Abstract
purpose. To determine corneal elasticity and its contribution in damping acute intraocular pressure spikes.
methods. Twenty corneas with intact scleral rims were excised from human donor eyes and mounted on an artificial anterior chamber. A watertight seal was obtained with 17 corneas. Saline was infused into the chamber at a rate of 10 mL/h, and subsequent changes in pressure were measured to generate a pressure–volume relationship. Real-time anterior segment OCT was used to measure the change in radius of curvature and corneal thickness in nine eyes.
results. The pressure-versus-volume curves of all corneal–scleral buttons were concave-up asymptotes, demonstrating elasticity. The range of the slope was 0.34 to 1.6 ± 0.29 mm Hg/μL. The mean change in the radius of curvature in the nine eyes that were visualized by optical coherence tomography (OCT) was 247 ± 106 μm (range, 168–412 μm). The OCT image was centered on the epithelial surface. In two eyes, the entire cornea was visible by OCT throughout the course of the experiment, and corneal thickness was measured and found to decrease by 116 ± 4 μm.
conclusions. Human eye bank corneas demonstrate elasticity ex vivo, with expansion and thinning in response to increases in anterior chamber pressure. These elastic properties may serve as a buffering mechanism for microvolumetric changes in the eye, thus protecting the eye from intraocular pressure surges in vivo.
The elastic characteristics of the eye were first demonstrated by several experiments conducted in the late 1800s and early 1900s in which whole globes were cannulated and slowly pressurized with saline while serial volume measurements were recorded.
1 These studies, conducted in animal models and human cadaveric eyes, demonstrated that pressure–volume curves of all eyes were asymptotic, with a concave-up shape. At low pressures, eyes are distensible and large volumes can be introduced with little change in intraocular pressure (IOP). The higher the pressure, the less distensible the eyes become, resulting in large increases in intraocular pressure from small increases in intraocular volume. Initial interest in ocular elasticity stemmed from the need to improve accuracy in tonometry measurements.
2 For any given true IOP, surface IOP measurements in rigid eyes are higher when compared to more distensible eyes.
3
Although these early studies clearly demonstrated that the eye was distensible, the common perception was that the cornea was a relatively inelastic structure and did not contribute significantly to the overall distensibility of the eye.
1 Because these studies were performed on whole globes, they did not differentiate the relative contribution to elasticity of the different sections of the ocular shell. Woo et al.
3 sectioned whole globes, performed stress-and-strain experiments on different sections, and then used the finite-element numerical method to predict pressure–volume relations. The pressure–volume curve of the anterior segment approximated the same concave-up, asymptotic shape as the original pressure–volume curves of whole globes.
1 Hollman et al.
4 examined elasticity in porcine corneas subjected to compressional and expansional deformations by using ultrasound microscopy with confocal processing to measure strain by tracking speckle in these images after deformation. Compressional and expansional deformations were found to be on the same order of magnitude, ranging from −3.5% to +3.5%. These results also correlated well with the finite element modeling.
With the introduction of refractive surgery, there has been a renewed interest in the biomechanical properties of the cornea. Recognizing that the cornea’s response to tissue ablation cannot be precisely predicted by an inelastic model, a newer model suggests that the cornea should be conceived as a series of stacked rubber bands (lamellae) with sponges between each layer (interlamellar spaces filled with extracellular matrix) (Dupps WJ, et al.
IOVS 1995;36:ARVO Abstract 3257; Veress AI, et al.
IOVS 1995;36:ARVO Abstract 3239; Dupps WJ, et al.
IOVS 1996;37:ARVO Abstract 252). The elastic model predicts the outcome of ablation more accurately and helps to explain the risk of ectasia in some corneas.
5 6 Mechanical modeling and outcomes of refractive surgery suggest that the cornea is much more elastic than Friedenwald and his contemporaries believed (Dupps WJ, et al.
IOVS 1995;36:ARVO Abstract 3257; Veress AI, et al.
IOVS 1995;36:ARVO Abstract 3239; Dupps WJ, et al.
