Intraocular pressure variation from ocular compression in low and high myopia

doi:10.21203/rs.3.rs-2003273/v1

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Intraocular pressure variation from ocular compression in low and high myopia

https://doi.org/10.21203/rs.3.rs-2003273/v1

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Introduction

Recent studies have monitored lamina cribrosa deformation using optical coherence tomography during ocular compression. Intraocular pressure (IOP) was measured only once immediately after ocular compression. This study aimed to evaluate IOP changes during and after ocular compression and compare the differences between low and high myopia.

Methods

Two groups of young, healthy adults were age-matched and underwent ocular compression. IOP was measured at baseline and monitored during a 2-min ocular compression followed by a 10-min recovery phase. Rebound tonometry was used and applied at 30-s intervals.

Results

Thirty low and 30 high myopes (60 right eyes) were included in the study. They had similar baseline IOP at 14.9mmHg. The immediate IOP rise was 10.2mmHg and 10.3mmHg from baseline in each group, respectively. Low myopes had faster IOP decay during ocular compression at -3.24mmHg/min than high myopes at -2.58mmHg/min (p = 0.0528). The IOP dropped below the baseline level after the release of the compressive force. Low myopes had IOP that returned to baseline levels faster (at 360 s) than high myopes (at 510 s).

Conclusion

Measuring IOP once immediately after ocular compression could under-estimate the effect of IOP increase on lamina cribrosa deformation. The difference in IOP dynamics from ocular compression between low and high myopia may be used to reflect aqueous humour outflow facilities.

IOP

ocular compression

aqueous dynamic

Myopia is a known risk factor for high-pressure glaucoma.^1–3 Lamina cribrosa (LC) is the site of glaucoma damage.^4,5 Studies on LC can enrich our understanding of the pathophysiology of glaucoma. With the development of spectral-domain optical coherence tomography (SD-OCT), the morphology of LC can be studied, including the anterior and posterior LC surfaces, as well as its thickness. Acute intraocular pressure (IOP) elevation through ocular compression is commonly used to study the biomechanical properties of the LC in glaucoma research.^6–9 Any morphological changes in the LC were monitored before and during ocular compression. Previous studies have measured the IOP immediately after ocular compression only. Investigators assumed IOP to be constant during ocular compression.^8,9

Our recent pilot study demonstrated an IOP drop during a 1-min ocular compression. IOP recovery after ocular compression took longer than 5 min (Lam, AKC & Xu, FY. IOVS 2020;61:ARVO E-Abstract 4627). Both IOP drop and recovery are related to aqueous humour dynamics, which requires further investigation.

Since high myopia is a risk factor for primary open-angle glaucoma (POAG), the evaluation of LC has important implications for understanding the correlation between high myopia and POAG.¹⁰ It is inappropriate to assume a constant IOP when the LC is scanned using OCT during ocular compression, especially when OCT scanning lasts for ≥2 min.⁹ In the current study, IOP was monitored during a 2-min ocular compression, and the IOP recovery phase was monitored after the release of the compressive force. We speculated that there was a continuous drop in IOP during ocular compression. We further investigated whether IOP variation could be different between eyes with low and high myopia.

Healthy low and high myopes were recruited from the university campus by hanging posters at various places. Written informed consent was obtained from each participant before ophthalmic assessment was initiated. The present study adhered to the tenets of the Declaration of Helsinki and was approved by the Institutional Review Board of The Hong Kong Polytechnic University (reference: HSEARS20200211003).

Low myopes should have spherical equivalent (sphere plus half the amount of negative cylinder) ≤ -0.50D up to -3.00D. High myopes had spherical equivalent ≤ -6.00D. Distance visual acuity was at least logMAR 0.00 in each eye. Participants with history of ocular disease, ocular trauma or surgery, who were currently taking any medication, were excluded. Participant with an IOP ≥ 21mmHg at baseline were also excluded. The workflow included rebound tonometry at baseline, followed by acute IOP elevation for 2 min through ocular compression. Tonometry was conducted at 30-s intervals during ocular compression and during a 10-min recovery phase. Only the right eye was used in this experiment.

Ocular compression

A phosphene pressure tonometer (Proview) was used to increase the IOP. The Proview was designed for patients to monitor IOP by themselves.¹¹ The spring compression device consists of a spring-loaded plunger with a flat applicator. The Proview was modified with an extension long enough for easy ocular compression (Fig. 1). Another modification was to incorporate a circuit to provide an audible sound whenever a pre-set compressive force was reached. In this study, the pre-set force was approximately 47g. Ocular compression was performed by pressing the lower eyelid. Figure 2 shows the mounting of the Proview at a chin-rest while the subject maintained fixation on a distant object. A rebound tonometer was mounted in front of the right eye.

