Rare case of optic pathway glioma with extensive intra-ocular involvement in a child with neurofibromatosis type 1.

We present a case of a 3-year-old girl with a positive family history of neurofibromatosis type-1 (NF1) presented with best corrected visual acuity of 20/40 in the right eye and <20/400 in the left eye. External ocular examination revealed left eye proptosis of 3 mm, grade II left relative afferent pupillary defect and full range of ocular motility with no strabismus. Slit lamp examination revealed iris lisch nodules bilaterally. Dilated fundus examination of the right eye was normal. Left eye disclosed a large mass extending from the optic nerve head, with associated subretinal fluid. There was neovascularization at the optic disc as well as a superior retinal hemorrhage. Computed tomography of brain/orbits showed an enlarged left optic nerve with a large mass at the optic nerve head, with no evidence of calcification. In addition, a large left optic pathway glioma (OPG), multiple hamartomas within the brain and a smaller low-grade right OPG was also reported. The remarkable feature of our case is the rare intraocular optic nerve involvement of the OPG. Early and regular ophthalmological assessment of all NF1 suspect/confirmed cases is of paramount importance in order to detect OPG early, resulting in timely intervention and salvage of vision.

INTRODUCTION

Optic pathway glioma (OPG) is a tumor known to occur in children with neurofibromatosis type-1 (NF1). Usually, such tumors occur within the extraocular portion of the optic nerve. In this case report, we present a rare case of the optic nerve glioma with extension into the intraocular portion of the optic nerve. Early and regular screening of children with NF1 is important for timely detection and treatment of OPG in order to preserve sight.

CASE REPORT

This was a case report of a 3-year-old girl was found to have multiple cafß-au-lait spots (CALs) on her skin and a positive family history of NF1. She was referred for routine ophthalmological assessment.

On ophthalmic examination, her best corrected visual acuities (BCVA) were 20/40 in the right eye and <20/400 in the left eye. External ocular examination revealed left eye proptosis of 3 mm, grade II left relative afferent pupillary defect and full range of ocular motility with no strabismus. Slit lamp examination revealed iris lisch nodules bilaterally. Dilated fundus examination of the right eye was normal. Left eye disclosed a large mass extending from the optic nerve head, with associated subretinal fluid. There was neovascularization at the optic disc as well as a superior retinal hemorrhage [Figure 1].

Figure 1

Color fundus photo of left eye at the time of presentation, showing large optic nerve head mass with vascularisation and surrounding subretinal fluid

An urgent computed tomography scan the of the brain and orbits showed an enlarged left optic nerve with a large mass at the optic nerve head, with no evidence of calcification. Follow-up magnetic resonance imaging findings were in keeping with a large left OPG and multiple hamartomas within the brain. A smaller low-grade right OPG was also reported [Figure 2].

Figure 2

(a) An axial T2-weighted magnetic resonance imaging with gadolinium showing fusiform enlargement of the left optic nerve involving the intra-ocularportion with no posterior extension to chiasm. (b) Coronal T2 weighted with fat suppression showing left optic nerve glioma

Genetic studies of her phenotype displayed hypertelorism, epicanthal folds and increased carrying angle at the elbow, which was suggestive of the NF-Noonan syndrome variant with a mutation c. 3721C> T (p.Arg1241X) in the NF1 gene.

The patient was referred to pediatric oncology for chemotherapy to treat the OPGs. The treatment regimen consisted of weekly vinblastine over a period of 70 weeks. She continues to receive weekly chemotherapy, repeat brain imaging and ophthalmic follow-up. At her most recent ocular examination (16 months post-diagnosis), her BCVA was no light perception left eye and 20/30 right eye. Ocular motility remains full with no strabismus. Fundoscopy shows a healthy disc and macula in the right eye and the left optic nerve head has become pale and atrophic.

DISCUSSION

NF-1 is an autosomal dominant phacomatosis that affects approximately 1 in 3000 individuals.1 It is characterized by the presence of 2 or more of the following: ≥6 CALs, ≥2 cutaneous neurofibromas, 1 plexiform neurofibroma, an OPG, ≥2 iris lisch nodules, axillary inguinal freckling, bony lesions (pseudoarthrosis), sphenoid wing hypoplasia or a first-degree relative with NF-1.2

OPGs are the most common neoplasm in young patients with NF-1, found in 15% of patients and may lead to blindness. They may be either unilateral or bilateral, invade the optic chiasm anteriorly or have full chiasmal involvement.3

The remarkable feature of our case is the rare intraocular optic nerve involvement of the OPG. To our knowledge only a handful of cases of OPG with intraocular extension have been reported in the literature.34 Initially, in this case the possibility of retinoblastoma (RB) was suggested; however, the absence of calcification of the tumor on imaging argued against a diagnosis of RB as up to 95% of RB show calcification.5 In addition, the ophthalmoscopic findings of a pale and salmon colored tumor at the optic nerve and a high intensity signal emission on the T2 weighted images are considered to be pathognomonic of an OPG.3

Aggressive and extensive OPG can cause progressive protrusion of the globe (as seen in our case) and eventually blindness. Other clinical findings in cases of OPG may include strabismus, papilledema, atrophy and occlusion of the central retinal artery. In general, chemotherapy is the first line therapy for children with progressive NF-1 associated OPG. Radiation therapy is considered in children older than 5 years of age, but not recommended because of associated risks of secondary malignancies and radiation induced vasculopathy.6

This case report presents a child who lost all useful vision in one eye due to the relatively late referral for ophthalmological assessment in an NF1 suspect. We emphasize the importance of knowledge of this diagnosis for the management, prognosticating to the parents the possible outcome of the ocular and general condition and for genetic counselling. Early and regular ophthalmological assessment of all NF1 suspect/confirmed cases is of paramount importance in order to detect OPG early, resulting in timely intervention and salvaging vision.