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1 The 1999 Bjerrum Lecture Tumors and pseudotumors of the optic disc* Jerry A. Shields ABSTRACT. There are many lesions that can present as an elevation of the optic disc. Since each of them has different ophthalmic and systemic significance, it is important for the ophthalmologist to recognize them and to plan strategies of management when necessary. Important inflammatory and benign congenital conditions should be differentiated from malignant neoplasms. This review covers the differential diagnosis of lesions that can cause an elevation of the optic disc. It includes selected congenital lesions, inflammatory conditions, non-inflammatory non-neoplastic disorders, benign hamartomas, and primary and secondary malignant neoplasms. Key words: Bjerrum Lecture tumors of the optic disc pseudotumors of the optic disc. Acta Ophthalmol. Scand. 2000: 78: Copyright C Acta Ophthalmol Scand ISSN It is a distinct honor and privilege to participate in the 1999 meeting of the Danish Ophthalmological Society and to deliver the Jannik Petersen Bjerrum Lecture. Professor Bjerrum was a great leader in Danish ophthalmology who became known internationally for his many contributions. While serving as Professor of Ophthalmology in Copenhagen, he pioneered techniques of visual field analysis and was honored by the scotoma that bears his name. It is quite fitting that this lecture be delivered annually in his honor. Since my colleagues and I pursue a fulltime practice of ophthalmic oncology at Wills Eye Hospital of Thomas Jefferson University in Philadelphia, I naturally elected to speak on some aspect of ocular tumors. In exploring the possibilities for a topic for the Bjerrum lecture, I realized that our prior publications had not included much on the subject of optic disc tumors. Therefore, I thought that it would be of interest to review the subject of elevated lesions of the optic disc, with emphasis on how to differentiate true tumors from pseudotumors. For readers inter- * Presented as Part 1 of the 1999 Bjerrum Lecture, Danish Ophthalmological Society, Copenhagen, Denmark, December 4, ested in further reading, tumors and pseudotumors of the optic disc have been discussed in more detail in recent textbooks (Shields & Shields 1992, 1999; Brown & Tasman 1983) and articles on the subject (Brown & Shields 1985). There are many lesions that can present as an elevation of the optic disc. Since each of them has different ophthalmic and systemic significance, it is important for the ophthalmologist to recognize them and to plan strategies of management when necessary. Important inflammatory and benign congenital conditions should be differentiated from malignant neoplasms. In this presentation, I will discuss primarily the clinical features of elevated lesions of the optic disc, with emphasis on tumors and pseudotumors. The presentation will follow the classification of elevated lesions of the optic disc proposed by the author (Table). Congenital non-neoplastic lesions There are several congenital lesions of the optic disc that can occasionally simulate neoplasms. These are generally unilateral, although bilateral involvement is not rare. Congenital pit of optic nerve The congenital pit of the optic nerve is a crater-like malformation that usually occurs on the temporal side of the optic disc (Brown et al. 1979, 1980). It can become symptomatic by producing a secondary serous detachment of the sensory retina, sometimes simulating a small elevated macular tumor. The pit sometimes has a charcoal gray color and has prompted referral to us because of suspected melanoma or melanocytoma (Fig. 1). Coloboma Coloboma is a developmental malformation that results from failure of the embryonic fissure to completely close (Brown & Tasman 1983). It can involve the iris, ciliary body, choroid, or optic nerve. Even though coloboma is a depressed lesion, it can sometimes be misinterpreted as an elevated yellow-white tumor when one uses monocular direct ophthalmoscopy. Some cases have been large enough to produce leukocoria and cause confusion with retinoblastoma. Myelinated nerve fibers Myelination of the optic nerve begins in the central nervous system of the embryo and passes down the optic nerve to stop at the lamina cribrosa at about the time of birth. Occasionally this process can extend into the juxtapapillary nerve fiber layer of the retina and appear as a whiteyellow thickening with a fibrillated margin. Myelinated nerve fibers can sometimes be atypical and can simulate tumors like astrocytic hamartoma, retinoblastoma or solitary granuloma (Fig. 2) (Shields & Shields 1999, Brown & Shields 1985). Morning glory disc anomaly Morning glory disc anomaly is a congenital malformation characterized by an enlarged optic nerve head that has a central 156
