Correlation of contrast sensitivity with ganglion cell/inner plexiform layer thickness and damage location in glaucoma with varying severity

Abstract

Objectives

To investigate the correlation of contrast sensitivity with macular region ganglion cell/inner plexiform layer (GC/IPL) thickness and damage location in open-angle glaucoma (OAG) of varying severity.

Methods

Cross-sectional study with 106 patients (203 eyes) who had OAG. Contrast sensitivity of each eye evaluated by quick contrast sensitivity function test based on intelligent algorithm. The GC/IPL thickness measured with optical coherence tomography; six sectors were delineated for localization of damage area. All eyes were grouped by the healthy macular sector and divided into pre-perimetric, early, moderate, and advanced stages, according to severity of visual field impairment.

Results

Mean GC/IPL thickness in the entire macular region and each sector were correlated with parameters that reflected contrast sensitivity (p < 0.01). The structure-function correlations were stronger nasally compared with temporally, and superiorly compared with inferiorly. Eyes with normal structure in inferior temporal sector had less visual field (p' = 0.024) and macular damage (p′ = 0.034) compared with eyes that had healthy superior nasal sector; there was no difference in contrast sensitivity (p = 0.898). The structure-function correlations were significant in early, moderate, and advanced glaucoma (p < 0.05) but not in pre-perimetric glaucoma (p = 0.116).

Conclusions

GC/IPL thinning in all sectors of the macular region in OAG was correlated with contrast sensitivity impairment, whereas the inferior temporal sector was least affected. Contrast sensitivity was supported as a severity evaluation indicator of early, moderate, and advanced glaucoma, but not of pre-perimetric glaucoma.

Introduction

Contrast sensitivity is an important functional vision index that reflects the ability to distinguish the difference between lightness and darkness of an object with its surroundings [1, 2]. In glaucoma, subjective symptoms caused by decreased contrast sensitivity are more common than visual field deficits [3], causing significant disruption to daily activities and quality of life [4–6]. A promising direction for clinical application is the use of contrast sensitivity as a monitoring index for the progression of open-angle glaucoma (OAG) [7]. Particularly in pre-perimetric or advanced glaucoma, there are limitations in the evaluation of visual field to measure progression. However, controversial structure-function correlations and uncertain mechanisms have hindered the use of contrast sensitivity in glaucoma clinical practice [7, 8].

The counts or density of retinal ganglion cells (RGCs) in the macular region may be the structural basis for determining the contrast sensitivity. Using spectral domain-optical coherence tomography, Chien et al. suggested that RGCs destruction in the macular region was correlated with increased contrast requirements for letter recognition [9]. Shamsi et al. verified by deep learning that the retinal layers in the macular region containing RGCs were key features in predicting contrast sensitivity [10]. However, Fatehi et al. found that contrast sensitivity was independent of the mean ganglion cell / inner plexiform layer (GC/IPL) thickness in the entire macular region and was correlated only in specific macular sectors and at particular spatial frequencies [8]. The findings of Fatehi et al. fail to support contrast sensitivity as a detection index of glaucoma progression, but the findings suggest the novel idea that RGC damage in specific macular regions may affect contrast sensitivity in glaucoma.

The quick contrast sensitivity function (qCSF) method is a novel computer-based test based on an artificial intelligence algorithm that assesses the contrast sensitivity function curves. The area under log [CSF] (AULCSF) from qCSF is an accurate and sensitive index for evaluating contrast sensitivity changes in various eye diseases, including keratoconus, age-related macular degeneration, and diabetes retinopathy [11–14]. We used the qCSF technique to analyze the effect of GC/IPL damage and different damage regions on contrast sensitivity of patients with OAG to provide clinical evidence for a mechanism of contrast sensitivity impairment. More importantly, we analyzed the correlation of contrast sensitivity with GC/IPL in glaucoma of varying severity to determine whether contrast sensitivity can be used as a severity evaluation indicator for pre-perimetric and advanced glaucoma.

