Four-State Hemodynamic Framework for Neovascular Age-Related Macular Degeneration: Mathematical Model Integrating Vascular Permeability, Lesion Transmural Pressure, Choroidal Excess Pressure, and Wall Stability
- 1Yokohama City University
Abstract
PurposeTo apply a mathematical model integrating vascular permeability, lesion transmural pressure, choroidal excess pressure, and wall stability to incomplete fluid response and massive submacular hemorrhage in neovascular age-related macular degeneration.
MethodsPermeability was calculated from aqueous vascular endothelial growth factor (VEGF). Windkessel gave usual lesion pressure from choriocapillaris pressure and high inflow from an arterial-level puncture pressure used as a working value. Choroidal excess pressure was calculated from choroidal thickness and a pachy index as increased outflow resistance. Exudative change used a revised Starling equation scaled to early central-retinal-thickness reduction, with 40-m threshold. A relative rupture-hazard index was calculated from Laplace wall stress and wall stability. VEGF, pressures, and that reduction were from the literature. Pressure was isolated from permeability and choroidal excess.
ResultsIn the model, raising lesion pressure from choroidal-excess lesion pressure to high inflow increased untreated exudative change from 150 to 760 m. Residual under saturation was 64 m as a lower-end reference (Monte Carlo 69-286 m; median, 170) and 90 m with high-hazard choroidal excess; both above 40 m. Reducing choroidal thickness in the thickened choroidal-excess state added 13-14 m, smaller than that residual. Lowering lesion pressure from high inflow to usual lesion pressure (21 to 10 mmHg) reduced the index to 0.64 of the high-hazard reference, and to 0.34 with wall stabilization.
ConclusionLesion transmural pressure due to high inflow left residual exudation even after permeability suppression with anti-VEGF. Fluid resolution on optical coherence tomography may not parallel a reduction in the rupture-hazard index, depending on wall stability.
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BibTeX
@misc{yanagi2026fourstate,
title = {{Four-State Hemodynamic Framework for Neovascular Age-Related Macular Degeneration: Mathematical Model Integrating Vascular Permeability, Lesion Transmural Pressure, Choroidal Excess Pressure, and Wall Stability}},
author = {Y. Yanagi and S. Inoda and K. Azuma and H. Takahashi and T. Inoue and M. Mayumura-Inoue and K. Kadonosono},
howpublished = {medRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.05.26364815},
url = {https://www.medrxiv.org/content/10.64898/2026.10.05.26364815v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Four-State Hemodynamic Framework for Neovascular Age-Related Macular Degeneration: Mathematical Model Integrating Vascular Permeability, Lesion Transmural Pressure, Choroidal Excess Pressure, and Wall Stability
AU - Y. Yanagi
AU - S. Inoda
AU - K. Azuma
AU - H. Takahashi
AU - T. Inoue
AU - M. Mayumura-Inoue
AU - K. Kadonosono
PY - 2026
DA - 2026/10/05
PB - medRxiv
DO - 10.64898/2026.10.05.26364815
UR - https://www.medrxiv.org/content/10.64898/2026.10.05.26364815v1
AB - PurposeTo apply a mathematical model integrating vascular permeability, lesion transmural pressure, choroidal excess pressure, and wall stability to incomplete fluid response and massive submacular hemorrhage in neovascular age-related macular degeneration. MethodsPermeability was calculated from aqueous vascular endothelial growth factor (VEGF). Windkessel gave usual lesion pressure from choriocapillaris pressure and high inflow from an arterial-level puncture pressure used as a working value. Choroidal excess pressure was calculated from choroidal thickness and a pachy index as increased outflow resistance. Exudative change used a revised Starling equation scaled to early central-retinal-thickness reduction, with 40-m threshold. A relative rupture-hazard index was calculated from Laplace wall stress and wall stability. VEGF, pressures, and that reduction were from the literature. Pressure was isolated from permeability and choroidal excess. ResultsIn the model, raising lesion pressure from choroidal-excess lesion pressure to high inflow increased untreated exudative change from 150 to 760 m. Residual under saturation was 64 m as a lower-end reference (Monte Carlo 69-286 m; median, 170) and 90 m with high-hazard choroidal excess; both above 40 m. Reducing choroidal thickness in the thickened choroidal-excess state added 13-14 m, smaller than that residual. Lowering lesion pressure from high inflow to usual lesion pressure (21 to 10 mmHg) reduced the index to 0.64 of the high-hazard reference, and to 0.34 with wall stabilization. ConclusionLesion transmural pressure due to high inflow left residual exudation even after permeability suppression with anti-VEGF. Fluid resolution on optical coherence tomography may not parallel a reduction in the rupture-hazard index, depending on wall stability.
ER -