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Sir,

Haematopoietic stem cell transplantation (HSCT) including peripheral blood stem cell transplantation (PBSCT) and bone marrow transplantation (BMT) is now well recognized as the curative treatment modality for severe aplastic anaemia and haematological malignancy. However, HSCT is associated with several complications. These result from the side effects of the treatment regimen such as high-dose chemotherapy, steroid treatment, and irradiation that induced pancytopenia after transplantation, and that of the immune reaction like graft-versus-host disease (GVHD).1 The ocular complications of the anterior segment after BMT are common while those of the posterior segment are not frequently reported. The most commonly reported posterior segment complications are either intraretinal or vitreous haemorrhages according to the literatures.2 We present two cases of exudative bullous retinal detachment (RD) in two patients after PBSCT who develop severe and potentially vision-threatening complications. Since our two cases died shortly after the diagnosis, bullous RD may be a poor prognostic factor for survival after PBSCT.

Case reports

Case I

A 42-year-old woman was diagnosed of acute myeloid leukaemia (AML) in April 2001 with initial presentations of fever and sore throat. Prior to allogenic PBSCT, remission induction chemotherapy was administered with standard cytosine arabinoside and idarubicin. She underwent an allogenic PBSCT in September 2001. After 3 months, multiple skin eruptions over abdomen, bilateral palms, and forearms were noted. Dry mouth with lichen planus of oral mucosa was also found. Lip biopsy showed inflammatory cells infiltration in basal layer of buccal mucosa tissue. Chronic GVHD was suspected and she was started with cyclosporine, azathioprine, and prednisolone (60 mg daily for 6 days; the dose tapered therefore). She suffered a relapse of AML later in April 2002, was successfully treated with high-dose chemotherapy including cytosine arabinoside, etoposide, and mitoxantrone and experienced second remission. One palpable mass lesion over the right side of the neck was accidentally noted in November 2002 and the results of biopsy revealed blast cells. However, she developed a second relapse of AML, proved by bone marrow cytology simultaneously.

During the second relapse of AML, she complained of blurred vision of left eye and dryness of both eyes 1½ years after allogenic PBSCT. Ophthalmologic examination showed corrected visual acuity of 6/6 in the right eye and 3/60 in the left eye. The anterior segments were unremarkable except conjunctival keratinization on both eyes. Funduscopy showed serous retinal detachment with whitish dots in the subretinal fluid involving the macula in the left eye, while the right eye was normal. Fluorescein angiography revealed exudative retinal detachment with multiple fine pinpoint fluorescein leakage at retinal pigment epithelium level in the left eye (Figure 1). Ultrasonogram of the left eye showed retinal detachment with diffuse choroid thickening. Her general condition got worse with neutropenic fever and respiratory distress developed a few days after the ophthalmic consultation. Subsequently, she died of heart arrest 17 months after allogenic PBSCT.

Figure 1
figure 1

(Case 1) Funduscopy (left) of case 1 showed serous retinal detachment involving the macula in the left eye. Fluorescein angiography (right) revealed exudative retinal detachment with multiple fine pinpoint fluorescein leakage in the left eye. The right eye was normal.

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Case II

A 15-year-old girl was admitted in October 2002 with 1-week history of easily petechiae and menorrhagia. On examination, pancytopenia was noted and bone marrow biopsy disclosed hypocellularity. Severe aplastic anaemia was diagnosed. She had received preconditioning therapy including chemotherapy of cyclophosphamide (50 g/kg/day for 4 days), hydrocortisone (0.2 g for 3 days), and total body irradiation (TBI) (200 cGy twice for 2 days) prior to transplantation. She underwent an HLA-matched unrelated allogenic BMT in December 2002. Standard-dose of cyclosporine (66 mg twice on day 2) combined with methotrexate (15 mg daily on day 2) were given as prophylaxis for acute GVHD. Bone marrow cytology on day 14 disclosed graft failure. She was arranged a rescue HLA-mismatched allo-PBSCT from her younger sister on day 20 after initial BMT. She developed persisting high fever with mucositis, gingivitis, and oral ulcer on day 44. Acute GVHD was suspected and was treated with cyclosporine and dexamethasone (10 mg daily on days 44–74).

She reported blurred vision of both eyes for several days after rescue allo-PBSCT. Ophthalmologic examination showed corrected visual acuity of 20/400 in the right eye and 20/800 in the left eye by near chart. Examinations of anterior segment showed severe bilateral conjunctival chemosis and moderate posterior subcapsular cataract. Esotropia and lateral limitation of ocular movement in the left eye were noted. Funduscopy showed bilateral serous bullous RD involving macula and the inferior portion and intraretinal haemorrhage in the right eye (Figure 2). Her general condition deteriorated with progressive bilateral pneumonia and pulmonary haemorrhage. She was transferred to intensive care unit for respiratory failure and died of massive pulmonary haemorrhage on day 72 after PBSCT.

Figure 2
figure 2

(Case 2) Fundus photographs of the right eye (left) and the left eye (right) showed bilateral serous bullous RD involving the macula and the inferior portion with intraretinal haemorrhage most prominent in the right eye.

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Comments

Recently, the availability of peripheral blood as additional sources of stem cells other than bone marrow has expanded the applicability of haematopoietic stem cell transplantation. Although PBSC transplant recipients engraft more quickly than BMT recipients, they develop more frequent late-onset chronic GVHD than marrow recipients.3 Acute GVHD, tumour relapse, and the survival rate, however, were similar in patients receiving PBSCs or bone marrow.3

Our two cases presented with exudative bullous RD after PBSCT whose pathogenesis may be due to systemic steroid reaction similar to central serous chorioretinopathy,4, 5 occlusive choroidal angiopathy by disseminated intravascular coagulopathy2 or leukaemic cells6 or GVHD4, 7 per se.

In the first case with chronic GVHD, blurred vision in the left eye, neck malignancy, and AML relapse occurred simultaneously 14 months after PBSC. The fluorescein angiographic pictures of diffuse pinpoint leakage confined to the RD area of the left eye, and the negative study of the right eye, however, is dissimilar to the pictures of typical central serous chorioretinopathy that present with multiple pigment epithelial detachment bilaterally. Fawzi had reported a case of chronic GVHD with unilateral exudative RD.4 The choroidal circulation may be compromised by the inflammatory cells during reaction of GVHD and leads to choroid hyperpermeability and multifocal CSC development.8 Leukaemic infiltration, another cause of exudative RD, may also decrease the choriocapillaris blood flow and subsequent retinal detachment.9 The definite diagnosis could be confirmed by retinal biopsy or autopsy.

In our second case, bilateral inferior bullous RD involving macula presented almost simultaneously with the obvious manifestations of acute GVHD such as mucositis, oral ulcer, and gingivitis. Our patient died of massive pulmonary haemorrhage prior to high-dose steroid treatment to control the acute GVHD. High-dose systemic corticosteroid and cyclosporine had been reported to resolve the conjunctival chemosis and CSCR that occurred in a patient with GVHD.7 Most investigators believe that GVHD represents an immunological process mediated by immunocompetent donor T-lymphocytes reacting to genetically determined histocompatibility differences in the host.10 The histopathologic changes in the choroid of patients with acute GVHD are peculiar histiocyte–like cells infiltration in the choriocapillary layer.8

These two patients died shortly after vision-threatening complications. Bullous RD may be a poor prognosis factor for survival after PBSCT. Although the bullous RD after PBSCT is unusual, ophthalmologists should keep in mind this complication and help seek the different underlying cause in the hope that early intervention might be life saving.