Controversies in the Management of Optic Nerve Sheath Meningiomas Jonathan W. Kim, MD Joseph F.

Rizzo, MD Simmons Lessell, MD

n Background
Optic nerve sheath meningiomas (ONSM) comprise 2% of orbital tumors and 1% of all intracranial meningiomas.15 Meningiomas arising from the sheath of the optic nerve are benign tumors originating from the outer cap cells of the arachnoid layer in the intraorbital, intracanicular, or intracranial segments of the optic nerve. The most common histologic subtypes of ONSM are benign meningothelial and transitional forms; malignant optic sheath meningiomas have never been reported. ONSM typically enlarge slowly within the subarachnoid space, compressing the optic nerve or its blood supply and causing visual deterioration.2 Despite the rarity of ONSM and their relatively benign behavior, meningiomas arising from the optic nerve sheath are important because they represent the archetype of a compressive optic neuropathy.

n Clinical Presentation
The classic triad of optic atrophy, visual loss, and optic nerve shunt vessels originally described by Hoyt and Spencer is present in only a minority of patients with ONSM.1,2 Vision loss is the presenting complaint in almost all patients with ONSM, with approximately half the patients having vision of 20/40 or better at diagnosis.2,3 Transient obscurations of vision have been reported by some patients, particularly gaze-induced visual disturbance.5 Visual eld defects are usually nonspecic, with blind spot enlargement and peripheral constriction being the most common perimetry ndings.1,2 The optic disc is either edematous or atrophic in
15

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almost all cases, but optociliary shunt vessels are present in only 30% of patients.2 Although measurable proptosis is present in 60% of cases, it is thought to be a late sign, and severe proptosis is unusual.1,4 Patients typically do not report pain or diplopia. The clinical ndings of ONSM can be subtle, and it is not uncommon for a patient to have visual symptoms for a prolonged period before the ONSM is recognized.1

n Diagnosis
Historically, it was common to obtain histologic conrmation of all patients with suspected meningiomas of the optic nerve.4 With modern imaging techniques, the radiographic ndings of ONSM obviate the need for tissue biopsy in almost all patients. Neuroimaging ndings associated with ONSM include perineural thickening and enhancement of the optic nerve, calcication, enlargement of the optic canal, and hyperostosis of the adjacent bone.3,6 The characteristic tram-track sign of ONSM is produced by perineural thickening of the optic nerve sheath by the tumor with relative sparing or radiographic lucency of the optic nerve. Although radiographic imaging can be used to make the correct diagnosis in most cases, other neuro-ophthalmic and orbital conditions may occasionally mimic ONSM. Enlargement of the optic nerve with perineural enhancement may be seen with optic nerve glioma, optic neuritis, sarcoidosis, syphilis, orbital pseudotumor, meningeal carcinomatosis, arachnoid cyst, and perineural hematoma.1,7 When considering treatment options, it is important to remember that the diagnosis of ONSM is almost always a presumptive one, and that patients need close monitoring to ensure that their clinical presentation and course are consistent with their presumed diagnosis.

n Natural History
Before embarking on treatment recommendations, it is important to review the natural history of ONSM, considering both the visual and systemic prognosis for patients managed conservatively. In 1992, Dutton performed a metaanalysis of all previously published cases of ONSM to determine the visual prognosis of ONSM.2 Dutton identied 64 patients with ONSM followed conservatively for 1 to 7 years; of these patients, 84% showed progressive visual acuity loss and all patients had visual eld deterioration during the follow-up period. Dutton commented that, without treatment, visual prognosis progresses slowly but inexorably to blindness in the affected eye.2 A more optimistic perspective was published by Egan and Lessell in 2002.8 In their series of 16 patients with ONSM followed by one examiner for an average of 6.25 years, 67% with 20/100 or better vision at the initial examination retained this level of

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acuity during the follow-up period. Additionally, 6 of 16 patients retained vision of 20/30 or better, with 3 patients actually showing slight improvement in acuity and visual eld. Saeed and Rootman published similar ndings in 2003; 71% of eyes in their study that had an initial visual acuity of 20/50 or better retained this level of vision over 5.2 years.3 Retrospective studies on the natural history of ONSM suggest that most patients experience a progressive loss of vision, but the rate and course of visual loss is variable. Many patients enjoy an extended period of stable visual acuity, and spontaneous improvement can rarely occur, although this is more common with patients who have moderate visual compromise at diagnosis. Overall, the majority of patients with vision of 20/50 or better may be expected to retain this level of acuity for at least 5 years. The systemic prognosis for patients with ONSM is excellent. Duttons review identied only 6 deaths in 228 cases of ONSM in the literature.2 However, among those 6 patients, there were no mortalities directly attributable to the ONSM. Four of the 6 patients died of operative complications, and 2 patients died of a second intracranial meningioma more than 20 years after the original diagnosis of ONSM.9 Because the ONSM did not directly cause the deaths of these patients, Dutton concluded that the overall tumor-related mortality from ONSM was 0%.
Young Patients

