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Editors Selection IGR 21-4

Medical Treatment: Assessing PG effects on IOP

Comment by Cynthia Roberts on:

81242 Latanoprost treatment differentially affects intraocular pressure readings obtained with three different tonometers, Sánchez-Barahona C; Bolívar G; Katsanos A et al., Acta Ophthalmologica, 2019; 97: e1112-e1115

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This is a well-designed study of an important question. How much of the intraocular pressure (IOP)-reducing effect of Latanoprost is true pressure reduction, and how much is artifact from alterations in corneal biomechanical properties from the MMP activity in the corneal stroma? The authors concluded that the apparent treatment induced IOP reduction in previously naive patients differed by which tonometer was used. This is incredibly important for glaucoma specialists, since the true IOP reduction is needed to effectively manage patients. However, the conclusions of the current study provide only a part of the answer, while also raising additional questions. Only the original biomechanical parameters from the Corvis ST are used in the current analysis, and not the newest values introduced several years ago and available with all software updates. Several of these new parameters have been shown to be relatively independent from IOP.¹ This is critical when evaluating the effect of an IOP-lowering medication. Due to the nonlinear biomechanical properties of the cornea, as IOP is lowered, the mechanical stress is also lowered, and the stiffness response will be reduced. In other words, any eye with a reduction in IOP, independent of the treatment to induce it, will have a reduction in stiffness response. It requires careful analysis to separate the IOP-reducing effects from the fundamental reduction in corneal stiffness that has been shown to occur with prostaglandin use.² The Corvis ST biomechanical parameters chosen in the current study are heavily dependent on IOP, including first applanation time (AT1), second applanation time (AT2), and deformation amplitude (DA).¹ AT1 occurs when the increasing magnitude of the applied air puff reaches a point where it overcomes the resistance of the cornea to deform. The lower the IOP, the sooner this occurs. DA is also primarily a function of IOP, with greater deformation associated with lower IOP. Therefore, the only biomechanical conclusion that can be drawn from the current study is that IOP was reduced.

The newer biomechanical parameters from the Corvis ST are a function of the shape of the deformation, rather than the magnitude. Integrated Inverse Radius (mislabeled Integrated Radius on the device) has been shown to be very sensitive to small differences in stiffness.³ Inverse radius is the definition of curvature, and integrated inverse radius is the area under the concave curvature profile between first and second applanation events. This parameter is robust and avoids potential artifacts from single point terms like maximum inverse radius. DA Ratio is the ratio between central deformation amplitude and peripheral deformation amplitude, and therefore conveys shape. Both Integrated Inverse Radius and DA Ratio are related to corneal stiffness with a smaller value, or smaller change in shape, indicating greater resistance to deformation and a stiffer response. Both are also relatively independent of IOP.¹ There are also three additional metrics of stiffness, which are Stress- Strain Index (SSI)⁴ and Stiffness Parameter at first applanation (SP-A1),⁵ both related to corneal stiffness, and Stiffness Parameter at highest concavity (SP-HC)⁵ which has been shown to be related to scleral stiffness.^6,7,8 With these three metrics, a higher value indicates a stiffer response. In total, these five values would provide valuable information on changes in corneal and scleral stiffness with prostaglandin usage. The authors are encouraged to investigate these values using the data already acquired in the current population.

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