Retinal Manifestations of Neurofibromatosis Diagnosis and Management Maryanna Destro, MD; Donald J. D'Amico, MD; Evangelos S. Gragoudas, MD; Robert J. Brockhurst, MD; Michael K. Pinnolis, MD; Daniel M. Albert, MD; Trexler M. Topping, MD; Carmen A. Puliafito, MD \s=b\ Five patients presented with vision\x=req-\ threatening retinal tumors and systemic signs of neurofibromatosis, including neurofibromatosis type 1 (four patients) and familial cafe-au-lait spots (one patient). These tumors included large retinal astrocytic hamartomas, multiple retinal capillary hemangiomas, and

combined hamartomas of the retina and retinal pigment epithelium, which resulted in rubeotic glaucoma, vitreous hemorrhage, and retinal detachment. Surgical therapy included retinal cryopexy, xenon and argon photocoagulation, scleral buckling, and pars plana vitrectomy with excisional retinal biopsy. Retinal tumors may result in marked visual loss in patients with neurofibromatosis, and vitreoretinal surgery may restore useful vision in some of these

patients. (Arch Ophthalmol. 1991;109:662-666) "M" eurofibromatosis is the most

com-

monly reported phakomatosis in the United States, with an estimated prevalence of 100 000 persons.' In the past, patients with neurofíbromatosis have been grouped together under the term "von Recklinghausen's disease." Recent advances in molecular genetAccepted for publication November 13,

1990. From the Retina Service (Drs Destro, D'Amico, Gragoudas, Pinnolis, and Puliafito) and Department of Ophthalmology (Drs Destro, D'Amico,

Gragoudas, Brockhurst, Pinnolis, Albert, Topping, and Puliafito), Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston. Reprint requests to Retina Service, Massachusetts Eye and Ear Infirmary, 243 Charles St, Boston, MA 02114 (Dr Destro).

ics, however, have shown that there are at least two genetically distinct

forms of neurofíbromatosis: neurofí¬ bromatosis type 1 (NF-1, previously described as "classic" or "peripheral" neurofíbromatosis) and neurofíbroma¬ tosis type 2 (NF-2, previously de¬ scribed as "central" or "bilateral acous¬ tic" neurofíbromatosis) (Table).2 Both NF-1 (affecting approximately 1 in 4000 individuals) and NF-2 (affecting approximately 1 in 50 000 individuals) are known to be dominantly inherited. The genetic mutation responsible for NF-1 has recently been identified on the long arm of chromosome 17, while that for NF-2 appears to be on the long arm of chromosome 22.2 In addition, variant forms are

thought

to

exist, including segmental

neurofíbromatosis and familial cafe-aulait spots.2"4 However, to date, the precise classification of these variant forms has not been well defined. While ophthalmic manifestations, such as iris Lisch nodules, ciliary body and choroidal neurofibromas, optic nerve gliomas, sphenoid bone dysplasias, and eyelid plexiform neuromas, have frequently been noted in patients with NF-l,*7 and juvenile posterior subcapsular lens opacities have fre¬ quently been noted in patients with NF-2,8,9 retinal lesions have rarely been described. In addition, one recent text has stated that "the ophthalmolo¬ gist has no medical or surgical manage¬ ment to offer patients with neurofíbro¬ matosis who have retinal or choroidal

lesions."10 We report the surgical management of five patients (aged 3 to 25 years)

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who presented with retinal tumors and neurofíbromatosis.