IOVS 1996;37:ARVO Abstract 252).
1 A study directly examining the corneal contribution to ocular elasticity has not yet been reported.
An understanding of how the cornea responds to changes in intraocular pressure may also provide a better explanation of the cornea’s role in the development and progression of glaucoma. This connection was first suggested by the findings of the Ocular Hypertension Treatment Study, which showed that patients with thicker central corneas were relatively protected against the progression of glaucoma damage.
7 This study has contributed to the renewed interest in the biomechanical properties of the cornea. Congdon et al.
8 showed that lower corneal hysteresis, a measurement of corneal resistance to deformation, is associated with visual field progression. One of the purposes of our investigation was to determine whether the cornea has a direct effect on pressure modulation and whether central corneal thickness is dynamic, reflecting position on the pressure–volume curve.
Twenty human globes were acquired from the North Carolina Eye Bank. A full-thickness circumferential excision of the posterior sclera was made just anterior to the vortex veins using scissors. The vitreous, retina, uvea, and lens were removed. The remaining corneal–scleral rim was mounted on a two-port artificial anterior chamber and secured in place. The chamber was constructed of rigid plastic and stainless steel by the Ophthalmic Biophysics Department at Duke University Eye Center (Durham, NC). The volume of the chamber with the corneal–scleral shell attached was approximately 2 mL (measured by draining fluid from the chamber) but varied between globes due to the radius of curvature. All air was flushed from the system, and the pressure monitor was zeroed, while the corneal–scleral shell was soft and open to atmospheric pressure. The system was closed while the pressure remained at 0. One port was attached via rigid tubing to a microinfusion pump (KD Scientific, Holliston, MA). The other port was attached via rigid tubing to a pressure monitor (model CMS 24 Omnicare; Hewlett-Packard, Palo Alto, CA).
An infusion of physiologic saline was initiated at a rate of 10 mL/h (2.78 μL/sec). As soon as the shell became inflated and the chamber pressure began to rise, the pressure was recorded every 5 seconds. A watertight seal was achievable in 17 of 20 shells. The three shells that leaked were discarded. The infusion pump was turned off once the pressure had reached 100 mm Hg in the first eight eyes and 200 mm Hg in the next nine eyes. As a control, the experiment was also conducted three times with the chamber removed from the system and the pressure monitor connected, via the same rigid tubing, directly to the transducer. During infusion, eyes 9 to 17 were imaged with a time–domain optical coherence tomography (OCT) system designed by the Biomedical Engineering Department at Duke University.
9 OCT imaging was not conducted on the first eight eyes, because it was not available at the time of the initial experiments. Featuring a high-speed scanning delay in the reference arm based on Fourier-transform pulse-shaping technology, this system uses a high-power broadband source and real-time image-acquisition hardware to allow for video-rate image capture (32 frames per second). This allowed for a dynamic measure of the radius of curvature. In two eyes, the change in the corneal thickness was measurable because the epithelial edge and endothelial edge of the cornea were visible throughout the entire range of pressures.
The pressure–volume curves of a corneal–scleral shell have the same shape as the pressure–volume curve of a whole globe. At low pressures, relatively large volumes can be introduced without a significant increase in pressure. At higher pressures, a significant increase in pressure is noted with a small increase in volume. There are two possible mechanisms for this phenomenon. First, the cornea may act as a reservoir and absorb volume during infusion—a sponge mechanism. However, if a sponge mechanism is in effect, corneal thickness would increase with rising pressure, and we did not observe this response. Second, the cornea may be elastic and stretch in response to pressure (demonstrating expansion and compression). Microcystic edema is known to develop when the eye is subjected to prolonged high IOP. However, this study demonstrates that the cornea responds in an elastic fashion with acute increase in IOP, supporting the elastic model.
