CLINICAL CHALLENGES PETER SAVINO AND HELEN DANESH-MEYER, EDITORS Optic Neuritis in Evolution Molly Gilbert, MD, 1 William A. Cantore, MD, 2 Pamela S. Chavis, MD, 3 and Susannah K. Mistr, MD 3 1 Neuro-ophthalmology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania; 2 Neuro-ophthalmology Service, Penn State University College of Medicine, Hershey, Pennsylvania; and 3 Neuro- ophthalmology Service, Storm Eye Institute, Medical University of South Carolina, Charleston, South Carolina, USA (In keeping with the format of a clinical pathologic conference, the abstract and key words appear at the end of the article.) Case Report. A 47-year-old woman with a history of breast cancer presented with loss of vision right eye (OD) and flashing lights left eye (OS). She was found to have a superior altitudinal visual field defect OD (Fig. 1) by another ophthalmologist. MRI of the brain and orbits demonstrated enhancement of the right optic nerve (Fig. 2). A spinal tap was normal. Her vision continued to decline in the right eye and she developed pain on eye movements. She was started on oral prednisone 60 mg daily. She did not regain any vision. Two weeks later she developed flashing lights in her left eye and was referred for neuro-ophthalmic examination. Her past medical history was significant for breast cancer diagnosed five months prior to her initial ophthalmic examination. She had undergone left mastectomy and chemotherapy. Visual acuity was no light perception with an amaurotic pupil OD and 20/20 OS. External examination, exophthalmometry, and slit-lamp ex- amination were unremarkable. She could identify no Ishihara color plates OD, but was 10/10 OS. Automated perimetry demonstrated a normal field OS. Dilated funduscopic examination is shown in Fig. 3. The funduscopic examination OS was normal. What are the diagnostic probabilities? What tests would you order? Comments Comments by Pamela Chavis, MD, and Susannah Mistr, MD This is a middle-aged patient with a history of breast cancer presenting with acute visual loss that was progressive to NLP despite steroid therapy. The patient’s age and initial, albeit painless, altitudinal defect could possibly be due to demyelinating optic neuritis associated with multiple sclerosis (MS) (Figs. 1 & 2). Although her age lies just beyond the typical age distribution (age 15--45), we recog- nize that late-onset optic neuritis can occur. How- ever, according to the Optic Neuritis Treatment Trial (ONTT) 92.2% of optic neuritis patients have some pain; it may be only mild in 50% and on eye movement in 51.2%. 1 Also, beyond the age of 40, 529 Ó 2007 by Elsevier Inc. All rights reserved. 0039-6257/07/$--see front matter doi:10.1016/j.survophthal.2007.06.008 SURVEY OF OPHTHALMOLOGY VOLUME 52 NUMBER 5 SEPTEMBER–OCTOBER 2007
Transcript
SURVEY OF OPHTHALMOLOGY VOLUME 52 � NUMBER 5 � SEPTEMBER–OCTOBER 2007
CLINICAL CHALLENGESPETER SAVINO AND HELEN DANESH-MEYER, EDITORS
Optic Neuritis in EvolutionMolly Gilbert, MD,1 William A. Cantore, MD,2 Pamela S. Chavis, MD,3
and Susannah K. Mistr, MD3
1Neuro-ophthalmology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania;2Neuro-ophthalmology Service, Penn State University College of Medicine, Hershey, Pennsylvania; and 3Neuro-ophthalmology Service, Storm Eye Institute, Medical University of South Carolina, Charleston, South Carolina, USA
(In keeping with the format of a clinical pathologic conference,the abstract and key words appear at the end of the article.)
