Comprehensive analysis of vitreous specimens for uveitis classification: a prospective multicentre observational study

BMJ Open. 2017 Nov 16;7(11):e014549. doi: 10.1136/bmjopen-2016-014549.

Abstract

Purpose: To determine the clinical relevance of vitreous biomarkers in patients with uveitis.

Design: Multicentre, prospective, observational study.

Setting: Uveitis outpatient clinics of two academic medical centres in Japan.

Patient population: This study included 234 eyes of 191 patients with various uveitis aetiologies: definitive sarcoidosis (61 eyes of 46 patients), suspected sarcoidosis (60 eyes of 45 patients), intraocular tumour (34 eyes of 27 patients), viral infection (20 eyes of 18 patients), non-sarcoidosis (16 eyes of 16 patients) and unknown aetiology (43 eyes of 39 patients).

Observation procedure: Vitreous samples (taken by pars planta vitrectomy) were analysed with flow cytometry, cytology and multiplex PCR analysis.

Main outcome measures: The primary outcome measures were the diagnostic values of various biomarkers (T cells, B cells and pathogen DNA) in vitreous samples. The secondary outcome was visual acuity after vitrectomy.

Results: Sarcoidosis showed higher CD4/CD8 or CD4+ measurements than other aetiologies (p<0.01). In samples with viral infection, pathogen DNA was detected, and CD8+ counts were higher than the other aetiologies (p<0.01). Eyes with tumour had higher CD19+ (p<0.05). Non-sarcoidosis had lower CD4/CD8 than sarcoidosis, higher CD8+ than sarcoidosis and lower CD19+ than tumour (p<0.01). Unknown uveitis had lower CD4/CD8 than sarcoidosis (p<0.01), and higher CD4/CD8 than non-sarcoidosis, viral infection or tumour (p<0.001). Visual acuity improved after vitrectomy (p<0.001).

Conclusions: Uveitis aetiologies had distinct vitreous biomarker profiles, especially of infiltrating lymphocytes. Analyses of CD4/CD8 ratio, T-lymphocyte and B-lymphocyte subset, and pathogen DNA in vitreous samples have good safety profiles and high diagnostic value for uveitis classification.

Trial registration number: UMIN000004980; Pre-results.

Keywords: cd4/cd8 ratio; flowcytometry analysis; uveitis; vitreous sample.

Publication types

  • Multicenter Study
  • Observational Study

MeSH terms

  • Antigens, CD19
  • Biomarkers / analysis
  • Biomarkers, Tumor / analysis
  • CD4-CD8 Ratio*
  • CD4-Positive T-Lymphocytes / pathology*
  • CD8-Positive T-Lymphocytes / pathology*
  • Eye Neoplasms / diagnosis
  • Eye Neoplasms / immunology
  • Flow Cytometry
  • Humans
  • Prospective Studies
  • Real-Time Polymerase Chain Reaction
  • Sarcoidosis / diagnosis
  • Sarcoidosis / immunology*
  • Sarcoidosis / microbiology
  • Sarcoidosis / virology
  • Sensitivity and Specificity
  • Uveitis / classification*
  • Vitrectomy
  • Vitreous Body / immunology*
  • Vitreous Body / microbiology
  • Vitreous Body / pathology
  • Vitreous Body / virology

Substances

  • Antigens, CD19
  • Biomarkers
  • Biomarkers, Tumor