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 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 32  |  Issue : 3  |  Page : 271-277

Clinical presentation and outcome of patients with optic pathway gliomas: A series of twenty patients


1 Department of Ophthalmology, Kasturba Medical College, Manipal, Karnataka, India
2 Department of Neurosurgery, Kasturba Medical College, Manipal, Karnataka, India

Date of Submission12-Apr-2020
Date of Decision16-Apr-2020
Date of Acceptance22-Apr-2020
Date of Web Publication23-Dec-2020

Correspondence Address:
Dr. Sudha Menon
Department of Ophthalmology, Kasturba Medical College, Manipal - 576 104, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/kjo.kjo_43_20

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  Abstract 


Background: Optic pathway gliomas (OPGs) are rare neoplasms where the management strategy is still evolving. The purpose of this study is to present our experience of twenty cases of OPGs with an intent to add to the general fund of knowledge. Materials and Methods: Retrospective chart review of patients with OPGs surgically managed in a single tertiary centre over a period of 5 years. Variables analysed include Age at diagnosis, sex, clinical manifestations, neurofibromatosis (NF1) status, tumour location, treatment modality, symptomatic progression, and complications. Results: Of the 20 patients with OPG in the study with a mean age of 12.8 years, four patients had NF1 and 16 had sporadic OPG. Dimness of vision (80%) and headache (55%) were the most common presenting symptoms. Majority of the tumours were chiasmatic (40%) in location and vision was affected bilaterally. Subtotal resection could be achieved in 12 (60%) partial decompression in 4 (30%) and gross total resection in 2 (10%). Four patients required additional shunt surgery for hydrocephalus. Postoperative radiotherapy was administered to thirteen patients and only one patient received chemotherapy. At the end of a mean follow up period of 44 months tumour recurrence was noticed in 11/20 (55%) patients. Vision improved in none, remained stable in fifteen and deteriorated in five. Three patients (15%) succumbed to tumour regrowth in the follow up period. Conclusions: OPGs are uncommon tumours with unpredictable outcome. Visual deficits are often irreversible and progressive. Curative resection is difficult and adjuvant therapy has variable response. Overall survival rates are good but progression free and survival rates are suboptimal.

Keywords: Chiasma, glioma, neurofibromatosis, optic nerve, orbit


How to cite this article:
Menon S, Menon G, Vyjayanth R, George N, Jagdish V. Clinical presentation and outcome of patients with optic pathway gliomas: A series of twenty patients. Kerala J Ophthalmol 2020;32:271-7

How to cite this URL:
Menon S, Menon G, Vyjayanth R, George N, Jagdish V. Clinical presentation and outcome of patients with optic pathway gliomas: A series of twenty patients. Kerala J Ophthalmol [serial online] 2020 [cited 2021 Apr 22];32:271-7. Available from: http://www.kjophthal.com/text.asp?2020/32/3/271/304556




  Introduction Top


Optic pathway gliomas (OPGs) constitute a rare yet challenging group of intracranial and orbital neoplasms.[1],[2],[3],[4] OPGs include a wide spectra of neoplasms with variable extensions, clinical manifestations and management challenges.[1],[2] Management strategies have been evolving recently with increasing focus on the role of chemotherapy. Outcome is variable but generally poor, both in terms of vision and overall quality of survival.[3],[4] Indian literature on this topic is limited and in the absence of large series a uniform standard of care treatment guideline is yet to be established.[5],[6],[7] We present our experience with twenty cases of OPGs with an intent to add to the general fund of knowledge.


  Materials and Methods Top


We retrospectively reviewed all patients who underwent surgery for an OPG at our institute from January 2015 to December 2019. Variables analysed include age at diagnosis, sex, clinical manifestations, neurofibromatosis (NF1) status, imaging findings, tumour location, treatment modality and recurrence. Visual acuity (VA) was analysed using Snellen Chart and field using Goldman's perimetry. Preoperative computerised tomography (CT) and magnetic resonance imaging (MRI) data were used to determine the location of the tumour. All tumours were classified according to the Dodge classification: Stage I-involving only the optic nerve; Stage II-involving the optic chiasm, with or without optic nerve involvement; and stage III-involving the hypothalamus and/or adjacent structures.[8] The postoperative MRI, was used to determine the extent of surgical resection which was grouped as follows– gross-total resection (GTR removal of >90% of the tumour), subtotal resection (STR removal of 50%–90% of the tumor), and Partial decompression (removal of <50% of the tumour). All patients except those undergoing GTR were advised three-dimensional conformal radiotherapy and/or adjuvant chemotherapy. Statistical analyses were performed using the Fisher exact test, Chi-square analysis, and unpaired t-test. P < 0.05 were considered significant.


