Enhanced depth imaging optical coherence tomography of precursor cell leukemic choroidopathy before and after chemotherapy.

Serous retinal detachment (SRD) can be the initial manifestation of leukemia. Herein, we explore the retinal and choroidal features on enhanced depth imaging optical coherence tomography (EDI-OCT) of SRD in a patient with undiagnosed leukemia. A 23-year-old male developed blurred visual acuity of 20/200 in the right eye oculus dexter (OD) and 20/200 in the left eye oculus sinister (OS). Funduscopically, he manifested serous macular detachment in both eyes oculi uterque (OU) without hemorrhagic retinal abnormalities. EDI-OCT disclosed macular detachment OU and homogeneous, marked choroidal opacification with thickening to 724 μm OD and estimated >600 μm OS and with loss of choroidal detail OU. Peripheral blood smears revealed severe thrombocytopenia and normal leukocyte count. Peripheral cytochemisty, immunophenotyping, and bone marrow aspirate confirmed the presence of atypical lymphoblasts, fulfilling criteria for precursor cell leukemia. Following systemic chemotherapy, the visual acuity improved to 20/25 OD and 20/20 OS. On EDI-OCT, the choroidal thickening resolved to 431 um OD and 443 um OS, leaving a normal choroidal appearance. Massive choroidal infiltration with leukemic cells could be the cause of serous macular detachment found in patients with newly diagnosed leukemia.

INTRODUCTION

Approximately 90% of patients with leukemia have ophthalmic manifestations, of which there are two major categories, including (A) primary (direct) leukemic infiltration and (B) secondary (indirect) involvement.12 Primary involvement includes infiltration into any tissue of the eye, orbit, or cranial nerves while secondary involvement is a consequence of associated hematologic abnormalities such as anemia, thrombocytopenia, hyperviscosity, or immunosuppression. Recently, the presence of leukemic retinopathy has been demonstrated to be associated with a poorer systemic prognosis.34

Serous retinal detachment (SRD) is a rare manifestation of leukemia, 1st reported in 1963 by Blodi5 and 1964 by Zimmerman and Thoreson6 in the setting of acute disease. Histopathological studies of leukemia patients with SRD have disclosed choroidal thickening and patchy choroidal infiltration of tumor cells presumed to cause retinal pigment epithelial (RPE) alterations and subsequent development of subretinal fluid.578 In 2012, Bajenova et al. described the relationship of serous macular retinal detachment with acute lymphocytic leukemia and observed choroidal thickening with enhanced depth imaging optical coherence tomography (EDI-OCT).9 Similar to prior histopathologic studies, this finding implied that the choroidal infiltration was in part responsible for accumulation of subretinal fluid. Herein, we describe a unique case in which the patient was preleukemic without elevated white cell count, but was found to have EDI-OCT choroidal infiltration of preleukemic cells as a cause for serous macular detachment.

CASE REPORT

A previously healthy 23-year-old Caucasian male noted a 1-week history of central vision loss and headache. On examination, best-corrected visual acuity was 20/200 in the right eye oculus dexter (OD) and 20/150 in the left eye oculus sinister (OS). There was no afferent pupillary defect. The anterior segment was unremarkable. Dilated fundus examination disclosed serous macular detachment in both eyes oculi uterque (OU) with no visible abnormality in the choroid and without retinal hemorrhages [Figure 1]. Systemic evaluation revealed history of cutaneous bruising and peridontal hemorrhage, with diffuse cutaneous petechiae on the torso, arms and legs.

Figure 1

Leukemic choroidopathy in a twenty-three years-old male. Fundus image of right (a) and left (b) eyes depicting shallow serous retinal detachment and slight yellow discoloration to the underlying choroid. Fluorescein angiography shows slight subretinal fluid staining (c and d) and pointpoint leakage (d) enhanced depth imaging optical coherence tomography reveals shallow retinal detachment (e and f) and homogenous infiltration of the choroid with flat surface topography and loss of vascular detail

Fluorescein angiography revealed diffuse subretinal fluid accumulation and mild leakage from the optic disc OU [Figure 1]. Indocyanine green angiography showed focal progressive punctate hyperfluorescence with late staining. EDI-OCT (Heidelberg Engineering, Heidelberg, Germany) confirmed serous macular detachment OU and additional diffuse choroidal thickening to 724 μm OD and estimated > 600 um OS. The choroid was optically dense with obliteration of vascular layers OU [Figure 1].

Complete blood count with a manual differentiation demonstrated profound thrombocytopenia (2 × 103/mm3) and normocytic anemia (8.4 g/dL) without leukocytosis. D-Dimer was elevated (408 ng/mL) while fibrinogen and prothrombin/partial thromboplastin times were normal.

Following admission, cytochemistry and immunophenotyping of peripheral blood revealed 30% lymphocytes of which 64% were abnormal precursor B-lymphoblasts. Bone marrow core biopsy disclosed 100% cellularity of the marrow, comprised entirely of blast cells. Full body computed tomography scans revealed pulmonary and peritoneal infiltration and an erosive frontal bone lesion. Lumbar puncture and magnetic resonance imaging of the brain was negative.

