Article Text

PDF

Electrophysiological abnormalities following intravitreal vitravene (ISIS 2922) in two patients with CMV retinitis
  1. H J ZAMBARAKJI,
  2. S M MITCHELL
  1. Department of Ophthalmology, Chelsea and Westminster Hospital, London, UK
  2. Department of Clinical Ophthalmology, Institute of Ophthalmology and Moorfields Eye Hospital, London, UK
  3. Department of Electrophysiology, Moorfields Eye Hospital, London, UK
  1. S LIGHTMAN
  1. Department of Ophthalmology, Chelsea and Westminster Hospital, London, UK
  2. Department of Clinical Ophthalmology, Institute of Ophthalmology and Moorfields Eye Hospital, London, UK
  3. Department of Electrophysiology, Moorfields Eye Hospital, London, UK
  1. G E HOLDER
  1. Department of Ophthalmology, Chelsea and Westminster Hospital, London, UK
  2. Department of Clinical Ophthalmology, Institute of Ophthalmology and Moorfields Eye Hospital, London, UK
  3. Department of Electrophysiology, Moorfields Eye Hospital, London, UK
  1. Dr Graham E Holder, Electrophysiology Department, Moorfields Eye Hospital, London EC1V 2PD, UK

Statistics from Altmetric.com

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.

CASE REPORTS

Patient 1

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).

Figure 1

Fundus fluorescein angiogram of the left eye of patient 1 demonstrates macular capillary dropout.

Figure 2

Patient 1: Right eye ERGs fall within the normal range. Left eye rod b-wave is subnormal; the maximal response shows a negative waveform; cone flicker ERG shows relative reduction and implicit time increase; the PERG is reduced in keeping with macular involvement. The EOG light rise was normal on the right but undetectable on the left (not shown). Patient 2: All left eye findings are severely reduced. Right eye rod ERG is borderline subnormal; the maximal ERG has a negative waveform; the 30 Hz flicker ERG is of markedly increased implicit time; the PERG shows only residual activity. The EOG light rise was reduced on the right, undetectable on the left (not shown). Patient 3: This patient with AIDS had CMVR, of similar extent to patients 1 and 2, treated with intravenous foscarnet and intravitreal ganciclovir. ERGs and EOG light rise (not shown) are normal.  

Patient 2

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).

COMMENT

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.

References

View Abstract

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.