Acute retinal necrosis is a syndrome characterized by peripheral necrotizing retinitis, retinal arteritis, and a prominent inflammatory reaction in the vitreous and anterior chamber.1 Varicella-zoster virus, herpes simplex virus types 1 and 2, cytomegalovirus, and, rarely, Epstein–Barr virus have been described as causative agents of acute retinal necrosis syndrome. Herpes simplex virus type 2 (HSV-2) is the most common cause of acute retinal necrosis identified in childhood.2
A 12-year-old boy presented in June 2005 with a 1-week history of blurred vision, pain, and redness in the right eye. His previous ophthalmologic history was remarkable for a chorioretinal scar in the right fundus, described at age 9 years as an inactive toxoplasmosis scar. The left eye was mildly amblyopic secondary to uncorrected myopia. His general medical history was unremarkable except for sickle cell trait, and direct questioning did not reveal any history of neonatal herpes.
On examination, visual acuity was 20/40 in both eyes. The right eye showed a severe anterior uveitis with large keratic precipitates and an intraocular pressure of 38 mm Hg. Funduscopy revealed a mild vitritis with an area of active retinitis and periphlebitis in the superotemporal vascular arcade surrounding an inactive pigmented chorioretinal scar in the same area (Fig. 1). The left eye was normal at this stage.
Figure 1. Fluorescein Angiogram of the Right Fundus Showing an Inactive Chorioretinal Scar.
The patient was treated for presumed toxoplasmic chorioretinitis using a standard pediatric regimen, and prednisolone 60 mg was started 24 hours after initiation of the antiparasital therapy. The raised intraocular pressure was treated with oral acetazolamide and topical therapy was initiated with latanoprost, fortified prednisolone, and cyclopentolate.
However, 1 week later, vision in the right eye had worsened. Visual acuity was 20/60, the vitritis had now become severe, and there was evidence of 2 clock hours of peripheral retinal necrosis. The left eye had also become involved, with anterior chamber reaction, mild vitritis, multiple areas of retinitis on the major vascular arcades, and associated retinal hemorrhages.
The patient was diagnosed as having presumed cytomegalovirus-induced retinal necrosis, admitted, and treated with intravenous ganciclovir. Anti-toxoplasmic treatment was continued empirically.
Despite the above treatment, visual acuity decreased to 20/200 in the right eye and 20/60 in the left eye. The right eye developed a more dense vitritis, which obscured the fundal view. The left fundus showed peripheral retinal necrosis from the 1 o’clock to 3 o’clock position with vascular sheathing (Figs. 2 and 3). Subsequently, intravenous therapy was changed from ganciclovir to acyclovir and an urgent paracentesis with polymerase chain reaction (PCR) analysis of the aqueous was performed; intra-vitreal foscarnet was also administered to the right eye. It was believed that, although HSV-2 reactivation can be diagnosed by antibody serology, there are high false-negative rates; therefore, a diagnostic paracentesis was warranted in this case.
Figure 2. Left Fundus Showing Vascular Sheathing, Widespread Hemorrhages, and Yellow-White Patches in the Periphery, Which Are Characteristic of Acute Retinal Necrosis.
Figure 3. Fluorescein Angiogram of the Left Fundus Showing Diffuse Dye Leakage from Retinal Veins.
PCR results were positive for HSV-2 and negative for varicella, herpes simplex virus type 1, and cytomegalovirus. The patient’s serology for toxoplasma antibodies IgM and IgG was negative, but maternal serology was positive for HSV-2. As a result, anti-toxoplasmosis treatment was stopped and the dose of both acyclovir and oral prednisolone was increased and titrated according to the vitreous inflammation.
Although the acute retinal necrosis was stabilized using the above treatment, the right eye developed an inferior retinal detachment. This was treated at a specialist pediatric center with vitrectomy and silicone oil implant, resulting in a complete reattachment of the retina.
The patient was treated with a decreasing regimen of intravenous acyclovir (administered through a Hickman line as an outpatient procedure) and oral foscarnet over 4 weeks, with regular indented funduscopy to check for reactivation or retinal detachment in the fellow eye.
At last follow-up, 3 months after initial presentation, acute retinal necrosis had not reactivated and the patient retained a visual acuity of 20/60 in the right eye and 20/40 in the left eye, with only minor changes in the peripheral visual field.
Chorioretinal scarring is a well-known feature of previous toxoplasmic chorioretinitis. In this case report, the preexisting chorioretinal scar described in the right fundus was caused by HSV-2, as con-firmed by PCR analysis of the aqueous. PCR is a sensitive and specific method to detect viral DNA in ocular samples from immunocompetent and immunocompromised patients presenting with necrotizing retinitis.3 Furthermore, serum toxoplasmosis antibodies IgM and IgG were reported as negative, indicating the chorioretinal scar initially described could not have been caused by toxoplasmosis.
Tran et al.4 described three patients with preexisting, inactive chorioretinal scars in HSV-2 acute retinal necrosis. In these patients, PCR testing was negative for toxoplasmosis. Only one patient had a history of neonatal herpes. Tan et al.5 described two patients with preexisting scars that were stigmata of previous chorioretinal disease in HSV-2 acute retinal necrosis. Thompson et al.6 described two patients with acute retinal necrosis caused by recrudescence of latent HSV-2 infection and the presence of bilateral chorioretinal scars. Schlingemann et al.7 described one patient with recurrent genital herpes, preexisting bilateral chorioretinal scars, and bilateral acute retinal necrosis.
