Glaucoma is a chronic and progressive optic neuropathy that is primarily characterized by a distinctive structural change in the optic nerve head, setting it apart from most other acquired optic neuropathies. A key feature of glaucoma is the gradual thinning of the neuroretinal rim, which leads to an enlargement of the optic cup, a process known as optic nerve cupping. This phenomenon occurs due to the progressive loss of retinal ganglion cell axons, along with associated supporting glial cells and vascular structures. In contrast, most other optic neuropathies result in pallor of the optic nerve without the development of cupping (1). Patients affected by glaucoma typically experience a gradual loss of peripheral vision, and without appropriate intervention, this may progress to complete vision loss. Although glaucoma is frequently associated with elevated intraocular pressure (IOP), it can also occur in individuals with normal IOP levels which are maintained in the eye by the continuous formation and drainage of aqueous humor. The aqueous humor, produced by the ciliary body, circulates throughout the anterior chamber and is drained primarily through the trabecular meshwork located in the iridocorneal angle. Increased intraocular pressure does not result from excessive aqueous humor production but rather from impaired aqueous outflow (2). The disease is classified based on variations in the anterior segment that contribute to elevated intraocular pressure. Glaucoma is broadly classified based on the appearance of the iridocorneal angle, which leads to its categorization into open-angle, closed-angle, and developmental types. These categories are further subdivided into primary and secondary forms. Primary open-angle glaucoma (POAG) can occur either with elevated intraocular pressure or in the absence of IOP elevation, with the latter variant referred to as normal-tension glaucoma. POAG is further classified based on the age of onset, into adult-onset disease - typically occurring after 40 years of age, and juvenile-onset disease manifesting between 3 and 40 years of age. Secondary open-angle glaucomas arise due to other underlying conditions, such as exfoliation syndrome or pigment-dispersion syndrome (3). Similarly, closed-angle glaucoma is categorized into primary and secondary types. Primary closed-angle glaucoma includes mechanisms such as pupillary block, whereas secondary closed-angle glaucomas may arise due to inflammatory or neovascular causes. Developmental glaucomas encompass conditions such as primary congenital glaucoma and those associated with genetic syndromes like aniridia or Axenfeld–Rieger syndrome. Among these various subtypes, POAG is the most common form of glaucoma. Despite its clinical classification, POAG likely represents a group of distinct yet clinically similar disease entities that share common pathological features. Global and Indian prevalence of POAG and its impact on public health. Epidemiological studies assessing glaucoma prevalence among adults aged 40 years and above in India have estimated its occurrence to range between 2.7% and 4.3% (4-8). Projections indicate that by the year 2040, approximately 27.8 million additional individuals in Asia will be affected by glaucoma, with India and China expected to bear the highest disease burden (9). Within India, glaucoma has been identified as one of the major causes of blindness in approximately 1.2 million individuals, accounting for nearly 5.5% of total cases of blindness (10). A thorough comprehension of RNFL and GCC changes throughout perimetric stages is of considerable clinical importance. Identifying patterns of structural degeneration linked to varying degrees of functional impairment can aid in: • Early Detection: Recognizing POAG prior to significant visual field deterioration, facilitating prompt intervention. • Accurate Staging: Enhancing disease classification to support improved clinical decision-making. • Treatment Monitoring: Assessing the efficacy of treatment strategies via longitudinal structural evaluations. By integrating OCT-derived RNFL and GCC measurements with visual field assessments, this research seeks to enhance diagnostic methodologies, improve disease staging, and contribute to the better management of glaucoma through evidence-based insights, ultimately reinforcing the structure-function relationship in POAG for superior clinical outcomes.

