Optic nerve tumors ppt

Optic nerve tumors ppt

1. OPTIC NERVE TUMORS Moderator: Dr. S.C. Bubanale Presenter: Dr. Arushi Prakash 1 Department of Ophthalmology, JNMC 29 th October ’14

2. Contents # Optic Nerve Anatomy Tumors of the Optic Nerve # Optic nerve G liomas # Primary Optic N erve S heath M eningioma # Secondary Optic Nerve Sheath Meningioma # Optic Nerve Melanocytoma # Malignant Astrocytoma # Astrocytic Hamartoma # Lymphoreticular Tumors # Metastatic Tumors Wednesday, October 29, 2014 2 Department of Ophthalmology, JNMC

3. Optic nerve : The optic nerve being a portion of central nervous system is a tract, and not really a nerve. However , as a convention the 1.2 million axons that derive from the retinal ganglion cells carry the name optic nerve, until they partially decussate at the optic chiasm. Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 3

4. Optic nerve is about 50 mm long and extends from the eye to optic chiasm. it carries about 1.2 million axons that derive from the retinal ganglion cells. It consists of 4 portions : A) intraocular portion: optic disc- 1 mm in antero posterior direction. B ) intra orbital portion : about 25 mm long. C) intra canalicular portion with in the optic canal : about 9mm long. D )intracranial portion : about 16mm long. Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 4

5. Constituent elements of optic nerve : Myelinated axons retinal ganglion cells. Oligidendrocytes : These are specialized glial cells that provide membranes for axonal myelination. Microglia : These immunocompetant cells play a role in protection of optic nerve from infection and also suggested that these cells probably play a role in apoptosis of retinal ganglion cells. Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 5

6. Astrocytes: - Astrocytes have extensive neurofibrillary processes that spread among nerve fibres . They form a part of blood brain barrier, and play a role in the nutritional and structural support of axons. -when axons are lost because of optic atrophy , astrocytes move and proliferate to fill the empty spaces . Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 6

7. OPTIC NERVE TUMORS Optic nerve is actually a tract of central nervous system,so primary tumors of the optic nerve are more similar histopathologically to brain tumors than to peripheral nerve tumors. Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 7

8. Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 8 Optic Nerve Glioma

9. Pilocytic hamartomas of the anterior visual pathways. More posterior gliomas are generally more aggressive variants. C omprise ∼1% of all intracranial tumors About half are confined to the orbit; the remainder have intracranial extension manifest themselves early most commonly in the first decade of life ( 70% detected during the first decade, 90% by second) no definite sex predilection Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 9

10. Roughly 29% of optic gliomas are associated with NF1 Among patients with NF1, optic gliomas have been estimated to occur in 14.7-17.4 % Isolated (without association to NF1) optic nerve gliomas are usually unilateral Bilateral involvement is believed to be pathognomonic of NF1 Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 10

11. Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 11 Enucleation specimen with optic nerve glioma from a patient with NF1.

12. Pathogenesis The NF1 gene product, neurofibromin , has a GTPase -activating protein domain that interacts with the Ras protein, which is crucial in regulating signal transduction and cell proliferation and differentiation. Patients with NF1 are at high risk for developing a number of different types of tumors because of this . At this point, the exact mechanism of action of development of these tumors is unknown. Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 12

13. Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 13 The most common presenting findings are proptosis (94%). visual loss (87.5%). optic disc pallor (59 %). disc edema (35%). and strabismus (27%). Patients infrequently present with asymptomatic isolated optic atrophy. An RAPD is usually present in unilateral or asymmetric cases Clinical Features

14. typical optic nerve- related visual field defect (if the patient is cooperative enough for visual field testing). Retinochoroidal collaterals may be present on the affected disc Central retinal vein occlusion or venous stasis retinopathy may occur. Large tumors may cause obstructive hydrocephalus with elevated ICP, headache, and papilledema. Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 14

15. Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 15 Face photo of a 5-year-old girl who developed noticeable proptosis OD and found to harbor an optic nerve glioma . (a) The right fundus of a 5-year-old girl with a right optic nerve glioma reveals an optic nerve with mild edema . Her visual acuity was moderately to severely reduced. (b) The left nerve was normal.

