Dysfunction and Morphological Involvement of Inner Macular Layers in Glaucoma

Abstract

Objectives: This study aimed to study the inner retina functional and morphological impairment of retinal ganglion cells (RGCs) from specific macular rings and sectors to identify whether selective macular regions were more vulnerable than others within the 20 central degrees in patients with open-angle glaucoma (OAG). Methods: In total, 21 OAG patients [mean age 50.19 ± 7.86 years, Humphrey Field Analyzer (HFA) 24-2 mean deviation (MD) between -5.02 and -22.38 dB, HFA 10-2 MD between -3.07 and -17.38 dB], providing 21 eyes, were enrolled in this retrospective case-control study. And 20 age-similar healthy subjects, providing 20 eyes, served as controls. The multifocal photopic negative response (mfPhNR) response amplitude density (RAD) from concentric rings and macular sectors and ganglion cell layer thickness (GCL-T) assessed by Spectral Domain-Optical Coherence Tomography (SD-OCT) was measured. Mean RAD and GCL-T values were compared between OAG and control ones by ANOVA. In OAG eyes, the relationship between mfPhNR and SD-OCT data was examined by linear regression analysis, and Pearson's correlation coefficients were computed. Results: In considering all rings and sectors, compared to the controls, the OAG group showed a significant (p < 0.01) reduction in mean mfPhNR RAD and in GCL-T values with the greatest reduction in the central area. In OAG eyes, a significant (p < 0.01) correlation between all mfPhNR RAD and GCL-T values, with significant (p < 0.01) correlation coefficients, were found. Conclusions: In OAG eyes, RGC dysfunction was detectable by abnormal mfPhNR responses in localized macular areas, mainly in the central one. Localized macular RGC dysfunction was linearly correlated with the GCL morphological changes.

Keywords: OCT; glaucoma; macula; mfPhNR; structure function.

Figure 1

Representative example of functional analysis of retinal ganglion cells (RGCs) assessed with multifocal photopic negative response (mfPhNR) and morphological analysis of ganglion cell layer thickness (GCL-T) in one control eye (#10) and in one open-angle glaucoma eye (OAG#2). (A) Multifocal PhNR rings and OCT areas. mfPhNR response amplitude density (RAD) measured in nanoV/degree² (nV/deg²) as baseline to trough with an implicit time between 50 and 90 milliseconds (ms) from the stimulus onset and indicated by an arrow (↕). Ring (R) analysis of averaged traces obtained from three circular areas with increasing eccentricity from the fovea, covering 0°–20° from the center. The traces derived from a circular area centered on the fovea with a radius of 5° are depicted in red [Ring 1 (R1)]; in green, an external annular area enclosed between 5° and 10° of foveal eccentricity [Ring 2 (R2)]; in purple, a more external annulus combining together the areas enclosed between 10° and 15° Ring 3 (R3)] and between 15° and 20° [Ring 4 (R4)] (R3 + R4). GCL-T data: the central area corresponds to Area 1 encompassing the superpixels in a 6.35° radius centered on the fovea; the annular parafoveal area corresponds to Area 2, analyzing the superpixels enclosed between 6.35° and 9.37° from the fovea; the annular perifoveal area corresponds to Area 3, analyzing the superpixels enclosed between 9.37° and 12.5° from the fovea. In each area, the GCL-T value is reported in micron (µm). (B) Multifocal PhNR and OCT sectors. mfPhNR response amplitude density (RAD) [measured in nanoV/degree² (nV/deg²)] obtained in each macular sector. The first sector (S1) corresponds to R1 and analyzes a circular area centered on the fovea with a radius of 5°. The superior temporal (ST), inferior temporal (IT), inferior nasal (IN), and superior nasal (SN) sectors were quarters of an annulus within 5° (inner border) and 20° (outer border) of eccentricity from the fovea, corresponding to the sum of R2 + R3 + R4. The averaged R2 + R3 + R4 RADs for each sector (ST, IT, IN, SN) were measured. GCL-T data report the averaged values from four macular sectors (ST in blue; IT in green; IN in orange; SN in purple), determined by the horizontal and vertical midlines of the posterior pole and intersection at the fovea. The ST, IT, IN, and SN sectors comprise 13 superpixels each, corresponding to the ST, IT, IN, and SN portion of the posterior pole, respectively. GCL-T measurements are provided in microns (µm). OAG#2 eye shows reduced mfPhNR RADs and GCL-T in all rings and sectors when compared to Control#10 eye.

Figure 2

Relationship between multifocal photopic negative response (mfPhNR) response amplitude density (RAD) and ganglion cell layer thickness (GCL-T) values detected in rings and sectors in open-angle glaucoma (OAG) eyes and controls. (A) The multifocal photopic negative response (mfPhNR) average response amplitude densities (RADs) measured in controls and OAG eyes recorded in Ring 1, Ring 2, and Ring 3 + Ring 4. (B) The ganglion cell layer thickness (GCL-T) values measured in controls and OAG eyes recorded in Area 1, Area 2, and Area 3. (C) The multifocal photopic negative responses (mfPhNR) average response amplitude densities (RADs) measured in controls and OAG eyes recorded in the superior temporal (ST), inferior temporal (IT), inferior nasal (IN), and superior nasal (SN) sectors. (D) The ganglion cell layer thickness (GCL-T) values measured in controls and OAG eyes recorded in the superior temporal (ST), inferior temporal (IT), inferior nasal (IN), and superior nasal (SN) sectors. In OAG eyes, the averaged mfPhNR RAD and GCL-T values were lower compared to those in the controls but with a similar decreasing pattern at increasing eccentricity (from Ring 1 to Ring 3 + Ring 4 and from Area 1 to Area 3), which was particularly evident in controls (A,B). Similarly, in OAG eyes, the averaged mfPhNR RAD and GCL-T values were lower compared to in controls in all sectors. However, no significant pattern of changes was found for both averaged mfPhNR RAD and GCL-T values (C,D).

Figure 3

Correlations between mutifocal photopic negative response (mfPhNR) and ganglion cell layer thickness (GCL-T) individual values detected in open-angle glaucoma (OAG) eyes. (A) The individual GCL-T values measured in OAG eyes in Area 1, Area 2, and Area 3 were plotted as a function of the corresponding values of the mfPhNR response amplitude densities (RADs) recorded in Ring 1, Ring 2, and Ring 3 + Ring 4. (B) The individual GCL-T values measured in OAG eyes in superior temporal (ST), inferior temporal (IT), inferior nasal (IN), and superior nasal (SN) sectors were plotted as a function of the corresponding values of the mfPhNR RADs recorded in the Ring 2 + Ring3 + Ring 4 (R2–R4) ST, IT, IN, and SN sectors. In OAG eyes, the reduction in mfPhNR RADs was significantly correlated to the reduction in GCL-T in all examined rings or sectors.