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Surgery as a safe and effective treatment option for spheno‐orbital meningioma: a systematic review and meta‐analysis of surgical techniques and outcomes

Abstract Purpose The effectiveness and safety of surgery for spheno‐orbital meningiomas remains subject of debate, as studies often describe different surgical approaches and reconstruction techniques with very heterogeneous outcomes. We aimed to systematically summarize and analyse the literature on spheno‐orbital meningiomas regarding presenting symptoms, surgical techniques, outcomes and complications. Methods Studies were retrieved from eight databases. Original articles were included if in ≥5 patients presenting symptoms, surgical treatment and outcomes were described. Fixed‐ and random‐effects meta‐analysis was performed to estimate weighted percentages with 95%CIs of presenting symptoms, outcomes and complications. Results Thirty‐eight articles were included describing 1486 patients. Proptosis was the most common presenting symptom (84%; 95%CI 76–91%), followed by unilateral visual acuity deficits (46%; 95%CI 40–51%) and visual field deficits (31%; 95%CI 20–43%). In 35/38 studies (92%), a pterional craniotomy was used. Decompression of the optic canal (82%) and the superior orbital fissure (66%) was most often performed, and usually dural (47%) and bony defects (76%) were reconstructed. In almost all patients, visual acuity (91%; 95%CI 86–96%), visual fields (87%; 95%CI 70–99%) and proptosis (96%; 95%CI 90–100%) improved. Furthermore, surgery showed improvement in 96% (95%CI 78–100%) for both diplopia and ophthalmoplegia. The most common surgical complications were hypesthesia (19%; 95%CI 10–30%), ptosis and diplopia (both 17%; 95%CI, respectively, 10–26% and 5–33%) and ophthalmoplegia (16%; 95%CI 10–24). Conclusion Patients with spheno‐orbital meningioma usually present with proptosis or unilateral decreased visual acuity. Surgery shows to be effective in improving visual acuity and visual field deficits with mostly minor and well‐tolerated complications.


Introduction
Meningiomas are central nervous system tumours, arising from the meninges (Whittle et al. 2004). Spheno-orbital meningiomas (SOM) represent 9-18% of all meningiomas (Cushing & Eisenhardt 1939;Maroon et al. 1994;Mirone et al. 2009;Leroy et al. 2016) and are characterized by substantial hyperostosis of the sphenoid wing with an en-plaque carpetlike soft-tissue component (Li et al. 2009). Due to the complex anatomical location in the anterior skull base and the tendency for invasion of the periorbit, intra-orbital growth, and sometimes the extensive hyperostosis of the optic canal, superior orbital fissure, and other cranial nerve foramina, resection of these tumours is challenging and is associated with possible neurological and visual deficits (Ringel et al. 2007). Due to this growth pattern, the most common presenting symptoms are progressive symptoms of proptosis, unilateral decrease of visual acuity and visual field deficits (Jiranukool et al. 2016). Aim of surgery is to improve or prevent further deterioration of these visual, neurological and cosmetic symptoms.
Studies published on spheno-orbital meningiomas are mostly small series, describing different surgical approaches and reconstruction techniques with very heterogeneous neurological and visual outcomes. As a result, the effectiveness and safety of spheno-orbital surgery, especially regarding visual outcomes, remains subject of debate. Therefore, the aim of this systematic review and meta-analysis was to systematically summarize the literature on used surgical approaches, extent of decompression/resection of hyperostotic bone, management of the periorbit, reconstruction techniques, visual and neurological outcomes, and complications in patients with spheno-orbital meningioma.

Methods
This systematic review and meta-analysis were reported according to the PRISMA criteria (Moher et al. 2009).

Search strategy
PubMed, Embase, Web of Science, COCHRANE Library, Emcare, PsychINFO, Academic Search Premier and Science direct were searched for relevant literature on 8-2-2018, and the search strategy was updated on 31-7-2019. The search strategy included terms for meningioma, sphenoid wing and spheno-orbital, and derivatives or synonyms of these words. The complete search strategy can be found in the supplements (Table S1).

Inclusion and selection of articles
All articles were screened on title and abstract, and potentially relevant articles were included based on full-text screening (Fig. 1). Original articles were included if at least five SOM patients were included in the study, and if information regarding the presenting symptoms, or surgical treatment or outcomes was reported. Only English articles were included. Studies presenting aggregated information on various pathologies were excluded. Literature reviews were also excluded. In case of multiple articles describing overlapping cohorts, the article with the largest study population was included. In case of articles describing the exact same cohort with the same study size, the most recent article was included. The selection of articles and the data extraction was done by two independent reviewers (A.H.Z.N. and F.L.F.).

