Geometry-Based Intravitreal Pharmacokinetics: A Theoretical Pharmacokinetic Modeling Study Using Triamcinolone...

To quantify how anatomical variation in vitreous cavity volume, estimated from axial length (AL) using the VIVEX formula, influences intravitreal drug concentration, therapeutic exposure duration, and immediate intraocular pressure (IOP) dynamics under fixed-dose intravitreal therapy.

This theoretical pharmacokinetic modeling study utilized the VIVEX equation {V = (π/6) × AL³ × [0.76 + 0.012(AL - 24)]} to calculate vitreous volume (VV) for three representative eye types: small hyperopic (AL 20 mm), emmetropic (AL 23.5 mm), and large myopic (AL 30 mm). A one-compartment first-order elimination model was applied to two commonly used intravitreal agents: triamcinolone acetonide (4 mg) and vancomycin (1 mg). Primary outcomes included initial concentration (C₀), duration above therapeutic threshold (t_eff), and modeled acute IOP rise. A Monte-Carlo simulation (10,000 virtual eyes) was performed to estimate population-level variability.

Modeled VV increased from 2.98 mL (AL 20 mm) to 11.76 mL (AL 30 mm), producing an approximately fourfold difference in C₀. For triamcinolone, C₀ decreased from 1.34 to 0.34 mg/mL and t_eff decreased from 67.4 to 31.8 days (≈50% reduction). For vancomycin, C₀ decreased from 0.336 to 0.085 mg/mL and t_eff decreased from 9.1 to 6.1 days. Predicted immediate IOP elevations were ~4.3 mmHg in small eyes versus ~1.1 mmHg in large eyes. Monte Carlo analysis suggested that anatomical variability accounts for ~30% of modeled pharmacokinetic variance.

Anatomical differences in VV substantially and predictably influence intravitreal pharmacokinetics. The modeled results demonstrate that fixed intravitreal dosing leads to substantial geometry-driven differences in drug exposure across eye sizes. Fixed dosing strategies may increase peak exposure and IOP load in small eyes and shorten effective therapeutic duration in large myopic eyes. Biometry-stratified clinical studies are warranted to validate these modeling predictions and to assess their clinical relevance in intravitreal antibiotic and corticosteroid therapies.