Long-term follow-up of herpetic non-necrotizing retinopathy with occlusive retinal vasculitis and neovascularization
© Albert et al.; licensee Springer. 2015
Received: 30 June 2014
Accepted: 7 February 2015
Published: 28 February 2015
Herpetic necrotizing retinitis is a well-recognized entity. A few cases of herpetic non-necrotizing retinitis were previously reported.
We retrospectively report two cases of herpetic non-necrotizing retinopathy with a long follow-up. A 19-year-old woman presented with a bilateral diffuse occlusive retinal vasculitis, peripheral neovascularization, and no signs of retinal necrosis. Long-lasting immunosuppressive treatment failed to control the vasculitis until herpes simplex virus type 1 (HSV1) was demonstrated by polymerase chain reaction (PCR) in the aqueous. Acyclovir was then added and immunosuppressive tapered and eventually stopped resulting in a resolution of vasculitis. Only two relapses occurred during the next 6 years and responded rapidly to oral acyclovir.
An 11-year-old boy presented with unilateral scar of stromal keratitis, severe vitritis, and optic disc neovascularization, followed 6 weeks later by peripheral occlusive retinal vasculitis. Therapeutic and diagnostic vitrectomy was performed, and PCR was found to be positive for varicella zoster virus (VZV) in a vitreous specimen. The inflammation responded to oral acyclovir therapy. Recurrence of anterior uveitis with iris depigmentation occurred 4 months after treatment was arrested. After 4 years, he presented again with a recurrence of anterior inflammation and cystoid macular edema (CME). No sign of inflammation was seen for the next 10 years.
These rare cases support the possible role of herpes viruses (HSV or VZV) in occlusive vasculitis without retinal necrosis. PCR was useful to raise the diagnosis and to adapt the treatment. A good response was obtained on oral antiviral therapy.
KeywordsUveitis Herpes Virus Simplex Zoster Retinal necrosis Polymerase chain reaction Non-necrotizing Vasculitis
Approximately one third of all uveitis cases are associated with infectious agents , and another third remains with an unknown etiology . Polymerase chain reaction (PCR) on intraocular fluids is a reliable and highly sensitive test for the diagnosis of infectious uveitis, including cytomegalovirus (CMV), herpes simplex virus (HSV), and varicella zoster virus (VZV) [3,4].
Several types of herpetic posterior uveitis have been described. The acute retinal necrosis (ARN) syndrome is characterized by peripheral retinal necrosis, retinal arteritis, and a prominent inflammatory reaction in the vitreous and anterior chamber of apparently immunocompetent patients . Progressive outer retinal necrosis syndrome is also a herpetic retinal necrosis with minimal vitreous inflammation occurring in severely immunocompromised patients . A few cases of herpes virus-related non-necrotizing posterior uveitis have been described. Bodaghi et al. described five patients with posterior uveitis unresponsive to steroids and a positive PCR for herpes viruses (HSV or VZV) in the aqueous. The disease did not respond to conventional therapy with systemic corticosteroids and/or immunomodulatory therapy, but favorable response was achieved when therapy was switched to systemic antiviral medication .
We report two new cases of herpetic non-necrotizing retinopathy with long follow-up.
Patients and methods
Patient files were retrieved and retrospectively reviewed. Ophthalmic and systemic data were collected in accordance with the ethic committee of the hospital.
A 19-year-old female was referred in September 1993 for the management of an intravitreal hemorrhage in the right eye, retinal neovascularization of the left eye, and bilateral retinal vasculitis.
Case reports of non-necrotizing herpetic uveitis have been reported very rarely [7,8]. Bodaghi et al. described five patients with posterior uveitis unresponsive to steroids and whose aqueous aspirates were PCR-positive for HSV or VZV. The clinical presentation consisted of retinal vascular involvement, retinal edema, and papillitis. Anterior inflammation was mild or absent. Posterior segment involvement included features masquerading as Birdshot retinochoroidopathy, Behçet’s disease, or idiopathic retinal vasculitis. All patients had chronic inflammation and no necrotizing forms of herpetic retinopathies that progress as an acute disease (ARN or PORN) .
Other cases of atypical variants of ARN have been reported, with a slowly progressive ARN and non-necrotizing forms presenting as vasculitis and/or papillitis or panuveitis . A retinal vasculitis has been described as a complication of primary varicella in an immunocompetent adult . Recently, a case of purely occlusive retinal vasculopathy following varicella zoster infection in an immunocompetent adult, without features of vasculitis or anterior and posterior uveitis, has been published . Chronic herpetic anterior uveitis with focal or multifocal areas of arteriolar sheathing without retinal vascular complications has also been described .
We report two new cases of non-necrotizing herpetic retinopathy characterized by occlusive vasculitis with initial neovascularization and a good response to antiviral therapy. The first patient had a history of bilateral recurrent posterior inflammation not responding to steroids and immunosuppressive treatment. This case occurred long before the first case of herpetic non-necrotizing retinopathy was described, which delayed the diagnosis and antiviral treatment. The second patient presented with a unilateral panuveitis. Both patients had early retinal neovascularization, which has not been described previously .
A herpetic etiology could be confirmed by PCR analysis of ocular fluids: case 1 had a positive PCR for herpes simplex virus type 1 (HSV1) on the aqueous while case 2 had a positive PCR for VZV on the vitreous. Aqueous analysis was contributory in 86.4% of patients with necrotizing viral retinopathies . Bodaghi et al. found that DNA amplification from aqueous could detect VZV and HSV in non-necrotizing herpetic retinopathies .
A remission was obtained in both cases after reaching the proper etiological diagnosis and initiating antiviral treatment. However, several recurrences occurred after arrest of antiviral treatment. The first patient showed relapses of vasculitis after 2 and 4 years, with fast improvement on oral acyclovir. The second patient showed two recurrences of ipsilateral anterior uveitis. Recurrent anterior uveitis following healed ARN has been reported , but to our knowledge, this is the first case of anterior uveitis recurrence after non-necrotizing retinopathy described in the literature. We had previously another patient with a recurrence of HSV2-related acute anterior uveitis demonstrated by PCR, several years after a HSV2-related ARN also demonstrated by PCR (L Caspers, unpublished data). Other types of uveitis tend to recur after an ARN episode [12,13]. Even multiple occurrences of ARN separated over long periods can rarely happen in the same eye .
Long-standing preventative antiviral therapy could be considered for such patients who present with recurrences of intraocular inflammation.
Our two cases confirm that herpes virus may cause non-necrotizing retinopathy with occlusive vasculitis with early retinal neovascularization. These cases point out the importance of ruling out all infectious, including viral, causes in vasculitis, even in the absence of retinal necrosis, before initiation of immunosuppressive therapy and/or when patients do not respond to immunosuppressive treatment. These two cases are, by our knowledge, the first cases of long-term follow-up of non-necrotizing retinopathy.
Written informed consent was obtained from the patients for the publication of this report and any accompanying images.
acute retinal necrosis
cystoid macular edema
herpes simplex virus
polymerase chain reaction
varicella zoster virus
The authors have no support from a funding body.
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