Primary and secondary tumours of the optic nerve, with emphasis on invasion by uveal malignant melanoma
Authors: Lindegaard Jens 
Published: March 2007

AbstractTumours of the optic nerve may originate in the optic nerve itself (i.e. primary tumours) or in structures adjacent to the optic nerve (i.e. secondary tumours). Furthermore, leukaemic infiltration and tumour metastases from distant solid tumours are also found in the optic nerve (i.e. secondary tumours). Large surveys have described primary optic nerve tumours and their treatment modalities, whereas secondary tumours have received little attention. Most reported work‐ups have been based on material from referral centres and specialized departments.The correlation between invasion of the optic nerve in uveal melanoma and the risk of death from the disease has not been fully elucidated. The impact on prognosis may be correlated with tumour cells left in the proximal nerve after enucleation. In addition, melanoma with secondary invasion of the optic nerve may represent a highly malignant invasive subcategory of uveal melanoma. Clinical factors that make the ophthalmologist aware of optic nerve invasion when investigating a uveal melanoma are most important.Melanomas that invade the optic nerve may histopathologically display different invasive patterns and represent different types of uveal melanoma. A subtype of uveal melanoma with a preponderance for neural invasion may exist. Such a subtype has been identified for cutaneous melanoma (desmoplastic/neurotropic).In order to investigate tumours of the optic nerve in a known population, we studied all optic nerve tumours that had been surgically removed in Denmark over a period of 25 years. Furthermore, in order to resolve questions about secondary invasion of the optic nerve in uveal melanoma, we investigated all eyes with uveal melanoma and optic nerve invasion enucleated in Denmark between 1942 and 2001 (n = 157).Tumours of the optic nerve in children were dominated by optic glioma and invasion from retinoblastoma, whereas tumours in adults mainly comprised optic nerve sheath meningioma and invasion from uveal melanoma.Optic nerve invasion of uveal melanoma was found in one in 20 patients. Increased IOP and juxtapapillary location were associated with both pre‐laminar/laminar and post‐laminar invasion of the optic nerve. Furthermore, age over 70 years, vision reduced to light perception, non‐visible fundus and large tumour size were associated with post‐laminar invasion. Only patients with optic nerve invasion had metastases to the CNS, kidney and heart.Histopathological features associated with optic nerve invasion were focal retinal invasion, neovascularization of the chamber angle and scleral invasion. Furthermore, non‐spindle cell type and rupture of the ILM were all associated with post‐laminar invasion.The optic nerve was invaded in four different ways:

by tumour extension from the neuroretina through the lamina cribrosa;
by direct extension into the optic nerve head between Bruch's membrane and the border tissue of Elschnig;
by direct invasion through the border tissue of Elschnig and,
by spreading along the ILM to the optic nerve head and through the lamina cribrosa.

Most melanomas with invasion of the optic nerve were large juxtapapillary tumours that invaded the nerve because of their close location to it, but a subcategory of neurotropic uveal melanomas with a diffuse invasive growth pattern was also found. These tumours invade the optic nerve and retina regardless of tumour size and location.Invasion of the optic nerve had no impact on prognosis per se, but was seen in association with a series of other prognostic factors (e.g. cell type, extrascleral extension).