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The efficacy of bone marrow transplantation (BMT) for the treatment of selected diseases of the haemopoietic system such as chronic myeloid leukaemia (CML) is well recognised. Graft versus host disease (GVHD) is however a common and potentially life threatening complication of this treatment, occurring in up to 75% of cases. It is thought to arise when immunocompetent donor T lymphocytes mount an immune response against host tissues. GVHD is characterised by a triad of enteritis, dermatitis, and hepatitis, but almost all organs may be targeted. Ocular involvement is frequently seen but is usually limited to the anterior segment. Posterior segment manifestations are rare.
This report describes two cases of GVHD with unusual posterior segment involvement that highlight the diversity of presentations in this condition.
A 45 year old white male presented with progressive bilateral blurred vision and floaters 10 months post-BMT for CML. He had no history of ocular disease. His symptoms started 10 days after discontinuation of cyclosporin A as a routine protocol and were accompanied by alopecia, poliosis, vitiligo, and oral mucositis. A presumptive diagnosis of acute GVHD was made and cyclosporin restarted together with prednisolone. His other medications were azathioprine, aciclovir, fluconazole, and ranitidine.
Best corrected visual acuity was 6/9 bilaterally, with no afferent pupillary defect. There was no evidence of inflammation in anterior segments or vitreous and normal intraocular pressures. There was mild disc pallor with swelling and surrounding radial choroidal folds and several pale subretinal perifoveal lesions on the left. Systemic examination revealed widespread patchy alopecia with poliosis, vitiligo of the arms, and mild oral mucositis. Fluorescein angiography showed mild dilatation of the disc capillaries and extensive focal leakage from the retinal pigment epithelium, but no evidence of cystoid macular oedema. Ultrasonography showed a thickened posterior sclera. Optical coherence topography (OCT) showed subretinal fluid bilaterally. Cerebral magnetic resonance imaging (MRI) and lumbar puncture revealed no abnormalities.
The clinical appearances were consistent with posterior scleritis together with a diffuse retinal pigment epitheliopathy. A reducing regimen of high dose steroids in combination with acetazolamide resulted in clinical improvement and visual stabilisation.
A 31 year old white female underwent total body irradiation and BMT for αβ-T cell splenic lymphoma. One month later she developed acute GVHD related erosive enteropathy resulting in life threatening exsanguination. Following successful resuscitation (which precipitated admission to intensive care for 6 weeks), she noted blurred left eye vision and described difficulty in dark adaptation and differentiating between shades of grey; there was right strabismic amblyopia. The patient’s medication comprised aciclovir, cyclosporin, penicillin, propranolol, and lansoprazole.
Visual acuity was 6/18 and N14 with the right eye, and 6/12 and N5 with the left. Colour vision was normal and visual fields were full. There was no afferent pupillary defect. The anterior chambers and vitreous were quiet. The optic discs were normal. At both maculas (Fig 1), there were deep subretinal cream coloured spots and retinal thickening and OCT evidence of subretinal fluid without cystoid changes. Fluorescein angiography showed a few hyperfluorescent spots consistent with focal retinal pigment epithelium dysfunction. Electrodiagnostic tests identified diffuse rod dysfunction.
Since there was biochemical evidence of renal impairment, acetazolamide was considered to be contraindicated to treat the subretinal fluid. By 4 months, the best corrected visual acuities were 6/12−2 right; 6/6+2 left. Repeat electrophysiology was unchanged, however by ten months the full field electroretinograms had improved to normal limits.
GVHD is presumed to be caused by donor T lymphocytes recognising minor histocompatibility antigens on recipient tissues that are then subjected to CD8-T lymphocyte mediated attack. Commonly reported ocular manifestations include pseudomembranous conjunctivitis, keratoconjunctivitis sicca, corneal epitheliopathy, and cataract.1 Posterior segment involvement is rare and includes cotton wool spots2 as well as central serous chorioretinopathy.3
In both of our cases, there seems to be a striking temporal association between the onset of visual symptoms and an adverse event in the course of the disease. In case 1, in whom the cessation of cyclosporin resulted in acute GVHD, the ocular findings were consistent with scleritis, a feature only once previously reported.4 Postmortem studies have demonstrated choroidal infiltrates in GVHD patients containing histiocyte-like large eosinophils5 and clinically these may be represented by the pale perifoveal lesions observed in the left eye. Subsequently this patient was shown to be HLA-DR4 positive, a finding common in individuals with Harada’s disease and frequently associated with chronic GVHD.6
By contrast, the ocular findings in the second case were not a result of acute but a consequence of previous life threatening GVHD during which exsanguination occurred. While interruption of blood flow to the optic nerve or visual cortex can account for visual loss following extreme haemorrhage, retinal ischaemia has also been documented.8 The rod photoreceptor system appears most vulnerable,7 a feature consistent with the electrophysiological findings in this case, and the patient’s difficulty with dark adaptation is in keeping with rod dysfunction. Of interest was the subsequent improvement in acuity and electrophysiological responses. Such a pattern parallels electrophysiological studies of children after respiratory or circulatory arrest where initially subnormal ERG responses return to normal levels within 8 months.9 The mechanism that mediates this recovery is not known.
Graft versus host disease is a common complication of bone marrow transplantation that usually presents to the ophthalmologist with anterior segment signs. However, GVHD may also present with posterior segment presentations of the types described here.