Focal Relationship Between Structure and Function Within the Central 10 Degrees in Glaucoma

Abstract

Purpose.: To investigate which measurements of inner macular thickness are the most useful for evaluating the focal relationship with visual sensitivity within the central 10° in glaucoma and which layers require correction for retinal ganglion cell (RGC) displacement.

Methods.: Sixty eyes of 60 subjects with glaucoma were included. Sensitivity of each test point of 10-2 standard automated perimetry was compared with the thickness of the retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), GCL+ inner plexiform layer (IPL), and RNFL+GCL+IPL (GCC), with and without RGC displacement, using Spearman's rank correlation coefficients. Visual sensitivity was evaluated by unlogged 1/Lambert (1/L) values.

Results.: Retinal nerve fiber layer thickness correlated significantly with the sensitivities of all test points except for some in the papillomacular bundle region when adjusting for RGC displacement (r_s = 0.287–0.767, P < 0.05). In the central 5.8°, the GCL and (GCL+IPL) thickness correlated significantly with the sensitivities of all test points when adjusting for RGC displacement (GCL: r_s = 0.363–0.729, P < 0.01; (GCL+IPL): r_s = 0.359–0.715, P < 0.01). The GCC thickness correlated significantly with the sensitivities of all 68 test points when adjusting for RGC displacement (r_s = 0.359–0.767, P < 0.01). RGC displacement improved the correlation between sensitivity and GCL, (GCL+IPL), and GCC in the central 4 points (GCL: r_s = from 0.270–0.470 to 0.421–0.540; (GCL+IPL): r_s = from 0.195–0.450 to 0.381–0.549; GCC: r_s = from 0.132–0.449 to 0.359–0.562).

Conclusions.: The GCC is the most useful parameter to evaluate structure and function within the central 10° in glaucoma. Adjusting for RGC displacement is essential to evaluate the relationship between structure of the GCL-related layer and function at the central macula.

Introduction

Even in the earliest stages of glaucoma, several research groups have reported that macula damage is common. ^1–3 However, total macular retinal thickness measured by optical coherence tomography (OCT) could not outperform the peripapillary retinal nerve fiber layer (RNFL) thickness in terms of glaucoma diagnosis. ⁴ The diagnostic performance of tests for glaucoma can be improved if macula measurements by OCT are focused on the inner retinal thickness. ^5,6 Recently, spectral-domain (SD) optical coherence tomography (OCT), which allows measurements of the inner retina thickness at the macula, has been used. Tan et al. ⁷ evaluated the combined RNFL, ganglion cell layer (GCL) and inner plexiform layer (IPL), the so-called ganglion cell complex (GCC), and its usefulness in the diagnosis of early glaucoma by measuring the GCC. Other researchers ⁸ have investigated the combined (GCL+IPL) instead of the GCC. 

Increasing attention has been paid to the relationship between structure and function, particularly in the macula, because SD-OCT allows three-dimensional (3D) measurement of macular thickness. Several groups ^9–11 have reported the global thickness of the inner retina and global sensitivity of the approximate corresponding area. Wang et al. ¹² reported the qualitative agreement between local (GCL+IPL) thickness measured by SD-OCT and local loss in visual field sensitivity. Raza et al. ¹³ reported that the local (GCL+IPL) thickness correlated well with local sensitivity loss in glaucoma. 

It is well known that retinal ganglion cells (RGCs) are displaced in the center of the macula. ^13–15 Raza et al. ¹³ reported that accounting for this displacement improved the correlation between the local (GCL+IPL) thickness and function at the macula. Thus, it is important to consider RGC displacement in the evaluation of the focal relationship between the local (GCL+IPL) thickness and function at the macula. However, it is unclear which layers need to be corrected for RGC displacement. Raza et al. ¹³ evaluated only (GCL+IPL), not GCC, because GCC contains RNFL, and the axons in the RNFL originate from different regions. With regard to the evaluation of the focal relationship between the inner retina structure and function at the macula, the most clinically useful, GCL, (GCL+IPL), or GCC have not been discussed. Therefore, in this study, we compared the sensitivity of each test point of 10-2 standard automated perimetry (SAP) with the corresponding thickness of RNFL, GCL, (GCL+IPL), and GCC with and without adjusting for RGC displacement. The purpose of our study was to determine the particular focal relationship between the structure of each of the inner layers and function at the macula. 

