Reduced systemic mitochondrial function is associated with faster rates of visual field progression in primary open angle glaucoma

Abstract

Purpose : Patients with primary open angle glaucoma (POAG) deteriorate despite intraocular pressure (IOP) reduction, suggesting other factors confer susceptibility. Evidence from our group and others implicates systemic mitochondrial (mt) function in glaucoma pathogenesis. We wanted to establish whether systemic mt function is associated with the rate of visual field (VF) progression in patients with POAG treated with IOP-lowering

Methods : Mt function parameters (Basal, ATP-linked, Maximal, Reserve), expressed as oxygen consumption rate (OCR) pmol/min/100,000 cells (XFe24 Analyzer), were measured in lymphocytes of 168 treated white-European POAG patients. Inclusion criteria: ≥6 reliable VFs and ≥3 years follow up. Exclusion criteria: secondary and narrow angle glaucoma, systemic conditions / drugs potentially affecting mt function. Both eyes of the same patient were included if eligible. Mixed-effect linear models were used to investigate the association between VF Mean Deviation (MD) rate of change and mt function, after adjusting for baseline age, central corneal thickness (CCT) and IOP during the observation period; separate IOP models for mean, peak, % reduction and standard deviation (SD) were generated

Results : A total of 211 eyes were included. Mean (±SD) age, IOP, and CCT were 72.6 (±10.0) years, 14.9 (±2.8) mmHg and 538 (±41) µm, respectively. Mean (±SD) rate of VF MD progression was -0.61 (±0.53) dB. In all models and for each measure of OCR, lower mt function was highly significantly associated with faster rates of VF progression. Table 1 shows results of the ‘SD IOP’ multivariable model; IOP mean, peak and % reduction were not significantly associated with VF progression. Figure 1a shows Basal OCR and SD IOP were significantly associated with MD rate of progression. Fig. 1b shows the relationship between basal OCR and VF progression rate. The model total marginal R² was 0.084. Semi-partial R² (proportion ‘variance accounted for’) was 0.020 and 0.074 for SD IOP and Basal OCR, respectively

Conclusions : Systemic (lymphocyte) mt function is highly significantly associated with the rate of VF loss in POAG patients treated with IOP lowering. Our findings suggest that measurement of mt function may help identify patients at high risk of more rapid progression. Mt function may be a new target for glaucoma treatment

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.