Risk Factor For Glaucoma Progression Research Articles

Prediction of glaucoma progression by 24-h contact lens sensor profile in patients with normal-tension glaucoma

A single-center prospective cohort study was conducted to investigate whether intraocular pressure (IOP)-related 24-h contact lens sensor (CLS) profile parameters can help predict glaucoma progression in patients with normal-tension glaucoma (NTG). CLS measurements (Triggerfish; SENSIMED, Etagnières, Switzerland) at baseline without medication were performed for 24 h in one eye, following diurnal IOP measurements using Goldmann applanation tonometry at 3-h intervals. Glaucoma progression during the follow-up period of ≥ 2 years was determined based on the Guided Progression Analysis of Humphrey visual fields and/or structural progression using fundus photographs. Among 79 patients (mean values: follow-up periods, 48.1 months; age, 51.5 years; baseline IOP, 14.0 mmHg; mean deviation, − 6.04 dB), 23 showed glaucoma progression. A smaller standard deviation of nocturnal ocular pulse amplitude in the CLS profile, a larger range of diurnal IOP at baseline, and the presence of optic disc hemorrhage (DH) during the study period were significant risk factors for glaucoma progression in the multivariate Cox proportional hazards model (hazard ratio, 0.30/mVeq, 1.23/mmHg, and 4.37/presence of DH; P = 0.016, 0.017, and 0.001, respectively). CLS measurements may be useful for assessing the risk of future glaucoma progression in patients with NTG, providing supplementary information to routine IOP measurements.

Fundamentals of a personalized approach at different stages of newly diagnosed glaucoma

The review is focused on the adherence of glaucoma patients to the immediate start of treatment after the condition has been diagnosed. A personalized strategy, which includes the assessment of the patient's clinical and socio-economic status and the use of medications with proven efficacy, contributes to the formation of long-term adherence to therapy. In particular, the strategy combines preventive and diagnostic measures depending on the patient’s individual characteristics and involves their direct participation. Over 250 risk factors are known to reduce a patient’s adherence to treatment, whereas insufficient adherence can itself be considered as a risk factor for glaucoma progression. The asymptomatic course of the disease or the lack of a noticeable effect of drops instilled often cause the regimen to be violated, whilst the long-term therapy requires determination and self-control of the patient. Combined measures to improve the adherence are based on the specific needs of the patients and are consistent with their lifestyle. As a rule, the patients need special instruction, good means of communication with the doctor, simplified treatment regimens, and an adequate interaction with the public health facilities. Importantly, the therapy start depends not only on the level of intraocular pressure, but also on the stage of the glaucomatous process at which it was first diagnosed.

Playing the Bagpipes - A Risk Factor for Glaucoma Progression?

Playing the Bagpipes - A Risk Factor for Glaucoma Progression?

Rates of visual field change and functional progression in glaucoma following trabecular microbypass implantation of iStent technologies: a meta-analysis

Background/aimWhile intraocular pressure (IOP) remains the only modifiable risk factor for glaucoma progression, the ultimate goal of glaucoma management is to preserve patients’ functional vision and quality of life. To...

Implications of Central Corneal Thickness-corrected Intraocular Pressure in Normal-tension Glaucoma with Reduced Central Corneal Thickness

Purpose: Reduced central corneal thickness (CCT) is a risk factor for glaucoma progression and can impact intraocular pressure (IOP) measurement. Therefore, we investigated the glaucoma progression pattern and associated risk factors among individuals with normal-tension glaucoma (NTG) and reduced CCT.Methods: This retrospective study enrolled 187 eyes of 187 NTG patients with an open angle and a baseline IOP < 20 mmHg, adjusted for CCT. Reduced CCT was defined as < 500 µm thickness in both eyes. Patients with a history of corneal disease or surgery affecting CCT were excluded. We used Goldmann tonometry to measure baseline and CCT-corrected IOP (ccIOP; [IOP - [CCT - 545]/50 × 2.5]). The participants were divided into progressing and stable subgroups.Results: The mean CCT was 481.2 ± 17.5 µm and the mean follow-up period was 6.3 ± 2.5 years. The baseline IOP and ccIOP were 13.7 ± 2.4 and 16.6 ± 2.5 mmHg, respectively. The average visual field progression rate was -0.79 ± 1.26 dB/yr. Of the participants, 47 (26.6%) and 140 (73.4%) were in the progressing and stable group, respectively. Participants in the progressing group were older, had a higher baseline ccIOP, and had a higher proportion of pseudophakia than those in the stable group. Multivariate analysis showed that baseline ccIOP was a significant risk factor.Conclusions: Individuals presenting with NTG and reduced CCT had a relatively stable glaucoma progression rate. However, glaucoma progression was associated with old age, pseudophakia, and high baseline IOP in individuals with reduced CCT. In particular, the only significant factor associated with glaucoma progression was ccIOP. Therefore, ccIOP is a clinically significant factor in individuals with NTG and reduced CCT.

