Authors: Fei Hu, Linlin Luo, Hong Yang, Ting Liu, Ling Yu
Categories: Research, Ocular hypertension, Intraocular pressure, Schlemm’s Canal, Iris characteristics, Corneal curvature
Source: BMC Ophthalmology
Authors: Fei Hu, Linlin Luo, Hong Yang, Ting Liu, Ling Yu
This study investigates the clinical characteristics of ocular hypertension (OHT) by analyzing factors such as Schlemm’s canal morphology, intraocular pressure (IOP), iris traits, angle configuration, lens thickness (LT), and retinal nerve fiber layer (RNFL) thickness.
A total of 60 OHT patients (120 eyes) and 60 healthy controls (120 eyes) underwent cross-sectional and case-control analyses using measurements like IOP, visual acuity, and anterior segment OCT imaging. Statistical analyses involved independent t-tests, Mann-Whitney U tests, correlation analysis, and multivariate logistic regression, with continuous adjustment for spherical equivalent (SE) and central corneal thickness (CCT).
Compared to controls, OHT patients had significantly higher Covirs-bIOP (22.67 ± 4.56 mmHg vs. 15.67 ± 2.17 mmHg, p < 0.001), CCT (578.79 ± 27.62 μm vs. 552.29 ± 33.24 μm, p < 0.001), AL (25.48 ± 1.32 mm vs. 24.91 ± 2.17 mm, p = 0.015), nasal AOD500 (0.87 mm vs. 0.78 mm, p = 0.004), and nasal LTM (1481.44 ± 282.06 μm vs. 1317.50 ± 277.49 μm, p < 0.001), along with a more negative SE (-4.32 D vs. -1.75 D, p < 0.001). Multivariate logistic regression showed increased CCT (OR = 1.45 per 10 μm, p = 0.001), longer AL (OR = 1.38 per mm, p = 0.030), wider nasal AOD500 (OR = 1.21 per 0.1 mm, p = 0.018), and greater nasal LTM (OR = 1.10 per 100 μm, p = 0.044) were independently associated with OHT after adjusting for SE and CCT as continuous covariates.
These observations indicate that certain structural characteristics of the anterior segment and cornea are of paramount importance in OHT, which emphasizes the necessity of high-resolution anterior segment assessment as part of risk stratification and early treatment.
Intraocular pressure (IOP), or ocular tension, is defined as the pressure applied by the contents of the eyeball onto the eye wall. IOP is typically measured in the range of 10 to 21 mmHg (1 mmHg = 0.133 kPa), with the reference standard being the Goldmann applanation tonometer to measure IOP [1, 2]. Increased IOP is a major risk factor for the progression of glaucoma, with studies confirming that for every 1 mmHg increase in IOP, the risk of developing glaucoma rises by 12% [3, 4]. High IOP contributes to glaucomatous optic neuropathy and visual field loss by damaging the optic nerve. While it is a primary risk factor for primary open-angle glaucoma (POAG), normal-tension glaucoma (NTG) can also occur in individuals with normal IOP levels [5, 6]. Studies have explored the relationship between IOP fluctuations and glaucoma progression, emphasizing the importance of consistent IOP management [7].
When multiple IOP measurements exceed the normal upper limit without evidence of glaucomatous optic nerve changes and/or visual field damage, and with a wide anterior chamber angle, a diagnosis of ocular hypertension (OHT) can be made. This excludes secondary glaucoma or factors such as thicker corneas and measurement errors that may cause pseudohypertonia. OHT is an ocular condition that is marked by a moderately high IOP (> 21 mmHg) with no glaucomatous damage or visual field loss. The diagnostic criteria are open anterior chamber angles as observed by gonioscopy and ruling out secondary pathologies like uveitis or trauma [8]. Comparative studies reveal that the average IOP in OHT patients was about 24.43 ± 3.17 mmHg, endearing differences when compared to those of healthy persons [9].
According to the 5th edition of the European Glaucoma Society (EGS) guidelines, the diagnostic criteria for OHT include the untreated IOP > 21 mmHg; normal visual field; open anterior chamber angle (confirmed by gonioscopy); no other ocular diseases or history/signs of steroid use; and no additional risk factors [10]. The China Expert Consensus on the Diagnosis,* Treatment*,* and Follow-up of Ocular Hypertension* (2020) states that the characteristics of OHT open anterior chamber angle confirmed by gonioscopy; untreated IOP exceeding 21 mmHg; no glaucomatous optic disc changes, such as cup enlargement or narrowing of the disc margin; no detectable nerve fiber layer defects; no visual field defects; possible co-occurrence of pigment dispersion or pseudoexfoliation; and exclusion of secondary ocular hypertension, such as that caused by ocular trauma or uveitis. According to previous literature, the IOP in OHT patients has been reported as 24.43 ± 3.17 mmHg [11], compared to 14.02 ± 2.33 mmHg in healthy individuals [12].
According to the epidemiological studies, the prevalence rate of OHT in the general population is about 6%, whereas the prevalence rate of POAG is about 2.4%. Approximately 0.5-2.0% of untreated patients with OHT develop POAG per year [13]. In China, the current prevalence of POAG is 2%. The prevalence of OHT varies by 3.1–8.6% in Caucasians, approximately 7.4% in African Americans, and about 1.4% in Asians [14]. The European Glaucoma Prevention Study (EGPS), a randomized controlled trial, found that age (for every 10-year increase, the risk of glaucoma increases by 26%), IOP (for every 1 mmHg increase, the risk of glaucoma increases by 9%), vertical and horizontal cup-to-disc ratios (for every 0.1 increase, the risk of glaucoma increases by 19%), visual field pattern standard deviation (for every 0.2 dB increase, the risk of glaucoma increases by 13%), and central corneal thickness (for every 40 μm decrease, the risk of glaucoma increases by 2.04 times) are significant risk factors. These can be used to assess the risk of progression from ocular hypertension to open-angle glaucoma [15].
The physiological IOP in healthy individuals is maintained through the dynamic balance between the production and outflow of aqueous humor (AH). AH is produced at a rate of 2.4 ± 0.6 µl/min, with an equal amount of AH being removed from the eyeball through its outflow pathways. The final volume of AH is approximately 0.31 mL [16]. The resistance to AH outflow primarily occurs at the trabecular meshwork (TM) in the trabecular or juxtacanalicular regions, as well as at the inner wall of Schlemm’s canal (SC) [17]. AH is produced by the non-pigmented epithelium of the ciliary body, flows through the posterior chamber and pupil, and reaches the anterior chamber. In the anterior chamber, AH plays a critical role in maintaining intraocular pressure, providing nutrients, regulating refraction, protecting intraocular tissues, and participating in immune responses [18]. Furthermore, AH facilitates waste removal through two the primary and non-primary (uveoscleral) routes [19, 20]. The primary pathway involves AH flowing through the TM and SC, ultimately joining the episcleral venous system, accounting for 70% to 90% of AH outflow. The remaining 10% to 30% drains via the uveoscleral pathway [21].
SC serves as the primary drainage pathway for AH and plays a critical role in the blood-aqueous barrier [22–24]. As a key channel for intraocular AH drainage, structural and functional abnormalities in SC are closely associated with the development of ocular hypertension [25]. Unlike normal vascular endothelial cells, the basement membrane beneath the inner wall (IW) of SC is incomplete. In normal vascular endothelial cells, vertical forces act from the apical to the basal side. However, in SC endothelial cells, the vertical forces are reversed, acting from the basal to the apical side [26]. SC resembles a lymphatic vessel, and Pawlak JB et al. identified lymphatic markers expressed in SC endothelial cells [27]. The inner wall of SC maintains relatively tight junctions between endothelial cells, resulting in greater pressure differences under the same volume of fluid. This unique characteristic makes SC more prone to deformation and collapse. AH outflow around the eye occurs in a segmental manner rather than uniformly. Studies have demonstrated that the nasal region of SC has a larger cross-sectional area compared to the temporal region in normal individuals [28–30].
SC was initially ignored and obscure to monitor because of its minute size and disguised position in old literature. The morphology of SC has received more attention as recently more minimally invasive glaucoma surgeries (MIGS) have been introduced specifically targeting SC, i.e., Ab-interno canaloplasty (ABiC), gonioscopy-assisted transluminal trabeculotomy (GATT) and penetrating canaloplasty (PCP) [5]. New technologies have led to enhanced capacity to visualize and treat SC through the application of techniques like ultrasound biomicroscopy (UBM), optical coherence tomography (OCT), and intraoperative fluorescein angiography. Through these dynamics, clinicians and researchers can optimize their practices, in terms of diagnosis as well as treatment methods, thereby promising to manage such IOP-related conditions.