Monitoring of IOP

Baseline IOP was measured using a rebound tonometer (iCare TA01i, Tiolat, Helsinki, Finland) at 30-s intervals for 1 min. Each measurement set consisted of six consecutive readings. An average was generated automatically, with an error bar indicating the variation within the six readings. Whenever the among the six readings was significant, a new set was obtained to ensure accuracy. The baseline IOP (B-IOP) before ocular compression was the average of three measurements within 1 min. IOP during and after ocular compression was also monitored at 30-s intervals. For 2 min of ocular compression, there were five IOP measurements: C-0, C-30, C-60-, C-90, and C-120. During a 10-min recovery phase, 21 measurements were made: R-0 to R-600.

Statistical analysis

Test-retest repeatability (TRR) of rebound tonometry was calculated as 2.77 times within-subject standard deviation (S_W) from the three IOP measurements before ocular compression. The difference between B-IOP and C-0 was calculated. It should be greater than 2.77 S_W or the subject was excluded to ensure significant IOP elevation from ocular compression. The IOP change for the 2-min ocular compression was fitted using linear regression. IOP during the recovery phase (R-0 to R-600) was compared with B-IOP using parametric or non-parametric analysis whenever appropriate to determine the time point at which IOP returned to the baseline level. The IOP dynamics of the two refractive groups were compared.

The TRR of rebound tonometry at the baseline was 2.4mmHg. Thirty low myopes and 30 high myopes were recruited and all of them had IOP elevation at C-0 greater than 2.4mmHg when compared with the B-IOP. Table 1 shows the demographic characteristics of the two groups. The low and high myopic groups had similar age (23.4 years and 24.3 years, respectively, Mann-Whitney U test, p = 0.153), and baseline IOP (14.9mmHg and 14.9mmHg, respectively, unpaired t-test, p = 0.988). The immediate IOP elevation (C-0 minus B-IOP) was similar between the low and high myopic groups (10.3mmHg and 10.2mmHg, unpaired t-test, p = 0.960). Figure 3 shows the IOP at each time point from the baseline, during ocular compression, and during the recovery phase. During ocular compression, low myopes demonstrated an IOP decline of -3.24mmHg/min (95% confidence interval, -3.84 to -2.64mmHg/min). High myopes had a slower IOP decline rate at -2.58mmHg/min (95% confidence interval, -3.24 to -1.98mmHg/min). The difference in the slopes was close to significant (t=-2.407, p = 0.0528). It took 360 s (post-hoc test after Friedman test) for low myopes to have IOP sustainably returned to baseline levels after ocular compression, while high myopes spent 510 s (post hoc test after repeated measures analysis of variance).

Table 1

Baseline information of the two refractive groups.
Parameters	Low myopes	High myopes	p-value
Age (years)	23.4 ± 3.0	23.9 ± 2.8	0.153*
Spherical equivalent (diopter)	-1.74 ± 0.82	-7.89 ± 1.39	< 0.001*
Baseline IOP (mmHg)	14.9 ± 2.8	14.9 ± 2.8	0.988^#
Immediate IOP rise (mmHg)	10.3 ± 4.7	10.2 ± 3.9	0.960^#
IOP: intraocular pressure
*Mann-Whitney test
^#unpaired t-test

We found that IOP was not stable during ocular compression. It is incorrect to assume a stable IOP when performing OCT during ocular compression.^6,9 To better estimate the IOP increase during OCT, investigators should measure IOP again at the end of OCT because this IOP is lower. The average IOP values from these two measurements (initial and final) could provide better IOP estimation. For example, if IOP is measured as 50mmHg immediately after ocular compression, IOP is 40mmHg at the end of OCT. Using an average of these two values, that is 45mmHg, could better relate the compression effect on the LC. In this example, deformation of the LC could have already been achieved at 45mmHg. Relying solely on one IOP measurement at the initial stage (i.e. 50mmHg) would under-estimate the effect of IOP on LC deformation.

During the course of this project, Chen et al.¹² reported a decline in IOP during a 4-min ocular compression. The dimensions of the Schlemm’s canal were monitored using SD-OCT. The Schlemm’s canal cross-sectional area was reduced from 5440.0µm² at baseline to 3947.6µm² at 38.6mmHg during ocular compression. The collapse of the Schlemm’s canal was positively associated with reduced aqueous outflow facilities, which caused an IOP increase. There was no significant difference in the trabecular meshwork thickness.