16. In rare cases, the optic glioma can resolve spontaneously Survival is typically reduced when hydrocephalus is present. Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 16

17. Diagnosis is confirmed by neuroradiologic findings Fusiform or globular enlargement of the optic nerve Thickening of both nerve and sheath by tumor Kinking or buckling of the optic nerve Regions of low intensity within the nerve (cystic spaces) Smooth sheath margins (no extradural extension) No calcification or hyperostosis on CT scan Isointense or mildly hypointense to brain on T1 -weighted MRI scan Hyperintense on T2-weighted MRI scan Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 17

18. Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 18

19. biopsy of the mass is generally not required : advent of high -resolution neuroimaging has raised diagnostic accuracy biopsy of sheath alone may be inaccurate with reactive meningeal hyperplasia in gliomas falsely suggesting meningioma biopsy of the optic nerve substance may produce additional visual loss the histopathologic appearance of the tumor is not necessarily predictive of biological behavior Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 19

20. Pathology When confined to the orbital portion of the optic nerve, a glioma often appears as a fusiform swelling Histologically , an optic nerve glioma is generally characterized as a juvenile pilocytic astrocytoma , characterized by cells with prominent eosinophilic processes called Rosenthal's fibers . Mixed gliomas and oligodendrogliomas have been reported as well. The tumor may infiltrate the normal optic nerve substance or be confined primarily to the subarachnoid space. Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 20

21. Department of Ophthalmology, JNMC 21 The tumour cells in optic nerve glioma have elongated or hair-like  appearance ( pilocystic ).Hence the name pilocystic astrocytoma. Rosenthal fibres in optic nerve glioma . These are degenerative   eosinophilic substances found within the cytoplasm of astrocytes.  There are characteristic but not diagnostic of optic nerve glioma

22. The latter type is more commonly found in patients with neurofibromatosis type 1 . Rarely , there is exophytic extension of intracranial optic- chiasmal gliomas . The overall histologic appearance is B enign , with a paucity of cellular atypia , mitosis, or tumor necrosis. Often , microcystoid extracellular spaces containing acid mucopolysaccharide produced by astrocytes are encountered. Such spaces may constitute a major portion of the optic nerve mass. Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 22

23. Natural history Variable patients with the diagnosis of NF1 tend to fare better with respect to growth and visual prognosis. Most tumors grow slowly or have self-limited growth. some tumors are more aggressive, resulting in a rapid increase in ipsilateral proptosis and visual loss. (more apt to occur in patients who do not have NF1) Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 23

24. Management There is no universally accepted management for optic nerve glioma . Observation is indicated for patients with relatively good vision and stable radiographic appearance. Most patients show stability or very slow progression over years and sometimes show spontaneous regression . Chemotherapy is emerging as the first-line treatment when visual loss is severe at presentation or there is evidence of progression. Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 24

25. Combination carboplatin and vincristine ( Oncovin ) is the most accepted regimen. Radiotherapy is controversial because of the inconclusive results and potential complications , including panhypopituitarism and mental retardation . stereotactic fractionated radiotherapy for optic nerve gliomas have been found to show good results Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 25

26. Surgical excision may be indicated in patients with severe visual loss in association with disfiguring proptosis . Surgery has been advocated to prevent advancement into the chiasm; however, extension to the chiasm is rare. Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 26

27. MALIGNANT GLIOMA OF ADULTHOOD Since the advent of CT and MRI, the exceedingly rare malignant gliomas of the optic nerve and chiasm are more frequently being diagnosed before death. Almost invariably, patients present with rapidly progressive unilateral or bilateral visual loss . Eye pain or headache may accompany the visual loss and blindness occurs within weeks of onset. Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 27