Materials and Methods

Participants

This prospective, cross-sectional study was conducted at Kanazawa University, Kyoto University, Tokyo University, and Tajimi Iwase Eye Hospital. The institutional review board and ethics committee of each participating institution approved the study, which adhered to the tenets of the Declaration of Helsinki. Written informed consent was obtained from each subject. 

Glaucoma patients who had experienced more than three 24-2 SAP or 10-2 SAP tests were enrolled in this study from January 2010 to July 2011. All participants underwent ocular examination, including autorefractometer measurements without cycloplegic agents, best-corrected visual acuity measurements with a 5-meter Landolt chart, slit-lamp examination, IOP measurements using a Goldmann applanation tonometer, dilated funduscopy, visual field testing using the Humphrey 24-2 Swedish Interactive Threshold Algorithm (SITA) Standard Strategy (Humphrey Field Analyzer; Carl Zeiss Meditec, Inc., Dublin, CA, USA), and 10-2 SITA Standard Strategy (Humphrey Field Analyzer), and SD-OCT examination with a 3D OCT 2000 version 7 (Topcon, Inc., Tokyo, Japan). All examinations were conducted within 3 months of SD-OCT examination. Exclusion criteria were contraindication to dilation; unreliable visual field, such as fixation loss of more than 20%; false-negative error or false-positive error of more than 15%; evidence of vitreoretinal disease; history of ocular surgery, including laser therapy; history of corticosteroid use; and neurologic disease, diabetic mellitus, or other systemic disease that might affect the eye or optic nerve. If both eyes were eligible, the eye with the worst mean deviation (MD) by 10-2 SAP was selected. 

Glaucoma was diagnosed based on glaucomatous changes in the optic disc, such as diffuse or local rim thinning, or vertical cup-to-disc ratio greater than the fellow eye by more than 0.2 with or without retinal nerve fiber layer defects (RNFLD). Glaucomatous visual field defects were defined on the basis of Humphrey 24-2 SAP results according to Anderson and Pattella, ¹⁶ with the presence of at least one of the following criteria: a pattern deviation probability plot showing a cluster of three or more points with a probability of less than 5% and at least one point with a probability less than 1% in an expected hemifield, a pattern SD with a probability of less than 5%, or a glaucoma hemifield test that indicated that the field was outside normal limits. Glaucomatous changes in the optic disc and/or RNFLD with normal SAP were defined as pre-perimetric glaucoma; glaucomatous changes in the optic disc and/or RNFLD with corresponding visual field defects were diagnosed as perimetric glaucoma. The spatial consistency of the structural and functional defects was confirmed. The eyes with perimetric glaucoma were classified into groups based on severity of disease: early glaucoma (MD of 24-2 > −6 dB), moderate glaucoma (−6 dB ≥ MD of 24-2 > −12 dB), and severe glaucoma (−12 dB ≥ MD of 24–2). 

Optical Coherence Tomography Examination

Spectral domain OCT examinations were performed with a 3D OCT-2000 after pupil dilation with 0.5% tropicamide and 2.5% phenylephrine. The SD-OCT is equipped with a nonmydriatic fundus camera function equivalent to a commercially available nonmydriatic fundus camera (TRC-NW200; Topcon, Inc.). The SD-OCT has a 6-μm depth resolution in tissue, a 20-μm transverse resolution, and acquires 50,000 axial scans per second. Three-dimensional imaging data of the macula were obtained using a raster protocol of 512 × 128 (vertical × horizontal) axial scans per image (total, 65,536 axial scans/image) within a cube of 7 × 7 mm centered at the fovea. The macula scans took 1.3 seconds. The examiner excluded images influenced by involuntary blinking, visible eye motion indicated by shifting of the vessels, or poor centrality. Only high-quality images, as indicated by a signal strength score (Q-factor) higher than 65, were used. 

