Journal of Neuro-Ophthalmology, September 2006, Volume 26, Issue 3

New Concepts in the Diagnosis and Management of Optic Nerve Sheath Meningioma

Optic nerve sheath meningiomas are by far the most common tumors of the optic nerve sheath. The diagnosis can be suspected in most cases from clinical findings and supported by the results of neuroimaging, obviating tissue biopsy in the majority of cases. Observation may be appropriate in patients with mild or no visual deficit or in whom visual loss is not progressing, whereas stereotactic fractionated radiation therapy has been demonstrated to improve or stabilize vision in progressive or advanced cases. Attempts at surgical excision, and even biopsy, of optic nerve sheath meningiomas are associated with a high risk of blindness and should be reserved for the rare case of an anteriorly located, primarily exophytic tumor with focal involvement of the dural sheath.

THE FIFTH HOYT LECTURE William Fletcher Hoyt, MD, professor emeritus of Ophthalmology, Neurology, and Neurosurgery, University of California, San Francisco, was born and raised in Berkeley, California. He took his undergraduate education at the University of California, Berkeley and his medical education at the University of California, San Francisco ( UCSF). After a year's study at the Wilmer Institute, Johns Hopkins University, under the mentorship of Frank B. Walsh, MD, he returned to UCSF in 1958 to found the neuro- ophthalmology service. During a 36- year academic career- all of it at UCSF- he authored 266 journal articles, co- authored ( with Frank B. Walsh, MD) the biblical third edition of Clinical Neuro- Ophthalmology, and trained 71 neuro- ophthalmology fellows. In 1983, he received the title of Honorary Doctor of Medicine from the Karolinska Institute. He is widely acknowledged as one of the titans of twentieth century neuro- ophthalmology. In recognition of his contributions, the North American Neuro- Ophthalmology Society ( NANOS), in conjunction with the American Academy of Ophthalmology, in 2001 initiated the Hoyt Lecture to be delivered each year at the Annual Meeting of the American Academy of Ophthalmology. New Concepts in the Diagnosis and Management of Optic Nerve Sheath Meningioma Neil R. Miller, MD Abstract: Optic nerve sheath meningiomas are by far the most common tumors of the optic nerve sheath. The diagnosis can be suspected in most cases from clinical findings and supported by the results of neuroimaging, obviating tissue biopsy in the majority of cases. Observation may be appropriate in patients with mild or no visual deficit or in whom visual loss is not progressing, whereas stereotactic fractionated radiation therapy has been demonstrated to improve or stabilize vision in progressive or advanced cases. Attempts at surgical excision, and even biopsy, of optic nerve sheath meningiomas are associated with a high risk of blindness and should be reserved for the rare case of an anteriorly located primarily exophytic tumor with focal involvement of the dural sheath. (/ Neuro- Ophthalmol 2006; 26: 200- 208) Optic nerve sheath meningiomas ( ONSMs) account for one- third of primary optic nerve tumors, are the second most common optic nerve tumors after gliomas, and are the most common tumors of the optic nerve sheath ( 1). Although ONSMs are said to comprise 1% to 2% of all meningiomas, their reported incidence has increased since Wilmer Eye Institute, the Johns Hopkins Hospital, Baltimore, Maryland. Address correspondence to Neil R. Miller, MD, Wilmer Eye Institute, the Johns Hopkins Hospital, Maumenee 127, 600 North Wolfe Street, Baltimore, MD 21287; Email: nrmiller@ jhmi. edu the development of more advanced neuroimaging tech­niques, which have also significantly contributed to earlier recognition of the disease. PRIMARY AND SECONDARY OPTIC NERVE SHEATH MENINGIOMAS ONSMs may be primary or secondary. Secondary ONSMs arise intracranially from dura on or near the planum sphenoidale and spread anteriorly within the con­fines of the optic nerve sheath through the optic canal to surround the orbital portion of the nerve, whereas primary ONSMs arise from arachnoid cap cells within the dural sheath surrounding the orbital or, less commonly, the canali­cular portion of the optic nerve ( 2,3). In this review, I address issues that relate equally to primary and secondary ONSMs except for those tumors that include an obvious midline soft tissue mass on the planum sphenoidale. Independent of the primary site