Materials and methods

Study design

The cross-sectional study was conducted at the Beijing Tongren Eye Center from June 2022 to April 2023. The Ethics Committee of Beijing Tongren Hospital, Capital Medical University approved the study protocol, which was conducted in accordance with the principles of the Declaration of Helsinki.

Participants

Participants in this study met the diagnostic criteria for OAG [15]; primary open-angle glaucoma and normal-tension glaucoma were included, and secondary open-angle glaucoma was excluded. All participants underwent rigorous ocular examination before the diagnosis, including logMar visual acuity, slit-lamp examination, gonioscopy, 24-h intraocular pressure monitoring (Goldmann tonometer), standard automated perimetry 24-2 test (Humphrey Field Analyzer III; Carl Zeiss Meditec, Dublin, CA, USA), and fundus photography. The participants were aged 18–50 years. Written informed consent was obtained prior to the study. Both eyes of all participants were included in this study, except eyes with other ocular or neurological diseases, eyes with abnormally sized pupils, and eyes that could not cooperate with the entire examination. For statistical analysis, all individuals obtained the following measurements within two hours: spectral domain-optical coherence tomography, qCSF, standard automated perimetry 24-2 test, and intraocular pressure (Full Auto Tonometer TX-F, Topcon, Tokyo, Japan).

Spectral domain-optical coherence tomography

All participants underwent spectral domain-optical coherence tomography (Cirrus HD-OCT, Carl Zeiss Meditec) examination, and the macular cube 200 × 200 protocols were used to measure GC/IPL thickness. In the macular ganglion cell analysis, GC/IPL thickness included the ganglion cell layer and the inner plexiform layer. The deviation map, a 6-mm scanning circle centred on the fovea of the macula, was composed of a macular GC/IPL deviation map with 30 × 30 pixels typically. According to built-in software, the macular scanning region was systematically divided into six sections, namely superior temporal, superior, superior nasal, inferior nasal, inferior, and inferior temporal. The thickness of the average GC/IPL in the macular region and the average GC/IPL thickness in each sector were obtained. Sectors with a mean GC/IPL thickness within the 90% reference interval for Asian populations were defined as healthy macular sectors (Fig. 1).

Fig. 1. The distribution of ganglion cell/internal plexiform layer (GC/IPL) thickness and the grouping principle for three different eyes.

Each deviation map was divided into six sectors, and the number on each sector represents the average thickness (μm) of GC/IPL in that region. The colour of each sector reflects whether the thickness of the sector was within the normal reference interval for the Asian population. Red means below the 1% level and yellow means below the 5% level of the population, which is abnormal. Green means within 90% of the population reference interval. A Only the inferior nasal sector was normal and included in the IN group; B Four sectors were normal and included in the S, ST, IT and I groups at the same time. C All sectors were abnormal and not included in any group.

Quick contrast sensitivity function test

The contrast sensitivity-related parameters in this study were obtained by the Manifold Contrast Vision Meter (Adaptive Sensory Technology, inc., San Diego, CA, USA) based on the qCSF method. Participants with optimal refractive correction viewed the stimuli (numbers) at a distance of three metres in a dark room. In each trial, three-digit stimuli were arranged as a 1 × 3 matrix and shown for ten seconds on the screen, participants were instructed to read out the number immediately. Each eye was tested in 25 trials. Please refer to previous studies for the detailed procedure [16, 17]. In this study, the area under log [CSF] (AULCSF) and CSF acuity, that is, the spatial frequency with contrast sensitivity equal to one, were recorded as study parameters.

Grading and grouping of the included eyes

All included eyes were graded as either pre-perimetric, early, moderate, or advanced glaucoma according to the severity of visual field damage. Pre-perimetric glaucoma was accompanied by normal visual fields despite already present structural damage. Normal visual fields were defined as mean deviation (MD) and pattern standard deviation within 95% reference interval, three consecutive adjacent points <5% were excluded, and a glaucoma hemifield test result within normal range. Eyes with glaucomatous damage in the visual field were graded according to MD values: MD ≥ −6 dB was early stage, MD < −12 dB was advanced stage, and the remainder were graded as moderate stage.

