Journal of Neuro-Ophthalmology, March 2011, Volume 31, Issue 1

Letters to the Editor

Orbital Involvement in Bing-Neel Syndrome We read the article ‘‘Orbital Involvement in Bing-Neel Syndrome'' by Stacy et al (1) with great interest and commend the authors for their excellent discussion of the manifestations of Waldenstro¨m macroglobulinemia (WM) in the orbit and brain. We had the opportunity recently to see a similar patient with WM and diffuse orbital in-volvement whose clinical course demonstrates that the vi-sual outcome in these patients may be poor despite aggressive therapy. A 57-year-old man was referred to a retina specialist with a 3-week history of progressive, painless, bilateral visual loss. His medical history was significant for WM diagnosed 9 years previously, for which he was treated with 5 cycles of cyclophosphamide, rituximab, and prednisone, most re-cently 1 year prior to presentation. On examination, visual acuity was 20/160, right eye, and 20/32, left eye. Anterior segments were quiet, eye movements were full, and there was no proptosis. Dilated fundus examination revealed bilateral optic disc edema greater in the right eye than in the left eye, with a normal appearance of the retinal vessels, macula, and periphery. Fluorescein angiography showed leakage and staining of the optic discs. Infiltrative optic neuropathy was suspected, and he was started on oral prednisone 80 mg daily and referred im-mediately to his oncologist. MRI of the orbits revealed enhancement of the orbital fat and optic nerves (Fig. 1). Serum IgM was elevated at 1,350 mg/dL (range, 40-230 mg/dL). Chemotherapy with cyclophosphamide, vincris-tine, prednisone, and rituximab was initiated. However, vision declined to hand motions, right eye and 20/50, left eye, within 3 weeks of initial presentation. A right orbital biopsy was performed, and histopathologic examination revealed fibroadipose tissue with patchy aggregates of small lymphocytes, scattered plasma cells, and histiocytes. Im-munoperoxidase staining of the lymphocytes was positive for CD20, CD79a, and CD138 and negative for CD23, CD5, CD10, and BCL-1. These matched markers from the patient's previous bone marrow biopsies, confirming orbital infiltration of WM. The patient was hospitalized for intravenous infusion of high-dose methotrexate and intrathecal cytarabine. A lumbar puncture yielded lymphocytes in insufficient number for flow cytometry. The patient received external beam orbital radiation therapy in 18 fractions for a total dose of 30.6 Gy. Despite treatment, the patient's vision declined to no light perception in each eye. Stacy et al (1) noted that other than slight resistance to retropulsion, their patient's external examination gave no hint of the diffuse infiltration of the orbital fat and optic nerves by malignant cells found on neuroimaging and confirmed with orbital biopsy. They suggested the absence of proptosis could be explained by an almost equal replacement of fat by tumor. Similarly, except for bilateral optic disc edema and progressive visual loss, our patient's clinical examination offered no clues to the extent of the orbital and optic nerve involvement found on MRI. Our case differed somewhat in that severe visual loss occurred early and progressed rapidly to complete bilateral blindness despite aggressive therapy. In addition, our pa-tient's MRI demonstrated involvement of the extraocular muscles. That such diffuse infiltration of orbital tissue can FIG. 1. Contrast-enhanced axial (A) and coronal (B) fat-suppressed T1 orbital MRI scans show patchy enhancement of orbital fat, enlargement of the extraocular muscles, and thickening and enhancement of the orbital segments of the optic nerves. Letters to the Editor 94 Doshi et al: J Neuro-Ophthalmol 2011; 31: 94-96 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. occur without proptosis or orbital congestion, and with preservation of eye movements, is striking. Rishi R. Doshi, MD Rona Z. Silkiss, MD, FACS Richard K. Imes, MD California Pacific Medical Center San Francisco, California [e-mail] Supported by the Pacific Vision Foundation, San Francisco, CA. The authors report no conflicts of interest. REFERENCE 1. Stacy RC, Jakobiec FA, Hochberg FH, Hochberg EP, Cestari DM. Orbital involvement in Bing-Neel syndrome. J Neuroophthalmol. 2010;30:255-259. Idiopathic Intracranial Hypertension With Dan and Beyond: The 2010 Jacobson Lecture Ahistorical note apropos of Quincke: In her masterly review of idiopathic intracranial hypertension (1), Friedman stated that Quincke described the lumbar puncture more than 100 years ago yet refers to his report on meningitis serosa (2), the terminological forerunner of idiopathic intracranial hypertension (3). It was in his 1891 articles that Quincke introduced the lumbar puncture (4,5). Felix Tyndel, MD, FRCPC Division of Neurology, University of Toronto Toronto, Ontario, Canada [e-mail] REFERENCES 1. Friedman DI. Idiopathic intracranial hypertension with Dan and beyond: the 2010 Jacobson lecture. J Neuroophthalmol. 