Comparing corneal biomechanical parameters between primary open-angle glaucoma and pseudoexfoliation glaucoma using corvis ST

Abstract

Background

To compare corneal biomechanical properties between primary open-angle glaucoma (POAG) and pseudoexfoliation glaucoma (PXG) using CorVis ST.

Methods

Thirty-three eyes of 33 patients with PXG and 29 eyes of 29 patients with POAG were enrolled in this cross-sectional study. All eyes underwent CorVis ST. Biomechanical parameters at the first and second applanation and highest concavity were measured. Man-Whitney U test and stepwise linear regression were used to compare the parameters between groups.

Results

The mean age was 67.1 ± 7.9 and 70.3 ± 7.1 years in the POAG and PXG groups, respectively (P = 0.072). Eighteen patients in each group were male (P = 0.549). Intraocular pressure (IOP) measured by Goldmann applanation tonometry was not different between groups (P = 0.112) while the PXG group had higher biomechanically corrected IOP (14.3 ± 3.5 mmHg vs. 15.9 ± 3.4 mmHg; P = 0.042). Central corneal thickness was lower in the PXG group (546 ± 29 μm vs. 523 ± 37 μm; P = 0.008). A2 velocity was lower in the PXG group (P = 0.008). The highest concavity (HC) deformation amplitude and deflection length and peak distance were lower in the PXG group (p < 0.05). The PXG eyes had a higher stress-strain index (1.29 ± 0.26 vs. 1.42 ± 0.27; P = 0.022).

Conclusion

The results of the current investigation are in favor of the presence of a stiffer cornea in the PXG group.

Introduction

Glaucoma is a multifactorial optic neuropathy characterized by a high cup-to-disc ratio and irreversible loss of visual field. There are several types of glaucoma, which are different in clinical presentation and pathophysiology. The most common type of glaucoma is primary open-angle glaucoma (POAG). Besides intraocular pressure (IOP) several factors have been introduced to explain the pathophysiology of POAG, like oxidative stress, dysregulation of cerebrospinal fluid, or dysregulation of blood supply to the optic nerve head [1].

Extracellular matrix deposition and remodeling have a role in the development of glaucomatous damage, especially in the pathophysiology of pseudoexfoliation glaucoma (PXG) [2]. Elastic microfibrillar deposition in the trabecular meshwork and lamina cribrosa can alter the susceptibility of the optic nerve head and ganglion cell axon to elevated IOP [3].

Recently, corneal biomechanics have been studied in the various types of glaucoma and has become a fascinating topic. Corvis ST (Corneal Visualization Scheimpflug Technology, Oculus; Wetzlar, Germany) is a device that can evaluate corneal biomechanical features in detail and measure the IOP by taking multiple cross-sectional images by scheimpflug camera. Also, it has been shown that Scleral rigidity and biomechanical features of lamina cribrosa play a role in optic nerve vulnerability to glaucomatous damage [2]. In POAG using the Corvis ST, the cornea showed less deformity than the normal cornea [4, 5]. On the other hand, there are contradictory results [6].

Since collagen fibers are the main component of the cornea and sclera, corneal rigidity and deformability could correlate with scleral deformity and susceptibility to glaucomatous optic nerve damage. There are a few studies that have measured the difference in corneal biomechanics between PXG and POAG using Corvis ST. Therefore, this study aimed to compare the corneal biomechanical parameters between eyes with PXG and POAG.

Methods

This was a cross-sectional study conducted at Khalili Hospital, a tertiary eye care center in Shiraz, Iran, between August 2020 to November 2022. The methodology adhered to the tenets of the Declaration of Helsinki for research involving human subjects. Written informed consent was obtained from all participants and the study was approved by the Shiraz University of Medical Sciences Ethics Committee. The participants included patients with POAG and PXG.

