Introduction

Optic nerve sheath meningioma (ONSM) is a relatively rare tumor, accounting for 1–2% of all meningiomas [1, 2]. Developing from the arachnoid cap cells of the optic nerve sheath, these benign and slowly progressive tumors cause optic nerve insult through compression and vascular compromise, resulting in severe visual impairment that may lead to blindness [3]. Tumor may grow intracranially through the optic canal to involve the optic chiasm and the contralateral optic nerve. Hence, it is of paramount importance to stop or reverse the growth of the tumor. In the treatment of ONSM, preservation of vision following tumor resection is known to be difficult, because surgery precipitates complications that damage the pial vascular plexus nourishing the optic nerve in many cases, leaving 95% of patients with severe postoperative visual impairment [1]. Surgery is currently indicated when esthetic issues arise following loss of vision or when intracranial tumor extension impacts prognosis for survival. In recent years, stereotactic radiotherapy (SRT), in the broad sense of the term, has been reported as an effective alternative to surgery [4, 5].

Intensity-modulated radiation therapy (IMRT) uses a device such as a multileaf collimator to adjust spatial and temporal radiation intensity and irradiate a precise focal target from multiple directions, thereby achieving optimal dose distribution on a three-dimensional plane. An advanced version of conventional stereotactic radiation therapy that is more effective and non-invasive, this new system reduces exposure to surrounding tissue by enabling modulation of dose intensity within the radiation field. Studies have already shown the advantages of IMRT for treating various intracranial tumors and skull base meningiomas [6,7,8,9]. The optic nerve is highly sensitive to radiation and therefore requires precision radiotherapy to avoid severe radiation-induced optic neuropathy. Detailed research into IMRT outcomes in the treatment of ONSM is lacking. As such, the present study examined the efficacy and complications associated with IMRT for ONSM by applying the technique to a large number of cases and comparing visual function before and after treatment.

Patients and methods

Design

This is single hospital-based, retrospective, observational study.

Patients

Analysis was performed of cases of ONSM that were between February 2012 and August 2017 in the Division of Neuro-Ophthalmology and Ocular Oncology Unit of the Department of Ophthalmology at the Jikei University Hospital. The observation period lasted until October 2017. Diagnosis of ONSM was based on (1) unilateral onset, (2) slowly progressive visual deterioration, (3) positive findings of a relative afferent pupillary defect, (4) optic disc findings, and (5) optic nerve swelling and tram-track sign detected on contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI) of the orbit. Although the tram-track sign can be also seen in sarcoidosis, perioptic neuritis, leptomeningeal carcinomatosis, lymphoma, leukemia, and orbital inflammation, these diseases exhibit rapid deterioration. We excluded subjects presenting acute onset or general complications. In this study, all patients had prolonged symptoms up to treatment. Although various morphological typologies have been proposed for tumor growth patterns, the present study categorized patterns into three types as diffuse (tubular), fusiform, or globular according to definitions used in several past studies [1, 3, 10].

IMRT was indicated if patients exhibited at least one of the following clinical features: (1) reduced best-corrected visual acuity (logMAR > 0), (2) visual field abnormality, or (3) intracranial tumor extension. Eyes with visual acuity at or below the ability to count fingers at the initial examination were excluded.

IMRT irradiation

IMRT was performed in the Division of Radiation Therapy at the Jikei University Hospital using a Clinac linear accelerator (Varian Medical Systems, Palo Alto, CA) (Supplement 1). After patients were fixed by immobilization equipment (ShellTM), gross tumor volume (GTV) was delineated using CT and MRI fusion images. GTV was the gross demonstrable extent and location of ONSM. Clinical target volume (CTV) was identical to the GTV. Planning target volume (PTV) was defined as the CTV with a margin of 3 mm. A 2-mm set-up margin was added to the organs at risk, such as the optic nerve, optic chiasm, retina, and pituitary gland. Cone beam CT (CBCT) was performed before each treatment using a 360-degree rotation of the linear accelerator, and CBCT-based GTV was precisely adjusted to planning GTV. Irradiation was provided as 50.4–54.0 Gy in 28–30 fractions, the known tolerance dose for the optic nerve.

