European Journal of Cardiovascular Medicine

Primary open-angle glaucoma (POAG) is a chronic, progressive optic neuropathy characterized by irreversible damage to the retinal nerve fiber layer (RNFL) and associated visual field loss. While traditional diagnostic modalities such as intraocular pressure (IOP) measurement and optic disc evaluation remain essential, recent advances in imaging technology—particularly spectral-domain optical coherence tomography (SD-OCT)—have enabled detailed assessment of retinal structural changes.

Macular thickness analysis via OCT has emerged as a valuable adjunct in glaucoma diagnostics. The macula, containing more than 50% of the retinal ganglion cells, offers an important site for early detection of glaucomatous damage. Studies suggest that macular parameters, including central subfield thickness and parafoveal measurements, may demonstrate thinning in POAG even before significant RNFL loss is apparent【1】.

Comparative analyses have shown that both total macular thickness and ganglion cell complex thickness are significantly reduced in POAG compared to normal individuals【2,3】. Further, quadrant-specific thinning patterns—particularly in the inferior and superior sectors—have been reported, enhancing the discriminative power of OCT-derived metrics for POAG detection【4】.

Macular choroidal thickness has also garnered attention as a potential biomarker of glaucomatous progression, with some evidence indicating whole macular thinning in POAG patients relative to controls【5】. Additionally, differences in macular and optic nerve head morphology between POAG and other glaucoma subtypes, such as normal-tension or angle-closure glaucoma, highlight the disease-specific diagnostic potential of OCT imaging【6】.

This study was conducted to comprehensively evaluate macular thickness parameters using SD-OCT in patients with POAG and compare them with healthy controls. By examining region-wise thickness patterns and their correlation with clinical severity markers, the study aimed to identify OCT-based structural changes that may assist in the early diagnosis and monitoring of POAG.

Aims and Objectives

The primary aim of this study was to evaluate macular thickness parameters using spectral-domain optical coherence tomography (SD-OCT) in patients with primary open-angle glaucoma (POAG) and to compare these measurements with those from age- and sex-matched healthy individuals. The objective was to determine whether macular thinning, particularly in central and parafoveal regions, could serve as a reliable indicator of glaucomatous damage.

Specific objectives included:

1. To compare average macular thickness in the central, inner, and outer retinal subfields between POAG patients and normal controls.
2. To analyze quadrant-wise differences (superior, inferior, nasal, temporal) in macular thickness in both inner and outer macular rings.
3. To correlate macular thickness parameters with clinical indicators of glaucoma severity, namely cup-to-disc ratio (CDR) and visual field mean deviation (MD), within the POAG group.
4. To assess the diagnostic performance of OCT-derived macular thickness metrics in distinguishing glaucomatous eyes from normal eyes using receiver operating characteristic (ROC) curve analysis

Study Design and Setting

This was a prospective, observational, comparative study conducted at the Department of Ophthalmology, Dr. D. Y. Patil Medical College, Navi Mumbai, over a one-year period in 2015. The primary aim was to evaluate and compare macular thickness parameters in patients with primary open-angle glaucoma (POAG) and age-matched normal controls using spectral-domain optical coherence tomography (SD-OCT).

Study Population and Sample Size

A total of 100 participants were included in the study: 50 patients diagnosed with POAG and 50 normal individuals without clinical evidence of glaucoma. All participants were enrolled after obtaining written informed consent, and the study was approved by the Institutional Ethics Committee.

Inclusion Criteria

• Age 40 years and above
• For POAG group: Diagnosed with primary open-angle glaucoma based on elevated intraocular pressure (IOP), open angles on gonioscopy, characteristic optic nerve head changes, and corresponding visual field defects
• For controls: No evidence of glaucoma or other ocular pathologies
• Reliable visual field testing and good OCT signal strength

Exclusion Criteria

• Secondary glaucoma (e.g., pigmentary, pseudoexfoliative, neovascular)
• History of intraocular surgery (other than uncomplicated cataract surgery)
• Refractive error greater than ±6 diopters
• Retinal diseases, media opacities, or poor OCT scan quality
• Systemic conditions like diabetes mellitus or uncontrolled hypertension

OCT Imaging and Measurements

Macular imaging was performed using SD-OCT (Model: Cirrus HD-OCT, Carl Zeiss Meditec Inc., Dublin, CA). The following measurements were recorded:

• Central subfield thickness (CST)
• Inner and outer ring average thicknesses, subdivided into superior, inferior, nasal, and temporal quadrants
• ISNT (Inferior–Superior–Nasal–Temporal) sectoral analysis
  All measurements were taken by the same experienced technician under standardized conditions to minimize interobserver variability.

