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RANGACHARI SESSION VIDEO

Authors :Zia S Pradhan, Shivani Dixit, Praveena Gudetti, Sathi Devi, Harsha L Rao.

ABSTRACT

Purpose: To compare the corneal biomechanical parameters between eyes with pseudoexfoliation glaucoma, pseudoexfoliation syndrome and normal eyes using Corvis ST.

Methods: This was a prospective, cross-sectional study of 142 treatment-naïve eyes which underwent Corvis ST. These included 49 normal eyes, 45 eyes with pseudoexfoliation syndrome without glaucoma (PXF), 13 eyes with pseudoexfoliation syndrome, raised intraocular pressure (IOP>21 mmHg) but no disc / visual field changes (PXF + OHT), and 35 eyes with pseudoexfoliation glaucoma (PXG). The corneal biomechanical parameters studied included corneal velocities, length of corneal applanated surface, deformation amplitude (DA), peak distance and radius of curvature. The means of the groups were compared using ANOVA and ANCOVA statistics.

Results: The 4 groups were demographically similar. The IOP was lower in the normal and PXF groups compared to the other 2 groups. The corneal pachymetry was similar across the 4 groups.The corneal biomechanical parameters compared between the 4 groups using the ANOVA statistic found the DA andcorneal velocities to be different between the groups. However, after adjusting for IOP using the ANCOVA statistic, there was no difference in any of the biomechanical parameters between the 4 groups.

Conclusion: Corneal biomechanical parameters measured on Corvis ST are not different between eyes with pseudoexfoliation syndrome and pseudoexfoliation glaucoma. This suggests that corneal biomechanics has a less important role in the diagnosis and pathogenesis of PXG since it is a high-pressure disease.

KEYWORDS: Corneal biomechanics, Pseudoexfoliation, pseudoexfoliation glaucoma

INTRODUCTION:-

Pseudoexfoliation syndrome (Pxf) is a disease of the extracellular matrix, characterized by abnormal fibrillar deposits in the anterior segment of the eye, including the lens capsule, the iris and trabecular meshwork. Deposition of this material in the trabecular meshwork, along with accumulation of extracellular matrix and pigment may obstruct the aqueous outflow and result in glaucoma. Although it is well established that eyes with Pxf have an increased risk of developing glaucoma, there in insufficient data on the factors which confer this increased risk.We hypothesized that amongst eyes with pseudoexfoliation deposits, those with weak corneal biomechanics may be at a higher risk for glaucoma.

Therefore, the aim of this study was to compare the corneal biomechanical parameters between eyes with pseudoexfoliation syndrome (PXF), pseudoexfoliation glaucoma (PXG) and normal eyes using Corvis ST.

METHODS:-

This was a prospective, observational study conducted at a tertiary eye care centre between August 2015 to January 2019. 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 Institute’s Ethics Committee.

The participants included patients with pseudoexfoliation deposits in the anterior segment of the eye (with and without glaucoma) and controls.

For the purpose of the study, pseudoexfoliation deposits were defined as:

  • the presence of whitish flakes on the anterior lens capsule in a typical distribution of a partial/complete peripheral band with or without a central disc, or
  • white material deposited on the pupillary border of the iris, or
  • uveal stage of pseudoexfoliation (pigments deposited on the anterior lens capsule in a distribution corresponding to the peripheral band with increased pigment in the anterior chamber angle).

Glaucoma was defined as characteristic optic disc changes as determined by glaucoma experts (rim notching, rim thinning, retinal nerve fibre layer defects, disc haemorrhages) with corresponding changes on optical coherence tomography (OCT) or visual fields (VF).

Based on these definitions, the study participants were divided in the following cohorts:

  1. Controls had normal anterior segment examination apart from a cataract, absence of pseudoexfoliation deposits, IOP <21 mmHg and normal posterior segment examination with non-glaucomatous optic discs, as assessed by glaucoma experts.
  2. Pseudoexfoliation syndrome (PXF) cohort had eyes with pseudoexfoliation deposits in the anterior segment with IOP <21mmHg and normal posterior segment examination with non-glaucomatous optic discs, as assessed by glaucoma experts.
  3. PXF with ocular hypertension (PXF + OHT) cohort had eyes with pseudoexfoliation deposits in the anterior segment with IOP >21 mmHg, normal posterior segment examination and no evidence of glaucoma.
  4. Pseudoexfoliation glaucoma (PXG) cohort had eyes with pseudoexfoliation deposits and glaucoma.

All participants underwent a comprehensive ocular examination, which included a detailed medical history, slit-lamp biomicroscopy (before and after pupillary dilatation), Goldmann applanation tonometry, gonioscopy, and a dilated fundus examination, following which some participants were excluded. Exclusion criteria were age less than 40 years, eyes with a history of trauma or inflammation. Patients with collagen vascular disorders and neurological diseases were not recruited. Eyes with any corneal pathology, angle closure disease or retinal pathology were also excluded. Eyes already on IOP-lowering drops were excluded. All eyes with history of any ocular surgery other than uncomplicated cataract surgery were removed from the final analysis.