Measurements of Inner Retinal Layer Thickness of the Macula

A previously reported, multilayer segmentation algorithm ^17,18 automatically calculated the mean of each macular layer thickness, including the RNFL, GCL, and IPL. This software automatically detects the foveal center and places a 6 × 6-mm square centered on the fovea. The RNFL thickness was measured from the inner limiting membrane to the boundary between the RNFL and GCL. The GCL was measured from the boundary between the RNFL and GCL to the boundary between the GCL and IPL. The IPL was measured from the boundary between the GCL and IPL to the boundary between the IPL and inner nuclear layer. All B-scan images were evaluated by an investigator (TF) and only images with appropriate segmentation lines were included in this study. The segmentation algorithm allows for manual corrections, so minor errors were corrected manually. We also calculated (GCL+IPL) and RNFL+GCL+IPL, which was defined as GCC. We calculated the total mean, the upper half mean, and the lower half mean of each layer in the 6 × 6-mm square area. Exploring the structure and function relationship of the macula, Hood et al. ¹⁹ and Raza et al. ¹³ emphasized that RGC displacement should be taken into consideration. The location adjusting for RGC displacement of OCT measurement area corresponding to each visual field test point of 10-2 SAP was approximated using a single equation (y = 1.29 × [x + 0.046]^0.67, y = RGC eccentricity, x = cone eccentricity), which relates cone and corresponding RGC eccentricity as defined by Sjöstrand et al. ¹⁴ We calculated the mean layer thickness of a 0.5-mm diameter circle corresponding to each visual field test point of 10-2 SAP, with and without adjusting for RGC displacement. ¹⁴ Figures 1A and 1B show the schema of the corresponding location of the 10-2 visual field test points and eccentricities of each test point. Figures 1C and 1D show the schema of the corresponding location after adjusting for RGC displacement and eccentricities of each test point, respectively. 

Figure 1

 

The scheme of location of measuring OCT thickness and eccentricities corresponding to the location of 10-2 visual field test points. (A) Scheme of location of measuring OCT thickness without RGC displacement. (B) The eccentricities of location of measuring OCT thickness without RGC displacement. (C) Scheme of location of measuring OCT thickness with RGC displacement. (D) The eccentricities of location of measuring OCT thickness with RGC displacement.

Macular Structural Deficits of RNFL, GCL+IPL (GCL+), and GCC (GCL++)

The internal software (software version 8.00; Topcon, Inc.) generated significance plots by color-coding 10 × 10 grids for each layer (RNFL, GCL+IPL [GCL+], and GCC [GCL++]) as follows: clear color (within the 95% normal limits), yellow (outside of the 95% normal limits and within the 99% normal limits), and red (outside of the 99% normal limits). If at least one grid was colored red, the eye was considered to have macular structural deficits. 

Visual Sensitivity of 10-2 SAP

Visual sensitivity and total deviation (TD) at each 10-2 test location were measured in decibels. We calculated the mean sensitivity of all 68 test points, as well as the lower hemifield and upper hemifield. Visual sensitivity and TD were calculated as unlogged 1/Lambert (1/L) values as follows: divide the decibel readings by 10 and then unlog the quotient. 

Classification of the 10-2 Visual Fields

The 10-2 visual fields were classified according to previous reports. ³ Briefly, 10-2 visual fields were classified as abnormal if there was a cluster of three contiguous points (5%, 5%, and 1% or 5%, 2%, and 2%) within a hemifield on pattern deviation plots. 

Statistical Analysis

Statistical analysis was performed using SPSS software version 17.0 (SPSS, Inc., Chicago, IL, USA). Spearman's rank correlation coefficients were used to evaluate the relationship between total mean sensitivity and total mean RNFL, GCL, (GCL+IPL), and GCC thickness measured by OCT. We also evaluated the relationship between mean sensitivity of the lower hemifield and upper hemifield and mean layer thickness of the corresponding hemiretina area using Spearman's rank correlation coefficients. Spearman's rank correlation coefficients were used to evaluate the relationship between visual sensitivity at each 10-2 test point and RNFL, GCL, (GCL+IPL), and GCC thickness measured by OCT with and without adjusting for RGC displacement. We also evaluated the correlation coefficients between TD at each 10-2 test point and each layer thickness when adjusting for RGC displacement. We evaluated the correlation coefficients between visual sensitivity at each 10-2 test point and each layer thickness by adjusting for RGC displacement according to two stages of disease severity: pre-perimetric or early glaucoma, and moderate or severe glaucoma. Correlation coefficients were compared after Fisher's z-transformation. The left eye was the mirror image of the right eye. The visual field was flipped across the horizontal midline to show a field view that was consistent with the OCT data. A P value less than 0.05 was considered statistically significant. 

