Purpose
To describe 3 cases of an acute zonal occult outer retinopathy–like illness responsive to valacyclovir hydrochloride.
Design
Retrospective, interventional case series.
Methods
Three patients were treated with valacyclovir and monitored by clinical examination, Goldmann visual field testing, and electroretinography.
Results
Patients with an acute zonal occult outer retinopathy–like illness presented following progressive vision loss. This course was immediately reversed by treatment with oral valacyclovir, and visual acuity and visual field improved significantly at 1 week and 1 month. Patients remained stable without treatment during a follow-up period ranging from 1 to 3 years.
Conclusions
Some conditions with features of acute zonal occult outer retinopathy may be attributable to a subacute herpetic viral infection that is responsive to oral antiviral medication.
There is a group of patients with acute vision loss that share 1 or more clinical features that include patchy or zonal visual field loss, photopsias, outer retinal or photoreceptor dysfunction, asymmetric electroretinographic abnormalities, vitreous cells, an antecedent flu-like illness, and a nearly normal fundus examination. In 1993 Gass described a series of such patients and suggested the term “acute zonal occult outer retinopathy” (AZOOR); Fletcher in 1988 had described other patients with acute idiopathic blind spot enlargement and no disc edema. Retinal vascular narrowing and retinal pigment epithelial atrophy similar to retinitis pigmentosa may develop in later stages. The visual field loss is often permanent, and the second eye may become involved within several years. The underlying etiology of these AZOOR-like illnesses is not known, but both autoimmunity and a viral etiology have been suggested.
Herpes-family virus is highly prevalent in the population, and seroconversion can be asymptomatic. Autopsy studies have established that latent herpesvirus is present in virtually every organ system. New and highly sensitive laboratory testing has shown that otherwise immunocompetent patients may develop subacute disease with viral reactivation. This may be attributable to subclinical immunosuppression where specific immunologic cells and signals in the innate and acquired immune system that normally suppress viral reactivation and shedding are affected. These observations have given rise to the concept of subacute herpetic viral infections with significantly greater variance in the clinical manifestations than previously appreciated. For example, patients who originally did not meet all the diagnostic criteria for herpetic encephalitis, but had some of the symptoms with less severity, seemed to respond to antiviral medication and were eventually found to have increased viral loads after DNA polymerase chain reaction (PCR) testing of the cerebrospinal fluid.
We encountered 3 patients with clinical features suggestive of AZOOR and considered the possibility of a subacute herpesvirus infection analogous to that described in other central nervous system disorders. These patients were treated with oral valacyclovir, and their cases are described.
Methods
A retrospective case series was assembled from the charts of 3 patients who were informed prior to treatment regarding the off-label use of the medication, lack of randomized clinical trial data to support its efficacy, and potential adverse effects. Subjects underwent eye examinations that included slit-lamp examination, dilated retinal biomicroscopy and indirect ophthalmoscopy, optical coherence tomography, Goldmann visual field testing, and electroretinography. Patients were given 3 grams of oral valacyclovir daily for 1 week and then 1 gram daily for an additional 3 weeks. The medication was then tapered over 1 month.
Results
Case 1
A 26-year-old male patient experienced a flu-like illness and over 2 weeks noticed rapid, progressive vision loss in both eyes. He was otherwise healthy, and an outside magnetic resonance image (MRI) and complete blood count were normal. On examination, his visual acuity was 20/20 in both eyes. The spectacle refraction was −4.00 OU. His intraocular pressures were 9 and 15 mm Hg. His anterior segment exam was unremarkable. A dilated fundus examination showed healthy optic discs, retinal vessels, maculas, and foveas ( Figure 1 , A and B). There were 1+ and trace vitreous cells in the right eye and left eye respectively. A Goldmann visual field revealed severe constriction of all isopters in the right eye. Defects in the left eye included scotomas and an enlarged blind spot ( Figure 1 , C and D). An electroretinogram demonstrated mild depression of the scotopic dim flash in the right eye relative to the left eye ( Figure 1 , I).
The patient was given the presumptive diagnosis of bilateral AZOOR and started on valacyclovir as described in the Methods. His vision stabilized immediately and began to improve within a few days. Visual field testing confirmed improvement at 1 week ( Figure 1 , E and F). In the next 4 weeks, the right visual field expanded significantly, leaving only a modest depression inferiorly ( Figure 1 , H). Subtle retinal pigment epithelial atrophy became apparent in the zone corresponding to his field loss ( Figure 1 , J). The left visual field also normalized. He has not had a recurrence in the last 3 years and his visual fields remain stable.
