Pulling and Tugging on the Retina: Mechanical Impact of Glaucoma Beyond the Optic Nerve Head

Abstract

Several retinal conditions have been recently revealed by optical coherence tomography (OCT) to occur more frequently in glaucoma than in healthy eyes: paravascular defects, peripapillary retinoschisis, and pseudo-cysts of the inner nuclear layer (INL). Here the clinical OCT findings described in these reports are reviewed and a framework that could explain why they are related and occur more frequently in glaucoma is proposed. Evidence suggests that these conditions all share in common a strong tendency to develop in association with severe and/or rapidly progressing disease and a likelihood of involving biomechanical forces and differential tissue deformation. Müller glia are mechanosensitive and known to react to shear and axial strain, and to participate in homeostasis of water and ion flux through the retina, and to provide spring-like capability to buffer of mechanical forces. Thus, Müller cell integrity is also likely to be involved in the development and/or response to such events. OCT has also revealed that Müller cell optical properties (scatter and attenuation) appear to be altered in at least two of these retinal conditions: peripapillary retinoschisis and pseudo-cysts of the INL. Future studies applying 3D strain mapping techniques might reveal structural changes over time (either acute or longer-term deformations) that predict the onset and location of these retinal defects and their relationship to progressive optic nerve head deformation, retinal nerve fiber layer, and retinal ganglion cell loss in glaucoma.

Association of Optic Nerve Head Prelaminar Schisis With Glaucoma

“…For example, we previously proposed that ONH prelaminar schisis may include detachment of the blood vessels and aspects of their adventitia from the glio-fibrillar meniscus of Kuhnt, the ILM of Elschnig, and in some cases also from underlying prelaminar tissue as posterior deformation of the ONH progresses -because the blood vessels are tethered throughout the retina and might thus be limited in how far posteriorly they can be displaced as "cupping" progresses. 10 We surmised this initially from scrutiny of structural OCT scans. However, Figure 7 shows an OCTangiography scan from an eye with prominent signs of ONH prelaminar schisis.…”

“…10 In that review article, we also reported several cases in which the ONH prelaminar tissue had exhibited OCT signs of "schisis" or splitting in association with variants of retinal anatomical disruption in glaucomatous eyes, such as peripapillary retinoschisis and paravascular defects. 10 While it will likely be informative to eventually determine whether there is an association between those (or other) retinal abnormalities and the ONH prelaminar schisis sign, it is more immediately important to determine if ONH prelaminar schisis occurs more frequently in glaucomatous eyes than in healthy eyes and whether its presence and/or apparent severity is associated with the degree of glaucomatous damage. Therefore, the purpose of this study was to compare the frequency of observing ONH prelaminar schisis by OCT in glaucoma and glaucoma suspect eyes versus healthy control eyes and to assess the association between ONH prelaminar schisis and other markers of glaucoma severity.…”

“…For example, we recently reviewed an array of findings from optical coherence tomography (OCT) studies, which demonstrated anatomical disruption within the retina of glaucomatous eyes, sometimes several millimeters from the ONH. 10 One potential explanation we proposed is that the mechanical forces driving ONH deformation and remodeling (e.g., in glaucoma and myopia), along with the resulting conformational changes themselves, exert an impact on distant tissue via the retinal blood vessels, internal limiting membrane (ILM) and macroglia (Müller cells). 10 In that review article, we also reported several cases in which the ONH prelaminar tissue had exhibited OCT signs of "schisis" or splitting in association with variants of retinal anatomical disruption in glaucomatous eyes, such as peripapillary retinoschisis and paravascular defects.…”

“…10 One potential explanation we proposed is that the mechanical forces driving ONH deformation and remodeling (e.g., in glaucoma and myopia), along with the resulting conformational changes themselves, exert an impact on distant tissue via the retinal blood vessels, internal limiting membrane (ILM) and macroglia (Müller cells). 10 In that review article, we also reported several cases in which the ONH prelaminar tissue had exhibited OCT signs of "schisis" or splitting in association with variants of retinal anatomical disruption in glaucomatous eyes, such as peripapillary retinoschisis and paravascular defects. 10 While it will likely be informative to eventually determine whether there is an association between those (or other) retinal abnormalities and the ONH prelaminar schisis sign, it is more immediately important to determine if ONH prelaminar schisis occurs more frequently in glaucomatous eyes than in healthy eyes and whether its presence and/or apparent severity is associated with the degree of glaucomatous damage.…”

Orbital Fat Volume After Treatment with Topical Prostaglandin Agonists

“…25,[27][28][29] Optical coherence tomography shows that when adduction exceeds 26 degrees, 30 deformations of the ON head and Bruch's membrane greatly exceed those during extreme IOP elevation, 31 or deformations recently proposed as pathological to retina. 32 The human horizontal oculomotor range is ± 55 degrees, meaning that people can maximally abduct and adduct to that angle. 33,34 Although eye movements are usually smaller during sedentary activities or when the head is restrained in the laboratory or clinic, saccades and vestibular quick phases of 25 to 45 degrees are intrinsic to the large gaze shifts that are typical when the head and body are unrestrained.…”