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 Table of Contents  
Year : 2022  |  Volume : 2  |  Issue : 4  |  Page : 208-211

Leukemic Optic Neuropathy: A Harbinger of Relapse in Acute Lymphoblastic Leukemia

1 Department of Ophthalmology, Dayanand Medical College and Hospital, Ludhiana, Punjab, India
2 Department of Pediatrics, Dayanand Medical College and Hospital, Ludhiana, Punjab, India
3 Department of Pathology, Dayanand Medical College and Hospital, Ludhiana, Punjab, India

Date of Submission28-Jun-2022
Date of Decision26-Oct-2022
Date of Acceptance31-Oct-2022
Date of Web Publication29-Nov-2022

Correspondence Address:
Dr. Ritesh Verma
3875 Sector 32-A, Chandigarh Road, Ludhiana, Punjab
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ipcares.ipcares_147_22

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Background: Leukemic infiltration of the optic nerve is a neuro-oncologic emergency and also a sign of extramedullary central nervous system relapse. It presents a clinical dilemma in the early stages due to multiple differentials. Patients with leukemia receive radiation and chemotherapy are thus, susceptible to inflammatory, toxic, and infectious causes of optic neuropathy, besides infiltration with tumor cells. Clinical Description: A 15-year-old boy treated for acute lymphoblastic leukemia (ALL) and in remission for 7 months, presented with the unilateral decreased vision for 7 days. A structured evaluation was done, comprising visual acuity, color vision, field of vision, fundus, ophthalmoscopy, ultrasound b-scan, and magnetic resonance imaging of the orbit. The final diagnosis was leukemic infiltration of the optic nerve. Cerebrospinal fluid (CSF) analysis confirmed the presence of atypical lymphocytes. Management: The patient was diagnosed with extramedullary relapse of ALL. Since there are no standard guidelines, a literature review was performed, and the treating team decided to start the patient on stand-alone chemotherapy. Symptomatic resolution became apparent within 10 days. On follow-up, the optic nerve lesion resolved with residual gliosis in the surrounding retina. The CSF has become clear, and the patient is now considered to be in remission. Conclusion: It is important to use a structured clinical approach coupled with investigations to recognize the ocular involvement of ALL (especially in younger patients). There is a need for a regular routine ophthalmological examination in patients in remission for early detection of a relapse. There is a strong felt need for pediatric hemato-oncologists to plan research in this area to generate data so that recommendations for the management of extramedullary relapses are formulated.

Keywords: Central nervous system metastasis, leukemia, optic nerve metastasis, optic neuropathy

How to cite this article:
Verma R, Gidwal K, Kakkar S, Selhi PK, Verma AS. Leukemic Optic Neuropathy: A Harbinger of Relapse in Acute Lymphoblastic Leukemia. Indian Pediatr Case Rep 2022;2:208-11

How to cite this URL:
Verma R, Gidwal K, Kakkar S, Selhi PK, Verma AS. Leukemic Optic Neuropathy: A Harbinger of Relapse in Acute Lymphoblastic Leukemia. Indian Pediatr Case Rep [serial online] 2022 [cited 2023 Apr 2];2:208-11. Available from: http://www.ipcares.org/text.asp?2022/2/4/208/362234

Acute lymphoblastic leukemia (ALL) is a malignancy of B- or T-lymphoblasts characterized by uncontrolled proliferation of abnormal, immature lymphocytes and their progenitors. The replacement of typical cellular components of bone marrow and other lymphoid organs with atypical cells results in the typical manifestations of ALL.[1] These include progressive pallor, petechiae, purpura, generalized lymphadenopathy, and hepatosplenomegaly.

The relapse of ALL in ocular tissues and the central nervous system (CNS) is rare and poses a diagnostic and therapeutic challenge. Due to its rarity, there are no standard guidelines and treatment is generally guided by previous case reports.[2],[3] Leukemic infiltration of the optic nerve is considered an emergency that requires an immediate initiation of therapy, including corticosteroids, chemotherapy, and/or radiation.[4]

We present a case of cerebrospinal fluid (CSF)-proven, isolated, CNS relapse of ALL, in which optic nerve infiltration was the first and sole manifestation. There was a complete resolution of the optic nerve infiltration and remission of the ALL with chemotherapy alone.

