was reviewed to delineate its clinical characteristics. DESIGN: The charts and imaging studies of 21 children with VPG who were followed up in our centre during the last 12 years were reviewed and summarised. RESULTS: VPG accounted for 13.1% of all brain tumours treated during this period. Sixty two per cent of the children with VPG had neurofibromatosis type 1 (NF-1). Among these, more than 60% were detected as part of routine work up. In some cases decreasing visual function preceded the appearance of the VPG on imaging studies. Tumour growth rate was markedly unpredictable. All treatment modalities employed led to tumour shrinkage and stabilisation for a variable period, but none was successful in totally eradicating the tumour. Complications were less severe after chemotherapy compared with radiotherapy. Three children died, none with NF-1, with a globular hypothalamic/chiasmatic tumour and accompanying electrolyte abnormalities. CONCLUSIONS: NF-1 is a favourable prognostic marker for VPG. Whenever possible a period of observation is necessary before treatment is initiated, during which time tumour size and visual function should be closely followed up; an untoward change in either of these is an indication for the start of treatment, preferably chemotherapy first. The combination of a globular hypothalamic/chiasmatic glioma and electrolyte abnormalities in a child without NF-1 are related to a poor prognosis.