Ophthalmic Surgery, Lasers and Imaging Retina

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Case Report 

Intravitreal Foscarnet Therapy for Acyclovir-Resistant Acute Retinal Necrosis After Herpes Simplex Encephalitis

Payal Patel; Ednan Ahmed, MD; Manju L. Subramanian, MD

Abstract

The development of acute retinal necrosis (ARN) is not uncommon among individuals with a history of herpes simplex encephalitis, as the virus may be capable of transport via axonal cells to the neuroretina. Though it is known that ARN severely threatens vision, timely initiation of effective therapy can help save a patient’s vision and retina. In this case report, clinical resistance to acyclovir was found. Subsequent treatment with intravitreal foscarnet resulted in immediate clinical improvement. This case suggests that patients with acute retinal necrosis can be considered for treatment with intravitreal foscarnet in the setting of systemic acyclovir resistance.

Abstract

The development of acute retinal necrosis (ARN) is not uncommon among individuals with a history of herpes simplex encephalitis, as the virus may be capable of transport via axonal cells to the neuroretina. Though it is known that ARN severely threatens vision, timely initiation of effective therapy can help save a patient’s vision and retina. In this case report, clinical resistance to acyclovir was found. Subsequent treatment with intravitreal foscarnet resulted in immediate clinical improvement. This case suggests that patients with acute retinal necrosis can be considered for treatment with intravitreal foscarnet in the setting of systemic acyclovir resistance.

Intravitreal Foscarnet Therapy for Acyclovir-Resistant Acute Retinal Necrosis After Herpes Simplex Encephalitis

From Boston University School of Medicine, Boston, Massachusetts.

The authors have no financial or proprietary interest in the materials presented herein.

Address correspondence to Payal Patel, 761 Harrison Ave., Apt. # 103, Boston, MA 02118.

Accepted: September 11, 2009
Posted Online: March 09, 2010

Introduction

Acute retinal necrosis (ARN) is a disorder that threatens vision by affecting the neuroretina and causing severe retinitis.1 The syndrome is linked to the reactivation of the herpes virus within the eye. Herpes simplex encephalitis (HSE), which occurs when active herpes simplex virus (HSV) accesses the brain, can precede ARN.2 Unfortunately, the natural history of ARN can be visually devastating, often resulting in permanent vision loss. In patients who have had HSE and usually have some neurological deficit from the disease, the loss of vision can add a severe morbidity.

Case Report

An immunocompetent 35-year-old man developed HSE and was treated with intravenous acyclovir. His clinical course was unremarkable, and although he recovered, he was left with anterograde memory loss, seizure disorder, and lower mental capabilities. The patient was not placed on chronic oral acyclovir antiviral therapy for prophylaxis. Twenty-four months later, he was referred to the vitreoretinal clinic after a recent diagnosis of panuveitis in the right eye (OD). He presented with a red and severely painful right eye, a vision of 20/100, an intraocular pressure of 34 mm Hg, and anterior chamber inflammation with 3+ cells OD. Fundoscopic examination revealed vitritis, sectoral edema of the optic disc, and a large area of whitish opaque retina just below the inferior arcade (Fig. 1). A tentative diagnosis of acute retinal necrosis was made.

Initial Presentation with ARN. Lesions are Mostly Inferior to Arcade

Figure 1. Initial Presentation with ARN. Lesions are Mostly Inferior to Arcade

He was immediately admitted to the hospital and started on intravenous acyclovir treatment of 10 mg/kg q8h. Topical drops initiated include pred forte, scopolamine, and brimonidine. After 4 days of treatment, there were no signs of improvement and the retinal necrosis continued to progress (Fig. 2). The acyclovir treatment dose was increased to 12 mg/kg q8h. Oral steroids were held because the patient still had progressive retinitis and the diagnosis was still in question. Due to a poor clinical response to IV acyclovir, he was started on biweekly intravitreal foscarnet (2.4 mg) injections in the affected eye for a total of three injections. Soon after administering the first injection, the vision and the lesions stabilized, his eye pain disappeared, and no further progression of the peripheral retinitis was observed (Fig. 3). As his diagnosis was unconfirmed and there was persistent vitritis, diagnostic vitrectomy following the third injection was performed. Viral cultures grew HSV I. Serologic lab tests were negative for cyto megalo virus (CMV), human immuno defficiency virus (HIV), HSV I, HSV II, and Lyme.

Lesions Progess on High Dose IV Acyclovir Therapy.

Figure 2. Lesions Progess on High Dose IV Acyclovir Therapy.

Lesions Stabilize on Foscarnet Therapy. The Vasculitis and Subretinal Fluid Above the Arcade Have Improved.

Figure 3. Lesions Stabilize on Foscarnet Therapy. The Vasculitis and Subretinal Fluid Above the Arcade Have Improved.

The patient subsequently developed a retinal detachment and underwent vitrectomy, lensectomy, endolaser, and silicone oil fill (Fig. 4). After surgery, there was persistent anterior segment inflammation. On the lastest follow-up visit, one year after the initial diagnosis, the patient had hand motion vision and a flat retina (Fig. 5). He remains aphakic with silicone oil in his right eye. His left eye remains at 20/20 with no evidence of disease. He is currently on life-long valacyclovir treatment of 1g 3 times a day.