All participants underwent an examination with the Corvis ST (Oculus, Wetzlar, Germany) which is a noncontract tonometer that records the entire dynamic reaction of the cornea to a fixed air-impulse. This is done using a high-speed Scheimpflug camera the details of which have been described earlier. [1] Apart from measuring the intraocular pressure and the central corneal thickness, the Corvis ST (CST) provides several corneal biomechanical parameters based on the deformation response. The air puff first 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 (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 2 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 L in mm) and velocity of the corneal apex (A2 Velocity m/s) are estimated.

All glaucoma patients and glaucoma suspects underwent VF examination using Humphrey Field analyzer II, model 720i (Zeiss Humphrey Systems, Dublin, CA), with the Swedish interactive threshold algorithm (SITA) standard 24-2 program. OCT imaging of the optic disc and peripapillary region was performed using Cirrus HD-OCT (Carl Zeiss Meditec Inc, Dublin, CA) if media clarity permitted good quality scans.

Statistical analyses were performed using Stata version 13.1 (Stata Corp, College Station, Tx) statistical software. Descriptive statistics included mean and standard deviation for continuous variables and percentages for categorical variables. Analysis of variance (ANOVA statistic) was used to evaluate the difference in means between the cohorts. Analysis of co-variance (ANCOVA) was used to compare corneal biomechanical parameters between groups after adjusting for confounders. A p value of ≤0.05 was considered statistically significant for the final analysis.

RESULTS:-

One hundred and forty-two eyes of 100 participants were included in the study. Table 1 shows that the 4 study groups were demographically similar. The clinical details are shown in Table 2. The IOP was lower in the PXF and normal groups compared to the other 2 groups. The corneal pachymetry was similar across the 4 groups. The visual field parameters were worse in the PXG group compared to the other 3 groups.

The Corvis ST measurements (Mean and SD) of the corneal biomechanical parameters are shown in Table 3. These were compared between the 4 groups using the ANOVA statistic and the DA, A1 velocity and A2 velocity were found to be different between the groups. However, previous literature has shown that corneal biomechanics is affected by age, central corneal thickness and IOP. [2,3] Since the IOP was significantly different between the groups, the analysis was performed after adjusting for IOP using the ANCOVA statistic. We then found no difference in any of the biomechanical parameters between the 4 groups as shown in Table 4.

DISCUSSION:-

Corneal biomechanics in glaucoma has been studied extensively in-vivo using the ocular response analyser (ORA) and, more recently, the Corvis ST. Apart from using these devises to understand the role of corneal biomechanics on IOP measurements, they have also been used to understand its association with the disease process in glaucoma. These studies have been done predominantly in eyes with primary open-angle glaucoma (POAG). Corneal hysteresis (CH) measured on ORA has been found to be lower in eyes with POAG compared to normal eyes. [4] Additionally, low CH has been associated with an increased risk of structural and functional progression in glaucoma. [5] Similarly, studies using Corvis ST have shown altered corneal biomechanics in POAG compared to normal eyes. [2,3,6,7]

There is limited data on the corneal biomechanics in PXG. The present study found no difference in the corneal biomechanical parameters between PXF, PXG and normal eyes using the Corvis ST. Although there are no previous studies examining the corneal biomechanics in PXF and PXG eyes using Corvis ST, there are a few studies that have evaluated CH in PXG. Ozkok et al. showed that CH was significantly lower in PXG (8.8 ± 1.4) compared to POAG (9.9±1.2). [8]Another study also showed that CH was lower in PXG compared to normal and POAG eyes. [9]

To conclude, corneal biomechanical parameters measured on Corvis ST are not different between eyes with pseudoexfoliation syndrome and pseudoexfoliation glaucoma. This suggests that corneal biomechanics has a less important role in the diagnosis and pathogenesis of PXG since it is a high-pressure disease.

