A Review of Corneal Biomechanics and Scleral Stiffness in Topical Prostaglandin Analog Therapy for Glaucoma

Abstract

Purpose: The mechanism of action underlying prostaglandin analog (PGA) therapy involves changes in the expression of different metalloproteases to increase permeability of the sclera and allow increased aqueous humor outflow through this alternative drainage pathway. This alteration of structure impacts cornea/scleral biomechanics and may introduce artifact into the measurement of intraocular pressure (IOP) in the clinical setting.

Methods: A literature search reviewing the impact of PGA therapy on corneal and scleral biomechanics was conducted including basic studies, clinical studies with treatment naïve patients, and a clinical study examining the cessation of PGA therapy. Additional literature including engineering texts was added for greater clarity of the concepts underlying ocular biomechanics.

Results: One study with an animal model reported significant corneal stiffening with PGA treatment. Most longitudinal clinical studies examining the effects of initiation of PGA therapy in PGA naïve subjects failed to report biomechanical parameters associated with stiffness using the Corvis ST and only included those parameters strongly influenced by IOP. One study reported a significant reduction in scleral stiffness with IOP as a co-variate, highlighting the need to account for the effects of IOP lowering when assessing clinical biomechanics. The report of cessation of PGA therapy on corneal biomechanics showed no change in corneal compensated IOP after 6 weeks, raising the question of reversibility of the PGA-induced structural alteration.

Conclusions: Given that the findings in several clinical studies may merely reflect a reduction in IOP, further studies are warranted using Corvis ST parameters associated with corneal and scleral stiffness. The gold standard for IOP measurement in the clinical setting is Goldmann applanation tonometry, a technique previously shown to be affected by corneal stiffness. Since PGA therapy has been reported to alter not only scleral biomechanics, but also corneal biomechanics, it is essential to consider alternative tonometry technologies in the clinic.

Keywords: Corneal biomechanics; Corvis ST; Ocular Response Analyzer; corneal hysteresis; intraocular pressure; prostaglandin analog.