Visual field fluctuations correlating with the menstrual cycle in a patient with optic pathway glioma

Abstract

Optic pathway gliomas are commonly associated with vision loss in children. We describe an 18-year-old woman with neurofibromatosis, type 1 and an optic nerve glioma who showed reproducible visual field defects that worsened midmenstrual cycle and returned to baseline during menses. To our knowledge, this is the first reported case of visual field fluctuations in a patient with an optic nerve glioma that correlated with her menstrual cycle.

Background

Optic pathway gliomas are often treated as part of a multidisciplinary team, including oncologists, ophthalmologists and neurologists. Treatment plans can be difficult to formulate, especially in cases of unclear progression. This case highlights a situation that required excellent communication between physicians and a holistic approach to treatment.

Case presentation

An 18-year-old woman with a history of neurofibromatosis type 1 and right optic nerve glioma had symptom of worsening of the vision in her right eye. She was initially diagnosed with neurofibromatosis type 1 at 6 months of age and then progressive right optic nerve glioma at 3 years of age. She was treated with carboplatin and vincristine (induction and eight cycles) between 3 and 5 years of age and then due to interval radiographic tumour growth, underwent another eight cycles of carboplatin and vincristine between 7 and 8 years of age. At 13 years of age, despite no radiological changes, Humphrey visual field testing of the right eye showed worsening of the superior and inferior arcuate defects compared with baseline obtained the prior year (figure 1A). Visual field testing of the left eye was full and within normal limits. The patient underwent 18 cycles of lenalidomide over the next 19 months resulting in restoration of the right visual field to baseline. Nine months after stopping lenalidomide when the patient was 16 years old, the right visual field again showed worsening of the inferior and superior arcuate defects without radiological changes. An additional 12 cycles of lenalidomide were administered over the next year with significant improvement of the visual field (figure 1A).

Figure 1.

Baseline clinical characteristics. (A) Pattern deviation plots of Humphrey visual field testing at 12 years of age showed inferior arcuate and early superior arcuate defects. At 13 years of age, worsening of the superior and inferior arcuate defects with correlative decreases in Visual Field Index (VFI) and mean deviation (MD) precipitated initiation of lenalidomide treatment. Following two courses (30 total cycles over 4 years) of lenalidomide, there was improvement of the arcuate defects, VFI, MD and pattern SD (PSD). (B) At 18 years of age, the right optic nerve was pale with thinning of the retinal nerve fibre layer compared with the left optic nerve. G, Global; N, Nasal; NI, Inferior-Nasal; NS, Superior-Nasal; N/T, Nasal:Temporal Ratio; PMB, perimacular bundle; T, Temporal; TI Inferior-Temporal; TS Superior-Temporal.

Six months after completing the second course of lenalidomide, at 18 years of age, the patient had symptom of worsening of the right visual field. Again, there was no evidence of radiographic tumour change. At that time, the patient’s best corrected visual acuity was 20/25 in the right eye and 20/20 in the left eye. She had an afferent pupillary defect in the right eye. Slit lamp examination of both eyes showed Lisch nodules. The right optic nerve was pale and there was thinning of the retinal nerve fibre layer (figure 1B) compared with the left optic nerve.

Due to the patient’s unusual clinical course, further treatment was deferred. Repeat testing 2 weeks later showed spontaneous restoration of the visual field back to baseline. Additional testing over the next 10 months demonstrated reproducible fluctuation of the visual field that correlated with her menstrual cycle, which had only become regular after stopping the lenalidomide. Specifically, there was worsening of the superior and inferior arcuate defects with a correlative decrease in mean deviation at midcycle with improvement to baseline during menses (figure 2).

Figure 2.

Visual field fluctuations correlated with menstrual cycle worsening of the inferior arcuate and early superior arcuate defects with associated decreases in Visual Field Index (VFI) and mean deviation (MD) were detected midcycle at ovulation when oestrogen levels are highest. The visual fields improved during menses when oestrogen levels are lowest. PSD, pattern SD.

Outcome and follow-up

This patient’s treatment plan has been changed in order to compensate for the changes seen throughout her menstrual cycle. Visual field examinations are now being scheduled strategically. The patient is aware of these changes and is able to monitor for changes throughout her cycle.