Case 2
A 14-year-old female patient was referred for evaluation of longstanding pigmentary retinopathy and unilateral vision loss in her right eye. She felt that her peripheral vision had gradually decreased 6 months prior to presentation and that her night vision had worsened. She was otherwise healthy. An outside MRI was normal. There was no family history of inherited eye disease. On examination, her visual acuity was 20/30 in the affected right eye and 20/20 in the asymptomatic left eye. The intraocular pressures were 13 and 9 mm Hg. Her anterior segment exam was unremarkable. A dilated fundus exam showed waxy pallor of the disc in the right eye and a normal disc in the left eye ( Figure 2 , A and B). The right fundus showed attenuated arterioles and patchy pigmentary changes in the peripheral retina with bone spicule–like pigmentation. There were mild vitreous cells in the right eye. Goldmann visual field testing demonstrated only a 10-degree I4e isopter in the right eye with a dense ring scotoma of the V4e (similar to Figure 2 , D). This contrasted sharply with her normal left eye. The left fundus appeared normal and demonstrated a normal 60- to 80-degree I4e isopter in the left eye (data not shown). Optical coherence tomography (OCT) imaging revealed extensive loss of the photoreceptor layer in the right eye but appeared to have a normal thickness in the asymptomatic left eye ( Figure 1 , H). These findings were consistent with a unilateral retinitis pigmentosa phenotype or a late-stage AZOOR-like illness. The patient refused electroretinography studies.
The patient returned 30 months later complaining of acute, progressive vision loss over the last 2 weeks in what had been her normal left eye, similar to what she had experienced in her right eye. She also reported a flu-like illness and a “pink” left eye 1 month prior. On examination, her visual acuity had deteriorated to hand motions in the right eye and 20/60 in the left eye. The intraocular pressures were 13 mm Hg in both eyes. Her anterior segment examination was normal. The optic discs and fundus examination appeared similar to her prior examination. There were no pigmentary changes in her newly symptomatic left eye. There were no posterior uveitis findings. Goldmann visual field testing, however, revealed 3 new central scotomas in the left eye ( Figure 2 , C). There were no changes in the right eye visual field or OCT.
Recurrent AZOOR in the fellow eye was suspected, and she was started on valacyclovir as described in the Methods. She reported that her vision stabilized immediately and improved during the first week of treatment. There was resolution of a central scotoma in the left eye on visual field testing at 1 week ( Figure 2 , E). Within 1 month of treatment, her symptoms improved along with her visual acuity, which returned to a 20/60 in the right eye and improved to 20/25 in the left eye. Goldmann visual field testing also showed the left eye central scotomas had disappeared ( Figure 2 , G), and she was tapered off the valacyclovir. She has not had any recurrences during her 18-month follow-up.
Case 3
A 37-year-old healthy female patient presented to the emergency department when she noticed dark spots with a few photopsias in her right eye for the past week. She did not report any floaters, pain, photophobia, or amaurosis. There was no family history of inherited eye disease. She was healthy without an antecedent viral infection, migraines, diabetes, or hypertension. On examination, her visual acuity was 20/25 in the right eye and 20/20 in the left eye. The intraocular pressures were 16 and 15 mm Hg. There was no relative afferent pupillary defect. Her anterior segment examination showed only mild conjunctival injection. A dilated fundus examination was unremarkable. The next day she complained of increased black spot size and she was referred to our service.
The vision in her symptomatic right eye decreased to 20/40 but remained 20/20 in her left eye. The fundus examination showed only a few small cuticular drusen and no evidence of a neovascular membrane ( Figure 3 , A and B). There were no signs of a posterior uveitis, vitreous detachment, retinal tear, or retinal detachment. Fluorescein angiography was normal. A multifocal electroretinogram, however, showed decreased amplitudes in the right eye but normal waveforms in the left eye ( Figure 3 , C). Goldmann and Humphrey visual field (insert) testing revealed scotomas in the central 10 and 30 degrees of the right visual field ( Figure 3 , E). The visual fields were normal in the asymptomatic left eye ( Figure 3 , D). Although the left eye OCT was also normal, the affected right eye imaging suggested asymmetric reflectivity of the outer nuclear layer in the area corresponding to the scotoma ( Figure 3 , F). There was no photoreceptor loss at the disc.
The patient was started on valacyclovir and reported that the dark spots began to disappear within the first few days of treatment, and were completely gone at her 1-month follow-up. Examination confirmed her visual acuity returned to 20/20 in the left eye and the central scotomas resolved ( Figure 3 , G). Since stopping valacyclovir over a year ago, she has not had a recurrent episode.
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