The effect of intraocular pressure and intraocular pressure lowering medications on aqueous humor unconventional outflow

Abstract

Purpose : To model human ocular aqueous humor (AH) flow dynamics in response to increased trabecular meshwork (TM) resistance R_TM and treatment of topical prostaglandins.

Methods : AH dynamics is the three-process interaction represented in Fig. 1: secretion from ciliary processes; bulk flow from posterior to anterior chamber (PC, AC); drainage through conventional (ConvOP) and unconventional (UncOP) outflow pathways. Secretion is modeled by electro-osmotic-oncotic pressure gradients from ciliary capillary (CC) into PC. Bulk flow is modeled by facilities L_PC and L_AC. Drainage is modeled by facilities L_Conv and L_Unc, this latter accounting for UncOP adaptive routes (AR) through the sum of L_Unc,IOP (pressure-dependent, PD) and L_Unc,Drug (drug-dependent, DrD).

Results : Fig. 2 (left column) studies TM progressive dysregulation by increasing R_TM with respect to baseline. Panel A illustrates the beneficial effect of the PD AR (with AR) in increasing the aqueous outflow compared to the case without AR (wo AR). Comparing Panel A and B demonstrates the efficacy of the PD component of UncOP over ConvOP as R_TMincreases. Fig. 2 (right column) studies a two-week therapy of Latanoprost 0.005% (one drop/day). Similarly to Fig. 2 (left colum), Panel C shows the beneficial effect of the DrD AR in increasing the aqueous outflow compared to the case wo AR. Comparing Panel C and D indicates that the DrD AR increases the Unc outflow by 133% of its baseline value while the decrease of Conv outflow due to DrD AR is of about 4% of its baseline value.

Conclusions : A computational virtual laboratory is developed on the basis of a theoretical model of AH dynamics which accounts for pressure and drug-dependent UncOP adaptive routes. Preliminary simulation results seem to support the conjecture that the UncOP acts as a relief valve under pathological conditions of the eye. The developed computational virtual laboratory provides a quantitative tool to complement in vivo studies and help design and optimize medications for ocular diseases.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

 

Fig. 1: Electric equivalent scheme of the anterior of the eye. p_CC=25mmHg, p_ev=8mmHg, p_s=11mmHg: ciliary capillary, episcleral vein and posterior suprachoroidal pressures

 

Fig. 2: Left column: sensitivity to % increase of R_TM with respect to baseline. Right column: sensitivity to the amount of Latanoprost 0.005%.