2 crater containing fibroglial tissue. The retinal vessels that emerge from the disc are often straightened and sheathed (Shields & Shields 1999, Kindler 1970). The striking appearance of this anomaly can lead to confusion with a neoplasm. Inflammatory lesions Several inflammatory conditions can cause elevation of the optic disc and simulate certain neoplasms (Wray 1994). A discussion of all causes of optic papil- Table. Classification of tumors and pseudotumors of the optic disc. litis is beyond the scope of this discussion. I. Congenital non-neoplastic lesions Congenital pit of optic nerve Coloboma Myelinated nerve fibers Morning glory disc anomaly Others II. Inflammatory lesions Nongranulomatous papillitis Demyelinating disease Ischemic optic papillopathy Diabetic papillopathy Others Granulomatous papillitis Idiopathic Sarcoidosis Others III. Non-inflammatory, non-neoplastic optic disc elevation Optic disc drusen Compressive papillopathy Papilledema Others IV. Tumors of the sensory retina and medullary epithelium Retinoblastoma Medulloepithelioma V. Vascular tumors of the retina Capillary hemangioma Cavernous hemangioma Racemose hemangioma VI. Glial tumors of the retina Astrocytic hamartoma Acquired retinal astrocytoma VII. Melanocytic tumors Melanocytoma Malignant melanoma Primary Secondary Combined hamartoma of the retina and retinal pigment epithelium Adenoma and adenocarcinoma of the retinal pigment epithelium VIII. Metastatic tumors IX. Lymphoid tumors and leukemias X. Anterior extension of retrobulbar optic nerve tumors Juvenile pilocytic astrocytoma Optic nerve sheath meningioma Nongranulomatous papillitis Nongranulomatous papillitis is an inflammation of the optic nerve that is usually unilateral and appears as a hyperemic thickening of the optic disc tissue. The optic disc margins are blurred and no distinct mass can be identified ophthalmoscopically. The differential diagnosis includes demyelinating disease (multiple sclerosis), ischemic optic neuropathy, diabetic papillopathy, radiation papillopathy, and other inflammatory conditions. The vascular component of these inflammatory disorders can often simulate a vascular tumor of the disc, such as capillary hemangioma. The details of these inflammatory conditions are beyond the scope of this discussion. Granulomatous papillitis Granulomatous papillitis is inflammation of the optic disc secondary to conditions that produce a granulomatous inflammatory reaction. In some instances, a distinct mass can be seen in the optic disc tissue that can simulate a neoplasm. It can be seen with sarcoidosis, syphilis, tuberculosis and other known entities. In many instances the etiology remains unknown in spite of a systemic survey for specific inflammatory diseases. The nodule is yellow to pink in color and may resemble a vascular tumor (Fig 3). Fluorescein angiography usually demonstrates that the mass is hypofluorescent in the vascular filling phases and becomes hyperfluorescent later. This contrasts with a capillary hemangioma (discussed later) which shows early hyperfluorescence. Non-inflammatory, nontumorous disc elevations There are several conditions in this category that can produce an elevation of the optic disc. It is important to recognize these conditions and to differentiate them from neoplasms of the optic disc. Optic disc drusen Optic nerve drusen are calcified bodies that occur in the substance of the optic disc. The epidemiology, clinical features, pathology, complications and systemic associations have been published elsewhere (Moazami et al. 1999). Drusen may lie deep in the substance and be invisible (buried drusen) in which case they may be difficult to differentiate from papilledema. In other instances, they may be visible ophthalmoscopically as multiple nodules in the substance of the disc. They should be differentiated from the calcified astrocytic hamartoma ( giant drusen ) that can occur on the optic disc in patients with tuberous sclerosis, to be discussed subsequently. Compressive papillopathy Compressive papillopathy is swelling of the optic disc secondary to compression 157
