Fall 2017 Newsletter

Follow our latest updates in our Summer 2019 Newsletter

Fall 2017 Newsletter
7th Residency Announcement

Exciting Residency Announcement!

ACGME approves seventh resident complement; first increase in over 30 years!

Grand Rounds

Grand Rounds and Case Studies

Check out our weekly presentations

OTEP

OTEP

Ophthalmic Technician Education Program

LARGEST STUDY ON CHINESE AMERICANS PUBLISHED

LARGEST STUDY ON CHINESE
AMERICANS PUBLISHED

USC Ophthalmology Researchers Find More
Effective Treatments For Blinding Eye Diseases

EDUCATION

Case Study: Blast from the past, ALL is no good

Presenter: Siwei Zhou, MD Discussant: Kimberely Gokoffski, MD, PhD
 

History

  • 52-year-old Filipino male presents for the evaluation of vision loss in the right eye
    • 10 days prior to presentation he started to develop graying in his vision lasting 30 minutes at a time. This progressively worsened in severity and duration, lasting for hours
    • 5 days prior to presentation, his vision completely went dark in the right eye
  • He was treated for orbital cellulitis at an outside hospital without improvement
  • Past medical history: Acute lymphocytic leukemia diagnosed in 2013, Philadelphia chromosome positive
    • Status post allogenic bone marrow transplant and full body radiation in 2014
    • Two prior relapses, including CNS relapse, currently achieved second remission
    • Current treatment: Intrathecal cytarabine and PO dasatinib

Exam Findings

  • VA
    • OD: NLP
    • OS: 20/30
  • Pupils
    • OD: Amaurotic
    • OS: Reactive
  • Ishihara color plates
    • OD: 0/8
    • OS: 7/8
  • Motility
    • OD: -2 supraduction, -2 abduction, -2 abduction, -3 infraduction
    • OS: Full OS
  • Alignment: 20 XT in primary
  • CN: V1, V2, V3, 7 symmetric
  • Pertinent anterior segment exam:
    • OD: Mild erythema and edema of upper and lower eyelids without significant proptosis, mild resistance to retropulsion, trace injection with no chemosis
    • OS: Unremarkable
  • Dilated Fundus Exam
    • OD: Significant optic disc edema with congestion, 360 degree flame and dot blot hemorrhages throughout, resembling blood and thunder appearance. Relative whitening of the retina. Areas of elevated retina consistent with serous retinal detachment
    • OS: 360 degree optic disc elevation with blurred disc margins, no obscuration of disc vessels. Lumpy bumpy appearance of optic nerve, superotemporal flame hemorrhage. Hemorrhage along superior arcade with white center. Scattered hemorrhages in all 4 quadrants in the periphery.
Figure 1: In leukemic infiltration of the optic disc, the features of the disc are obscured by a whitish fluffy infiltrate that is often associated with true disc swelling and peripapillary hemorrhage (Fig. 8.16B). The visual acuity in such patients is minimally affected unless the infiltration or associated edema and hemorrhage extend into the macula.
Figure 2: Infiltration of the proximal optic nerve just posterior to the lamina cribrosa usually produces markedly decreased visual acuity associated with true optic disc swelling. Such patients have a variety of visual field defects, and a relative afferent pupillary defect is invariably present unless the infiltration is bilateral and symmetric. In addition, there are often peripapillary and peripheral retinal hemorrhages.

 

Differential Diagnosis

  • Inflammatory:
    • Sarcoidosis
    • IgG4 disease
    • Idiopathic orbital inflammation
    • Thyroid ophthalmopathy
  • Infectious:
    • Tuberculosis
    • Syphilis
    • Invasive fungal sinus infection
  • Neoplastic:
    • Primary Tumors:
      • Invasive head and neck tumors
      • Neurofibroma, meningioma
    • Secondary Tumors:
      • Metastasis
      • New leukemia
      • Lymphoma