To determine the effect on contrast sensitivity from macular RGCs located at different sectors, we included eyes accompanied by a particular healthy macular sector (the mean GC/IPL thickness of that sector was within the 90% reference interval of population) in the same group. Eyes in this study were divided into six groups according to the six wedge-shaped sectors, which were defined as ST group with normal superior temporal sector, S group with normal superior sector, SN group with normal superior nasal sector, IN group with normal inferior nasal sector, I group with normal inferior sector, and IT group with normal inferior temporal sector. Eyes with multiple healthy macular sectors were included in more than one group at the same time, and some examples of eye groupings are shown in Fig. 1.

Statistical analysis

SPSS 26.0 was used for statistical analysis of the data. Quantitative data were expressed as mean ± standard deviation. If the two data were consistent with normal distribution, Pearson correlation analysis was used; otherwise, Spearman correlation analysis was used. Two-sided test and Kruskal–Wallis H test were used to compare groups. The significance level was set to 0.05 and adjusted to 0.003 according to Bonferroni correction method when Post Hoc test was performed. The adjusted p-value was expressed as p’.

Results

One hundred six patients with OAG (63 men and 43 women) were enrolled in the study, 74 with primary open-angle glaucoma and 32 with normal-tension glaucoma. The participant mean age was 40.97 ± 7.31 years. After excluding ineligible eyes, 203 eyes were included in the final analysis, including 34 eyes in the pre-perimetric stage, 67 eyes in the early stage, 48 eyes in the moderate stage, and 54 eyes in the advanced stage. For all the included eyes, the average GC/IPL thickness was 66.19 ± 9.50 μm, the MD of visual field was −8.27 ± 7.60 dB, the BCVA was 0.06 ± 0.17, the AULCSF was 0.98 ± 0.29, and the CSF Acuity was 1.24 ± 0.18 log10 units. Other ocular characteristics of the total and individual stage eyes are described in detail in Table 1.

Table 1.

Ocular characteristics of the included eyes.

	Total	Pre-perimetric	Early	Moderate	Advanced
Sample (eye)	203	34	67	48	54
GC/IPL(μm)	66.19 ± 9.50	72.32 ± 4.74	71.01 ± 9.27	63.31 ± 7.52	58.61 ± 7.18
GC/IPL-ST(μm)	66.15 ± 10.81	73.71 ± 4.69	71.22 ± 9.51	63.94 ± 10.11	57.00 ± 8.56
GC/IPL-S(μm)	69.19 ± 11.09	74.82 ± 6.40	73.64 ± 11.27	68.25 ± 9.84	61.07 ± 9.41
GC/IPL-SN(μm)	71.09 ± 13.01	76.79 ± 6.51	76.04 ± 12.07	69.65 ± 11.55	62.57 ± 13.80
GC/IPL-IN(μm)	67.72 ± 11.69	73.18 ± 7.09	72.46 ± 11.35	64.79 ± 10.34	60.69 ± 11.17
GC/IPL-I(μm)	62.22 ± 10.16	67.15 ± 7.59	66.76 ± 11.34	57.92 ± 7.83	56.65 ± 6.46
GC/IPL-IT(μm)	60.97 ± 10.99	68.56 ± 6.63	66.09 ± 11.93	55.56 ± 7.80	53.83 ± 6.18
AULCSF	0.98 ± 0.29	1.15 ± 0.19	1.08 ± 0.22	0.98 ± 0.26	0.74 ± 0.30
CSF Acuity	1.24 ± 0.18	1.31 ± 0.14	1.30 ± 0.13	1.25 ± 0.16	1.13 ± 0.21
logMar	0.06 ± 0.17	0.01 ± 0.13	0.04 ± 0.17	0.10 ± 0.22	0.07 ± 0.13
IOP (mmHg)	15.56 ± 3.06	16.18 ± 2.76	15.78 ± 3.14	15.60 ± 3.36	15.00 ± 2.77
MD (dB)	−8.27 ± 7.60	−1.03 ± 1.12	−3.06 ± 1.79	−8.70 ± 1.72	−18.91 ± 5.48

