OSA's Digital Library

Biomedical Optics Express

Biomedical Optics Express

  • Editor: Joseph A. Izatt
  • Vol. 5, Iss. 5 — May. 1, 2014
  • pp: 1391–1402
« Show journal navigation

Scleral birefringence as measured by polarization-sensitive optical coherence tomography and ocular biometric parameters of human eyes in vivo

Masahiro Yamanari, Satoko Nagase, Shinichi Fukuda, Kotaro Ishii, Ryosuke Tanaka, Takeshi Yasui, Tetsuro Oshika, Masahiro Miura, and Yoshiaki Yasuno  »View Author Affiliations


Biomedical Optics Express, Vol. 5, Issue 5, pp. 1391-1402 (2014)
http://dx.doi.org/10.1364/BOE.5.001391


View Full Text Article

Acrobat PDF (6203 KB)





Browse Journals / Lookup Meetings

Browse by Journal and Year


   


Lookup Conference Papers

Close Browse Journals / Lookup Meetings

Article Tools

Share
Citations

Abstract

The relationship between scleral birefringence and biometric parameters of human eyes in vivo is investigated. Scleral birefringence near the limbus of 21 healthy human eyes was measured using polarization-sensitive optical coherence tomography. Spherical equivalent refractive error, axial eye length, and intraocular pressure (IOP) were measured in all subjects. IOP and scleral birefringence of human eyes in vivo was found to have statistically significant correlations (r = −0.63, P = 0.002). The slope of linear regression was −2.4 × 10−2 deg/μm/mmHg. Neither spherical equivalent refractive error nor axial eye length had significant correlations with scleral birefringence. To evaluate the direct influence of IOP to scleral birefringence, scleral birefringence of 16 ex vivo porcine eyes was measured under controlled IOP of 5−60 mmHg. In these ex vivo porcine eyes, the mean linear regression slope between controlled IOP and scleral birefringence was −9.9 × 10−4 deg/μm/mmHg. In addition, porcine scleral collagen fibers were observed with second-harmonic-generation (SHG) microscopy. SHG images of porcine sclera, measured on the external surface at the superior side to the cornea, showed highly aligned collagen fibers parallel to the limbus. In conclusion, scleral birefringence of healthy human eyes was correlated with IOP, indicating that the ultrastructure of scleral collagen was correlated with IOP. It remains to show whether scleral collagen ultrastructure of human eyes is affected by IOP as a long-term effect.

© 2014 Optical Society of America

1. Introduction

Recent studies have suggested that the biomechanical property of sclera of myopic and glaucomatous eyes is different from that of normal eyes [1

1. N. A. McBrien and A. Gentle, “Role of the sclera in the development and pathological complications of myopia,” Prog. Retin. Eye Res. 22(3), 307–338 (2003). [CrossRef] [PubMed]

3

3. J. A. Rada, S. Shelton, and T. T. Norton, “The sclera and myopia,” Exp. Eye Res. 82(2), 185–200 (2006). [CrossRef] [PubMed]

]. Sclera of the myopic eye is known to have increased creep [4

4. J. T. Siegwart Jr and T. T. Norton, “Regulation of the mechanical properties of tree shrew sclera by the visual environment,” Vision Res. 39(2), 387–407 (1999). [CrossRef] [PubMed]

], decreased thickness, and smaller collagen fibril diameter [1

1. N. A. McBrien and A. Gentle, “Role of the sclera in the development and pathological complications of myopia,” Prog. Retin. Eye Res. 22(3), 307–338 (2003). [CrossRef] [PubMed]

,5

5. N. A. McBrien, L. M. Cornell, and A. Gentle, “Structural and ultrastructural changes to the sclera in a mammalian model of high myopia,” Invest. Ophthalmol. Vis. Sci. 42(10), 2179–2187 (2001). [PubMed]

]. These changes are believed to be associated with the remodeling of the sclera and the axial elongation of the eyeball. Although the alignment of scleral collagen fibers in glaucomatous eyes is not known well, Pijanka et al. reported that sclerae of some glaucomatous eyes had decreased fiber anisotropy of collagen fibers in two quadrant sectors around the optic nerve head [6

