Optic nerve and eye tumours

This article gives an overview of the tumours affecting the eye and the optic nerve. The links lead to more detailed accounts of specific tumours. You may also find the following separate articles relevant: Orbital Swellings (covering orbital tumours) and Diagnosing Conjunctival Problems (covering conjunctival tumours).

Background

Tumours in the eye principally occur in the middle layer and inner layers of the eye. The middle layer consists of the uveal tract: iris, ciliary body and choroid; the inner layer of the retina and optic nerve. The outer layer (cornea and sclera) is more prone to infections and degenerative disorders than to tumour - see the separate Corneal Problems - Acute and Non-acute article.

Referring for suspected eye cancer

As with any suspected cancer, patients need to be referred urgently to secondary care.

There are national ocular oncology centres based in London (St Bartholomew's Hospital), Liverpool (Royal Liverpool University Hospital), Sheffield (Royal Hallamshire Hospital) and Glasgow (Gartnaval General Hospital). There are dedicated retinoblastoma services in London (Moorfields Eye Hospital) and Birmingham (Birmingham Children's Hospital).

The National Institute for Health and Care Excellence (NICE) recommends considering urgent referral (for an appointment within two weeks) for ophthalmological assessment for retinoblastoma in children with an absent red reflex.¹

NICE also recommends:²

• Refer immediately children with new-onset squint that occurs together with loss of red reflex in one or both eyes to ophthalmology services.

• Refer immediately children with new-onset squint that occurs together with ataxia, vomiting or headache to acute paediatric services.

• Refer urgently children with paralytic squint for neurological assessment, even in the absence of other signs and symptoms of raised intracranial pressure.

Tumours of the uveal tract

Melanoma³

Uveal melanomas have an incidence of 6 per million per year. Most are choroidal, with the remainder arising from the iris and ciliary body. The melanoma arises in the pigmented uveal tract (the middle layer of the eye, between the sclera and the retina).^{4 5}

Choroidal melanoma
This is the most common site (90%) - it is the most common primary intraocular malignant tumour. See the separate Choroidal Melanoma article.

Iris melanoma⁶
4% of uveal melanomas. Iris melanoma is the least common site of primary uveal melanoma but it has the best prognosis. It is three times more common in blue/grey irides and rare in people of Afro-Caribbean ethnicity. Predisposing conditions include dysplastic cutaneous naevi, familial melanoma and neurofibromatosis. The increased iris pigmentation associated with latanoprost does not appear to be a risk factor.⁷

• Presentation: fifth to sixth decade - usually a nodule of ≥3 mm in diameter (may or may not be pigmented) which has a high surface vascularity. There may be pupil distortion ± an associated cataract. The patient may complain of visual decline (pupil distortion, cataract), pain (elevated intraocular pressure) or be asymptomatic.

• Management: early on, the lesion may simply be observed, as some may be apparently inactive. However, this is lifelong, as further growth may prompt surgical treatment or radiotherapy. Diffusely growing tumours may require enucleation (removal of the eyeball).

• Prognosis: primary iris melanomas are usually well differentiated and rarely metastasise (rate is about 5%). They are generally slow-growing tumours with an excellent prognosis. However, there is a small group of aggressive variants which grow diffusely and are associated with a poorer prognosis.

Ciliary body melanoma
6% of uveal melanomas:

• Presentation: these tend to develop in the sixth decade of life, usually causing visual symptoms (refractive errors due to the tumour pressing on the lens). Occasionally, they are an incidental finding. Depending on the size and location, there may be dilated episcleral vessels, anterior extension through the sclera, subluxation of the lens or cataract and retinal detachment.

• Management: surgery, radiotherapy/brachytherapy/proton therapy or enucleation.

• Prognosis: these melanomas are more likely to progress than iris melanoma and five-year survival is around 70%.⁸

Other iris tumours

Iris naevi
Unlike melanomas, naevi tend to be flat or only very slightly raised. They are usually <3 mm in diameter and are always pigmented. They can cause pupillary distortion.

Iris cysts
Primary cysts of the iris are rare but harmless. The vast majority do not progress and are asymptomatic. Secondary cysts can form as a result of parasitic infection, tumours or long-term use of long-acting miotics.

Other tumours of the choroid

See the separate Tumours of the Choroid article.

Tumours of the retina

The separate Retinoblastoma and Retinal Tumours articles give detail on these topics.

Tumours of the optic nerve⁹

Optic nerve gliomas account for 3-5% of all paediatric brain tumours. They are most commonly World Health Organization (WHO) grade 1 pilocytic astrocytomas and frequently occur in patients with neurofibromatosis type 1. The location of these tumours results in visual loss and blindness, endocrine and hypothalamic dysfunction, hydrocephalus, and premature death. Their involvement of the visual pathways and proximity to other brain structures typically prevents complete resection or optimal radiation dosing without causing significant neurological injury. Surgical interventions that can be performed include biopsy, cerebrospinal fluid diversion, and partial or radical resection.

Optic nerve sheath meningiomas are rare benign neoplasms of the meninges surrounding the optic nerve. Although the mortality rate is practically zero, these tumours can cause severe sight impairment and disfigure patients.¹⁰

Optic nerve glioma and optic nerve sheath meningioma

These are the principal tumours of the optic nerve. Gliomas tend to be a disease of early life: 90% present by age 20. Meningiomas have a peak incidence between 30 and 60 years of age. 95% are unilateral and there is a 4:1 female preponderance.