GC/IPL ganglion cell/ inner plexiform layer thickness, ST superior temporal sector, S superior sector, SN superior nasal sector, IN inferior nasal sector, I inferior sector, IT inferior temporal sector, AULCSF area under the logarithm of the contrast sensitivity function, CSF Acuity cutoff special frequencies of contrast sensitivity function, logMar logarithmic vision, IOP intraocular pressure, MD mean deviation.

For all 203 included eyes, not only the total average GC/IPL thickness was positively correlated with AULCSF (r = 0.572, p < 0.001), but also the GC/IPL thickness of the six macular sectors was positively correlated with AULCSF (p < 0.001). Among them, the correlation of nasal GC/IPL (including superior nasal and inferior nasal sectors; r = 0.564, 0.530) was stronger than that of temporal (including superior temporal and inferior temporal sectors; r = 0.498, 0.320). The correlation of superior GC/IPL (r = 0.533) was stronger than that of inferior (r = 0.370). In addition, logMar visual acuity and MD of visual field were also significantly correlated with AULCSF (r = −0.296, r = 0.484; p < 0.001). There was no correlation between intraocular pressure and AULCSF (r = 0.011, p = 0.877). The results of the correlation analysis of CSF Acuity were similar to those of AULCSF (Table 2). To avoid skewing the correlation results in Table 2 by including both eyes of the same participant, we re-performed the correlation analysis on 106 participants, each of whom included only one eye (if both eyes met the criteria, the right eye was included), and the results were similar (eTable 1).

Table 2.

Correlation between ocular parameters and contrast sensitivity.

	AULCSF		CSF Acuity
	r	p	r	p
GC/IPL	0.572	<0.001	0.459	<0.001
GC/IPL-ST	0.498	<0.001	0.382	<0.001
GC/IPL-S	0.533	<0.001	0.393	<0.001
GC/IPL-SN	0.564	<0.001	0.443	<0.001
GC/IPL-IN	0.530	<0.001	0.446	<0.001
GC/IPL-I	0.370	<0.001	0.322	<0.001
GC/IPL-IT	0.320	<0.001	0.254	<0.001
logMar	−0.296	<0.001	−0.254	<0.001
IOP	0.011	0.877	−0.028	0.689
MD	0.484	<0.001	0.365	<0.001

Statistically significant p values (p < 0.05) were in boldface.

AULCSF area under the logarithm of the contrast sensitivity function, CSF Acuity cutoff special frequencies of contrast sensitivity function, GC/IPL ganglion cell/ inner plexiform layer thickness, ST superior temporal sector, S superior sector, SN superior nasal sector, IN inferior nasal sector, I inferior sector, IT inferior temporal sector, logMar logarithmic vision, IOP intraocular pressure, MD mean deviation.

On the basis of the healthy macular region of each included eye, we divided the 203 eyes into 6 groups (see “Methods” for grouping criteria): 55 eyes in the ST group, 62 eyes in the S group, 82 eyes in the SN group, 69 eyes in the IN group, 33 eyes in the I group, and 28 eyes in the IT group. As shown in Fig. 2, the MD of visual field and GC/IPL thickness were different in the six groups (H = 16.03, 21.02; p = 0.007, 0.001), whereas there were no significant differences in AULCSF and logMar visual acuity (H = 1.63 and 6.48, p = 0.898 and 0.262). The comparison between groups is shown in eTable 2. The difference of MD between the SN and IT groups was the most significant (Z = −65.71, p′ = 0.024). The difference of GC/IPL thickness between the SN group and I group was the most significant (Z = −76.48, p′ = 0.001), followed by the SN-IT and S-I groups (Z = −63.33, −62.21; p′ = 0.034, 0.035).

