Abstract
Purpose: The aim of the proposed analysis is to provide both a qualitative description and a quantitative assessment of how variations in aqueous humor (AH) flow parameters influence intraocular pressure (IOP) and the outcome of IOP-lowering medications.Methods: We developed a mathematical model that describes the steady-state value of IOP as the result of the balance between AH production and drainage. We performed stochastic simulations to assess the influence of different factors on the IOP distribution in ocular normotensive and ocular hypertensive subjects and on the IOP reduction following medications.Results: The distribution of the relative frequency of a given IOP value for ocular normotensive subjects fits a right-skewed Gaussian curve with a frequency peak of 25% at 15.13 mmHg and a skewness of 0.2, in very good agreement with the results from a population-based study on approximately 12,000 individuals. The model also shows that the outcomes of IOP-lowering treatments depend on the levels of pre-treatment IOP and blood pressure. The model predicts mean IOP reductions of 2.55 mmHg and 4.31 mmHg when the pre-treatment IOP mean values are 15.13 mmHg and 20.12 mmHg, respectively; these predictions are in qualitative and quantitative agreement with clinical findings.Conclusion: These findings may help identify patient-specific factors that influence the efficacy of IOP-lowering medications and aid the development of novel, effective, and individualized therapeutic approaches to glaucoma management.
Highlights
Aqueous humor (AH) flow plays an important role in determining the level of intraocular pressure (IOP).[1,2,3] AH production and drainage can be modulated via topical medications aimed at lowering IOP in glaucoma patients.[4]
We report in the sequel the results obtained using the polynomial chaos reduced model. This model is used to compute the IOP distribution in four different cases of clinical interest: (i) ocular normotensive healthy subjects (ONT); (ii) ocular hypertensive subjects (OHT); (iii) ONT subjects treated with IOP-lowering medications (ONTm); and (iv) OHT subjects treated with IOP-lowering medications (OHTm)
ONT subjects treated with IOP-lowering medications (ONTm) We model the effect of IOP-lowering medications by reducing the active ionic secretion by 25%, which sets the mean value of the blood/AH osmotic pressure difference to Δπs = 0.75 Δπs; the mean values of the other parameters remained at control state
Summary
Aqueous humor (AH) flow plays an important role in determining the level of intraocular pressure (IOP).[1,2,3] AH production and drainage can be modulated via topical medications aimed at lowering IOP in glaucoma patients.[4] clinical and experimental studies have elucidated some of the mechanisms of action of many IOP-lowering agents, important questions concerning the significant variability of their efficacy observed among individuals still remain unanswered.[5,6,7,8] For example, latanoprost, a prostaglandin analog (PGA), seems to induce larger IOP reductions when pre-treatment IOP is higher[7,8] and when the glaucomatous damage is at its early stages.[7] Travoprost, another PGA, seems to be more effective in lowering IOP in African American patients when compared to non-African Americans.[9] Age, gender and eye color have been suggested as potential factors influencing the IOP-lowering efficacy, but the results are not consistent among the different studies.[5,7,10,11] In addition, the circadian rhythm has been shown to alter the drug efficacy between day and night for some IOP-lowering agents but not for others.[6,12,13,14,15]
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