of origin, ONSMs usually spread around the optic nerve through the subdural and subarachnoid spaces following pathways of least resis­tance such as vessels and dural septa ( 2,4). As they spread they compromise the function of the nerve by impairing blood supply to the nerve and by interfering with axon transport. The tumors thus are interposed between the nerve substance and its extradurally- derived blood supply ( Fig. 1) making the majority of ONSMs not amenable to resection. Some ONSMs remain localized to a small segment of the optic nerve, whereas others spread to surround the entire length of the orbital and canalicular portions of the 200 J Neuro- Ophthalmol, Vol. 26, No. 3, 2006 Fifth Hoyt Lecture J Neuro- Ophthalmol, Vol. 26, No. 3, 2006 Neil Richard Miller, MD Neil Richard Miller, MD, was born in Wichita Falls, TX and grew up in Omaha, NE. He graduated from Harvard College in 1967 with a magna cum laude in biochemistry. He completed medical school, medical internship, and ophthalmology residency at Johns Hopkins University, and after a neuro- ophthalmology fellowship at the University of California- San Francisco from 1975 to 1976, returned to the Wilmer Eye Institute at Johns Hopkins University, rising through the academic ranks to become the Frank B. Walsh Professor of Neuro- ophthalmology in 1987. Widely regarded as a scholar's scholar, he is generally the last word on virtually any subject in the field of neuro- ophthalmology. His academic output is unrivalled. The author of over 360 peer- reviewed journal articles and 60 book chapters, he is also the co- author of eight books, among them the biblical Walsh & Hoyt's Clinical Neuro- Ophthalmology, now in its 6th edition. William F. Hoyt, MD, who had largely written the 3rd edition, selected Dr. Miller as the author of the 4th edition. Dr. Miller has trained some of the finest neuro- ophthalmologists in the world, and has been president of the North American Neuro- Ophthalmology Society ( NANOS) ( 2000- 2002) and the International Neuro- Ophthalmology Society ( INOS) ( 1980- 1982, 1990- 1992). nerve. Rarely, the tumor infiltrates the dura and spreads beyond the confines of the nerve to infiltrate adjacent orbital structures, including fat, extraocular muscles, and bone. When the tumor spreads to adjacent bone, it may enter the Haversian canal system, inciting hyperostosis and bone proliferation ( 5). In a meta- analysis by Dutton in 1992 ( 1), the mean age at presentation for ONSMs was 41 years ( range, 3- 80 years) with women being affected more frequently than men ( 3: 2). Patients with neurofibromatosis had a higher incidence of ONSM compared with the general population. Almost all cases ( 95%) were unilateral. The majority of ONSMs were intraorbital with 8% confined to the optic canal. Interestingly, canalicular meningiomas had a higher incidence of bilaterality ( 38%) than ONSMs within the orbit. In a subsequent series reported by Saeed et al in 2003 ( 6), half of the patients with bilateral ONSMs had tumors along the planum sphenoidale in continuity with the lesions in both optic canals. Thus, it would appear that some cases of apparently bilateral ONSMs are truly bilateral, whereas others represent either the spread of a planum sphenoidale meningioma to both optic canals or of a unilateral ONSM across the planum to the contralateral optic canal. Approximately 4% to 7% of ONSMs occur in childhood ( 1,2). Unlike ONSMs that occur in adults, there is no gender predilection and they are often associated with neurofibromatosis type 2. In addition, ONSMs in children often behave in a more aggressive fashion characterized by faster growth and more frequent intracranial and bilateral involvement than occurs in adults ( 6). Meninges and. $ loa& 5uj> r> L Qrl^ tal Optic Neroe Extra d. u. ru. 1 Yew 3) urc j : <= » - - £< tr « . iiu. ia( Atttru FIG. 1. Meninges and blood supply of the orbital part of the optic nerve. ( Reproduced from Lindenberg R, Walsh FB, Sacks JG. Neuropathology of Vision: An Atlas. Philadelphia: Lea and Febiger; 1973: 77.) =->=^ i=) rs^ sr 201 J Neuro- Ophthalmol, Vol. 26, No. 3, 2006 Miller CLINICAL MANIFESTATIONS The majority of ONSMs present with a slowly progressive optic neuropathy characterized by a variable loss of visual acuity ( 1,6- 8). In the Dutton study ( 1), 45% of patients had a visual acuity of 20/ 40 or better, whereas fewer than 25% had counting fingers or worse. Even patients who do not have significant reduction in visual acuity