  Results Top


Patients' characteristics

A total of 20 patients with OPG were included in the study. Four patients (20%) had NF1 and 16 had sporadic (non-NF related) OPG. The study group included nine females and eleven males. All the four NF1 patients were males. Their age at surgery ranged from 2 to 40 years, with a mean age of 12.8 years. The demographics and clinical characteristics of the study groups are shown in [Table 1].
Table 1: Patient demographics and clinical characteristics

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Signs and symptoms at diagnosis

All the patients were symptomatic before diagnosis. The most common symptoms were diminution of vision (16/20; 80%) and headache (11/20; 55%). One patient presented with an intratumoral bleed and altered sensorium. Two patients (10%) with postchiasmatic lesions with frontal and temporal lobe extensions presented with seizures and contralateral weakness. The most common signs were decreased VA (77.5%), visual field deficits in the form of temporal filed cuts (10/20; 50%), optic atrophy (13/20; 65%) and nystagmus (32.5%). One patient with diplopia and a lateral rectus palsy secondary to raised intracranial pressure. Both the patients with prechiasmatic optic nerve gliomas (Dodge I) tumours had evidence of mild proptosis. Hypothalamic disturbance was noted in the form of obesity (2 patients), polydipsia and polyuria (1) and developmental delay (1).

Surgical management

The location of the tumour was predominantly chiasmatic (Dodge II 14/20; 70%), followed by post chiasmatic (Dodge II 4/20; 20%) and two Dodge I tumours [Figure 1], [Figure 2], [Figure 3]. Of the four patients with NF1, two had Dodge II, one each had Dodge I and Dodge III tumours. All the patients underwent surgery. Pterional craniotomy and a transylvian approach was the preferred approach for most (16/20; 80%) chiasmal tumours. Two patients with Dodge III tumours underwent a sub temporal approach. The two patients with optic nerve gliomas underwent transcranial frontal approach to the orbit. Gross total resection could be achieved in only two tumours (both pre chiasmatic). The rest of the patients had either sub total (12/20) or partial decompression (06/20). Hydrocephalus on diagnosis was detected in eight patients (40%) four (20%) of whom required a shunt in the postoperative period. On histopathology, 17 patients (85%) had a pilocytic astrocytoma (PA) (World Health Organization [WHO] Grade I), 2/20 patients had a diffuse astrocytoma (WHO Grade II) and one patient had anaplastic astrocytoma. Thirteen patients underwent postoperative radiotherapy and one received adjuvant chemotherapy also [Table 2].
Figure 1: Axial T1 (a), axial T2 (b) and axial contrast T1 (c) images of a Dodge I optic nerve glioma with evidence of axial proptosis

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Figure 2: Axial (a), sagittal (b) and coronal (c) magnetic resonance imaging of a Dodge II chasmal tumour with extension up to the floor of the third ventricle (d) Fundoscopy showing primary optic atrophy

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Figure 3: Axial contrast (a), coronal contrast (b) and sagittal contrast (c) magnetic resonance images of a Dodge III tumour with extensive spread along the hypothalamus and bilateral optic tracts (red arrows)

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Table 2: Radiological features, management strategy and outcome in our series of ONG patients

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Complications and mortality

The mean follows up period was 44 months. The overall 3-year survival rate was 85.71% (17/20). Three patients-two boys and one girl, died from tumour progression. All of these three patients had sporadic tumours, two Dodge III (Post chiasmatic) and one Dodge II (Chiasmatic) tumours. All of them had only STR of the tumour and all had undergone postoperative radiotherapy. All the three had evidence of tumour progression on follow up with raised intracranial pressure symptoms which resulted in mortality. One of these patients had an anaplastic astrocytoma on histology. Three patients developed postoperative infection with meningitis which responded well to appropriate antibiotics.

Recurrence

A total of 11 patients (55%) had tumour progression on MRI. Six of these recurrences were symptomatic with worsening of visual symptoms and raised intracranial pressure. Four of them underwent ventriculo peritoneal shunt and two underwent repeat surgery for further decompression [Table 2]. Both the pre chiasmatic tumours who underwent GTR remained clinically and radiologically stable at the end of nearly 4 years.

Visual outcome

VA outcome was uniformly poor in our series. None of the patients showed improvement following surgery, five deteriorated and fifteen remained static [Table 2]. Visual deterioration correlated with tumour progression in all these five patients. Interestingly, even patients (6/15; 40%) with stable VA showed a progression of field deficits on close follow up. [Table 2] has no mention of visual field. So shift the reference to [Table 2] line 9.

