Spotlight Case: Not Your Average Eye Infection
A 52-year-old immunocompetent male with moderate developmental delay presented with a 10-day history of red eye, photophobia, and decreased vision in the left eye. Per his caregiver, he had a history of viral encephalitis nearly 10 years ago. At that time, a herpes simplex virus (HSV) polymerase chain reaction (PCR) cerebrospinal fluid (CSF) test came back negative. There was no history of maternally transmitted infection or other infectious or pertinent medical history. The patient denied any occurrence of ocular disease, injury, or surgery.
Upon examination, visual acuity was 20/30 in the right eye and hand motions vision in the left eye. An afferent pupillary defect was present in the left eye, and intraocular pressure (IOP) in both eyes was within normal limits.
The anterior segment in the right eye was unremarkable. In the left eye, the patient had 2+ conjunctival injection, granulomatous “mutton fat” keratic precipitates (KP), and 3+ anterior chamber cell.
Fundus examination was normal in the right eye. Fundus photographs of the left eye (Figures 1 and 2) revealed moderate vitreous haze, disc edema, and a yellow-white placoid retinal lesion in the superotemporal macula with overlying small intraretinal hemorrhages. A similar lesion and diffuse peripheral retinal whitening were also seen in the nasal periphery.
Optical coherence tomography (OCT) through the macula showed a pocket of subretinal fluid in the macula and temporal full-thickness retinal necrosis (Figure 3). B-scan ultrasonography showed peripapillary retinal thickening with subretinal fluid in the macula and temporal retinal thickening (Figure 4).
What’s your diagnosis?
The most likely diagnosis is infectious unilateral panuveitis with retinitis. Differential diagnosis included:
- Acute retinal necrosis (ARN) HSV vs varicella zoster virus (VZV)
- Cytomegalovirus (CMV) retinitis
- Toxoplasmosis retinitis
The diagnosis was ARN.
The patient underwent vitreous tap, and the fluid was sent for:
- CMV PCR
Blood was sent for:
- Rapid plasma reagin (RPR)
- Fluorescent treponemal antibody-absorption (FTA-ABS)
- Human immunodeficiency virus (HIV)
- Complete blood count (CBC)
- Comprehensive metabolic panel (CMP)
The patient was also sent for a chest X-ray.
The patient was administered 2.4 mg/0.1 mL intravitreal foscarnet, started on 1 g PO TID valganciclovir and 0.05% difluprednate every 2 hours while awake, and given a topical cycloplegic.
The next day, the serous detachment through the macula appeared worse and extended to the inferior arcade. RPR, FTA-ABS, and HIV were negative. The patient was continued on intravitreal foscarnet every 3 days.
On day 6, the eye appeared less inflamed, macular lesions were more consolidated, and subretinal fluid had resolved, but more peripheral lesions emerged (Figures 5-7).
Figure 5: Optos fundus photograph 6 days after initiation of antiviral therapy showed consolidated retinal lesions.
At this point, the patient was administered another injection of foscarnet, and valganciclovir was increased to 2 g PO TID. On day 7, HSV PCR from the vitreous fluid came back positive.
By 2-week follow-up, the patient had received 4 foscarnet injections and was continuing oral antiviral therapy. Fundus photograph showed that the macular and peripheral lesions appeared more consolidated, but multiple peripheral retinal holes were apparent (Figure 8).
ARN was first described in 1971 and is characterized by:
- Acute necrotizing retinitis
- Retinal arteritis
- Late-onset retinal detachment secondary to breaks in atrophic retina
Retinitis is generally multifocal, beginning in the peripheral retina and then spreading to the macula. Vision loss occurs due to vitritis, retinitis, and optic neuropathy. The active phase of the disease lasts approximately 1 month, leaving behind an extremely atrophic retina.
Retinal breaks frequently occur at the junction between atrophic and normal retina, leading to a 75% incidence of rhegmatogenous retinal detachment in untreated patients. The contralateral eye can be involved simultaneously or up to 6 weeks following initial presentation.
Because of its association with meningoencephalitis, the physician should look for signs and symptoms of neurological disease and have a low threshold for obtaining magnetic resonance imaging (MRI). Accordingly, a history of HSV encephalitis is a significant risk factor for the development of ARN.
Although ARN was first described in immunocompetent, healthy hosts, it can manifest in immunocompromised individuals with a fulminant course. Multiple members of the herpes virus family have been implicated, with the most common being VZV and HSV. Pathological specimens demonstrate full-thickness retinal necrosis with retinal arteritis, and exudative retinal detachments have rarely been identified in ARN.
A case report by Duker et al described a fulminant case of ARN with extensive macular involvement and exudative detachment that presented with no light perception (NLP). Similar to our case, the infectious etiology was HSV, but in our case, exudation initially increased and then rapidly resolved after appropriate treatment.
The natural history of ARN carries a poor prognosis secondary to complications such as:
- Macular scarring
- Optic neuropathy
- Rhegmatogenous retinal detachment
The initial management of ARN included induction therapy with intravenous acyclovir followed by oral acyclovir or valganciclovir, but with the recent introduction of intravitreal antivirals, outpatient management has increased. Adjunctive systemic treatment is still necessary, however, to prevent involvement of the contralateral eye.
- Exudative retinal detachment in the setting of ARN may indicate aggressive disease and suggest HSV as a possible etiology.
- Development of neurological changes should be monitored and requires urgent neuroimaging.
- The most common long-term complication of ARN is rhegmatogenous retinal detachment.
- Systemic therapy and intravitreal injections are necessary to prevent involvement of the contralateral eye.
- Urayama A, Yamada N, Sasaki T, et al. Unilateral acute uveitis with retinal periarteritis and detachment. Jpn J Clin Ophthalmol. 1971;25:607-619.
- Duker JS, Nielsen JC, Eagle RC Jr, Bosley TM, Granadier R, Benson WE. Rapidly progressive acute retinal necrosis secondary to herpes simplex virus, type 1. Ophthalmol. 1990;97(12):1638-1643.
- Carney MD, Peyman GA, Goldberg MF, Packo K, Pulido J. Nicholson D. Acute retinal necrosis. Retina. 1986;6(2):85-94.
- Lau CH, Missotten T, Salzmann J, Lightman SL. Acute retinal necrosis features, management, and outcomes [published online December 20, 2006]. Ophthalmol. 2007;114(4):756-762.
Dr. Palejwala - None.
Dr. Lin - None.
Dr. Hau - SEQUENOM: Speaker, Honoraria; THROMBOGENICS, INC: Other, Honoraria.
Dr. Choudhry - None.