Sir,

We report a case of bilateral serous retinal detachment (SRD) as an initial sign of relapse of acute lymphocytic leukemia. A 31-year-old woman with acute pre B-cell lymphocytic leukemia in complete remission, who presented with symptoms of visual blurring, was found to have bilateral SRD. A bone marrow aspirate revealed relapse of the disease. Her maculopathy completely resolved following systemic chemotherapy.

Case report

A 31-year-old woman with acute pre B-cell lymphocytic leukemia achieved complete remission 3 months after treatment with chemotherapy (CALGB881), brain radiation, and intrathecal methotrexate. She was designated for allogenic bone marrow transplantation (BMT) and treated with Fludarabine, Cytosar, and Cytosine arabinoside as salvage therapy, and with Piperacillin, Amphotericin B, Amikacin, and Hydrocortisone for suspected septicemia. While waiting for the BMT, she complained of bilateral blurred vision.

On presentation BCVA was 20/50 in both eyes. Full ophthalmologic examination revealed clear and quite anterior segments, and on fundus examination SRD, involving the posterior pole OU, accompanied by a small retinal hemorrhage in the inferior arcade OD (Figures 1a and b).

Figure 1
figure 1figure 1

Fundus photograph (a) of the right eye showing SRD in the posterior pole (b) left eye showing SRD in the posterior pole. Fluorescein angiography of the left eye (c) and right eye (d) showing early multifocal hyperfluorescence foci beneath the detachment, with late subretinal diffuse leakage. Optical coherence tomography of the left eye (e) and right eye (f) showing subretinal fluids.

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Fluorescein angiography showed multifocal, pinpoint hyperflourescent spots beneath the detachment with diffuse late subretinal leakage (Figures 1c and d).

Optical coherence tomography disclosed large amount of subretinal fluid OU (Figures 1e and f).

As the patient was treated with hydrocortisone at the time, a possible diagnosis of central serous retinopathy (CSR) was suspected, and discontinuation of hydrocortisone treatment was advised. However, no resolution of the SRD was noticed. We then suspected that the SRD may be a sign of disease relapse and insisted on repeated systemic evaluation, which indeed revealed disease relapse. Another chemotherapy protocol (FLA-IDA) was initiated. Seven days later, BCVA improved to 20/20 OU and complete resolution of the SRD OU was seen (Figures 2a and b).

Figure 2
figure 2

Fundus photograph (a, b) of both eyes showing complete resolution of the serous detachment with residual hypopigmented small spots in the RPE.

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Later on, the patient underwent the planned BMT, but unfortunately suffered from severe fungal septicemia and passed away 1 month later.

Comment

Retinal manifestations are estimated to occur in up to 90% of persons with acute leukemia,1, 2 and include large spectrum of small vessel disease, ranging from mild ischemia with scattered cotton wool spots, and few retinal hemorrhages (round or flame shaped, often with a white component, which consists of leukemic cells and debris, platelet fibrin aggregates, or septic emboli) to proliferative retinopathy.1, 2, 3

Histopathological examination shows discrete and diffuse hemorrhages and leukemic infiltration.3 The hemorrhages and infiltrates are found at all levels of the retina, but especially in the inner layers with focal destruction.

These retinal findings are observed commonly, but SRD in leukemia is rare4, 5, 6, 7, 8, 9, 10 and seldom seen during complete remission.10, 11 The posterior manifestations of leukemia are probably due to leukemic infiltration of the choroid,1 or from hematological abnormalities associated with leukemia, such as anemia, thrombocytopenia, hyperviscosity states, or opportunistic infections.1, 2

The SRD observed in leukemia is reported to be shallow in the posterior pole1, 7, 11 and could be attributed to direct invasion of lymphoblasts to the choroidal vasculature causing dysfunction of the choroid—retinal pigment epithelial (RPE) complex, resulting in ischemia of the RPE and disruption of their pumping ability and accumulation of fluid beneath the retina.

The involvement of the choroid by leukemic cells tends to be perivascular, and may be patchy or diffuse.3 The choroid at the posterior pole may be significantly thickened. The overlying RPE may show secondary alterations, including atrophy and hypertrophy.

Fluorescein angiography demonstrates multifocal deep hyperfluorescent foci beneath the detachment in the early phase and diffuse leakage to the subretinal space in the late phase,1, 2 as seen in our case.

This angiographic finding is probably due to RPE disturbances secondary to circulatory or metabolic changes in the underlying choriocapillaris. Stewart et al4 postulated that leukemic infiltration of the choroid caused decreased blood flow in the choriocapillaris, resulting in ischemia to the overlying RPE and disruption of the intercellular tight junctions.

The intraocular manifestations of leukemia are usually treated with systemic chemotherapy, and when this fails, ocular radiation is recommended.1, 2

In our case, shortly after systemic chemotherapy was administered, the SRD resolved and BCVA improved.

This case suggested that SRD caused by leukemia may mimic CSR. However, the appearance of SRD in a patient with ALL, although on apparent remission, should alert the ophthalmologist for a relapse of the disease.