vision-threatening systemic signs of

REPORT OF CASES CASE 1.—A 16-year-old white male ado¬ lescent presented with a 3-month history of decreased vision in his right eye. Best corrected visual acuity was light perception in the right eye and 20/20 OS. Slit-lamp examination and funduscopic examination of the left eye yielded normal findings. However, funduscopic examination of the right eye revealed a total retinal detach¬ ment with a large, irregular, yellow retinal mass in the superonasal periphery. The mass was highly vascularized, and en¬ gorged vessels were noted extending from the optic disc toward and away from this peripheral mass. In addition, a retinal dialy¬ sis was present at the tumor's anterior

margin (Fig 1, top). Ultrasonography revealed marked retinal thickening with a normal underlying cho¬ roid, and computed tomography of the or¬

bits confirmed a noncalcified retinal mass. Fluorescein angiography showed abnormal¬ ly large retinal arterioles and venules feed¬ ing and draining the mass, with fluorescein leakage from the intrinsic tumor vascula¬ ture (Fig 1, bottom). Physical examination revealed numerous large cafe-au-lait spots on his trunk and limbs and a neurofibroma on his arm. His mother was noted to have similar findings, and both he and his mother were subsequently confirmed to have NF-1. The patient's retinal tumor was believed to represent an astrocytic retinal hamartoma associated with a rhegmatogenous retinal detachment and NF-1. He subse¬ quently underwent a pars plana vitrectomy with excisional retinal biopsy. Intraoper¬ atively, the tumor was outlined with intra¬ ocular diathermy, excised en bloc with in¬ traocular scissors, and withdrawn through the superotemporal pars plana sclerotomy.

Diagnostic Criteria for Neurofíbromatosis Type 1 (NF-1) and Neurofíbromatosis Type 2 (NF-2)2 NF-1

Diagnosis requires following:

two or more of the

cafe-au-lait spots >5 in diameter in prepubescent or >15 mm in diameter in

1. Six

or more

mm

postpubescent individuals. 2. Two

or more

neurofibromas of any

type or one plexiform neurofibroma. 3. Freckling of axillary, inguinal, or other intertriginous areas. 4. Optic nerve glioma. 5. >:2 iris Lisch nodules. 6. A distinctive

sphenoid

osseous

bone

lesion, such as or thinning

dysplasia

of the long-bone cortex, with or without pseudoarthrosis. 7. A first-degree relative with NF-1 per above criteria._

_the NF-2

Diagnosis requires either: 1. Bilateral eighth-nerve masses seen with appropriate neuroradiologic imaging techniques. or:

first-degree relative with NF-2 and a unilateral eighth-nerve mass or two of the following: (a) neurofibroma, (b) meningioma, (c) glioma, (d) schwannoma, or (e) juvenile posterior subcapsular

2. A

either

cataract.

noted to be very stiff, of the sclerotomy to 4 mm to allow atraumatic removal from the eye. An air-fluid exchange was performed, resulting in complete reattachment of the retina. Two rows of endolaser photocoagu¬ lation burns were placed around the poste¬ rior margins of the biopsy site, and a single row of transscleral cryopexy was placed along the anterior margin. The intraocular air was exchanged with 16% perfluoropropane gas, and the patient was placed in a The tumor

was

requiring enlargement

position postoperatively. Histopathologic examination of the ex¬ cised 8x9-mm specimen revealed a large glial (astrocytic) hamartoma of the retina. Whorls of spindle-shaped tumor cells were present with long cellular processes, consis¬ prone

tent with retinal

astrocytes. Numerous vas¬ cular channels were also present (Fig 2). Transmission electron microscopy con¬ firmed the presence of proliferating retinal astrocytes with characteristic nuclear in¬ dentations, margination of the nuclear chromatin, and 6-nm glial filaments within the long cellular processes. The jjatient initially did well; however, he returned 4 weeks postoperatively with se¬ vere proliferative vitreoretinopathy associ¬ ated with giant retinal tears in the inferotemporal and superonasal quadrants and a total redetachment of the retina. Repeated pars plana vitrectomy combined with pars plana lensectomy, a 360° retinotomy, and injection of intravitreal silicone oil resulted in successful reattachment of the retina. He later underwent silicone oil removal with additional epiretinal membrane peeling, and, on the most recent follow-up visit 4

