Association between Oral Active-Matrix Metalloproteinase-8 Levels and Subretinal Fibrosis among Wet Age-Related Macular Degeneration Patients

Curr Eye Res. 2024 Mar;49(3):288-294. doi: 10.1080/02713683.2023.2280442. Epub 2023 Nov 17.

Abstract

Purpose: Periodontitis causes low-grade systemic inflammation and has been associated with elevated active-matrix metalloproteinase (aMMP-8) levels, blood-ocular barrier breakdown and a risk of wet age-related macular degeneration. To assess the association between aMMP-8 levels and macular status among patients with wet age-related macular degeneration (AMD).

Methods: Patients on anti-VEGF treatment for wet AMD were enrolled for oral aMMP-8 rinse test in Mehiläinen Private Hospital, Helsinki, Finland. Macular status was examined from spectral-domain optical coherence tomography (SD-OCT) scans by a medical retina specialist and aMMP-8 levels were analyzed with chairside point-of-care oral rinse (PerioSafe®) test and real-time quantitated by a dentist using the ORALyzer®- reader with a 10 ng/ml cut-off for aMMP-8 activity.

Results: Elevated aMMP-8 levels were found in 10 out of 32 patients. Age, gender, anti-VEGF (bevacizumab or aflibercept) distribution, cumulative number of anti-VEGF injections and treatment interval were comparable between patients with aMMP-8 levels below and above the point-of-care level. Macular status differed in regard to aMMP-8 activity; among patients with aMMP-8 levels below the point-of-care subretinal fibrosis was found in 6 out of 22 eyes, whereas among patients with aMMP-8 levels above the point-of-care subretinal fibrosis was found in 8 out of 10 eyes (p = 0.005). Respectively, the mean thickness of subretinal fibrosis at fovea was 19.5 ± 44.1 and 92.3 ± 78.3 µm (p = 0.018). No differences were found in the presence and in the area of geographic atrophy, or fluid distribution, whereas thicknesses of serous pigment epithelial detachment (65.5 ± 99.5 and 12.9 ± 27.9 µm, p = 0.038) and neuroretina (204.2 ± 57.8 µm and 143.0 ± 43.7 µm, p = 0.006) were greater in the eyes of patients with physiological aMMP-8 levels compared to those with elevated aMMP-8 levels.

Conclusion: Elevated aMMP-8 levels may account for subretinal fibrosis formation in wet AMD.

Keywords: Active MMP-8; blood-ocular-barrier breakdown; macular fibrosis; periodontitis; wet age-related macular degeneration.

MeSH terms

  • Angiogenesis Inhibitors* / therapeutic use
  • Fibrosis
  • Humans
  • Intravitreal Injections
  • Matrix Metalloproteinase 8 / therapeutic use
  • Ranibizumab
  • Retrospective Studies
  • Subretinal Fluid
  • Tomography, Optical Coherence / methods
  • Vascular Endothelial Growth Factor A / therapeutic use
  • Wet Macular Degeneration* / complications
  • Wet Macular Degeneration* / diagnosis
  • Wet Macular Degeneration* / drug therapy

Substances

  • Angiogenesis Inhibitors
  • Vascular Endothelial Growth Factor A
  • Matrix Metalloproteinase 8
  • Ranibizumab