Multi-Scale Analysis of Segmental Outflow Patterns in Human Trabecular Meshwork with Changing Intraocular Pressure

Abstract

Abstract

Purpose:

Aqueous humor filtration in the trabecular meshwork is believed to be non-uniform or “segmental” such that only a fraction of trabecular meshwork is filtration-active at any given instant. The goal was to quantify the filtration-active fraction of human trabecular meshwork and to determine how filtration patterns change with outflow facility and intraocular pressure (IOP).

Methods:

Six pair of enucleated human eyes were perfused with fluorescent tracer microspheres (0.2 μm) at 7 or 30 mmHg. Tracer patterns were imaged over the “macro-scale” (0.1–10 mm) using epifluorescence microscopy and “micro-scale” (10–100 μm) using confocal microscopy. Quantitative image analysis was used to measure the tracer-labeled fraction and to examine co-localization with trabecular pigmentation and the location of collector channel ostia.

Results:

Tracer distribution was segmental over both macro-scale and micro-scale dimensions. No more than approximately one-third of the trabecular meshwork appeared to be filtration-active on the macro scale (29%±5%; mean±SD) and micro scale (21%±6%). There was weak co-localization between macro-scale tracer intensity and pigmentation (r=0.17, P=0.017), and collector channel ostia tended to coincide with regions of high macro-scale tracer intensity. Tracer patterns were relatively insensitive to changing IOP over hour-long time scales and did not correlate with outflow facility.

Conclusions:

Filtration patterns in human trabecular meshwork appear segmental over both macro-scale and micro-scale dimensions, with only approximately one-third of the trabecular meshwork actively contributing to outflow. Segmental outflow may limit the efficacy of outflow drugs by preventing delivery to non-filtering trabecular regions that may contribute the most to outflow obstruction in glaucoma.