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Editors Selection IGR 24-1

Anatomical Structures: Do laminar biomechanics depend on Ethnicity?

Comment by Michael Girard on:

80516 Racioethnic differences in the biomechanical response of the lamina cribrosa, Behkam R; Kollech HG; Jana A et al., Acta biomaterialia, 2019; 88: 131-140

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Individuals of African descent (AD) have been shown to be three to four times more susceptible to develop primary open-angle glaucoma (POAG) than individuals of European descent (ED). A high POAG prevalence has also been ob-served in individuals of Hispanic ethnicity (HE). While several explanations have been provided, including differences in blood pressure, in optic nerve blood flow, and in optic nerve head (ONH) anatomy, we have yet to fully grasp the underlying mechanisms in the ethnic groups that are at higher risk of developing glaucoma. Recently, several research groups have hypothesized that it is not only differences in ONH anatomy, but also differences in ONH biomechanical behavior that may provide increased susceptibility to glaucoma.

To this end, the proposed study aimed to assess the biomechanics of ONH tissues in human donor eyes from three ethnic groups (AD, ED, and HE). The authors developed a custom device to pressurize the posterior pole, centered on the ONH, in an ex-vivo setting. The lamina cribrosa (LC) - a critical biomechanical structure of the ONH - was then imaged using second harmonic generation microscopy and local LC strains (deformations) were mapped in 3D for various levels of IOP (from five to 45 mmHg). The authors were able to map IOP-induced LC strains in 24 healthy eyes, including nine AD, six ED, and nine HE eyes, and found significant differences in the biomechanical behavior of the LC across ethnic groups. Notably, ED eyes exhibited significantly higher LC strains in the superior quadrant, and interestingly LC strains in ED eyes were considerably less heterogeneous than those observed in AD and HE eyes, suggesting different underlying connective tissue microarchitecture across these groups. This work provides an important preliminary step to understand how ethnic variations may influence ONH biomechanics and may predispose certain eyes to develop glaucoma.

The work is not yet able to conclude whether a specific strain pattern for any given ethnicity would be responsible for the development and progression and glaucoma

However, the work is not yet able to conclude whether a specific strain pattern for any given ethnicity would be responsible for the development and progression and glaucoma. Further ex-vivo and in-vivo studies are warranted. Specifically, the authors would benefit from adding more samples to their study (including glaucoma eyes), as less than ten eyes per group remains on the low side. In addition, since age varied between 53 and 95 years, and is an important factor affecting tissue biomechanics, age-matched groups should also be considered.

Finally, it is also worth noting that the results may not be directly comparable with in-vivo data that were, for example, obtained in Fazio et al.¹ Performing ex-vivo experiments offers a nicely controlled environment where a single load (here IOP) can be studied and varied (here between five and 45 mmHg) independently of all other loads. This has value to better understand the physics of the eye across ethnicities, but this cannot be taken as fully representative of an in-vivo setting. Indeed, in vivo, multiple loads act simultaneously on the ONH including, but not limited to: IOP, the cerebrospinal fluid pressure, the orbital fat pressure, choroidal swelling during the cardiac cycle, optic nerve traction during eye movements, and the ciliary muscle pulling force transmitted to the ONH via the choroid and Bruch's membrane during accommodation. In-vivo ONH strains are thus more representative of what ONH cells directly experience. However, it is important to keep in mind that knowledge from both in-vivo and ex-vivo strain mapping studies will ultimately be needed to create the best clinical tool to predict visual field progression.

In-vivo ONH strains are thus more representative of what ONH cells directly experience

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