Fig. 2. Comparison between groups of mean deviation (MD), the area under log [CSF] (AULCSF), and ganglion cell / internal plexiform layer (GC/IPL).

Among the six groups of superior temporal (ST), superior (S), superior nasal (SN), inferior nasal (IN), inferior (I) and inferior temporal (IT): A MD existed differently between groups, and there was a difference between the SN group and the IT group. B AULCSF did not differ among the groups. C GC/IPL existed differently between groups, and there were differences between S-I group, SN-IT group and SN-I group. The p values in the figures were all adjusted.

The structure-function correlations for varying severity of glaucoma are shown in Table 3. In pre-perimetric stage eyes, the GC/IPL thickness of inferior nasal and inferior sectors was correlated with the AULCSF (r = 0.397, 0.453, p = 0.020, 0.007), and the overall GC/IPL thickness was not correlated with the AULCSF (r = 0.275, p = 0.116). In early, moderate, and advanced eyes, overall GC/IPL thickness and GC/IPL thickness in the superior temporal, superior, superior nasal, and inferior nasal sectors were all correlated with AULCSF (p < 0.05).

Table 3.

Association between area under log contrast sensitivity function and ganglion cell/inner plexiform layer thickness in glaucoma of different severity.

	Pre-perimetric		Early		Moderate		Advanced
	r	p	r	p	r	p	r	p
GC/IPL	0.275	0.116	0.380	0.002	0.471	0.001	0.463	<0.001
GC/IPL-ST	0.038	0.833	0.248	0.043	0.442	0.002	0.276	0.043
GC/IPL-S	0.025	0.886	0.379	0.002	0.584	<0.001	0.383	0.004
GC/IPL-SN	0.096	0.589	0.490	<0.001	0.662	<0.001	0.441	0.001
GC/IPL-IN	0.397	0.020	0.417	<0.001	0.332	0.021	0.472	<0.001
GC/IPL-I	0.453	0.007	0.224	0.068	−0.011	0.939	0.210	0.128
GC/IPL-IT	0.213	0.226	0.119	0.338	−0.021	0.887	−0.03	0.784

Statistically significant p values (p < 0.05) were in boldface.

GC/IPL ganglion cell/ inner plexiform layer thickness ST superior temporal sector, S superior sector, SN superior nasal sector, IN inferior nasal sector, I inferior sector, IT inferior temporal sector.

Discussion

We found that macular GC/IPL thickness and localization of damage were significantly correlated with contrast sensitivity in OAG and differed between glaucoma of varying severity. The results provide evidence for the mechanism of impairment of contrast sensitivity in OAG. The findings also describe the feasibility of contrast sensitivity as a severity evaluation indicator in different stages of glaucoma.

About half a century ago, contrast sensitivity was noted to be first encoded by RGCs [18, 19]. Kwon’s team found that thinning of the GC/IPL in the macular region caused by glaucoma or aging led to increased contrast requirements for letter recognition [9]. They subsequently used deep learning to confirm that the thickness of GC/IPL was the structural basis for the Pelli-Robson contrast sensitivity [10]. In moderate non-proliferative diabetic retinopathy, thinning of the GC/IPL is significantly correlated with decreased AULCSF [13]. Our previous study showed that macular ganglion cell complex had a greater effect than peripapillary retinal nerve fibre layer on contrast sensitivity at 1 and 1.5 spatial frequencies in glaucoma patients, and the result implied that damage to RGCs in the macular region has a greater effect on contrast sensitivity than damage in the surrounding retina [20]. However, in a clinical study of glaucoma, Fatehi et al. found that mean GC/IPL thickness in the entire macular region did not correlate with contrast sensitivity at multiple spatial frequencies measured by the CSV-1000 test; only GC/IPL thickness in the inferior temporal and inferior nasal macular regions correlated with contrast sensitivity [8]. In this study, we found that GC/IPL was correlated with AULCSF both in individual sectors and the entire macular region.