Results

Sixty eyes of 60 subjects with glaucoma were included in this study. Table 1 shows the demographic characteristics of the study subjects. Fourteen eyes were diagnosed as pre-perimetric glaucoma, 27 eyes had early glaucoma, seven eyes had moderate glaucoma, and 12 eyes had severe glaucoma. Seven (50%) of 14 eyes with pre-perimetric glaucoma on 24-2 visual fields were classified as abnormal on 10-2 visual fields. All eyes of early, moderate, and severe glaucoma on 24-2 visual fields were classified as abnormal on 10-2 visual fields. All eyes of 60 eyes had macular structural deficits in RNFL and GCC (GCL++). Fifty-seven eyes (95%) of 60 eyes had macular structural deficits in GCL+IPL (GCL+). 

Table 1

 

Characteristics of the 60 Subjects

	Mean ± SD (Range)
Age, y	58.7 ± 13.0 (27 ∼ 82)
Sex, male/female	25/35
Eye, right/left	39/21
Spherical equivalent, diopters	−1.91 ± 2.42 (−6.0 ∼ +2.63)
24-2 Mean deviation, dB	−5.16 ± 5.96 (−28.42 ∼ +1.67)
10-2 Mean deviation, dB	−5.49 ± 5.74 (−20.25 ∼ +2.94)

Table 2 shows the correlation of mean thickness of each layer and mean visual field sensitivity of the corresponding area. RNFL, GCL, (GCL+IPL), and GCC thickness significantly correlated with mean sensitivities in the total area and in each hemifield (r_s = 0.520–0.815, P < 0.0001). Figures 2A through 2D show the correlation of each test point between visual sensitivity and RNFL, GCL, (GCL+IPL), and GCC without RGC displacement, respectively. Figures 3A through 3D show the correlation of each test point between visual sensitivity and RNFL, GCL, (GCL+IPL), and GCC with RGC displacement, respectively. Figures 4A through 4D show the correlation of each test point between TD and RNFL, GCL, (GCL+IPL), and GCC with RGC displacement. The area surrounded by the red frame shows the central four points. The area surrounded by the blue frame shows the area within 5.8°. The red letters indicate that the correlation was not significant. The RNFL thickness significantly correlated with sensitivities of all test points except some points of the papillomacular bundle region with and without adjusting for RGC displacement (without RGC displacement: r_s = 0.284–0.771; with RGC displacement: r_s = 0.287–0.767). In the central 5.8°, GCL and (GCL+IPL) thickness significantly correlated with sensitivities and TDs of all test points when adjusting for RGC displacement (GCL: r_s = 0.363–0.729; (GCL+IPL): r_s = 0.359–0.715). When adjusting for RGC displacement, the area of good correlation between sensitivity and the RNFL was found in the periphery of the central 10°, and the area of good correlation between sensitivity and the GCL and (GCL+IPL) was found in the central 5.8° area (Figs. 3A–C). The area of good correlation between TD and the RNFL, GCL, and (GCL+IPL) was consistent with that of sensitivity (Figs. 4A–C). The GCC thickness significantly correlated with sensitivities and TDs of all 68 test points of 10-2 SAP when adjusting for RGC displacement (sensitivities: r_s = 0.331–0.767; TDs: r_s = 0.279–0.809). Although RGC displacement improved the correlation between sensitivity and GCL, (GCL+IPL), and GCC in the central four points of 10-2 (GCL: r_s = from 0.270–0.470 to 0.421–0.540; (GCL+IPL): r_s = from 0.195–0.450 to 0.381–0.549; GCC: r_s = from 0.132–0.449 to 0.359–0.562), the correlation coefficients were not significantly different when data without and with RGC displacement were compared at all the central four points of all layers. Although two of the four central points of (GCL+IPL) and GCC thickness without RGC displacement did not significantly correlate with sensitivity, all the central four points of GCL, (GCL+IPL), and GCC thickness with RGC displacement significantly correlated with sensitivity. 

Figure 2

 

The correlation between visual sensitivity and inner retinal thickness of each test point without RGC displacement. The gray-scale r_s ranges are shown at the bottom right. The upper-case characters show Spearman rank correlation coefficients. The lower-case characters show P values of Spearman rank correlation coefficients. T, temporal; N, nasal. The area surrounded by the red frame shows the central four points. The area surrounded by the blue frame shows the area within 5.8°. *P < 0.05; **P < 0.01. The red letters indicate that the correlation was not significant. (A) RNFL. (B) GCL. (C) GCL + IPL. (D) GCC.

