The impact of ocular hemodynamics and intracranial pressure on intraocular pressure during acute gravitational changes

Abstract

Exposure to microgravity causes a bulk fluid shift toward the head, with concomitant changes in blood volume/pressure, and intraocular pressure (IOP). These and other factors, such as intracranial pressure (ICP) changes, are suspected to be involved in the degradation of visual function and ocular anatomical changes exhibited by some astronauts. This is a significant health concern. Here, we describe a lumped-parameter numerical model to simulate volume/pressure alterations in the eye during gravitational changes. The model includes the effects of blood and aqueous humor dynamics, ICP, and IOP-dependent ocular compliance. It is formulated as a series of coupled differential equations and was validated against four existing data sets on parabolic flight, body inversion, and head-down tilt (HDT). The model accurately predicted acute IOP changes in parabolic flight and HDT, and was satisfactory for the more extreme case of inversion. The short-term response to the changing gravitational field was dominated by ocular blood pressures and compliance, while longer-term responses were more dependent on aqueous humor dynamics. ICP had a negligible effect on acute IOP changes. This relatively simple numerical model shows promising predictive capability. To extend the model to more chronic conditions, additional data on longer-term autoregulation of blood and aqueous humor dynamics are needed.NEW & NOTEWORTHY A significant percentage of astronauts present anatomical changes in the posterior eye tissues after spaceflight. Hypothesized increases in ocular blood volume and intracranial pressure (ICP) in space have been considered to be likely factors. In this work, we provide a novel numerical model of the eye that incorporates ocular hemodynamics, gravitational forces, and ICP changes. We find that changes in ocular hemodynamics govern the response of intraocular pressure during acute gravitational change.

Keywords: intracranial pressure; intraocular pressure; ocular blood flow; ocular compliance; space physiology; visual impairment and intracranial pressure.

Fig. 1.

Schematic of the six-compartment lumped-parameter eye model. The model’s components are the “passive” compartment (dark gray shaded region), aqueous humor, retrobulbar subarachnoid space (rSAS), and ocular arterial, capillary, and venous blood compartments. The “globe” denotes the passive + aqueous humor + blood compartments. See text for other symbols.

Fig. 2.

Determination of globe and blood-to-globe compliance. A: pressure-volume relation for living and enucleated human eyes. [Replotted from (47), Curr Eye Res, published by Taylor & Francis, http://www.informaworld.com]. Note, we follow (47) and adjust the volume change to be zero when IOP = 5 mmHg (see text). B: compliance vs. IOP for human eyes. C_{g,in vivo} and C_g,enucleated describe the living and enucleated eye, respectively, and C_bg is the difference between the two, which is attributed to blood dynamics.

Fig. 3.

Change in anterior-posterior position of the anterior surface of the LC (y_LC) resulting from surgical lowering of intraocular pressure in acute primary angle glaucoma patients, as measured by optical coherence tomography. z_LC refers to lateral position away from the center of the LC. Error bars represent standard deviation. [Data are replotted from Park et al. (40) with permission of Association for Research in Vision and Ophthalmology from Investigative Ophthalmology, Park HY, Shin HY, Jung KI, and Park CK, vol. 55, 2014; permission conveyed through Copyright Clearance Center, Inc.].

Fig. 4.

Time histories of measured mean arterial pressure (MAP; top) and normalized gravity (denoted as G_z-level; bottom) during parabolic flight for seated subjects. Superimposed on these traces are approximate fits to the data used as input into the numerical model. The fit to MAP is piecewise linear; the fit to G_z is linear in microgravity and hypergravity, and exponential in the transition regions. [Adapted from Schlegel et al. (41)].

Fig. 5.

Time histories of measured central venous pressure (CVP; top) and gravity levels (bottom) during parabolic flight for supine subjects. Superimposed on the CVP trace is an approximate piecewise linear fit. [Adapted from Lawley et al. (28), with permission of Federation of American Societies for Experimental Biology, from FASEB J, Lawley J, Williams M, Petersen L, Zhang R, Whitworth T, and Levine BD, 29, and 2015; permission conveyed through Copyright Clearance Center, Inc.].

Fig. 6.

Predicted response of ocular pressures and volumes to parabolic flight, assuming a baseline IOP of 15 mmHg and G_z profile as in Fig. 4. P_a is specified by Eq. 20, while P_v and EVP are calculated from Eq. 22. A: IOP response when MAP varies (as per Fig. 4) or is constant at 97.5 mmHg. B: volume changes when MAP varies as per Fig. 4. Over the 1.2-min simulation, aqueous humor volume is essentially unchanged (black, short dashes), and practically all changes in globe volume (black, long dashes) are due to changes in blood volume (gray, long dashes) associated with increases in P_a and P_v. The gray shaded regions represent entry into and exit from microgravity.

Fig. 7.

Comparison of experimental data (31) and model predictions for changes in IOP during parabolic flight. The horizontal axis is the baseline IOP of the subject; the vertical axis is the change in IOP occurring during the microgravity portion of the flight. For all simulations, MAP was variable as per Fig. 4. Experimental data are represented by the black diamonds and its linear regression is the solid black line. The other black lines represent the 95% confidence interval (CI) for the data (dotted) and the regression (dashed). Model predictions are shown in solid gray. The “error bars” shown on the model predictions demonstrate the range of IOP predicted during the entire period of microgravity.

Fig. 8.

Predicted responses to head-down tilt. The tilting process was initiated at time 15 s, and was completed at 25 s, after which, the subject remained tilted for 21 min. Similar to the inversion case, there was a rapid increase in IOP upon tilt, followed by a very gradual continuing increase. The symbols are experimental IOP data (mean across all subjects) derived from Xu et al. (52); error bars are estimates of standard deviation, as described in the text. These data are for the case where P_v and EVP were determined from Eq. 24.

Fig. 9.

Predicted responses to postural inversion. The inversion process was initiated at time 15 s, and was completed at 25 s, after which the subject remained inverted for 5 min. There was a rapid jump in IOP upon inversion, as shown by the simulation (black line) and two experimental data sets (4, 14).

Fig. B1.

The dependence of the modified blood-to-globe compliance ($C_{\mathrm{bg}}^{\prime }$, Eq. B3) on the vascular transmural pressure difference in the eye (IOP − P_v), where IOP is the intraocular pressure, P_v is the venous ocular pressure. ${\text{P}}_v^{\text{ref}}$ is a reference venous pressure appropriate for the supine posture. This can be compared against the original compliance C_bg in Fig. 2B in the main article.

Fig. C1.

IOP and EVP values in human subjects at different orientations under 1 G conditions. θ is the angle between the body axis and the horizontal, i.e., sin(θ) = 1 refers to upright posture, while sin(θ) = −1 is inverted posture. Symbols and error bars are experimental data and standard error of the mean replotted from Linder et al. (30) The upper solid line is a fit to the experimental IOP data. The lower dotted line is the corresponding deduced EVP data (see text), while the lower dashed line is the EVP prediction from the hydrostatic offset Eq. 22.

Fig. C2.

Effect of hydrostatic vs. empirical description of ocular venous pressure, as compared against experimental data. EVP and P_v are calculated from the hydrostatic Eq. 20 (solid black line) and using the empirical correlation (Fig. C1, dashed black line). Data after Xu et al. (52).