3 Fig 5. Retinoblastoma involving the optic disc and juxtapap- illary retina. Fig 1. Dark colored congenital pit of the optic disc, simulating a small pigmented tumor. Fig 2. Myelinated nerve fibers of the optic disc simulating a white retinal tumor. Fig 6. Capillary hemangioma of the optic disc in a patient with von Hippel-Lindau syndrome. Fig 3. Idiopathic presumed granuloma involving the optic disc. Fig 7. Racemose hemangioma affecting the optic disc in a patient with the Wyburn-Mason syndrome. Fig 4. Papilledema secondary to increased intracranial pressure. Fig 8. Astrocytic hamartoma involving the optic disc and juxtapapillary retina in a patient with tuberous sclerosis. 158
4 Fig 9. Acquired astrocytoma involving the optic disc in an adult with no findings of tuberous sclerosis. Fig 13. Optic nerve invasion by juxtapapillary choroidal melanoma. Fig 10. Typical melanocytoma of the optic disc. Fig 14. Combined hamartoma of the retina and retinal pigment epithelium. Fig 15. Adenoma of the juxtapapillary retinal pigment epi- thelium simulating a melanocytoma. The eye was obtained postmortem and the diagnosis was confirmed. Fig 11. Central retinal vascular obstruction secondary to melanocytoma of the optic disc. The eye was enucleated and melanocytoma was confirmed histopathologically. Fig 12. Primary malignant melanoma of the optic nerve. The eye was enucleated with a long section of optic nerve and the melanoma was confirmed histopathologically. Fig 16. Metastatic carcinoma to the optic disc. 159
5 of the optic nerve, usually from a space occupying lesion in the orbit (Shields 1989). It is best known to occur in cases of dysthyroid orbitopathy (Graves disease). In such instances, it is often bilateral and occurs from inflammatory enlargement of the extraocular muscles near the orbital apex. Compressive optic neuropathy can also develop secondary to orbital pseudotumors, benign tumors, or malignant neoplasms. There is initially blurring of the disc margin. The retinal veins can become dilated and tortuous and superficial retinal hemorrhage can occur in advanced cases. Papilledema Papilledema is swelling of the optic disc secondary to increased intracranial pressure. The affected patient usually has fairly good visual acuity until the disc swelling is very advanced. Clinically, it appears in the early stages as a thickening of the nasal portion of the optic disc. With more severe increase in intracranial pressure, there is marked bilateral elevation of the optic papilla with blurred disc margins and obliteration of the optic cup (Fig. 4). Hemorrhage and exudation can occur as the process advances. Fluorescein angiography demonstrates progressive hyperfluorescence of the optic disc with intense late staining. Since pseudotumor cerebri and brain tumor are the most important etiologic considerations, the affected patients should undergo ocular and systemic evaluation with cranial imaging studies like computed tomography (CT) and magnetic resonance imaging (MRI) with contrast enhancement. Tumors of the sensory retina and medullary epithelium The neuroepithelial inner layer of the primitive optic cup can give rise to tumors that arise from nuclear layers of the formed retina (retinoblastoma) or from the primitive anterior neuroectoderm that give rise to the embryonic medullary epithelium (medulloepithelioma). Retinal tumors that affect the optic disc can also be of vascular or glial origin. Retinoblastoma Retinoblastoma, the most common intraocular malignant tumor of childhood, usually occurs in the sensory retina away from the optic disc (Shields & Shields 1992, 1999). In most instances, the diagnosis can readily be made based on the typical clinical features. Occasionally a small retinoblastoma can be located over part of the optic disc. It appears as a small, circumscribed gray-white lesion often with retinal feeder vessels that dip into the tumor (Fig. 5). Optic nerve invasion of retinoblastoma has important prognostic significance (Shields et al. 1994). If the tumor occupies the portion of the optic nerve anterior to the lamina scleralis, the prognosis is generally quite good. The prognosis is somewhat worse with postlaminar involvement and