Case Report. A 47-year-old woman with a history ofbreast cancer presented with loss of vision right eye(OD) and flashing lights left eye (OS). She wasfound to have a superior altitudinal visual fielddefect OD (Fig. 1) by another ophthalmologist. MRIof the brain and orbits demonstrated enhancementof the right optic nerve (Fig. 2). A spinal tap wasnormal. Her vision continued to decline in the righteye and she developed pain on eye movements. Shewas started on oral prednisone 60 mg daily. She didnot regain any vision. Two weeks later she developedflashing lights in her left eye and was referred forneuro-ophthalmic examination.
Her past medical history was significant for breastcancer diagnosed five months prior to her initialophthalmic examination. She had undergone leftmastectomy and chemotherapy.
Visual acuity was no light perception with anamaurotic pupil OD and 20/20 OS. Externalexamination, exophthalmometry, and slit-lamp ex-amination were unremarkable. She could identify noIshihara color plates OD, but was 10/10 OS.Automated perimetry demonstrated a normal field
52
� 2007 by Elsevier Inc.All rights reserved.
OS. Dilated funduscopic examination is shown inFig. 3. The funduscopic examination OS was normal.
What are the diagnostic probabilities? What tests wouldyou order?
Comments
Comments by Pamela Chavis, MD, and SusannahMistr, MD
This is a middle-aged patient with a history ofbreast cancer presenting with acute visual loss thatwas progressive to NLP despite steroid therapy. Thepatient’s age and initial, albeit painless, altitudinaldefect could possibly be due to demyelinating opticneuritis associated with multiple sclerosis (MS)(Figs. 1 & 2). Although her age lies just beyondthe typical age distribution (age 15--45), we recog-nize that late-onset optic neuritis can occur. How-ever, according to the Optic Neuritis TreatmentTrial (ONTT) 92.2% of optic neuritis patients havesome pain; it may be only mild in 50% and on eyemovement in 51.2%.1 Also, beyond the age of 40,
9
0039-6257/07/$--see front matterdoi:10.1016/j.survophthal.2007.06.008
530 Surv Ophthalmol 52 (5) September--October 2007 GILBERT ET AL
patients with multiple sclerosis are less likely topresent with an isolated optic neuritis and are morelikely to have motor disturbances at onset (49.1% vs.22.5% of patients less than 40 years old) and to haveprogressive neurologic disease as well.20 In fact,associated or heralding neurologic deficits occurredin 93% of patients (n 5 58) with onset of MS beyondage 40 years.20 This clinical presentation is also
atypical for optic neuritis associated with MS in that
the visual symptoms progressively worsened overseveral weeks while on steroid treatment. Thesymptoms eventually included pain on eye move-ments, but this symptom with this clinical course ismore typical of a perioptic optic neuropathy duemore to a compressive or autoimmune abnormalitythan demyelinating disease.17 There is also nocomment about initial asymptomatic involvementof the other optic nerve which can occur in up to43--48% of demyelinating optic neuritis in the formof visual field changes.8,34 Hence, this somewhatatypical presentation as well as atypical progressionof optic neuritis—along with a cancer history—necessitates further investigations to rule out moreominous causes.
Before we associate this with her cancer history, letus consider the fundus and MRI presentation.Although there is also no comment on initialfunduscopic examination (prior to symptoms OS),retinal etiologies and anterior ischemic neuropa-thies need to be excluded and clues to otherinflammatory etiologies should be sought by historyand the laboratory evaluation targeted accordingly.This patient is having pain on eye movement, withfundus evidence of retinal and optic nerve ischemia;there are hemorrhages, venous dilation, and retinaledema with box-carring compatible with centralretinal artery and vein occlusion (Fig. 3).
Although cancer-related issues are certainly para-mount, infectious, toxic, and inflammatory etiolo-gies should be excluded in a patient who hasreceived chemotherapy; this should especially in-clude syphilis, tuberculosis, sarcoidosis, toxoplasmo-sis, crytococcus, and cat-scratch disease screening.
Fig. 3. Funduscopic examination OD showing CRVOwith boxcarring of vessels, macular hemorrhage, opticnerve pallor, and retinal edema.