This study was an observational study conducted on patients who attended the Outpatient Department of Ophthalmology at Mahatma Gandhi Medical College and Hospital (MGMCH), Sitapura, Jaipur. The study aimed to estimate the Retinal Nerve Fibre Layer (RNFL) and Ganglion Cell Complex (GCC) thickness in patients diagnosed with Primary Open Angle Glaucoma (POAG) across different perimetric stages. The Study was approved by the institutional ethics committee. Subjects were explained about the procedure and written informed consent was taken and was conducted over a period of 18 months. The sample size was estimated using the single proportion estimation method, considering a prevalence of POAG at three percent (11) with an absolute precision of five percent and a level of significance of five percent. Based on these calculations, final sample size came out to be 45. Total number of patients included in the study are 50. Patient Recruitment and Data Collection • Patients coming to the Eye OPD of Mahatma Gandhi Hospital were examined for this study. • A thorough history was taken, which included personal details, chief complaints, any significant past and family history for systemic/ophthalmic diseases, surgical history, drug history and personal history. Each participant underwent the following ophthalmological examinations: I. Visual Acuity Measurement II. Intraocular Pressure (IOP) Measurement III. Central Corneal Thickness (CCT) Assessment IV. Torch Light Examination V. Slit Lamp Biomicroscopy VI. Gonioscopy VII. Automated Visual Field Perimetry VIII. Dilated fundus examination IX. Optical Coherence Tomography (OCT) Inclusion Criteria: • Patients aged 18 to 50 years (12). • Patients of either gender. • Patients who voluntarily provided informed written consent. • Patients diagnosed with Primary Open Angle Glaucoma. Exclusion Criteria: • Presence of other ocular conditions affecting RNFL and GCC thickness. • History of prior ocular surgery. • Patients who were unable to cooperate for OCT and Perimetry. Diagnostic Techniques Used Automated Visual Field Perimetry: • Perimetry was performed using the Carl Zeiss Humphrey Field Analyzer 3. • The patient was instructed to fixate on a central target within a dome-shaped instrument. • Small flashes of light appeared at different locations, and the patient pressed a button each time they perceived a flash. • The instrument generated a visual field map that helped assess glaucomatous damage. 2. Optical Coherence Tomography (OCT): • OCT was conducted using the Carl Zeiss Cirrus HD-OCT Model 500. • The procedure was non-invasive and took approximately 10 minutes. • If required, pupil dilation was performed to obtain a wider retinal view. • The patient was instructed to place their chin on a rest and look at a fixation target. • The scan measured the RNFL and GCC thickness, providing quantitative data for analysis. Criteria for diagnosis of Primary Open Angle Glaucoma (13) Definitive diagnosis for Primary Open-Angle Glaucoma includes the following- o Characteristic optic nerve appearance. o Visual field defects o Unobstructed open angle on gonioscopy o Intra ocular pressure maybe normal or high, but is usually on the higher side.

Table 1: Frequency distribution of age of patients Age Interval (In Yrs.) n = 50 In % 18 - 25 5 10% 26 - 30 4 8% 31 - 35 7 14% 36 - 40 8 16% 41 - 45 15 30% 46 - 50 12 24% Table 2: Frequency distribution of gender of patients Gender n = 50 In % Male 24 48% Female 26 52% Table 3: Primary open angle glaucoma stage wise descriptive statistics of average RNFL of patients Average RNFL (In µm) Minimum Maximum Median (IQR) Stage 1 94 114 103 (99-107) Stage 2 72 90 80.5 (78.25-83.75) Stage 3 63 78 69.5 (66.5-73.5) Stage 4 49 72 58 (55.5-64.5) Stage 5 28 56 43 (37-45) RNFL: Retinal Nerve Fibre Layer; IQR: Inter-quartile range Table 4: Primary open angle glaucoma stages wise descriptive statistics of GCC thickness of patients GCC Thickness (In µm) Minimum Maximum Median (IQR) Stage 1 72 85 77 (74.5-81) Stage 2 59 76 67 (62.5-71) Stage 3 47 64 57 (53.25-60.25) Stage 4 40 54 48 (42.5-51.5) Stage 5 26 41 36 (33-38) GCC: Ganglion Cell Complex; IQR: Inter-quartile range Table 5: Comparing average RNFL, GCC thickness between different stages of primary open angle glaucoma of patients by using ANOVA statistics Variables Stage 1 Stage 2 Stage 3 Stage 4 Stage 5 Anova P-Value Average RNFL Thickness 103.3 ± 7.12 80.9 ± 5.15 70.2 ± 5.31 59.55 ± 6.85 41.4 ± 8.72 91.75 < 0.0001 GCC Thickness 77.83 ± 4.92 67 ± 5.46 56.3 ± 5.38 47.09 ± 5.05 35 ± 5.03 82.2 < 0.0001 Mean ± SD: Mean ± Standard deviation