considerably worse when the tumor extends to the line of surgical transection of the optic nerve. The management of optic nerve involvement by retinoblastoma can be complex and depends on the clinical circumstances. Most retinoblastomas that involve the optic disc are managed by enucleation and require some form of supplemental chemotherapy or irradiation. Medulloepithelioma Medulloepithelioma is an embryonal neoplasm that usually arises from the medullary epithelium that is destined to form the nonpigmented ciliary body epithelium in adults. In very rare instances, it can develop more posteriorly in the optic nerve (Shields & Shields 1992, 1999; O Keefe et al. 1997). When it occurs on the optic disc, it appears as a yellow-white vascular tumor that may be impossible to differentiate from retinoblastoma. Vascular tumors of the retina There are several vascular tumors that can occur on the optic disc. It is important for the clinician to be familiar with the different vascular tumors since each of them has different ocular complications and systemic associations. They generally occur as part of neuro-oculocutaneous syndromes (phakomatoses) (Shields & Shields 1992, 1999). Capillary hemangioma Retinal capillary hemangioma can occur as an isolated retinal tumor or it can be a part of the von Hippel-Lindau syndrome. When it occurs in the extrapapillary portion of the retina, it has classic features of a red to pink lesion with a dilated, tortuous retinal feeding artery and draining vein. Leakage from the fine vessels in the tumor leads to intraretinal exudation and sometimes to an exudative retinal detachment (Shields & Shields 1992, 1999). Retinal capillary involving the optic disc has the same association with von Hippel-Lindau syndrome, as does peripheral lesion. When retinal capillary hemangioma assumes a location over part or all of the optic disc, it appears as a nodular or sessile reddish mass (Fig. 6). The retinal feeder blood vessels that characterize the peripheral lesion are not usually visible. In many cases, intraretinal exudation accumulates in the posterior fundus and this can lead to an exudative retinal detachment. Retinal capillary hemangioma that involves the optic disc can be extremely difficult to manage. Asymptomatic lesions can be safely followed at periodic intervals. Lesions that cause progressive exudation and visual loss can be treated with surface laser or thermotherapy in hopes of preventing further visual loss. If the exudative retinal detachment does not resolve with laser treatment to the tumor, then vitrectomy with endolaser to the tumor can be attempted. It has been necessary to perform enucleation in some cases that caused total exudative retinal detachment and neovascular glaucoma. Cavernous hemangioma Retinal cavernous hemangioma can also occur as an isolated retinal tumor or it can be a component of a neuro-oculocutaneous syndrome characterized by similar vascular lesions in the central nervous system and skin. It usually occurs in the extrapapillary retina, but can occasionally occur over the optic disc. Clinically the lesion appears as a cluster of reddish-blue aneurysms. Unlike the retinal capillary hemangioma, the cavernous hemangioma does not produce retinal exudation but it can cause recurrent intraretinal and vitreal hemorrhage with secondary fibrosis (Shields & Shields 1992, 1999). The management of retinal cavernous hemangioma is usually observation. In rare instances in which extensive vitreous hemorrhage does not resolve, vitrectomy with endolaser or cryotherapy to the tumor is considered to be the best treatment. 160
6 Racemose hemangioma Retinal racemose hemangioma is a vascular malformation in which a large retinal vessel communicates directly with a retinal vein without an intervening capillary bed. It can be located partly over the optic disc (Fig. 7). This lesion can also occur as an isolated phenomenon or it can be part of the Wyburn-Mason syndrome, characterized by similar vascular malformations in the midbrain, maxilla, mandible, and pterygoid fossa (Shields & Shields 1992, 1999). Most of them do not cause complications but vitreous hemorrhage and branch retinal vein obstruction can sometimes occur. The management of retinal cavernous hemangioma is usually observation. Glial tumors of the retina The glial tissue of the sensory retina can also give rise to benign hamartomas