OPTIC NEURITIS IN EVOLUTION 531
Serum or cerebrospinal fluid (CSF) cells, sugar,protein, crytococcal antigen, antibody and venerealdisease research laboratory (VDRL) testing willreadily eliminate cryptococcus and syphilis; angio-tensin converting enzyme (ACE), chest x-ray (CXR),purified protein derivative (PPD), Bartonella henselaeserology, and, in an endemic area for Lyme disease,serology for Borellia burgdorferi and CSF Lyme-ELISAshould be considered.21 Toxoplasmosis has beenrarely reported to show longer segments of opticnerve involvement and to be bilateral.19 However,visual progression to no light perception (NLP) wasnot noted in several series of ocular presentations oftoxoplasmosis even with anterior optic nerve in-volvement.4,6 Futhermore, there was no evidence ofretinochoroiditis or vasculitis in this patient. Retinalvasculitis with vitritis is also characteristic of syphi-lis.48 Even in an endemic area, optic neuritis is anuncommon presentation of Lyme disease; papille-dema and/or papillitis with optic nerve enhance-ment on MRI may rarely occur, but not generally inisolation and more commonly with febrile illness,meningeal signs, facial nerve palsy, arthritis, anderythema migrans (EM).41 Extraocular muscleinvolvement with proptosis in Lyme disease has beenreported, but this patient also had fever and EM;therefore, a segment of optic nerve involvementwithout accompanying features would appear toeliminate Lyme disease.18 Optic nerve enhancementwith cat-scratch disease has been reported to beunilateral and localized to the optic nerve-globejunction extending only locally 3--4 mm; anteriorischemic optic neuropathy, if it shows enhancement,can also be localized to this area.35 Brain MRI lesionsin cat-scratch can include gray and white matterabnormalities, including the basal ganglia.37
Cancer patients are also at increased risk for otheroptic neuropathies. Synchronous, second primarytumors such as meningiomas can occur especially inwomen over 40.36 In a large series of orbitalneoplasms, meningiomas comprised about 28% ofprimary optic nerve tumors, second only to opticnerve glioma.38,39 Women over 40 with diabetes andhypertension appear to be at greater risk formeningioma; blood group B and perhaps obesityis more common in meningioma.36 Moreover,women with a history of breast cancer may be at1.57--1.90 times increased risk for meningioma; thelatter show a higher rate of progesterone receptorsthan estrogen receptors, which is just the reverserate for breast cancer but, obviously, the overlap canbe significant.24,26,36,43 Importantly, estrogen recep-tor-negative breast cancer is more likely to developbrain metastases as the initial site of metastaticdisease.36 Therefore, it would be useful to knowwhat receptor type the patient’s cancer was.
Her-2/nu oncogene overexpression is an impor-tant receptor marker signifying isolated brainmetastasis with breast cancer,that is, a propensityfor CNS metastasis and, thus, shorter disease-freeand survival time.10,46 Her-2 is in the epidermalgrowth factor receptor family and via gene amplifi-cation is overexpressed in 20--30% of breast carci-noma.46 Trastuzumab is a monoclonal antibodyused in treating Her-2/nu overexpression; 34% ofpatients treated with trastuzumab developed brainmetastasis, it was the first site of symptomatic diseaseprogression in 82% and the only site of diseaseprogression in 69% of patients.15,46
In patients with known systemic metastatic breastcancer, the presence of increased pretreatmentserum lactate dehydrogenase, as well as liver, lung,and lymph node metastasis are predictive of CNSinvolvement.33 It may be that several factors are atplay including prolonged survival and improvedtreatment of systemic involvement; micrometastasismay be surviving in the CNS since some of the newertreatments do not cross as effectively into brainparenchyma but are very effective systemically.12