All participants underwent complete ophthalmological examinations including measurement of visual acuity, slit lamp examinations, gonioscopy, IOP measurement with Goldmann applanation tonometer (GAT), and retinal examination after dilation. All eyes had newly diagnosed glaucoma and were treated with topical latanoprost 0.005%. A follow-up examination was conducted in one month and additional medications were prescribed if needed. During this period imaging with Corvis ST was done for both eyes. The data from both eyes were extracted from the device, but the analysis was performed only on one eye of each patient, and the data from the other eye was used for confirmation.

POAG was defined as the presence of an open angle on gonioscopy, characteristic glaucomatous optic neuropathy (generalized enlargement of the cup, neuroretinal rim notching, retinal nerve fiber layer defects, optic disc hemorrhages) with corresponding changes on optical coherence tomography (OCT) or visual fields (VF). PXG was defined as the presence of typical pseudoexfoliative material on the anterior lens capsule or at the pupil border, after mydriasis along with characteristic glaucomatous optic neuropathy and/or visual field defect.

Exclusion criteria for each group were: age under 50 years; history of diabetes mellitus, high myopia, patients using topical antiglaucoma medications more than one month before investigation; any corneal abnormality that affects CorVis ST measurements such as corneal ectasia, opacity and ocular surface disease e.g., dry eye syndrome; and experience of any surgical/laser ophthalmic intervention, such as cataract surgery, trabeculotomy, trabeculectomy, laser trabeculoplasty, corneal or scleral refractive surgery. It was also tried to match the age, which may have non-negligible effects on the biomechanical properties of the eye, between the two groups.

Corvis ST

The high-speed Scheimpflug camera recorded 140 images of the cornea before and after a transient indentation of the cornea, which occurred within 30 ms after the application of an air impulse. The corneal response is characterized by two applanations during inward and outward corneal movements, which occur before and after the maximum displacement of the corneal apex. Because the cornea is viscoelastic, it dissipates some of the applied energy, and the corneal shape at the second applanation during the outward movement of the cornea is different from that at the first applanation. Apart from measuring the IOP and the central corneal thickness (CCT), the Corvis ST provides several corneal biomechanical parameters based on the deformation response. The air puff causes the cornea to move inwards and flatten. At this first applanation phase (A1), the length of the applanated cornea (A1 Length in mm) and the velocity of the corneal apex movement (A1 Velocity in m/s) are measured. The cornea then continues to move inwards to reach a point of highest concavity. Three biomechanical parameters are measured here. The deformation amplitude (DA in mm) is the total displacement of the corneal apex from the start of deformation to the point of highest concavity. The peak distance (PD in mm) is the distance between the two bending points of the concave cornea. The radius of curvature (RC) is the curvature of the central concave cornea. As the cornea begins to assume its normal, convex shape, it passes through the second applanation point (A2) where, again, the length of the flattened cornea (A2 Length in mm) and velocity of the corneal apex movement (A2 Velocity m/s) are estimated. The Corvis ST parameters were compared between the two groups. The data from both eyes were taken from the device, but the analysis was performed only on one eye of each patient, and the data from the other eye was used for confirmation.

Statistical analysis

Statistical analysis was performed using SPPS version 26. Numeric data are presented as mean (SD) and categorical data as percentages. Mann-Whitney U and Chi-square tests were used to compare numerical and categorical data, respectively. Stepwise linear regression was conducted to assess the possible independent association of glaucoma type with different Corvis corneal biomechanical factors. The included dependent parameters in the model were age, sex, GAT IOP, CCT, mean keratometry, and glaucoma type.

Results

Sixty-two eyes of 62 participants were included. The study cohort comprised 33 eyes with POAG and 29 eyes with PXG. The demographic and baseline characteristics of the participants are summarized in Table 1. The mean age was 67.1 ± 7.9 for the POAG group and 70.3 ± 7.1 for the PXG group (P = 0.072). Both groups were matched for age and sex.

Table 1 The baseline characteristics of the patients in both groups

The mean GAT IOP was 15.7 ± 3.9 mmHg for the POAG group, while it was 16.9 ± 3.7 mmHg for the PXG individuals (P = 0.112). Although both groups were matched in terms of GAT-IOP, the biomechanically-corrected IOP (bIOP) was different between the groups; 14.3 ± 3.5 mmHg Vs 15.9 ± 3.4 mmHg in POAG and PXG, respectively (P = 0.042).