months later, his retina was attached; how¬ ever, his visual acuity was limited to hand motions from residual subretinal fibrosis distorting the macula. Case 2.—A 15-year-old white male ado¬ lescent presented with sudden decreased vision in his right eye, associated with pain and photophobia. Best corrected visual acu¬ ity was 20/100 OD and 20/20 OS. Slit-lamp examination of the right eye revealed neo¬ vascularization of the iris associated with iritis and elevated intraocular pressure (40 mm Hg). No iris Lisch nodules were seen. Funduscopic examination of the right eye revealed a superior retinal detachment associated with a retinal dialysis. The de¬ tached retina directly posterior to the reti¬ nal dialysis appeared to be abnormally thickened and vascularized. Physical examination revealed multiple cafe-au-lait spots, and the patient, his moth¬ er, and his sister had been previously diag¬ nosed as having NF-1. Following medical control of his iritis and glaucoma, a scierai buckling procedure was performed on the right eye associated with external drainage of subretinal fluid and cryopexy of the margins of the superior retinal dialysis. On the first postoperative day, the retina was reattached. However, it was recognized at that time that the abnormally thickened, vascularized retina posterior to the retinal dialysis actually represented a retinal mass. This mass was believed to be a peripheral astrocytic hamartoma in a patient with NF-1. The patient's visual acuity initially im¬ proved to 20/70 OD; however, shifting sub¬ retinal fluid was present inferiorly, which appeared to be originating from the superi¬ or, vascularized mass. Intense, confluent argon laser photocoagulation was applied to this mass in multiple sessions during the next several months. However, shifting subretinal fluid persisted, and the patient eventually lost all light perception second¬ ary to chronic exudative retinal detachment and neovascular glaucoma. Case 3.—A 3-year-old white boy was noted to have progressive exotropia with decreased vision in his left eye. Visual acuity was 20/30 OD and hand motions in the left eye. Slit-lamp examination revealed two small nodules on his inferior left iris. Funduscopic examination revealed bilateral retinal masses. In the left eye, a thickened, peripapillary retinal mass was present asso¬ ciated with lipid exudation, overlying gliosis, and distortion of the retinal vessels and macula (Fig 3, left). In the right eye, a large yellow retinal mass was noted in the far temporal periphery associated with en¬ gorged retinal vessels. In addition, hyperpigmentation was noted surrounding the posterior margins of the mass (Fig 3, right). Physical examination revealed multiple cafe-au-lait spots on his trunk, and the patient's brother, maternal aunt, and ma¬ ternal cousin were also known to have cafeau-lait spots, although a definitive diagnosis of NF-1 or NF-2 had not been established. The patient's fundus lesions were be¬ lieved to represent combined hamartomas of the retina and retinal pigment epithelium associated with familial cafe-au-lait spots.

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No treatment was administered at that time. However, 4 months later, visual acu¬ ity in his right eye had decreased to count¬ ing fingers secondary to a vitreous hemor¬ rhage originating from the peripheral retinal mass. This mass was subsequently treated with retinal cryopexy, with use of a single freeze-thaw technique. This resulted in involution of the vascularized mass, with clearing of the vitreous hemorrhage. Eight months later, at the most recent follow-up visit, his visual acuity had improved to 20/60 OD. Case 4.—A 25-year-old white woman with a history of NF-1 presented with acute vision loss in her left eye. Visual acuity was 20/20 OD and hand motions in the left eye. Slit-lamp examination revealed numerous iris Lisch nodules bilaterally (Fig 4, top). Funduscopic examination of the right eye yielded normal findings. However, fundu¬ scopic examination of the left eye revealed a total retinal detachment with a large retinal tear in the inferotemporal far periphery. The retina surrounding this tear appeared abnormally thickened and irregular, and posterior to this area, a smaller, discrete intraretinal lesion was also noted associated with overlying gliosis and a surroundingrim of hyperpigmentation (Fig 4, center). Fluorescein angiography revealed abnormal vascularization of this smaller, posterior retinal lesion, as well as blockage of fluores¬ cence by its surrounding rim of pigment

(Fig 4, bottom). Physical examination revealed axillary freckling, multiple cafe-au-lait spots, and peripheral neurofibromas on her trunk and limbs, and a skeletal deformity of her left leg.