This is also true of treatment with epirubicin anddocetaxel, with subsequent rates of CNS involve-ment being as high as 30%. Otherwise, occult brainmetastasis may be present in 18% of patients withdisseminated cancer in autopsy and clinical series.29
Both breast and lung cancer can be metastatic todura/meninges, and both have been documentedto metastasize to a vascular meningeal tumor, that is,meningioma.3,7,45 Even though it is rare and onlyoccurs in 1--7% of metastases to the orbit, isolatedinfiltrative metastatic disease to the optic nerve itselfhas been reported most often in with breast (45%),and lung (27%) cancer.11,28,39,40 Metastatic opticnerve disease can present a further diagnosticchallenge and mimic meningioma or optic neuri-tis.5,31,32 However, decreasing vision over severalmonths is the most common presentation, and thedisk may demonstrate a diffuse enlargement, visiblemass, pallor, edema, hyperemia, and/or hemor-rhage.28,40 If there is hyperostosis on skull series orCT, then that is more typical of meningioma;whereas metastasis is more likely to show bonydestruction if any changes are present.26 The MRimages of metastasis and meningioma can beindistinguishable by conventional techniques be-cause both can be hypo- or isointense on T1, iso- tohyperintense on T2, and show homo- or heteroge-neous enhancement with flare; however, metastasiscan show low cerebral blood volume maps.23 Shortof this new diagnostic technique, histologicalverification is essential to differentiate meningiomafrom dural metastasis.42 As it was also necessary todiagnosis lymphomatous infiltration of the optic
532 Surv Ophthalmol 52 (5) September--October 2007 GILBERT ET AL
nerve in a patient whose visual acuity continued todecline despite significant corticosteroid treatment;lymphoma and leukemia more commonly areassociated with a vitritis or meningitis which wouldhave mitigated the need for an optic nerve/sheathbiopsy by presenting other fluids/tissue for analy-sis.9,27 Vascular occlusions of the optic nerve andretina can occur via direct lymphomatous infiltra-tion but this is also uncommon.25 After hematoge-nous spread to the meninges there can also bespread along the neural and cerebrospinal fluidpathways, and venous plexus. Carcinomatous men-ingitis may cause an optic neuropathy that canmimic anterior or posterior ischemic neuropathybut this patient’s neuroimaging did not support thisconsideration.27
Chemotherapy with vincristine, cisplatin, carpo-platin, methotrexate, tamoxifen, and paclitaxel cancause an optic neuropathy.14,16,47 Toxic optic neu-ropathies are classically painless, bilateral, and fairlysymmetrical with central or centroceccal scotomasaccompanying disk edema or pallor. There are alsoa few case reports of 5-fluoruracil associated opticneuropathy, and a recent case stresses the signifi-cance of dihydropyrimidine dehydrogenase (DPD)deficiency in increasing the risk of neurotoxicity.16
High-dose carmustine and cisplatin have beenreported to show segmental cotton-wool spotscompatible with branch retinal artery occlusions ina metastatic breast cancer patient.44 A retinal anddisk microvasculopathy has been noted in patientsreceiving high-dose chemotherapy (cyclophospha-mide, cisplatin, BCNU, and/or paclitexal) andautologous progenitor cell support; 26% of patientshad cotton-wool spots or retinal hemorrhages.Although visual acuity was variable, none of thepatients were NLP.22 This patient was not treatedwith radiation, an additional risk for optic neurop-athy in cancer patients requiring radiation to theparanasal sinuses, brain, or other focus in the headand neck.30
Unfortunately, a single negative lumbar puncture(for which cytology was presumably performed) isnot sufficient to rule out malignancy. Initial lumbarpuncture cytology was diagnostic in only 50% ofcases in a small case series of eight breast cancerpatients with carcinomatous meningitis.49 It isestimated that four to five additional spinal tapsmay be required before malignant cells might becaptured for a diagnosis of carcinomatous meningi-tis.27 Repeat lumbar punctures with cytology arenecessary.