Figure 3

 

The correlation between visual sensitivity and inner retinal thickness of each test point with RGC displacement. The gray-scale r_s ranges are shown at the bottom right. The upper-case characters show Spearman rank correlation coefficients. The lower-case characters show P values of Spearman rank correlation coefficients. The area surrounded by the red frame shows the central four points. The area surrounded by the blue frame shows the area within 5.8°. *P < 0.05; **P < 0.01. The red letters indicate that the correlation was not significant. (A) RNFL. (B) GCL. (C) GCL + IPL. (D) GCC.

Figure 4

 

The correlation between total deviation and inner retinal thickness of each test point with RGC displacement. The gray-scale r_s ranges are shown at the bottom right. The upper-case characters show Spearman rank correlation coefficients. The lower-case characters show P values of Spearman rank correlation coefficients. The area surrounded by the red frame shows the central four points. The area surrounded by the blue frame shows the area within 5.8°. *P < 0.05; **P < 0.01. The red letters indicate that the correlation was not significant. (A) RNFL. (B) GCL. (C) GCL + IPL. (D) GCC.

Table 2

 

Correlation of Mean Thickness of Each Layer and Mean VF Sensitivity (1/L) of the Corresponding Area

OCT Section	Layer	VF Section	Spearman's r	P Value
Total	RNFL	All	0.759	<0.0001
	GCL		0.577	<0.0001
	GCL+IPL		0.520	<0.0001
	GCC		0.691	<0.0001
Upper half	RNFL	Lower hemifield	0.687	<0.0001
	GCL		0.656	<0.0001
	GCL+IPL		0.597	<0.0001
	GCC		0.690	<0.0001
Lower half	RNFL	Upper hemifield	0.815	<0.0001
	GCL		0.626	<0.0001
	GCL+IPL		0.533	<0.0001
	GCC		0.781	<0.0001

 VF, visual field.

Figures 5A through 5D show the correlation between visual sensitivity and RNFL, GCL, (GCL+IPL), and GCC, respectively, with RGC displacement of each test point in pre-perimetric and early glaucoma. In pre-perimetric and early glaucoma, RNFL, GCL, (GCL+IPL), and GCC thickness of most of the upper halves did not significantly correlate with sensitivities. Figures 6A through 6D show the correlation between visual sensitivity and RNFL, GCL, (GCL+IPL), and GCC, respectively, with RGC displacement of each test point in moderate and severe glaucoma. In these subjects, RNFL thickness significantly correlated with sensitivities of all 68 test points of 10-2 SAP except for six points (91.2%). GCL and (GCL+IPL) thickness significantly correlated with sensitivities of 21 (30.9%) of 68 test points, whereas GCC thickness significantly correlated with sensitivities of 43 (63.2%) of 68 test points. In moderate and severe glaucoma, the area of good correlation between sensitivity and GCL and (GCL+IPL) thickness was found only in the central and nasal areas of 10-2 SAP. 

Figure 5

 

The correlation between visual sensitivity and inner retinal thickness of each test point with RGC displacement in pre-perimetric and early glaucoma. The gray-scale r_s ranges are shown at the bottom right. The upper-case characters show Spearman rank correlation coefficients. The lower-case characters show P values of Spearman rank correlation coefficients. The area surrounded by the red frame shows the central four points. The area surrounded by the blue frame shows the area within 5.8°. *P < 0.05; **P < 0.01. The red letters indicate that the correlation was not significant. (A) RNFL. (B) GCL. (C) GCL + IPL. (D) GCC.

Figure 6

 

The correlation between visual sensitivity and inner retinal thickness of each test point with RGC displacement in moderate and severe glaucoma. The gray-scale r_s ranges are shown at the bottom right. The upper-case characters show Spearman rank correlation coefficients. The lower-case characters show P values of Spearman rank correlation coefficients. The area surrounded by the red frame shows the central four points. The area surrounded by the blue frame shows the area within 5.8°. *P < 0.05; **P < 0.01. The red letters indicate that the correlation was not significant. (A) RNFL. (B) GCL. (C) GCL + IPL. (D) GCC.

