Optic Neuropathy due to Chronic Lymphocytic Leukemia Proven With Optic Nerve Sheath Biopsy and Chronic Myelogenous Leukemia Relapse Presenting With Central Nervous System Blast Crisis and Bilateral Optic Nerve Infiltration: Comment

Letters to the Editor Optic Neuropathy due to Chronic Lymphocytic Leukemia Proven With Optic Nerve Sheath Biopsy and Chronic Myelogenous Leukemia Relapse Presenting With Central Nervous System Blast Crisis and Bilateral Optic Nerve Infiltration: Comment W e read with great interest the articles by Khan et al (1) and Mbekeani et al (2) entitled "Optic neuropathy due to chronic lymphocytic leukemia proven with optic nerve sheath biopsy" and "Chronic myelogenous leukemia relapse presenting with central nervous system blast crisis and bilateral optic nerve infiltration," respectively. We found these articles intriguing and particularly pertinent to a case in which we struggled over the correct therapy. A 30-year-old woman reported a 2-month history of buttock pain radiating down her left leg and a 1-month history of painless progressive visual loss in her left eye. She denied any previous ophthalmic problems. She had a history of acute myelogenous leukemia (AML), and 9 months ago she had received induction chemotherapy and 4 cycles of consolidation chemotherapy resulting in complete remission. Examination showed a visual acuity of 20/25, right eye and count fingers, left eye. Color vision was normal in the right eye but the patient could not identify any of the Ishihara color plates with the left eye. There was a left relative afferent pupillary defect (RAPD). Confrontation visual field was normal in the right eye and severely constricted in the left eye. Ocular motility was normal, and there was no ptosis or proptosis. Trigeminal and facial nerves were intact. Anterior and posterior segment examinations were unremarkable. Contrastenhanced fat-suppressed brain and orbital magnetic resonance imaging (MRI) studies showed focal enlargement and enhancement of the intracranial segment of the left optic nerve (Fig. 1A), and gadolinium-enhanced MRI of the lumbar spine and sacrum showed diffuse leukemic vertebral body marrow infiltration, enlargement and enhancement of lower exiting lumbar nerve roots as well as distal cauda equina nerve roots, and enlargement of the S1 and S2 nerve roots bilaterally (Fig. 1B). The patient was admitted to the hospital, prescribed high dose IV methylprednisolone, and received intravenous cytarabine (Ara-C) 4,600 mg over 3 hours every 12 hours and a 70-mg intrathecal injection of Ara-C. The patient's vision did not improve over the next 5 days, and we thought we would have to consider radiotherapy. However, on day 7, to our amazement, the patient's left visual acuity was 20/20 with normalization of the rest of the neuro-ophthalmologic examination including a lack of an RAPD. A variety of therapies have been proposed for leukemic infiltration of the optic nerve for chronic lymphocytic leukemia, chronic myelogenous leukemia, and AML including intrathecal chemotherapy and radiotherapy (1-6). Our case supports the observations of Khan et al (1) and Mbekeani et al (2) that chemotherapy alone may be enough to restore normal acuity and radiotherapy may not be necessary, at least initially during the acute episode of visual loss. Michael S. Vaphiades, DO Lina Nagia, DO Elizabeth B. Keeble, MD Glenn H. Roberson, MD Departments of Ophthalmology (MSV, LN, EK) and Radiology (GR), University of Alabama, Birmingham, Alabama The authors report no conflicts of interest. FIG. 1. Postcontrast axial T1 magnetic resonance imaging with fat suppression reveals thickening and enhancement of the prechiasmal portion of the left optic nerve (arrow) (A), and enlargement of the spinal sacral nerve roots (arrows) (B). Letters to the Editor: J Neuro-Ophthalmol 2016; 36: 221-229 223 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Letters to the Editor REFERENCES 1. Khan K, Malik AI, Almarzouqi SJ, Morgan ML, Yalamanchili S, Chevez-Barrios P, Lee AG. Optic neuropathy due to chronic lymphocytic leukemia proven with optic nerve sheath biopsy. J Neuroophthalmol. 2016;36:61-66. 2. Mbekeani JN, Fattah MA, Nounou RA, Chebbo W, Dogar MA. Chronic myelogenous leukemia relapse presenting with central nervous system blast crisis and bilateral optic nerve infiltration. J Neuroophthalmol. 2016;36:73-77. 