Additional Investigations

  • B-scan: confirmed serous retinal detachments OD
  • OCT RNFL:
    • OD: Poor signal strength, segmentation error
    • OS: Moderate signal strength, average RNFL thickness 158, diffuse edema
  • HVF:
    • OD: Unable
    • OS: Moderate reliability, infero-central scotoma with scattered superior depression
  • MRI brain and orbits with and without contrast:
    • T1 post-contrast with fat suppression axial cuts through the orbits demonstrates ring of enhancing soft tissue circumferentially surrounding both optic nerves, extending along the entire length of both optic nerves into the orbital apices
    • There is also a 4 mm nodular enhancing focus at the right optic disc and 1 mm enhancing focus at the left optic disc
  • Lumbar punctures:
    • Initial: 2 WBC, 241 RBC, normal protein and glucose, CSF cytology negative for malignant cells
    • Repeat 4 days later: Cytology positive for malignant cells
Figure 3: On T2 weighted sequence– can more obviously see 1 focus at the left optic disc – also enhances post-contrast.

Diagnosis

  • Leukemic infiltration of bilateral optic nerves, OD greater than OS
  • Infiltrative orbitopathy OD
  • Secondary:
    • CRVO OD
    • Ophthalmic artery occlusion OD
    • Serous retinal detachment OD

Pathophysiology

  • Acute lymphoblastic leukemia (ALL) is a malignant transformation of cells destined to be a lymphocyte, which occurs at the level of the bone marrow, and affects the lymphoid stem cell lineage, predominantly affecting immature cells
  • The eye is an immunoprivileged site, often with poor penetration of chemotherapeutic agents, and therefore cannot be a site of clinical recurrence in the setting of systemic remission
  • Most ophthalmic changes seen in leukemia and lymphoma are secondary, resulting from the sequala of immature/dysplastic cells or as an effect of chemotherapy, including anemia, thrombocytopenia, hyperviscosity
    • These changes are typically seen in the retina, including intraretinal hemorrhages, white centered hemorrhages, dilated tortuous veins, cotton-wool spots, vitreous hemorrhage, central retinal vein occlusion
    • Typically do not need dedicated treatment
  • Primary ophthalmic changes, resulting from direct infiltration of leukemic cells
    • These include orbital infiltration (proptosis), optic nerve infiltration, choroidal infiltration (serous retinal detachments)
    • Require further localized treatment
  • Infiltration of the optic nerve can occur with 2 distinct clinical appearance, with the dividing anatomic structure being of the lamina cribrosa
    • Infiltration at the optic disc head anterior to the lamina cribrosa: The features of the disc are obscured by a whitish fluffy infiltrate, or cheesy appearance, often associated with true disc swelling and peri-papillary hemorrhage. The visual acuity in such patients is typically minimally affected unless the infiltration or associated edema and hemorrhage extend into the macula
    • Infiltration of the immediate retro-laminar portion of the proximal optic nerve: The appearance is that of true optic disc swelling, usually with marketed the decreased visual acuity, a variety of visual field defects, and a relative afferent pupillary defect, unless the infiltration is bilateral and symmetric. There may also be peri-papillary and peripheral retinal hemorrhages
  • The classic definition of CNS involvement in lymphoma and leukemia includes the presence of leukemic blasts in CSF, or greater than 5 mononuclear cells/millimeter cubed of CSF
    • 95% specificity
    • 50% sensitivity
    • Often numerous high-volume lumbar puncture are required to demonstrate CNS involvement and optic nerve infiltration, often delaying or confounding the diagnosis
  • Other definitions of CNS involvement also include imaging documenting lesions consistent with leukemia, including cranial nerve enhancement, or brain and spinal lesions related to leukemia or lymphoma
    • Typical MRI findings in patients with leukemia and positive CSF cytology
      • Pachymeningeal enhancement (29%)
      • Leptomeningeal enhancement (19%)
      • Cranial nerve enhancement (29%)
      • Mass-like enhancement (10%)
    • However, around 25% of patients with positive CNS cytology do not MRI findings
  • A last resort to diagnose optic nerve infiltration can include optic nerve sheath biopsy, however, most surgeons/clinicians will advocate for at least 3 large volume lumbar punctures to be sent for cytology prior to pursuing biopsy of tissue