The validity of our conclusions assumes that the elasticity of the cornea accounts for the amount of volume infused. The volume may escape from the system unnoticed, through the chamber, the tubing, or the scleral rim. However, by comparing the predicted radius of curvature with the measured radius of curvature, we can be better assured that no significant volume was lost from the system. The volume of the chamber was approximately 2 mL. Therefore, the predicted radius of the chamber is based on solving for radius (
r) in the equation for half the volume of a sphere:
\[(0.5)4/3({\pi})r^{3}\ {=}\ \mathrm{volume\ of}\frac{1}{2}\mathrm{sphere}\]
and therefore
\[(0.5)4/3(3.14)r^{3}\ {=}\ 2\ \mathrm{cm}^{3}r{=}9850{\mu}\mathrm{m}.\]
If we take the average infused volume of 231 μL at 200 mm Hg, then the predicted new radius is given by the equation: (0.5)4/3(3.14)r 3 =2.23 mL; r = 10,200 μm. The predicted change in radius (Δr) = 10,200 − 9850 = 350 μm. Therefore, Δr = 350 μm. This is the inner radius, which equals the change in the outer radius plus the change in the corneal thickness (ΔT). The average measured outer Δr = 247 μm. The average measured ΔT = 110 μm. Therefore, the measured inner radius equals Δr + ΔT = 357 μm. This corresponds very closely to the predicted inner radius of 350 μm. An exact prediction is limited by the fact that the cornea may not have uniform elasticity, and the calculations are based only on the central corneal thickness.
The purpose of the study was to isolate the corneal contribution to eye elasticity, but a small scleral rim was included to mount the cornea on the chamber. OCT images demonstrate corneal contribution to elasticity, but there was not complete isolation from the noncorneal elasticity of the globe. An attempt was made to measure the elasticity of scleral shells separately. However, it was not possible to get a watertight seal secondary to the openings in the sclera where the vortex veins exit. Because the diameter at which the corneal–scleral shell was clamped was fixed and uniform, the only variation in the width of the scleral shell between eyes would be the effect of the difference in corneal diameter, which was not directly measured. The corneal diameter may be a factor in corneal elasticity and may help explain the differences in elasticity between eyes. As OCT demonstrates, corneal diameter, like central corneal thickness (CCT), is dynamic. Future studies should be conducted to include the cornea diameter versus pressure relationship and the CCT versus pressure relationship (as noted, the change in CCT was measured by OCT in two eyes).
A possible source of introduced variability in elasticity is death-to-preservation time. To minimize this effect, no corneas were included in the study that had not beem preserved within 22 hours. However, as with any cadaveric study, the question must be raised as to the applicability of this data to the living human cornea. Although, there is no way to isolate the corneal contribution to elasticity in vivo, we must still ask whether a cadaveric eye should be expected to be more or less elastic than a living eye. Viernstein and Cowan
10 compared static and dynamic measurements of the pressure–volume relationship in eyes of living and dead rabbits. For both dynamic and static measurements, the ΔP/ΔV for each pressure was higher in eyes of dead rabbits. Therefore, at least for whole rabbit eyes, cadaveric studies should underestimate compliance.
Because only the central cornea was imaged, no information was obtained regarding variations in elasticity in different sections of the cornea. Moreover, no information was obtained to delineate variations in elasticity within different layers of the cornea.
This study showed considerable variability in the elasticity of different eyes. For example, eye number 16 was relatively rigid, with a 110-μL increase in volume, increasing the pressure from 6 to 140 mm Hg. Conversely, eye 13, was relatively elastic. The same increase in volume raised the pressure from 4 mm Hg to only 25 mm Hg. This cornea accommodated a 10% increase in volume without the chamber pressure exceeding 25 mm Hg. Does this disparity in elasticity have any implications for the health of the eye? One possibility is that the damping of pressure that the cornea provides serves to protect the eye from sudden pressure spikes brought about by activities such as blinking, straining, and rubbing, which cause microvolumetric changes. If this is true, then a patient with glaucoma should have a less distensible cornea. In fact, Ridley first observed that a glaucomatous eye is less distensible than a normal eye.