28. Central scotomata altitudinal field defects and hemianopias have all been reported. At ophthalmoscopy, the optic disk may be normal in appearance; alternatively , edema or atrophy of the optic disk may be present. Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 28

29. Significant enhancement of the optic nerve after gadolinium infusion may indicate the presence of optic nerve glioma even before marked expansion of the anterior visual pathway Even with aggressive radiation therapy prolonging survival, there is invariably rapid spread of tumor intracranially , and death occurs within month. Histologically , the tumor may be characterized as either astrocytoma or glioblastoma multiforme . Cells spread in the subpial space , resulting in progressive vascular occlusion and demyelination. Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 29

30. # Key Features Associated with painless and slowly progressive vision loss Diagnosis is typically in the first decade of life although they may occur at any age When associated with neurofibromatosis type 1, a familial preponderance may be seen Patients with and without neurofibromatosis type 1 who harbor optic nerve gliomas should be followed conservatively for sometime to determine rate of growth Wednesday, October 29, 2014 30 Department of Ophthalmology, JNMC

31. Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 31 Optic nerve sheath meningioma

32. INTRODUCTION Optic nerve sheath meningiomas (ONSM) are separated into two types: primary and secondary. The primary variety arises from the cap cells of the intraorbital or intracanalicular optic nerve sheath while the secondary form arises intracranially in the region of the sphenoid wing , tuberculum sella , or olfactory groove . Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 32

33. PRIMARY OPTIC NERVE SHEATH MENINGIOMA A rises from proliferations of the meningoepithelial cells lining the sheath of the intraorbital or intracanalicular optic nerve Although these tumors are uncommon ( 1%-2% of all meningiomas ), they account for one third of primary optic nerve tumors . Usually detected in adults age 40-50 Women affected 3 times more than men Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 33

34. 4%-7% of optic nerve sheath meningiomas occur in children. M ay occur more frequently in patients with neurofibromatosis type 2 and may be bilateral. Bilateral tumors , albeit rare, tend to present at an earlier age Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 34

35. Clinical Features Patients may present with the classic diagnostic triad: Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 35

36. Clinical Features There often is little if any proptosis . Roughly 50% will present with disk edema while the other half will demonstrate pallor. Some patients will also show choroidal folds due to compression behind the globe. Optociliary vein collaterals in the presence of vision loss and optic disk pallor should suggest the diagnosis of an ONSM Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 36

37. Clinical Features Visual fields typically show central and paracentral scotomata as well as altitudinal defects, which progress over time Despite the typical progression of reduction in visual function, some patients maintain stable acuity for years, or up to 30% may even improve. Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 37

38. Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 38 (a ) Fundus of a man with slowly progressive vision loss OD and neuro -imaging consistent with an optic nerve sheath meningioma of the right optic nerve. The optic disk is mild elevated and there are several cilioretinal shunt vessels of the surface of the nerve substance. (b) The left nerve is normal.

39. Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 39 optic disc atrophy, with optociliary shunt vessels ( retinochoroidal collaterals visible at the 8 and 12 o'clock positions)

40. Neuroradiologic Features of Optic Nerve Sheath Meningioma Diffuse tubular enlargement of the optic nerve Sheath thickening and enhancement, with relative sparing of optic nerve substance ("tram track“ or " railroad track" signs) Apical expansion of the tumor Extradural tumor extension Calcification of the nerve sheath on CT scan Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 40

41. Adjacent bony hyperostosis on CT scan Isointense or mildly hyperintense to brain on Tl - and T2-weighted MRI scan Prominent contrast enhancement on CT and MRI scan Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 41

42. Axial MRI through the orbit with gadolinium and fat suppression in a 35-year-old woman demonstrating an enhancing mass along the right optic nerve. There is also depression of the posterior globe on the right and the right optic nerve is visible protruding into the vitreous due to disk edema .

