Acute lymphoblastic leukemia is the most common malignant disease of childhood, with a median age at diagnosis of 2 to 3 years. Prognosis is heavily correlated to age at diagnosis, with a 90% 5-year survival rate in children diagnosed at younger than the age of 15 years and a 75% 5-year survival rate for children diagnosed between the ages of 15 and 19 years. Risk factors include radiation exposure, inherited mutations that damage DNA repair, and conditions such as Down syndrome, neurofibromatosis, and ataxia telangiectasia, although most patients have no identifiable risk factors.
Leukemia can recur anywhere in the body and can involve any structure of the eye.1 Therefore, ophthalmologists should maintain a high level of suspicion for leukemia recurrence. Isolated optic nerve infiltration by leukemic cells has rarely been reported as an initial presentation of disease recurrence.2,3
We present the case of a 4-year-old boy with a history of pre-B cell acute lymphoblastic leukemia involving the central nervous system diagnosed at the age of 2 years. He had an isolated central nervous system relapse 11 months after diagnosis during the first maintenance cycle with a reportedly abnormal left optic nerve. He was considered to be at intermediate risk after his early relapse. He was lost to follow-up when his family moved across the country and was admitted to our institution 14 months later. At that time, he was diagnosed as having pre-acute lymphoblastic leukemia because his peripheral smear showed 1% blasts, with 5% blasts considered diagnostic for a relapse. Ophthalmology was consulted due to his history of central nervous system involvement.
The patient was found to have visual acuity of 20/30 by Allen in both eyes, which was normal for his age. Color vision by Hardy–Rand–Rittler was normal in each eye and pupils were equally reactive to light and accommodation without relative afferent pupillary defect. Anterior segments of both eyes and fundus examination of the right eye were normal. Fundus examination of the left eye revealed a fluffy white mass obscuring the optic disc with peripapillary vascular sheathing (Figure 1).
Fundus photograph of the left eye showing a fluffy white mass (arrow) covering the optic nerve head.
The magnetic resonance imaging (MRI) scans of the brain and orbits did not demonstrate any enhancement of the optic nerves or brain tissue (Figure 2). Cerebrospinal fluid revealed rare cells suspicious for blasts. The patient was treated with intrathecal methotrexate and vincristine in addition to his chemotherapy protocol, and did not receive ocular radiation due to the asymptomatic nature of the condition to preserve his vision. He was monitored closely.
Axial contrast magnetic resonance imaging of the orbits showing normal optic nerves. Left eye demonstrates non-enhancing mass covering the optic disc (arrow).
Three weeks later, visual acuity was preserved and the optic nerve mass disappeared and was replaced by gliosis with good visualization of the optic nerve head (Figure 3). Fluorescein angiography was normal without neovascularization (Figure 4). Cerebral spinal fluid pathology showed blasts, and relapse of acute lymphoblastic leukemia was confirmed with hypercellular bone marrow. The patient was treated with chemotherapy for the next 6 months and his good vision was maintained.
Optic nerve head glial scar (arrow) and peripapillary vascular sheathing 3 weeks after starting intrathecal methotrexate.
Fluorescein angiography 3 weeks after starting intrathecal methotrexate represents normal fluorescein uptake confirming the complete resolution of the optic nerve leukemic infiltrate. There is no residual tumoral lesion at the level of the optic nerve. There is no optic nerve enhancement seen in the (A) retinal arterial, (B) capillary transition, (C) early venous, or (D) late venous stages.
Our patient had asymptomatic optic nerve infiltration with preserved visual acuity, color vision, and pupillary function. Most interestingly, the lesion resolved completely with intrathecal methotrexate, with complete preservation of vision. Previous cases reported have been treated with urgent radiation of the eye due to reported risks of compression necrosis or vascular occlusion.2–6 This treatment caused decreased vision due to radiation neuropathy and atrophy. In the current case, we decided to monitor closely and avoid the risks of radiation.
Another particular finding in this patient was the non-enhanced appearance on MRI. One would expect optic nerve enhancement with leukemic infiltration; however, studies have shown that this occurs in only 20% of cases.7 The role of screening MRI in leukemia survivors has not been established, but clinicians should be aware that optic nerve infiltration can occur even with a normal MRI scan.7
Optic nerve infiltration may be the first sign of acute lymphoblastic leukemia relapse. In our case, the vision, color vision, and pupillary reflexes were normal and consistent throughout the evolution of the disease. Of note, the absence of enhancement on MRI does not exclude neoplastic infiltration. We recommend routine ophthalmological examinations for all patients with a history of acute lymphoblastic leukemia to exclude optic nerve involvement without systemic symptoms or signs.
- Sharma T, Grewal J, Gupta S, Murray PI. Ophthalmic manifestations of acute leukaemias: the ophthalmologist's role. Eye (Lond). 2004;18:663–672. doi:10.1038/sj.eye.6701308 [CrossRef]
- 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. doi:10.1038/sj.eye.6700701 [CrossRef]
- Bandyopadhyay S, Das D, Das G, Gayen S. Unilateral optic nerve infiltration as an initial site of relapse of acute lymphoblastic leukemia in remission. Oman J Ophthalmol. 2010;3:153–154. doi:10.4103/0974-620X.71902 [CrossRef]
- Nikaido H, Mishima H, Ono H, Choshi K, Dohy H. Leukemic involvement of the optic nerve. Am J Ophthalmol. 1988;105:294–298. doi:10.1016/0002-9394(88)90013-X [CrossRef]
- Lin HF, Dai MS, Kao WY, Chao TY. Unilateral optic nerve leukemic infiltration with sudden vision loss heralding a systemic relapse of acute lymphoblastic leukemia [article in Chinese]. Journal of Medical Sciences (Taiwan). 2005;25:97–100.
- Camera A, Piccirillo G, Cennamo G, et al. Optic nerve involvement in acute lymphoblastic leukemia. Leuk Lymphoma. 1993;11:153–155. doi:10.3109/10428199309054745 [CrossRef]
- Porter RP, Kaste SC. Imaging findings of recurrent acute lymphoblastic leukemia in children and young adults, with emphasis on MRI. Pediatr Radiol. 2004;34:400–408. doi:10.1007/s00247-003-1137-9 [CrossRef]