11
Although we now recognize the importance of diurnal IOP variation in patient susceptibility to glaucoma damage,
12 the importance of momentary fluctuations in IOP is unclear. Testing this hypothesis is limited by the need to correlate momentary pressure changes over a long period with glaucomatous damage. However, we know that these momentary fluctuations exist. Weinreb et al.
13 demonstrated that inverting a patient to a totally dependent, head-down position will raise the average pressure from 16.8 ± 2.8 to 32.9 ± 7.9 mm Hg in healthy, nonglaucomatous eyes and from 21.3 ± 2.3 to 37.6 ± 5.0 mm Hg in glaucomatous eyes. Ordinary blinking causes a 10-mm Hg increase in IOP, and hard lid-squeezing can increase it to nearly 90 mm Hg.
14 Patients with relatively inelastic eyes may have more exposure to high pressures when they blink or rub their eyes and valsalva because their eyes do not damp the pressure adequately.
For elastic materials, thinness increases distensibility. If elasticity protects the eye, then we would expect patients with thinner corneas to be relatively protected from glaucomatous damage. We know from the ocular hypertension treatment study that the opposite is true.
7 Moreover, Medeiros et al.
15 found that a thinner central cornea predicted the development of visual field conversion in both univariate and multivariate models. Herndon et al.
16 demonstrated that, in patients with glaucoma, a lower CCT is a powerful clinical factor associated with a worsened Advanced Glaucoma Intervention Study score, worsened mean deviation of visual field, increased vertical and horizontal cup-to-disc ratios and increased number of glaucoma medications. Why then is a thinner cornea a risk factor for glaucoma progression? The observation that the cornea has an asymptotic shaped pressure–volume curve suggests that a thinner cornea may represent a stretched cornea (a cornea that is already on the steep portion of this curve.) As OCT imaging demonstrates, the cornea thins as volume is increased. IOP measured at the slit lamp may be normal or low, but when the patient’s eye is subjected to microvolumetric increases, the pressure may increase precipitously.
This theory explains the finding that patients with normal-tension glaucoma have significantly thinner corneas when compared to normal patients.
17 18 Moreover, it offers a solution, beyond the mere measurement phenomenon, to the seemingly paradoxical finding that patients with ocular hypertension have thicker corneas.
17 18 19 A thicker cornea should be less elastic, yielding a greater increase in pressure for the same increase in volume. However, a thicker cornea that is not a stretched cornea is still on the flat portion of the pressure–volume curve. Therefore, when volume is added, the pressure may remain relatively stable. The starting position on the IOP–volume curve and the shape of the curve may be more important than the thickness of the cornea in relation to glaucomatous injury.
Our study demonstrates the elasticity of the human cornea and shows that the greater the elasticity the more protected the eye is from pressure surges. Further studies are needed to determine whether this relationship translates to an in vivo correlation between degree of elasticity and progression of optic nerve damage.
Supported by a Research to Prevent Blindness Career Development Award (NAA).
Submitted for publication June 27, 2006; revised December 15, 2006; accepted April 16, 2007.
Disclosure:
C.S. Johnson, None;
S.I. Mian, None;
S. Moroi, None;
D. Epstein, None;
J. Izatt, None;
N.A. Afshari, None
The publication costs of this article were defrayed in part by page charge payment. This article must therefore be marked “
advertisement” in accordance with 18 U.S.C. §1734 solely to indicate this fact.
Corresponding author: Natalie A. Afshari, Duke University Eye Center, P.O. Box 3802, Durham, NC 27710;
afsha003@mc.duke.edu.
Table 1. Average Infusion Volume Necessary to Reach a Given Pressure
Table 1. Average Infusion Volume Necessary to Reach a Given Pressure
Pressure (mm Hg) | Average Volume Infused (μL) | Range (μL) | SD |
20 | 80 | 42–125 | 23 |
40 | 116 | 69–166 | 29 |
60 | 140 | 83–208 | 38 |
80 | 160 | 111–236 | 40 |
100 | 182 | 125–264 | 46 |
150 | 187 | 83–319 | 74 |
200 | 231 | 111–361 | 93 |
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