Implication of inflammatory cytokines in the aqueous humour for management of macular diseases

Acta Ophthalmol. 2020 May;98(3):e309-e315. doi: 10.1111/aos.14248. Epub 2019 Sep 18.

Abstract

Purpose: To characterize profile of cytokines in aqueous humour of common macular diseases during intravitreal anti-VEGF therapy.

Methods: Aqueous humour from eyes with central retinal vein occlusion (CRVO), branch retinal vein occlusion (BRVO), diabetic macular oedema (DME), neovascular age-related macular degeneration (nAMD) or pathologic myopia associated choroidal neovascularization (pmCNV) was sampled prior to 1st (n = 144) and 2nd (n = 48) intravitreal anti-VEGF therapy. Cytokines including vascular endothelium growth factor (VEGF), intercellular adhesion molecule 1 (ICAM-1) and interleukin 6 (IL-6) were quantitated and analysed along with retinal thickness data by optical coherence tomography (OCT) across two intravitreal injections and five macular disease types.

Results: ICAM-1, IL-6 and VEGF are positively associated in the aqueous humour of naive eyes (r = 0.39-0.77, p = 0.018 to <0.0001). ICAM-1, VEGF and IL-6 were significantly higher in CRVO and DME while lowest in pmCNV (p < 0.0001). Reduction of central retinal thickness (CRT) as a favourable response to anti-VEGF therapy was in the order of CRVO, BRVO, DME and nAMD/pmCNV (p < 0.0001). The strongest predictor for favourable CRT reduction was baseline CRT (p < 0.0001) followed by baseline ICAM-1 (p = 0.04). After the 1st intravitreal anti-VEGF therapy, VEGF in aqueous humour lowered significantly but ICAM-1 and IL-6 levels remained unchanged. ICAM-1 was not predictive for CRT reduction following 2nd anti-VEGF therapy.

Conclusion: Rate of cytokine production is disease-dependent and higher in CRVO and DME. Anatomical response to intravitreal anti-VEGF therapy is disease-specific and best in RVO patients. A combination therapy using both anti-VEGF and anti-inflammatory therapeutics may be superior to single anti-VEGF therapy, at least for RVO and DME.

Keywords: VEGF; ICAM-1; IL-6; anti-VEGF; anti-inflammation; aqueous humour; macular disease management.

MeSH terms

  • Adult
  • Aged
  • Aqueous Humor / drug effects
  • Aqueous Humor / metabolism*
  • Cytokines / metabolism*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Intercellular Adhesion Molecule-1
  • Interleukin-6 / metabolism
  • Male
  • Middle Aged
  • Retinal Diseases / drug therapy*
  • Tomography, Optical Coherence
  • Vascular Endothelial Growth Factor A / administration & dosage*
  • Vascular Endothelial Growth Factor A / metabolism
  • Visual Acuity

Substances

  • Cytokines
  • ICAM1 protein, human
  • Interleukin-6
  • Vascular Endothelial Growth Factor A
  • Intercellular Adhesion Molecule-1