43. Axial CT through the orbits of a 47-year-old man complaining of transient visual obscurations in the right eye. The scan shows a hyperdense , calcified lesion over the optic nerve, but the most anterior part demonstrates the typical tram-tracking that is seen with an optic nerve sheath meningioma. Axial CT through the orbits demonstrating a bright, calcified lesion of the optic nerve sheath on the left side. The lesion extends most of the length of the orbital optic nerve to the optic canal.

44. There is a cystic lesion of the optic nerve on the right on this T1-weighted MRI scan with gadolinium and fat suppression. The mass was revealed pathologically to be an ONSM. The optic disk is protruding into the vitreous due to edema from the tumor .

45. Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 45 CT scan reveals " tramtrack sign"; diffuse enlargement of the right in traorbital optic nerve extending anteriorly to the globe, with enhancement of the optic nerve sheath

46. Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 46 Ring sign" in meningioma. Coronal orbital MRI scan shows similar sheath enhancement surrounding relatively normal, darker optic nerve on the right.

47. Pathology Meningiomas probably arise from cap cells that line the outer arachnoidal surface. Two characteristic features- whorls and psammoma bodies. Some meningiomas , called fibroblastic, consist of elongated cells, suggestive of fibroblasts. Syncytial tumors have indistinct cell borders, and those with prominent vessels are called angioblastic . Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 47

48. Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 48 characteristic whorls and psammoma bodies of an optic nerve meningioma

49. Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 49 P ossible locations of intraorbital meningiomas . Tumor cells may arise from the planum sphenoidale (1 ) or from the optic canal (2 ) and migrate into the subdural space of the intraorbital optic nerve. Tumors may also arise de novo from within the optic nerve sheaths and remain intradural ( 3) or become exophytic masses ( 4). Atopic nests of arachnoidal cells within the orbit (5 and 6) may also give rise to meningiomas .

50. characteristic neuro -imaging leave exact diagnosis rarely in doubt and biopsy can be deferred. due to the mimicry exhibited by metastatic breast tumors , biopsy in patients with an optic nerve sheath mass and a history of breast carcinoma. Breast tumors may also metastasize to an ONSM . Arachnoid cysts and sarcoidosis of the optic nerve sheath should also be considered Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 50

51. Left alone, most unilateral ONSMs slowly but inexorably progress to produce blindness of the involved eye. However, this is not always the case. Some patients maintain stable vision for years . Intraorbital and intracanalicular meningiomas extend intracranially only rarely and are not fatal . In contrast, tumors that begin intracranially often extend to involve the chiasm and other structures adjacent to the optic nerve and may lead to blindness of the other eye. Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 51

52. Radiation therapy may also change the clinical appearance of the fundus. As the tumor shrinks, the optociliary venous collaterals may regress . several reports of radiation retinopathy as well as iritis , dry eye, or orbital pain. Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 52

53. Surgery not indicated due to the high likelihood of inducing blindness. ( unavoidable dissection of the pial vascular supply of the optic nerve) should be reserved for those patients with eyes that are already blind or intracranial extension feared to extend to adjacent critical structures. Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 53

54. Recently, several series have been published documenting treatment outcomes with stereotactic fractionated radiotherapy. indicated that some patients will have improvements in acuity, but more commonly enjoy improvement in visual field. A greater number of patients develop stability in their visual acuity and visual fields while only a small number worsen. Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 54

55. Introduction Secondary optic nerve meningiomas result from meningeal tumors that arise inside the intracranial vault near the sphenoid wing, tuberculum sella , and inferior frontal lobes. They cause vision loss typically due to direct compression of the optic nerve Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 55

56. Epidemiology It is very difficult to determine the epidemiology of these tumors . Most likely, these tumors are predominantly seen in middle-aged and older women. Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 56

