Which comes first: structural or functional glaucoma progression?

Abstract

Purpose : To determine the frequency by which glaucoma progression is first detected by structural change versus functional change.

Methods : A prospective longitudinal cohort study of open angle glaucoma patients was conducted. To be included in the study, patients required at least 4 study visits, which included yearly dilated eye exams, disc photography (DP), Humphrey visual field 24-2 testing (HVF), spectral domain optical coherence tomography (SD-OCT) retinal nerve fiber layer (RNFL) thickness scans, and high-density optic nerve volume SD-OCT scans (Spectralis, Heidelberg Engineering, Heidelberg, Germany), all performed on the same day. From high-density optic nerve volume scans, custom-built software calculated the minimum distance band (MDB) thickness, a three-dimensional (3D) neuroretinal rim parameter. Event-based analysis was used to classify patients as glaucoma progressors or non-glaucoma progressors. Progression by DP and HVF occurred when 3 masked glaucoma specialists unanimously concurred. Progression by RNFL and MDB thickness occurred if there was change greater than test-retest variability. Structural change occurred if there was glaucoma progression by DP, RNFL thickness, or MDB thickness. Functional change occurred if there was progression by HVF testing. Chi-square tests were used for categorical variables, and unpaired 2-tailed t-tests were used for continuous variables.

Results : One hundred twenty-four patients were followed for an average of 66.9 ± 16.4 months. Of the 124 eyes, 97 eyes were classified as glaucoma progressors. Of these, 56 (57.7%) progressed first by structural change, 27 (27.8%) progressed first by functional change, and 14 (14.4%) progressed by simultaneous structural and functional changes. The functional change cohort consisted of eyes with more advanced glaucoma at baseline compared to the structural change cohort, and this was true when glaucoma staging was assessed by both Hodapp–Anderson–Parrish criteria (22.2% versus 12.5% severe glaucoma, p=.006) and by HVF mean deviation (-8.3± 6.3 dB versus -5.6 ± 5.7 dB, p<.05).

Conclusions : Classic teaching suggests that glaucomatous structural progression precedes functional progression. In contrast, nearly one third of glaucoma progressors exhibited functional change before structural change, and functional change occurred first in patients with more advanced glaucoma or worse baseline mean deviation.

This abstract was presented at the 2023 ARVO Imaging in the Eye Conference, held in New Orleans, LA, April 21-22, 2023.