REFERENCES:-

  1. Jiaxu Hong, Jianjiang Xu, Anji Wei, et al. A New Tonometer—The Corvis ST Tonometer: ClinicalComparison with Noncontact and Goldmann ApplanationTonometers. Invest Ophthalmol Vis Sci. 2013;54:659–665.
  2. Wang et al. Corneal deformation response in patients with POAG and healthy subjects analyzed by Corvis ST. IOVS 2015; 56: 5557.
  3. Asaoka et al. Relationship between Corvis ST Tonometry Measured Corneal Parameters and IOP, CCT and Corneal Curvature. PLoS ONE 10 (10): e0140385. doi:10.1371/journal.pone.0140385
  4. Deol M et al. Corneal hysteresis and its relevance to glaucoma. CurrOpinOphthalmol 2015; 26:96
  5. Medeiros FA, Meira-Freitas D, Lisboa R, et al. Corneal hysteresis as a riskfactor for glaucoma progression: a prospective longitudinal study. Ophthalmology2013; 120:1533–1540.
  6. Lei Tian, Dajiang Wang, Ying Wu, et al. Corneal biomechanical characteristics measured bythe CorVisScheimpflug technology in eyes withprimary open-angle glaucoma and normal eyes. Acta Ophthalmol 2015: doi: 10.1111/aos.12672
  7. Maria L. Salvetat, Marco Zeppieri, Claudia Tosoni, et al. Corneal Deformation Parameters Provided by the Corvis-STPachy-Tonometer in Healthy Subjectsand Glaucoma Patients. J Glaucoma 2015;24:568–574)
  8. Ozkok A, Tamcelik N, Ozdamar A, et al. Corneal viscoelastic differencesbetween pseudoexfoliative glaucoma and primary open-angle glaucoma.J Glaucoma 2013; 22:740–745.
  9. Ayala M. Corneal hysteresis in normal subjects and in patients with primaryopen-angle glaucoma and pseudoexfoliation glaucoma. Ophthalmic Res2011; 46:187–191.

TABLES

Table 1: Demographic data of study participants

Normal PXF PXF + OHT PXG P VALUE
No. of eyes 49 45 13 35
Mean Age (SD) /years 64.3 (12) 68.3 (7) 67.2 (7) 67.9 (8) 0.31
No. of males (%) 23 (67) 19 (61)  5 (50) 14 (56) 0.70
No. of Diabetics 12 (35) 11 (35) 3 (30) 7 (28) 0.92

Table 2: Clinical data of study participants

Normal PXF PXF + OHT PXG P VALUE
Mean IOP GAT /mmHg 15.9 (3) 16.5 (3) 24.5 (3) 25.7 (7) 0.0001
Mean IOP Corvis /mmHg 17.3 (3) 17.7 (3) 22.5 (4) 24.7 (8) 0.0001
Mean CCT (SD) /µ 534 (37) 533 (45) 548 (51) 529 (34) 0.53
Mean MD (SD) /dB -3.3 (4) -1.3 (2) -3.0 (3) -13.4 (10) 0.0001
Mean VFI (SD) / % 94.5 (9) 97.3 (2) 92.8 (6) 63.5 (34) 0.0003

Table 3: Comparison of corneal biomechanical parameters derived from Corvis ST between the 4 groups using ANOVA statistics

Normal PXF PXF + OHT PXG P VALUE
A1 length /mm 1.87(0.2) 1.82 (0.2) 1.92 (0.2) 1.91 (0.3) 0.33
A1 velocity /ms-1 0.14 (0.02) 0.15 (0.02) 0.13 (0.02) 0.12 (0.03) 0.003
Def Amplitude /mm 1.11 (0.14) 1.09 (0.12) 0.93 (0.14) 0.90 (0.19) <0.001
Peak distance /mm 4.18 (1.3) 3.88 (1.2) 3.73 (1.0) 3.71 (1.1) 0.31
Radius of Curvature /mm 7.07 (0.88) 7.01 (0.86) 7.4 (0.88) 7.5 (1.4) 0.16
A2 length /mm 1.81 (0.36) 1.83 (0.36) 1.85 (0.39) 1.92 (0.36) 0.56
A2 Velocity/ms-1 -0.39(0.18) -0.37 (0.10) -0.28 (0.08) -0.27 (0.10) 0.0004

Table 4: Comparison of corneal biomechanical parameters derived from Corvis ST between the 4 groups after adjusting for the difference in intraocular pressure using ANCOVA statistic

Normal PXF PXF + OHT PXG P VALUE
A1 length /mm 1.92(0.03) 1.87 (0.03) 1.83 (0.06) 1.80 (0.04) 0.24
A1 velocity /ms-1 1.13(0.03) 1.14 (0.03) 1.15 (0.06) 1.14 (0.04) 0.23
Def Amplitude /mm 1.02 (0.02) 1.02 (0.02) 1.06 (0.02) 1.06 (0.03) 0.54
Peak distance /mm 3.9 (0.18) 3.7 (0.18) 4.1 (0.3) 4.1 (0.2) 0.48
Radius of Curvature /mm 7.2 (0.2) 7.1(0.2) 7.2 (0.2) 7.2 (0.3) 0.98
A2 length /mm 1.90 (0.05) 1.91 (0.05) 1.71 (0.10) 1.74 (0.07) 0.25
A2 Velocity/ms-1 -0.36(0.02) -0.34(0.02) -0.34 (0.03) -0.33 (0.04) 0.91

 

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