often have disturbances of color vision and visual field. Less common symptoms in patients with ONSMs include periocular or retrobulbar pain or discomfort, double vision, and transient visual obscurations ( 1,6- 8). The obscurations of vision are almost always associated with optic disc swelling and in some cases are exacerbated or induced by eye movement. Almost all patients with a unilateral ONSM have an ipsilateral relative afferent pupillary defect and most have optic disc swelling without peripapillary hemorrhages or soft or hard exudates ( 1,6- 8). Other ophthalmoscopic findings include macular swelling contiguous with a swol­len optic disc, choroidal folds, and acquired retinochoroidal shunt vessels ( Fig. 2). Indeed, the triad of visual loss, optic disc pallor, and retinochoroidal shunts is almost pathogno­monic for ONSM, although this triad tends to occur relatively late in the course of the disorder ( 9). Orbital signs such as proptosis are present in 30% to 65% of patients with ONSMs depending on the series ( 1,6). Mechanical restric­tion of ocular motility is found in 39% of patients ( 6) but is usually asymptomatic. IMAGING The diagnosis of an ONSM may be made by a variety of imaging studies, most often high- resolution CT scanning ( 10), thin- section MRI ( 11), or ultrasonography ( 12). These studies generally obviate the need for tissue biopsy in most cases, making an early diagnosis possible without poten­tially damaging the optic nerve during surgery. Neverthe­less, metastatic infiltration of the optic nerve and optic nerve sheath ( 13,14), as well as lymphoma ( 15) and in­flammatory lesions such as sarcoid ( 16,17) or sclerosing orbital inflammation ( 18), may mimic ONSMs, and these should be considered in the differential diagnosis of a pa­tient with a presumed ONSM. ONSMs have 3 main morphologic patterns on imaging: tubular, fusiform, and globular ( 6). CT typically shows enlargement of the optic nerve with an increased density peripherally and decreased density centrally ( the " tram- track" sign) ( 19). These changes are particularly well seen after intravenous injection of iodinated contrast material ( Fig. 3). In addition, in some cases of ONSM, calcifications surrounding the nerve are present on CT, although they may be masked by contrast enhancement and thus are best identified on precontrast soft tissue and bone-windowed images ( 10). The presence of such calcifications is thought to indicate slow growth ( 6). MRI provides somewhat better detail of ONSMs than does CT ( 11). In particular, the soft tissue component of the tumor is readily visible, particularly when Tl images are viewed in contrast- enhanced, fat- saturated images. The appearance of the optic nerve on enhanced coronal MRI images is most often that of a hypodense area ( the optic nerve) surrounded by an enhancing thin, fusiform, or globular ring of tissue ( the tumor) ( Figs. 4- 6). Careful FIG. 2. Fundus of a patient with a left optic nerve sheath meningioma shows slightly swollen, superiorly pale optic disc with multiple retinochoroidal shunt vessels ( arrows). FIG. 3. Precontrast axial CT of a presumed left optic nerve sheath meningioma demonstrates a hyperintense left optic nerve sheath with central lucency corresponding to the nerve ( the " tram- track" sign). 202 © 2006 Lippincott Williams & Wilkins Fifth Hoyt Lecture J Neuro- Ophthalmol, Vol. 26, No. 3, 2006 FIG. 4. Tubular optic nerve sheath meningioma. A. Postcontrast T1 axial fat- suppressed MRI demon­strates tubular enhancement of the optic nerve sheath with irregular margins suggesting orbital fat in­vasion. B. Postcontrast T1 coronal fat- suppressed MRI in another pa­tient shows enhancing tissue sur­rounding the right optic nerve. The nerve itself appears as a small hypo-dense central area. Note the irregu­lar borders of the enhancing region. examination discloses that, rather than having a perfectly smooth outline, all forms of ONSMs have very fine extensions into the orbital fat ( Fig. 5). MRI also provides sufficient tissue detail that one can assess intracranial extension ( 1,6,11). Ultrasound of the orbit can also be helpful in the diagnosis of an ONSM. Echographic evaluation of an ONSM characteristically shows an enlargement in the diameter of the nerve with predominantly medium- to- high reflectivity and an irregular acoustic structure. There may be shadowing from internal calcification ( 1). In many cases, a 30° test reveals solid thickening of the nerve, whereas