|Year : 2022 | Volume
| Issue : 3 | Page : 356-359
Bilateral serous retinal detachment: An initial presentation of mixed phenotype acute leukemia in an adult
Khulood Al Kalbani1, Ahmed Al Hinai2, Aisha Al Busaidi2
1 Ophthalmology Residency Program, Oman Medical Specialty Board, Muscat, Sultanate of Oman
2 Department of Ophthalmology, Sultan Qaboos University Hospital, Al Khoudh, Muscat, Oman
|Date of Submission||08-Apr-2022|
|Date of Decision||07-Aug-2022|
|Date of Acceptance||23-Sep-2022|
|Date of Web Publication||02-Nov-2022|
Khulood Al Kalbani
Ophthalmology Resident R4, Oman Medical Specialty Board
Sultanate of Oman
Source of Support: None, Conflict of Interest: None
| Abstract|| |
A 60-year-old female presented with acute onset painless loss of vision in both eyes. Clinical examination and ocular investigations revealed bilateral serous retinal detachments (SRDs) over the macula. There was no obvious intraocular or extraocular cause to the presentation. A blood count showed leukocytosis with the presence of blast cells on the peripheral smear. Further workup confirmed the diagnosis of Philadelphia chromosome-positive mixed phenotype acute leukemia with central nervous system disease stage three. Anatomic improvement in the SRD followed intensive intravenous and intrathecal chemotherapy. Limited functional improvement was attributed to the development of pigment epitheliopathy manifesting as leopard spot chorioretinopathy. This permanent disturbance could be attributed to leukemic infiltration and ischemia to the choroid.
Keywords: Leukemic infiltration, mixed phenotype acute leukemia, serous detachment
|How to cite this article:|
Al Kalbani K, Al Hinai A, Al Busaidi A. Bilateral serous retinal detachment: An initial presentation of mixed phenotype acute leukemia in an adult. Oman J Ophthalmol 2022;15:356-9
|How to cite this URL:|
Al Kalbani K, Al Hinai A, Al Busaidi A. Bilateral serous retinal detachment: An initial presentation of mixed phenotype acute leukemia in an adult. Oman J Ophthalmol [serial online] 2022 [cited 2023 Jan 27];15:356-9. Available from: https://www.ojoonline.org/text.asp?2022/15/3/356/360427
| Introduction|| |
The choroid is the most frequent ocular tissue exhibiting leukemic infiltration due to its high blood flow rate and oxygen availability. Choroidal infiltration may present itself clinically as serous retinal detachment (SRD). The presence of unilateral or bilateral SRD can be one of the manifestations of acute leukemia either as a primary sign or relapse. This uncommon presentation has been well documented over the years in diverse types of leukemias.
Ophthalmologists may be the first to uncover leukemia. In this report, we describe an adult with symptomatic bilateral SRD as a presenting sign of underlying mixed-phenotype acute leukemia (MPAL). To the best of our knowledge, this is the first report associated with this rare subtype of acute leukemia.
| Case Report|| |
A 60-year-old female presented 2 weeks after experiencing acute onset painless loss of vision in both eyes. Her ocular history was unremarkable but her medical history was significant for well-controlled hypertension on amlodipine and valsartan, bronchial asthma on fluticasone and salbutamol inhalers, and dyslipidemia on simvastatin. She reported a remote history of undergoing a craniotomy for a benign brain tumor; details of which was unavailable to us. A detailed review of systems revealed mild fatigue recently. She denied night sweats, fever, headache, and other neurological or auditory symptoms.