Yet, little evidence has been generated as to how all these structural parameters of anterior segment anatomy, trabecular meshwork dimensions, and corneal biomechanics affect IOP in young OHT patients utilizing a multimodal imaging approach [31]. The majority of existing studies examine older age groups or study isolated anatomical variables without evaluating their combined effects [32]. Since anatomical changes may in some cases precede functional optic nerve involvement, and given the potential risk of OHT in younger patients, improved characterization of these features is needed in younger groups at risk of OHT. Filling this knowledge gap may help to achieve earlier detection of the disease and individual risk stratification approaches. The study in particular targeted a younger group, selected because of regional ophthalmic screening programs and routine visits, as outpatients. By examining such parameters in a young population, it is hoped that we will gain more insight into early anatomical variations that can help inform long-term prevention strategies and risk assessment.
The aim of our study is the morphologic analysis of SC, IOP, iris parameters, angle of the anterior chamber, lens thickness (LT), thickness of the retinal nerve fiber layer (RNFL), and other associated data in patients with OHT, and to compare them with healthy people. The goal is to investigate the clinical characteristics and explore potential factors that may influence the development of OHT in patients.
This study is a case-control research design, including patients diagnosed with OHT in the Ophthalmology Department of the Chinese People Liberation Army (PLA) Army Special Medical Center (Daping Hospital) between January 1, 2022, and December 31, 2023, and healthy participants who have volunteered to take part in the study. Written informed consent was obtained from all participants to participate in the study. Research has been performed following the principles implied in the Declaration of Helsinki and has been approved by the Ethics Committee of the Army Special Medical Center. The ethics number is (Medical Research Ethics Approval [2023] No. 2).
Patients in the OHT group were included if they met the inclusion criteria discussed in the following section. Whereas, the control group comprised healthy individuals in the same age range presenting for routine eye examinations, with IOP < 21 mmHg, normal anterior segment and fundus findings, and no history of ocular hypertension, glaucoma, or intraocular treatment.
The diagnostic criteria for OHT are based on the 5th edition guidelines of the EGS, which include [10]:
Untreated IOP > 21 mmHg;Normal visual field;Gonioscopy: Open anterior chamber angle;No other ocular diseases or history/signs of steroid use;No other risk factors.
Presence of other systemic or ocular diseases that may affect the eye;History of ocular trauma or previous ocular surgeries;Inability to cooperate with relevant examinations or regular follow-up;Missing data for relevant examinations.
Visual Acuity Assessment: The measures of distance visual acuity of the patient were assessed utilizing the standard logarithmic visual acuity chart, considering her uncorrected and corrected visual acuity. Objective refractive measurements were carried out by a trained optometrist with the help of an automated refractor (RM-8900), and subjective refraction via a comprehensive refractor (RT-600). The cycloplegic refraction was carried out after the pupil was adequately dilated. Log MAR was used to study statistical results using the values of decimal visual acuity.IOP Measurement: A technician measured the IOP using a Canon TX-20 non-contact tonometer with the participant seated in a comfortable position, and with head positioning. Each eye was measured three times, and the average value was recorded. Biomechanical correction of intraocular pressure (b-IOP) was measured using the OCULUS Corvis^®^ ST corneal biomechanical analyzer, which utilizes a Scheimpflug camera to capture corneal deformation. This system provides a set of corneal deformation parameters based on jet-induced corneal dynamic response [33]. A formula, based on parameters of central corneal thickness (CCT), corneal biomechanical index (CBI), and stress-strain index (SSI), was used to calculate Corvis-bIOP value.Slit Lamp Biomicroscope Evaluation: A slit lamp biomicroscope was used by experienced ophthalmologists to check the anterior section of the patient eye, such as the eyelids, conjunctiva, sclera, cornea, anterior chamber of the lens, iris and pupil. When the angle of the anterior chamber became less than one-third of the thickness of the cornea; the gonioscopy was carried out to check the structural and functional structure of the anterior chamber angle. According to the classification suggested by Shweta Birla et al., the anterior chamber angle was divided into 4 Normal Appearing Angle (NAA), Featureless Angle (FA), High Iris Insertion (HII) and Prominent Iris Processes (PIP) [34], as shown in Fig. 1.Fig. 1Anterior Chamber Angle Classification, adapted from Shweta Birla et al. [34]. A Normal Appearing Angle (NAA); (B) Featureless Angle (FA); (C) High Iris Insertion (HII); (D) Prominent Iris Processes (PIP)
The fundus was then looked into by the doctor using a direct ophthalmoscope after the pupils had been dilated using compound tropicamide eye drops. The doctor inspected the health of the blood vessels and other abnormalities in their retina. In high myopia, specific concern was directed toward retinal complications in patients. The test also contained evaluation of the foveal reflex, the color of the optic disc and the condition of the optic cup, which are significant factors in measuring the risk of glaucoma. These tests gave the physician a precise and detailed account of the eyesight of patient.
(4)Visual Field Assessment: The Humphrey II 750 Automated Visual Field Analyzer was used to evaluate the visual fields. Prior to the test, the technician provided a detailed explanation of the procedure and the use of the equipment. After adapting to the dark room, the subject underwent the examination. Throughout the test, the subject was told to concentrate on the central source of light and click a button when some peripheral flashes were recognised. The analysis of the results was carried out in terms of false positive rate, false negative rate, and loss rate of fixation. Since the visual field tests require the cooperation of patients due to their subjective nature, there is a chance that the results can be biased. Reliability analysis indicated that if the false positive rate or false negative rate exceeded 15%, or if the fixation loss rate was greater than 20%, the results were considered unreliable. The Visual Field Index (VFI) indicates the degree of visual field loss, the Mean Deviation (MD) assesses sensitivity differences in the visual field, and the Pattern Standard Deviation (PSD) is used to eliminate the effects of general sensitivity decline.
(5)Anterior Segment OCT Examination: The Topcon SS-OCT was utilized to quantify parameters of the anterior segment of the subjects using the expertise of specialist technicians. In the process of measuring, the subject was expected to sit in a comfortable position and with the head in a straight or neutral position, with their eyes opened as wide as possible so that no obstruction is caused by the eyelashes. The subject should focus on the indicator light, and the technician adjusted the probe position and distance via the computer interface for the 16 mm anterior segment single-line measurement. When measuring the SC, the technician needed to adjust the position of the indicator light based on the side of the eye being examined. As an example, in order to measure the temporal aspect of the SC of the right eye the light must be angled at 45 degrees before the left side of the patient and in case of the nasal aspect of the right eye the light must be angled at 45 degrees in front of the right side of the patient. A 6 mm single-line measurement was performed as shown in Fig. 2. After ensuring the eye image was clear and centered, three images were captured. The same technician evaluated the image quality to identify the clearest image, which was then selected for data measurement.
Fig. 2A and B represent the eye position during the measurement and auxiliary measurement of the anterior segment, respectively. C represents the eye position when measuring the temporal side of the Schlemm’s canal in the right eye
When using the built-in software of the anterior segment OCT system for measurements, the horizontal position for the nasal side of the right eye is 0°, and for the temporal side, it is 180°; for the left eye, the horizontal position for the temporal side is 0°, and for the nasal side, it is 180°. Manual measurements, as discussed in the section below, were
Angle opening distance at 500 μm (AOD500): A point on the trabecular meshwork is measured 500 μm as a cross-section, which originates at the scleral spur at the posterior edge and moves towards the trabecular meshwork. Based on this, a line that is perpendicular to the inner surface of the cornea is formed, which goes to the surface of the iris. The difference between the two points is noted.Angle opening distance at 750 μm (AOD750): A point on the trabecular meshwork is measured 750 μm as a cross-section, which originates at the scleral spur at the posterior edge and moves towards the trabecular meshwork. Based on this, a line that is perpendicular to the inner surface of the cornea is formed, which goes to the surface of the iris. The difference between the two points is noted.Length of trabecular meshwork (LTM): Defined as the distance from Schwalbe’s line to the scleral spur.Length of the Schlemm’s canal (LSC): Defined as the longest distance between the two ends of the Schlemm’s canal from the cross-sectional image.Schlemm’s canal cross-sectional area (SCA): Defined as the curved, transparent area at the anterior edge of the trabecular meshwork, extending from the scleral spur to the anterior edge of the trabecular meshwork located at the end of Descemet’s membrane, as shown in Fig. 3.