2010;30: 380-385. 2. Quincke H.U¨ ber meningitis serosa and verwandte Zusta¨nde. Deutsch Z Nervenheilk. 1897;9:149-168. 3. Pearce JMS. From pseudotumour cerebri to idiopathic intracranial hypertension. Pract Neurol. 2009;9: 353-356. 4. Quincke HI. Ueber Hydrocephalus. Verh Congr Inn Med. 1891;10:321-339. 5. Quincke HI. Die Lumbalpunction des Hydrocephalus. Berl Klin Wochenschr. 1891;28:929-933, 965-968. Cup-to-Disc Ratio in Patients With Idiopathic Intracranial Hypertension Is Smaller Than in Normal Subjects? We read with interest the article by Geddie et al (1) that might better have been titled ‘‘Cup-to-Disc Ratio in Patients With IIH and Frise´n Grade 0-2 Is Smaller Than in Normal Subjects.'' The authors should be commended for tackling a diffi-cult and complicated study. There are a variety of obstacles with a study like this, but a main one is the inclusion of cases with optic disc edema. The authors state that grade 0-2 is minimal or resolved optic disc edema. Frise´n Grade 2 can be mild or moderate but is usually not minimal edema. To test the hypothesis that there is no difference in the vertical cup-to-disc ratio between idiopathic intracranial hypertension (IIH) patients and normal controls, we ana-lyzed data from our prospective study of 50 IIH patients (2). It is well known that as optic disc edema progresses, the optic cup fills in (3). So, in our analysis, we included only Frise´n grade 0 papilledema. Twenty-one of our IIH patients had grade 0 optic disc edema at their final visit. The average cup size was 0.19160.14 in the right eye and 0.18760.13 in the left eye. This compares to the results of Geddie et al of 0.143 in the right eye and 0.127 in the left eye. Another issue is that differences in cup size relate to the grading process itself. This is more subjective than it ap-pears. The grader (B.E.G.) only graded papilledema eyes. No controls were intermixed. Was the grader aware of the hypothesis being tested? If so, could this have influenced the results? It would appear necessary in a study like this for masked graders to evaluate intermixed controls and these values be used rather than controls graded by others. Another confounding factor is that it has been our ex-perience that some swollen optic discs never completely defervesce following treatment for IIH, even when they are Letters to the Editor Wall and Corbett: J Neuro-Ophthalmol 2011; 31: 94-96 95 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. technically grade 0. The mechanism may be either similar to skin not returning to normal after prolonged stretching or the effect of the presence of intermittent, prolonged, mild, increased intracranial pressure. This mechanism, we believe, can also result in a smaller optic cup appearance in IIH. In our opinion, the study of Geddie et al does not ad-equately demonstrate that cup-to-disc ratio is smaller in IIH patients. As stated above, this is a complicated and difficult study to undertake. Ideally, one would want to grade optic disc photographs taken before the onset of IIH. Given that this is not realistic, we urge the authors to reanalyze their data set as follows: 1. Grade a large number of intermixed normal controls with proportions intermixed to reflect racial differ-ences in cup size. 2. Use 3 graders masked to the diagnosis and take the mean of the measures. 3. Limit the analysis to grade 0 optic disc edema, where the disc does not appear elevated on stereoscopic fundus photographs. If this is performed and their results are the same, we would have more confidence in their title and conclusions. Michael Wall, MD James J. Corbett, MD Department of Neurology College of Medicine, University of Iowa Iowa City, Iowa [e-mail] This study was supported by NEI U10 EY017281, a VA Merit Review Grant, and an unrestricted grant to the Department of Ophthalmology, University of Iowa, from Research to Prevent Blindness, New York, NY. REFERENCES 1. Geddie BE, Altiparmak UE, Eggenberger ER. Cup-to-disc ratio in patients with idiopathic intracranial hypertension is smaller than that in normal subjects. J Neuroophthalmol. 2010;30:231-234. 2. Wall M, George D. Idiopathic intracranial hypertension (pseudotumor cerebri): a prospective study of 50 patients. Brain. 1991;114:155-180. 3. Hayreh MS, Hayreh SS. Optic disc edema in raised intracranial pressure. I. Evolution and resolution. Arch Ophthalmol. 1977;95:1237-1244. 96 Wall and Corbett: J Neuro-Ophthalmol 2011; 31: 94-96 Letters to the Editor Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.