The patient further loses vision and developsflashing lights or photopsias in the contralateral eye.This phenomenon is suspicious for an additionalretinal process either ischemic or inflammatory; and
the obvious link is a paraneoplastic syndrome inwhich autoantibodies raised in the face of malig-nancy cross react with retinal photoreceptor pro-teins in either the inner or outer layer of RPE.13 AnERG may be helpful in the diagnosis of thissyndrome. A paraneoplastic optic neuropathy(PON) can occur as well, but the patients havevisual loss with optic nerve swelling accompanied byauto-antibodies such as anti-CV-2 or CRMP-5.16
Regardless, this progression from an assumednormal fundus to ischemia and CRVO suggestsa progressive impingement of the nerve correspond-ing to increased infiltration of the nerve. Based onthe imaging results and clinical picture, our leadingsuspicion at this point is infiltrating metastaticdisease to the right optic nerve with secondaryvascular occlusions as well as paraneoplastic syn-drome presenting with photopsias in the left eye. Werecommend a repeat MRI scan of the brain andorbits, a series of lumbar punctures to look formalignant cells in the CSF and electroretinographyto evaluate for a paraneoplastic process OS. Opticnerve biopsy could be considered if the other testingdid not establish the diagnosis.
Case Report (Continued)
Lumbar puncture with cytology was repeated andwas again found to be negative. ERG was normal
excluding a paraneoplastic process but some ische-mic associated with subclinical involvement of theleft eye is possible. Repeat MRI is shown in Figs. 4and 5.
What would you next recommend?
Comments (Continued)
Comments by Dr. Chavis and Dr. MistrImaging shows scattered white matter intensities
and we are most certainly observing metastaticspread to the brain. No malignant cytol2ogy appearsin the CSF, but biopsy is unlikely to changemanagement plan for presumed intracranial meta-static disease. Whole brain radiation could beconsidered. Recurrence of the primary cancershould be addressed with appropriate chemothera-peutic treatment according to the patient’s wishes.Mean survival for a patient with metastatic diseaseinfiltrating the optic nerve is 6--13 months.12,40
Radiation for metastatic disease to the optic nervehas been attempted, but it appears an increaseddose may be necessary for optic nerve metastasiscompared to uveal metastases.2,3
Case Report (Concluded)
Discussion with her primary oncologist andneurologist yielded the decision that the MRI
Fig. 5. Repeat MRI showing multiple white matterhyperintensities.
findings were sufficiently diagnostic of intracranialspread of the carcinoma to merit whole brainradiation without a tissue diagnosis from the opticnerve or elsewhere.
References
1. ___: The clinical profile of optic neuritis. Experience of theOptic Neuritis Treatment Trial. Optic Neuritis Study Group.Arch Ophthalmol 109:1673--8, 1991
2. Allaire GS, Corriveau C, Arbour JD: Metastasis to the opticnerve: clinicopathological correlations. Can J Ophthalmol30:306--11, 1995
3. Arnold AC, Hepler RS, Badr MA, et al: Metastasis ofadenocarcinoma of the lung to optic nerve sheath menin-gioma. Arch Ophthalmol 113:346--51, 1995
4. Atmaca LS, Simsek T, Batioglu F: Clinical features andprognosis in ocular toxoplasmosis. Jpn J Ophthalmol 48:386--91, 2004
5. Backhouse O, Simmons I, Frank A, et al: Optic nerve breastmetastasis mimicking meningioma. Aust N Z J Ophthalmol26:247--9, 1998