We found a faster IOP drop during ocular compression in low myopes than in high myopes. The differences approached statistical significance. Johnstone¹³ suggested that IOP rise induced by ocular compression through ophthalmodynamometry or the water drinking test was regulated by pulsatile aqueous outflow. From the current study, it appears that low myopes have better regulation of aqueous outflow and IOP during ocular compression. When the compressive force was released, the IOP dropped below the baseline level and gradually returned to the baseline IOP. Lower myopes had a faster recovery rate than high myopes. Johnstone¹³ also suggested that pulsatile aqueous flow could stop when the IOP is reduced below its physiological point.

It would be interesting to observe different IOP profiles between the two myopic groups. A recent study demonstrated genetic influences between high myopia and POAG as well as the causal effect of myopia on POAG.¹⁴ The study of aqueous humour dynamics would be useful to better understand the pathophysiology of POAG in patients with high myopia. If high myope has poor IOP regulation, it could be a risk factor for the development of glaucoma.

Can IOP variation during and after ocular compression be used as an indicator of aqueous outflow facilities? Aqueous outflow facilities are not routinely measured in clinical practice. It requires placing a weighted tonometer on the eye, such as the Schiötz tonometer. A pneumatonometer is also used and rate of IOP recovery is measured for several minutes while maintaining the pneumatonometer on the eye.¹⁵ The aqueous outflow facility coefficient C can be determined using the following equation:

F = (P_IOP − P_EPI ) × C + F_UVEO

where F is the aqueous perfusion rate, P_IOP is the IOP, P_EPI is the episcleral venous pressure, and F_UVEO is the uveoscleral outflow. Aqueous perfusion rate demonstrated diurnal variation and also an age-related reduction.¹⁶

Clinically, the water drinking test may indicate outflow facility.¹⁷ Fluorophotometry is a more common method for measuring outflow facilities. A high dose of fluorescein is applied topically at mid-night, followed by continuous fluorophotometric measurements the following morning.^18,19 This method is still used in research work nowadays but is difficult to conduct routinely in clinical practice.^20,21 A more invasive method for measuring outflow requires a manometric tonographic technique. Karyotakis et al.²² found that the outflow coefficient decreased with a high IOP. The aqueous outflow facility coefficient at 40mmHg was more than double that at 20mmHg. We further evaluated the usefulness of ocular compression and IOP changes in indicating aqueous outflow facilities in another study.

Our study has several limitations. Our sample size was small and only healthy young adults were included. Older adults, particularly POAG patients, should be recruited in future study. Measurement of the Schlemm’s canal was not included and the change of Schlemm’s canal dimension and IOP variation was based on the previous study by Chen et al.¹²

Investigators using ocular compression to study LC shape should measure IOP at both the initial and final stages of ocular compression.

Acknowledgement

We would like to thank Editage (www.editage.com) for English language editing.

Data availability

Datasets used or analysed during the present study are available from the corresponding author on reasonable request.

Disclosures

The authors declare no competing interests.

Author contributions

F.X. and A.K.C.L designed the study, F.X. performed the experiment, F.X. and A.K.C.L analysed the data, F.X. and A.K.C.L wrote and edited the manuscript.