Primary Open Angle Glaucoma

Primary open angle glaucoma is the most frequent type among the glaucomas. It is characterized by a progressive loss of retinal ganglion cells and a corresponding visual field loss. Risk factors include older age, ethnicity, family history of glaucoma and, most important, an elevated intraocular pressure (IOP). The IOP is the only modifiable risk factor for glaucoma progression. Therapeutic approaches aim to lowering the IOP and incorporate topical pressure lowering medication, laser treatment, and different surgical approaches. Surgery aims to reducing the outflow resistance of the aqueous humor. This may be achieved by surgically opening the trabecular meshwork or Schlemm's canal. Penetrating glaucoma surgery comprises classic trabeculectomy and other draining devices.

Preparation, in vitro and in vivo evaluation of solid-in-oil dispersion-based formulation the anti-glaucoma drug, timolol maleate

Lowering Intraocular pressure (IOP) is a main therapeutic objective in glaucoma patients because IOP is an important risk factor for glaucoma progression. The objective of this work was to formulate and evaluate, in vitro and in vivo, a stable and effective Solid in Oil (S/O) topical formulation of the antiglaucoma drug, timolol maleate (TM). S/O dispersions were prepared by emulsification of aqueous TM solutions in cyclohexane using different amount of the span 85 then lyophilizing the emulsion to produce TM – Span 85 complexes. The complexes were then dispersed in castor oil using tip sonicator to produce S/O nanodispersions. S/O nanodispersions were evaluated in terms of particle size, polydispersity index, encapsulation efficiency, morphology, physical stability, as well as transcorneal permeation and accumulation of TM. In addition, the in vivo tolerability and efficacy of the prepared formulation in lowering intraocular pressure were evaluated in rabbits.
 Spherical nanoparticles of TM with a particle size of about 134-155 nm were successfully prepared and found to be physically stable. The encapsulation efficiency was high and was found to be dependent on the level of Span 85 used.
 In comparison to TM solution, S/O nanodispersion enhanced TM permeation and decreased accumulation in transcorneal diffusion studies. In addition, application TM S/O nanodispersion onto rabbit eyes resulted in a significant reduction in IOP in comparison to TM aqueous solution.

Visual field‐based AI in glaucoma

AbstractArtificial intelligence (AI) has recently evoked tremendous excitement for research in the field of Ophthalmology and glaucoma. One of the areas where AI could come into play relates to the prediction of visual field progression. Currently linear trend‐based analysis is the most widely used method for assessing visual field progression. In the recent years a variety of deep learning based approaches have been proposed to better predict visual field progression. Techniques including archetypal analysis, Gaussian mixture model with expectation maximization and Visual Geometry Group standard deep Convolutional Neural Network (CNN) will be discussed. AI has also been used to study mapping of structure to function in glaucoma. This is of importance because it may be used to reduce the variability of visual field data. Hence it may increase our ability to study functional progression by combining perimetry and OCT data. Moreover, the structure/function relationship has been shown to be an independent risk factor for glaucoma progression.

Pharmacogenetics and pharmacogenomics in glaucoma therapeutics: the way to personalized therapy.

Pharmacogenetics and pharmacogenomics in glaucoma therapeutics: the way to personalized therapy.

Characterization of the human iridocorneal angle in vivo using a custom design goniolens with OCT gonioscopy.