The following reasons exist for the difference in results between our study and the study by Fatehi et al.: Cataract and pseudophakic eyes change the refractive media to affect contrast sensitivity [21]. The mean age of the individuals in Fatehi et al.’s study was 68 years and 42% had pseudophakic eyes. Our study was conducted to assess the effect of glaucomatous structural damage on contrast sensitivity in a relatively ideal context; we excluded patients who were more than fifty years old, or who had ocular media opacity or pseudophakic eyes. We used AULCSF as an assessment index. The qCSF test establishes a contrast sensitivity function by measuring contrast sensitivity at 19 spatial frequencies using 128 contrast levels to identify small changes in contrast sensitivity. In contrast, the CSV-1000 that Fatehi et al. used evaluated only 4 spatial frequencies and 8 contrast levels.

A novel hypothesis is that there are differences in the effect of RGCs on contrast sensitivity in different macular sectors [8]. In our study, the association of GC/IPL thickness with contrast sensitivity was stronger on the nasal side than temporal side and stronger on the superior side than inferior side (Table 2). This differential association may be related to the distribution of RGCs, with more RGCs on the nasal side of the macula than on the temporal side and more on the superior side than the inferior side in macaque and human eyes [22, 23]. Structural damage of macular regions with more RGCs is more detrimental to contrast sensitivity, which supports the idea that changes in count or density of RGCs are potential mechanisms of contrast sensitivity impairment. More interestingly, Sato et el. reported that the association between the regional retinal structure and function acquired by microperimetry was more pronounced in the inferior temporal macular region [24], whereas we found that inferior temporal structural damage had the least effect on behavioural contrast sensitivity. Table 3 shows that GC/IPL thickness in the inferior temporal macular region did not correlate with AULCSF when analyzed separately for each stage of glaucoma. In addition, the damage in the visual field and GC/IPL was less severe in the IT group compared with the SN group; however, there was no difference in contrast sensitivity (Fig. 2). RGCs in the inferior temporal macular region are susceptible to glaucomatous damage [25, 26], and, in the present study, this region was healthy in only some pre-perimetric, early, and a few moderate glaucoma eyes, which was the reason for the IT group having milder visual field impairment and less GC/IPL damage. As mentioned earlier, the low distribution of RGCs in the inferior temporal macula may lead to a mismatch between the severity of contrast sensitivity impairment and visual field deficit in this region because structural damage has a large effect on its regional retinal function and a small effect on behavioural contrast sensitivity. The lack of intrinsically photosensitive RGCs in the inferior temporal macular region or differences in the number of retinal nerve fibres afferent to the centre for contrast perception are also potential explanations for this phenomenon [7, 27]; these explanations remain to be investigated extensively.

A reasonable structure-function correlation is the basis for contrast sensitivity as a monitoring index of glaucoma progression. The lack of functional indexes for progression detection in patients with pre-perimetric and advanced glaucoma is mainly due to the fact that the visual field becomes impaired only after the number of damaged RGCs exceeds 40%, and for advanced glaucoma the test becomes more difficult to perform and is less accurate than for less advanced stages [28, 29]. In our study, contrast sensitivity and GC/IPL were significantly associated in early, moderate, and advanced glaucoma, and, considering the presence of a “floor effect” in GC/IPL [25], AULCSF changes are potentially a useful addition to the monitoring of disease progression in advanced glaucoma. Of course, this application needs to be verified by prospective studies. In pre-perimetric glaucoma, the correlation between contrast sensitivity and GC/IPL was not significant, probably due to the fact that macular damage is more common in the inferior temporal macular region; however, inferior temporal GC/IPL changes have a limited effect on contrast sensitivity. The controversy of whether structural or functional changes occur first persists among investigators and clinicians; thus, the fact that contrast sensitivity does not correlate with GC/IPL in pre-perimetric glaucoma cannot negate the value of clinical application of contrast sensitivity for such patients. Patients with suspected glaucoma have worse contrast sensitivity compared with controls [30–32]. Bierings et al. suggested that, even in intact areas of the visual field, glaucoma patients still have worse visual performance than healthy controls [33]. The value of contrast sensitivity in pre-perimetric glaucoma needs to be validated.

