Association of Seasonal Hyperacute Panuveitis Syndrome with S. pneumoniae Endophthalmitis

Purpose: To identify potential infectious agents in cases of seasonal hyperacute panuveitis syndrome (SHAPU) from vitreous biopsies of patients with this disorder. Design: Retrospective cohort analysisSubjects: Vitreous biopsies were obtained during course of care from 53 subjects with SHAPU.Methods: DNA extraction and whole genome shotgun sequencing was performed using Oxford Nanopore long read sequencing.Sequences were matched against microbial and human databases.Visual outcomes at presentation and at six months were recorded.Main Outcome Measure: Identification and characterization of metagenomic sequences in vitreous isolates from subjects with SHAPU.Results.Adequate DNA for sequencing was obtained from 32 SHAPU subjects.15 samples yielded bacteria on culture, with 14 S. pneumoniae and one S. aureus isolate recovered.Bacterial DNA was detected by whole genome sequencing in 29/32 cases.S. pneumoniae was the predominant organism recovered.Bacterial genomic loads ranged up to 10,000 bacteria/human cell indicating active infection.No pathogens were detected in control samples.Reconstruction of bacterial genome was possible in 7 SHAPU cases and indicated diverse S. pneumoniae subtypes associated with individual cases.Sufficient DNA remained for analysis of torque teno virus by qualitative PCR in 17 cases, of which 13 were positive.Visual outcomes were mixed, with seven patients having hypotonous eyes at 6 months but 8 patients having better than 20/200 vision.No relationship could be discerned between presenting bacterial load and visual outcome.Conclusions.The majority of SHAPU cases show molecular evidence for concurrent S. pneumoniae infection.Good visual results are possible in treating SHAPU as endophthalmitis.