Intraocular pressure (IOP) is the only modifiable risk factor for glaucoma progression, and many treatments target the trabecular meshwork (TM). Imaging this region in vivo is challenging due to optical limitations of imaging through the cornea at high angles. We propose a gonioscopic OCT approach using a custom goniolens and a commercially available OCT device to improve imaging of the TM, Schlemm's canal (SC) and adjacent structures within the iridocorneal angle (ICA). The goniolens is modified with a plano-convex focusing lens and placed on the eye optically mated with goniogel and aided by a 3D adjustable mount. Gonioscopic OCT volume scans are acquired to image SC. Transverse enface images allowed measurements of SC over a 45° section of the ICA for the first time and revealed locations of SC narrowing. The band of extracanalicular limbal lamina and corneoscleral bands were imaged in most subjects and these bands were confirmed using exterior OCT imaging. The polarization dependence of the visibility of these structures is studied by polarization rotation the OCT beam with a half-wave plate, allowing increased contrast of SC. Gonioscopic OCT has successfully been used to image the human ICA in 3D in vivo. This approach provides more detailed characterization of the TM and SC, enhancing their contrast against their birefringent backgrounds.

Dual Orexin Receptor Antagonist Attenuates Increases in IOP, ICP, and Translaminar Pressure Difference After Stimulation of the Hypothalamus in Rats.

PurposeIntraocular pressure (IOP) remains the only modifiable risk factor for glaucoma progression. Our previous discovery that stimulation of nuclei within the hypothalamus can modulate IOP, intracranial pressure (ICP), and translaminar pressure difference (TLPD) fluctuations led us to investigate this pathway further. Our purpose was to determine the role of orexin neurons, primarily located in the dorsomedial hypothalamus (DMH) and perifornical (PeF) regions of the hypothalamus, in modulating these pressures.MethodsSprague Dawley rats were pretreated systemically with a dual orexin receptor antagonist (DORA-12) at 30 mg/Kg (n = 8), 10 mg/Kg (n = 8), or vehicle control (n = 8). The IOP, ICP, heart rate (HR), and mean arterial pressure (MAP) were recorded prior to and following excitation of the DMH/PeF using microinjection of the gamma-aminobutyric acid (GABA)A receptor antagonist bicuculline methiodide (BMI).ResultsAdministration of the DORA at 30 mg/Kg significantly attenuated peak IOP by 5.2 ± 3.6 mm Hg (P = 0.007). During the peak response period (8–40 minutes), the area under the curve (AUC) for the 30 mg/Kg DORA cohort was significantly lower than the control cohort during the same period (P = 0.04). IOP responses for peak AUC versus DORA dose, from 0 to 30 mg/Kg, were linear (R2 = 0.18, P = 0.04). The ICP responses during the peak response period (4–16 minutes) versus DORA dose were also linear (R2 = 0.24, P = 0.014). Pretreatment with DORA significantly decreased AUC for the TLPD following stimulation of the DMH/PeF (10 mg/kg, P = 0.045 and 30 mg/kg, P = 0.015).ConclusionsDORAs have the potential to attenuate asynchronous changes in IOP and in ICP and to lessen the extent of TLPDs that may result from central nervous system (CNS) activation.

Tag-Nacht-Schwankungen des Augeninnendrucks als eigenständiger Risikofaktor für das primäre Offenwinkelglaukom

Purpose. Purpose: In addition to the static observation of intraocular pressure at an arbitrary time point, the dynamic observation of intraocular pressure in the 24-hour rhythm is considered to be clinically useful in order to better assess the extent of day-night fluctuations. Material and Methods. The literature review includes the current state of knowledge regarding the 24-hour fluctua- tions in intraocular pressure as an independent risk factor for primary open-angle glaucoma. The literature search was performed with PubMed. Results. The intraocular pressure is neuronally regulated and is involved in the circadian regulation via the nucleus supra- chiasmaticus; the normal fluctuation in intraocular pressure is 5 mmHg. In the context of systemic neurodegeneration in primary open-angle glaucoma, there is also a disturbance of the cir- cadian rhythm. The fluctuations in intraocular pressure can be 10 mmHg or more and are an independent risk factor for glaucoma progression. Conclusion. Thus, the goal of successful glaucoma therapy is not only to achieve an individual target pressure range, but also to normalise abnormal circadian intraocular pressure fluctuations. Keywords glaucoma, circadian rhythm, neurodegeneration, oxidative stress

Risk Factors for the Structural Progression of Myopic Glaucomatous Eyes with a History of Laser Refractive Surgery.