Her retinal mass was believed to repre¬ sent a combined hamartoma of the retina and retinal pigment epithelium associated

with a rhegmatogenous retinal detachment and NF-1. Subsequently, she underwent a scierai buckling procedure with cryopexy to the margins of the retinal tear and to the pigmented mass posterior to the retinal tear. At the most recent follow-up visit 1 month later, her visual acuity was 5/200 and her retina was completely reattached. Case 5.—A 17-year-old white female ad¬ olescent complained of decreased vision in her left eye. At the age of 10 years, she had presented with a superonasal retinal de¬ tachment in her right eye associated with a retinal dialysis. At that time, her visual acuity was 20/70 OD and 20/40 OS, and her retinal dialysis was thought to be secondary to a previous motor vehicle accident. How¬ ever, examination of the left eye had re¬ vealed an incidental finding of a single, small, retinal capillary hemangioma, lo¬ cated several disc diameters temporal to the fovea. She subsequently underwent a successful scierai buckling procedure in the right eye with xenon photocoagulation of the angioma in the left eye. On presentation 7 years later, her visual acuity in the right eye was unchanged at 20/70, but visual acuity in her left eye had decreased to counting fingers at 20 ft. Slitlamp examination yielded normal findings. Funduscopic examination of the right eye revealed an attached retina with a supero-

nasal scierai buckle. In

addition, retinal

capillary hemangiomas were noted along the superotemporal vessels associated with hard exúdate and preretinal fibrosis. Fun¬ duscopic examination of the left eye re¬ vealed chorioretinal scarring along the in¬ ferotemporal arcade extending into the posterior pole. In addition, numerous reti¬ nal capillary hemangiomas were present in the posterior pole and midperiphery associ¬ ated with extensive retinal edema and lipid

exudation. Her physical examination revealed multi¬ ple cafe-au-lait spots and peripheral neuro¬ fibromas, one of which was confirmed on histologie examination. Her neurologic and otologie examinations otherwise yielded normal findings, as did computed tomogra¬ phy of the orbits, brain, and brain stem. Both she and her father were subsequently diagnosed as having NF-1. She underwent xenon photocoagulation of the hemangiomas in her left eye, which resulted in résorption of the retinal edema and exudation. Examination 6 years later revealed visual acuities of 20/60 OD and 20/400 OS. Findings of funduscopic exami¬ nation of the right eye were unchanged, and examination of the left eye revealed chor¬ ioretinal scarring without evidence of reti¬ nal hemangiomatosis or lipid exudation. Two years later, however, several new hemangiomas were noted in the left eye, which subsequently regressed following fo¬ cal argon laser photocoagulation. COMMENT

Review of two recent surveys of the manifestations of NF-15,6 and two surveys of the ophthalmic manifestations of NF-2WI failed to re¬ veal any eyes with retinal tumors. Among the combined 130 patients with NF-1, more than one third displayed flat choroidal lesions thought to be choroidal neurofibromas. Six patients had retinal findings, including one pa¬ tient with a sectoral chorioretinal scar, one patient with myelinated nerve fi¬ bers, one patient with peripheral retinoschisis, and three patients with con¬ genital hypertrophy of the retinal pigment epithelium. None of the pa¬ tients with NF-28'9 was reported to have retinal lesions. However, there have been occasion¬ al reports of retinal tumors in patients with neurofíbromatosis, including astrocytic (glial) hamartomas, combined hamartomas of the retina and retinal pigment epithelium, and retinal capil¬

ophthalmic

lary hemangiomatosis.11"1"

Retinal Astrocytic Hamartomas and Neurofíbromatosis

Astrocytic hamartomas in neurofí¬ bromatosis have most frequently been noted to involve the optic nerve and have resembled the small, white "mul¬ berry" astrocytic hamartomas seen in patients with tuberous sclerosis. How-

ever, these tumors have occasionally been noted to be much more extensive.