Evaluation of treatment efficacy

Visual acuity, visual fields, optic disc, and radiology findings were assessed before and after IMRT. Counting fingers and hand motions were quantified as a logMAR value of − 2. Improvement and deterioration of vision was defined as changes in logMAR values of <− 0.2, and > + 0.2, respectively, whereas stable vision was defined as − 0.2 ≤ logMAR ≤ + 0.2. Visual fields were assessed using Goldmann perimetry performed by an expert examiner with extensive experience. Poor visual acuity due to central scotoma was difficult to evaluate with Humphry field analyzer. In addition, the evaluation of peripheral visual field defect was required. Therefore, we selected Goldmann perimetry first.

Statistical analysis

Using SPSS Statistics version 25 software (IBM, Tokyo, Japan), pre- and post-IMRT measurements of visual acuity were compared using the Wilcoxon signed-rank sum test.

Results

Patients

The 15 patients selected for analysis comprised 14 women and only 1 man, with ages ranging from 33 to 77 years (median, 49 years). Eight right eyes and 7 left eyes were affected, and disease duration from subjective symptoms to treatment ranged from 5 months to 25 years. Minimum and maximum post-treatment observation periods were 8 months, and 4 years and 9 months, respectively (median, 1 year and 11 months). Individual patient data are shown in Table 1.

Table 1 Clinical data of all patients
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Radiology findings

In terms of ONSM morphology, 5 eyes showed diffuse growth with 2 eyes showing intracranial extension, 8 eyes showed fusiform growth with 1 eye showing intracranial extension, and 2 eyes showed globular growth (Table 1, Figs. 1, 2, and 3). After IMRT, tumor enlargement was not detected in any eyes, and tumor reduction was seen in 2 eyes. Intracranial invasion was not found in cases with intraorbital ONSM after IMRT.

Fig. 1
figure 1

Case 12 (diffuse type). a (Contrast-enhanced orbital MRI): finding of an intraorbital diffuse-type ONSM in the left eye with intracranial extension (circled area). b (Immediate post-IMRT GP of the right eye): inferior visual field loss (best-corrected logMAR visual acuity was 0.30). c (Orbital CT): IMRT dose distribution map. d (pre-IMRT GP of the right eye): inferior visual field improvement (best-corrected logMAR visual acuity was 0.15)

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Fig. 2
figure 2

Case 6 (fusiform type). a (Orbital MRI): finding of an intraorbital fusiform-type ONSM in the right eye (circled area). b (Pre-IMRT GP of the right eye): temporal visual field loss (best-corrected logMAR visual acuity was 0.40). c (Orbital CT): IMRT dose distribution map. d (Immediate post-IMRT GP of the right eye): temporal visual field improvement (best-corrected logMAR visual acuity was − 0.08)

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Fig. 3
figure 3

Case 4 (globular type). a (Contrast-enhanced orbital MRI): finding of an intraorbital globular-type ONSM with the tram-track sign in the left eye (circled area). b (pre-IMRT GP of the left eye): finding of a central scotoma and a superior temporal scotoma (best-corrected logMAR visual acuity was 0.52). c (Orbital CT): IMRT dose distribution map. d (Immediate post-IMRT GP of the left eye): disappearance of the central scotoma and reduction of the superior temporal scotoma (best-corrected logMAR visual acuity was − 0.08)

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Optic disc findings

Before treatment, swelling, atrophy, and optociliary shunt vessels were observed in the optic discs of 7, 3, and 5 eyes, respectively, whereas no abnormalities were found in 5 eyes (Table 2). After treatment, optic disc atrophy was detected in 3 eyes and anterior ischemic optic neuropathy was detected in 1 eye. No changes in optic discs findings were observed in the remaining 11 eyes. In addition, no post-treatment changes were seen in the 5 eyes with optic discs negative for pre-treatment abnormalities.

Table 2 Changes in optic disc findings from pre- to post-treatment
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Visual acuity

Immediate post-treatment visual acuity (IPostVA), which reflects effects and complications immediately after 28 to 30 times radiation treatment, improved in 5 eyes, remained stable in 9 eyes, and deteriorated in 1 eye (Table 3). No significant difference between pre-treatment visual acuity (PreVA) and IPostVA was detected (p = 0.050). Final post-treatment visual acuity (FPostVA) improved in 7 eyes, remained stable in 4 eyes, and deteriorated in 4 eyes. No significant difference between PreVA and FPostVA was detected (p = 0.330).

