Dynamic Viral Load Monitoring and Metagenomic Sequencing in Acute Retinal Necrosis Caused by Varicella-Zoster Virus

Abstract

Purpose: To analyze the trend of intraocular viral load after antiviral treatment in patients with varicella-zoster virus (VZV) induced acute retinal necrosis (ARN), and to explore the effect of viral genotypes on clinical manifestations. Methods: In this case series, viral load was detected using polymerase chain reaction from aqueous humor during treatment; viral load curves were fitted, and the time required to reach the inflection point between plateau phase and logarithmic reduction phase (Tinflection) was estimated. Variations in viral genomes were detected by metagenomic sequencing. Results: Twenty eyes of 20 patients were included. The median (interquartile range) initial viral load was 5.9×107 (1.1×107-1.1×108) copies/mL. The average duration of retinitis was 5±3 weeks. The average Tinflection was 4.2±1.6 days. Tinflection was correlated with the duration of retinitis (P=0.025). Patients with VZVs carrying the p.S715* variation in ribonucleotide reductase (RNR) subunit 1 gene had lower initial viral loads (median 1.3×107 copies/ml) than those without (median 1.1×108 copies/ml; adjusted P=0.030). Conclusions: The inflection of viral load curve is helpful to estimate the length of plateau phase and the duration of retinitis during antiviral treatment in ARN patients. Loss-of-function variation in RNR gene might be correlated with lower virulence of VZV.