57. Pathogenesis Recent advances in genetics have allowed researchers to investigate the frequency of mutations that arise in these tumors . Mutations have been found on chromosome 22 , the chromosome linked with neurofibromatosis type 2. Up to 60% of sporadic meningiomas arise from inactivation of the NF2 tumor suppressor gene , leaving 40% caused by unknown factors. These deletions do not appear to be more frequent in more aggressive meningiomas . Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 57

58. The non-NF2 meningiomas are more often of the meningothelial subtype and are located preferentially in the anterior skull base. Loss of heterozygosity of 18p may occur in a small number of sporadic meningiomas Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 58

59. There are likely hormonal influences regarding the growth of meningiomas . The evidence that implicates gender-specific hormones in the pathogenesis of meningiomas emanates from data showing increased growth of meningiomas during pregnancy and change in size during menses. Estrogen receptor expression is lost or reduced in more benignly growing meningiomas , whereas loss of progesterone receptor expression is an indicator of early recurrence.The finding of progesterone receptors in only a few meningioma cells is a favorable prognostic indicator for prolonged disease-free survival . Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 59

60. Human epidermal growth factor receptor type 2 ( HER2 ) represents a well-known prognostic factor in various tumors such as breast carcinomas. rate of tumor recurrence shown to be significantly higher in meningiomas with HER2 over expression than in HER2-negative meningiomas Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 60

61. Clinical Presentation Sphenoid wing meningiomas typically are associated with much more severe proptosis than primary ONSM. Tuberculum sella meningiomas may also be associated with vision loss and cranial neuropathies causing diplopia. The clinical course for these tumors is slow. Rarely, patients who have undergone resection of a sphenoid wing meningioma may have intermittent reversal of postoperative proptosis . Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 61

62. Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 62 Face shot of a woman complaining of proptosis of the left eye. Neuro -imaging revealed a left sided sphenoid wing meningioma. The left eye shows lid retraction and lagophthalmos with protrusion of the left globe. (b) Picture taken from above the patient demonstrating the degree of proptosis visually.

63. Radiologic Corelates MRI is the imaging modality of choice in these tumors . CT may show characteristic calcification within the mass on noncontrast imaging. MRI imaging with gadolinium will show more detail regarding a dural tail or other features, akin to a tumor of the dural sheath The tumors typically enhance homogeneously. Coronal sections through the cavernous sinus using T1-weighted images with gadolinium and fat suppression are ideal for identifying the degree of tumor spread. Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 63

64. Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 64 Coronal T1-weighted MRI scan of the brain with gadolinium in a 48-year-old woman with vision loss in the left eye. The scan demonstrates a large left sphenoid wing meningioma and there are visible meningeal attachments laterally under the left temporal lobe as well as medially through the cavernous sinus. There is midline shift of the brain and hydrocephalus is noted in the left lateral ventricle in the temporal lobe.

65. Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 65 Axial T1-weighted MRI scan of the brain with gadolinium, but without fat suppression in a 21-year-old woman with left sided vision loss. There is a large left sphenoid wing meningioma that extends into the left cavernous sinus. There is also intraorbital tumor , but due to the lack of fat suppression on the scan, it is difficult to tell what the extent of it is.

66. Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 66 Coronal T1-weighted MRI scan of the brain with gadolinium in a 54-year-old woman complaining of vision loss OD only. She had frontal lobe findings and a flat affect. There is a very large falcine meningioma that likely arose from the right olfactory groove although this is difficult to prove on this imaging. There is midline shift and direct compression on brain tissue.