On examination, she appeared healthy looking with normal blood pressure (BP). Best-corrected visual acuity (BCVA) was 0.2 (with + 9.00 D) in the right eye (OD) and 0.25 (with + 5.75 D) in the left eye (OS). Both external and anterior segment examinations were noncontributory apart from early cortical cataracts. The vitreous was clear in both eyes but fundoscopy revealed a bilateral swollen macula. In addition, there was a yellowish deep scattered subretinal discoloration at the poster pole of OD [Figure 1]a more than OS and subtle signs of retinopathy with a Roth spot OD [Figure 1]b and an occasional spot retinal hemorrhage OS [Figure 1]c. No other retinal or vascular changes were evident, and the optic nerves were of normal appearance. Optical coherence tomography of the macula displayed subretinal fluid in the macular area of OD indicating neurosensory retinal detachment with some irregularity of the retinal pigment epithelium [Figure 2]a. OS showed a large bacillary layer detachment and a small serous detachment [Figure 2]b.
|Figure 1: (a) Fundus photography of the right eye showing a serous retinal detachment involving the macula. (b) A cotton wool spot and an adjacent Roth spot over the inferior arcade of the right eye. (c) The left eye showing a serous retinal detachment involving the macula with a small preretinal hemorrhage over the superior arcade|
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|Figure 2: Optical coherence tomography of the macula showing bilateral detachments of the neurosensory retina. (a) Right eye and (b) left eye|
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Laboratory data showed abnormal complete blood count consisting of a low hemoglobin level (8.7 g/dL) and an alarmingly elevated white cell count (62.8 × 109/L). There was an elevated erythrocyte sedimentation rate level (143 mm/hr). Infectious workup for tuberculosis, syphilis, human immunodeficiency virus, and herpes simplex virus were all negative. A chest X-ray was reported normal. The patient's blood film showed a leukoerythroblastic picture with circulating blasts of more than 85% of the total white cells. The patient was immediately referred to hemato-oncology for further workup. A bone marrow biopsy and cerebrospinal fluid (CSF) analysis revealed morphologic evidence of lymphoblasts. A brain magnetic resonance imaging with contrast showed dural enhancement suggestive of infiltration and leptomeningeal dissemination without compressive masses along the optic nerves. Following a complete morphological, immunophenotypic, and cytogenetic analysis, she was diagnosed with MPAL, Philadelphia chromosome-positive, with the central nervous system (CNS) disease stage three.
Induction chemotherapy was started with dasatinib, vincristine, dexamethasone, and triple intrathecal injections of methotrexate, cytarabine, and hydrocortisone. A month later, the patient showed complete resolution of serous detachments with minimal residual subretinal fluid [Figure 3]a and [Figure 3]b. With clinical resolution, there was an improvement in the hyperopic shift but limited improvement in visual acuity with BCVA OD/OS of 0.2 (with + 3.50 D) and 0.25 (with + 2.00 D), respectively. Posttreatment fundus examination [Figure 4]a and [Figure 4]b and autofluorescence [Figure 5]a and [Figure 5]b revealed retinal pigment epithelial (RPE) mottling in a “leopard spot” pattern.
|Figure 3: Optical coherence tomography of the macula showing resolution of the SRD in (a) right eye and (b) left eye, with minimal residual subretinal fluid and schisis. SRD: Serous retinal detachment|
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|Figure 4: Fundus photography showing resolution of the SRD in both eyes with residual leopard-spot pattern retinopathy. Please note images are slightly overexposed, and apparent disc pallor was not clinically appreciated. (a) Right eye and (b) left eye. SRD: Serous retinal detachment|
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|Figure 5: Fundus autofluorescence showing hyperautofluorescent spots in a leopard spot pattern. (a) Right eye and (b) left eye|
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| Discussion|| |
Our patient's unusual presentation with bilateral serous macular detachments in the context of her demographics, lack of intraocular inflammation, and a previous history of brain tumor resection, raised our suspicion of a masquerade syndrome such as choroidal metastasis, paraneoplastic syndrome, or hematological malignancy. Targeted history and clinical examination excluded other possible causes of SRD that may be secondary to vascular, inflammatory, or infectious etiologies. The patient's age, gender, and presence of pre-retinal hemorrhage made the diagnosis of central serous chorioretinopathy unlikely. Her BP was well controlled which also excluded hypertensive choroidopathy as a cause. Posterior scleritis was unlikely since she reported no eye pain. She did not experience any prodromal/auditory symptoms and had no other integumentary signs that might be suggestive of Vogt-Koyanagi-Harada syndrome. Iatrogenic causes were excluded as there was no history of ocular procedures such as cryotherapy or photocoagulation. Primary and secondary choroidal tumors were excluded as there were no obvious lesions clinically. The diagnosis was made by a simple blood count and further workup eliminated infections as a cause. The shallow nature of the detachments and the location being confined to the posterior pole were generally what was reported in association with leukemia. The yellowish deep subretinal discoloration indicates deep diffuse infiltrates and aggregates of leukemic cells. Despite the evidence of CNS disease on CSF analysis, there was no invasion of the optic nerve or symptoms suggestive of CNS involvement.