In one such case reported by Martyn and Knox,12 a 12-year-old girl with NF1 and light perception visual acuity in the right eye was noted to have large, yellow retinal tumors around the optic disc and in the superotemporal periph¬ ery associated with engorged retinal vessels extending to the peripheral retinal mass. She subsequently devel¬ oped a blind, painful eye from rubeotic glaucoma, retinal detachment, and subretinal hemorrhage, and histologie examination following enucleation con¬ firmed the diagnosis of astrocytic (gli¬ al) hamartoma of the retina. Similarly, our first two patients (pa¬ tients 1 and 2) appeared to have large, peripheral, vascularized, retinal astro¬ cytic hamartomas. In both of these patients, rhegmatogenous retinal de¬ tachments were present associated with retinal dialyses along the anterior margin of the hamartoma. These find¬ ings suggest that traction from the gliotic retinal masses may have con¬ tributed to the development of the retinal dialyses and subsequent retinal detachments. A possible suppressor gene has re¬ cently been discovered located on chro¬ mosome 17, whose deletion might be responsible for the central nervous system astrocytomas seen in patients with neurofíbromatosis and in those without associated phakomatoses.19 Combined Hamartoma of the Retina and Retinal Pigment Epithelium and Neurofíbromatosis

A second hamartomatous lesion— combined hamartoma of the retina and retinal pigment epithelium (CHRRPE)—has also been reported in patients with neurofíbromatosis.18"1'1* Gass14 initially described a patient with CHR-RPE with cutaneous signs sug¬ gestive of neurofíbromatosis. In addi¬ tion, he reported having viewed photo¬ graphs of a patient with bilateral CHR-RPE who had been diagnosed as having "von Reckinghausen's neurofí¬ bromatosis," and both Cotlier15 and Landau et alis have subsequently de¬ scribed patients with NF-2 and CHRRPE involving the optic disc and mac¬ ula. Likewise, Gass has examined three children with cafe-au-lait spots and CHR-RPE, two of whom had bi¬ lateral hamartomas and one of whom had a solitary hamartoma (J.A.M. Gass, MD, Univeristy of Miami, Bas¬ com Palmer Eye Institute, written

communication,

August

1,

1988).

One of these patients was a 30-month-old girl with an elevated, partially pigmented mass in the macu-

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lar

region associated with overlying She subsequently developed

gliosis.11 an

exudative retinal detachment with

secondary neovascular glaucoma, and her eye was enucleated. Histologie ex¬ amination confirmed the diagnosis of CHR-RPE.

Similarly, our patients 3 and 4 ap¬ peared to have CHR-RPE associated with systemic signs of neurofíbromato¬ sis. In patient 3, these tumors resulted

in macular distortion and spontaneous vitreous hemorrhage. In patient 4, a retinal tear developed anterior to the retinal mass associated with the devel¬ opment of a total retinal detachment. Contraction of this gliotic retinal mass may have contributed to the develop¬ ment of the retinal tear and retinal detachment. Retinal Capillary Hemangiomatosis and Neurofíbromatosis

A third retinal hamartomatous le¬ sion—retinal capillary hemangiomato¬ sis—has also been reported to occur in patients with neurofíbromatosis. Frenkel16 described a 31-year-old man with NF-2 who presented with bilateral, small retinal hemangiomas along the superior and inferior temporal ar¬ cades. In addition, Thomas et al1' de¬ scribed three members of a family who displayed ocular and systemic findings of both neurofíbromatosis and von Hippel-Lindau disease. Similarly, our patient 5 developed bilateral retinal capillary hemangiomas associated with NF-1. These hemangi¬ omas resulted in extensive retinal ede¬ ma and lipid exudation. Neither she nor members of her family displayed evidence of concurrent von HippelLindau disease.