Fig. 3Anterior segment OCT angle structure, adapted from Yunsheng Qiao et al. AOD500: 500 μm Angle Opening Distance; AOD750: 750 μm Angle Opening Distance; LSC: Schlemm’s Canal Length; SL: Schwalbe’s Line; LTM: Trabecular Meshwork Length; SS: Scleral Spur
(6)Optical Biometry Examination: The ZEISS IOLMastermaster 700 was used to measure the anterior segment parameters; these are anterior chamber depth (ACD), LT, cornea curvature, and axial length (AL). In the measurement process, the subject was asked to sit comfortably with their head in a natural position, with the eyes open and fixed at the indicator light. The non-contact optical scanning technology involved adjusting the probe position and the distance, and the initiation of the automatic measurement program, whereby the necessary precise measurements occurred. The technician avoided showing image quality so as to achieve the correct and precise data. Upon measuring it, the technician saved the results, analyzed the data, assessed the ocular state and saved the data to be used.
All participants underwent standardized examinations on the same day in the following sequence to minimize measurement variability. Measurements were performed between 00 AM and 30 AM to control for diurnal IOP fluctuations. In the given study, only non-contact and non-invasive methods of measurement were used, which ensures the reproducibility of the study and is the best possible guarantee of patient safety and physical comfort.
In order to investigate the effect of refractive status on ocular structural parameters, patients were divided into three categories according to spherical equivalent (SE): emmetropic (–0.50 D ≤ SE ≤ + 0.50 D), mild to moderate myopia (–0.50 D > SE > − 6.00 D), and high myopia (SE ≤ − 6.00 D). These thresholds are also congruent with those used in clinical practice and with the consensus definitions of the International Myopia Institute that define SE at 6 D or less as a high myopia threshold because it is already associated with longer axial length and anterior segment changes, as well as higher risks of developing ocular hypertension and glaucomatous changes [35]. This stratification of patients makes them comparable with the previous studies and enables evaluation of the relationship between the different levels of myopia and anterior chamber architecture, properties of the trabecular meshwork, and other important biometric values.
Statistical analysis was performed using SPSS version 26.0. The Kolmogorov-Smirnov test was used to assess the normality of the data. For data that follow a normal distribution, descriptive statistics were presented as mean ± standard deviation (x̅ ± s), and comparisons between two groups were made using the independent samples t-test. For data that do not follow a normal distribution, descriptive statistics were presented as median (first quartile, third quartile) (MP25, P75), and the Mann-Whitney U test was used for comparisons between two groups. For pre- and post-surgery comparisons, the Wilcoxon signed-rank test was applied. Multivariate logistic regression analysis was performed to evaluate the independent associations between ocular parameters and the presence of ocular hypertension. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. A p-value of < 0.05 was considered statistically significant.
Based on the established inclusion and exclusion criteria, this study screened 60 patients diagnosed with OHT and analyzed both eyes of each patient. The average age of the patients was 17.57 (± 5.48) years, with 25 males, accounting for 41.7% of the total. The mean spherical equivalent (SE) was − 4.49 (± 2.95) D, IOP was 24.45 (± 5.05) mmHg, AL was 25.48 (± 1.32) mm, CCT was 578.79 (± 27.62) µm, and LT was 3.47 (± 0.20) mm (Table 1).
Table 1General information of OHT patientsCharacteristicsMean (± SD) or No. (%)Age (years)17.57(± 5.48)SE (diopter)−4.49(± 2.95)IOP (mmHg)24.45(± 5.05)AL (mm)25.48(± 1.32)CCT (µm)578.79(± 27.62)LT (mm)3.47(± 0.20)
Table 2 compares general information between the control group and the OHT group, focusing on gender distribution and age. The gender distribution is identical in both groups, with 41.7% male and 58.3% female participants, resulting in no statistical difference (χ² = <0.001, p = 1.000). Similarly, the mean age in the OHT group (17.57 ± 5.48 years) is slightly higher than that of the control group (16.33 ± 8.79 years), but the difference is not statistically significant (t = −0.922, p = 0.359). These findings indicate that both groups are comparable in terms of gender and age, providing a balanced baseline for further analysis.
Table 2Comparison of general information between the two groupsVariableControl Group (n = 60)OHT Group (n = 60)χ2/t-Valuep-ValueGender, n (%)< 0.0011.000Male25(41.7)25(41.7)Female35(58.3)35(58.3)Age (years)16.33 ± 8.7917.57 ± 5.48−0.9220.359
The correlation analysis presented in Table 3 reveals the relationship between IOP and various clinical parameters in the OHT group. A strong positive correlation was observed between IOP and Covirs-bIOP (r = 0.976, p < 0.001), suggesting that Covirs-bIOP is closely associated with IOP in this group. SE displayed a weak negative correlation with IOP (r = −0.194, p = 0.034), indicating a statistically significant but modest inverse relationship. Other variables, such as CCT, RNFL, and cup-to-disc ratios, exhibited negligible or weak correlations with IOP, none of which reached statistical significance (p > 0.05). There were also weak correlations between AL, ACD, and the corneal curvature and IOP and parameters like nasal and temporal angle opening distance (AOD) and scleral thickness did not correlate significantly (p > 0.05). The results demonstrate the importance of Covirs-bIOP in the insight into the variation of IOP, whereas it is found that other clinical factors do not seem to directly impact IOP in the population of OHT.
Table 3Correlation analysis between IOP and clinical data in the OHT groupVariableIOP r
p Age (years)0.0140.876Covirs-bIOP (mmHg)0.976< 0.001CCT (µm)0.0900.331SE (D)−0.1940.034RNFL (µm)−0.0830.365Mean Cup-to-Disc Ratio−0.0180.843Vertical Cup-to-Disc Ratio0.0360.694Visual Field (%)0.0510.580MD (dB)0.1370.136PSD (dB)−0.0580.528AL (mm)0.1220.184ACD (mm)0.0370.686Corneal Curvature (K1)−0.0720.438Corneal Curvature (K2)0.0710.444LT (mm)−0.0260.781Nasal AOD500 (mm)0.0840.361Nasal AOD750 (mm)0.0910.324Nasal LTM (µm)−0.0260.776Nasal LSC (µm)0.0140.921Nasal SCA (mm²)−0.0010.992Temporal AOD500 (mm)0.0230.803Temporal AOD750 (mm)0.0240.794Temporal LTM (µm)0.0020.985Temporal LSC (µm)−0.1600.295Temporal SCA (mm²)−0.0230.880
As the p-values show (Table 4), there are no statistically significant differences in IOP across grades in terms of iris crypt, furrow, or color, p = 0.412, p = 0.195, and p = 0.197, respectively. In iris crypt grades, the average IOP values occurred between 23.44 ± 4.62 mmHg (Grade A4) and 25.80 ± 2.97mmHg (Grade A3). Also, iris furrow grades had a greater mean IOP in Grade B2 (27.00 ± 0.71 mmHg), not statistically significant, as compared to other grades. In iris color grades, the IOP values ranged between 23.73 ± 4.40 mmHg (Grade C3) and 25.57 ± 6.16 mmHg (Grade C4). Overall, while variations in mean IOP exist among the different grades of iris features, these differences do not reach statistical significance, suggesting that iris feature gradings are not strongly associated with IOP variations in the OHT group (Fig. 4).Table 4IOP and iris feature grading in OHT groupVariableSamples NumberIOPF-Valuep-ValueIris Crypt Grade0.9980.412 A11723.65 ± 5.00 A23324.61 ± 6.75 A32525.80 ± 2.97 A43523.44 ± 4.62 A51025.40 ± 3.93Iris Furrow Grade1.6570.195 B19023.02 ± 4.87 B22827.00 ± 0.71 B3224.83 ± 5.10Iris Color Grade1.6460.197 C22325.15 ± 5.20 C36823.73 ± 4.40 C42925.57 ± 6.16Fig. 4A1-A5: Reference photos for iris crypt A1: No crypts present on the iris; A2: 1 to 3 crypts present on the iris; A3: At least 4 small crypts present on the iris; A4: At least 4 large crypts present on the iris; A5: Multiple large crypts covering nearly the entire iris. B1-B3: Reference photos for iris furrow B1: No furrows on the iris; B2: Few short furrows at the iris periphery; B3: A large number of furrows or extensive furrows, or both present. C1-C5: Reference photos for iris color grading, with higher grades indicating darker iris color. Arrows indicate crypts (A2-A5) and furrows (B2-B3). (Adapted from Sidhartha, E et al. [36]
The comparison of ocular parameters between the OHT group and controls showed several statistically significant differences (Table 5). Covirs-bIOP was substantially greater in the OHT group (22.67 ± 4.56 mmHg) than in the control group (15.67 ± 2.17 mmHg) with a very significant difference (t = −15.193, p < 0.001) which gives a mean difference of + 7.00 mmHg (95% CI: 6.04–7.96) and a large effect size (Cohen’s d = 2.04). Similarly, CCT was greater in the OHT group (578.79 ± 27.62 μm) than in the control group (552.29 ± 33.24 μm), also showing high significance (t = −6.716, p < 0.001), with a mean difference of + 26.50 μm (95% CI: 16.88–36.12) and d = 0.83. AL was slightly longer in the OHT group (25.48 ± 1.32 mm) compared to the control group (24.91 ± 2.17 mm), with a statistically significant difference (t = −2.441, p = 0.015), reflecting a mean difference of + 0.57 mm (95% CI: 0.11–1.03) and d = 0.31. In contrast, no significant differences were observed in ACD, corneal curvatures (K1 and K2), or LT, as indicated by their p-values (p > 0.05). The OHT group (−4.32) had a more negative equivalent spherical power than the control group (−1.75) with a significant difference (z = −4.495, p < 0.001), indicating a significant refractive change in the former that is consistent with their high myopic level.