7. Baratelli GM, Ciccaglioni B, Dainese E, et al: Metastasis ofbreast carcinoma to intracranial meningioma. J NeurosurgSci 48:71--3, 2004
8. Beck RW, Kupersmith MJ, Cleary PA, et al: Fellow eyeabnormalities in acute unilateral optic neuritis. Experienceof the optic neuritis treatment trial. Ophthalmology 100:691--7, discussion 697--8, 1993
9. Behbehani RS, Vacarezza N, Sergott RC, et al: Isolated opticnerve lymphoma diagnosed by optic nerve biopsy. Am JOphthalmol 139:1128--30, 2005
10. Burstein HJ, Lieberman G, Slamon DJ, et al: Isolated centralnervous system metastases in patients with HER2-over-expressing advanced breast cancer treated with first-linetrastuzumab-based therapy. Ann Oncol 16:1772--7, 2005
11. Cantore WA: Neural orbital tumors. Curr Opin Ophthalmol11:367--71, 2000
12. Carey LA, Ewend MG, Metzger R, et al: Central nervoussystem metastases in women after multimodality therapy forhigh risk breast cancer. Breast Cancer Res Treat 88:273--80,2004
14. Clare G, Colley S, Kennett R, et al: Reversible opticneuropathy associated with low-dose methotrexate therapy.J Neuroophthalmol 25:109--12, 2005
15. Clayton AJ, Danson S, Jolly S, et al: Incidence of cerebralmetastases in patients treated with trastuzumab for meta-static breast cancer. Br J Cancer 91:639--43, 2004
16. Delval L, Klastersky J: Optic neuropathy in cancer patients.Report of a case possibly related to 5 fluorouracil toxicityand review of the literature. J Neurooncol 60:165--9, 2002
17. Dutton JJ, Anderson RL: Idiopathic inflammatory periopticneuritis simulating optic nerve sheath meningioma. Am JOphthalmol 100:424--30, 1985
18. Fatterpekar GM, Gottesman RI, Sacher M, et al: OrbitalLyme disease: MR imaging before and after treatment: casereport. AJNR Am J Neuroradiol 23:657--9, 2002
19. Gass A, Moseley IF: The contribution of magnetic resonanceimaging in the differential diagnosis of optic nerve damage.J Neurol Sci 172(Suppl 1):S17--22, 2000
20. Hawkins SA, McDonnell GV: Benign multiple sclerosis?Clinical course, long term follow up, and assessmentof prognostic factors. J Neurol Neurosurg Psychiatry 67:148--52, 1999
21. Jacobson DM, Marx JJ, Dlesk A: Frequency and clinicalsignificance of Lyme seropositivity in patients with isolatedoptic neuritis. Neurology 41:706--11, 1991
534 Surv Ophthalmol 52 (5) September--October 2007 GILBERT ET AL
22. Johnson DW, Cagnoni PJ, Schossau TM, et al: Optic disc andretinal microvasculopathy after high-dose chemotherapyand autologous hematopoietic progenitor cell support.Bone Marrow Transplant 24:785--92, 1999
23. Kremer S, Grand S, Remy C, et al: Contribution of dynamiccontrast MR imaging to the differentiation between duralmetastasis and meningioma. Neuroradiology 46:642--8, 2004
24. Kubo M, Fukutomi T, Akashi-Tanaka S, et al: Association ofbreast cancer with meningioma: report of a case and reviewof the literature. Jpn J Clin Oncol 31:510--3, 2001
25. Lee LC, Howes EL, Bhisitkul RB: Systemic non-Hodgkin’slymphoma with optic nerve infiltration in a patient withAIDS. Retina 22:75--9, 2002
26. Lieu AS, Hwang SL, Howng SL: Intracranial meningiomaand breast cancer. J Clin Neurosci 10:553--6, 2003
28. Mack HG, Jakobiec FA: Isolated metastases to the retina oroptic nerve. Int Ophthalmol Clin 37:251--60, 1997
29. Miller KD, Weathers T, Haney LG, et al: Occult centralnervous system involvement in patients with metastaticbreast cancer: prevalence, predictive factors and impact onoverall survival. Ann Oncol 14:1072--7, 2003