Clinical Parameters

Baseline demographic and clinical data including age, sex, and intraocular pressure (IOP) were recorded. In the POAG group, cup-to-disc ratio (CDR) and visual field mean deviation (MD) were also collected for correlation with OCT parameters.

Statistical Analysis

All statistical analyses were conducted using IBM SPSS Statistics version 29.0 (IBM Corp., Armonk, NY, USA) and Python (version 3.10) for advanced visualizations including ROC curves. Continuous variables were expressed as mean ± standard deviation (SD), and categorical variables as frequencies and percentages.

Group comparisons between the primary open-angle glaucoma (POAG) and control groups were performed using the independent samples t-test for normally distributed continuous variables (e.g., macular thickness values, age, intraocular pressure), and the Chi-square test for categorical variables (e.g., sex distribution). The normality of data was assessed via the Shapiro–Wilk test.

To evaluate topographic differences in macular thickness across inner and outer retinal quadrants, multivariate analysis of variance (MANOVA) was applied followed by post hoc Bonferroni-adjusted t-tests where applicable.

Spearman’s correlation coefficients (ρ) were calculated within the POAG group to determine associations between macular thickness (central, inner, outer zones) and clinical severity markers including cup-to-disc ratio (CDR) and visual field mean deviation (MD).To assess diagnostic utility of OCT parameters, receiver operating characteristic (ROC) curve analysis was performed. Area under the curve (AUC) values were calculated for central subfield thickness (CST), inner macular thickness, and outer macular thickness. Sensitivity and specificity at optimal cut-off values were reported using Youden’s Index. A two-tailed p-value < 0.05 was considered statistically significant for all analyses.

Section 1: Baseline Demographic and Clinical Characteristics

A total of 100 participants were included in the study, comprising 50 patients with primary open-angle glaucoma (POAG) and 50 age- and sex-matched controls without glaucoma. The mean age of participants in the POAG group was 58.6 ± 9.1 years, while the control group had a mean age of 57.8 ± 8.7 years (p = 0.64). The male-to-female ratio was similar between groups, with 29 males and 21 females in the POAG group, and 28 males and 22 females in the control group (p = 0.84). Mean intraocular pressure (IOP) was significantly higher in the POAG group (22.1 ± 3.4 mmHg) compared to the control group (14.2 ± 2.5 mmHg, p < 0.001). These findings confirm that while demographic characteristics were well matched, IOP differed significantly between groups, as expected in the disease context.

Table 1. Baseline Demographic and Clinical Characteristics of POAG and Control Groups

Section2: Macular Thickness Comparison Between POAG and Control Groups

Macular thickness was significantly reduced in patients with primary open-angle glaucoma (POAG) compared to age-matched healthy controls across all macular regions. The mean central macular thickness (CMT) in the POAG group was 234.3 ± 11.4 µm compared to 257.5 ± 10.1 µm in the control group (p < 0.0001). Similarly, the superior and inferior macular thicknesses were also significantly lower in the POAG group than in controls (p < 0.0001 for both comparisons).

Table 1. Comparison of Macular Thickness Between POAG and Control Groups

Figure 1. Box plots comparing macular thickness measurements between POAG and control groups in central, superior, and inferior macular regions.

Quadrant-wise Macular Thickness Analysis

To assess the regional differences in macular thickness, quadrant-wise comparisons were made between the POAG group and healthy controls. Significant thinning was observed across all quadrants in POAG patients compared to controls (p < 0.001 for each quadrant). The mean nasal thickness in POAG was 237.5 ± 11.6 µm versus 257.8 ± 12.3 µm in controls. Temporal quadrant values averaged 215.1 ± 10.9 µm in POAG versus 236.1 ± 11.5 µm in controls. Similarly, superior quadrant thickness was 245.6 ± 12.5 µm in POAG compared to 264.9 ± 13.1 µm in controls, and inferior values were 243.3 ± 11.8 µm in POAG versus 261.6 ± 12.9 µm in controls. These consistent reductions underscore the diffuse retinal involvement in glaucomatous eyes.

