Macular Vascular Integrity is Associated with Retinal Ganglion Cell Dysfunction in Pre-perimetric Glaucoma

Abstract

Purpose : Most studies have focused on abnormalities in large vessels and capillaries that supply the optic nerve head (ONH) in glaucoma but there is little evidence on macular microvascular abnormalities in pre-perimetric glaucoma (PPG) and their effects on retinal ganglion cells (RGC) function. The purpose of this cross-sectional prospective study was to determine the relationship between foveolar avascular zone (FAZ) area, a biomarker for macular vascular integrity and RGC function assessed by pattern electroretinogram (PERG)

Methods : Twenty consecutive PPG participants (31 eyes) with normal visual fields tests and suspicious glaucomatous ONH appearance were enrolled in this study conducted at Manhattan Eye Ear & Throat hospital and underwent a complete ophthalmologic examination, standard automated perimetry, optical coherence tomography-angiography (OCTA) and PERG. FAZ area was measured using ImageJ software, with ICC of 0.99 between 2 raters. Mediation analysis Process by Andrew Hayes was tested using the Sobel test, and the bias corrected nonparametric bootstrapping procedure with 5000 bootstrapped samples, at 95% CI. The indirect effect (IE) was significant if the CI did not contain zero. p<0.05 was used

Results : After controlling for risk factors for glaucoma [age, sex, intraocular pressure (IOP), central corneal thickness (CCT) and refractive error (RE)], PERG parameters Magnitude (Mag), and MagnitudeD (MagD) were significantly correlated with FAZ (r>-0.503, p<0.028), all PERG parameters correlated with superior quadrant RNFL (r>0.498, p<0.030), with superior (S), superior temporal GCL-ILP thickness (r>0.545, p<0.016); MagD and MagD/Mag ratio with average and minimum GCLIPL thicknesses (r>0.495, p<0.031). Mediation analysis revealed that FAZ area was a significant mediator in the relationship between MagD and S GCL-ILP thickness, independent of CCT and RE (effect =4.92, p=0.0033, 95% CI [0.41-9.44). While the direct effect of MagD remained significant (effect = 4.92, p = 0.033, 95% CI [0.41-9.44]), the indirect effect was also significant, indicating that FAZ area partially mediated the effect of MagD on S sector GCL+IPL (effect = 2.71, 95% CI [0.22–6.06]).

Conclusions : RGC dysfunction is associated with structural thinning of the GCL-IPL layer, and this effect is partially mediated by the disruption of the macular vascular integrity and FAZ enlargement

This is a 2021 ARVO Annual Meeting abstract.