Prognosticators

Optic atrophy on diagnosis was a definite prognosticator for visual deterioration and five of the thirteen patients with optic atrophy on admission deteriorated in vision. Vision was more likely to remain stable with chiasmatic lesions rather than pre or post chiasmatic lesions, but this observation lacked statistical significance. Age, sex, location of the tumour, extent of resection did not have statistically significant correlation on vision or recurrence [Table 3] and [Table 4]. P value of sex with visual outcome-significant.
Table 3: Predictors of visual outcome following surgery

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Table 4: Predictors of recurrence following surgery

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  Discussion Top


Epidemiology

OPGs are relatively rare neoplasms, comprising <1% of all CNS neoplasms in the general population and about 5% of central nervous system tumours in children.[1],[2],[3],[4],[5],[6],[7],[8],[9] The mean age at diagnosis ranges between 2.7 and 5.4 years and majority (80%–90%) of all patients belong to the first two decades of life.[10],[11],[12] Our study group had a mean age of 12.8 years, but we had nearly eight patients (40%) aged above 20 years. There is no gender predisposition and both men and females are equally affected. We did not notice any sex predilection in our series also.

OPGs are commonly associated with NF1 and appear in almost 30% of NF1 patients.[3] The mean age at diagnosis in NF1 patients is generally younger than generic patients. In a large series published recently by Nicolin et al. the mean age was 5.9 years, and there was a high proportion of Dodge II and III patients.[13] Bilateral OPGs are considered pathognomonic for NF1 and usually they tend to be located anteriorly.[14] Generally NF1 OPGs are considered relatively indolent tumours with less evidence of progression, an observation recently being challenged.[15] Surprisingly, the mean age of patients with NF1 (19.5 years) in our series was higher than that of sporadic OPG (11.12 years).

Location and classification

OPGs are low-grade glial neoplasms (WHO grade I) that originate from any location along the visual system such as the optic nerve, optic chiasm, optic tracts, and rarely, the optic radiation.[16] Various classification systems have been proposed for OPGs.[8],[16],[17] They were first classified in 1958 by Dodge and the old system is still widely followed. This system was modified in 2008 and where in each group was subdivided into further categories taking into account factors such as the existence of NF1 or leptomeningeal dissemination.[17] In Fred Epstein's classification proposed in 1985 the tumour component is rated anatomically (T1: One ON, T2: Both ONs, T3: OC, and T4: Hypothalamus/thalamus) and functionally (V0: Normal; V1: Impaired, one eye; V2: Impaired, both eyes, or blind, one eye; V3: Blind, one eye and impaired, one eye or field defect; and V4: Blind both eyes).[17] A comprehensive classification which takes into account additional parameters like age, NF, hydrocephalus, imaging features etc., has also been recently proposed by Shofty et al.[16] We adopted the earlier Dodge system in view of its ease in application.

Clinical presentation

Symptomatology can be variable depends on the location and extent of the lesion. Visual complaints dominate in almost all patients and neurological problems, such as headaches, vomiting, and seizures, are present in only 16% of patients.[12] Anterior optic nerve gliomas present with decreased VA, visual field cuts, nystagmus, and proptosis and the visual examination may reveal optic atrophy.[12] Posterior chiasmal tumours may produce endocrinological and hypothalamic symptoms like precocious puberty, obesity, short stature and somnolence.[16] Large tumours reaching up to the third ventricle may produce raised intracranial pressure symptoms due to hydrocephalus. Diencephalic syndrome (cachexia, macrocephaly, nystagmus, and visual deficit) is seen in 21% of infants with chiasmatic/hypothalamic tumors.[18] The clinical manifestations in our series is almost similar to that mentioned in literature. One distinct difference was the relatively less incidence of hypothalamic disturbance in spite of the fact that majority of the tumours were Dodge II variety. One of our patients presented with an intratumoral bleed, an extremely uncommon finding in OPGs.

Radiology

OPGs are usually isointense on T1, hyperintense on T2, and show variable contrast enhancement. Tumours of the optic nerve appear as gross thickening of the nerve itself.[16],[19] Differential diagnosis include other suprasellar tumours like craniopharyngiomas, pituitary adenomas, hypothalamic hamartomas etc., DTI tractography help in tracing the visual tract and is a useful adjunct for surgical planning.[20],[21] Optical coherence tomography (OCT) has been shown to detect loss of retinal nerve fibre layer in patients with OPG.[22],[23]

Pathology

PA accounts for the vast majority of these tumours and the rest include fibrillary and pilomyxoid astrocytomas (PMA), oligodendrogliomas, and gangliogliomas. PMA usually present in younger patients and show a more aggressive behaviour, and seeding through cerebrospinal fluid (CSF) pathways, higher mortality, decreased odd survival.[24],[25] Malignant transformation of low-grade OPG is rarely seen; most frequently associated with irradiation.[26] In our series majority were PAs but we had one patient with a malignant anaplastic variant.