The Central Corneal thickness (CCT) was 546 ± 29 microns for the POAG group and 523 ± 37 microns for the PXG patients (P = 0.008). Moreover, the pachymetry slope which represents the slope of pachymetry changes from the center toward the periphery was 30.2 ± 9.9 microns and 23.9 ± 9.6 in POAG vs. PXG (P = 0.027). Thus, the PXG patients had thinner cornea than the POAG ones, not only in the center but also in the corneal periphery.

The corneal biomechanical parameters

Table 2 represents the biomechanical parameters in 2 groups. While the mean A2 Time was 21.48 ± 0.56 and 21.13 ± 0.51 milliseconds in POAG and PXG (P = 0.007), the mean A2 velocity was − 0.24 ± 0.03 and − 0.22 ± 0.04 in POAG and PXG, respectively (p = 0.008). In the highest concavity (HC) phase, HC Deformation Amplitude, HC deflection length, and peak distance were different between groups. In such a way, all three parameters were smaller in PXG than in the POAG group (P = 0.049, P = 0.001, and P = 0.04, respectively). The mean Stress-Strain index (SSI) was 1.29 ± 0.27 and 1.42 ± 0.28 in POAG vs. PXG groups respectively (P = 0.022), implying the PXG group had stiffer corneas than POAG ones. The other Corvis ST parameters were not statistically significantly different between groups (P > 0.05).

Table 2 The Corvis ST Biomechanical indices in both groups

The results of a stepwise multiple regression analysis, including age, sex, GAT IOP, CCT, mean keratometry, and the type of glaucoma (PXG vs. POAG) as independent factors and Corvis ST biomechanical indices as dependent parameters are summarized in Table 3. As presented in Fig. 1, the time of second applanation (A2) is shorter in PXG than in POAG patients. Moreover, the deflection length at both first applanation (A1 deflection length) and highest concavity (HC deflection length) was shorter in PXG than in POAG ones.

Table 3 Regression analysis of the possible associations between the glaucoma type (PXG vs. POAG) and Corvis ST Biomechanical parameters

Fig. 1

Comparison of corvis ST biomechanical parameters between PXG and POAG. The PXG group has a shorter A2 Time(left figure), shorter A1 Deflection Length(middle figure), and also shorter HC deflection length(right figure) PXG = Pseudoexfoliation Glaucoma; POAG = Primary Open-Angle Glaucoma; HC = Highest Concavity

Discussion

In the current investigation, we showed that the PXG eyes compared to the POAG eyes have lower A2 velocity and smaller HC deformation amplitude, HC deflection length, and peak distance. Also, the PXG eyes had shorter A2 time and deflection length at first applanation and HC in multiple regression analysis.

The role of corneal biomechanics in glaucoma has been evaluated in numerous studies. Corneal biomechanics can either play a role in the measurement of IOP or may present as a risk factor for glaucoma [7, 8]. Ocular response analyzer (ORA) and CorVis ST provide corneal compensated IOP (IOPcc) and bIOP to involve the biomechanical properties of the cornea for accurate measurement of IOP [8]. On the other hand, altered corneal biomechanics may be a risk factor for progression of the glaucoma [9].

The main site of damage in glaucomatous optic neuropathy is lamina cribrosa. As the biomechanical properties of the lamina cribrosa cannot be measured directly, different studies have focused on the cornea as the representative of the lamina cribrosa and ocular wall [10]. The ocular response analyzer provides corneal hysteresis (CH) and corneal resistance factor (CRF) to present the biomechanical status of the cornea. Various studies have shown the correlation between lower CH and the risk of development of glaucoma, thinner retinal nerve fiber layer thickness, and faster visual field deterioration [11,12,13]. Studies comparing CH and CRF in POAG and PXG eyes have reported lower CH and CRF in PXG eyes [14, 15]. Also, faster structural and functional progression of glaucoma in PXG has been the subject of some investigations [16, 17]. The lower ocular stiffness and weaker ocular wall in PXG eyes may have a role in the more destructive course of the PXG.