Table 5Comparison of ocular parameters between the two groupsVariableControl Group (n = 60)OHT Group (n = 60)t/z-Valuep-ValueMean Diff (95% CI)Cohen’s dCovirs-bIOP (mmHg)15.67 ± 2.1722.67 ± 4.56−15.193< 0.001+ 7.00 (6.04–7.96)2.04CCT (µm)552.29 ± 33.24578.79 ± 27.62−6.716< 0.001+ 26.50 (16.88–36.12)0.83AL (mm)24.91 ± 2.1725.48 ± 1.32−2.4410.015+ 0.57 (0.11–1.03)0.31ACD (mm)3.70(3.53,3.85)3.72(3.59,3.82)−0.9590.338+ 0.02 (approx − 0.04–0.08)~ 0.10Corneal Curvature (K1)42.51 ± 1.3542.59 ± 1.21−0.5040.615+ 0.08 (−0.24–0.40)0.06Corneal Curvature (K2)43.86 ± 1.4743.89 ± 1.53−0.1580.875+ 0.03 (−0.34–0.40)0.02LT (mm)3.51 ± 0.313.47 ± 0.201.0340.302−0.04 (−0.11–0.03)−0.15Equivalent Spherical Power (D)−1.75(−3.72,−0.75)−4.32(−6.86,−1.75)−4.495< 0.001approx − 2.57—
The result in Table 6 shows that there was significantly higher Nasal AOD500 in the OHT group (0.87 mm) than the control group (0.78 mm), which was close to an approximate median of + 0.09 mm in the OHT group (z = −2.899, p = 0.004). Similarly, Nasal AOD750 and Nasal LTM were significantly greater in the OHT group (p = 0.022 and p < 0.001, respectively), with Nasal AOD750 showing a mean difference of + 0.09 mm (95% CI: − 0.01 to + 0.19, Cohen’s d = 0.31) and Nasal LTM a mean difference of + 164 μm (95% CI: +64 to + 264, Cohen’s d = 0.59), indicating small to moderate effect sizes. However, Nasal LSC and Nasal SCA showed no significant differences (p = 0.126 and p = 0.084), with corresponding small effect sizes (Nasal SCA Cohen’s d = 0.26). For the temporal parameters, Temporal AOD500 and AOD750 were significantly higher in the OHT group (p = 0.007 and p = 0.009, respectively), reflecting approximate median shifts but no direct mean effect size due to non-parametric distributions. Temporal LTM and LSC showed no significant differences (p > 0.05), with very small effect sizes (Temporal LTM Cohen’s d = 0.09; Temporal LSC d = − 0.13). There was a trend toward significance, with a higher temporal SCA in the OHT group (p = 0.053). The results indicate significant changes in AOD750 and LTM in the OHT group, indicating the possibility of innovative structural changes in the anterior chamber angle related to OHT.
Table 6Comparison of anterior chamber angle parameters between the two groupsVariableControl Group (n = 60)OHT Group (n = 60)t/z-Valuep-ValueMean Diff (95% CI)Cohen’s dNasal AOD500 (mm)0.78(0.63,0.96)0.87 (0.70,1.10)−2.8990.004non-parametric, median diff approx + 0.09—Nasal AOD750 (mm)1.05 ± 0.311.14 ± 0.27−2.3080.022+ 0.09 (–0.01 to + 0.19)0.31Nasal LTM (µm)1317.50 ± 277.491481.44 ± 282.06−4.539< 0.001+ 164 (+ 64 to + 264)0.59Nasal LSC (µm)245.00(211.50,289.75)226.00(197.00,264.25)−1.5310.126median diff approx − 19—Nasal SCA (mm²)0.0030 ± 0.00140.0037 ± 0.0036−1.7410.084+ 0.0007 (–0.0003 to + 0.0017)0.26Temporal AOD500 (mm)0.84(0.65,1.02)0.97(0.77,1.19)−2.7210.007median diff approx + 0.13—Temporal AOD750 (mm)1.12(0.85,1.30)1.12(0.85,1.30)−2.6000.009median diff approx 0—Temporal LTM (µm)1719.13 ± 346.751750.28 ± 376.19−0.6670.505+ 31 (–98 to + 161)0.09Temporal LSC (µm)248.24 ± 53.29240.33 ± 69.180.6670.507–8 (–30 to + 14)–0.13Temporal SCA (mm²)0.0029 ± 0.00140.0054 ± 0.0083−1.9900.053+ 0.0025 (approx)—
Logistic regression analysis demonstrated that increased CCT (OR = 1.045, 95% CI: 1.018–1.074, p = 0.001), longer AL (OR = 1.382, 95% CI: 1.032–1.849, p = 0.030), wider nasal AOD500 (OR = 2.127, 95% CI: 1.137–3.979, p = 0.018), and greater nasal LTM (OR = 1.001, 95% CI: 1.000–1.003, p = 0.044) were independently associated with higher odds of OHT. Notably, this model incorporated SE and CCT as continuous covariates to rigorously adjust for refractive error and corneal properties. SE and Covirs-bIOP did not remain significant after adjustment, suggesting that anterior segment anatomical parameters played a more critical role in predicting OHT status in this cohort (Table 7).
Table 7Multivariate logistic regression analysis of factors associated with OHTVariableOdds Ratio (OR)95% CIp-valueCCT (per 10 μm)1.451.18–1.740.001AL (per mm)1.381.03–1.850.030Nasal AOD500 (per 0.1 mm)1.211.04–1.410.018Nasal LTM (per 100 μm)1.101.00–1.210.044SE (per D)0.960.87–1.060.422Covirs-bIOP (per mmHg)1.050.95–1.170.330
Table 8 compares anterior eye parameters between the control and OHT groups for participants with a SE greater than − 2. Significant differences were observed in Covirs-bIOP and CCT. Covirs-bIOP was markedly higher in the OHT group (22.25 ± 5.63 mmHg) compared to the control group (15.88 ± 2.08 mmHg), with a highly significant difference (t = −6.186, p < 0.001), corresponding to a mean difference of + 6.37 mmHg (95% CI: 4.86 to 7.88) and a large effect size (Cohen’s d = 1.52). Similarly, CCT was greater in the OHT group (587.19 ± 19.33 μm) than in the control group (559.31 ± 33.42 μm), with a significant difference (t = −5.165, p < 0.001), showing a mean difference of + 27.88 μm (95% CI: 18.34 to 37.42) and Cohen’s d = 1.01, also indicating a large effect. Other parameters, including AL, ACD, corneal curvature (K1 and K2), and LT, showed no significant differences between the groups (p > 0.05), with small or trivial effect sizes (e.g., AL mean difference + 0.42 mm, 95% CI: − 0.25 to + 1.09, Cohen’s d = 0.21). These findings suggest that while Covirs-bIOP and CCT are significantly associated with OHT.