and acquired neoplasms. The most important glial tumor is the astrocytic hamartoma. Astrocytic hamartoma Retinal astrocytic hamartoma is a congenital tumor composed of fibrillary astrocytes (Shields & Shields 1992, 1999). It can also occur as a solitary lesion or as a component of tuberous sclerosis. It can appear as a calcified or noncalcified variant. Both types can occur in the extrapapillary retina or they can partly or entirely cover the optic disc. The noncalcified type appears as a yellow gray lesion in the superficial aspect of the sensory retina. The calcified type is characterized by the presence of yellow glistening nodules (Fig 8). When the calcified type is located over the optic disc, it has been called giant drusen on the optic disc. This terminology is unfortunate, since the calcified astrocytic hamartoma is quite different from true drusen of the optic disc. In most instances, the retinal astrocytic hamartoma is a stationary lesion with little or no tendency to progress. The best management is usually periodic observation. The patient should be evaluated for other signs of tuberous sclerosis. Acquired retinal astrocytoma The acquired retinal astrocytoma is probably a noncongenital mass composed of retinal astrocytes. Unlike the astrocytic hamartoma of tuberous sclerosis, it is often a slowly progressive lesion that produces exudation and secondary retinal detachment. It is often located partly or entirely over the optic disc and extends for a variable distance into the sensory retina (Fig. 9) (Shields & Shields 1992, 1999; Ramsay et al. 1974) It is uncertain whether this tumor represents an unusual forme fruste of tuberous sclerosis or a true acquired neoplasm of astrocytes, similar to glioblastoma of the central nervous system. The management is not well-established. Small asymptomatic tumours should probably be observed but those that show progressive exudation and retinal detachment may be treated with laser photocoagulation, cryotherapy, or plaque brachytherapy. Enucleation has occasionally been performed for more aggressive tumors with total retinal detachment because uveal melanoma or other malignancy could not be excluded. Melanocytic tumors There are several melanocytic tumors that can affect the optic disc. These include melanocytoma, choroidal melanoma, primary optic nerve melanoma, combined hamartoma, and acquired neoplasms (adenoma and adenocarcinoma). Melanocytoma Melanocytoma of the optic nerve is a congenital pigmented nevus that often involves part or all of the optic disc (Shields & Shields 1992, 1999; Zimmerman 1965; Joffe et al. 1979). It is usually black in color and may have a juxtapapillary choroidal component identical to a deeply pigmented choroidal nevus. It can also extend into the nerve fiber layer of the retina where it displays a feathery margin (Fig. 10). Before the rather typical features of this lesion were recognized, it was often mistaken for malignant melanoma both clinically and pathologically. It is now recognized to be a benign condition with a very low probability of evolving into melanoma. The patient s visual acuity is usually normal but the tumor can be associated with an afferent pupillary defect and visual field defects, particularly an enlarged blind spot or arcuate scotoma. About 40% of patients have a juxtapapillary choroidal component contiguous with the lesion. Slight growth can be detected in about 15% of patients with long follow up (Joffe et al. 1979). Acute visual loss can occur secondary to spontaneous necrosis of an optic nerve melanocytoma. Occasionally, this necrosis can also induce an obstruction of the central retinal vein and hemorrhagic retinopathy (Shields et al. 2000) (Fig. 11). Although rare, there are documented cases of malignant transformation into melanoma (Shields et al. 1990). Malignant melanoma Malignant melanoma can occasionally involve the optic disc. Primary melanoma of the optic disc has been recognized, but it is exceedingly rare. Most optic disc melanomas occur secondary to direct extension from juxtapapillary choroidal melanomas. Such invasion is more likely to occur from a diffuse choroidal melanoma. Nodular choroidal melanomas are less likely to exhibit invasion of the optic nerve. Primary melanoma confined to the optic nerve is exceedingly rare. It occurs as a dark mass in the nerve head that may be very similar to a melanocytoma (Erzurum et al. 1992, DePotter et al. 1996) (Fig. 12). Choroidal melanoma can often occur in a juxtapapillary location. Only rarely does a typical nodular juxtapapillary melanoma invade the optic nerve (Shields & Shields 1992, 1999). (Fig. 13). The diffuse variant of choroidal melanoma, however, has a marked tendency to actively invade the optic nerve and to produce secondary disc edema and obstruction of the central retinal vein. Such cases are best managed by enucleation with a long section of optic nerve. Combined hamartoma of the retina and retinal pigment epithelium Combined hamartoma of the RPE and sensory retina is a peculiar fundus lesion that is difficult to categorize. Although it is generally considered to represent a hamartoma, the pathogenesis is not clearly established and a similar lesion may result from intraocular inflammation or trauma. The combined hamartoma most often occurs on or near the optic disc and appears as a gray sessile lesion with stretched or tortuous vessels that are partly obscured by white fibroglial tissue (Shields & Shields 1992, 1999) (Fig. 14). This surface glial tissue tends to gradually contract, leading to further stretching of the blood vessels and retinal striae, which may distort the fovea. Chronic vitreoretinal traction can lead to accumulation of subfoveal exudation, secondary retinoschisis, and retinal hole. Fluorescein shows rather typical fea- 161
7 tures. During the arterial phase, there is relative hypofluorescence of the lesion. By the early venous phase numerous fine blood vessels may be recognized within the lesion. These vessels gradually leak fluorescein to stain most of the mass in the late angiograms, although the central portion of the lesion may remain relatively hypofluorescent. Histopathologically, combined hamartoma consists of thickening of the sensory retina and optic nerve from replacement of these tissues by glial cells, vascular tissue, and strands and sheets of pigment epithelial cells. Adenoma and adenocarcinoma of the RPE Adenoma of the RPE is an uncommon tumor that is usually situated in the peripheral fundus, but can occur adjacent to the optic disc (Shields & Shields 1992, 1999; Shields et al. 1999). When it is located on the optic disc, it can resemble a melanocytoma (Shields et al. 1992) or choroidal melanoma (Shields et al. 1999) (Fig. 15). Fluorescein angiography of an adenoma of the RPE generally shows early hypofluorescence and mild late staining. It does not show the double circulation that characterizes many choroidal melanomas. A scan ultrasonography generally shows moderately high internal reflectivity and B-scan demonstrates an irregular contour with acoustic solidity. In cases where the diagnostic is uncertain, a transocular fine needle biopsy can assist in the diagnosis (Shields et al. 1994). Small suspected adenomas of the RPE can sometimes be safely observed for a period of time and treatment withheld until growth is documented. A progressive lesion located near the optic disc may sometimes require enucleation. Metastatic tumors Although most ocular metastasis involve the uveal tract, they can affect the optic disc. In a review of 660 consecutive patients with intraocular metastasis, there were 30 patients in whom the optic disc was involved (5%) (Shields et al. 2000). There was an adjacent juxtapapillary choroidal component to the metastatic disc lesion in 23 (74%) and the optic disc was involved without a retinal or choroidal component in 8 cases (26%). Like uveal metastasis, neoplasms of the breast and lung account for most cases, but there were also cases of disc metastasis from alimentary tract, kidney and prostate. In 20% of cases, the primary neoplasm was never clearly detected, in spite of widespread carcinomatosis. In cases where the diagnosis is uncertain, fine needle aspiration biopsy can be helpful in establishing the diagnosis. The characteristic clinical features of optic disc metastasis include a swollen optic disc sometimes with white patches of tumor tissue and flame shaped hemorrhages (Fig 16). The prognosis is poor. Lymphoid tumors and leukemias Lymphoma can also involve the intraocular structures, often in the form of retinal and vitreal infiltration as part of primary central nervous system lymphoma (Shields & Shields 1992, 1999). However, pure optic disc involvement is uncommon. It appears as a thickening