in others, the tumor is located more posteriorly and the anterior enlargement of the nerve is the result of cerebrospinal fluid trapped by the tumor ( 12). In rare cases, small tumors located within the optic canal are impossible to detect using currently available neuroimaging procedures. Such lesions are usually discov­ered during exploratory craniotomy and unroofing of the canal. The lesions may be suspected, however, in any patient with slowly progressive, unilateral loss of vision associated with signs of optic neuropathy. In addition, the presence of enlarged, aerated, posterior ethmoid and sphenoid sinuses, a condition known as pneumosinus dilatans, is believed by some authors to be pathognomonic of an ONSM even when such lesions are not obvious on neuroimaging ( 20). HISTOLOGY Two histologic patterns are seen in ONSMs ( 21). In the meningothelial or syncytial pattern, polygonal cells are arranged in sheets separated by vascular trabecula. Mitoses are uncommon. In the transitional pattern, spindle or oval cells are arranged in whorls. Psammoma bodies are common in this form and develop from hyalinization and deposition of calcium salts in the degenerated centers of the whorls. MANAGEMENT Biopsy The imaging characteristics of ONSMs are so typical that rarely is biopsy required for diagnosis. As noted previously, however, some processes such as sarcoidosis may produce an appearance that mimics that of an ONSM. Thus, under certain circumstances such as an atypical clinical course characterized by sudden or rapidly pro­gressive visual loss, it may be appropriate to biopsy the nerve. In such cases, one can reach the nerve from the lateral or medial orbital side or, if the lesion is in the optic canal, from an intracranial or transnasal endoscopic approach. The biopsy should be limited to the dural sheath and subdural tissue without violating the nerve itself. Surgery Traditionally, ONSMs have either been observed without intervention or treated by excision of the tumor FIG. 5. Fusiform optic nerve sheath meningioma. A. PrecontrastTI axial MRI shows fusiform mass surround­ing the right optic nerve. The nerve can just barely be identified coursing through the mass. B. Postcontrast T1 axial fat- suppressed MRI shows the enhancing nature of the mass, which surrounds the relatively hypo-intense optic nerve. 203 J Neuro- Ophthalmol, Vol. 26, No. 3, 2006 Miller FIG. 6. Globular optic nerve sheath meningioma. Post-contrast T1 sagittal MRI shows a well- circumscribed globular lesion that appears to be adjacent to the optic nerve. Note some enhancement of the optic nerve sheath beneath the tumor. The lesion was thought to be a caver­nous hemangioma, but surgery disclosed a meningioma. The lesion was removed without loss of vision, which has remained normal for several years. ( Photo courtesy of S. Pitz.) along with the nerve because of concern for intracranial extension. In such cases, the patient is blind after surgery, and disturbances of eyelid function and eye movements are often present ( 1). Attempts to excise these tumors while keeping the optic nerve itself intact are usually unsuccess­ful, and most patients are blind in the eye after such surgery ( 2,6,22- 24). The only exceptions are ONSMs that are primarily extradural ( 1). In such cases, the bulk of the tumor can be excised ( 25), although rarely if ever can the entire tumor be removed, because at least some of the tumor remains behind in the subdural or subarachnoid space sur­rounding the nerve ( 1,6). In other cases, particularly those with acute visual loss, some authors recommend opening the optic nerve sheath to decompress the nerve ( 6,26). I believe that this procedure should be used only if followed by fractionated radiation therapy ( see subse­quently). Otherwise, the visual improvement is only temporary and tumor may subsequently spread throughout the orbit. Medication To date, trials of medical therapy for ONSM have not been successful. Because meningioma cells often express a variety of hormone receptors, most commonly for estrogen or progesterone ( 27), it might be expected that treatment with estrogen or progesterone antagonists would result in destruction of the tumor or at least reduction in its size and extent, but this does not seem to be the case. Similarly, although hydroxyurea has been said to be helpful in some cases of intracranial meningioma, I am aware of only one case report in which the treatment of an ONSM with hydroxyurea resulted in visual