67. DIFFERENTIAL DIAGNOSIS Tumors in region of the sella may be difficult to differentiate from one another. Some masses originally thought to be meningiomas turn out to be pituitary tumors at pathological examination, and vice versa. Both of these tumors are benign and typically show fairly homogeneous enhancement , whereas more malignant tumors may show cystic changes and other features suggestive of a more aggressive character. Rarely , a suspected meningioma may be found to actually be Rosai – Dorfman disease. Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 67

68. TREATMENT Since these are slow growing tumors , conservative management until symptoms appear . visual fields , and regular MRI scans with gadolinium enhancement are appropriate for patients who have good vision and no evidence of intracranial or intracanalicular extension of tumor . appropriate to follow a small amount of intracranial extension with serial MRI Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 68

69. C raniotomy reserved for patients with documented progressive intracranial extension of tumor . A standard pterional craniotomy using microsurgical technique appears to provide the necessary exposure required for aggressive resection and with minimal complications. Radiation therapy may be coupled with conservative resection, and shows similar outcomes when compared to aggressive resection. Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 69

70. Aggressive resection has the benefit of eliminating the risk of future complications of radiation toxicity, however. Complete surgical resection is often not possible in cases of sphenoid wing meningiomas . This is often due to invasion of the surrounding structures such as the cavernous sinus and orbit More of these cases require concurrent treatment with radiation therapy and are associated with tumor regrowth. Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 70

71. * Olson and colleagues Given the histopathological evidence of the presence of hormone receptors on meningioma cells , the effect of drugs targeting these receptors has been studied. In in vitro studies by, meningioma cells were inhibited by mifepristone (RU 486), estradiol-17β, and progesterone. Tamoxifen stimulated growth of meningioma cells in vitro . Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 71

72. # Key Features Associated with painless and slowly progressive vision loss Average age of onset in the fifth decade of life Minimal proptosis , if any Optociliary vein collaterals may be present on the optic disk Neuroimaging is the mainstay for diagnosis in a typical case Radiation is treatment of choice in an eye with documented progressive vision loss Wednesday, October 29, 2014 72 Department of Ophthalmology, JNMC

73. Melanocytoma Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 73

74. Melanocytomas are benign melanocytic tumors that occur typically on the surface of the optic disk, in the anterior uveal tract, or, more rarely, in the choroid, although they have been reported to occur in the sclera or conjunctiva . Also termed ‘ magnocellular naevus ’, which is also appropriate. This term is concordant with the histopathologic appearance of these lesions which are composed of large, regular cells . Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 74

75. Melanocytoma of Disc Relatively rare tumors with unknown prevalence Mean age at diagnosis 40-50 years Slight female predominance Generally unilateral Left and right side affected with similar frequency Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 75

76. Clinical Presentation The clinical presentation of melanocytomas depends on their size and extension. may be confined to the optic disk or may infiltrate the adjacent choroid and optic disk without prolapsing through the retina Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 76 Subretinal melanocytoma situated on the optic disk and adjacent choroid. (a) Ophthalmoscopy. (b) Fluorescein angiography, early phase

77. May infiltrate the retina, thereby resulting in the classical appearance of a filamentous border Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 77 Large melanocytoma situated on the optic disk and choroid and invading the nerve fiber layer.

78. they can also induce papilledema and may invade the optic nerve. Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 78 Melanocytoma of the optic disk associated with papilledema. (a) Ophthalmoscopy. ( b) Fluorescein angiography, arteriovenous phase

79. lesions are invariably dark brown or black and, apart from rare exceptions, coloration is homogeneous. S ize variable, generally do not exceed 2–3 mm in greatest dimension. A djacent choroid involved in 47-86% of cases retina is involved in 30-67% of cases . That portion of the optic disk that is spared by the tumor may appear physiologic or, in ∼25% of the cases, may reveal papilledema on ophthalmoscopic examination Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 79

80. Another 25% of the cases will show papilledema only on fluorescein angiography The tumor can, in rare cases, be accompanied by a serous retinal detachment, retinal edema, lipid deposits, or intraretinal haemorrhage and, more rarely, by polypoidal choroidal vasculopathy The vitreous is generally clear, but pigment dispersion secondary to tumor necrosis may be observed and may, in some cases, extend to the anterior chamber Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 80

81. Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 81 Melanocytoma of the optic disk associated with marked pigment dispersion in the vitreous.

