OD: Mild erythema and edema of upper and lower eyelids without significant proptosis, mild resistance to retropulsion, trace injection with no chemosis
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.
Idiopathic orbital inflammation
Invasive fungal sinus infection
Invasive head and neck tumors
B-scan: confirmed serous retinal detachments OD
OD: Poor signal strength, segmentation error
OS: Moderate signal strength, average RNFL thickness 158, diffuse edema
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
Initial: 2 WBC, 241 RBC, normal protein and glucose, CSF cytology negative for malignant cells
Repeat 4 days later: Cytology positive for malignant cells
Leukemic infiltration of bilateral optic nerves, OD greater than OS
Infiltrative orbitopathy OD
Ophthalmic artery occlusion OD
Serous retinal detachment OD
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
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
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
lactate dehydrogenase isozyme 5
immunoglobulin heavy chain rearrangement
Positive CSF cytology and tissue biopsy remain the current gold standards for diagnosis of CNS involvement
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