The medical records of our patient with ARN were retrospectively reviewed. An 80-year-old woman developed blurred vision in both eyes 1 month before presenting to JR Sapporo Hospital. Upon entering, an examination found evidence of iritis, vitreous opacity, a mild vitreous hemorrhage and extensive multifocal exudation around the optic disc in her right eye (fig. 1a), as well as mild vitreous opacity, an optic disc hemorrhage and peripheral white granulomatous exudation in her left eye (fig. 1b). A fluorescein fundus angiography demonstrated hyperfluorescence of the optic disc and a wide range of occlusive vasculitis in her right eye (fig. 1c), and retinal vasculitis in the nasal area in her left eye (fig. 1d). The aqueous humor of the right eye was subsequently collected for pathogen analysis by the PCR system. Since the serological analysis was positive for cytomegalovirus (CMV) IgG, she was presumed to have CMV retinitis. She received ganciclovir (75 mg/day) orally, but this triggered no effective response. The uveoretinitis in her right eye deteriorated, and after 1 week, she was transferred to our hospital. Upon admittance, she disclosed that she had been taking oral methotrexate for over 10 years for rheumatoid arthritis.
The initial ophthalmic examination showed a best-corrected visual acuity of light perception in the right eye and 20/25 in the left eye. The intraocular pressure was 13 mm Hg in the right eye and 10 mm Hg in the left eye. A slit-lamp examination demonstrated moderate cell infiltration in the anterior chamber, severe vitreous infiltration, an inferior vitreous hemorrhage and massive exudation in the posterior pole in her right eye. There was no sign of apparent progression in her left eye (fig. 1f). Both eyes showed substantial anterior chamber depth without goniosynechia, and mild senile cataracts.
Results of the laboratory investigations of serum including antinuclear antibodies, anti-double stranded DNA antibodies, an adult T-cell leukemia antigen and antineutrophil cytoplasmic antibodies were unremarkable except for a high rheumatoid factor value. Serological analyses indicated that there was no active infection of syphilis, tuberculosis, human T-cell lymphoma virus 1 or toxoplasma gondii. The virus antibody titer screen was negative for IgM and positive for IgG for HSV, VZV, and CMV. The EBV antibody test showed negative for either IgG against an early antigen or IgM against a viral capsid antigen and positive for both IgG against a viral capsid antigen and IgG against a nuclear antigen.
The patient received continuous administration of topical betamethasone and intravenous aciclovir (700 mg/day) upon admission. Due to the progressive symptoms in her right eye, vitrectomy, retinal photocoagulation and silicone oil tamponade were applied, and phacoemulsification surgery was conducted 5 days after admission. The fundus findings during surgery showed the occlusive vasculopathy of the entire retina, retinal fibrosis and retinal detachment with retinal breaks and vitreous traction (fig. 1e). The vitreous fluid was collected for cytology and pathogen screening. The cytological examination of infiltrated cells in vitreous fluid showed lymphocytes and a few neutrophils but no atypical cells. The culture examination using vitreous fluid was negative for bacteria or fungus. The genomic DNA in vitreous fluid was analyzed by comprehensive PCR to screen infectious pathogens including bacteria, parasites and viruses. The PCR analysis was performed in the laboratory for retinal regeneration at Riken's Center for Developmental Biology (Kobe, Japan), as previously described.
Both the aqueous humor that was collected at the former hospital and vitreous fluid that was collected during surgery showed high copies of EBV but were negative to HSV, VZV, CMV and other pathogens (table 1). Two days after surgery, the patient received oral valaciclovir (1,500 mg/day) and predonisolone (30 mg/day). The dosage of valaciclovir and predonisolone administration was reduced gradually without recurrence of retinitis or development of side effects. Retinal atrophy occurred in her right eye in the necrosis area, and optic nerve atrophy also developed. This resulted in a loss of light perception in the eye. The lesion in her left eye was diminished by the drug treatment. No relapse was observed in 1 year.