  Clinical Description Top

A 15-year-old boy, who was a follow-up case of ALL under treatment presented in the seventh month of remission with the blurring of vision of the right eye and headache for 7 days. The blurred vision was not associated with any ocular pain, congestion, discharge, lesions, foreign body sensation, or preceding trauma. The headache was severe, generalized, and not associated with projectile vomiting or any diurnal variation. There was no history of fever, fatigue, bony pains, rash, or bleeding for any site. Appetite was unaffected. There was a significant history of his receiving chemotherapy as per the ALL-Berlin-Frankfurt-Munich 90 protocol (BFM90), as depicted in [Figure 1].[5] The child was off treatment from 6 months when he presented with the aforementioned symptoms.
Figure 1: The ALL-Berlin-Frankfurt-Munich 90 protocol (BFM90) that the child received. ALL: Acute lymphoblastic leukemia

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The vital parameters at the time of examination were heart rate of 98/min, respiratory rate of 22/min, the temperature of 98.40F, and blood pressure of 110/70 mm Hg (right upper limb, supine position), all of which were normal. The child's weight was 34 kg (on 3rd centile), height 143 cm (<3rd centile), and body mass index was 16.6 kg/m2. There was no pallor, icterus, cyanosis, clubbing, edema, or lymphadenopathy. The testicular examination was normal. The child was conscious, cooperative, and oriented to time, place, and person. The cranial nerve examination did not reveal any involvement except for an absent pupillary reflex on the right side. The sensory and motor system examination was unremarkable. There were no meningeal signs. No additional systemic findings could be documented on the respiratory, cardiovascular, and abdominal examinations.

On structured ocular examination, the visual acuity was 20/60 in the right eye and 20/20 in the left eye. There was no restriction of the ocular motility, and there was no anisocoria, but there was a relative afferent pupillary defect in the right eye. Color vision was also impaired in the right eye, but the confrontation fields were normal. On fundus examination, a large mass lesion measuring 5mm × 4 mm × 2mm with telangiectatic vessels and surrounding splinter hemorrhage in the inferotemporal region was seen in the right eye [Figure 2]a. The left eye was normal. An ultrasound B-scan of the eye was planned, which revealed a dome-shaped homogeneous lesion with medium reflectivity over the optic disc in the right eye [Figure 3]a. These ocular findings were consistent with a diagnosis of optic nerve infiltration secondary to leukemic cells. The clinical implications were a relapse, and further investigations were planned accordingly.
Figure 2: (a) Fundus image of the right eye showing a large mass lesion with surrounding telangiectatic vessels (blue arrow) and hemorrhage (orange arrow) in the inferotemporal region. (b) Postchemotherapy fundus picture showing regression of the optic disc lesion with the presence of refractile bodies inferior to the optic disc (green arrows) and the residual gliotic retinal changes in the area of the tumor (black arrows)

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Figure 3: (a) Ultrasound B-scan axial view of the right eye showing a homogenous dome-shaped lesion with medium internal reflectivity, no posterior shadowing, lying over the optic disc (blue arrow; orange arrow pointing at the optic nerve). (b) A T1-weighted fat-suppressed axial MRI image or the brain and orbits showing a hyperintense lesion overlying the right optic disc associated with mild thickening of the right optic nerve (white arrow). MRI: magnetic resonance imaging

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A complete hemogram revealed predominantly normocytic normochromic red blood cells with no immature cells. The bone marrow biopsy showed a hypocellular marrow exhibiting normal morphology and maturation of all hematopoietic elements with no minimal residual disease.

Contrast-enhanced magnetic resonance imaging of the brain and orbit revealed thickened enhancing multiple cranial nerves and infiltration at the level of optic disc on the right side [Figure 3]b. CSF examination identified malignant cells, thus confirming extramedullary relapse. The patient was classified as extramedullary early relapse (reinduction phase-intermediate risk) and was started on chemotherapy according to the UK ALL R3 protocol.[6]

There was improvement in vision and resolution of headache by day 10 posttreatment. He was discharged and kept under a close follow-up. At the 6-month visit, his visual acuity has improved to 20/30, the fundus examination showed a complete regression of the optic disc lesion with the presence of refractile bodies inferior to the optic disc, and the residual gliotic retinal changes in the area of the tumor [Figure 2]b. Subsequent CSF serial analysis was free of malignant cells.

  Discussion Top

Leukemic infiltration of the optic nerve is a neuro-oncologic emergency and a sign of extramedullary CNS relapse. It is uncommon and presents a clinical dilemma in the early stages since it may mimic other etiologies, besides nerve infiltration with tumor cells. Since patients with leukemia are subjected to radiation and strong intravenous chemotherapeutic agents, they are susceptible to inflammatory, toxic, and infectious causes of optic neuropathy. Therefore, in such a setting, a detailed history and examination are invaluable in deciding the direction of the investigation. In our case, the presence of a large mass lesion made the diagnosis of leukemic infiltration quite obvious. However, it can be quite challenging in the early stages when the only sign is optic disc edema. Then, it becomes imperative to rule out the other probable causes of optic nerve infiltration.

An invasive intravitreal biopsy can also be done in cases of clinical suspicion of ocular involvement. A literature review by Myers et al.[4] showed that optic neuropathy was the initial presentation in only two of the 19 patients of ALL with infiltrative optic neuropathy, and eight had malignant cells in the CSF. Most of the previously published reports had a presumptive diagnosis of optic nerve infiltration, and a biopsy had been performed in only one case.