Treatment

  • Optic nerve infiltration is a neuro oncologic emergency, requiring:
    • Emergent orbital and whole brain radiation
    • Pulse dose steroids
    • Systemic and intrathecal chemotherapy
  • Timely diagnosis and treatment is essential, as delaying treatment can lead to irreversible blindness

Prognosis and Future Directions

  • Overall, CNS involvement is a poor prognostic factor in leukemia and lymphoma
  • Timely diagnosis and treatment is essential, as delaying treatment can lead to irreversible blindness and overall mortality
  • Given the poor sensitivity of CSF cytology, there have been investigations of other methods to detect malignant cells in CSF
    • Flow cytometry
    • lactate dehydrogenase isozyme 5
    • β2-microglobulin
    • immunoglobulin heavy chain rearrangement
  • Positive CSF cytology and tissue biopsy remain the current gold standards for diagnosis of CNS involvement

References

  • Miller NR, Subramanian PS, Patel VR. Walsh & Hoyt’s Clinical Neuro-ophthalmology, The Essentials, Third Edition. Wolters Kluwer. 2016:61-69.
  • Reddy, S. C., Jackson, N., & Menon, B. S. (2003). Ocular Involvement in Leukemia – A Study of 288 Cases. Ophthalmologica, 441–445.
  • Myers, K. A., Nikolic, A., Romanchuk, K., Weis, E., Brundler, M., Lafay-cousin, L., & Costello, F. (2017). Neuro-Oncology Practice lymphoma : diagnostic approach to a neuro-oncologic emergency. Neuro-Oncology Practice, 4(1), 60–66.
  • Thomas, X., Le, Q., Thomas, X., & Le, Q. (2013). Central nervous system involvement in adult acute lymphoblastic leukemia Central nervous system involvement in adult acute lymphoblastic leukemia. Hematology, 8454.
  • Ellis, W., & Little, H. L. (1973). Leukemic Infiltration of the Optic Nerve Head. American Journal of Ophthalmology, 75(5), 867–871.
  • Guenette JP, Tirumani SH, Keraliya AR, Shinagare AB, Ramaiya NH, Jagannathan JP (2016) MRI findings in patients with leukemia and positive CSF cytology: a single-institution 5-year experience. AJR Am J Roentgenol 207:1278–1282.
  • Cheung, M., Fang, B., & Lee, R. (2019). Optic neuropathy as the first sign of central nervous system relapse in acute myeloid leukaemia: MRI findings and its diagnostic challenge. BMJ Case Reports, 1–4.
  • Khan K, Malik AI, Almarzouqi SJ, Morgan ML, Yalamanchili S, Chevez- Barrios P, Lee AG (2016) Optic neuropathy due to chronic lymphocytic leukemia proven with optic nerve sheath biopsy. J Neuroophthalmol 36(1):61–66.
  • Ahluwalia MS, Wallace PK, Peereboom DM. Flow cytometry as a diagnostic tool in lymphomatous or leukemic meningitis: ready for prime time? Cancer. 2012;118(7):1747-175322025088.
  • Scott BJ, Douglas VC, Tihan T, Rubenstein JL, Josephson SA. A Systematic Approach to the Diagnosis of Suspected Central Nervous System Lymphoma. JAMA Neurol. 2013;70(3):311–319. doi:10.1001/jamaneurol.2013.606.

Contact

Section Editors

Scroll Up To Top

USC Roski Eye Institute

1450 San Pablo St., 4th Floor,
Los Angeles, CA 90033
323-442-6335

USC Roski Eye Institute
Arcadia

65 N. First Ave., Suite 101,
Arcadia, CA 91006
626-446-2122

USC Roski Eye Institute
Pasadena

625 S. Fair Oaks Ave., Suite 400,
Pasadena, CA 91105
323-442-6335

USC Roski Eye Institute
USC Village

835 W. Jefferson Blvd., Suite 1720
Los Angeles, CA 90089
213-740-6960

Children’s Hospital
Los Angeles

4650 Sunset Blvd.,
Los Angeles, CA 90027
323-660-2450

View Full Desktop Version

Coronavirus (COVID-19) Announcement

Due to ongoing developments with COVID-19, we are only able to see patients with urgent eye problems at this time. If you have any questions or concerns, please call us at 323-442-6335.