Table 3 Changes in visual acuity from pre- to post-treatment
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Among diffuse tumor, IPostVA improved in 1 eye and remained stable in 4 eyes, whereas FPostVA improved in 3 eyes, and deteriorated in 2 eyes (Fig. 4a). Among fusiform tumor, IPostVA improved in 3 eyes, remained stable in 4 eyes, and deteriorated in 1 eye, whereas FPostVA improved in 3 eyes, remained stable in 3 eyes, and deteriorated in 2 eyes (Fig. 4b). Among globular tumor IPostVA improved and remained stable in 1 eye each, whereas FPostVA improved and remained stable in 1 eye each (Fig. 4c). At final post-treatment follow-up, eyes with fusiform and globular growth maintained better visual acuity compared with pre-treatment levels, whereas 2 of 5 eyes with diffuse growth showed reduced vision (40%) (Fig. 4d).

Fig. 4
figure 4

Changes in pre-IMRT, immediate post-IMRT, and final post-IMRT visual acuity by tumor growth pattern. a Diffuse. b Fusiform. c Globular. d Comparison of means by tumor growth pattern

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Among the 5 eyes negative for optic disc abnormalities, improvement was seen in 4 eyes, whereas 1 eye remained stable (Fig. 5a). Among the 7 cases of optic disc swelling, IPostVA remained stable in 6 eyes and deteriorated in 1 eye, whereas FPostVA improved in 1 eye, remained stable in 3 eyes, and deteriorated in 3 eyes (Fig. 5b). Among the three cases of optic disc atrophy, IPostVA improved in 1 eye and remained stable in 2 eyes, whereas FPostVA improved, remained stable, and deteriorated in 1 eye each (Fig. 5c). Figure 5d compares mean PreVA, IPostVA, and FPostVA among the three optic disc patterns (no apparent abnormality, edema, and atrophy). In all three patterns, vision improved immediately after treatment. At final post-treatment follow-up, all 5 eyes with no apparent abnormality maintained better visual acuity compared with pre-treatment levels, whereas 6 of 7 eyes with edema and 2 of 3 eyes with atrophy remained stable or showed reduced vision.

Fig. 5
figure 5

Changes in pre-IMRT, immediate post-IMRT, and final post-IMRT visual acuity by optic disc findings. a No abnormality. b Swelling. c Atrophy. d Comparison of means by optic disc finding

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Visual field

Various visual field abnormalities were found to have accompanied ONSM (supplement 2). As for affected eyes, after treatment, abnormalities improved in 14 eyes. Improvements were seen in all 5 eyes with optic discs negative for pre-treatment abnormalities. Final post-treatment visual field abnormalities improved in 11 eyes, deteriorated in 3 eyes, and were not assessed in 1 eye (Table 4). As for fellow eyes, scotomas were observed in 3 eyes before treatment, but improved after treatment.

Table 4 Changes of affected eye in visual field from pre- to post-treatment
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Adverse events

Adverse events identified during IMRT included skin redness in 3 patients, lacrimation in 3 patients, eye/retrobulbar pain in 4 patients, heaviness in the rear of the eye in 2 patients, headache in 4 patients, heavy-headedness in 1 patient, nausea in 2 patients, light-headedness in 2 patients, dizziness in 2 patients, fatigue/malaise in 11 patients, and dryness in the nose in 1 patient. All adverse events improved rapidly during the IMRT treatment period.

One eye (case 7) with a diffuse growth pattern that had maintained visual acuity immediately after IMRT developed an acute case of ischemic optic neuropathy on day 127 post-treatment. Another eye (case 1) showed reduced visual acuity due to a cataract on day 653. No cases of systemic complications including endocrine disorders or hair loss were observed.

Discussion

In the context of visual function, increases in visual acuity from pre-treatment levels were achieved immediately after IMRT, and the absence of significant differences between PreVA and FPostVA indicates that vision was preserved in the overall sample. Furthermore, following IMRT, visual field improvements were seen in 14 eyes immediately after IMRT.