Walsh was the rst to suggest that meningiomas in younger patients behave more aggressively.10 Since then, several authors have suggested that young patients with ONSM have a worse prognosis. Indeed, higher recurrence rates have been reported after surgery in patients under age 20, suggesting aggressive tumor growth rates in this age group.5,9 Higher rates of intracranial extension in younger patients with ONSM support this view.8 Young patients also appear to have a higher incidence of bilateral ONSM tumors, although the basis for this observation is controversial. Because of their more aggressive behavior, Wright recommended biopsy in younger patients to differentiate ONSM from optic nerve gliomas, although with current neuroimaging modalities, this recommendation may no longer be appropriate.4,5 It can be surmised from published reports that ONSM in patients under the age of 20 are more locally aggressive, with higher rates of recurrences after surgery, higher rates of intracranial extension, and perhaps a greater incidence of multifocal lesions (ie, bilateral tumors). Therefore, these patients need close follow up of their visual function and regular radiographic monitoring for evidence of progressive intracranial growth.
Intracranial Extension

Intracranial extension is not a rare complication of ONSM, being reported in 15% to 23% of patients.1,2 Although intracranial extension of

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ONSM is readily visualized with modern neuroimaging techniques, particularly magnetic resonance imaging (MRI), its prognostic implications remain controversial. Some authors recommend complete tumor extirpation for all patients with ONSM who have lost useful vision to prevent intracranial extension.4,5,11 However, there have been no documented cases of hydrocephalus or hypothalamic abnormalities in adults associated with ONSM with extension into the intracranial space.2 Wright described an 11-year-old boy with a meningioma that extended into the optic chiasm with extensive spread of the tumor into the middle cranial fossa.4,5 Documented cases of contralateral optic nerve involvement from a unilateral ONSM are exceedingly rare.4,5,12,13 Whether such cases represent multifocal tumors, bilateral cases with a common intracranial origin, or true contralateral extension from one optic nerve sheath to the other is unclear. Almost all patients with ONSM lose acuity over time, but many retain useful levels of acuity for many years. Because systemic morbidity is essentially nil with ONSM, the clinical implications of intracranial extension are uncertain, and therapeutic recommendations should be individualized based on the clinical and radiographic course of each patient.

n Treatment Goals
The overall goal of treatment with ONSM is to preserve or improve vision. Preventing intracranial extension is certainly a therapeutic consideration, but because the systemic prognosis of ONSM is excellent, the primary focus of the clinician in recommending treatment should be to preserve the vision of the involved eye. As previously discussed, observation is a viable option for many patients with ONSM. The natural history of ONSM provides an insight into what patients can expect if they choose to observe.

n Surgical Biopsy, Debulking, and Excision

Before considering surgery for ONSM, the clinician must be clear about the surgical objectives: will the procedure be performed to obtain a tissue diagnosis, debulk the tumor, or to achieve a surgical cure? Surgical planning should then be individualized for each patient based on the surgical objective and the level of visual compromise. Surgical biopsy occasionally plays an important role in the diagnosis of ONSM, particularly when the clinical presentation is atypical. Because of the location of ONSM in the apex of the orbit or optic canal, obtaining a representative sample of the tumor requires a wide approach and perhaps even a craniotomy to perform the procedure safely. Even when an adequate sample has been obtained, diagnostic confusion may exist, particularly with gliomas of the optic nerve, which can produce reactive