of disc tissue, often with yellow-white infiltration, similar to that seen with metastasis. Leukemia can also diffusely involve the optic disc, usually in association with exacerbation of systemic disease. It appears as an edematous mass, frequently with hemorrhage, choroidal and retinal infiltration, and secondary retinal detachment (Shields & Shields 1992, 1999). It must be differentiated from opportunistic infection that can cause similar findings. Anterior extension of retrobulbar optic nerve tumors Finally, the optic disc can rarely be involved by anterior extension of retrobulbar optic nerve tumors. This is most likely to occur in cases of juvenile pilocytic astrocytoma and optic nerve sheath meningioma. Both produce a fleshy pink or white infiltration of the optic disc, frequently with signs of central retinal vein obstruction. The diagnosis can usually readily be made by imaging studies of the orbit. Acknowledgements Supported by the Eye Tumor Research Foundation, Philadelphia, PA and by the Award of Merit in Retina Research, Houston TX (and the Macula Foundation, New York, NY). References Brown GC & Shields JA (1985): Tumors of the optic nerve head. Surv Ophthalmol 29: Brown GC, Shields JA & Goldberg RE (1980): Congenital pits of the optic nerve head. II. Clinical studies in humans. Ophthalmology 87: Brown GC, Shields JA, Goldberg RE & Patty B (1979): Congenital pits of the optic disc. I. Experimental studies in animals. Arch Ophthalmol 97: Brown GC & Tasman WS (1983): Congenital Anomalies of the Optic Disc. New York, Grune & Stratton. DePotter P, Shields CL, Eagle RC Jr, Shields JA & Lipkowitz J (1996): Malignant melanoma of the optic nerve. Arch Ophthalmol 114: Erzurum SA, Jampol LM, Territo C & O Grady R (1992): Primary malignant melanoma of the optic nerve simulating a melanocytoma. Arch Ophthalmol 110: Joffe L, Shields JA, Osher R & Gass JDM (1979): Clinical and follow-up studies of melanocytomas of the optic disc. Ophthalmology 86: Kindler P (1970): Morning glory syndrome: Unusual congenital optic disk anomaly. Am J Ophthalmol 69: Moazami G, Odel JG & Behrens MM (1999): Optic disc drusen. In: Guyer DR, Yannuzzi LA, Chang S, Shields JA, Green WR. Retina-Vitreous Macula. Philadelphia, W.B. Saunders Co O Keefe M, Fulcher T, Kelly P, Lee W & Dudgeon J (1997): Medulloepithelioma of the optic nerve head. Arch Ophthalmol 115: Ramsay RC, Kinyoun JL, Hill CW et al. (1974): Retinal astrocytoma. Am J Ophthalmol 88: Shields JA (1989): Office examination of the patient. In: Shields JA. Diagnosis and Management of Orbital Tumors. Philadelphia, W.B. Saunders P34. Shields JA, Eagle RC Jr, Barr CC, Shields CL & Jones DE (1994): Adenocarcinoma of the retinal pigment epithelium arising from a juxtapapillary histoplasmosis scar. Arch Ophthalmol 112: Shields JA, Eagle RC Jr, Shields CL & De Potter P (1992): Pigmented adenoma of the optic nerve head simulating a melanocytoma. Ophthalmology 99: Shields JA & Shields CL (1992): Intraocular Tumors. A Text and Atlas. Philadelphia, WB Saunders, pp Shields JA & Shields CL (1999): Atlas of Intraocular Tumors, Philadelphia, Lippincott Williams & Wilkins pp Shields CL, Shields JA, Baez K, Cater J&De- Potter P (1994): Optic nerve invasion of retinoblastoma. Metastatic potential and clinical risk factors. Cancer 73: Shields JA, Shields CL, Eagle RC Jr, Singh 162
8 AD, Berrocal MH & Berrocal JA. Central retinal vascular obstruction secondary to melanocytoma of the optic disc. In press. Shields JA, Shields CL, Eagle RC, Lieb WE & Stern S (1990): Malignant melanoma associated with melanocytoma of optic disc. Ophthalmology 97: Shields JA, Shields CL, Gunduz K & Eagle RC Jr (1999): Neoplasms of the retinal pigment epithelium. The 1998 Albert Ruedemann Sr. Memorial Lecture. Part 2. Arch Ophthalmol 117: Shields JA, Shields CL & Singh AD. Metastatic neoplasms involving the optic disc. The 1999 Bjerrum Lecture. Part 2. Arch Ophthalmol, in press. Wray SH (1994): Optic neuritis. In: Albert DM, Jakobiec FA. Principles and Practice of Ophthalmology Vol 4. Philadelphia, WB Saunders Co pp Zimmerman LE (1965): Melanocytes, melanocytic nevi and melanocytomas. The Jonas S. Friedenwald Memorial Lecture. Invest Ophthalmol 4: Corresponding author: Jerry A. Shields, M.D. Director, Ocular Oncology Service Wills Eye Hospital 900 Walnut Street Philadelphia, PA,
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