Cell - Vessel Mismatch in Glaucoma: Correlation of Ganglion Cell Layer Soma and Capillary Densities

Abstract

Purpose: The purpose of this study was to characterize the relationship between retinal ganglion cell layer (GCL) soma density and capillary density in glaucomatous eyes.

Methods: Six glaucoma subjects with known hemifield defects and 6 age-matched controls were imaged with adaptive optics - optical coherence tomography (AO-OCT) at 6 locations: 3 degrees, 6 degrees, and 12 degrees temporal to the fovea above and below the midline. GCL soma density and capillary density were measured at each location. Coefficients of determination (pseudo R2) and slopes between GCL soma and capillary density were determined from mixed-effects regressions and were compared between glaucoma and control subjects, between more and less affected hemifield in subjects with glaucoma, and between subjects with early and moderate glaucoma, both in a local, bivariate model and then a global, multivariable model controlling for eccentricity and soma size.

Results: The global correlation between GCL soma and capillary density was stronger in control versus subjects with glaucoma (R2 = 0.59 vs. 0.22), less versus more affected hemifields (R2 = 0.55 vs. 0.01), and subjects with early versus moderate glaucoma subjects (R2 = 0.44 vs. 0.18). When controlling for eccentricity and soma size, we noted an inverse soma-capillary density local relationship in subjects with glaucoma (-388 ± 190 cells/mm2 per 1% change in capillary density, P = 0.046) and more affected hemifields (-602 ± 257 cells/mm2 per 1% change in capillary density, P = 0.03).

Conclusions: An inverted soma-capillary density local relationship in areas affected by glaucoma potentially explains weaker global correlations observed between GCL soma and capillary density, suggesting cell-vessel mismatch is associated with the disease.

Conflict of interest statement

Disclosure: R. Villanueva, None; C. Le, None; Z. Liu, adaptive optics–optical coherence tomography technology (P); F. Zhang, adaptive optics–optical coherence tomography technology (P); L. Magder, None; D.X. Hammer, None; O. Saeedi, Heidelberg Engineering (F)

Figures

Figure 1.

AO-OCT methods for GCL soma and capillary (SVP and ICP) density measurement. (A) Six AO-OCT locations imaged in the temporal macula with respect to the horizontal mid-line and fovea. (B, C) En face AO-OCT images of GCL of single plane at 3T2.5I in one healthy control subject with and without GCL somas marked (blue crosses). (D) AO-OCT B-scan demonstrating relative locations of the SVP, ICP, and DCP. En face AO-OCT projection and corresponding binarized vessel map of (E, F) the SVP and (G, H) the ICP.

Figure 2.

A comparison of GCL soma density and GC-IPL capillary density between control and subjects with glaucoma at 3°T, 6°T, and 12°T. (A) The mean GCL soma density for glaucoma and control subjects at all three locations. (B) Average GC-IPL capillary density at each location. The error bars represent standard deviation. (C) The relationship between GC-IPL capillary density and GCL soma density is fit by a slope from our bivariate mixed-effects regression (red lines indicate 95% confidence intervals for glaucoma [solid] and control [dashed], respectively). Open and filled symbols represent control and glaucoma subjects, respectively (* P value < 0.05).

Figure 3.

The relationship between GC-IPL capillary and GCL soma density in glaucoma hemifield locations. (A) Average GCL soma density at each location for more and less affected hemifield location. (B) Average GC-IPL capillary density at each location. The error bars represent standard deviation. (C) The relationship between GC-IPL capillary density and GCL soma density for hemifield locations is fit by a slope from our bivariate mixed-effects regression (red lines indicate 95% confidence intervals; * P value < 0.05).

Figure 4.

The relationship between GCL soma and GC-IPL capillary density in subjects with early and moderate glaucoma. (A) Average GCL soma density values for the three eccentricities. (B) Average GC-IPL capillary density values for the three eccentricities. The error bars represent standard deviation. (C) The relationship between GC-IPL capillary density and GCL soma density for subjects with early and moderate glaucoma is fit by a slope from our bivariate mixed-effects regression (red lines indicate 95% confidence intervals, *P value < 0.05).