Data extraction
The extracted study characteristics consisted of study, patient, tumour and treatment characteristics: the institution, study period, number of patients, age and sex, definition used for hyperostotic SOMs, other tumour location in case of multiple meningioma, WHO grade, SOM tumour diameter, radiological findings of tumour location and invasion, surgical approach, percentage patients who underwent reoperation, extent of decompression and resection of hyperostotic bone, Simpson grade, management of periorbit, reconstruction technique of both the bony and dural defects, previous therapies, and postoperative radiotherapy. The following presenting symptoms and postoperative outcomes were also extracted from the included articles: unspecified visual deficits, visual acuity, visual fields, proptosis, cranial nerve deficits, complications of surgery (specific for SOM surgery and general surgical complications), progression-free survival, and follow-up length. As there is no commonly accepted terminology for the anatomy, reconstruction material and visual outcomes, multiple different terms could have been used describing the same concepts. Therefore, we combined some of the terms for surgical approach, visual outcomes and reconstruction materials (Table S2).

Risk of bias
The risk of bias assessment for the individual articles was performed using a modified QUIPS (quality of prognostic factors) scale (Hayden et al. 2013), a standard tool of the Cochrane. Included elements in our assessment were patient population (description of study period, consecutive inclusion of patients and description of baseline demographics), clear description of intervention and outcome measurement (comparison of pre-and postoperative outcomes and reporting of reducible percentages), and less than 10% loss to follow-up (Table S3). An overall low risk of bias was given when seven or more points were scored out of a maximum of nine points. Low risk of bias for the separate components was given if the complete amount of points possible was scored.

Analyses
Estimated weighted percentages of presenting symptoms, clinical outcomes (improved/stable versus worsened) and complications were calculated using random-effects (n ≥ 5 studies) or fixed-effects (n < 5 studies) models. Some articles only mentioned improvement of symptoms, and for these studies, only this outcome was pooled. The Freeman-Tukey arcsine transformation was used to prevent exclusion of studies with extreme outcomes (0 or 100%; Nyaga et al. 2014). The I 2 statistic was used for quantification of between-study heterogeneity for analysis with ≥5 articles. In case of <5 studies, no reliable quantification of between-study heterogeneity can be estimated (Higgins et al. 2003;Hippel 2015). Pooled results are reported as percentages with 95% confidence intervals (95%CIs). Subgroup analysis was performed on outcomes and complications of studies using the pterional approach in more than 95% of the patients. Analyses were performed with STATA version 14.1 (StataCorp LLC, College Station, TX, USA). Reported information on surgical approaches, extent of resection and reconstruction techniques, including the periorbit, were not analysed through meta-analysis, but systematically summarized and presented. To assess the possible impact in heterogeneity in follow-up lengths and study period, number of operated cases per year and reporting quality, multiple additional subgroup analyses were performed for the main visual outcomes (proptosis, visual field and visual acuity), only including studies (1) with a minimum mean or median follow-up length of ≥2 years, (2) published after 2000, and (3) classified as low risk of bias. The cut-off of ≥2 years follow-up was based on our own clinical experience, as deterioration in visual outcomes tend to happen after the first two years after surgery.

Results
A total of 621 unique articles were identified on 18-2-2018, of which 177 were read full text. Of those, 37 articles were included in the study. With the update of the literature search, 26 new unique articles were identified, of which one was included. Eventually, 38 articles were included in this study ( Fig. 1) describing 1486 patients. All studies were retrospective cohort studies. The median sample size was 30 patients (range: 6-130) with a follow-up range between 3 and 135 months. For a median of 14% of patients (IQR 3-21%), outcomes were described of a reoperation. For all study characteristics, see Table 1.

Risk of bias individual studies
The scoring of the risk of bias assessment is shown in Table S4. For description of the patient population, 20/38 (53%) of the articles were classified as low risk of bias, for intervention 28/38 (74%), for outcome measurement 35/38 (92%) and for follow-up only 8/38 (21%). A total of 24 studies had an overall low risk of bias (24/38; 63%). For the complete scoring of risk of bias, see Table S4.

Presenting symptoms
Presenting symptoms regarding visual symptoms, cranial nerve palsies and other neurological deficits are depicted in Fig. 2.

Surgical approach
Different surgical approaches were used to resect spheno-orbital meningiomas. The (extended) pterional approach was the most used approach as used in 37 of 38 studies (97%). For a schematic representation of the (extended) pterional approach, see Fig. 3. The surgeon's view after a pterional approach on the sphenoid bone is shown in Fig. 4. One article did not mention their surgical approach (2%). In 2008, the first approach other than pterional was described, the lateral orbitotomy. Since a few years, endoscopic resection in selected SOM patients is also performed and is described in three articles (3/38; 8%). For the complete table of surgical approaches, see Table S5.