Natural history and prognosis

The natural history of OPGs is variable and not definite. Some tumours regress, some remain static and some grow and metastasize. Earlier considered benign, OPGs are increasingly being categorised as tumours with malignant potential.[27],[28],[29] Out of the 5% of low-grade gliomas that undergo leptomeningeal spread, OPGs represent ~ 50% and such spread is more commonly seen with sporadic OPG patients.[29] Patients with BRAF-KIAA 1549 fusion protein are known to have a better prognosis and molecular analysis for this marker protein may help in management decisions and surveillance.[15] None of the patients in our series exhibited spontaneous regression and none had leptomeningeal or CSF spread either.

Treatment

The exact timing of treatment is controversial. Patients with significant deficits, mass effect or hydrocephalus require immediate intervention. Treating an incidentally detected asymptomatic patients is controversial and is best managed by watchful expectancy and masterly inactivity.[12],[30],[31],[32] For those with stable lesions, imaging and neuro-ophthalmological examinations (including visual field and OCT if available) needs to be done every 6 months. Treatment options include surgery, chemotherapy, and irradiation.

Surgery

For tumors with characteristic MRI appearance that are epicentered on the optic pathway, especially in an NF1 patient, no biopsy is required.[5],[33] Biopsies are indicated if the tumor has an atypical appearance on MR, for an unusual age group (older than 10 years old or younger than 1-year-old), or with unusual clinical characteristics.[5],[16] For Dodge I, isolated optic nerve gliomas surgery is best delayed and performed only when vision is severely compromised, when patient has intractable pain or progressive proptosis. Globe-sparing-resection of the lesion along with optic nerve is often carried out preferably through a transcranial approach. Surgical management of chiasmatic/hypothalamic tumours is challenging and controversial. Maximal safe resection especially of the exophytic multi compartmental lesion is the recommended surgical approach. Aim of surgery is to decompress the optic apparatus and open CSF pathways.[34],[35],[36] Ventriculoperitoneal shunt may be required is some cases if hydrocephalus persists.[37] Our surgical strategy too was directed along the above lines with an aim to preserve function at the expense of radical tumour clearance.

Chemotherapy

Chemotherapy is progressively being considered the first line of treatment in most cases of children with progressive OPG. “Gentle Chemotherapy” with vincristine and carboplatin was introduced in 1987 by Packer et al. and is now an accepted first-line treatment.[38] This regimen reported progression free survival rates (PFS) rates of 75% at 2 years and 68% at 3 years for chiasmatic tumours.[38] Weekly vinblastine is an option for patients with allergy to carboplatin.[39] Unfortunately, only one patient in our series received adjuvant chemotherapy.

Radiotherapy

Radiotherapy provides comparable results like chemotherapy and used to be the preferred approach before introduction of chemotherapy. With the usual dose of 45–60 Gy in 1.6–2 Gy fractions, 5-year PFS and overall survival rates are reported to be in the range of 82%–85% and 93%–94%, respectively.[40] Stereotactic radiosurgery, gamma knife and proton beam therapy are also reported to provide equally comparable results similar to conformal radiotherapy.[41],[42],[43]

Outcome

OPG outcome is generally favourable in terms of survival, but not so in terms of vision. Long-term survival rates are excellent, ranging between 80 and 96% in numerous series over the last 10 years.[4],[13],[30] The overall 10-year survival rate was 84%, and anterior tumors (nerve and chiasm) have a better 10-year survival of 95% then posterior tumors 76%.[44] In general, post treatment, 32% experience improvement in their VA, 40% stabilize, and 28% experience further deterioration.[45] Our mortality rate was higher in comparison to published literature. We had a 15% (3/20) mortality, all due to tumour regrowth. Our visual outcome, was not encouraging either, with vision remaining stable in fifteen patients (75%) and deteriorating in the rest. Eleven postoperative patients developed recurrence of whom six were symptomatic. Radiotherapy too did not seem to influence risk of recurrence was same in patients who underwent RT (53.84%) and who did not (57.14%).

Outcome prognosticators

As our series was small none of the parameters had a statistically significant influence on outcome prediction. However, we observed that presence of optic atrophy preoperatively and a Dodge III type of tumour had an adverse influence on outcome.


  Conclusion Top


OPGs are uncommon with unpredictable outcome. Visual deficits are often irreversible and progressive. Curative resection is difficult and adjuvant therapy has variable response. Overall survival rates are good but progression free survival rates are suboptimal. The goal of visual control in OPG has not yet been reached. Further studies and research are needed to improve our current understanding about this enigmatic neoplasm.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflict of interest.



 
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    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

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