improvement ( 28). Radiation Radiotherapy for ONSM was initially used only as an adjuvant to surgery because meningiomas in general were once considered to be completely radioresistant. In 1981, however, Smith et al ( 29) reported the successful treatment of 5 patients with ONSMs using conventional fractionated radiotherapy. These authors documented improvement in visual acuity in 2 patients, an improvement in the visual field in 3, and regression of retinochoroidal shunt vessels in 2 patients. Kennerdell et al ( 23) subsequently treated 6 pa­tients with fractionated radiation therapy and documented improvement in visual acuity and visual fields in 5 and stabilization in 1 patient. No complications were observed during a follow- up period that ranged from 3 to 7 years. In 2002, Turbin et al ( 30) reported a retrospective series of 64 patients with ONSMs who had been managed with observation alone, surgery, surgery with radiation, or radiation alone. The study included patients from the original report of Kennerdell et al ( 23). The follow- up in this study ranged from 51 months to 516 months with a mean follow- up of 150 months. The authors ( 30) concluded that treatment with radiation alone resulted in the best long- term visual outcome, although approximately one- third of patients treated in this fashion developed complications from the radiation, including radiation retinopathy, retinal vascular occlusion, persistent iritis, and temporal lobe atrophy. The study did not describe which radiation technique was used, but given the era during which the study was conducted and the length of time the patients were followed, it is likely that the majority of the patients were treated with conventional rather than conformal or three- dimensional ( stereotactic) treatment techniques that maximize dose to the tumor and minimize collateral damage ( see " Management" subsequently). The major concern with radiotherapy for ONSMs is late toxicity. Not only can radiation damage the optic nerve itself, but adjacent tissues can also be damaged, including the retina, pituitary gland, and the white matter tracts of the brain ( 31). Retinal injury has been described with expo­sures of more than 50 Gy ( 32,33), but coexistence of diabetes mellitus may lower the threshold for retinal or optic nerve damage to 45 Gy ( 33,34). Late pituitary dys­function is a rare complication of radiation as is small-vessel injury in the anterior temporal lobe after irradiation of ONSMs that extend intracranially ( 23,35). The threshold for radiation damage to the optic nerve, optic chiasm, or both has been estimated to be 8 to 10 Gy for a single dose ( 34). Because lower doses of radiation have an uncertain effect on benign tumors such as ONSMs, and a large, single dose of radiation is associated with 204 © 2006 Lippincott Williams & Wilkins Fifth Hoyt Lecture J Neuro- Ophthalmol, Vol. 26, No. 3, 2006 a high risk of tissue damage ( 36), single- dose stereotactic radiosurgery is not widely used to treat ONSMs ( 37,38). Stereotactic fractionated radiotherapy ( SFR) appears to offer the potential for delivering a sufficient amount of radiation to an ONSM in a manner more focused than that of conventional fractionated radiation therapy, thus mini­mizing the complications from exposure of the surrounding tissue to high doses of radiation. SFR requires complex planning, which is facilitated by sophisticated software and three- dimensional imaging. The pretreatment imaging ( CT and/ or MRI) and radiation delivery require the patient to be repeatedly immobilized although the newest linear accelerator ( LINAC) units such as the CyberKnife ( Accuray Incorporated, Sunnyvale, CA) use a tracking system that eliminates the need for rigid immobilization during the treatment phase. Unlike con­ventional radiation therapy, the LINAC system delivers the radiation in noncoplanar fields that take into account the characteristics of the surrounding tissue. Every beam is size- adjusted and shape- adjusted by different devices, microleaf collimators being the most advanced way of achieving a high degree of conformality to the tumor, thus minimizing irradiation of the surrounding tissue ( 39). In 1996, the first case report ( 40) documented im­provement of vision after conformal irradiation of ONSM. Since then, at least 7 published series have documented improvement or stabilization of vision after SFR ( 6,35, 41- 45). These series are discussed in detail below. PREFERRED TREATMENT