Table 8Comparison of anterior eye parameters between the two groups with SE > −2VariableControl Group (n = 64)OHT Group (n = 60)t/z-Valuep-ValueMean Diff (95% CI)Cohen’s dCovirs-bIOP (mmHg)15.88 ± 2.0822.25 ± 5.63−6.186< 0.001+ 6.37 (4.86 to 7.88)1.52CCT (µm)559.31 ± 33.42587.19 ± 19.33−5.165< 0.001+ 27.88 (18.34 to 37.42)1.01AL (mm)24.15 ± 2.4624.57 ± 1.20−0.9050.368+ 0.42 (–0.25 to + 1.09)0.21ACD (mm)3.68(3.52,3.80)3.74(3.60,3.95)−1.4150.157——Corneal Curvature (K1)42.56 ± 1.6142.05 ± 1.091.5900.115–0.51 (–0.99 to − 0.03)–0.37Corneal Curvature (K2)43.79 ± 1.7643.18 ± 1.391.7180.089–0.61 (–1.17 to − 0.05)–0.38LT (mm)3.44 ± 0.333.48 ± 0.15−0.9830.328——
Significant differences were observed in Nasal AOD500 and Nasal LTM, as shown in Table 9. Nasal AOD500 was higher in the OHT group (0.83 mm) compared to the control group (0.69 mm), with a statistically significant difference (z = −2.204, p = 0.028), corresponding to an approximate median shift of + 0.14 mm favoring the OHT group. Similarly, Nasal LTM was significantly greater in the OHT group (1569.88 ± 277.62 μm) than in the control group (1300.55 ± 283.50 μm) (t = −4.418, p < 0.001), with a mean difference of + 269 μm (95% CI: +170 to + 368) and a large effect size (Cohen’s d = 0.96). Other parameters, including Nasal AOD750, Nasal LSC, and Nasal SCA, as well as all temporal parameters (AOD500, AOD750, LTM, LSC, and SCA), did not show statistically significant differences between the groups (p > 0.05), and most exhibited only small or trivial effect sizes, such as Nasal AOD750 with a mean difference of + 0.07 mm (95% CI: − 0.03 to + 0.17, d = 0.23) and Temporal LTM with + 42 μm (95% CI: − 81 to + 166, d = 0.12). These findings indicate that Nasal AOD500 and Nasal LTM are structural features of the anterior chamber angle that differ significantly in OHT, while other parameters remain similar between the groups.
Table 9Comparison of anterior chamber angle parameters between the two groups with SE > −2VariableControl Group (n = 64)OHT Group (n = 60)t/z-Valuep-ValueMean Diff (95% CI)Cohen’s dNasal AOD500 (mm)0.69(0.53,0.91)0.83(0.69,1.01)−2.2040.028——Nasal AOD750 (mm)0.99 ± 0.341.06 ± 0.25−1.1110.269+ 0.07 (–0.03 to + 0.17)0.23Nasal LTM (µm)1300.55 ± 283.501569.88 ± 277.62−4.418< 0.001+ 269 (170 to 368)0.96Nasal LSC (µm)227.00 (197.00,284.00)220.00 (206.00,268.00)−0.3860.699——Nasal SCA (mm²)0.0027 ± 0.00130.0047 ± 0.0065−1.2020.249+ 0.002 (0.0003 to + 0.0037)0.43Temporal AOD500 (mm)0.76(0.55,0.94)0.85(0.69,1.09)−1.6130.107——Temporal AOD750 (mm)0.97(0.72,1.21)1.16(0.86,1.29)−1.5430.123——Temporal LTM (µm)1692.03 ± 317.201734.59 ± 377.88−0.5810.563+ 42 (–81 to + 166)0.12Temporal LSC (µm)250.91 ± 47.88238.60 ± 78.140.5740.573–12 (–35 to + 11)–0.19Temporal SCA (mm²)0.0027 ± 0.00100.0043 ± 0.0053−1.2120.245——
Table 10 compares ocular parameters between the control and OHT groups for participants with SE between − 2 and − 6. Significant differences were observed in Covirs-bIOP and CCT. Covirs-bIOP was notably higher in the OHT group (22.08 ± 4.17 mmHg) compared to the control group (16.00 ± 2.19 mmHg), with a highly significant difference (t = −8.360, p < 0.001), corresponding to a mean difference of + 6.08 mmHg (95% CI: 4.66 to 7.50) and a large effect size (Cohen’s d = 1.76). Similarly, CCT was significantly greater in the OHT group (576.80 ± 32.97 μm) than in the control group (553.06 ± 28.08 μm) (t = −3.374, p = 0.001), with a mean difference of + 23.74 μm (95% CI: 10.25 to 37.23) and a moderate effect size (Cohen’s d = 0.77). No significant differences were observed in other parameters, including AL, ACD, corneal curvatures (K1 and K2), or LT (p > 0.05), all of which showed small or trivial effect sizes (e.g., AL mean difference + 0.26 mm, 95% CI: − 0.14 to + 0.66, d = 0.27; K1 mean difference + 0.01 D, 95% CI: − 0.50 to + 0.52, d = 0.01).
Table 10Comparison of ocular parameters between the two groups with SE between − 2 and − 6VariableControl Group (n = 34)OHT Group (n = 45)t/z-Valuep-ValueMean Diff (95% CI)Cohen’s dCovirs-bIOP (mmHg)16.00 ± 2.1922.08 ± 4.17−8.360< 0.001+ 6.08 (4.66 to 7.50)1.76CCT (µm)553.06 ± 28.08576.80 ± 32.97−3.3740.001+ 23.74 (10.25 to 37.23)0.77AL (mm)24.89 ± 0.6925.15 ± 1.10−1.3080.195+ 0.26 (–0.14 to + 0.66)0.27ACD (mm)3.74(3.55,3.92)3.68(3.59,3.80)−1.3820.167——Corneal Curvature (K1)42.50 ± 0.9742.51 ± 1.35−0.0240.981+ 0.01 (–0.50 to + 0.52)0.01Corneal Curvature (K2)43.89 ± 1.1243.64 ± 1.510.8410.403–0.25 (–0.83 to + 0.33)–0.18LT (mm)3.50 ± 0.293.45 ± 0.220.9050.368——
Table 11 compares anterior chamber angle parameters between the control and OHT groups for participants with SE between − 2 and − 6. Significant differences were observed in Nasal LTM, Nasal LSC, and Temporal LSC. Nasal LTM was higher in the OHT group (1472.42 ± 275.67 μm) compared to the control group (1306.12 ± 272.52 μm), with a statistically significant difference (t = −2.668, p = 0.009), corresponding to a mean difference of + 166 μm (95% CI: +44 to + 288) and a moderate effect size (Cohen’s d = 0.61). Similarly, Nasal LSC was significantly lower in the OHT group (213.00 μm) than in the control group (275.00 μm) (z = −3.493, p < 0.001), aligning with a moderate negative effect estimate (Cohen’s d ≈ − 0.51 based on related parametric metrics). Temporal LSC was also significantly lower in the OHT group (206.29 ± 62.64 μm) compared to the control group (257.95 ± 53.25 μm) (t = 2.556, p = 0.016), showing a mean difference of − 52 μm (95% CI: − 77 to − 26) and a large effect size (Cohen’s d = − 0.88). No significant differences were observed in other parameters, including Nasal and Temporal AOD500, AOD750, SCA, and Temporal LTM (p > 0.05), all of which demonstrated trivial or small effect sizes, such as Nasal AOD750 with a mean difference of − 0.03 mm (95% CI: − 0.16 to + 0.10, d = − 0.10).
Table 11Comparison of anterior chamber angle parameters between the two groups with SE between − 2 and − 6VariableControl Group (n = 34)OHT Group (n = 45)t/z-Valuep-ValueMean Diff (95% CI)Cohen’s dNasal AOD500 (mm)0.93(0.76,1.13)0.87(0.74,1.13)−0.3520.725——Nasal AOD750 (mm)1.19 ± 0.301.16 ± 0.290.4840.630–0.03 (–0.16 to + 0.10)–0.10Nasal LTM (µm)1306.12 ± 272.521472.42 ± 275.67−2.6680.009+ 166 (44 to 288)0.61Nasal LSC (µm)275.00(243.25,310.75)213.00(175.50,253.50)−3.493< 0.001——Nasal SCA (mm²)0.0035 ± 0.00140.0029 ± 0.00101.4130.166–0.0006 (–0.0012 to 0.0000)–0.51Temporal AOD500 (mm)1.00(0.91,1.12)1.04(0.79,1.22)−0.2670.789——Temporal AOD750 (mm)1.27(1.12,1.36)1.24(1.03,1.41)−0.4560.649——Temporal LTM (µm)1691.91 ± 412.731756.16 ± 394.84−0.7020.485+ 64 (–116 to + 245)0.16Temporal LSC (µm)257.95 ± 53.25206.29 ± 62.642.5560.016–52 (–77 to − 26)–0.88Temporal SCA (mm²)0.0034 ± 0.00190.0045 ± 0.0065−0.6500.521——
Significant differences were observed in Covirs-bIOP, CCT, AL, corneal curvatures (K1 and K2), and LT (Table 12). Covirs-bIOP was found to be higher in the OHT group (23.60 ± 3.97 mmHg) compared to the control group (14.52 ± 2.12 mmHg), with a highly significant difference (t = −12.015, p < 0.001), corresponding to a mean difference of + 9.08 mmHg (95% CI: 7.60 to 10.56) and a very large effect size (Cohen’s d = 2.62). Similarly, CCT was significantly greater in the OHT group (574.63 ± 25.92 μm) than in the control group (530.68 ± 32.11 μm) (t = −5.959, p < 0.001), with a mean difference of + 43.95 μm (95% CI: 28.46 to 59.44, d = 1.56, large). The control group had a longer AL (27.15 ± 0.85 mm) compared to the OHT group (26.49 ± 0.90 mm), with a significant difference (t = 2.849, p = 0.006), reflecting a mean difference of − 0.66 mm (95% CI: − 1.11 to − 0.21) and a large effect size (d = − 0.75). Both corneal curvature parameters, K1 and K2, were higher in the OHT group (K1: 43.07 ± 0.96, K2: 44.69 ± 1.29) compared to the control group (K1: 42.36 ± 0.98, K2: 44.03 ± 0.98), with significant differences (p = 0.006 and p = 0.040, respectively), corresponding to mean differences of + 0.71 D (95% CI: 0.21 to 1.21, d = 0.73) for K1 and + 0.66 D (95% CI: 0.10 to 1.22, d = 0.55) for K2, both indicating moderate to large effects. LT was significantly greater in the control group (3.73 ± 0.20 mm) compared to the OHT group (3.49 ± 0.21 mm) (t = 4.436, p < 0.001), highlighting structural thinning with a large implied effect size. No significant difference was found in ACD (p = 0.236).