Primary open-angle glaucoma (POAG) represents a chronic, progressive optic neuropathy characterized by the degeneration of retinal ganglion cells and their axons, ultimately leading to irreversible visual field loss. As one of the leading causes of blindness worldwide, POAG poses a significant public health challenge, particularly given its typically asymptomatic onset and late presentation (14). The global burden of glaucoma continues to rise, with projections estimating a marked increase in affected individuals by 2040, especially in aging populations and underserved regions (15). Age is universally recognized as the most significant non-modifiable risk factor for POAG. Our study revealed a major representation of patients in the 41–50-year age group, with a substantial proportion below the age of 40. This age distribution suggests that although POAG has been traditionally associated with older adults, its onset can manifest significantly earlier in specific subpopulations, particularly in those with underlying risk factors or genetic predisposition. Age Distribution: In our study, the patients ages ranged from 24 to 48 years, with a mean of 35.5 ± 7.43 years and a median of 34.5 years, indicating a high proportion of relatively young individuals diagnosed with POAG. This contrasts with the traditional perception of POAG as a disease predominantly affecting older populations and reflects a growing global trend of earlier diagnosis. Gender distribution- Gender distribution in the present study revealed a slight female predominance (52%) compared to males (48%) among patients diagnosed with primary open-angle glaucoma (POAG). This nearly equal distribution is consistent with a broad range of population-based studies which have documented minimal or no significant gender bias in POAG occurrence, although minor variations may be influenced by geographic, ethnic, or lifestyle-related factors. Hence, our study showed no predilection for either gender. In our study, the stage-wise analysis of primary open-angle glaucoma (POAG) revealed that early-stage disease (Stage 1) was the most frequently observed, comprising 14% of males and 16% of females. This trend suggests a reasonably effective level of early detection within the studied cohort. Stage 2 glaucoma was equally distributed among both genders (12%), while Stage 3 showed a slight predominance among females (10%) compared to males (8%). Stages 4 and 5 demonstrated an equal distribution across sexes (8% and 6%, respectively). This relatively balanced representation across all disease stages between males and females indicates that POAG progression is not significantly influenced by gender in this cohort, echoing a gender-neutral disease pattern. Retinal Nerve Fibre Layer (RNFL) Thickness: RNFL thickness, an important marker of axonal loss in glaucoma, ranged from 28 µm to 114 µm with a mean of 68.67 ± 20.1 µm. This wide variation reflects the presence of both early and advanced disease stages. RNFL thinning is directly proportional to visual field loss and optic nerve damage, and its measurement has become a cornerstone of structural glaucoma diagnosis. The stage-wise inverse correlation between RNFL thickness and POAG severity in the current study supports the growing consensus on its role as a primary structural biomarker. In particular, the sharply reduced RNFL levels in Stage 5 (median: 43 µm) underscore the extensive axonal loss in advanced disease, while relatively preserved values in Stage 1 reinforce the utility of early OCT-based screening in at-risk individuals. These findings are pivotal for both diagnosis and follow-up, as RNFL loss typically precedes measurable functional decline on perimetry. Ganglion Cell Complex (GCC) Thickness: GCC thickness ranged from 26 µm to 85 µm, with a mean of 55.1 ± 14.9 µm. GCC analysis has gained importance due to its close correlation with early functional visual impairment. The present study observed a progressive decline in Ganglion Cell Complex (GCC) thickness with advancing stages of Primary Open Angle Glaucoma (POAG), a trend consistent with the known pathophysiological mechanism of retinal ganglion cell degeneration. In Stage 1, patients demonstrated a median GCC thickness of 77 µm (IQR: 74.5–81 µm), indicative of preserved inner retinal structural integrity. This thickness gradually reduced through Stages 2 and 3, with medians of 67 µm and 57 µm respectively, and showed further marked reductions in Stage 4 (48 µm) and Stage 5 (36 µm; IQR: 33–38 µm). The minimum value of GCC thickness in males was found to be 29 µm and 26 µm in females, likewise the maximum GCC thickness in males was 82 µm and 85 µm in females. Mean GCC thickness was comparable between males (55.71 ± 15.12 µm) and females (54.69 ± 15.01 µm), with the t-value of 0.221 and p-value of 0.8261, indicating a lack of significant gender-based variation. Our study further provides critical insight into the progressive structural degeneration in primary open-angle glaucoma (POAG) by comparing the average thickness of the retinal nerve Fibre layer (RNFL) and ganglion cell complex (GCC) across five disease stages using ANOVA statistical analysis. The findings reveal a consistent and statistically significant decrease in both RNFL and GCC thickness as disease severity advances, substantiating their role as essential structural biomarkers in glaucoma evaluation. The mean RNFL thickness observed in Stage 1 was 103.3 ± 7.12 µm, closely approximating normative values, indicating preserved axonal architecture in the early phase of the disease. This thickness showed a steep and graded reduction across successive stages—80.9 ± 5.15 µm in Stage 2, 70.2 ± 5.31 µm in Stage 3, 59.55 ± 6.85 µm in Stage 4, and reaching 41.4 ± 8.72 µm in Stage 5. The ANOVA analysis demonstrated a highly significant F-statistic (F = 91.75) and a p-value of < 0.0001, confirming that these differences were not due to random variation but reflected a real and consistent structural decline with increasing POAG severity.

In conclusion, the combination of Retinal Nerve Fibre Layer (RNFL) and Ganglion Cell Complex (GCC) thickness assessment through spectral-domain Optical Coherence Tomography (OCT), in conjunction with standard functional evaluations such as visual field perimetry, provides a thorough and effective strategy for the diagnosis and management of POAG. These metrics not only facilitate early detection and staging but also function as critical instruments for monitoring disease progression and customizing treatment plans aimed at preserving visual function and enhancing quality of life.

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