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meningeal hyperplasia. Because of the high visual morbidity associated with surgical biopsy of optic nerve lesions, patients with useful levels of vision are not ideal candidates for the procedure. Surgical debulking is rarely indicated for ONSM, because exophytic growth into the orbit causing proptosis and corneal decompensation is quite unusual. Rarely, surgical debulking of extensive orbital masses may be indicated to relieve intractable pain or to improve ocular motility. When considering surgical excision, one must consider the biologic behavior of the disease process as well as its anatomic location in deciding whether a surgical cure is possible. As previously described, ONSM are benign tumors, and a large surgical margin is not required to eliminate recurrences. Unfortunately, pial blood vessels of the intraorbital and intracanalicular segments of the optic nerve are incorporated into the growth pattern of ONSM, and therefore it is virtually impossible to extirpate these tumors without resultant infarction of the nerve. Although there have been rare reports of visual recovery after surgery of small, anterior lesions, surgical resection of ONSM typically results in blindness.14 Duttons review showed that after surgery, 78% of operated eyes had no light perception vision.2 The patients who retain vision after surgery for ONSM can be presumed to have subtotal resections, and it is not surprising that Duttons review also showed an overall tumor recurrence of 24% after surgical resection.2 What are the surgical options available for patients who are already blind from ONSM? In an early report, Wright commented that surgery in the patients reported in this paper has been directed towards total removal of the meningioma once useful vision had gone. The rationale for surgery for a blind patient with ONSM is to prevent the visual and systemic complications of intracranial extension. As discussed previously, the impact of intracranial extension on the patients prognosis is uncertain. Therefore, performing a craniotomy and neurosurgical resection to remove a benign optic nerve tumor in a blind patient is controversial. In our opinion, surgical excision for a patient who has lost useful vision from ONSM should only be considered if there is documented growth toward the contralateral optic nerve or a progressive treat to the chiasm and hypothalamus. Achieving a surgical cure for ONSM and preserving vision are incompatible goals with ONSM. The systemic benets of achieving a surgical cure with ONSM are dubious. Therefore, the available data suggests that surgical indications for optic nerve sheath meningiomas are limited and must be carefully considered for each patient.

n Radiation Treatment
Meningiomas of the optic nerve sheath were generally considered to be unresponsive to radiation therapy. Spencer commented in 1972 that radiation seems to be of little help with most meningiomas, and Dutton

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in 1992 stated that little information is available on the use of this modality for ONSM.2,17 However, several early reports hinted at the potential of external beam irradiation to stabilize vision with ONSM.15,18 Smith reported on 5 patients with ONSM treated with radiation. Although he was not able to document a decrease in size of these tumors by computed tomography, there was regression of optociliary veins, and visual stability was achieved with a short follow up of 2 years and less.15 In 1988, Kennerdell reported visual results on 6 patients who had been treated with external beam radiotherapy, reporting improved vision in 5 patients over a follow up of 3 to 7 years.16 In 2002, Turbin reported a multicenter retrospective analysis on 64 patients with ONSM followed for a mean of 150.2 months.19 The radiation-treated group had the lowest rate of radiographic progression, because only 2 of 18 patients progressed. From a visual standpoint, the radiation group was the only one that did not show overall evidence of visual decline, and 44% of patients treated with radiation showed at least 2 lines of visual improvement. Patients who were treated with surgical resection in this study experienced a high complication rate (67%), and 7 of 12 patients showed evidence of radiographic progression during follow up. These results prompted Turbin to make the following recommendation: we currently recommend radiation therapy to patients as soon as serial examinations document a new decline in visual acuity and/or visual eld.19
Radiation Complications

Although well tolerated by most of patients, therapeutic doses of radiation therapy have been associated with both transient and permanent complications. Side effects can be transitory such as nausea, dry eyes, skin erythema, and alopecia or permanent, including cataracts, cranial nerve paresis, neuromyotonia, pituitary dysfunction, brain necrosis, hearing loss, and tumor induction. In Turbins series of patients with ONSM treated with external beam radiotherapy, 33% of cases had major or permanent side effects, with 4 patients losing vision and one patient developing temporal lobe atrophy.19 Radiation optic neuropathy is a dose-related complication of orbital or parasellar irradiation. Almost all patients developing radiation optic neuropathy have received greater than 60 Gy of a radiation dose.20 The lowest dose was reported by Goldmsith in 1992 in a patient who developed radiation optic neuropathy after receiving 54 Gy of radiation.21 In Parsons study, doses in excess of 60 Gy administered at 1.9 Gy per fraction produced optic neuropathy in 5 (8%) of 61 nerves.21 When the daily fraction size was >1.9 Gy, neuropathy developed in 10 (40%) of 25 optic nerves that received >60 Gy. From this data, it has been calculated that the optic nerve can safely tolerate a dose per fraction of 1.8 Gy to a total dose of 54 Gy. The occurrence of optic neuropathy after doses as low as 45 to 50 Gy