HSV-2 acute retinal necrosis has been reported in children with documented neonatal herpes infection.4,6 It has been postulated that HSV-2 acute retinal necrosis occurring in children and young adults without a history of neonatal herpes, as in this case report, in fact represents reactivation of subclinical congenital or neonatal HSV infection. Recurrence of congenital HSV-2 infection is suggested by the presence of chorioretinal scars, maternal seropositivity for HSV-2, and the lack of previous ocular or extraocular HSV-2 infection. This case manifested each of these three features.
Following initial anti-parasite treatment and steroid-induced immunosuppression, bilateral acute retinal necrosis developed, suggesting high-dose steroids might play a triggering role in acute retinal necrosis related to HSV-2. Tran et al.4 described three patients with HSV-2 acute retinal necrosis triggered by oral and systemic corticosteroids. Browning8 described two patients who developed acute retinal necrosis following epidural corticosteroid injections for back pain.
Retinal detachment associated with proliferative vitreoretinopathy is the main complication of acute retinal necrosis.9,10 In our case, this complication was recognized and treated early, with good results. Early vitrectomy and silicone oil tamponade is the treatment of choice to stabilize retinal structure and preserve visual acuity.11
Prophylactic argon laser retinopexy has been recommended in acute retinal necrosis.12,13 However, this procedure is not always feasible because of vitreous clouding, as in this case. Furthermore, reports of retinal detachment despite prophylactic argon laser retinopexy have made this practice outdated.9,10
In cases of vitritis and retinitis in children and young adults, where there has been previous documentation of chorioretinal scarring, recurrence of HSV-2 must be considered early in the differential diagnosis. Where reactivation of toxoplasmosis carries a relatively indolent clinical course with appropriate treatment, HSV-2 can lead to visually devastating acute retinal necrosis, which is often bilateral, as in this case.
Careful clinical examination and daily follow-up are important for early recognition, and the treatment of choice is high-dose intravenous acyclovir. The role of steroids is somewhat controversial. It is postulated that immunosuppression may compound the pathogenicity of the HSV-2 lesions; however, some regard steroid treatment of inflammation as important in preventing secondary complications such as retinal detachment.
Treatment of the condition often requires long inpatient admissions to administer high-dose intravenous therapy. However, treatment must be tapered slowly to minimize chances of reactivation; coupled with intense follow-up, this can allow for an ultimately satisfactory visual result.
- : Holland GN. Standard diagnostic criteria for the acute retinal necrosis syndrome. Am J Ophthalmol. 1994;117:663–667.
- : Ganatra JB, Chandler D, Santos C, Kuppermann B, Margolis TP. Viral causes of the acute retinal necrosis syndrome. Am J Ophthalmol. 2000;129:166–172. doi:10.1016/S0002-9394(99)00316-5 [CrossRef]
- : Tran THC, Rozenberg F, Cassoux N, Rao NA, LeHoang P, Bodaghi B. Polymerase chain reaction analysis of aqueous humour samples in necrotising retinitis. Br J Ophthalmol. 2003;87:79–83. doi:10.1136/bjo.87.1.79 [CrossRef]
- : Tran THC, Stanescu D, Caspers-Velu L, Frith PA, Graham EM. Clinical characteristics of acute HSV-2 retinal necrosis. Am J Ophthalmol. 2004;137:872–879. doi:10.1016/j.ajo.2003.12.036 [CrossRef]
- : Tan J, Byles D, Stanford M, et al. . Acute retinal necrosis in children caused by herpes simplex virus. Retina. 2001;21:344–347. doi:10.1097/00006982-200108000-00008 [CrossRef]
- : Thompson WS, Culbertson WW, Smiddy WE, Robertson JE, Rosenbaum JT. Acute retinal necrosis caused by reactivation of herpes simplex virus type 2. Am J Ophthalmol. 1994;118:205–211.
- : Schlingemann RO, Bruinenberg M, Wertheimvan Dillen P, Feron E. Twenty years’ delay of fellow eye involvement in herpes simplex virus type 2-associated bilateral acute retinal necrosis syndrome. Am J Ophthalmol. 1996;122:891–892.
- : Browning DJ. Acute retinal necrosis following epidural steroid injections. Am J Ophthalmol. 2003;136:192–194. doi:10.1016/S0002-9394(03)00095-3 [CrossRef]
- : Müller B, Velhagen KH, Pleyer U. Acute retinal necrosis syndrome: analysis, therapy and long-term follow up of 14 eyes [article in German]. Klin Monatsbl Augenheilkd. 2000;217:345–350. doi:10.1055/s-2000-9573 [CrossRef]
- : Morel C, Metge F, Roman S, et al. . Acute retinal necrosis: clinical presentation, treatment, and prognosis in a series of 22 patients [article in French]. J Fr Ophtalmol. 2004;24:7–13.
- : Hou CH, Chen SN, Ho JD, Ho CL. Surgical treatment of retinal detachment following acute retinal necrosis syndrome: surgical results in four patients. Chang Gung Med J. 2003;26:835–842.
- : Hudde T, Althaus C, Sundmacher R. Acute retinal necrosis syndrome: argon laser coagulation for prevention of rhegmatogenous retinal detachment [article in German]. Ophthalmologe. 1998;95:473–477. doi:10.1007/s003470050299 [CrossRef]
- : Sternberg P Jr, Han DP, Yeo JH, et al. . Photocoagulation to prevent retinal detachment in acute retinal necrosis. Ophthalmology. 1988;95:1389–1393.