A simple mathematical approach to identifying baseline predictors of the effectiveness of carbonic anhydrase inhibitors in intraocular pressure reduction.

Purpose: To identify mathematically the baseline physiological predictors of the intraocular pressure (IOP)-lowering effectiveness of topical carbonic anhydrase inhibitors (CAIs). Materials and Methods: Assuming a steady state of aqueous humor flow, mathematical equations describing IOP were formulated by incorporating related physiological variables. Global sensitivity analysis was then performed, in which all variables were varied simultaneously across their clinically reported ranges. This computational approach quantified the percentage reduction in IOP achieved by CAIs and identified the key determinants underlying variability in their effectiveness. Results: A reduction in the solute influx via active transport by the ciliary epithelium, mediated by CAIs, was positively associated with the magnitude of IOP reduction. Among the physiological parameters in this model-trabecular outflow facility, uveoscleral outflow fraction, episcleral venous pressure, mean arterial pressure, plasma protein concentration, albumin/globulin ratio, and plasma osmolarity-a higher baseline trabecular outflow facility was the strongest predictor of reduced effectiveness of CAIs, in terms of the percentage of IOP reduction. Other baseline physiological parameters had no significant effect on the effectiveness of CAIs. Conclusions: Certain patient characteristics may be associated with compromised effectiveness of CAIs in terms of percentage IOP reduction. These characteristics, potentially associated with higher trabecular outflow facility, may include a lower baseline IOP or prior use of other trabecular outflow-enhancing medications before CAI initiation. Further studies are required to validate the clinical significance of these findings.