Based on the diagnosis of precursor B-cell acute lymphoblastic leukemia, induction chemotherapy was begun with intravenous mitotaxone and cytarabine and intrathecal methotrexate. Visual acuity improved steadily over the 6 week hospital admission. At 8 weeks follow-up, the subretinal fluid had completely resolved and choroidal anatomy normalized to thickness of 431 μm OD and 443 μm OS [Figure 2]. Choroidal vascular detail was visible. Best corrected visual acuity returned to 20/25 OD and 20/20 OS.

Figure 2

Eight weeks following chemotherapy, visual acuity improved, serous retinal detachment resolved (a and b), and the choroidal infiltration responded, leaving visible vascular architecture

DISCUSSION

Ophthalmic involvement in patients with leukemia occurs far more often in acute than chronic disease and can involve any portion of the ocular and adenexal anatomy.2 Leukemic involvement can be through direct infiltration of tissue by leukemic cells or by indirect effects on tissue from hematologic abnormalities (anemia, thrombocytopenia, hyperviscosity), opportunistic infections, and consequences of chemotherapy, radiotherapy, or bone marrow transplantation.1011 Prior to the advent of modern chemotherapy, it was estimated that up to 69% of all patients had ophthalmic fundus changes at some point in their disease course and it was not uncommon to see dense leukemic infiltration associated with hemorrhage and destruction of retinal architecture.112 Funduscopic changes in leukemia include hemorrhage at all levels, perivascular infiltration, microaneurysms, vascular occlusion, peripheral neovascularization, and retinitis, or vitritis (primary or secondary to opportunistic infections).2 Notably, vitritis due to leukemia is uncommon as the internal limiting membrane generally serves as an effective barrier to leukemic cell infiltration.13 Our case highlighted a very unusual example of direct leukemic infiltration of the choroid and associated bilateral SRD without other clinically evident pigmentary, vascular, or retinal findings.

Although retinal involvement is most commonly observed in patients with leukemia, patchy or diffuse choroidal leukemic infiltration and associated choroidal thickening is consistently found histopathologically, but was not previously well-documented clinically due to subtle associated changes.18 These changes include pigmentary alterations due to RPE atrophy or hypertrophy, drusen, or SRD.2 Leukemic infiltration into the choroid classically manifests with a shallow SRD in the macular region, often leading to visual acuity loss.1415 Fluorescein angiography demonstrates multifocal pinpoint hyperfluorescence or “starry sky” appearance with diffuse late leakage of fluorescein into the subretinal space. Based on histopathologic studies, SRD with leukemia is believed to be related to the patchy choroidal infiltration leading to RPE alterations, disruption of tight junctions and later accumulation of subretinal fluid.28

With the advent of EDI-OCT, we now visualize the retina and choroid in vivo with 4 μm resolution. In our case, we were able to document the SRD, as well as choroidal leukemic infiltration on EDI-OCT., The direct leukemic infiltration of the choroidal tissue with obliteration of the vasculature on EDI-OCT is similar to that described histopathologically by Leonardy et al.78 The only previous report of in vivo choroidal leukemic infiltration on EDI-OCT by Bajenova et al. depicted similar choroidal thickening, but with relative conservation of the choroidal vascular anatomy.9 In our case, the choroid was markedly thickened to >600 μm OU, and the vascular anatomy was replaced by a homogeneous, optically dense tissue. It is conceivable that our patient had greater tumor load and/or secondary edema compared with that reported by Bajenova et al.9 In both cases, systemic chemotherapy resulted in prompt resolution of SRD and normalization of choroidal anatomy on EDI-OCT.

Our case additionally demonstrated the optic disc leakage, suggestive of optic nerve infiltration. Despite negative lumbar puncture, this finding necessitated intrathecal chemotherapy. Leukemic optic nerve infiltration is considered an ophthalmic emergency and carries a poor systemic and visual prognosis.111617

The primary treatment for leukemic-related SRD is systemic chemotherapy for the underlying leukemia.12 If vision does not improve with appropriate treatment, secondary causes due to hematologic abnormalities, opportunistic infection, or treatment side effects should be considered. In cases nonresponsive to systemic treatment, choroidal biopsy via fine needle aspiration biopsy or retinotomy is appropriate.1819 Once a definitive diagnosis of leukemic infiltration is confirmed in an eye nonresponsive to systemic chemotherapy, escalating treatment with localized radiotherapy is advised.12

Rapid evaluation, diagnosis, and initiation of systemic therapy were instrumental in our patient's systemic and visual outcome. The sudden appearance of SRD in a young person should raise suspicion for leukemia. Choroidal thickening and hyper-reflectivity on EDI-OCT can be a marker of leukemic choroidopathy. Future studies correlating choroidal changes on EDI-OCT to lymphocytic cell load, response to chemotherapy, and histopathology will be instrumental in furthering our understanding of ophthalmic manifestations of systemic leukemia.