As laser refractive surgeries (LRS) have been widely performed to correct myopia, ophthalmologists easily encounter patients with glaucoma who have a history of LRS. It is well known that intraocular pressure (IOP) in eyes with glaucoma is not accurate when measured using Goldmann applanation tonometry. However, risk factors for glaucoma progression, particularly those associated with measured IOP, have rarely been studied. We analysed data for 40 patients with a history of LRS and 50 age-matched patients without a history of LRS. Structural progression was defined as significant changes in thickness in the peripapillary retinal nerve fibre layer as identified using optical coherence tomography event-based guided progression analysis. Risk factors were determined via Cox regression analysis. Disc haemorrhage (DH) was associated with glaucoma progression in both the non-LRS group and LRS group (hazard ratio (HR): 4.650, p = 0.012 and HR: 8.666, p = 0.019, respectively). However, IOP fluctuation was associated with glaucoma progression only in the LRS group (HR: 1.452, p = 0.023). Our results show that DH was a significant sign of progression in myopic glaucoma eyes. When treating patients with myopia and glaucoma, IOP fluctuation should be monitored more carefully, even if IOP seems to be well controlled.

Synergic effect of corneal hysteresis and central corneal thickness in the risk of early-stage primary open-angle glaucoma progression.

To evaluate corneal hysteresis (CH), acquired with ocular response analyzer (ORA), as a risk factor for glaucoma progression in early-stage primary open-angle glaucoma (POAG). In a historical cohort study, patients diagnosed in 2011 with early-stage POAG according to the Hodapp, Parrish and Anderson classification modified for Octopus perimetry and followed up until glaucomatous progression development; otherwise, observations were censored in October 2018. Cox regression was used to obtain hazard ratios (HR) to evaluate baseline variables (CH, central corneal thickness, gender, age IOP and glaucoma family history) as risk factors for perimetric glaucoma progression. A likelihood ratio test for interaction was performed in order to assess the effect of the combination of CH and CCT on the risk of progression. Of the cohort of 1573 patients, 11.38% developed early-stage POAG progression during the follow-up. The mean follow-up time was 3.28 ± 1.92years. Patients without progression had a higher CH (11.35 ± 1.43 vs 9.07 ± 1.69mmHg; p < 0.001) and CCT (570.75 ± 17.71 vs 554.51 ± 23.20; p < 0.001). In the multivariate analysis, each 1mmHg of lower CH was associated with an increase of 2.13 times in the HR of progression (95% CI: 1.92-2.32; p < 0.001). CH hazard ratio was modified by CCT, with higher values of CCT and CH resulting in a higher HR of early glaucoma progression (p < 0.001). CH can be considered as a risk factor of progression in early-stage POAG. The risk associated with CH changed depending on CCT values, acting synergistically slowing the risk of glaucoma progression with higher values.

Myopia and glaucoma progression among patients with juvenile onset open angle glaucoma: A retrospective follow up study.

To identify the risk factors for glaucoma progression, especially the association with myopia, among treated juvenile open angle glaucoma (JOAG) patients. Glaucomatous progression was analysed in the eyes of JOAG patients with at least 5-years of follow up in this retrospective study. Baseline variables such as age, inheritance pattern, baseline intraocular pressure (IOP), baseline central corneal thickness, visual acuity, baseline refractive error, spherical equivalent (SE) and duration of follow-up were noted. Stereoparametric global trend analysis and Moorfields Regression Analysis on confocal scanning laser ophthalmoscopy were used to detect progression. Variables associated with glaucoma progression, with respect to progressors (PG) and non-progressors (NPG) were analysed. Since both eyes of a patient were taken for analysis, a generalised estimating equation method was used to correct the bias. Among 74 eyes (37 subjects), glaucoma progression was noted in 11 eyes (14.9%) of 8 patients, with a median time to progression of 7.4years (range 5-15.5years). For myopes (SE≤-1.00D), glaucoma progression was 18 times more likely than mild and no myopes (>-1DS) (p=0.03, 95% CI: 1.14, 217.44). The prevalence of myopia in the JOAG, PG and NPG cohorts was 70.3%, 87.5%, and 65.5%, respectively. Myopia progression was noted at follow up in 70% patients. One-unit increase in baseline vertical cup disc ratio, 1mmHg increase in IOP fluctuations and 1dB year-1 depression of visual field were associated with 0.44, 0.06 and 0.07D year-1 increases in the rate of myopia progression, respectively. JOAG progressors had a greater baseline myopic refraction and a faster myopia development over time. The development of myopia in JOAG eyes could be an indicator of glaucoma progression, and hence progressing myopic (≤-1D) JOAG patients should be followed up more rigorously.