Discussion

Our study showed that without adjusting for RGC displacement, the correlation between sensitivity and the thickness of each of the inner retinal layers (RNFL, GCL, [GCL+IPL], and GCC) in the four central points was worse. With adjusting for RGC displacement, the correlation between sensitivity and the GCL and (GCL+IPL) was good within the central 5.8° and worse in the periphery of the central 10°. The results of (GCL+IPL) were consistent with those of a previous report. ¹³ Raza et al. ¹³ suggested that the reason there was a weaker relationship outside approximately 7.2° on the retina (approximately 6° on the visual field) was that the (GCL+IPL) thickness decreased markedly beyond this region, even in normal eyes. The (GCL+IPL) thickness at these eccentricities, which were associated with near normal sensitivities, did not differ from those associated with severe visual loss. On the other hand, even with adjusting for RGC displacement, the correlation between sensitivity and RNFL was worse in the papillomacular bundle region and good in the periphery of the central 10°. The area of good correlation between sensitivity and the RNFL was found in the periphery of the central 10°, and the area of good correlation between sensitivity and the GCL and (GCL+IPL) was found in the central area. With regard to the correlation with sensitivities, the GCC has both characteristics of the RNFL and the GCL or (GCL+IPL), and the GCC thickness correlated significantly with sensitivities of all 68 test points of 10-2 SAP when adjusting for RGC displacement (r_s = 0.359–0.767). The characteristics in the distribution of the correlation between sensitivities and each inner macular layer in the central 10° became clear by considering RGC displacement. With regard to evaluating the correlation with sensitivities, it would be best to use the GCL or (GCL+IPL) in the central 5.8°, to use the RNFL in the periphery of the central 10°, and to use the GCC within all areas of the central 10°. If we evaluate only (GCL+IPL) in the macular area, the analysis of the periphery of the central 10° could become suboptimal. In an evaluation of the macula, it seems that adding the assessment of the RNFL and the GCC to (GCL+IPL) could improve the diagnosis power and the correlation between the structure and the function of the periphery of the central 10°. In analysis of the macular area, it will be necessary to consider the characteristics of each inner layer in the future. 

Retinal ganglion cell displacement improved the correlation between sensitivity and GCL, (GCL+IPL), and GCC in the central four points. In addition, all central four points of GCL, (GCL+IPL), and GCC thickness with RGC displacement significantly correlated with sensitivity. The results of (GCL+IPL) were consistent with those of previous reports. ^13,20 Our results showed that it is essential to consider RGC displacement to evaluate the relationship between function and structure for all of the GCL-related layer parameters, including GCL, (GCL+IPL), and GCC. In previous studies of the focal macula structure and function relationship, Raza et al. ¹³ and Sato et al. ²⁰ analyzed only (GCL+IPL) to evaluate structure, but our study included GCL, (GCL+IPL), and GCC. Raza et al. ¹³ analyzed the focal macula structure and function relationship according to eccentricities. Sato et al. ²⁰ analyzed the focal macula structure and function relationship by sectors, whereas Takahashi et al. ²¹ analyzed the focal macula structure and function relationship of all 68 visual field test points of 10-2 SAP without adjusting for RGC displacement. Our current study evaluated the focal macula structure and function relationship of all 68 visual field test points of 10-2 SAP when considering RGC displacement. This study used the RGC displacement method according to Sjöstrand et al., ¹⁴ whereas Raza et al. ¹³ and Sato et al. ²⁰ used the RGC displacement equation described by Drasdo et al. ¹⁵ The degrees of RGC displacement by Drasdo et al. ¹⁵ were larger than those of Sjöstrand et al. ¹⁴ in all test points and the difference was largest in the nasal central two points (the model of Sjöstrand et al. ¹⁴ : eccentricity of all central four points = 2.6°; the model of Drasdo et al. ¹⁵ : eccentricity of the nasal central two points = 3.5°, eccentricity of the temporal central two points = 3.2°). Although the correlation coefficients of the nasal central two points of GCL, GCL+IPL, and GCC were improved when using RGC displacement by Drasdo et al. ¹⁵ compared with RGC displacement by Sjöstrand et al., ¹⁴ the differences were not significant (GCL: r_s = from 0.427–0.491 to 0.528–0.560; (GCL+IPL): r_s = from 0.420–0.481 to 0.489–0.586; GCC: r_s = from 0.359–0.464 to 0.525–0.576). The correlation coefficients of the temporal central two points by Drasdo et al. ¹⁵ were similar to those of Sjöstrand et al. ¹⁴ (GCL: r_s = from 0.421–0.540 to 0.425–0.527; (GCL+IPL): r_s = from 0.381–0.549 to 0.417–0.539; GCC: r_s = from 0.394–0.562 to 0.434–0.559). Other test points may not influence the results of the correlation between structure and function because our study measured the mean layer thickness of a 0.5-mm diameter circle. 