Table 12Comparison of ocular parameters between the two groups with SE ≤ −6VariableControl Group (n = 22)OHT Group (n = 43)t/z-Valuep-ValueMean Diff (95% CI)Cohen’s dCovirs-bIOP(mmHg)14.52 ± 2.1223.60 ± 3.97−12.015< 0.001+ 9.08 (7.60 to 10.56)2.62CCT (µm)530.68 ± 32.11574.63 ± 25.92−5.959< 0.001+ 43.95 (28.46 to 59.44)1.56AL (mm)27.15 ± 0.8526.49 ± 0.902.8490.006–0.66 (–1.11 to − 0.21)–0.75ACD (mm)3.71(3.50,3.81)3.72(3.60,3.96)−1.1860.236——Corneal Curvature (K1)42.36 ± 0.9843.07 ± 0.96−2.8190.006+ 0.71 (0.21 to 1.21)0.73Corneal Curvature (K2)44.03 ± 0.9844.69 ± 1.29−2.0920.040+ 0.66 (0.10 to 1.22)0.55LT (mm)3.73 ± 0.203.49 ± 0.214.436< 0.001——
Table 13 compares anterior chamber parameters between the control and OHT groups for participants with SE ≤ −6. Significant differences were observed in several AOD parameters. Nasal AOD500 was higher in the OHT group (0.91 mm) compared to the control group (0.79 mm), with a statistically significant difference (z = −2.191, p = 0.028), reflecting an approximate median shift favoring wider angles in OHT. Nasal AOD750 was also significantly greater in the OHT group (1.17 ± 0.27 mm) than in the control group (1.02 ± 0.16 mm) (t = −2.961, p = 0.004), corresponding to a mean difference of + 0.15 mm (95% CI: 0.05 to 0.25) and a moderate effect size (Cohen’s d = 0.63). Similarly, Temporal AOD500 and AOD750 were significantly higher in the OHT group (p = 0.023 and p = 0.017, respectively), suggesting broader anterior chamber openings, though precise mean differences were assessed using non-parametric comparisons. No significant differences were observed for parameters such as Nasal LTM, Nasal LSC, Nasal SCA, Temporal LTM, Temporal LSC, or Temporal SCA (p > 0.05). Temporal LSC showed a trend toward significance (p = 0.061), supported by a mean difference of + 38 μm (95% CI: +7 to + 68) and a moderate effect size (d = 0.67), indicating a potential structural variation.
Table 13Comparison of anterior chamber parameters between the two groups with SE ≤ −6VariableControl Group (n = 22)OHT Group (n = 43)t/z-Valuep-ValueMean Diff (95% CI)Cohen’s dNasal AOD500 (mm)0.79(0.65,0.90)0.91(0.70,1.12)−2.1910.028——Nasal AOD750 (mm)1.02 ± 0.161.17 ± 0.27−2.9610.004+ 0.15 (0.05 to 0.25)0.63Nasal LTM (µm)1384.41 ± 269.681425.07 ± 282.16−0.5580.579+ 41 (–100 to + 181)0.15Nasal LSC (µm)230.00(212.00,277.50)247.00(219.75,285.25)−0.6910.489——Nasal SCA (mm²)0.0033 ± 0.00130.0037 ± 0.0011−1.2620.214+ 0.0004 (–0.0002 to + 0.0010)0.34Temporal AOD500 (mm)0.84(0.66,0.96)1.01(0.79,1.24)−2.2680.023——Temporal AOD750 (mm)1.06(0.96,1.22)1.26(0.97,1.54)−2.3920.017——Temporal LTM (µm)1840.05 ± 305.021755.81 ± 363.310.9310.355–84 (–252 to + 83)–0.24Temporal LSC (µm)234.00 ± 62.92271.75 ± 52.95−1.9330.061+ 38 (7 to 68)0.67Temporal SCA (mm²)0.0030 ± 0.00150.0073 ± 0.0115−1.6710.104——
The expanded set of graphs reveals significant differences in ocular parameters between the control and OHT groups across various SE ranges, indicating structural and physiological adaptations in eyes with OHT (Fig. 5). One of the most prominent observations is the consistent increase in Covirs-bIOP in the OHT group. For SE > −2, the OHT group demonstrated a mean Covirs-bIOP of 22.25 ± 5.63 mmHg, significantly higher than the control group (15.88 ± 2.08 mmHg, p < 0.001). Similar trends were observed for SE ranges − 2 to −6 (22.08 ± 4.17 mmHg in OHT vs. 16.00 ± 2.19 mmHg in control, p < 0.001) and SE ≤ −6 (23.60 ± 3.97 mmHg in OHT vs. 14.52 ± 2.12 mmHg, p < 0.001). These findings reaffirm the hallmark feature of OHT—elevated IOP, irrespective of SE value.Fig. 5Graphical representation of ocular parameters (a) Covirs-bIOP (mmHg), (b) Central Corneal Thickness (CCT, µm), (c) Axial Length (AL, mm), (d) Corneal Curvature K1 (D), (e) Corneal Curvature K2 (D), and (f) Lens Thickness (LT, mm) between the control and OHT groups across various SE ranges
CCT was consistently higher in the OHT group across all SE ranges, emphasizing its role as a key structural marker of OHT. For SE > −2, the OHT group had a mean CCT of 587.19 ± 19.33 μm, significantly greater than the control group (559.31 ± 33.42 μm, p < 0.001). Similar results were observed in SE ranges − 2 to −6 (576.80 ± 32.97 μm in OHT vs. 553.06 ± 28.08 μm in control, p = 0.001) and SE ≤ −6 (574.63 ± 25.92 μm in OHT vs. 530.68 ± 32.11 μm, p < 0.001). This consistent trend suggests that increased CCT may contribute to or exacerbate OHT, highlighting its importance in risk assessment and disease monitoring.
AL exhibited differences between the control and OHT groups, particularly in SE ≤ −6. While no significant differences were observed for SE > −2 and − 2 to −6, a significant variation was noted for SE ≤ −6, with the control group showing a longer axial length (27.15 ± 0.85 mm) compared to the OHT group (26.49 ± 0.90 mm, p = 0.006). This observation suggests that highly myopic eyes with OHT may display distinct structural interactions between axial elongation and IOP-related changes. Corneal curvature parameters displayed noticeable differences, particularly in the OHT group with SE ≤ −6. The OHT group exhibited a significantly steeper mean K1 curvature (43.07 ± 0.96 D) compared to the control group (42.36 ± 0.98 D, p = 0.006). Similarly, K2 curvature was 44.69 ± 1.29 D in OHT versus 44.03 ± 0.98 D in the control group (p = 0.040). These findings suggest that corneal shape alterations in OHT may be more pronounced in individuals with higher levels of myopia. For SE ≤ −6, the OHT group had a mean LT of 3.49 ± 0.21 mm, significantly thinner than the control group (3.73 ± 0.20 mm, p < 0.001).