Decompression/resection of hyperostotic bone
The extent of decompression or resection of hyperostotic bone per article is shown in Fig. 5. The most frequently decompressed structure was the optic canal (31/38; 82%), followed by decompression of the superior orbital fissure (SOF, 25/38; 66%) and resection of the anterior clinoid process (ACP, 22/28; 58%) and the lateral orbital wall (21/38; 55%). There was no trend over the years in the extent of decompression or resection of hyperostotic bone (see Table S6).

Reconstruction
The most used reconstruction materials for dural defects were fascial grafts (7/ 38; 18%) and pericranium (6/38; 16%). The most used reconstruction materials for bony defects were titanium mesh  . 6). Abdominal fat was used to fill up the remaining cavity in eight articles (9/38; 24%). In Table S7, the usage of reconstruction materials over time is presented. Regarding dural defect reconstruction, in recent years more artificial dural reconstruction materials were used.

Periorbit
In 22/38 articles (58%), infiltrated periorbit was resected in some cases. Eleven articles (11/38; 29%) reported they (sometimes) opened the periorbit (Fig. 7). It was maintained in only two of 38 articles (5%). Nine articles did not mention their management of the periorbit (24%). In Table S8, it is shown that resection of the periorbit has been performed from the early days on. Only opening the periorbit was first reported in 2005 by Schick et al. (2006).
In subgroup analysis only including studies using the (extended) pterional approach (Fig. S1), diplopia improved in 94% of the cases (95%CI 73-100%). In 93% (95%CI 69-100%), ophthalmoplegia improved. Existing visual acuity deficits improved in 91% (95% CI 86-95%) and visual field deficits in  Outcomes of sensitivity analysis only including articles published after 2000, with a follow-up ≥2 years, and scored with a low risk of bias were overall similar to the main analysis (Figs S2-S4).
For a table of comparison of the complete analysis and subgroup analysis, regarding clinical outcomes and complications, see Table S9.

Discussion
Resection of spheno-orbital meningioma is a safe and effective therapeutic option, as it results in excellent improvement of visual and neurological symptoms with low complication rates. Therefore, it is stimulated and advised to refer these patients for surgery to prevent further progression of their presenting visual and neurological symptoms. Over the years, there is no clear trend in change of surgical approach and reconstruction technique, except for opening of the periorbit instead of periorbit resection and the use of endoscopic and multiportal approaches in recent years for selected cases.

Surgical decompression and resection
While different surgical approaches are possible for SOMs, the aim of surgery should always be a maximum safe resection with improvement or  Maximum safe decompression and resection of hyperostotic bone should be performed to improve presenting visual deficits or to prevent further deterioration, while minimizing the risk for complications such as development of new cranial nerve deficits, possibly leading to an impaired HRQoL (Mirone et al. 2009;Gonen et al. 2018). Nevertheless, subtotal resection of affected bone increases the risk for recurrence and the possible need for second operation or radiotherapy with its potential risks. In addition, recent PET-CT studies reported presence of pathological hyperostotic cells in areas not identified by surgeons, supporting the need for a maximum resection (Kunz et al. 2017).
There is especially strong evidence for the safety and effectiveness of the pterional approach. The pterional approach is specifically a useful approach, as it enables access to the middle cranial fossa, anterior cranial fossa and the orbit through one approach. Recently, transorbital approaches have been reported, primarily for decompression of hyperostotic bone for optimal cosmetic results and in combination with other approaches (i.e. multiportal approaches including transnasal approach) for optimal multi-angle surgical resection and decompression of hyperostotic bone (Zimmer & Theodosopoulos 2009;Dallan et al. 2015).