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seems to be a problem unique to patients with pituitary tumors and likely is a reection of preexisting optic nerve and chiasm compression.20 There are also several reports of optic neuropathy occurring after irradiation to doses in the range of 40 to 49 Gy in patients concurrently or previously treated with chemotherapy.20 Advanced age has also been implicated as a risk factor in the development of radiation optic neuropathy.20 Although there is no single threshold dose for radiation optic neuropathy, the optic nerve of a patient with ONSM and no other concomitant risk factors should be able to tolerate a total dose of 54 Gy or lower administered at <1.9 Gy per fraction, and this protocol is commonly prescribed in many centers for patents with ONSM receiving radiation therapy.
Stereotactic Radiation Therapy

Reports on the use of 3-dimensional conformal, planned fractionated radiation therapy for ONSM have appeared in the past decade.2227 Stereotactic or conformal radiation uses multiple beams of radiation and specialized software programs to focus treatment at the tumor site. This technique allows administration of radiation with improved precision, which may limit collateral damage to adjacent tissues. Conformal radiotherapy should be distinguished from stereotactic radiosurgery, which uses a high single dose of radiation that is thought to be toxic to the optic nerve. If one summarizes the 4 recent reports on conformal radiation for ONSM with at least 3 years of follow up, the visual data is as follows: in 50 patients treated with a mean follow up of 38 to 51 months, 10 patients with improved acuity, 38 patients with stable vision, and 2 patients with decreased acuity.2427 Approximately 10% of these patients developed major or permanent complications.2427 Despite the encouraging visual results, no tumor shrinkage was observed on sequential imaging studies.25 Because of the limited sample size of these early studies, a comparison of conformal radiotherapy with 3-dimensional conformal radiotherapy is difcult to perform. However, the early results of conformal radiotherapy for ONSM suggests that the more precise targeting offered by conformal radiotherapy may reduce the risk of complications while offering tumor control and visual stabilization in the majority of patients.

n Treatment Summary
The natural history of ONSM suggests that most patients will lose vision over their lifetime, although many patients retain functional levels of vision for many years without treatment. The overall systemic prognosis of patients with ONSM is excellent. Intracranial extension of ONSM occurs in some patients and although its prognostic importance is uncertain,

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patients with tumor extension into the intracranial space need close monitoring. Radiation therapy for ONSM has proven to be effective in stabilizing vision in most of patients, and 20% to 44% of patients will enjoy some improvement of their vision with radiation.20,2527 However, it should be kept in mind that untreated patients with vision of 20/50 or better have a 71% chance of retaining their vision for at least 5 years.3 Even with the increasingly sophisticated methods of delivering radiation to the optic nerve, the current complication rate is at least 10%.19,2227 Therefore, the therapeutic benet of radiation therapy is most compelling for patients with ONSM and functionally compromised vision. Because of the location of ONSM and its proximity to critical neurovascular structures, surgery has a limited role in the treatment of sheath meningiomas. Although a randomized study comparing radiation and surgery for ONSM has not been performed, the paper by Turbin et al suggests that radiation is superior to surgery in stabilizing tumor growth with a better visual outcome and lower complication rate.19 Given the available information on radiation treatment, we recommend reserving radiation treatment until there is a documented visual decline below reading acuity (eg, worse than 20/50). The therapeutic advantage offered by radiation for preserving vision is less convincing for patients with good levels of acuity. For patients with vision worse than 20/50, radiation offers a better chance at visual improvement and preservation than observation, with a complication risk of 10% or more. Radiation should be considered before surgery for most patients because of lower recurrence rates, better visual outcomes, and fewer complications. For patients who have been treated with radiation but have no useful vision, we do not recommend surgical resection for intracranial extension unless there has been documented growth toward the chiasm, hypothalamus, or contralateral optic nerve.

n References
1. Sibony PA, Krauss HR, Kennerdell JS, et al. Optic nerve sheath meningiomas. Clinical manifestations. Ophthalmology. 1984;91:13131326. 2. Dutton JJ. Optic nerve sheath meningiomas. Surv Ophthalmol. 1992;37:167183. 3. Saeed P, Rootman J, Nugent RA, et al. Optic nerve sheath meningiomas. Ophthalmology. 2003;110:20192030. 4. Wright JE. Primary optic nerve meningiomas: clinical presentation and management. Trans Am Acad Ophthalmol Otolaryngol. 1977;83:617625. 5. Wright JE, McNab AA, McDonald WI. Primary optic nerve sheath meningioma. Br J Ophthalmol. 1989;73:960966. 6. Lindblom B, Truwit CL, Hoyt WF. Optic nerve sheath meningioma. Denition of intraorbital, intracanalicular, and intracranial components with magnetic resonance imaging. Ophthalmology. 1992;99:560566. 7. Dutton JJ, Anderson RL. Idiopathic inammatory perioptic neuritis simulating optic nerve sheath meningioma. Am J Ophthalmol. 1985;100:424430.