OPTIONS Observation The natural history of ONSMs is loss of visual acuity that progresses slowly in most patients over many years ( 6- 8,46). ONSMs are not associated with any mortality or neurologic morbidity and they do not metastasize. Thus, their only adverse effect is on visual sensory function. In a series reported by Narayan et al ( 42), 6 of the 7 patients with initial visual acuity of 20/ 40 or better who were followed without intervention had nearly complete loss of vision over an average duration of 9 years. Nevertheless, observation is appropriate if there is no significant visual dysfunction, no significant progression of visual loss, or no significant intracranial extension of the tumor. In such cases, a clinical examination, including assessment of visual acuity, color vision, and visual fields, should be conducted twice a year for 2 to 3 years and then once a year if the patient's visual function has remained stable. Patients should be counseled to contact their physician if they note any visual loss in the interim. Neuroimaging at 6- month intervals is appropriate for the first 1 to 2 years, then once a year for 2 to 3 years, and then every 3 to 4 years assuming the clinical examination is stable ( 47,48). Because younger patients are more likely to have larger or more rapidly de­veloping tumors, children and young adults with presumed ONSMs should be followed clinically and with neuro­imaging at more frequent intervals. Stereotactic Fractionated Radiotherapy Several published series ( 6,35,41,42- 45) describe SFR as a primary treatment option for ONSMs ( Table 1). Overall disease control in 70 patients was 94.3%. Im­provement of visual function occurred within the first 3 months after treatment in 54.7%. No patient had neuro­imaging evidence of tumor enlargement during the period of follow- up and 3 patients had imaging evidence of a slight decrease in tumor volume. Acute effects of SFR included headache, nausea, local erythema, and focal alopecia. None of these complications was severe or permanent, but radiation retinopathy was observed in 2 patients within 4 years of treatment. The retinopathy was severe in one patient and was associated with vitreous hemorrhage ( 45); the other patient had only retinal microaneurysms ( 41). This latter patient had a large tumor involving the proximal optic nerve adjacent to the globe, and portions of the retina received 54 Gy Even so, visual acuity improved from 20/ 50 to 20/ 25 and remained stable. In a more recent report ( 49), radiation retinopathy occurred 22 months after SFR resulting in loss of visual acuity from 20/ 25 to 20/ 200. The posterior retina in this patient had received 50 Gy to 54 Gy. Other late ophthalmic complications of SFR included cataract in 1 patient, dry eye in 1, and iritis in 2 patients. None of the patients developed radiation optic neuropathy; however, 2 patients continued to lose vision from tumor progression. Late nonocular side effects included pituitary dysfunction in 3 patients and imaging evidence of punctate white matter lesions in the cerebral hemispheres in 1 patient. Both findings are a potential concern after irradiation for posteriorly located ONSMs, particularly those with mild but definite intracranial extension. Interval monitoring of pituitary function in such patients is thus appropriate. Surgery Extensive removal of ONSMs that extend for some distance within the optic nerve sheath or are located in the posterior orbit and/ or optic canal is generally indicated only in rare cases in which there is aggressive tumor growth that extends intracranially and across the planum sphenoidale, thus presenting a risk to the contralateral optic nerve or disfiguring proptosis. Along with unavoidable and perma­nent blindness, such procedures may also cause temporary or permanent ophthalmoparesis, ptosis, or both. Unroofing the optic canal was previously advocated as a method of improving or at least maintaining visual sensory function in patients whose ONSMs were located entirely within the 205 J Neuro- Ophthalmol, Vol. 26, No. 3, 2006 Miller Authors ( reference number) Eyes Period Mean follow- up Treatment modality Treatment regimen Liu et al ( 45) Pitz et al ( 46) Narayan et al ( 42) Saeed et al ( 6) Andrews et al ( 47) Baumert et al ( 48) Richards et al ( 35) Authors ( reference number) Liu et al ( 45) Pitz et al ( 46) Narayan et al ( 42) Saeed et al ( 6) Andrews et al ( 47) Baumert et al ( 48) Richards et al ( 35) 5 12 14 1 l i t 23 4 