Acute retinal necrosis (ARN) typically presents as focal, well-demarcated areas of peripheral retinal necrosis with rapid, circumferential progression.1 An occlusive vasculitis and prominent inflammatory reaction in the vitreous and anterior chamber is sometimes present, and the clinical course can be complicated by retinal detachment.2 The specific viral etiology of the infection is associated with patient age. Herpes simplex virus type 2 (HSV-2) is often implicated as the causative agent of ARN in young patients; HSV type 1, varicella zoster virus, and cytomegalovirus are more common in older patients with ARN. HSV-associated ARN frequently occurs with HSV meningitis or encephalitis.2,3
Transmission of HSV can occur in pregnancy, during delivery, or postnatally. With primary infection in the mother, very high titers of the virus are shed from the vulva and cervix, and infection can occur in newborns during labor (direct genital contact) or by ascending amnionitis after rupture of membranes (transplacental). Reactivated herpetic lesions are usually vulval, and transmission occurs during passage through the birth canal. Infected neonates often have dissemination involving the central nervous system, retina, and visceral organs, especially the liver. Recognition of infection after birth is often after neurological sequelae are already manifest.
The authors have identified several case reports in the literature, including a series of 13 patients from both the Bascom Palmer Eye Institute at the University of Miami and Byers Eye Institute at Stanford University, which contained only three neonatal cases.4 The authors present an additional three cases of neonatal acute retinal necrosis secondary to HSV-2.
A 2-month-old female infant delivered vaginally at 32 weeks of gestation with a history of seizures, intracranial hemorrhage, diffuse encephalopathy, and periventricular leukomalacia was transferred to Jackson Memorial Hospital/Bascom Palmer Eye Institute (JMH/BPEI) for evaluation of posterior uveitis.
The dilated fundus examination revealed dense vitritis and a total exudative retinal detachment with peripheral whitening in her right eye, consistent with ARN, as seen in Figure 1. The posterior segment of the left eye was unremarkable. Aqueous fluid tap was performed at the bedside while the infant was awake. Polymerase chain reaction (PCR) analysis of aqueous fluid in the right eye was positive for HSV-2. Cerebrospinal fluid PCR analysis was negative for HSV. A diagnosis of herpetic meningoencephalitis with ocular involvement was made, and the patient was started on a 3-week course of intravenous acyclovir. Topical prednisolone acetate 1% and cyclopentolate 0.5% were added as adjuvants.
Montage of the right eye exhibiting circumferential retinal necrosis, subretinal exudation, and vitritis in case 1.
At 1-week follow-up, areas of vasculitis and retinitis were present in the left eye. Systemic steroid treatment was started, and the lesions showed rapid improvement.
A 2-month-old female infant delivered vaginally at 37 weeks of gestation with a history of seizures, intracranial calcifications, and serum positivity for HSV-2 was admitted to JMH/BPEI for evaluation of poor vision in the left eye as noted by the parents.
Dilated fundus examination revealed partial posterior vitreous separation with areas of vitreoretinal traction, peripheral retinitis, and vitreous hemorrhage in the left eye, consistent with ARN. The posterior segment findings in the right eye were unremarkable. Laser demarcation was performed in the left eye without complications. Serology indicated high titers for HSV-2, although there was no identification of the virus via PCR or culture initially. Subsequent PCR confirmed HSV-2. A diagnosis of HSV retinitis was made, and the patient was treated with oral acyclovir. The patient’s vision, vitreoretinal tractions, and vitreous hemorrhage improved progressively at subsequent follow-up visits, and no surgery was required.
A 5-week-old male infant delivered via cesarean delivery due to twin gestation at 29 weeks gestation with skin lesions near the umbilicus and left buttocks was transferred to JMH/BPEI due to suspected bilateral HSV retinitis.
The dilated fundus examination showed active retinitis and vitritis bilaterally. The retina was vascularized to zone II without a demarcation line. Indirect ophthalmoscopy showed bilateral vitreous opacifications with associated temporal retinal whitening, consistent with ARN. Corneal haze was present in both eyes. Aqueous fluid tap was performed at the bedside while the infant was awake. PCR analysis of aqueous fluid in the right eye was positive for HSV-2. Magnetic resonance imaging of the brain showed non-specific findings.
Prophylactic laser treatment was applied bilaterally due to high risk of retinal detachment. Two weeks after treatment, the patient developed a tractional retinal detachment in his right eye that was repaired with a scleral buckle and laser retinopexy.
After 8 weeks of intravenous and oral treatment with acyclovir, only a corneal stromal scar was present in the left eye. There was inactive macular dragging and pigmented retinal atrophy at the temporal periphery bilaterally (Figures 2 and 3).
Right eye after laser retinopexy and scleral buckle in case 3.
Left eye after laser retinopexy in case 3.
ARN affects patients of all ages, with HSV-2 as the primary causative agent in infants and children. Infant inoculation may occur through the placenta or via direct contact of the infant cornea with the genital tract. Neonates, especially those born prematurely, may be at increased risk for HSV-2 ARN secondary to relative immunocompromised state.