Discussion

Optic pathway gliomas are slow-growing pilocytic astrocytomas that are typically diagnosed during the first decade of life. The tumours can involve the optic nerve, optic chiasm and hypothalamus and often result in vision loss and endocrine abnormalities. Especially when progressive, optic nerve and chiasmal gliomas may present with proptosis, nystagmus, strabismus and vision changes. Definitive diagnosis is made radiologically with characteristic MRI findings showing the extent and location of the tumour.^{1 2}

Chemotherapy has become the first-line treatment for optic pathway gliomas that are causing vision loss or cosmetic deformity. Carboplatin and vincristine are the most commonly used chemotherapeutic agents and show 50%–75% long-term progression-free survival.^{3 4} Monitoring for tumour progression is challenging as there is not strong correlation between radiographic findings and visual changes. Visual field assessment may be most sensitive, however, accurate testing is challenging in the paediatric population.^{5 6} Predictive factors for postchemotherapy progression include posterior location (chiasm or hypothalamic) and tumours not associated with neurofibromatosis. Additional treatment options for refractory tumours include radiation, surgery and more recently bevacizumab and lenalidomide.²

Our patient’s clinical course which involved four rounds of chemotherapy and tumour progression well into her teenage years is highly uncharacteristic of optic pathway gliomas. Thus, when the patient showed progression again at 18 years of age, no treatment was initiated. Careful observation of her visual fields allowed for the detection of reproducible and quantifiable fluctuations that were eventually correlated with her menstrual cycle. While the patient reached menarche during her second round of lenalidomide, she only started to have regular, predictable menstrual cycles 6 months after completing the chemotherapy which coincided with her visual field changes. We hypothesise that changes in oestrogen levels over the menstrual cycle may play a role in this patient’s tumour fluctuation. This patient’s visual field was worse midcycle when oestrogen levels are highest. In contrast, the visual field returned to baseline during menses when oestrogen levels are lowest.

Young women with neurofibromatosis type 1 and optic pathway gliomas are much more likely to suffer vision loss and require chemotherapy compared with men, indicating sexual dimorphism in tumour behaviour.⁷ These findings are mirrored in an optic pathway glioma mouse model in which female mice showed greater retinal nerve fibre layer thinning and ganglion cell loss compared with males. In addition, either oophorectomy or pharmacological inhibition of the oestrogen receptor-ß in females restored retinal nerve fibre layer thickness and ganglion cell survival.⁸ This suggests that oestrogen adversely affects optic pathway gliomas and causes compression or loss of retinal ganglion cells within the optic nerve and subsequent vision changes. Additional studies are required to fully understand the effects of oestrogen on optic pathway gliomas at the molecular level and the ramifications of this in clinical practice.

Previous studies have examined fluctuations in visual fields in women throughout the menstrual cycle. In contrast to our patient, visual fields have been shown to be constricted premenstrually and menstrually in healthy women.⁹ Further, mean deviations in automated perimetry are decreased during menstruation compared with ovulation in healthy subjects, women with mild diabetic retinopathy and women with migraine headaches.^10–12 Additional studies also show fluctuations in cerebral hemispheric visual attention over the menstrual cycle,¹³ however, these field changes would be present in both eyes, which was not the case with our patient. Thus, it is unlikely that normal non-tumour related physiological variation is the cause of our patient’s visual field fluctuations.

To the best of our knowledge, this is the first report of visual field fluctuations correlating with the menstrual cycle in a young woman with neurofibromatosis type 1 and an optic nerve glioma. Patients with optic pathway gliomas require continued radiographic and visual field monitoring. Our experience suggests that in women, attention to their menstrual cycles may be important in validating tumour progression and visual field changes.

Learning points.

• There are hormonal influences on optic nerve pathway glioma development and growth.

• Serial visual field examinations need to be analysed carefully in order to avoid unnecessary treatment.

• Female patients with optic pathway gliomas may warrant a treatment plan specific to women of childbearing age, including examinations placed in the context of the menstrual cycle.