82. About 75% of the patients are asymptomatic, and the tumor is discovered incidentally. Blurred vision, floaters, flashes, metamorphopsias , or micropsias are the symptoms most frequently reported in the other cases . Visual field examination often demonstrates enlargement of the blind spot or peripheral or fascicular field defects, or, more rarely, major defects that cause tunnel vision. No correlation has been established between tumor size and tumor extension, or between the presence of papilledema and the size of the visual field defect . Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 82

83. Melanocytoma of the optic disk has been reported in association with ocular melanocytosis,congenital hypertrophy of the pigment epithelium , choroidal nevus , and retinitis pigmentosa Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 83

84. Investigations Ophthalmoscopy generally sufficient to establish the diagnosis of melanocytoma . The various complementary investigations are performed primarily to document the shape and extension of the tumor and to detect possible complications . Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 84

85. FLUORESCEIN ANGIOGRAPHY The part of the tumor that is invading the retina remains hypofluorescent on all phases of fluorescein angiography. A fine network of telangiectatic capillaries is occasionally observed on the surface of the tumor, and the filamentous edges are clearly visible. In contrast, the part of the tumor invading the choroid and situated underneath the pigment epithelium has the same angiographic features as do choroidal nevi. Fluorescein angiography can, however, detect or confirm the presence of papilledema . Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 85

86. B-SCAN OCULAR ULTRASOUND This examination can be used to measure tumor thickness, but does not provide any additional information .   HEIDELBERG RETINA TOMOGRAPHY This examination can be used to precisely measure the tumor surface in three dimensions, and is therefore useful to detect any changes in tumor volume Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 86

87. Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 87 HRT, tumor apex/retinal surface distance: 0.5 mm, and study of the horizontal and vertical profile of the tumor

88. Melanocytomas are composed mainly of intensely pigmented, large polyhedral nevus cells. On ultrastructural examination, the cytoplasm contains few organelles, but a large number of giant melanosomes . The nucleus is oval, generally without a nucleolus, and there is a low nucleocytoplasmic ratio Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 88

89. DIFFERENTIAL DIAGNOSIS Certain benign or malignant tumors of the choroid, pigment epithelium, and optic disk, as well as certain malformations, can mimic melanocytoma . The main differential diagnoses are choroidal melanoma adjacent to and invading the optic disk, primary melanoma of the optic disk, and adenoma or adenocarcinoma of the juxtapapillary pigment epithelium . Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 89

90. CLINICAL COURSE AND COMPLICATIONS Melanocytomas of the optic disk are benign tumors that generally remain stationary. Over a long period of observation, ∼40% of these tumors show some slow growth, and ∼2% undergo malignant transformation. Progression of a melanocytoma may be complicated by partial or total visual loss due to partial or total vascular occlusion or nerve fiber necrosis, both of which are secondary to pressure exerted by the tumor. Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 90

91. Visual loss may occasionally be transient. In conclusion, although melanocytomas of the optic disk are benign, they do present a low risk of malignant transformation. They can also induce complications that lead to severe loss of visual function, and therefore require close surveillance. Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 91

92. Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 92 Malignant astrocytomas

93. Malignant astrocytomas R are neoplasms involving the anterior visual pathway almost always occur in adulthood, with a mean age in the 60s they are minimally more common in males ( 1.3:1). Patients present with acute onset of pain and either unilateral or bilateral visual loss, depending on whether the optic nerve or the chiasm is initially involved. Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 93

94. With unilateral lesions, the second eye is invariably involved within weeks. optic disc may be normal or pale at presentation , but in cases of more anterior tumors , retinal venous occlusive disease and disc edema are common secondary to obstruction of the central retinal vein within the intraorbital optic nerve Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 94

