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Acute retinal necrosis (ARN) is a rare but serious ophthalmic manifestation of infection by the herpesvirus family. In the immunocompetent, the viral agent most frequently identified is varicella zoster (VZV) followed by herpes simplex (HSV-1 and HSV-2) and rarely cytomegalovirus and Epstein-Barr virus. The condition, which may present with synchronous or metachronous systemic or cerebral herpetic infection (encephalitis) is now recognised to occur at all ages,1 though VZV tends to affect the more elderly and herpes simplex the young.
The majority of patients present with a short history of blurred vision, floaters, and mild ocular discomfort. In the immunocompetent, clinical examination reveals one or more well demarcated foci of retinal necrosis outside the major arterial arcades typically with a dense vitritis that may preclude a detailed view of the posterior segment. Disease progression is rapid with coalescence and posterior extension of areas of retinitis. Often there is an occlusive, sometimes haemorrhagic, vasculitis either adjacent to areas of retinitis or at the optic nerve. The visual prognosis for untreated cases is very poor.2
We report three immunocompetent patients with no evidence of concurrent herpesvirus infection in whom ipsilateral optic neuritis associated with a panuveitis was the presenting feature of their acute retinal necrosis syndrome.
A 20 year old healthy white male, with no history of herpesvirus infection, presented with a 10 day history of progressive blurred right vision with floaters, significant periocular discomfort, and pain on ocular motility. Acuity was 20/200 right eye, 20/20 left eye, with a right relative afferent pupillary defect (RAPD). There was swelling of the right optic nerve (Fig 1A) together with increasing non-granulomatous pan uveitis. The left eye was unaffected. Fluorescein angiography (Fig 1B) showed marked optic disc hyperfluorescence and peripheral retinal ischaemia. Seven days later (Fig 1C and D), several enlarging foci of retinitis, typical of ARN, developed in the retinal mid-periphery. PCR of a vitreous biopsy amplified HSV-1. There was no further reduction in visual acuity following intravitreal foscarnet and encephalitic doses (10 mg/kg three times daily) of intravenous aciclovir for 10 days.
A 47 year old healthy white female, with no history of prior herpesvirus infection, presented with a 3 day history of progressive blurred left vision. She also complained of significant periocular discomfort exacerbated by eye movement. Acuity was 20/40 left eye, 20/15 right eye, with a left RAPD. There was swelling of the left optic nerve head together with a moderate non-granulomatous panuveitis. The right eye was unaffected. Fluorescein angiography showed marked optic disc hyperfluorescence and peripheral retinal ischaemia. Six days later, several enlarging foci of retinitis, typical of ARN, developed in the inferior retinal periphery. Polymerase chain reaction (PCR) of a vitreous biopsy amplified HSV-1. There was no further reduction in visual acuity following encephalitic doses (10 mg/kg three times daily) of intravenous aciclovir for 10 days.
An 81 year old white male, who had suffered herpes simplex meningoencephalitis and synchronous right acute retinal necrosis (acuity reduced to 20/200) 17 years earlier, presented with a 2 day history of profound reduction in left acuity to perception of light only. Clinical findings included a left RAPD, haemorrhagic optic disc swelling, and increasing hypertensive panuveitis. Five days later, three demarcated areas of retinal necrosis appeared superiorly in the same eye. PCR of a vitreous biopsy amplified HSV-1. There was no further reduction in visual acuity following intravitreal foscarnet and 10 days of encephalitic doses (10 mg/kg three times daily) of intravenous aciclovir.
There have been two previous reports in immunocompromised patients of optic neuritis preceding the development of ARN.3,4 In these, preceding or concurrent cutaneous herpes zoster infection suggested altered viral behaviour in the context of deficient immunity. Even in the healthy individual, there is evidence of an immunogenetic predisposition to the development of the disease.5 The novel mode of presentation of our three immunocompetent patients suggests they might share a similar background of immunity that modifies viral behaviour, thereby predisposing to involvement of the optic nerve before the development of retinitis. In this regard, it is interesting that none of our cases developed clinically evident encephalitis. This is a common accompaniment to human HSV-1 ARN and observed in the Szily animal model in which inoculation of the anterior chamber or vitreous with HSV virus produces in ipsilateral anterior uveitis, relative sparing of the ipsilateral retina, and necrotising contralateral chorioretinitis with encephalitis. It has been shown that viral spread to the brain and the fellow eye results from viral invasion of the optic nerve.6 The ability of the host to resist this appears determined by the animal's immune background.7
The recent report in a single case of ARN subsequent to central retinal vascular obstruction in the fellow eye is most likely a manifestation of a different VZV mediated disease process8 but emphasises the ability of members of the herpesvirus family to directly invade blood vessel walls.
The combination of optic neuritis, peripheral retinal ischaemia, and panuveitis is very unusual. In white patients, the differential diagnosis would include conditions such as sarcoidosis and demyelinating disease for which steroid therapy is often routine and may prove beneficial. This report highlights that herpesvirus infections may also present in this fashion. Since progression to profound and irreversible visual loss is rapid, close daily retinal examination, and early diagnostic vitreous biopsy must be recommended for these patients before commencement of immunosuppressives.
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