Although comparison of PreVA and IPostVA showed that IMRT was effective for all three tumor growth patterns, FPostVA of the entire sample was found to have decreased from IPostVA (Fig. 4a–c). FPostVA tended to decrease from PreVA among eyes with diffuse tumors, but it tended to increase among eyes with fusiform and globular tumors. ONSM is characterized by progressive visual loss, and although one study demonstrated that visual function prognosis is the worst in cases of diffuse tumor growth exhibiting apical expansion [3]. Other research into the prognoses of individual growth patterns is still lacking. The FPostVA findings of the present study suggest that IMRT is favorably indicated for fusiform and globular tumors. In contrast, it was difficult to reach any conclusions in terms of diffuse tumors, because the present sample was not compared with a control group undergoing natural disease progression. Therefore, the effectiveness of IMRT for treating diffuse tumors remains a priority moving forward. IMRT can be performed with high precision by adjusting to the shape of the lesion. Therefore, the difference in treatment effect among tumor growth pattern could result from the extent of the damage or preservation of the optic nerve depending on the shape of the tumors rather than the difference in the dose distribution.

With respect to optic disc findings, of the 5 eyes negative for pre-treatment optic disc abnormalities, there were significant improvements in IPostVA and field performance regardless of the degree of visual loss and visual field impairment present before IMRT; a decline in FPostVA compared with IPostVA was observed in only 1 eye in the present study. On the other hand, post-treatment visual acuity and field performance for 10 eyes with pre-treatment optociliary shunt vessels and optic disc swelling and atrophy were inconsistent and ranged from improvement to no change to deterioration. Since eyes negative for optic disc abnormalities showed only a small reduction in FPostVA (i.e., late-stage vision), we believe that early treatment with IMRT before the appearance of atrophy, swelling, and other types of optic disc insult may lead to better outcomes for visual function.

In terms of SRT for ONSM, it has been reported that no relationship exists between the timing of radiotherapy and prognosis [10], that better visual acuity performance can be gained with early treatment [11], that treatment efficacy is greater in eyes with PreVA ranging from 20/40 to 20/30 [12], and that treatment is indicated when visual acuity is ≤ 20/40 or when visual field impairment is detected [13].

Because the present study showed that treatment was effective regardless of the degree of visual loss, and FPostVA was better among eyes administered IMRT before developing optic disc impairment, we believe that early IMRT is desirable when patients experience subjectively reduced vision and visual field disturbances.

A search of the literature identified studies that examined the efficacy of IMRT for treating ONSM, and there were only 25 cases in total [7, 8, 11, 14,15,16,17,18]. Furthermore, only 5 cases in total could be followed up for more than 5 years after IMRT as monotherapy [16, 18]. According to these studies, IMRT resulted in visual acuity improvement and stability in 19 eyes, no response in 3 eyes, and deterioration in 3 eyes, and it was associated with late adverse events, including lens opacification in 3 patients, dry eye in 3 patients, radiation-induced retinopathy in 2 patients with diabetes mellitus, keratitis in 2 patients, and blepharitis, otitis media with effusion, and early menopause in 1 patient each. The number of eyes examined in the present study is so far the greatest in a single institute.

Comparing different types of stereotactic irradiation techniques, SRT uses fractionated irradiation to deliver a uniform dose within the radiation field, IMRT delivers a non-uniform dose that mitigates exposure to proximal organs at risk, and stereotactic radiosurgery delivers a uniform dose within the radiation field in a single session. IMRT allows for more non-invasive treatment, because dose intensity can be modulated within the targeted field, thus lessening irradiation of surrounding tissue.

Various studies have reported the advantages of SRT for treating ONSM [19, 20], but they have also reported both ocular and systemic complications. IMRT is anticipated to achieve better local tumor control and visual improvement with a lower complication rate than conventional SRT [21, 22]. Acute complications observed in the present study disappeared soon after completion of IMRT. In terms of late complications, 1 eye developed ischemic optic neuropathy after IMRT. Although hypopituitarism after SRT for ONSM is reported [21], there were no symptoms related to this complication in the present study.

We showed the efficacy of IMRT in a large number of cases in a single facility. However, several limitations of this study should be acknowledged. First, because of the various follow-up period, the time when the final visual function was evaluated is different in each case. Second, due to the short observation period, the late complications of IMRT have not been evaluated. The longest observation period is 4 years and 9 months in this study.

There are few reports of long-term prognosis of IMRT because IMRT is a novel radiation therapy compared with conventionally fractionated stereotactic radiotherapy and conformal radiotherapy. We will continue to follow up the cases and evaluate long-term post-treatment visual function and complications in further study.

IMRT for the treatment of ONSM achieved improvement and preservation of visual function. We believe that early treatment with IMRT before the appearance of optic disc abnormalities can be more effective for improving visual function, particularly among patients with fusiform and globular growth patterns. Moreover, the risk of serious post-treatment complications is considered low.