Stable 1 7 7 0 10 5 0 1994- 2001 1989- 1986 1976 1996 1996 1999 - 2000 - 2001 - 1999 - 2001 - 2003 - 2002 Improved 4 5 5 • H- 1 16 5 1- 7 years 37 months 51.3 months 12 months 20.7 months 20 months 2 years Worse 0 0 2 • H- 0 2 0 FSR FSR 3D- CFR CSFR FSR CSFR FSR Imaging 0 0 0 0 0 0 0 25- 30 X 1.8 28 X 1 28- 31 X 1 28 X 1 28- 30 X 1 25- 30 X 1 25- 27 X 1 8 8 6 8 8- 2.0 7- 1.75 Complications* 0 Hyperprolactinemia ( 2) Partial hypophyseal in sufficiency ( 1) Dry eye ( 1) Iritis ( 2) Microaneurysms ( 1) Cataract ( 1) 0 Radiation retinopathy 4 years after treatment ( vitreous hemorrhage) ( 1) Radiologically evident cerebral punctuate small vessel fall out in the field of irradiation ( 1) Eyes = The subset of eyes with measurable vision ( counting fingers and better). Treatment regimen = The number of fractions X doses per fraction ( Gy). Stable, improved, worse = The treatment effect on visual acuity and visual fields at the last follow- up, as defined by author. 3D- CFR = 3- dimensional conformal fractionated radiotherapy. CFSR = Highly conformal stereotactic radiotherapy. SFR = Stereotactic fractionated radiotherapy. "" Transient complications not listed. f The number of eyes with primary ONSM. ^ Patient initially improved but 8 months later developed a sudden visual defect. TABLE 1. Summary of primary stereotactic radiotherapy series canal ( 26); however, this treatment has been supplanted by radiation therapy ( see previously) in large part because of the temporary nature of the improvement/ stabilization with canal unroofing. On the other hand, as noted previously, in rare cases of anteriorly located, primarily exophytic tumors with focal involvement of the dural sheath, surgical excision is a potential treatment choice and can be performed without undue risk of iatrogenic visual loss ( 6), although most such cases are identified at surgery because it is extremely difficult to distinguish exophytic tumors from other lesions such as cavernous hemangiomas and solitary fibrous tumors that are simply adjacent to the optic nerve. Furthermore, optic nerve sheath decompres­sion with release of trapped cerebrospinal fluid or removal of some tumor followed by radiation therapy may also be beneficial in some cases of acute visual loss ( 50), although as noted previously, when improvement does occur, it is likely to be transient unless stereotactic or conformal fractionated radiation therapy follows. A potential draw­back of surgery is that it exposes the orbit to tumor extension. CONCLUSION The main goals in the management of ONSMs are ensuring a favorable visual outcome, establishing local control of the tumor, and minimizing the risks of treatment-related morbidity. Limitations for any treatment study of ONSMs include both the rarity and usually very slow course of the disease, the fact that there often is no tissue diagnosis so that some patients in a treatment trial could 206 © 2006 Lippincott Williams & Wilkins Fifth Hoyt Lecture J Neuro- Ophthalmol, Vol. 26, No. 3, 2006 have lesions other than an ONSM ( sarcoidosis), the necessity of pooling data from multiple different treatment centers, and the need for a long (> 10 years) follow- up period to detect late recurrences and late side effects of the treatment. In the 7 studies described here ( 6,35,41- 45), the short- term efficacy of SFR in preserving or improving vision appears to be excellent with more than half of the patients having improvement within 3 months after treatment. The results also suggest that earlier treatment might offer a better chance of preserving useful vision. Based on the results of published studies, as well as my own experience, I believe that SFR is the best option for most cases of progressive or advanced disease. However, because of improved imaging, patients with presumed ONSMs associated with mild progressive or stable visual loss are being diagnosed earlier, and the choice between observa­tion and radiation has become more difficult. I agree with others ( 51) that longer follow- up is needed to establish the incidence of enduring benefit and late toxicity after SFR and to clarify the optimal management of these cases. REFERENCES 1. Dutton JJ. Optic nerve sheath meningiomas. Surv Ophthalmol 1992; 37: 167- 83. 2. Alper MG. Management of primary optic meningiomas. Current status- therapy in controversy. J Clin Neuroophthalmol 1981; 1: 101- 17. 3. Wilson WB. Meningiomas of the anterior visual system. 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