6. J. K. Pijanka, B. Coudrillier, K. Ziegler, T. Sorensen, K. M. Meek, T. D. Nguyen, H. A. Quigley, and C. Boote, “Quantitative mapping of collagen fiber orientation in non-glaucoma and glaucoma posterior human sclerae,” Invest. Ophthalmol. Vis. Sci. 53(9), 5258–5270 (2012). [CrossRef] [PubMed]

]. The stiffness of the peripapillary sclera of glaucomatous eyes was different from that of normal eyes in the cases of experimental monkeys and postmortem humans [7

7. J. C. Downs, J.-K. F. Suh, K. A. Thomas, A. J. Bellezza, R. T. Hart, and C. F. Burgoyne, “Viscoelastic material properties of the peripapillary sclera in normal and early-glaucoma monkey eyes,” Invest. Ophthalmol. Vis. Sci. 46(2), 540–546 (2005). [CrossRef] [PubMed]

10

10. H. Yang, H. Thompson, M. D. Roberts, I. A. Sigal, J. C. Downs, and C. F. Burgoyne, “Deformation of the early glaucomatous monkey optic nerve head connective tissue after acute IOP elevation in 3-D histomorphometric reconstructions,” Invest. Ophthalmol. Vis. Sci. 52(1), 345–363 (2011). [CrossRef] [PubMed]

]. Glaucomatous human eyes had lower density of collagen fibers in peripapillary sclera than that of normal human eyes [11

11. H. A. Quigley, M. E. Dorman-Pease, and A. E. Brown, “Quantitative study of collagen and elastin of the optic nerve head and sclera in human and experimental monkey glaucoma,” Curr. Eye Res. 10(9), 877–888 (1991). [CrossRef] [PubMed]

].

Although the scleral biomechanics has important roles for myopia and glaucoma, in vivo scleral biomechanics has been poorly investigated. Recently, we showed that the elasticity of ex vivo porcine sclera correlated with the birefringence that was measured by polarization-sensitive optical coherence tomography (PS-OCT) [12

12. S. Nagase, M. Yamanari, R. Tanaka, T. Yasui, M. Miura, T. Iwasaki, H. Goto, and Y. Yasuno, “Anisotropic alteration of scleral birefringence to uniaxial mechanical strain,” PLoS ONE 8(3), e58716 (2013). [CrossRef] [PubMed]

,13

13. M. Yamanari, K. Ishii, S. Fukuda, Y. Lim, L. Duan, S. Makita, M. Miura, T. Oshika, and Y. Yasuno, “Optical rheology of porcine sclera by birefringence imaging,” PLoS ONE 7(9), e44026 (2012). [CrossRef] [PubMed]

]. The result can be understood from two known facts that highly organized collagen fiber has high birefringence [14

14. R. Oldenbourg, E. D. Salmon, and P. T. Tran, “Birefringence of single and bundled microtubules,” Biophys. J. 74(1), 645–654 (1998). [CrossRef] [PubMed]

,15

15. S. K. Nadkarni, M. C. Pierce, B. H. Park, J. F. de Boer, P. Whittaker, B. E. Bouma, J. E. Bressner, E. Halpern, S. L. Houser, and G. J. Tearney, “Measurement of collagen and smooth muscle cell content in atherosclerotic plaques using polarization-sensitive optical coherence tomography,” J. Am. Coll. Cardiol. 49(13), 1474–1481 (2007). [CrossRef] [PubMed]

] and that highly organized collagen fiber has high elasticity [1

1. N. A. McBrien and A. Gentle, “Role of the sclera in the development and pathological complications of myopia,” Prog. Retin. Eye Res. 22(3), 307–338 (2003). [CrossRef] [PubMed]

,16

16. C. J. Doillon, M. G. Dunn, E. Bender, and F. H. Silver, “Collagen fiber formation in repair tissue: development of strength and toughness,” Coll. Relat. Res. 5(6), 481–492 (1985). [CrossRef] [PubMed]

18

18. G. D. Pins, D. L. Christiansen, R. Patel, and F. H. Silver, “Self-assembly of collagen fibers. influence of fibrillar alignment and decorin on mechanical properties,” Biophys. J. 73(4), 2164–2172 (1997). [CrossRef] [PubMed]

].