Reconstruction techniques
The primary goal of reconstruction of the orbital walls is to prevent enophthalmos, especially pulsatile enophthalmos, which after reconstruction occurs between 2,3% and 30,0% of patients (Gaillard et al. 1997;Honeybul et al. 2001;Bikmaz et al. 2007;Ringel et al. 2007;Mirone et al. 2009;Saeed et al. 2011;Amirjamshidi et al. 2015;Terrier et al. 2018). Reconstruction of dural defects is done to prevent CSF leaks, and reduce the risk of wound infection and meningitis (Talacchi et al. 2014;Leroy et al. 2016), which after reconstruction occurs in respectively 5%, 3% and 6% of patients. The periorbit can be opened or removed to gain access to intra-orbital tumour extension. However, possible complications for intra-orbital tumour resection are ophthalmoplegia (Maroon et al. 1994). Therefore, in the majority of cases the periorbit is only resected/opened when invaded. In these cases, resection of periorbit may be necessary to minimize the risk of recurrence and get significant proptosis reduction. Terrier et al also suggested that there is a correlation between opening the periorbita and the reduction of proptosis after surgery (Terrier et al. 2018). The percentages represent the part of the total articles, which performed this decompression/resection. The numbers given next to the bullets, represent the number of articles using this reconstruction material in this year. most symptoms, especially proptosis and cranial nerve deficits which improved in almost all patients, but also visual acuity and visual field deficits which improved respectively in 91% and 87% of patients. While ophthalmoplegia is one of the most occurring complications in approximately 16%, almost all patients with ophthalmoplegia as a presenting symptom showed improvement (96%). Accordingly, the presence of these symptoms and the aim to improve these symptoms seem a proper indication for surgery. There is no clear evidence in literature on the effect of timing of surgery on visual and neurological outcomes. However, Bikmaz et al. reports that surgery in an early stage will stabilize the condition of the patient, with a small risk for permanent visual complications (Bikmaz et al. 2007).
There are several predictors for postoperative visual outcomes, which should be taken into account during surgical decision-making. Invasion of the optic canal is a negative predictor for both postoperative visual acuity and visual field deficits. Extension into the periorbit is a negative predictor for postoperative visual acuity, and intracranial soft-tissue component for postoperative visual field (Yannick et al. 2012;Forster et al. 2014). Excision of the periorbit seems to have a positive effect on the reduction of proptosis, while radiological involvement of the optic canal is a predictor for residual postoperative proptosis (Yannick et al. 2012;Terrier et al. 2018).

Strengths and limitations of this study
This is the first systematic review and meta-analysis systematically evaluating surgical aspects and clinical outcomes of SOM patients. While we performed an extensive and systematic literature search, there were no studies reporting results separately for other approaches than the pterional approach, and therefore, we could not compare outcomes of different surgical approaches. However, our systematic review showed that the pterional approach is the most used approach and sound analysis could be conducted to present  outcomes for this approach. In addition, the articles described heterogenous case series regarding extent of resection and decompression, reconstruction techniques, and management of the periorbit, which therefore could not be analysed separately. Also, it was not possible to distinguish between transient and permanent complications and between transient and permanent improvements of signs and symptoms, because not all articles specified this in their results. Similarly, it was not possible to estimate outcomes separately for patients who underwent a first operation or reoperation. Similarly, most articles did not report separate percentages for patients with improved and normalized symptoms. Nevertheless, we could assess whether over the years there was a trend of change in these surgical aspects.
Although multiple subgroup analyses were performed to assess the impact of between-study heterogeneity, which added to the robustness of the reported results, we were not able to perform additional analyses to assess the impact of important prognostic variables, such as tumour size, degree of hyperostosis and comorbidities, as these variables were scarcely reported in the included studies. International collaboration is needed to harmonize data collection and increase patient numbers of clinical studies to assess the impact of important prognostic variables on surgical outcomes.

Implications and future perspective
This systematic review and meta-analysis showed that there is firm evidence that surgery, especially the pterional approach, is a rather safe and effective treatment option for spheno-orbital meningioma patients presenting with visual or neurological deficits. While complications occur frequently, up to one in five patients, they are minor and well tolerated. We therefore encourage ophthalmologist to refer these patients for surgery. Over the last 40 years, no consensus emerged in the details of surgery; still a large variety is reported in the extent of resection or decompression of hyperostotic bone, management of the periorbit, and dural and bone reconstruction techniques. Also, the role of radiotherapy has not been clarified yet. The preferred surgical techniques and treatment strategies can therefore not yet be determined. Future studies are needed to assess how spheno-orbital meningioma surgery can be optimized regarding these topics. As there is paucity in HRQoL data, these studies should not only focus on conventional outcomes, but also patient-reported outcomes .

Supporting Information
Additional Supporting Information may be found in the online version of this article: Figure S1. Outcomes subgroup (pterional + extended approach). Figure S2. Sensitivity analysis only including articles published after 2000. Figure S3. Sensitivity analysis only including articles with a follow-up ≥2 years. Figure S4. Sensitivity analysis only including articled scores with a low risk of bias. Figure S5. Complications subgroup (pterional + extended approach). Table S1. Search strategies used for the systematic review. Table S2. Combined terms (surgical approaches, presenting symptoms and reconstruction materials). Table S3. Description of risk of bias assessment. Table S4. Risk of bias assessment. Table S5. Surgical approach of included studies, presented per year of publication. Table S6. Decompression/resection over time. Table S7. Reconstruction materials over time. Table S8. Management of the periorbit over time. Table S9. Improved outcomes and complications of the whole patient population and of the subgroup (pterional + extended approach).