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8. Egan RA, Lessell S. A contribution to the natural history of optic nerve sheath meningiomas. Arch Ophthalmol. 2002;120:15051508. 9. Alper MG. Management of primary optic nerve meningiomas. J Clin Neuroophthalmol. 1981;1:101117. 10. Walsh FB. Meningiomas, primary within the orbit and optic canal. In: Glaser JS, Smith JL, eds. Neuro-ophthalmology. St. Louis, CV Mosby; 1975:166190. 11. Miller NR. Orbital tumor. In: Long DM, ed. Current Therapy in Neurological Surgery. St. Louis, CV Mosby; 1985:57. 12. Trobe JD, Glaser JS, Post JD, et al. Bilateral optic canal meningiomas: a case report. Neurosurgery. 1978;3:6874. 13. Hart WM Jr, Burde RM, Klingele TG, et al. Bilateral optic nerve sheath meningiomas. Arch Ophthalmol. 1980;98:149151. 14. Mark LE, Kennerdell JS, Maroon JC, et al. Microsurgical removal of a primary intraorbital meningioma. Am J Ophthalmol. 1978;86:704709. 15. Smith JL, Vuksanovic MM, Yates BM, et al. Radiation therapy for primary optic nerve meningiomas. J Clin Neuroophthalmol. 1981;1:8599. 16. Kennerdell JS, Maroon JC, Malton M, et al. The management of optic nerve sheath meningiomas. Am J Ophthalmol. 1988;106:450457. 17. Spencer WH. Primary neoplasms of the optic nerve and its sheaths: clinical features and current pathogenetic mechanisms. Trans Am Acad Ophthalmol. 1972;70:490528. 18. Sarkies NJ. Optic nerve sheath meningioma: diagnostic features and therapeutic alternatives. Eye. 1987;1:597602. 19. Turbin RE, Thompson CR, Kennerdell JS, et al. A long-term visual outcome comparison in patients with optic nerve sheath meningioma managed with observation, surgery, radiotherapy, or surgery and radiotherapy. Ophthalmology. 2002;109:890899; discussion 9900. 20. Parsons JT, Bova FJ, Fitzgerald CR, et al. Radiation optic neuropathy after megavoltage external-beam irradiation: analysis of time-dose factors. Int J Radiat Oncol Biol Phys. 1994;30:755763. 21. Goldsmith BJ, Rosenthal SA, Wara WM, et al. Optic neuropathy after irradiation of meningioma. Radiology. 1992;185:7176. 22. Andrews DW, Faroozan R, Yang BP, et al. Fractionated stereotactic radiotherapy for the treatment of optic nerve sheath meningiomas: preliminary observations of 33 optic nerves in 30 patients with historical comparison to observation with or without prior surgery. Neurosurgery. 2002;51:890902; discussion 34. 23. Paridaens AD, van Ruyven RL, Eijkenboom WM, et al. Stereotactic irradiation of biopsy proved optic nerve sheath meningioma. Br J Ophthalmol. 2003;87:246247. 24. Liu JK, Forman S, Hershewe GL, et al. Optic nerve sheath meningiomas: visual improvement after stereotactic radiotherapy. Neurosurgery. 2002;50:950955; discussion 57. 25. Becker G, Jeremic B, Pitz S, et al. Stereotactic fractionated radiotherapy in patients with optic nerve sheath meningioma. Int J Radiat Oncol Biol Phys. 2002;54:14221429. 26. Narayan S, Cornblath WT, Sandler HM, et al. Preliminary visual outcomes after threedimensional conformal radiation therapy for optic nerve sheath meningioma. Int J Radiat Oncol Biol Phys. 2003;56:537543. 27. Pitz S, Becker G, Schiefer U, et al. Stereotactic fractionated irradiation of optic nerve sheath meningioma: a new treatment alternative. Br J Ophthalmol. 2002;86:12651268.