In this paper, we show the relationships between birefringence of in vivo human sclera and biometric parameters of the human eye. In addition, we show that the birefringence of sclera is not significantly influenced by short-term alteration of intraocular pressure (IOP) in the case of ex vivo porcine eyes. Regionally different fiber structures of the ex vivo porcine sclera are also visualized using second-harmonic-generation (SHG) microscopy.

2. Methods

2.1 Measurement of in vivo human sclera

Axial eye length, spherical equivalent refractive error, and IOP of the healthy human eyes were measured by IOL Master (Carl Zeiss Meditec, Dublin, CA, USA), auto kerato-refractometer (RT-7000, Tomey Corp., Nagoya, Aichi, Japan), and Goldmann applanation tonometer, respectively.

Birefringence of the sclera was measured by our prototype of PS-OCT [26

26. Y. Lim, M. Yamanari, S. Fukuda, Y. Kaji, T. Kiuchi, M. Miura, T. Oshika, and Y. Yasuno, “Birefringence measurement of cornea and anterior segment by office-based polarization-sensitive optical coherence tomography,” Biomed. Opt. Express 2(8), 2392–2402 (2011). [CrossRef] [PubMed]

]. In brief, the system used a frequency-swept light source with center wavelength and scanning speed of 1.31 μm and 30 kHz, respectively. The axial resolution was 9.2 μm in tissue. Using polarization modulation and polarization-sensitive detection, the system measures a tomography of Jones matrix of a sample, which represents the polarization property of the sample. Using this system, we measured volumetric data in a lateral measurement range of 6 mm × 3 mm on the sample, with 512 × 128 A-scans. Figure 1(a)
Fig. 1 Representative OCT intensity (a) and local birefringence (b) images of human sclera in vivo. Red outlined areas show the extracted region used to calculate averaged birefringence in each sample. Scale bar represents 500 μm × 500 μm.
shows a representative OCT intensity image of human sclera near the limbus. The angle of anterior chamber was included in the right side of the image as a landmark of the measurement.

To analyze the polarization property of the sclera, we calculated local birefringence from the measured Jones matrix. To calculate the local birefringence of the sclera, we used a similar method developed previously [13

13. M. Yamanari, K. Ishii, S. Fukuda, Y. Lim, L. Duan, S. Makita, M. Miura, T. Oshika, and Y. Yasuno, “Optical rheology of porcine sclera by birefringence imaging,” PLoS ONE 7(9), e44026 (2012). [CrossRef] [PubMed]

]. The Jones matrices were moving-averaged with a kernel size of 3 pix (axial) × 5 pix (transversal) (18 μm × 59 μm) in each B-scan after cancelling the relative global phase among the Jones matrices [26

26. Y. Lim, M. Yamanari, S. Fukuda, Y. Kaji, T. Kiuchi, M. Miura, T. Oshika, and Y. Yasuno, “Birefringence measurement of cornea and anterior segment by office-based polarization-sensitive optical coherence tomography,” Biomed. Opt. Express 2(8), 2392–2402 (2011). [CrossRef] [PubMed]

]. Local birefringence of sclera was calculated using the method published previously [31

31. S. Makita, M. Yamanari, and Y. Yasuno, “Generalized jones matrix optical coherence tomography: performance and local birefringence imaging,” Opt. Express 18(2), 854–876 (2010). [CrossRef] [PubMed]

]. The local birefringence was calculated from the depth-oriented alteration of the polarization property in a small depth-region. The size of the region was 8 pix (49 μm) in tissue, which represented the spatial resolution of the measured local birefringence. Figure 1(b) shows the local birefringence image of human sclera. Some domains that have high birefringence are visible in the sclera, which would represent inhomogeneity in collagen fibers.

