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

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 (T inflection ) 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 5.9×10 7 (1.1×10 7 -1.1×10 8 ) copies/mL. The average duration of retinitis was 5±3 weeks. The average T inflection was 4.2±1.6 days. T inflection 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 1.3×10 7 copies/ml) than those without (median 1.1×10 8 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.