3. Hon C, Ma ES, Yau K, Au WY. CNS manifestations of malignancies: case 3. Leukemic optic neuropathy Diagnostic Algorithm for Patients With Suspected Giant Cell Arteritis: Comment B ecause of my long term interest in giant cell arteritis (GCA), I feel compelled to comment on the study by El-Dairi et al (1) dealing with "Diagnostic algorithm for patients with suspected giant cell arteritis." Their conclusions were based on retrospective study of 204 patients with temporal artery biopsy (TAB) for GCA. We did a similar, but a prospective study of 363 patients with TAB for GCA (2), and other studies of GCA patients examining ocular manifestations (3), occult GCA (4), and also in 408 patients (121 with positive and 287 with negative TAB) with thrombocytosis (5). To begin with, the report by El-Dairi et al was based on retrieval of a "pathology electronic data base" and "corresponding electronic and paper medical records" of 204 patients-49 with positive TAB results and 12 "suggestive." The authors admit that "medical records reviewed may have had incomplete documentation of symptoms, signs, and laboratory results and a number of patients were not tested for C-reactive protein (CRP) and platelet count, and the clinical examination of the superficial temporal artery was not always documented." In our study of 363 patients (106 with positive and 257 with negative TAB for GCA), at initial visit all underwent a complete physical and hematologic evaluation, and TAB, in our department. Length of temporal artery specimen and serial sectioning are important to eliminate "skip areas." In the study by El-Dairi and colleagues, pathologic study of TAB was based on retrospective retrieval of the biopsy information. The length of most of the biopsy specimens was less than 1 inch and in one case only "9 mm" (0.36 inch); they examined 10 slides and "500 mm" of "6-10 cross sections" only. In our study, TAB specimen was at least 1 inch long and all had serial sectioning. In addition, two-thirds of their patients with positive TAB were on corticosteroid therapy before TAB-10 of them for more than 3 weeks, 8 for more than 2 months, and 2 for more than 1 year. We know that corticosteroid therapy rapidly ameliorates systemic, hematologic, and histopathologic parameters. Our patients were evaluated before the start of corticosteroid therapy. 224 complicating leukemia cutis. J Clin Oncol. 2005;23:4229- 4230. 4. Lin YC, Wang AG, Yen MY, Hsu WM. Leukaemic infiltration of the optic nerve as the initial manifestation of leukaemic relapse. Eye (Lond). 2004;18:546-550. 5. Madani A, Christophe C, Ferster A, Dan B. Peri-optic nerve infiltration during leukaemic relapse: MRI diagnosis. Pediatr Radiol. 2000;30:30-32. 6. Sharma T, Grewal J, Gupta S, Murray PI. Ophthalmic manifestations of acute leukaemias: the ophthalmologist's role. Eye (Lond). 2004;18:663-672. Our study showed a very different prevalence of systemic signs and symptoms from that in the study by El-Dairi et al. We found the following statistically significant differences between those with positive TAB for GCA and those with negative biopsy: jaw claudication (P , 0.0001), neck pain (P = 0.0003), anorexia/weight loss (P = 0.0005), and fever (P = 0.040). Scalp tenderness was almost significant (P = 0.058). On further analysis, we found that odds of a positive TAB were 9.0 times greater with jaw claudication (P , 0.0001), 3.4 times with neck pain (P = 0.0085), 2.0 times with an erythromycin sedimentation rate (ESR) of 47- 107 mm/hour (P = 0.0454), 3.2 times with CRP above 2.45 mg/dL (P = 0.0208) and 2.0 times for age 75 years or more (P = 0.0105). In addition, we reported our findings on occult GCA (4), where patients have no systemic symptoms at all and visual loss is the only presenting symptom; in them GCA is sometime missed, because of a firm belief that all GCA patients must have systemic symptoms and/or elevated ESR. With regard to headache, El-Dairi et al attributed the following statement to our study: "A new onset of severe headache had been reported in approximately two-thirds of patients with GCA"; this is not true. We stated that a history of any type of headache (not "new onset of severe headache") was present in 55.7% of patients with positive TAB and 45.5% with negative TAB (P = 0.084). El-Dairi et al concluded that when a patient had only 1 positive finding in their algorithm for TAB, "evaluate for alternative diagnosis." Yet according to our study, in persons 50 years and older, the presence of jaw claudication alone is a strong indication for TAB. Also, in persons 50 years and older, suspicion for GCA should be high in patients presenting with recent onset of recurrent episodes of amaurosis fugax, anterior ischemic optic neuropathy, central retinal artery occlusion, cilioretinal artery, or ocular ischemic syndrome. Fundus fluorescein angiography should be performed promptly in all of them to demonstrate evidence of posterior ciliary artery occlusion, because its presence indicates GCA unless proven otherwise. El-Dairi et al performed fluorescein angiography in only 7 of their patients. However, it is not clear when in the clinical course, angiography was performed. If it was done weeks after the onset of visual loss, collateral circulation in the choroid may have been established, which can result in misleading information (6). Letters to the Editor: J Neuro-Ophthalmol 2016; 36: 221-229 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.