Management of Retinal Tumors Associated With Neurofíbromatosis There

are

few

guidelines in the liter¬

regarding the management of retinal tumors in patients with neurofí¬ bromatosis. Our cases demonstrate that these lesions may be visually threatening and may respond to surgi¬ cal intervention. Three of our patients underwent surgical repair of associat¬ ed rhegmatogenous retinal detach¬ ments, and two developed exudative intraretinal and subretinal detach¬ ments requiring treatment with photocoagulation and/or retinal cryopexy. While the visual outcome in our pa¬ tients has been limited, to date three of five have retained ambulatory vision (53=5/200) in their affected eye(s). When a child or adolescent presents with a retinal mass, entities such as retinoblastoma, Coats' disease, toxocariasis, and toxoplasmosis most freature

Fig 3.—Left, Fundus photograph of the left eye of patient 3 demonstrates a peripapillary mass associated with lipid exudation and overlying gliosis. Right, Fundus photograph of the right eye of patient 3 demonstrates a peripheral yellow retinal mass associated with abnormal vascularization and surrounding hyperpigmentation.

Fig 1.—Top, Fundus appearance in patient 1 included a yellow retinal mass in the superonasal periphery associated with a retinal dial¬ ysis and total retinal detachment. Bottom, Fluorescein angiogram from patient 1 dem¬ onstrates a vascularized retinal mass.

Fig 2.—Light microscopic appearance in patient 1 reveals an astrocytic hamartoma of the retina composed of uniform, spin¬ dle-shaped cells with small, oval nuclei and long cytoplasmic processes (hematoxylin-eosin, original magnification 40).

Fig 4.—Top, Iris photograph from patient 4 demonstrates multi¬ ple Lisch nodules. Center, Fundus photograph from patient 4 demonstrates a small, gliotic retinal lesion with surrounding hyperpigmentation (at center of photograph). Anterior to this lesion, the retina was abnormally thickened and contained a large retinal tear. The retina was totally detached. Bottom, Fluorescein angiogram from patient 4 demonstrates abnormal vascularization of the small retinal

mass.

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quently come to mind. Factors such as age at onset, clinical presentation and progression, associated ocular and/or systemic findings, roentgenographic and laboratory values, and family his¬ tory are all very helpful in determining the correct diagnosis and treatment. In this differential diagnosis, it must be recognized that retinal hamarto¬ mas occasionally develop in patients with neurofíbromatosis. Furthermore,

it appears that these retinal tumors may be visually threatening and may develop without the more familiar oph¬ thalmic and orbital signs associated with neurofíbromatosis. Recognition of these tumors may alert the physician to the presence of neurofíbromatosis and may prevent the unnecessary enu¬ cleation of these eyes,20 which, on occa¬ sion, have been mistakenly thought to harbor a retinoblastoma or malignant

melanoma. It should be cautioned, however, that various malignant neo¬ plasms have been reported in patients with neurofíbromatosis,3 and the pres¬ ence of neurofíbromatosis does not preclude the rare occurrence of intrao¬ cular malignant neoplasms, such as choroidal malignant melanomas21 and

retinoblastomas.22

References 1. Rubenstein AE, Yahr F. Neurofibromatosis: Informationfor Patients and Their Families. New York, NY: The National Neurofibromatosis Foundation Inc; 1989. 2. National Institutes of Health Consensus De-

velopment Conference Statement of Neurofibromatosis. Arch Neurol. 1988;45:575-580. 3. Riccardi VM. von Recklinghausen neurofibromatosis. N Engl J Med. 1981;305:1617-1626. 4. Carey JC, Baty BJ, Johnson JP, Morrison T, Skolnick M, Kivlin J. The genetic aspects of neurofibromatosis. Ann N Y Acad Sci. 1986;486:45-56. 5. Lewis RA, Riccardi VM. von Reckinghausen neurofibromatosis: incidence of iris hamartomata.

Ophthalmology. 1981;88:348-354. 6. Huson S, Jones D, Beck L. Ophthalmic manifestations of neurofibromatosis. Br J Ophthalmol.