Another important aspect to consider is the age. In this case, the patient was old enough to express his visual impairment, but this might be missed in younger children with ALL. Isolated infiltrative optic neuropathy is most commonly seen in ALL and B-cell nonHodgkin's lymphoma (NHL), though it has also been reported with acute myeloid leukemia, chronic myelogenous leukemia, T-cell NHL, Hodgkin's lymphoma, and histiocytic lymphoma.[4],[7]

Therefore, we suggest that all patients with leukemia must undergo a baseline ophthalmological examination and a repeat exam every 3 months, or earlier if any visual symptoms develop. A long-term follow-up study of patients in the remission phase of ALL can help establish standardized guidelines for follow-up and management of patients presenting with optic nerve infiltration. With respect to management, in four of the case reports reviewed by Myers et al., ALL patients with optic nerve involvement were treated with adjunct radiotherapy based on the hypothesis that drug delivery is limited across the blood-ocular barrier.[8],[9],[10],[11] There were only two cases, besides ours, in which the patients with ocular involvement had recovered fully with chemotherapy alone.[12],[13]

The aim of this report was to highlight the two aspects of the management of children with ALL, which may get overlooked if not actively sought. First, the importance of using a structured clinical approach coupled with investigations to recognize ocular involvement of ALL (especially in younger patients); and second, the need for a regular routine ophthalmological examination in patients in remission so that a relapse may be detected early. Obviously, the findings of a single case report or review cannot be generalized for the management of similar cases. There is a strong felt need for pediatric hemato-oncologists to plan cohort studies to identify patients at high risk of extramedullary relapse and generate data so that recommendations for management can come into existence.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Roberts KG. Genetics and prognosis of ALL in children versus adults. Hematology Am Soc Hematol Educ Program 2018;2018:137-45.  Back to cited text no. 1
Pui CH, Howard SC. Current management and challenges of malignant disease in the CNS in paediatric leukaemia. Lancet Oncol 2008;9:257-68.  Back to cited text no. 2
Patel SA. Acute myeloid leukemia relapse presenting as complete monocular vision loss due to optic nerve involvement. Case Rep Hematol 2016;2016:3794284.  Back to cited text no. 3
Myers KA, Nikolic A, Romanchuk K, et al. Optic neuropathy in the context of leukemia or lymphoma: Diagnostic approach to a neuro-oncologic emergency. Neurooncol Pract 2017;4:60-6.  Back to cited text no. 4
Xie Y, Zhang Y, Zheng W, et al. Outcomes of dose-adjusted Berlin-Frankfurt-Münster-90 regimen without radiotherapy in adolescents and adults with T cell lymphoblastic lymphoma. Med Oncol 2015;32:110.  Back to cited text no. 5
Parker C, Waters R, Leighton C, et al. Effect of mitoxantrone on outcome of children with first relapse of acute lymphoblastic leukaemia (ALL R3): An open-label randomised trial. Lancet 2010;376:2009-17.  Back to cited text no. 6
Charif Chefchaouni M, Belmekki M, Hajji Z, et al. Ophthalmic manifestations of acute leukemia. J Fr Ophtalmol 2002;25:62-6.  Back to cited text no. 7
Lin YC, Wang AG, Yen MY, et al. Leukaemic infiltration of the optic nerve as the initial manifestation of leukaemic relapse. Eye (Lond) 2004;18:546-50.  Back to cited text no. 8
Hu A, Chan AT, Micieli JA. Complete recovery of vision after optic nerve relapse of acute lymphoblastic leukemia. Can J Neurol Sci 2020;47:431-3.  Back to cited text no. 9
Bandyopadhyay S, Das D, Das G, et al. Unilateral optic nerve infiltration as an initial site of relapse of acute lymphoblastic leukemia in remission. Oman J Ophthalmol 2010;3:153-4.  Back to cited text no. 10
[PUBMED]  [Full text]  
Nagpal MP, Mehrotra NS, Mehta RC, et al. Leukemic optic nerve infiltration in a patient with acute lymphoblastic leukemia. Retin Cases Brief Rep 2016;10:127-30.  Back to cited text no. 11
Caty J, Grigorian AP, Grigorian F. Asymptomatic leukemic optic nerve infiltration as presentation of acute lymphoblastic leukemia relapse. J Pediatr Ophthalmol Strabismus 2017;54:e60-2.  Back to cited text no. 12
da Costa DR, Fernandes RD, Susanna FN, et al. Complete reversal of bilateral optic nerve infiltration from lymphoblastic leukemia using chemotherapy without adjuvant radiotherapy. BMC Ophthalmol 2021;21:335.  Back to cited text no. 13


  [Figure 1], [Figure 2], [Figure 3]


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