This is the first case reported with the subtype MPAL presenting with serous macular detachments. In contrast to acute lymphoblastic leukemia (ALL), in which there is a proliferation of immature B or T cells, and acute myelogenous leukemia (AML) which consists of immature myeloid lineage cells, MPAL fails to show commitment to the myeloid, B lymphoid, or T lymphoid lineages. Therefore, it falls under the umbrella of acute leukemias of ambiguous lineage. MPALs can further be subclassified as either biphenotypic or bilineal. The former comprises a single blast population expressing antigens of more than one lineage and the latter comprises two distinct populations of blasts. The expression of specific antigens helps further assign the subtype of MPAL [Table 1]. Our patient expressed myeloperoxidase, as well as CD19 and CD79A which labels her as MPAL and B/myeloid.
|Table 1: The World health organization classification of acute leukemia of ambiguous lineage revised 4th edition|
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A systematic review on SRD as a leukemic choroidopathy reported its association with other subtypes such as ALL (41.9%), AML (23.3%), relapsed ALL (27.9%), and relapsed AML (6.9%). Half of them occurred between ages 17 and 45 years without any sex predominance. Like our case, most had bilateral involvement and the majority were observed before the diagnosis of acute leukemia.
The mechanism underlying SRDs associated with leukemia is less well understood. The choroidal involvement results in secondary alterations of the overlying RPE in the form of serous detachment. Proposed mechanisms include abnormal choroidal perfusion and/or damage to the outer blood–retinal barrier along with neoplastic choroidal infiltration, localized choroidal hypoxia, or alterations to local oncotic and/or hydrostatic forces. Yabas Kiziloglu et al. postulated that choroidal infiltration by leukemic cells leads to a decrease in blood flow at the choriocapillaris with subsequent ischemia. This disrupts the RPE tight intercellular junctions which thereby lead to serous detachment of the neurosensory retina or RPE necrosis.
The resolution of SRD after systemic chemotherapy confirmed the infiltration of choroid by leukemic cells in the SRD area. In contrast to previous reports showing that visual function can be fully restored after appropriate therapy, visual recovery in our case was not as expected. An electroretinogram (ERG) and visual evoked potential (VEP) were carried out. The full field ERG showed a nonspecific, moderate rod–cone dysfunction, whereas the multifocal ERG was consistent with central maculopathy OD and paracentral maculopathy OS. The VEP showed no evidence of optic pathway dysfunction. The appearance of retinal pigment of retinal pigment epitheliopathy in the form of leopard spot pattern is a rare entity and has been mainly reported in reported in association with leukemia recurrence in children, chronic leukemia, and cases of acute leukemia undergoing chemotherapy. It is thought to be due to the invasion of the choriocapillaris by leukemia cells resulting in ischemia and dysfunction of the retinal pigment epithelium. Additional factors such as drug toxicity have been postulated., This could likely explain the permanent damage to the RPE as a sequela of malignancy or toxicity from chemotherapy. The slight delay in presentation could have also contributed to this sequela.
This case report highlights that a new diagnosis of SRD without an obvious cause should raise suspicion of masquerade syndromes like leukemias. The earlier the diagnosis is suspected, the more likely the patient will receive timely treatment and be able to restore vision. A visit to the ophthalmologist may be the patient's first encounter in diagnosing such serious, life-threatening conditions.
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 initial s will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed
The authors would like to thank Dr. Washoo Mal, Department of Ophthalmology, Sultan Qaboos University Hospital, Al Khoudh, Muscat, Sultanate of Oman.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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