Retinal Detachment Developed 3 Weeks After Initial Diagnosis.

Figure 4. Retinal Detachment Developed 3 Weeks After Initial Diagnosis.

Retina Reattached After Vitrectomy and Silicone Oil Fill. There is a Retinectomy Below the Inferior Arcade.

Figure 5. Retina Reattached After Vitrectomy and Silicone Oil Fill. There is a Retinectomy Below the Inferior Arcade.

Discussion

This patient developed acute retinal necrosis 2 years after herpes simplex encephalitis. ARN following HSE is well reported in the literature. About 13.5% of people with ARN had a prior history of encephalitis. Reports show the average time to development of ARN after encephalitis to be approximately 20.6 months.3 This apparent incubation period may represent the time it takes for retrograde axonal transport of the virus from the central nervous system (CNS) to the retina. The concept of retrograde axonal transport has been demonstrated in animal models.4

In this case, there was a similar incubation period, with a 24 month interval from initial onset of HSE to development of acute retinal necrosis. However, in contrast to previously reported cases, this patient did not appear to respond immediately to administration of intravenous acyclovir. Instead, the retinal necrosis was progressive until intravitreal foscarnet was administered, causing immediate control and stabilization of the retinal lesions. The use of other systemic antiviral agents, such as oral valacyclovir and famciclovir, was discussed by his providers. While limited pilot data showed that these oral agents may be effective in the treatment of acute retinal necrosis, it was decided that further studies were needed to determine its efficacy for initial treatment, so use of these alternative antiviral agents was deferred.5–6 In addition, the authors requested sensitivity data on the vitreous specimen to test for acyclovir resistance, but the microbiology lab was unable to do it.

Acyclovir resistance is rare but has been previously reported.7–8 The viral resistance in this case may have been related to prior treatment with acyclovir or resistance to the more neuro-virulent strain of HSV, which causes encephalitis. For this patient, stabilization of necrosis and quiescence of the eye following foscarnet therapy is strong evidence of its effectiveness.

As most vitreoretinal specialists are aware, acute retinal necrosis is a disorder well known for its acute onset and rapid progression, as well as its potentially blinding complications. Hence, immediate and aggressive treatment is imperative. The authors’ experience with this case suggests that intravitreal foscarnet can be considered as a potential drug of choice, initiated immediately once resistance to systemic acyclovir is suspected. Further data is required to determine if intravitreal foscarnet, started as sole treatment or in combination with systemic acyclovir, will play a key role as first line therapy for all cases of acute retinal necrosis.

References

  1. Maertzdorf J, Van der Lelij A, Baarsma GS, et al. Herpes simplex virus type 1 (HSV-1) induced retinitis following herpes simplex encephalitis: indications for brain-to-eye transmission of HSV-1. Ann Neurol. 2001;49:104–106. doi:10.1002/1531-8249(200101)49:1<104::AID-ANA15>3.0.CO;2-Y [CrossRef]
  2. Vandercam T, Hintzen RQ, de Boer JH, et al. Herpetic encephalitis is a risk factor for acute retinal necrosis. Neurology. 2008Oct14;71(16):1268–74. doi:10.1212/01.wnl.0000327615.99124.99 [CrossRef]
  3. Vandercam T, Hintzen RQ, de Boer JH, Van der Lelij A. Herpetic encephalitis is a risk factor for acute retinal necrosis. Neurology. 2008Oct14;71(16):1268–74. doi:10.1212/01.wnl.0000327615.99124.99 [CrossRef]
  4. Vann VR, Atherton SS. Neural spread of herpes simplex virus after anterior chamber inoculation. Invest Ophthalmol Vis Sci. 1991; 32:2462–2472.
  5. Aizman A, Johnson MW, Elner SG. Treatment of acute necrosis syndrome with oral antiviral medications. Ophthalmology. 2007Feb;114(2):307–12. doi:10.1016/j.ophtha.2006.06.058 [CrossRef]
  6. Emerson GG, Smith JR, Wilson DJ, Rosenbaum JT, Flaxel CJ. Ophthalmology. 2006Dec;113(12):2259–61. doi:10.1016/j.ophtha.2006.05.063 [CrossRef]
  7. Duan R, de Vries RD, Osterhaus AD, Remeijer L. Acyclovir-resistant corneal HSV-1 isolates from patients with herpetic keratitis. J Infect Dis. 2008Sep1;198(5):659–63. doi:10.1086/590668 [CrossRef]
  8. Chibo D, Druce J, Sasadeusz J, Birch C. Molecular analysis of clinical isolates of acyclovir resistant herpes simplex virus. Antiviral Res. 2004; 61:83–91. doi:10.1016/j.antiviral.2003.08.018 [CrossRef]
Authors

From Boston University School of Medicine, Boston, Massachusetts.

The authors have no financial or proprietary interest in the materials presented herein.

Address correspondence to Payal Patel, 761 Harrison Ave., Apt. # 103, Boston, MA 02118.

10.3928/15428877-20100215-92

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