CorVis ST as a tool for evaluating corneal biomechanics provides several parameters. In the current investigation, the PXG group had lower CCT. The studies comparing CCT between PXG eyes and the control group have mixed results. Altered keratocyte function and reduced extracellular matrix production have been proposed for decreased corneal thickness and endothelial dysfunction has been proposed for a higher CCT in PXG [18, 19]. The main point is the relation between CCT and corneal stiffness. A higher CCT usually is associated with a stiffer cornea [20, 21]. In our study, the PXG eyes had lower A2 velocity, HC deflection length, and peak distance while the POAG eyes had higher HC deformation amplitude. Also, the SSI was significantly higher in PXG eyes. In the stepwise multiple regression analysis, A1 and HC deflection length was shorter in PXG eyes. Our results were partially in favor of stiffer cornea in PXG eyes which can be explained by the deposition of the fibrillar material in the corneal tissue. Our findings are partially in line with Pradhan et al. study which showed lower deformation amplitude and A2 velocity in PXG eyes. Also, A2 velocity was lower in PXG eyes with marginal insignificance. The IOP was different between their groups and after adjustment of IOP, there was no statistically significant difference in CorVis ST parameters between groups [6]. The GAT IOP was not different between our groups and was not a limiting factor. Other studies comparing corneal biomechanical properties between POAG and normal tension glaucoma (NTG) have shown that NTG eyes have more deformable cornea which is presented by lower A1 velocity and stiffness parameter index 1 and higher deformation amplitude and integrated radius [22,23,24,25]. In a study by Zarei et al., the PXG eyes had weaker cornea compared to the normal control eyes which was presented by a smaller radius of curvature [26]. In another study comparing PXG and normal control eyes, PXG eyes had lower deformation amplitude and corneal velocities which are representative of stiffer cornea but the difference was not significant after adjustment for age and IOP [27].

The interpretation of the results of the current investigation is complicated. As mentioned earlier various studies have shown lower CH in PXG eyes [14, 15]. The results of our study were in favor of stiffer cornea in PXG eyes. Also, PXG compared to the POAG is more likely to progress [28]. So, other factors such as thinner lamina cribrosa and lower blood supply may be responsible for the PXG as the risk factor for glaucomatous progression [29, 30].

Our study has several limitations. First, as a major limitation, we did not recruit a control group. Comparing the corneal biomechanical parameters between POAG, PXG, and control eyes may clarify the complexities in the findings by revealing that these differences are specific to glaucoma subtypes or are a part of a broader trend. Second, there was a small sample size in each group. Recruiting a bigger sample size helps to draw more meaningful results and overcome type II error. Third, age and systemic comorbidities like diabetes mellitus alter the corneal biomechanical properties [31, 32]. Albeit there was no significant difference in age between the groups in the current investigation. Also, we excluded the patients with a history of diabetes. Fourth, topical antiglaucoma medications, e.g. prostaglandin analogs, may potentially alter corneal biomechanical properties [33]. To overcome this limitation, we only enrolled the patients with newly diagnosed glaucoma who used topical antiglaucoma medication for less than one month. Although the eyes were newly diagnosed the length of glaucomatous involvement was not clear which makes it the fifth limitation. Sixth, as the visual field data was not available at the time of study the stage of glaucomatous damage was not reported.

In conclusion, our findings were partially in favor of stiffer cornea in PXG eyes which was presented by lower A2 velocity, shorter HC deformation amplitude and deflection length, and higher SSI. Also, deflection length at both the first applanation (A1 deflection length) and highest concavity (HC deflection length) were shorter in PXG in stepwise multiple regression analysis. Albeit, other parameters did not show statistically significant differences which highlights the necessity of future studies with bigger sample sizes.