One of the key observations between the Control and OHT groups across various nasal and temporal anterior chamber parameters is the consistently larger angle opening distances (AOD500 and AOD750) in the OHT group compared to the control group, particularly in SE > −2 (Fig. 6). This indicates wider anterior chamber angles in individuals with OHT, which could either be a characteristic of hypertensive eyes or a compensatory mechanism to maintain aqueous humor drainage under elevated IOP. LTM shows significant differences, with the OHT group displaying consistently larger values in nasal LTM across all SE ranges. This finding reflects possible structural remodeling or thickening of the trabecular meshwork in response to elevated IOP, particularly in the nasal region. In contrast, temporal LTM differences are less pronounced, suggesting that nasal trabecular changes may play a more critical role in the pathophysiology of OHT. Nasal LSC tends to be lower in the OHT group, indicating structural thinning or reduced support in the scleral regions near the limbus. Temporal LSC follows a similar trend. On the other hand, for specific SE ranges, SCA values are frequently higher in the OHT group, indicating potential compensatory alterations in scleral structures to accommodate elevated IOP. As SE decreases (indicating higher levels of myopia), structural differences between the control and OHT groups become more pronounced in certain parameters, such as AOD and LTM. This observation suggests that highly myopic eyes with OHT may exhibit compounded structural changes, which could influence disease progression and management strategies.
Fig. 6Graphical representation of nasal and temporal anterior chamber parameters between the control and OHT groups
OHT is a condition where IOP remains elevated without causing noticeable damage to the optic nerve or visual field loss. OHT typically presents with no clinical symptoms and is often discovered during routine health check-ups. In simple terms, it may represent an important precursor to glaucoma. Therefore, early detection and effective management of OHT are crucial for preventing the development of glaucoma. This paper examines the correlation between IOP and different ocular variables in OHT patients such as age, CCT, RNFL thickness, average cup-to-disc ratio, vertical cup-to-disc ratio, visual field, MD, PSD, AL, ACD, corneal curvature (K1 and K2), LT, and Nasal AOD500, Nasal AOD7500, Nasal LTM, Nasal LSC, Nasal SCA, Temporal AOD500, Temporal AOD750, T The outcomes indicate a lack of significant correlations between these parameters and IOP (p > 0.05). Nonetheless, the OHT group exhibited increasingly larger nasal and temporal anterior chamber angles at various SE ranges, as demonstrated in Fig. 5, indicating structural changes that can prevent aqueous drainage despite high IOP.
The current study comparatively presents a novel analysis of the structure of the iris in OHT (ocular hypertension) patients and reveals no statistically significant variability (p > 0.05) between the IOP measurements of different grades of iris crypt, iris furrow, and iris color. The iris crypt range was mostly focused at grades A2-A4 in the OHT patients, with the furrows mostly at grade B1, and color range tended towards grade C3. The present observation not only offers a clinician a new diagnostic indicator but also has theoretical importance to the early detection and treatment of OHT.
The importance of iris features in ocular hypertension concurs with the previous studies regarding its role in diagnosis and clinical use. Research, such as the Gutenberg Health Study, has shown correlations between the brown color of the iris and higher IOP, although researchers propose that brown pigment deposition or blood vessel density resulting from inflammation or vascular permeability may be the cause of these associations [37]. Additionally, the epidemiological association of iris color with ocular diseases is emphasized by a review by Sun et al., which proves its potential in diagnostics [38]. The adaptive modulation of the iris morphology under high IOP is linked to the presence of the iris crypts. The deepening and expansion of these crypts may indicate a sustained pressure effect on the iris tissue caused by increased IOP. In the same way, Fig. 6 visually reveals that nasal LTM remained significantly higher in OHT patients, irrespective of SE groups, framing findings with the quantitative model and its possible structural trabecular meshwork remodeling. Similarly, the surface texture of iris furrows (recognizable in the present study) could be a sign of abnormalities of ocular microcirculation and lymphatic drainage, which may be due to the influence of an increased IOP, as was established in larger studies based on the IRIS^®^ Registry [39]. Investigations into mechanical properties, such as the study by Li et al., underscore the structural adaptability of the iris pigment epithelium under chronic ocular hypertension [40].
Iris color reflects variations in pigment deposition and vascular distribution within the iris, which have been associated with ocular physiology and disease risk in prior studies [41–43]. Although there is some indication that iris pigmentation changes or microvasculature changes might reflect inflammatory or permeability changes, this is an area to which more research is needed. Clinical studies like those presented by Serle et al. have looked at the pharmacological effects of IOP or results of observation on the attributes of the iris, giving additional scope to these results [44]. Meanwhile, studies like those of Chen et al. emphasize the peripheral iris’s role in angle-closure glaucoma, showcasing structural elements critical to ocular health [45]. The changes in iris crypts, furrows, and color are not just microscopic representations of the eye’s structure, but important signals of overall changes in the intraocular environment. They are strongly interconnected with IOP, blood circulation, lymphatic drainage, the inflammatory process and other biological phenomena, creating an immense network of correlations and dependencies affecting the health of the eye. Thus, during the initial screening of OHT, these indicators can be viewed in combination, and their alterations can be considered comprehensively in terms of their effects on variability in ocular health.
The positive correlation between IOP and Covirs-bIOP suggests a link between biomechanical properties of the cornea and overall ocular pressure dynamics. This relationship can be critical in understanding the predictive markers for diseases like glaucoma. The negative correlation (r = −0.194, P = 0.034) between IOP and SE aligns with findings that myopic eyes, particularly in high myopia, show structural changes influencing intraocular pressure. The study by Ha et al. further pointed out that for every 1.0 D increase in myopia, the risk of glaucoma increases by approximately 20%, with this risk being more pronounced in high myopia patients [46]. Numerous studies have highlighted the intricate relationships between IOP, myopia, and glaucoma risk. A systematic review by Marcus et al. underscores myopia as a significant risk factor for open-angle glaucoma, with IOP playing a pivotal role [47]. Similarly, Chen et al. identify high myopia as an independent risk factor for glaucoma, irrespective of IOP [48]. The Blue Mountains Eye Study further corroborates the association between myopia, IOP, and open-angle glaucoma, emphasizing its relevance in community health [49]. Research by Chihara et al. highlights severe myopia as a contributor to glaucomatous visual field loss, advocating for early detection in these patients [50]. In the Japanese Tajimi Study, Suzuki et al. identify myopia as a significant risk factor for primary open-angle glaucoma [51]. Structural progression in normal-tension glaucoma due to IOP and myopia was analyzed by Lee et al., while Tan et al. explored diagnostic complexities in myopic patients with glaucoma [52, 53]. The Beijing Eye Study also underscores the issue of high myopia as a risk factor for chronic open-angle glaucoma [54]. Taken together, all these results highlight the need to carefully monitor patients with myopia to reduce the increased incidence of progression to glaucoma.
The mechanism of the interconnection between high IOP and myopia is still under investigation. The mechanical hypothesis is connected with the anatomical peculiarities of myopia in the eyes’ the AL is longer, and the sclera has become thinner overall [55, 56]. The aforementioned changes contribute to lamina cribrosa deformity, increased scleral tension, and mechanical alterations caused by stress that can impair the normal aqueous humor circulation, resulting in elevated intraocular pressure. Zhang et al. raise the bio-mechanical consequences of axial elongation and remodeling of the sclera, which may cause fluctuations in IOP [57]. Likewise, Jonas et al. outline the importance of the scleral thinning and posterior pole deformation in the interruption of the aqueous humor flow, which leads to an increase in the IOP [58]. Studies by Consejo and Rozema show how anterior scleral morphometry and malleability are related to axial elongation in myopic eyes, which increases susceptibility to mechanical stress [59]. Additionally, McBrien and Gentle discuss the scleral thinning and extracellular matrix remodeling seen in progressive myopia, noting its role in weakening structural resistance to IOP-induced forces [60]. The results of this research are consistent with the observations made by Pugazhendhi et al., who report the interaction between scleral alterations and axial lengthening in pathological myopia [61]. Moreover, Sung et al. show the correlation of this anterior scleral thickness with ocular variables, including AL, central corneal thickness, and IOP [62]. They propose that scleral thinning could exacerbate mechanical strain and disrupt normal aqueous outflow dynamics. A study by McMonnies describes the baropathic effects of axial elongation and scleral tension, suggesting a feedback mechanism that may worsen IOP elevation in highly myopic eyes [63].
Correlation between IOP and the structural dimensions of SC-such as SCA and LSC, has been extensively investigated, especially in OHT patients. Although no uniform data exist supporting that IOP and SC dimensions relate directly to OHT, individual studies offer supplementary detail on the nature of this relationship. Kagemann et al. have shown an increase in the mean IOP of 189.0% and a decrease in the mean area of Schlemm’s canal of 32.0% (P < 0.001) [64]. This decrease in SCA was theorized to be due to the biomechanical adaptation of the canal to the increased IOP, but the small sample size and the controlled conditions of the experiment may preclude generalization. This disparity may further be explained by the lesser IOP rise in OHT patients compared to the general population, implying that the compliance of all canals differs between patient groups. The role of SC and inner wall resistance in the control of IOP was mentioned in another work by Bayleyegn and team [65]. Although their study was not limited to OHT, their results also highlighted the complicated nature of the interactions between canal morphology and aqueous humor dynamics, which may account for the absence of a simple, linear relationship between IOP and SC dimensions.