Marcus, M. W., de Vries, M. M., Junoy Montolio, F. G. & Jansonius, N. M. Myopia as a risk factor for open-angle glaucoma: a systematic review and meta-analysis. Ophthalmology 118, 1989–1994.e1982, doi:10.1016/j.ophtha.2011.03.012 (2011).
Chon, B., Qiu, M. & Lin, S. C. Myopia and glaucoma in the South Korean population. Invest Ophthalmol Vis Sci 54, 6570–6577, doi:10.1167/iovs.13-12173 (2013).
Shen, L. et al. The Association of Refractive Error with Glaucoma in a Multiethnic Population. Ophthalmology 123, 92–101, doi:10.1016/j.ophtha.2015.07.002 (2016).
Quigley, H. A., Addicks, E. M., Green, W. R. & Maumenee, A. E. Optic nerve damage in human glaucoma. II. The site of injury and susceptibility to damage. Arch Ophthalmol 99, 635–649, doi:10.1001/archopht.1981.03930010635009 (1981).
Hernandez, M. R. & Ye, H. Glaucoma: changes in extracellular matrix in the optic nerve head. Ann Med 25, 309–315, doi:10.3109/07853899309147290 (1993).
Tun, T. A. et al. Shape Changes of the Anterior Lamina Cribrosa in Normal, Ocular Hypertensive, and Glaucomatous Eyes Following Acute Intraocular Pressure Elevation. Invest Ophthalmol Vis Sci 57, 4869–4877, doi:10.1167/iovs.16-19753 (2016).
Beotra, M. R. et al. In Vivo Three-Dimensional Lamina Cribrosa Strains in Healthy, Ocular Hypertensive, and Glaucoma Eyes Following Acute Intraocular Pressure Elevation. Invest Ophthalmol Vis Sci 59, 260–272, doi:10.1167/iovs.17-21982 (2018).
Tun, T. A. et al. Association of Functional Loss With the Biomechanical Response of the Optic Nerve Head to Acute Transient Intraocular Pressure Elevations. JAMA Ophthalmol 136, 184–192, doi:10.1001/jamaophthalmol.2017.6111 (2018).
Zhang, L. et al. In Vivo Measurements of Prelamina and Lamina Cribrosa Biomechanical Properties in Humans. Invest Ophthalmol Vis Sci 61, 27, doi:10.1167/iovs.61.3.27 (2020).
Shoji, T. et al. Correlation between lamina cribrosa tilt angles, myopia and glaucoma using OCT with a wide bandwidth femtosecond mode-locked laser. PLoS One 9, e116305, doi:10.1371/journal.pone.0116305 (2014).
Lam, D. S. et al. Pressure phosphene self-tonometry: a comparison with goldmann tonometry in glaucoma patients. Invest Ophthalmol Vis Sci 45, 3131–3136, doi:10.1167/iovs.04-0115 (2004).
Chen, W. et al. Acute Effects of Intraocular Pressure-Induced Changes in Schlemm's Canal Morphology on Outflow Facility in Healthy Human Eyes. Invest Ophthalmol Vis Sci 61, 36, doi:10.1167/iovs.61.8.36 (2020).
Johnstone, M. A. Intraocular pressure regulation: findings of pulse-dependent trabecular meshwork motion lead to unifying concepts of intraocular pressure homeostasis. J Ocul Pharmacol Ther 30, 88–93, doi:10.1089/jop.2013.0224 (2014).
Choquet, H. et al. Association Between Myopic Refractive Error and Primary Open-Angle Glaucoma: A 2-Sample Mendelian Randomization Study. JAMA Ophthalmol, doi:10.1001/jamaophthalmol.2022.2762 (2022).
Brubaker, R. F. Goldmann's equation and clinical measures of aqueous dynamics. Exp Eye Res 78, 633–637, doi:10.1016/j.exer.2003.07.002 (2004).
Brubaker, R. F. Flow of aqueous humor in humans [The Friedenwald Lecture]. Invest Ophthalmol Vis Sci 32, 3145–3166 (1991).
Danesh-Meyer, H. V. The water-drinking test: the elegance of simplicity. Clin Exp Ophthalmol 36, 301–303, doi:10.1111/j.1442-9071.2008.01782.x (2008).
Brubaker, R. F. & McLaren, J. W. Uses of fluorophotometry in glaucoma research. Ophthalmology 92, 884–890, doi:10.1016/s0161-6420(85)33939-8 (1985).
Hayashi, M., Yablonski, M. E. & Novack, G. D. Trabecular outflow facility determined by fluorophotometry in human subjects. Exp Eye Res 48, 621–625, doi:10.1016/0014-4835(89)90004-3 (1989).
Guo, T. et al. Aqueous humour dynamics and biometrics in the ageing Chinese eye. Br J Ophthalmol 101, 1290–1296, doi:10.1136/bjophthalmol-2016-309883 (2017).
Alaghband, P. et al. The Effect of High-Intensity Focused Ultrasound on Aqueous Humor Dynamics in Patients with Glaucoma. Ophthalmol Glaucoma 3, 122–129, doi:10.1016/j.ogla.2019.12.002 (2020).
Karyotakis, N. G., Ginis, H. S., Dastiridou, A. I., Tsilimbaris, M. K. & Pallikaris, I. G. Manometric measurement of the outflow facility in the living human eye and its dependence on intraocular pressure. Acta Ophthalmol 93, e343-348, doi:10.1111/aos.12652 (2015).

No competing interests reported.

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Intraocular pressure variation from ocular compression in low and high myopia

Status:

Version 1

Abstract

Introduction

Methods

Results

Conclusion

Figures

Introduction

Methods

Ocular compression

Monitoring of IOP

Statistical analysis

Results

Discussion

Declarations

References

Additional Declarations

Status:

Version 1