Longitudinal Growth Differentiation Factor 15 (GDF15) and Long-term Intraocular Pressure Fluctuation in Glaucoma: A Pilot Study.

PurposeGrowth Differentiation Factor 15 (GDF15) was previously identified as a molecular marker of retinal ganglion cell stress in rodent models of glaucoma and was elevated in the aqueous humor (AH) of patients with primary open-angle glaucoma as a possible risk factor for glaucoma progression. The purpose of this study was to determine whether changes in the AH GDF15 levels were associated with intraocular pressure (IOP) changes in eyes undergoing glaucoma surgery.Methods Here, we performed a prospective, longitudinal pilot study in nine patients to determine whether changes in AH GDF15 levels from surgery to post-surgery follow-up were associated with IOP fluctuation. An initial AH sample was taken from the peripheral corneal paracentesis during planned glaucoma surgery, and a second sample was taken during an outpatient follow-up visit, approximately six months later.ResultsThere was a statistically significant correlation between GDF15 fold change and IOP standard deviation (r = 0.87, P = 0.003), IOP range (r = 0.87, P = 0.003), and maximum IOP (r = 0.86, P = 0.003). There was no correlation between the GDF15 fold change and baseline IOP (r = 0.50, P = 0.17), final IOP (r = 0.038, P = 0.92), or mean IOP (r = 0.40, P = 0.28).ConclusionOur findings in this pilot study suggest that longitudinal changes in AH GDF15 may be associated with IOP fluctuation during the postoperative period. Further studies are necessary to corroborate these findings in a larger patient population and to explore the possibility that AH GDF15 may be used not only to improve treatment algorithms but also as a surrogate endpoint in clinical trials.

Coefficient of biomechanical stress in assessment of the degree of intraocular pressure compensation

To determine the range of normal values of the Kbs coefficient, and to evaluate its specificity and sensitivity as a criterion for the degree of intraocular pressure compensation. Two consecutive studies on representative clinical material were used to determine the range of normal Kbs values in patients without significant ophthalmic pathologies (400 patients, 800 eyes) and establish the sensitivity and specificity of the coefficient in the diagnosis of glaucoma in patients with newly diagnosed glaucoma (673 patients, 1346 eyes). The age and gender composition of patients in both study groups was similar. The cut-off value for Kbs is 1.0. In the range of values from 1.0 to 1.09, additional risk factors for glaucoma progression must be taken into account to assess intraocular pressure compensation. In cases when Kbs is equal to or exceeds 1.1, the intraocular pressure is considered elevated and a high risk of disease development or progression is predicted. In glaucoma patients with uncompensated intraocular pressure, the specificity of Kbs is 81.5%, the relative specificity (including the borderline range) is 98%. With Kbs values over 1.1, its specificity reaches 100%. The performed clinical and statistical analysis demonstrates high sensitivity and specificity of the biomechanical stress coefficient in the diagnosis and treatment of glaucoma.

Comparison of the hypotensor effect between latanoprost versus selective laser trabeculoplasty obtained with the water drinking test.

Glaucoma is the main cause of irreversible blindness worldwide. Peak intraocular pressure is one of the main risk factors for glaucoma progression, and intraocular pressure reduction remains the only therapeutic strategy for all types of glaucoma. The main purpose of our study was to compare the baseline and peak intraocular pressure reduction obtained with the water drinking test between the two eyes of the same patients using 0.005% latanoprost in one eye and selective laser trabeculoplasty application in the contralateral eye. This was a prospective, interventional, longitudinal, and randomized clinical trial, in which 30 consecutive glaucomatous patients, medically controlled using latanoprost monotherapy, were recruited from a single ophthalmological center. The patients' eyes were randomized, and one eye was selected for SLT treatment and topical 0.005% latanoprost was introduced in the contralateral eye. The baseline intraocular pressure and peak intraocular pressure were evaluated 1 month (water drinking test 2) and 6 months (water drinking test 3) after treatment. There was no significant difference between the mean pre-washout intraocular pressure in the randomized eyes for selective laser trabeculoplasty and latanoprost (13.6 ± 2.1 and 13.3 ± 1.8 mmHg, respectively; p=0.182). Regarding baseline intraocular pressure, there was no significant difference in the water drinking test 2 (p=0.689) and water drinking test 3 (p=0.06) between the groups. There was no significant difference in the intraocular pressure peak between the SLT and latanoprost groups at water drinking test 2 (p=0.771) or water drinking test 3 (p=0.774). The intraocular pressure reduction efficacy is similar between latanoprost and selective laser trabeculoplasty. Glaucomatous patients who are medically controlled with latanoprost and switch treatment to selective laser trabeculoplasty maintain control of intraocular pressure.