1987;71:235-238. 7. Woog JJ, Albert DM, Solt LC, Hu DN, Wang

WJ. Neurofibromatosis of the eyelid and orbit. Int Ophthalmol Clin. 1982;22:157-187. 8. Kaiser-Kupfer ML, Freidlin V, Datiles MB, et al. The association of posterior capsular lens opacities with bilateral acoustic neuromas in patients with neurofibromatosis type 2. Arch Oph-

thalmol. 1989;107:541-544. 9. Zwaan J, Martuza RL. Ophthalmic findings in central neurofibromatosis (bilateral acoustic neuromas). Ophthalmology. 1989;9(suppl 96):129. 10. Ferry AP, Combs JL. Other phakomatoses. In: Ryan SJ, ed. Retina. St Louis, Mo: CV Mosby

Co; 1989;1:581-590. 11. Ulbright TM, Fulling KH, Helveston EM. Astrocytic tumors of the retina: differentiation of sporadic tumors from phakomatosis-associated tumors. Arch Pathol Lab Med. 1984;108:160-163. 12. Martyn LJ, Knox DL. Glial hamartoma of the retina in generalized neurofibromatosis: von Recklinghausen's disease. Br J Ophthalmol. 1972;56:487-491. 13. Gass JDM. Stereoscopic Atlas of Macular Diseases: Diagnosis and Treatment. 3rd ed. St Louis, Mo: CV Mosby Co; 1987:620-632. 14. Gass JDM. An unusual hamartoma of the pigment epithelium and retina simulating choroidal melanoma and retinoblastoma. Trans Am Ophthalmol Soc. 1973;71:171-185. 15. Cotlier E. Cafe-au-lait spots of the fundus in neurofibromatosis. Arch Ophthalmol. 1977;95: 1990-1992.

16. Frenkel M. Retinal angiomatosis in a patient with neurofibromatosis. Am J Ophthalmol. 1967; 63:804-808. 17. Thomas JV, Schwartz PL, Gragoudas ES. von Hippel's disease in association with von Recklinghausen's neurofibromatosis. Br J Ophthalmol.

1978;62:604-608. 18. Landau K, Dossetor FM, Hoyt WF, Muci\x=req-\

Mendoza R. Retinal hamartoma in neurofibromatosis 2. Arch Ophthalmol. 1990;108:328-329. 19. el-Azouzi M, Chung RY, Farmer GE, et al. Loss of distinct regions on the short arm of chromosome 17 associated with tumorigenesis of human astrocytomas. Proc Natl Acad Sci U S A. 1989; 86:7186-7190. 20. Ramsay RC, Kinyoun JL, Hill CW, Aturaliya UP, Knobloch WH. Retinal astrocytoma. Am J

Ophthalmol. 1979;88:32-36. 21. Wiznia RA, Freedman JK, Mancini AD, Shields JA. Malignant melanoma of the choroid in neurofibromatosis. Am J Ophthalmol. 1978;86:684\x=req-\

687. 22. Hasanreisoglu B, Or M, Akbatur H. Neurofibromatosis associated with retinoblastoma: case report. Br J Ophthalmol. 1988;72:139-141.

Currently in Other AMA Journals ARCHIVES OF NEUROLOGY Cardiac Sources of Cerebral Embolism Raul C. Rey; David A. Monteverde; Roberto E. P. Sica (Arch Neurol. 1991;48:359) Positron Emission Tomography in Progressive Supranuclear Palsy Mohit H. Bhatt, MD; Barry J. Snow, MBChB, FRACP; W. R. Wayne Martin, MD, FRCPC; Richard Peppard, MBBS, FRACP; Donald B. Calne, DM, FRCP, FRCPC (Arch Neurol.

1991;48:389-391)

Idiopathic Intracranial Hypertension Without Papilledema John Marcelis, MD, Stephen D. Silberstein, MD (Arch Neurol. 1991;48:392-399)

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