Gemcitabine‐induced retinopathy in a diabetic patient

Abstract

Editor, Gemcitabicine, a nucleoside analogue, has been approved for the treatment of a variety of cancers (bladder, ovarian, pancreatic, etc). The major dose-limiting side-effect seems to be myelosuppression (Noble & Goa 1997). We report the case of a 58-year-old white man suffering from a bladder carcinoma who developed a retinal microangiopathy after being treated with gemcitabine (Gemzar®, Lilly, France). The patient was given a combination of gemcitabine and a platinium salt after surgical management from March to June 2006 with good response. Past medical history included insulin-dependent diabetes and hypertension, which were well controlled. In July 2006, visual acuity decreased to 20/40 in both eyes after four cycles of chemotherapy. Dilated fundus examination showed mild retinal oedema associated with cotton-wool spots and haemorrhages in both eyes (Fig. 1A). Fluorescein angiogram demonstrated microaneurysms, and capillary vascular leakage (Fig. 1D). Optical coherence tomography (OCT) revealed thickening of the macula [right eye (OD) = 319 μm; left eye (OS) = 282 μm] and of the retinal nerve fibre layer (RNFL) of both eyes (OD = 133.48 μm; OS = 126.31 μm) (not shown). Retinopathy induced by chemotherapy was diagnosed. Gemtabicine was discontinued and carboplatine was maintained. Gemcitabine-induced retinopathy of the right eyes after four cycles of chemotherapy with cotton-wool spots, intraretinal haemorrhages and microaneurysms (A) and capillary vascular leakage at late phase of fluorescein angiogram (D). One month after discontinuation of gemcitabine, cotton-wool spots and haemorrhages have mostly reabsorbed (B). Late phase of fluorescein angiogram showed persistence of microaneurysms and resolution of vascular leakage (E). Retinopathy reappeared one month after re-exposure to gemcitabine with cotton-wool spots, intraretinal haemorrhages (C) and capillary vascular leakage (F). In August 2006, visual acuity improved to 20/25 OD and 20/30 OS. Fluorescein angiogram showed resolution of vascular leakage and persistence of microaneurysms (Fig. 1E). Macular and RNFL thickness decreased on OCT. A follow-up retinal examination in September showed that retinopathy had improved and cotton-wool spots and haemorrhages had mostly reabsorbed (Fig. 1B). The patient remained asymptomatic and was monitored every 4 weeks until his bladder cancer relapsed in February 2007. Reintroduction of gemcitabine was attempted. One month later, retinopathy appeared with cotton-wool spots, intraretinal haemorrhages (Fig. 1C) and mild vascular leakage on fluorescein angiogram without change in visual acuity (Fig. 1F). Discontinuation of gemcitabine was decided and the patient died 4 months later. Retinal changes found in this case included aneurysms, cotton-wool spots, intraretinal haemorrhages and vascular leakage on fluorescein angiogram. Clinical improvement after gemcitabine withdrawal and relapse of retinopathy from re-exposure to the drug strongly suggest gemtabicine to be causative for the retinopathy. The retinopathy occurs within 1 month at reintroduction of gemcitabine and may be asymptomatic. Our patient presented decreased vision caused by macular involvement (haemorrhages, oedema) after four cycles of chemotherapy when he was first treated, and retinopathy appeared without vision change when gemcitabine was reintroduced. The prognosis is good with resolution of retinal changes after gemcitabine discontinuation. Banach & Williams first reported a Purtscher retinopathy and necrotizing vasculitis after gemcitabine therapy in a diabetic patient. This retinopathy was associated with digital necrosis, ESR and antinuclear antibody elevation (Banach & Williams 2000). In our patient, diabetes and hypertension may be the risk factors to develop gemcitabine-induced retinopathy. The direct drug-induced endothelial damage suggested by some authors (Moake 2002) may be the pathogenic mechanism, leading to retinal capillary changes including capillary dilatation and capillary closure. Exudative phenomena resulting from retinal vascular incompetence may occur, as in our case. Damage to mitotically active endothelial cells eventually leads to occlusive vascular disease (Archer et al. 1995), causing necrotizing retinopathy, as reported previously (Banach & Williams 2000). Carboplatine is known to cause optic neuritis (Caraceni et al. 1997), and might not be responsible for the retinopathy because improvement was observed when the treatment was maintained. However, the possibility that carboplatine combination is pathogenic for the development of this retinopathy cannot be excluded completely. To the best of our knowledge, this is the first report of gemcitabine-induced retinal microangiopathy with causative evidence. This case highlights the need for fundus examination during gemcitabine therapy, especially in patients with diabetes and hypertension. Early diagnosis and careful follow-up are recommended in order to avoid progression to irreversible changes.