There have been few previous case reports of HSV-2–associated ARN in neonates, many of whom already presented with neurological findings.4–7 Common findings of ARN include necrotizing retinitis with a confluence of white patches peripherally. Traction and exudative retinal detachment can also occur; however, characterizing the degree of visual loss in a newborn is challenging.8
Treatment involves antiviral therapy with acyclovir or famciclovir for resolution of infection and for protection of the fellow eye.2,9,10 Some have suggested the use of prophylactic laser retinal photocoagulation to prevent retinal detachment, and surgical repair by pars plana vitrectomy with silicone oil tamponade should retinal detachment occur.11 Pediatricians who treat patients with symptoms of HSV meningoencephalitis should consider a rapid referral to ophthalmology to ensure a timely diagnosis of ARN and appropriate treatment of the retinitis or potential retinal detachment if present.5 If the eye is infected, dissemination along the central nervous system and visceral organs is usually seen, sometimes with fatal consequences.12,13 The presence of HSV should be considered in patients with a history of central nervous system disease and fulminant ARN with or without retinal detachment.
With the increasing incidence of genital herpes, clinicians should anticipate an increasing incidence of ARN secondary to HSV-2.5 Thus, it may be beneficial to determine serum HSV-2 titers in all mothers during prenatal screening if cervical PCR testing results are positive, especially given that congenital HSV can occur without a known history of in utero infection.2 In addition, because seronegative women with seropositive partners can seroconvert at any time, testing of couples can identify women at risk and enable preventive measures such as prophylactic acylovir for protection or early treatment of the neonate.14,15
- Muthiah MN, Michaelides M, Child CS, Mitchell SM. Acute retinal necrosis: a national population-based study to assess the incidence, methods of diagnosis, treatment strategies and outcomes in the UK. Br J Ophthalmol. 2007;91(11):1452–1455. doi:10.1136/bjo.2007.114884 [CrossRef]
- Van Gelder RN WJ, Holland GN, Kaplan HJ. Herpes simplex virus type 2 as a cause of acute retinal necrosis syndrome in young patients. Ophthalmology. 2001;108(5):869–876. doi:10.1016/S0161-6420(01)00556-5 [CrossRef]
- Ganatra JB, Chandler D, Santos C, Kuppermann B, Margolis TP. Viral causes of the acute retinal necrosis syndrome. Am J Ophthalmol. 2000;129(2):166–172. doi:10.1016/S0002-9394(99)00316-5 [CrossRef]
- Silva RA, Berrocal AM, Moshfeghi DM, Blumenkranz MS, Sanislo S, Davis JL. Herpes simplex virus type 2 mediated acute retinal necrosis in a pediatric population: case series and review. Graefes Arch Clin Exp Ophthalmol. 2013;251(2):559–566. doi:10.1007/s00417-012-2164-8 [CrossRef]
- Kychenthal A, Coombes A, Greenwood J, Pavesio C, Aylward GW. Bilateral acute retinal necrosis and herpes simplex type 2 encephalitis in a neonate. Br J Ophthalmol. 2001;85(5):629–630. doi:10.1136/bjo.85.5.625f [CrossRef]
- Wong RK KA, Sun G, Heier LA, Saffra N, Chan RVP. Acute retinal necrosis and cystic encephalomalacia in a premature neonate. Retinal Cases Brief Rep. 2009;4(2):202–205. doi:10.1097/ICB.0b013e3181ad3900 [CrossRef]
- Gupta A, Rani PK, Bagga B, Dore P, Mittal A, Jalali S. Bilateral herpes simplex-2 acute retinal necrosis with encephalitis in premature twins. J AAPOS. 2010;14(6):541–543. doi:10.1016/j.jaapos.2010.08.011 [CrossRef]
- Itoh N, Matsumura N, Ogi A, Nishide T, Imai Y, Kanai H, et al. High prevalence of herpes simplex virus type 2 in acute retinal necrosis syndrome associated with herpes simplex virus in Japan. Am J Ophthalmol. 2000;129(3):404–405. doi:10.1016/S0002-9394(99)00391-8 [CrossRef]
- Ezra E PR, Etchells DE, Gregor ZJ. Delayed fellow eye involvement in acute retinal necrosis syndrome. Am J Ophthalmol. 1995(120):115–117. doi:10.1016/S0002-9394(14)73770-5 [CrossRef]
- Abe T, Sato M, Tamai M. Correlation of varicella-zoster virus copies and final visual acuities of acute retinal necrosis syndrome. Graefes Arch Clin Exp Ophthalmol. 1998;236(10):747–752. doi:10.1007/s004170050153 [CrossRef]
- Figueroa MS GI, Gutierrez C, Fortun J. Famciclovir for the treatment of acute retinal necrosis (ARN) syndrome. Am J Ophthalmol. 1997(123):255–257. doi:10.1016/S0002-9394(14)71045-1 [CrossRef]
- Suh Y.L, Kim H, Chi J.G., Byun H.R., Lee K. Disseminated neonatal herpes simplex virus infection with necrotizing encephalitis--an autopsy case. J Korean Med Sci. 1987;2(2):123–127. doi:10.3346/jkms.1922.214.171.124 [CrossRef]
- Greer C. Bilateral necrotizing retinitis complicating fatal encephalitis probably due to herpes simplex virus type 2. Int J Ophthalmol Zeitschrift fur Augenheilkunde. 1980;180(3):146–150. doi:10.1159/000308969 [CrossRef]
- Kulhanjian JA SV, Au DS, Bronzan RN, et al. Identification of women at unsuspected risk of primary infection with herpes simplex virus type 2 during pregnancy. N Engl J Med. 1992;326(14):916–920. doi:10.1056/NEJM199204023261403 [CrossRef]
- Watts DH, Brown ZA, Money D, Selke S, Huang ML, Sacks SL, et al. A double-blind, randomized, placebo-controlled trial of acyclovir in late pregnancy for the reduction of herpes simplex virus shedding and cesarean delivery. Am J Obstet Gynecol. 2003;188(3):836–843. doi:10.1067/mob.2003.185 [CrossRef]