Clinical correlation of glaucoma with systemic hypertension and its effect on visual morbidity

Glaucoma and hypertension share a common pathophysiology of altered sodium transport in the renal and ciliary epithelium and can co exist. High blood pressure is a significant risk factor for glaucoma progression due to intraocular pressure spikes.This study was performed to evaluate the association of hypertension with glaucoma and to assess the extent of optic disc damage, the role of anti hypertensive medications and visual morbidity.This is a prospective, multidisciplinary study performed on a cohort of118 hypertensive patients over 1 year. Ophthalmic examination, ancillary ocular investigations, systemic tests and multi speciality referrals were obtained for all patients.Among 118 hypertensive patients, 64 (54.8%) had glaucoma. 65 patients (55.1%) were female and 53 patients (44.1%) male. Age group most frequently affected was between 60 and 70 years. There was increased incidence of ocular hypertension which was statistically significant (p value of 0.02). The range of IOP in those on anti hypertensive medications was 10-16 mmHg which was statistically significant (p value = 0. 03).Risk of glaucoma in hypertension was higher in women. An elevation of diastolic blood pressure is more significant than systolic BP in raising IOP. Decreased IOP was highest among patients taking calcium channel blockers.: Hypertension can cause both reduction and elevation in IOP. Treatment of hypertension does lower the IOP and prevent further progression of glaucoma and prevent any visual loss.

Corneal Stiffness Parameters Are Predictive of Structural and Functional Progression in Glaucoma Suspect Eyes

To investigate corneal stiffness parameters (SPs) as predictors of future progression risk in glaucoma suspect eyes. Prospective, longitudinal study. Three hundred seventy-one eyes from 228 primary open-angle glaucoma suspects, based on optic disc appearance, with normal baseline Humphrey Visual Field (HVF; Carl Zeiss Meditec) results. Baseline corneal SPs were measured using Corvis ST (Oculus Optikgeräte GmbH). Participants were followed up every 6 months with clinical examination, HVF testing, and OCT. The baseline SP at first applanation (SP-A1) and highest concavity predicted the prospective outcome measures. Structural progression was measured by the OCT rate of thinning of the retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL). Functional progression was assessed by permutation analysis of pointwise linear regression criteria on HVF testing. Stiffness parameters correlated positively with central corneal thickness (CCT), which was adjusted for in all analyses. A higher SP-A1, suggestive of a stiffer cornea, was associated with a faster rate of RNFL thinning (P < 0.001), synergistic with thinner CCT (P= 0.004) over a mean follow-up of 4.2 years. Eyes with higher SP-A1 and thinner CCT (thin and stiff corneas) showed accelerated RNFL thinning by 0.72 μm/year relative to eyes with lower SP-A1 and thicker CCT (95% confidence interval [CI], 0.17-1.28; P= 0.011) and were at 2.9-fold higher likelihood of fast RNFL progression of more than 1 μm/year (95% CI, 1.4-6.1; P= 0.006). Consistent results also were observed with GCIPL thinning. Furthermore, a higher SP-A1 was associated with a greater risk of visual field progression (P= 0.002), synergistic with thinner CCT (P= 0.010). Eyes with higher SP-A1 and thinner CCT were at 3.7-fold greater risk of visual field progression relative to eyes with thicker CCT and lower SP-A1 (95% CI, 1.3-10.5; P= 0.014). Glaucoma suspect eyes with higher corneal SPs and lower CCT, suggestive of thin and stiff corneas, are at greater risk of progression. Corneal SPs seem to act synergistically with CCT as risk factors for glaucoma progression.