30. Miller NR: Radiation-induced optic neuropathy: still notreatment. Clin Experiment Ophthalmol 32:233--5, 2004
31. Newman NJ, Grossniklaus HE, Wojno TH: Breast carcinomametastatic to the optic nerve. Arch Ophthalmol 114:102--3,1996
33. Ryberg M, Nielsen D, Osterlind K, et al: Predictors of centralnervous system metastasis in patients with metastatic breastcancer. A competing risk analysis of 579 patients treated withepirubicin-based chemotherapy. Breast Cancer Res Treat 91:217--25, 2005
34. Sanders EA, Volkers AC, van der Poel JC, et al: Estimation ofvisual function after optic neuritis: a comparison of clinicaltests. Br J Ophthalmol 70:918--24, 1986
35. Schmalfuss IM, Dean CW, Sistrom C, et al: Optic neuropathysecondary to cat scratch disease: distinguishing MR imagingfeatures from other types of optic neuropathies. AJNR Am JNeuroradiol 26:1310--6, 2005
36. Schneider B, Pulhorn H, Rohrig B, et al: Predisposingconditions and risk factors for development of symptomaticmeningioma in adults. Cancer Detect Prev 29:440--7, 2005
37. Seah AB, Azran MS, Rucker JC, et al: Magnetic resonanceimaging abnormalities in cat-scratch disease encephalopa-thy. J Neuroophthalmol 23:16--21, 2003
38. Shields JA, Bakewell B, Augsburger JJ, et al: Classificationand incidence of space-occupying lesions of the orbit.A survey of 645 biopsies. Arch Ophthalmol 102:1606--11,1984
39. Shields JA, Shields CL, Scartozzi R: Survey of 1264 patientswith orbital tumors and simulating lesions: The 2002Montgomery Lecture, part 1. Ophthalmology 111:997--1008, 2004
42. Tagle P, Villanueva P, Torrealba G, et al: Intracranialmetastasis or meningioma? An uncommon clinical diagnos-tic dilemma. Surg Neurol 58:241--5, 2002
43. Wahab M, Al-Azzawi F: Meningioma and hormonalinfluences. Climacteric 6:285--92, 2003
44. Wang MY, Arnold AC, Vinters HV, et al: Bilateral blindnessand lumbosacral myelopathy associated with high-dosecarmustine and cisplatin therapy. Am J Ophthalmol 130:367--8, 2000
45. Watanabe T, Fujisawa H, Hasegawa M, et al: Metastasis ofbreast cancer to intracranial meningioma: case report. Am JClin Oncol 25:414--7, 2002
46. Weil RJ, Palmieri DC, Bronder JL, et al: Breast cancermetastasis to the central nervous system. Am J Pathol 167:913--20, 2005
47. Weisfeld-Adams JD, Dutton GN, Murphy DM: Vincristinesulfate as a possible cause of optic neuropathy. PediatrBlood Cancer 48:238--40, 2007
48. Yokoi M, Kase M: Retinal vasculitis due to secondary syphilis.Jpn J Ophthalmol 48:65--7, 2004
49. Yu H, Mitsumori M, Nagata Y, et al: Meningeal carcinoma-tosis in patients with breast cancer: report of 8 patients.Breast Cancer 8:74--8, 2001
The authors have no proprietary or commercial interest in anyproduct mentioned or concept discussed in this article.Supported in part by an unrestricted grant to SEI from Researchto Prevent Blindness, New York, NY.
Reprint address: Molly E. Gilbert, MD, Wills Eye Hospital, 840Walnut Street Suite 930, Philadelphia, PA 19107.
Abstract. A case of progressive optic neuropathy in a woman with a history of breast cancer ispresented. Differential diagnoses including optic neuritis, infiltrative optic neuropathy, carcinomatousmeningitis, and toxic optic neuropathies are discussed. Risk factors for metastatic brain lesions are alsodiscussed. (Surv Ophthalmol 52:529--534, 2007. � 2007 Elsevier Inc. All rights reserved.)
