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Editor,—Vitravene (ISIS 2922, formerly known as fomivirsen sodium) is a phosphorothioate oligonucleotide with potent and specific anticytomegalovirus (CMV) activity.12Vitravene binds to human CMV mRNA and inhibits the synthesis of proteins responsible for regulating virus gene expression. It is given intravitreally and its site of action differs from currently available therapies therefore reducing viral cross resistance. Minimal adverse effects have been reported3 including peripheral visual field loss and retinal pigment changes at high doses but the mechanism of this is not known.4
We report two patients in whom negative electroretinograms (ERGs) were observed following prolonged intravitreal vitravene.
A 51 year old man with AIDS developed CMV retinitis (CMVR) in the left eye in zones 2–3. The right eye was normal and visual acuity was 6/5 right, 6/6 left. The patient failed to respond to standard intravenous therapies or intravitreal ganciclovir. Intravitreal vitravene (330 μg in 0.05 ml) was administered on days 1, 8, and 15, and then fortnightly for 6 months, with good effect. Although vision remained at 6/6 without active CMVR and no zone 1 involvement, the patient described mild photophobia, colour desaturation, and poor dark adaptation in the left eye. An altered macular reflex was noted and fluorescein angiography demonstrated slow choroidal filling and capillary dropout at the macula (Fig 1). Electrophysiology was performed to look at retinal function (Fig2).
A 52 year old man with AIDS developed CMVR in the right eye of similar extent to that in patient 1. His left eye was normal and visual acuity was 6/36 in the amblyopic right eye, 6/4 on the left. Treatment with intravenous cidofovir was successful. The left eye developed macular CMVR, which failed to respond to intravenous ganciclovir or intravitreal ganciclovir and foscarnet.
CMVR reactivated 1 year later in the right eye. Intravitreal vitravene (330 μg in 0.05 ml) was administered on days 1 and 15 and then monthly for 14 months. No further CMVR reactivation was observed in the vitravene treated eye and no new ocular symptoms developed. Retinal function was examined by electrophysiology (Fig 2).
Two cases of CMVR with negative ERGs following intravitreal vitravene are described. A “negative” ERG indicates post-phototransduction dysfunction, usually post-receptoral. The normal a-wave is consistent with normal photoreceptor function; the reduced EOG light rise also observed therefore suggests additional dysfunction at the level of the RPE/photoreceptor complex. The abnormal pattern ERGs show macular involvement.
RPE involvement in AIDS CMVR has been demonstrated ophthalmoscopically5 and confirmed by histology, immunohistochemistry6 and electro-oculography.7 The magnitude of EOG light rise reduction in AIDS related CMVR does not correlate with ERG a-wave amplitude, suggesting that the EOG changes are not secondary to photoreceptor dysfunction.7 There is however good correlation with the extent of RPE involvement,7 and EOG may thus be a good indicator of disease activity. Although ERG b-wave reduction may occur in AIDS related CMVR,78 the occurrence of a negative ERG in two eyes following intravitreal vitravene, and the normal ERG in a “control” eye with CMVR of similar magnitude which also received intravitreal medication, are in keeping with a causal relation.
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