Acute retinal necrosis (ARN) is a devastating ocular disease with poor visual prognosis and is most often caused by varicella zoster virus (VZV) or herpes simplex virus (HSV)-1 and less frequently by HSV-2 and cytomegalovirus.1
ARN is characterized by peripheral necrotizing retinitis, retinal arteritis, and a prominent inflammatory reaction in the vitreous and anterior chamber.3
This disease may present several years after a primary infection, or it may occur following systemic herpetic infection. The prevalence of the disease is equal in both genders, and it occurs in the 5th–7th decade of life.4
Though the diagnosis of ARN is made clinically in most patients, polymerase chain reaction (PCR) analysis of the aqueous humor or vitreous is known as a confirmative method to detect the causative virus. Cases who presented with unilateral or bilateral ARN following herpes simplex viral encephalitis (HSE) have been uncommonly reported.5
However, the reverse situation of HSE following ARN has been reported in one case, who was an immune-suppressed patient.10
Herein, we present an unusual case of HSE following ARN in an immune-competent patient.
A 57-year-old man was referred to Samsung Medical Center with abrupt confusion, fever, and loss of vision in both eyes. The patient was in his usual state of health until two weeks prior, when he began to develop sudden loss of vision in his right eye. In another hospital, he was diagnosed with retinal vasculitis in his right eye and was prescribed oral prednisolone, 60 mg/day for three days, followed by 120 mg/day for three days. The retinal vasculitis did not respond to oral prednisolone, so he was treated with intravenous methylprednisolone, 1 g/day for five days. Two days after initiation of intravenous methylprednisolone, he complained of decreased vision in his left eye. One week after initiation of intravenous methylprednisolone, he became drowsy and high fever occurred, and he was then referred to Samsung Medical Center. On neurological examination, he was drowsy and confused to time and place orientation. Mini-mental status examination was 18. He consistently complained of severe headache and bilateral ocular pain. However, his extraocular movement did not show any limitation in all directions. Neck stiffness and meningeal irritation sign were not definite. Other focal neurologic deficits were not found.
His brain magnetic resonance imaging (MRI) showed a hyper-intense lesion in the left medial temporal and bilateral medial occipital areas on T2-weight images, suggestive of HSE (Fig. 1
). Cerebrospinal fluid (CSF) study revealed 11 cells/mL (lymphocytes 90%), low protein (19.3 mg/dL), and normal range glucose concentration (63 mg/dL compared to 110 mg/dL in serum). An empirical antiviral agent (acyclovir 30 mg/kg/d) was administered intravenously. One week later PCR of the CSF was revealed to be positive for HSV-1 DNA. On the night of admission, the patient experienced a generalized tonic-clonic seizure during sleep. His electroencephalography showed sharp waves in left or right anterior temporal areas (F7T7, F8T8 maximum) with a frequency of 1/min and diffuse slow waves. An antiepileptic drug (phenytoin 300 mg/d) was administered and no more epileptic seizure recurred.
On the day of admission, his visual acuity was perception of light in both eyes. Fundus examination showed retinal hemorrhage, confluent retinal necrosis affecting almost the whole retina, vascular sheathing involving both arterioles and venules, optic disc swelling, and exudative retinal detachment in both eyes (Fig. 2A
). Fluorescein angiography revealed multiple vascular occlusions and vascular leakage. Ultrasonography shows retinal detachment in both eyes (Fig. 2B
). Infectious retinitis including acute retinal necrosis was suspected, but in terms of the location of necrosis, his clinical features were not typical of ARN Diagnostic vitrectomy confirmed the presence of HSV-1. Finally, he was diagnosed with ARN with optic neuropathy by HSV-1.
After administration of intravenous acyclovir for 14 days, his systemic symptoms consistent with encephalitis slowly resolved, but his vision was not restored. On follow-up examination, retinal necrosis did not progress, but he still suffered from severe bilateral ocular pain with partial improvement of the exudative retinal detachment (Fig. 2C, D
). Thus, intravitreal ganciclovir injection (5,000/0.05 μg/mL) causes pain relief and decreased intraocular inflammation. But his visual acuity could not perceptany light. Bilateral rhegmatogenous retinal detachment with optic atrophy was found six weeks later, thus vitrectomy with silicone oil tamponade was done in the right eye.
Cases with ARN following HSE have been uncommonly reported,5
and to our knowledge, this is the first report of the reverse situation, HSE following ARN, in even an immune-competent patient. ARN associated with HSE is known to be caused by axonal transmission of a reactivated latent virus from the brain to the retina, and retinitis occasionally occurs after the encephalitis. As shown by our patient, opposite direct transmission from the retina to the brain seems to be possible. This is consistent with the finding that herpes virus uses bidirectional fast-axonal transport in neurons.11
ARN usually presents as retinal necrosis with discrete borders located in the peripheral retina, rapid progression, circumferential spread, occlusive vasculopathy with arterial involvement, and a prominent inflammatory reaction in the vitreous and anterior chamber.3
Our patient was initially diagnosed with retinal vasculitis and treated with a high-dose systemic corticosteroid, which was not effective. Corticosteroids are known to affect cellular immunity and may promote viral replication. Intraocular or systemic corticosteroids may induce retinal necrosis in patients with viral infection. Thus, it is recommended that corticosteroids should be used in combination with antiviral agents or after beginning antiviral therapy.12
In this patient, the contralateral eye became infected, and HSE occurred during initial corticosteroid therapy without antiviral medication. In cases with an unusual clinical course, especially in retinal vasculitis with arterial involvement, viral uveitis including HSV infection should be suspected. Diagnostic vitrectomy to obtain a vitreous specimen is appropriate in those cases.
In summary, ARN may be a risk factor for HSE, even in an immune-competent patient. The virus may reach the brain from the eye by a trans-axonal route. Systemic steroid therapy may have exacerbated herpes viral infection in the retina, with subsequent spread to the contralateral eye and brain.