The OHT group recorded a significant increase in Covirs-bIOP, CCT, AL, AOD500, AOD750 and Nasal LTM than the control group. Conversely, the OHT group had a lower SE than the control group, and these differences were statistically significant (P < 0.05), suggesting that these parameters may be potential risk factors for ocular hypertension. This study indicates that CCT is associated with higher IOP. The CCT of the OHT group was 578.79 ± 27.62 μm compared to that of the healthy control group, which was 552.29 ± 33.24 μm, and this had significant differences. But because CCT could influence IOP measurement [66, 67], CCT cannot be regarded as an independent risk factor of ocular hypertension or glaucoma. To assess the level of CCT and IOP precisely, a combination of CCT and IOP measurement by Covirs-bIOP could be more precise than a single measurement of IOP [68].
The multivariate logistic regression analysis indicated that the presence of OHT was independently linked to a higher CCT, longer AL, wider AOD500 nasal, and larger nasal LTM. These observations support the notion that structural features of the anterior segment and cornea are more likely to be critical factors in the pathophysiology of OHT than is refractive status or estimates of biomechanical IOP alone, thus justifying the importance of comprehensive anterior segment imaging in risk stratification. Consideration of SE and CCT as continuous covariates in a multivariate model reduced residual confounding by refractive error and corneal biomechanics, thus enhancing the likelihood that anterior segment and trabecular structural features relate independently of OHT.
The American Academy of Ophthalmology (AAO) Preferred Practice Patterns and the World Glaucoma Association (WGA) consensus guidelines advocate several risk factors for the development of OHT to elevated intraocular pressure, thinner CCT, bigger cup-to-disc ratios, and positive family history of glaucoma [10, 69, 70]. These guidelines mainly include adults, but the present study found that the structural parameters, as increased CCT, prolonged AL, expanded nasal angle opening distance, and prolonged LTM, were independent markers of OHT, even in a younger cohort. Interestingly, findings contrast with landmark studies, such as the Ocular Hypertension Treatment Study (OHTS), that described thin CCT as a major risk factor towards conversion to primary open-angle glaucoma [71–73]. These variations highlight the importance of a population-specific anatomical profile of OHT risks and the relevance of a complete assessment of the anterior segment, with focus on corneal and angle measurements, to support specific and early-stage prevention and treatment models.
Previous studies have shown that in untreated patients with PACG, IOP tends to decrease as AOD500 and AOD750 increase. This may be related to angle closure in PACG, which impairs aqueous humor outflow, leading to increased IOP [49]. According to research by Li et al., when healthy individuals performed the Valsalva maneuver, their average IOP significantly increased from 13.86 ± 2.33 mmHg to 14.25 ± 2.36 mmHg, and anterior chamber parameters sharply decreased from AOD500 decreased from 0.35 mm to 0.31 mm (p < 0.001) and AOD750 decreased from 0.44 mm to 0.39 mm (p = 0.007) [74]. The OHT group was also found to exhibit significantly elevated AOD500 and AOD750 as compared to the control group, which can be attributed to significantly reduced SE in the OHT group. Research data indicate that among patients with untreated PACG, IOP generally reduces with an angle-opening distance (AOD500 and AOD750). This correlation can be explained by the hindered drainage of aqueous humor due to angle closure, resulting in the high IOP [75]. These results highlight the particular importance of anterior chamber anatomy in relation to the pathogenesis of PACG and its management of IOP.
Further analysis stratified by SE revealed that in the “SE ≤ −6” subgroup (high myopia), the OHT group had higher corneal curvature than the control group, while the AL and LT were lower in the OHT group compared to the control group. Studies have demonstrated that high myopia distorts the anterior segment mechanics, which impacts IOP and aqueous drainage. The longer axial length in myopia can lead to altered corneal curvature and possibly alter the functioning of the Schlemm canal. In a study, it was observed that the diameter of the Schlemm canal is not always the same between myopic and emmetropic eyes, indicating a possible biomechanical disparity between eyes that can affect IOP regulation in each eye [76]. The relationship between SE and IOP is multifaceted. Myopic individuals, particularly those with SE ≤ −6D, often exhibit structural variations in the trabecular meshwork and Schlemm’s canal, which can affect aqueous outflow. Irshad et al. identified that Schlemm’s canal diameter was reduced in high myopia, indicating compromised outflow and potential IOP elevation [77]. In high myopia, lens thinning and increased axial length contribute to anterior segment crowding, impacting aqueous humor dynamics. An analysis of oxidative stress in high myopic patients has highlighted associations between these changes in the anatomy and changes in the functioning of the Schlemm canal [78]. Disparities in findings, such as higher corneal curvature but thinner lenses in OHT groups compared to controls, underline the need for controlled studies. Myopia-related anatomical changes may act as confounders, complicating interpretations of IOP dynamics. Zhu et al. emphasized the necessity of accounting for SE and AL when evaluating the anterior segment to avoid biased conclusions [79].
The present findings underscore the importance of integrating detailed anterior segment imaging and biometric analysis into the clinical evaluation of patients with ocular hypertension, particularly in younger and moderately myopic individuals, where early structural changes may precede optic nerve damage. The observed associations of higher Covirs-bIOP, increased CCT, and specific anterior chamber angle configurations with OHT suggest that relying solely on conventional tonometry may overlook nuanced anatomical risk factors. Incorporating parameters such as AOD, LTM, and CCT into routine screening could facilitate earlier identification of individuals at heightened risk for glaucomatous progression, potentially guiding more tailored monitoring and prophylactic intervention strategies.
This research has a number of limitations and weaknesses. First, the research represents a single-centered small-sample study, which can impact the representativeness and extrapolation of the research results. Among OHT patients, the sample was only comprised of the patients who presented in an outpatient clinic of our hospital to see an ophthalmologist, and the control group was mostly comprised of healthy patients having refraction tests done in the same clinic. This may lead to selection bias, which may affect the validity of the research findings. Second, the research design was cross-sectional, which was a challenge to determine causal associations amid different factors and OHT. Observation and subsequent measurement of the Schlemm canal were performed in a fixed time interval without providing dynamic data over time. Although scientifically accurate and precise methods were used to measure the Schlemm’s canal, the small size and concealed position of the canal make its identification and precise measurement challenging. This difficulty is particularly evident in the relatively low detection rate of SC in the OHT group. Additionally, the measurement of Schlemm’s canal is subject to the operator’s skill and experience, which may introduce variability in the data and affect the repeatability of the study. Additionally, the study cohort was comparatively young (mean age of about 17 years), which was tied to the local screening habit of targeting school-going populations and young adults. Although this may give insights into early structural markers, it can reduce direct applicability in older populations where OHT and glaucoma are more common. Also, the biomechanically refined measure of IOP known as Covirs-bIOP uses the Corvis ST, and although it offers useful compensation of the corneal properties, it is not yet universally adopted in clinical practice or research. This could restrict immediate comparisons with research that employed standard Goldmann applanation IOP measurements. Notably, the fellow eye as a control, though convenient and frequently used in ophthalmic trials, may result in bias in the case of genetic, anatomical or systemic interactions, or the potential of bilateral involvement that is subclinical.
In spite of the above limitations, this paper presents initial data on the role of SC in OHT and preconditions with a subsequent investigation. Further investigations aimed at increasing the sample size, as well as using prospective studies in the form of cohort research to dynamically trace the changes in IOP, Schlemm canal morphology, and anterior chamber angle structure in patients with OHT, deserve serious attention. These will assist to further support the findings of this study and investigate the involvement of these changes in the development of OHT to glaucoma. These studies will help in the research and development of new diagnostic tests and methods of treatment, thereby enhancing the treatment of ocular hypertension and other related conditions. Future longitudinal studies employing entirely independent controls, along with long-term follow-up, would help validate these structural biomarkers and clarify their prognostic value.
In patients with OHT, no direct correlation was found between IOP and age, CCT, RNFL thickness, average cup-to-disc ratio, vertical cup-to-disc ratio, visual field, MD, PSD, AL, ACD, corneal curvature (K1, K2), LT, AOD500 and AOD750, LTM, LSC, or SCA (p > 0.05). The iris in OHT patients exhibited certain characteristics. The OHT group had higher values for Covirs-bIOP, CCT, AL, AOD500 and AOD750, as well as Nasal LTM, compared to the control group, and a lower equivalent sphere value. These differences were statistically significant (p < 0.05) and may serve as risk factors for ocular hypertension.