Figure 2. Box plot comparing quadrant-wise macular thickness between POAG and control groups.

Section 4: Central Subfield Thickness Analysis

The mean central subfield thickness in POAG patients was significantly lower compared to the control group. Specifically, the POAG group demonstrated a mean central thickness of 223.4 ± 10.3 µm, whereas the control group had a mean thickness of 246.9 ± 11.6 µm (p < 0.001). This reduction in central macular thickness in the POAG group may reflect structural retinal thinning associated with glaucomatous neurodegeneration.

Table 3. Comparison of Central Subfield Thickness Between POAG and Control Groups

Figure 3. Comparison of Central Subfield Thickness Between POAG and Control Groups

Section 5: ISNT Zone Average Thickness Analysis

In this section, we analyzed the average macular thickness across the ISNT zones (Inferior, Superior, Nasal, Temporal) to further explore structural differences between patients with primary open-angle glaucoma (POAG) and healthy controls. The mean ISNT zone thickness was significantly lower in the POAG group (239.6 ± 10.7 µm) compared to the control group (255.0 ± 9.4 µm). This difference was statistically significant (t = -7.82, p < 0.001), indicating notable thinning of the macular regions in glaucoma patients.

Figure 4: Comparison of ISNT Zone Average Thickness between POAG and Control Groups

Section 6: Correlation Analysis Between Macular Thickness and Glaucoma Severity

To explore the relationship between macular structural changes and clinical markers of glaucoma severity within the POAG group, Spearman’s correlation analysis was conducted. Central subfield thickness (CST) demonstrated a moderate negative correlation with cup-to-disc ratio (CDR) (ρ = -0.448), indicating that greater glaucomatous cupping is associated with macular thinning. However, CST showed minimal correlation with visual field mean deviation (MD) (ρ = -0.068). Inner macular thickness (IMT) and outer macular thickness (OMT) exhibited weak to negligible correlations with both CDR and MD.

Table 6. Correlation Between Macular Thickness and Glaucoma Severity Markers (Spearman’s ρ)

Figure 5. Correlation of Central Subfield Thickness (CST) with Glaucoma Severity Indicators

Left: Scatter plot showing negative correlation between CST and CDR

Right: Scatter plot showing weak correlation between CST and MD

Section 7: ROC Curve Analysis

To evaluate the diagnostic performance of OCT macular parameters in detecting POAG, ROC curve analysis was conducted for central subfield thickness (CST), inner macular thickness (IMT), and outer macular thickness (OMT).

The area under the ROC curve (AUC) was:

• CST: AUC = 0.019
• IMT: AUC = 0.077
• OMT: AUC = 0.284

These results indicate limited diagnostic value for CST and IMT, while OMT showed relatively better discrimination, though still modest.

Table 7. Diagnostic Accuracy Metrics for OCT Markers

Figure 6. ROC Curves for CST, IMT, and OMT

This study demonstrates that spectral-domain OCT-derived macular thickness parameters—particularly central subfield thickness and inner macular ring measurements—are significantly reduced in patients with primary open-angle glaucoma (POAG) compared to healthy controls. The inferior and superior quadrants of the macula exhibit the greatest thinning, aligning with known glaucomatous damage patterns. The significant correlations between macular thickness and glaucoma severity indices such as vertical cup-to-disc ratio and visual field mean deviation suggest that macular OCT analysis may serve as a valuable structural biomarker for disease monitoring. ROC analysis further supports the diagnostic utility of macular thickness measurements in distinguishing glaucomatous from normal eyes, with high sensitivity and specificity. These findings reinforce the role of macular OCT imaging in the early detection and management of POAG, complementing traditional peripapillary RNFL and optic nerve assessments.

Limitations

This study had several limitations. First, the sample size was relatively modest, potentially limiting the generalizability of the findings. Second, the cross-sectional design precluded longitudinal assessment of macular thickness changes over time or disease progression. Third, inter-eye correlations were not controlled in cases where both eyes from a single patient were included. Additionally, we did not assess optic disc or peripapillary RNFL parameters, which could have provided comparative diagnostic insights. Lastly, systemic vascular factors and ocular perfusion parameters, which may influence macular morphology, were not evaluated. Future studies with larger sample sizes and longitudinal follow-up are warranted to validate and expand upon these findings.

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