We did not validate macular structural deficits of the GCL because we did not have a normal data base of GCL, so we investigated macular deficits of RNFL, (GCL+IPL), and GCC. However, our criteria of macular deficits might be too sensitive. All 60 eyes had macular structural deficits in the RNFL and GCC (GCL++). Fifty-seven eyes (95%) of 60 eyes had macular structural deficits in the GCL+IPL (GCL+). Fifty percent of eyes with pre-perimetric glaucoma and 24-2 visual fields were classified as abnormal on 10-2 visual fields in our study. In this study, we selected the eye with the worst MD by 10-2 SAP if both eyes were eligible for selection so there was a selection bias. Nevertheless, our study showed that macular deficits are common and that early visual field defects in the macula are common, which is in agreement with previous reports. ^1–3  

It was reported that the correlation between structure and function in glaucoma was dependent on disease severity. ²² In the present study, RNFL, GCL, (GCL+IPL), and GCC thickness of most of the upper half did not significantly correlate with sensitivities in eyes with pre-perimetric and early glaucoma. This suggests that the superior macula (inferior visual field) region is less susceptible to glaucoma damage, whereas the inferior macula (superior visual field) region is susceptible to glaucoma damage. ¹ The range of visual sensitivity is narrow in healthy ²⁰ and early glaucoma eyes. Our study also showed that in moderate and severe glaucoma, GCL and (GCL+IPL) thickness only significantly correlated with sensitivities in 30.9% of test points. RNFL may be the most useful parameter to evaluate the relationship between structure and function at the central 10° in moderate and severe glaucoma. However, only 19 eyes in our study were diagnosed with moderate or severe glaucoma. Further studies with a larger number of patients are needed to confirm the effects of disease severity. 

Our study has several limitations. First, although inner retinal thickness (GCC) decreases with age ^17,23 and the sensitivity of SAP decreases with age, ^24,25 we did not consider the effect of age. We evaluated both the sensitivity and TD. The sensitivity was not compared with normal data and we did not compensate for age-related changes in thickness. Previously, it was reported that the effects of age on OCT thickness were relatively small. ^1,17 Therefore, the effects of age on OCT thickness may be less important than on SAP sensitivity. We also evaluated the correlation coefficients of TD, which was compared with normal data and thickness of each layer. The results of TD were similar to the results of sensitivity. We think the influence of age in this study is limited. Further studies with a larger number of patients will clarify the influence that age has to the relationship between structure and function. 

Second, we did not consider eye movements and ocular rotation. If microperimetry, which assesses retinal sensitivity during a direct examination of the ocular fundus, were used instead of 10-2 SAP to assess function like Sato et al., ²⁰ the correlation coefficient between function and structure might be improved. However, 10-2 SAP, but not microperimetry, is a standard examination to manage glaucoma. 

In conclusion, with regard to evaluating correlations with sensitivities, it would be best to use the GCL or (GCL+IPL) in the central 5.8°, to use the RNFL in the periphery of the central 10°, and to use the GCC within all areas of the central 10°. The GCC is the most useful parameter to evaluate structure and function within the central 10° of the macula in glaucoma. Adjusting RGC displacement is essential to evaluate the relationship between structure and function at the central macula. The focal macular GCC thickness can predict focal function within the central 10° in glaucoma. 

Acknowledgments

Supported by a Grant-in-Aid for Scientific Research (20592038) from the Japan Society for the Promotion of Science (MH). 

Disclosure: S. Ohkubo, Topcon (C), Nidek (C); T. Higashide, None; S. Udagawa, None; K. Sugiyama, Nidek (C); M. Hangai, Topcon (I), Nidek (I), Santen (I), Canon (C); N. Yoshimura, Topcon (F), Nidek (I), Canon (F, I); C. Mayama, None; A. Tomidokoro, None; M. Araie, Topcon (I), Kowa (I),Carl Zeiss Meditec (I), Santen (I); A. Iwase, Topcon (I), Carl Zeiss Meditec (I); T. Fujimura, Topcon (E)