This study aimed to investigate histologic changes of trabecular meshwork (TM) in normal-tension glaucoma (NTG) and determine whether trabeculectomy specimens from NTG patients can serve as normal controls for analyzing other types of high-tension glaucoma using TM analysis software (TMAS) based on light microscopy.

Prospective comparative case series.

Trabeculectomy specimens from 23 NTG patients (65.4±9.2 years old), including associated clinical data, as well as 12 autopsy eyes (66±11.2 years old, P = .86), were retrospectively analyzed. Light microscopy images of trabeculectomy specimens were captured, and TM spaces, TM cellularity, and pigment granule accumulation in TM were evaluated using TMAS. TMAS1 assessed regional variations in the juxtacanalicular tissue (JCT), corneoscleral meshwork (CSM), and uveal meshwork (UVM) by dividing these regions into anterior, middle, and posterior segments, whereas TMAS2 measured the total areas of JCT, CSM, and UVM.

Intraocular pressure, outflow facility, axial length, periods of topical glaucoma medication, spaces in JCT, corneoscleral and uveal meshwork, trabecular meshwork cellularity, and pigment granule accumulation were measured.

NTG patients exhibited features such as myopia (–5.5±4.7 D), long axial length (26±2.5 mm), advanced stage of visual field defect (Aulhorn-Greve classification: stage 4.6±0.9), prolonged use of topical glaucoma medications (13.0±5.0 years), and subnormal outflow facility (0.24±0.09 µL/min/mm Hg). TM space measurements showed no notable differences between TMAS1 and TMAS2 in NTG eyes. However, TMAS2 detected a significantly greater reduction in TM spaces (JCT: P < .001, CSM: P < .001) and a lower TM cell count (JCT: P = .029, UVM: P < .001) in NTG specimens compared with autopsy eyes.

NTG should not be regarded as a normal variant, as structural abnormalities are present despite normal intraocular pressure. These abnormalities may arise from subtle irregularities in the TM, which may be less pronounced than those in high-tension primary open-angle glaucoma, prolonged use of topical glaucoma medications, or other contributing factors such as increased axial length. TMAS2 has proven to be a useful instrument for assessing not only NTG but also a potential means of identifying different types of high-tension glaucoma through the analysis of trabeculectomy specimens.