Differing Associations between Optic Nerve Head Strains and Visual Field Loss in Normal- and High-Tension Glaucoma Subjects

Abstract

PurposeTo study the associations between optic nerve head (ONH) strains under intraocular pressure (IOP) elevation with retinal sensitivity in glaucoma subjects.DesignClinic based cross-sectional study.Participants229 subjects with primary open angle glaucoma (subdivided into 115 high tension glaucoma (HTG) subjects and 114 normal tension glaucoma (NTG) subjects).MethodsFor one eye of each subject, we imaged the ONH using spectral-domain optical coherence tomography (OCT) under the following conditions: (1) primary gaze and (2) primary gaze with acute IOP elevation (to approximately 33 mmHg) achieved through ophthalmodynamometry. A 3-dimensional (3D) strain-mapping algorithm was applied to quantify IOP-induced ONH tissue strain (i.e. deformation) in each ONH. Strains in the pre-lamina tissue (PLT) and the retina, the choroid, the sclera and the lamina cribrosa (LC) were associated (using linear regression) with measures of retinal sensitivity from the 24-2 Humphrey visual field test (Carl Zeiss Meditec, Dublin, CA, USA). This was done globally, then locally according to the regionalization scheme of Garway-Heath et al.Main Outcome MeasuresAssociations between ONH strains and values of retinal sensitivity from visual field testing.ResultsFor HTG subjects, we found that (1) there were significant negative linear associations between ONH strains and retinal sensitivity (p<0.001) (on average, a 1% increase in ONH strains corresponded to a decrease in retinal sensitivity of 1.1 dB), (2) high strain regions co-localized with anatomically-mapped regions of high visual field loss, (3) the strongest negative associations were observed in the superior region and in the PLT. In contrast, for NTG subjects, no significant associations between strains and retinal sensitivity were observed except in the supero-temporal region of the LC.ConclusionWe found significant negative associations between IOP-induced ONH strains and retinal sensitivity in a relatively large glaucoma cohort. Specifically, HTG subjects who experienced higher ONH strains were more likely to exhibit lower retinal sensitivities. Interestingly, this trend was in general less pronounced in NTG subjects, which could suggest a distinct pathophysiology between the two glaucoma subtypes.

How Myopia and Glaucoma Influence the Biomechanical Susceptibility of the Optic Nerve Head

“…The errors observed here could arise from various sources such as OCT registration errors (intrinsic to the OCT machine), rotation of subjects' head during OCT acquisition, OCT speckle noise and IOP fluctuations from ocular pulsations, 73 all of which were difficult to control. However, displacement error magnitudes were still lower than the OCT voxel resolution; 20 thus, these errors should not have significantly affected our observed trends.…”

“…For each eye in the primary gaze position, we applied a constant force of 0.65 N to the temporal side of the lower eyelid using an opthalmodynamometer (ODM), as per an established protocol. 20, 21, 34 The force was applied for approximately 2 to 3 minutes throughout the OCT scan duration and varied for no more than one minute across subject. This force raised IOP to about 35 mmHg and was maintained constant.…”

“…To this end, each OCT volume under a biomechanical load (adduction, abduction, or elevated IOP) was digitally aligned with its corresponding primary gaze OCT volume using a commercial software Amira (version 2020.1, FEI, Hillsboro, Oregon, USA), as described in our previous publication. 20…”

“…34,36,37 Details of the DVC algorithm used in this study, including how the strain values are derived and the validation of our DVC algorithm were provided in our previous paper. 20 For each OCT volume, IOP-and gaze-induced effective strains were averaged across the entire ONH region within a 2,800 x 2,800 μm en-face region centered on the BMO center (Figure 1). To take into account potential variations in acute IOP elevation across eyes, the IOP-induced effective strains were normalized according to the following equation:…”

“…17 Several studies have employed biomechanical stress tests to assess the robustness of the ONH, using either IOP, or optic nerve traction as the primary mechanical stimulus (ours and others). [20][21][22][23][24][25] Previous literatures have used such tests to elucidate the role of IOP elevation or optic nerve traction in glaucoma pathogenesis, but no studies have investigated the in vivo ONH responses of a spectrum of myopic eyes under biomechanical loads. With much evidence suggesting a possible biomechanical link between glaucoma and myopia, we believe that a biomechanical stress test to tease out ONH structural robustness in myopic eyes will give us further insight into the link between the two diseases; this may also help us identify myopic individuals that are at risk of developing glaucoma.…”