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Editors Selection IGR 21-4

Clinical Forms of Glaucoma: Corneal Biomechanics in Pseudoexfoliation and Open-Angle Glaucoma

Comment by Cynthia Roberts on:

91065 A comparison of the corneal biomechanics in pseudoexfoliation glaucoma, primary open-angle glaucoma and healthy controls using Corvis ST, Pradhan ZS; Deshmukh S; Deshmukh S; Dixit S et al., PLoS ONE, 2020; 15: e0241296

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Although it is important to study potential biomechanical differences between pseudoexfoliation glaucoma (PXG), primary open-angle glaucoma (POAG), and healthy controls, this study fails to determine whether these differences exist or do not exist, due to an incomplete study design and lack of reporting of essential information to be able to draw meaningful conclusions.

It is well known that intraocular pressure (IOP) is the strongest predictor of deformation amplitude (DA), with multiple studies cited by the authors, and yet this was the parameter chosen for a sample size calculation. Therefore, the reported sample size would be appropriate to detect a difference in IOP between groups, but not stiffness. The dynamic response parameters strongly associated with stiffness are those describing the shape of the deformation, including deformation amplitude ratio (DARatio) and Integrated Inverse Radius (IR), neither of which were reported in this study. Stiffness Parameter at first applanation (SP-A1) has recently been shown to predict progression in glaucoma suspects,¹ but this parameter was also not included in the current study. Radius of concave curvature and peak distance can be considered shape parameters and were reported by the authors. One of these would have been more appropriate for a sample size calculation to detect a difference in stiffness. It is likely that a much greater sample size would have resulted.

The calculated sample size of 40 eyes assumed independence of the parameter on which the calculation is based. Since eyes are not independent, and the authors even state they may be correlated, at a minimum this should be 40 subjects per group for a total of 120 subjects. Yet, there were only 82 subjects enrolled, which means the study is underpowered.

The authors recognize that IOP is a confounding factor when evaluating biomechanical response, and they appropriately incorporate IOP as a co-variate in their analysis. However, they did not identify whether Goldmann Applanation Tonometry (GAT) or Corvis IOP was used as the co-variate. Also, the Corvis ST reports two IOP values, one is uncorrected, and one is biomechanically corrected (bIOP). Again, which Corvis IOP value used is not specified so one must assume the uncorrected IOP value was used. The concern is evidenced in Table 2, which shows the mean Corvs IOP is greater by about 1 mmHg in Controls, but GAT is greater by about 1 mmHg in POAG and GAT is also greater by more than 1 mmHg in PXG. The shift in the sign of the GAT-Corvis IOP error function between healthy controls and both forms of glaucoma generates suspicion that biomechanical response has been altered with disease, especially without a difference in central corneal thickness between groups.

The authors make multiple references that the lower corneal hysteresis (CH) in glaucoma that is reported in the literature is indicative of a 'weaker' cornea, which is not accurate. CH is a viscoelastic term that indicates ability to dissipate energy.² It does NOT indicate stiffness. For example, increased IOP is correlated with lower CH due to the reduced ability of the eye to dissipate energy. Higher IOP is also associated with a stiffer response due to the nonlinear properties of the cornea and sclera. In this example, lower CH is associated with a stiffer eye. Lower CH in glaucoma indicates that the glaucomatous eye is less able to dissipate energy than the healthy eye. Therefore, CH and stiffness are both important in the discussion of biomechanics in glaucoma with different interpretations.

Lower CH in glaucoma indicates that the glaucomatous eye is less able to dissipate energy than the healthy eye

Ultimately, the current study does not add to our understanding of the biomechanics in glaucoma. A larger study and inclusion of additional biomechanical parameters related to stiffness are needed in order to be conclusive.

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