95. An MRI scan most often shows diffuse intrinsic enlargement and enhancement of the affected optic nerves, chiasm, and optic tracts, with inhomogenecity due to cystic spaces within the tumor Occasionally , a large exophytic component may encroach on the suprasellar cistern . Histologically , malignant optic nerve gliomas are classified as anaplastic astrocytomas or glioblastoma multiforme . Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 95

96. Visual loss is severe and rapidly progressive. Treatment is rarely successful, although radiotherapy and chemotherapy have been attempted, with blindness usually developing 2-4 months after onset of visual loss . The tumor is aggressively infiltrative, and death from hypothalamic and brainstem involvement usually occurs within 6- 12 months . Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 96

97. Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 97 Astrocytic Hamartoma

98. Astrocytic hamartomas of the retina, most common in tuberous sclerosis and neurofibromatosis, may take the form of so-called mulberry lesions . When located adjacent to the disc, they may closely resemble optic disc drusens , and in early reports they were termed giant drusen of the optic disc . In contrast to true optic disc drusens , disc hamartomas originate at the disc margin, with extension to the peripapillary retina arise in the inner retinal layers and typically obscure retinal vessels may have a fleshy, pinkish component do not autofluoresce and may show tumorlike vascularity on fluorescein angiography Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 98

99. Optic disc drusen Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 99 Astrocytic hamartoma

100. Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 100

101. Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 101 LYMPHORETICULAR TUMORS

102. LYMPHORETICULAR TUMORS Leukemia is a well-recognized cause of infiltrative optic neuropathy. Vision loss may occur abruptly or over the course of several days and is often bilateral. Many patients have a known history of leukemia at the time of diagnosis. The fundus may show abundant retinal hemorrhages and bilateral optic nerve edema Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 102

103. Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 103 Fundus of the right eye of a 21-year-old man with acute lymphocytic leukemia . There is severe edema of the nerve, exudates, and retinal hemorrhages due to carcinomatous invasion of the optic nerve and its sheath. (b) The left fundus shows much more severe retinal hemorrhages .

104. Although a spinal tap is required to confirm the diagnosis of leukemic invasion, an MRI can show signs characteristic of infiltration. Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 104 Axial MRI through the orbits with gadolinium and fat suppression, revealing enhancement and enlargement of the optic nerve sheaths bilaterally in a 21-year-old man with acute lymphocytic leukemia . He had severe vision loss. (b) Coronal MRI through the orbits showing a cross section of the enhancement and enlargement of the optic nerve sheaths in the same patient.

105. Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 105 METASTATIC TUMORS OF THE OPTIC NERVE

106. METASTATIC TUMORS OF THE OPTIC NERVE A number of carcinomas are known to metastasize to the optic nerve. Patients frequently present with only mild vision loss neuro -imaging may initially appear normal or with only subtle findings. Common primaries include breast, lung, and bowel tumors . Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 106

107. Renal carcinomas may also cause an optic neuropathy. These tumors may infiltrate the optic nerve, producing symptoms either as an initial manifestation or as part of a more generalized meningeal involvement . Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 107

108. Take home message Not infrequently, the ophthalmologist is called on to determine whether or not visual loss is caused by infiltrative or compressive lesions of the anterior visual pathway. This is determined through careful clinical evaluation of the visual acuity, color vision, pupils, visual fields, and fundus. Knowledge of the more common tumors will assist the ophthalmologist in advising patients on a course of action, and deciding which patients should be followed and which require referral to neurosurgeons or radiation oncologists Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 108

109. Bibliography Wednesday, October 29, 2014 Department of Ophthalmology, JNMC 109 # Anatomy and Physiology of the Eye by AK Khurana ; 2 nd Edition # Albert Jakobiec’s Principles and Practice of Ophthalmology. Section 14, Section 17; 3 rd Edition # American Academy of Ophthalmology BCSC. Section 5 ; 2011-2012 # Yanoff & Duker Ophthalmology; 3 rd Edition

110. THANKYOU October 29, 2014 Department of Ophthalmology, JNMC 110 