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Editors Selection IGR 23-4

Basic Science: Modelling the biomechanics of the ONH and cornea

Arthur Sit

Comment by Arthur Sit on:

107711 The Effects of Negative Periocular Pressure on Biomechanics of the Optic Nerve Head and Cornea: A Computational Modeling Study, Safa BN; Bleeker A; Bleeker A; Bleeker A; Berdahl JP et al., Translational vision science & technology, 2023; 12: 5


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The Multi-Pressure Dial system (MPD; Equinox Ophthalmic, Inc., Newport Beach, CA) is an investigational device that produces a vacuum in the periocular region as a potential treatment for patients with glaucoma by purportedly reducing intraocular pressure (IOP). Previous research from this group using analytical mathematical models predicted an increase in ocular volume with application of negative periocular pressure (NPP), which would presumably lead to tissue distension (strain) similar to what would occur with elevation of IOP.1 This leads to important questions about how IOP should be defined. The authors define IOP as the pressure difference between the intraocular environment and the rest of the body. However, this is very different from the conventional definition of IOP as transcorneal pressure, which reflects the difference in pressure between the intraocular environment and the air surrounding the eye. If pressure is decreased uniformly around the eye, tissue strain would be expected to increase throughout the eye, equivalent to an increase in IOP. In this case, transcorneal pressure would be the correct definition of IOP. However, the current study from Safa et al. suggests that the effects of NPP may be more complex, causing different effects on the anterior segment versus the optic nerve head. In this case, the appropriate definition of IOP under NPP becomes more difficult.

This study investigated the effects of NPP on the biomechanics of the anterior segment and optic nerve head. The authors developed a finite element model based on existing models and published values for tissue properties. The model was optimized and validated by comparison with published ocular compliance data. Tensile and compressive strains were analyzed in four regions: lamina cribrosa (LC), prelaminar tissue (PLT), limbus, and corneal apex. A robust range of parameters were analyzed in four different simulations: 1. Normotensive case with IOP of 15.8 mmHg (baseline); 2. Goggle case with -7.9 mmHg NPP applied; 3. Hypertensive case with IOP of 31.6 mmHg; and 4. IOP fixed case with NPP applied but a constant IOP of 15.8 mmHg. They found that the hypertensive case resulted in markedly increased tensile strain in all four regions assessed compared to baseline. In contrast, application of NPP (cases 2 and 4) resulted in increased corneal and limbus tensile strain (although less than the hypertensive case) but decreased tensile strain in the PLT and LC suggesting a beneficial effect in the optic nerve head. The effect of different NPP distributions was also assessed, including vacuum linearly decreasing from the corneal apex to the optic nerve, vacuum only at the anterior segment, and vacuum uniform from the apex to the anterior margin of the peripapillary sclera. None of these resulted in significant differences in outcomes.

The authors are to be commended for this thorough study examining the effects of NPP on ocular tissue biomechanics. Boundary conditions are key determinants of results from finite element analysis and the authors have examined a wide range of conditions. However, one critical boundary condition that was kept constant in all the simulations was retrolaminar tissue pressure (RLTP). In their simulations, LC tensile strain increased when translaminar pressure difference (TLPD) increased (Hypertensive case), decreased when TLPD decreased (Goggle case), and was essentially unchanged when TLPD was unchanged (IOP fixed case). If RLTP was not constant but instead decreases due to NPP, then any potential beneficial effect on PLT and LC strain may be reduced or even adversely affected due to increased TLPD.

One argument for not varying RLTP could be that CSF pressure is determined by intracranial pressure, which would not be affected by NPP. However, the relationship between intracranial pressure and optic nerve CSF pressure is complex, particularly in glaucoma patients. Morgan et al. previously demonstrated that the translaminar pressure gradient is no longer dependent on CSF pressure when CSF pressure drops below a threshold.2 Further, CSF flow in the optic nerve appears to be impaired in normal tension glaucoma patients.3,4 Another argument could be that NPP does not affect peripapillary pressure. Shafer et al. investigated the effect of NPP on retrobulbar pressure in human cadavers.5 While there was no immediate change in retrobulbar pressure with application of the vacuum, there was a gradual decrease in pressure with extended application in one of the two eyes studied. Further, cadaver models cannot fully replicate the complexity of a living eye with changes in ocular and periocular blood flow resulting from application of vacuum. Regardless of the limitations, the authors have produced a thought-provoking study highlighting the complexity of changes that occur with NPP. Further studies are required to model the changes that occur in eyes with a dynamic retrolaminar tissue pressure under negative periocular pressure and explore the changes that occur in living human eyes.

References

  1. Ethier CR, Yoo P, Berdahl JP. The effects of negative periocular pressure on intraocular pressure. Exp Eye Res. 2020;191:107928. doi: 10.1016/j. exer.2020.107928. Epub 2020 Jan 9. PMID: 31926968.
  2. Morgan WH, Yu DY, Alder VA, et al. The correlation between cerebrospinal fluid pressure and retrolaminar tissue pressure. Invest Ophthalmol Vis Sci. 1998;39(8):1419-1428. PMID: 9660490.
  3. Pircher A, Montali M, Wostyn P, et al. Impaired cerebrospinal fluid dynamics along the entire optic nerve in normal-tension glaucoma. Acta Ophthalmol. 2018;96(5):e562-e569. doi: 10.1111/aos.13647. Epub 2018 Mar 12. PMID: 29532640.
  4. Boye D, Montali M, Miller NR, et al. Flow dynamics of cerebrospinal fluid between the intracranial cavity and the subarachnoid space of the optic nerve measured with a diffusion magnetic resonance imaging sequence in patients with normal tension glaucoma. Clin Exp Ophthalmol. 2018;46(5):511-518. doi: 10.1111/ ceo.13116. Epub 2017 Dec 28. Erratum in: Clin Exp Ophthalmol. 2019;47(2):309. PMID: 29178525.
  5. Shafer B, Ferguson TJ, Chu N, Brambilla E, Yoo P. The Effect of Periocular Negative Pressure Application on Intraocular and Retrobulbar Pressure in Human Cadaver Eyes. Ophthalmol Ther. 2022;11(1):365-376. doi: 10.1007/s40123-021-00442-2. Epub 2021 Dec 15. PMID: 34910290; PMCID: PMC8770790.


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