• Presentation:

  • Gradual, painless fogging or dimming of vision (rarely, the tumour may bleed into itself causing sudden visual loss).

  • Meningiomas can also cause exophthalmos and an ipsilateral dilated pupil that does not react to direct light stimulation but might contract on consensual light stimulation.

  • Children may present with strabismus.

  • Optic nerve sheath meningiomas occasionally cause gaze-evoked amaurosis.

  • There can be overlap in symptoms with optic neuritis.¹¹

  • Examination may reveal poor visual acuity, loss of colour vision, visual field loss, optic disc swelling or optic atrophy.

  • If the tumour is large, there may be proptosis ± limitation of eye movements.

  • Signs are usually unilateral unless there is chiasmal involvement.

• Diagnosis:

  • Glioma: CT or MRI scan.

  • Meningioma: short TI inversion recovery MRI.

• Management:
  

  • Childhood gliomas are generally benign and only treated if there is hypothalamic involvement or progressive visual field loss. Surgical excision is reserved for extreme presentation (blind eye, severe proptosis).

  • Adult gliomas may be highly aggressive, there may be pain and there is a very high mortality rate despite treatment.

  • Chemotherapy remains a mainstay of optic nerve glioma treatment.¹²

  • Meningiomas should be treated with radiotherapy or surgery, depending on individual circumstances. A combination of both (gamma knife surgery) is proving to be successful in some cases.¹³

• Prognosis: childhood gliomas tend to be benign, unlike the aggressive adult type. Lifelong review is needed in all optic nerve tumours.

Optic nerve melanocytoma

This tumour is made up of melanocytes and melanin and is usually benign. It is static (or grows extremely slowly) and any symptoms are due to local pressure effects rather than malignant infiltration.

• Presentation:

  • If the tumour grows, it may cause a relative afferent pupillary defect, accumulation of subretinal fluid or an enlarged blind spot.

  • If the optic nerve is compressed or the optic disc involved, visual acuity may be reduced or lost.¹⁴

  • Compressive vascular problems can also occur - eg, central retinal vein occlusion.

  • If growth compresses the artery, ischaemia and necrosis with inflammation can ensue.

• Management: as most do not grow, they are managed by watchful waiting, aiming to catch any growth early so that complications of growth (described above) can be managed promptly.

• Prognosis: generally good. Rare instances of transformation into melanoma have been described, presenting acutely with pain and glaucoma.¹⁵

Other brain tumours can affect vision, due to optic pathway nerve fibre compression. Some of these are covered by the separate articles Meningiomas, Pituitary Tumours, Craniopharyngiomas, Space-occupying Lesions of the Brain, Brain Tumours in Adults and Brain Tumours in Children.

Lymphoma¹⁶

Background^{17 18}

Primary intraocular central nervous system (CNS) lymphoma is a highly malignant lymphoma which involves the globe in the absence of any other CNS or systemic lymphoma. It is usually a large, aggressive, diffuse B-cell (non-Hodgkins) lymphoma. Risk factors include immunosuppression (including HIV) and Epstein-Barr virus infection. Diagnosis is typically delayed because presenting features can look nonspecific and benign.

Presentation

The condition can masquerade as chronic uveitis, which can lead to delay in diagnosis. Clinical suspicion is needed as, in general, patients do not have the systemic symptoms or lymphadenopathy typical of lymphoma at other sites and they most often complain of blurred vision and floaters.¹⁹

CNS features
Four different pathological pictures are seen:

• Solitary/multiple intracranial nodules.

• Diffuse meningeal/periventricular lesions.

• Localised intradural spinal masses.

• Intraocular involvement.

Ocular features
Usually presents with a uveitis-type picture which often precedes CNS involvement by several months or even years:

• In 80% of cases, both eyes are eventually affected.

• In addition to the inflammation of uveitis, large infiltrates can be seen underneath the retinal pigment epithelium (they look like a dim spot of light in the fog: hazy yellow patches under the retina that may form a ring - pathognomonic).

Investigations

The diagnosis of ocular lymphoma is difficult to make and requires tissue samples obtained under image guidance. Investigation is with vitreous biopsy, combined with neurological evaluation and MRI. Staging should include CT scanning of the chest, abdomen and pelvis; testicular ultrasonography in elderly males; lumbar puncture, cytology, flow cytometric analysis and immunoglobulin gene rearrangement studies. HIV testing forms part of the work-up.

Management

All patients who are fit enough are offered chemotherapy as first-line treatment. This is aggressive therapy involving combined intrathecal and intravenous chemotherapy, followed by radiotherapy to both eyes ± whole brain radiotherapy. Intravitreal methotrexate (MTX) may be used for recurrent disease that is confined to the eyes.

Prognosis¹⁹

Intraocular lymphoma is a highly malignant tumour. Five-year survival is around 60%. Therapies that have been successful in systemic lymphoma have not been reliably effective in primary ocular lymphoma. Prognosis depends on tumour type and stage.

Poorer prognostic indicators include age >60 years, raised LDH, raised CSF protein and involvement of deep brain matter. Prognosis has improved since the introduction of high-dose systemic MTX-based combination chemotherapy (which crosses the blood-brain barrier) followed by combination chemotherapy with MTX and rituximab. Initial response to treatment can be good but the relapse rate is high and long-term treatment-related neurological toxicity remains a major problem.²⁰ See the separate Non-Hodgkin's Lymphoma article for further details about this condition.

Dr Mary Lowth is an author or the original author of this leaflet.