The following shortcomings may exist in our study: First, we conducted the study under relatively ideal conditions, with exclusion of patients who had other diseases affecting contrast sensitivity. To realize the clinical application of contrast sensitivity in glaucoma, further studies are needed to exclude the influence of other diseases on contrast sensitivity, and to improve the assessment methods of contrast sensitivity that are not affected by media opacities. Second, 40% of our included participants had a peak IOP below 21 mmHg. It is controversial whether normal-tension glaucoma and primary open-angle glaucoma are on a uniform disease spectrum, and whether their aetiologic differences have an impact on the structure-function correlation needs further study. Third, we included 203 eyes; however, in the grouping for different healthy macular regions, some subgroups had small sample sizes. Enlarging the sample size and avoiding the inclusion of eye overlap in group comparisons may provide more valuable information. Fourth, the determination of the healthy macular region was based on a GC/IPL thickness within the 90% reference interval of the healthy population; we could not eliminate the possibility that some patients had minor structural damage.

In conclusion, for patients with OAG, AULCSF was significantly correlated with GC/IPL thickness in the entire macular region and each of the six sectors. The degree of correlation was stronger in the nasal versus the temporal region and in the superior versus the inferior region of the macula. Eyes with a healthy inferior temporal macular sector had less visual field and macular GC/IPL damage than eyes with a healthy superior nasal macular sector; however, there was no difference in contrast sensitivity, and the inferior temporal macular region had the least effect on behavioural contrast sensitivity. The structure-function correlation was significant for patients with early, moderate, and advanced OAG. AULCSF did not correlate with GC/IPL in pre-perimetric glaucoma. Our study supports the use of AULCSF as a complementary index to structural examination for severity evaluation of advanced glaucoma, although the study findings do not support the use of AULCSF for severity evaluation of pre-perimetric glaucoma. Whether AULCSF can be used as an indicator for the progression of glaucoma needs to be investigated with additional prospective studies.

Summary

What was known before

• Persons with glaucoma have decreased contrast sensitivity.

• Lack of accurate functional indexes to detect disease progression in patients with advanced or pre-perimetric glaucoma.

What this study adds

• Contrast sensitivity correlates significantly with the thickness of macular region ganglion cell / internal plexiform layer in open-angle glaucoma.

• Retinal ganglion cells in the inferior temporal macular region have the least effect on contrast sensitivity among the macular sectors.

• Contrast sensitivity is a potential severity evaluation indicator for early, moderate, and advanced open-angle glaucoma but not for pre-perimetric glaucoma.

Author contributions

NW contributed to design, acquisition of funding and general supervision of the research group. RP and JTP contributed to design, analysis of results, collection of data and drafting of the manuscript. KC contributed to the data analysis. ZLL and QZ contributed to the manuscript revision. All authors reviewed and edited the manuscript and approved the final version of the manuscript.

Funding

The study is funded by National Natural Science Foundation of China (82130029 and 82070960). The funding organization had no role in the design or conduct of this research.

Data availability

All data generated or analyzed during this study are included in this published article and its supplementary information files.

Competing interests

ZLL holds intellectual property interests in visual function measurement and rehabilitation technologies, and equity interests in Adaptive Sensory Technology, Inc. (San Diego, CA, USA) and Jiangsu Juehua Medical Technology, Ltd (Jiangsu, China). There is no other conflict of interest in the submission of this manuscript.

Ethics approval

The Medical Ethics Committee of Beijing Tongren Hospital approved all study procedures.

Supplementary information

The online version contains supplementary material available at 10.1038/s41433-023-02887-0.