A scleral region was extracted semi-automatically as indicated by the outlined red areas shown in Fig. 1(a) and 1(b). In addition, the pixels that had lower effective signal to noise ratio than 10 dB or lower degree of optic axis uniformity than 0.9 [13

13. M. Yamanari, K. Ishii, S. Fukuda, Y. Lim, L. Duan, S. Makita, M. Miura, T. Oshika, and Y. Yasuno, “Optical rheology of porcine sclera by birefringence imaging,” PLoS ONE 7(9), e44026 (2012). [CrossRef] [PubMed]

] were excluded from the subsequent analysis. The measured local birefringence value was converted to an estimated birefringence value using a Monte Carlo-based estimator [32

32. L. Duan, S. Makita, M. Yamanari, Y. Lim, and Y. Yasuno, “Monte-carlo-based phase retardation estimator for polarization sensitive optical coherence tomography,” Opt. Express 19(17), 16330–16345 (2011). [CrossRef] [PubMed]

]. By averaging the estimated birefringence value in each volume of sclera, a true averaged local birefringence value was obtained [32

32. L. Duan, S. Makita, M. Yamanari, Y. Lim, and Y. Yasuno, “Monte-carlo-based phase retardation estimator for polarization sensitive optical coherence tomography,” Opt. Express 19(17), 16330–16345 (2011). [CrossRef] [PubMed]

].

2.2 Inflation response of ex vivo porcine sclera

To observe the influence of short-term alteration of IOP on the birefringence of the sclera, we measured the birefringence of porcine sclera with controlled IOP. Sixteen porcine eyes obtained from a local abattoir were used for the experiment within the same day of the sacrifice. Extraocular tissues and conjunctiva were removed before the experiment.

Figure 2
Fig. 2 Schematic of the experiment designed to measure the inflation response of scleral birefringence.
shows the schematic of the experiment designed to measure birefringence of the ex vivo porcine sclera in response to the inflation of the eye. IOP was controlled by a reservoir of phosphate-buffered solution (PBS) (BSS Plus, Alcon, Fort Worth, TX, USA). The reservoir was connected to a 24G cannula inserted into the optic nerve head of the porcine eye. IOP was monitored by a pressure sensor (MLT0699, ADInstruments, Bella Vista, NSW, Australia) that was located at the same height as the eye. The height of the liquid level was controlled manually to change the IOP of the eye from 5 to 60 mmHg with eight steps (5, 10, 14, 18, 22, 30, 45, and 60 mmHg).

Birefringence of the porcine sclera was measured at each controlled IOP using the PS-OCT. Figure 3
Fig. 3 Representative OCT intensity (a) and local birefringence (b) images of porcine sclera ex vivo. Red outlined areas show the extracted region used to calculate averaged birefringence in each sample. Scale bar represents 500 μm × 500 μm.
shows representative OCT intensity and local birefringence images. The measured region and the processing method to calculate the birefringence were the same as the experiment using the in vivo human sclera.

2.3 SHG imaging of porcine sclera

To observe the structure of collagen fibers in the sclera, we measured backscattering from the sclera with SHG microscopy. The light source was a femtosecond laser (center wavelength, 800 nm; pulse width, ~100 fs; repetition rate, 80 MHz; average output power, ~30 mW). The incident state of polarization was controlled to be circular polarization with a quarter waveplate so that the signal intensity of the SHG did not depend on the orientation of the collagen fiber. The light illuminates the sample from the bottom side through an inverted light microscope (TE2000-U, Nikon, Tokyo, Japan) where the light is focused by an oil-immersion lens (20 × , NA = 1) that contacts a glass slide. The sample was set on the glass slide. Backscattered SHG signal was separated from the fundamental wavelength, and detected by a photomultiplier tube. The gain of the detector was controlled to optimize the image contrast for each image.

Six porcine eyes were dissected for this measurement by SHG microscopy. Two scleral strips with a size of 5 mm square were extracted from each eye at the superior side of the cornea and at the posterior pole that did not include a peripapillary region. The scleral strip extracted at the superior side of the cornea was directly mounted on a glass slide, and measured by SHG microscopy. Both external and internal surfaces of the sclera were measured for each strip. The other scleral strip extracted at the posterior pole was immersed in paraffin, frozen by liquid nitrogen, sectioned in a low temperature cryostat at a thickness of 30 μm, and at a depth of 600 μm from the external surface of the sclera, mounted on a glass slide, and measured by SHG microscopy.

3. Results

Figure 4
Fig. 4 Plots of local birefringence of the human sclera and spherical equivalent (a), axial eye length (b), and IOP (c).
shows the plots of birefringence as a function of biometric parameters of spherical equivalent refractive error (a), axial eye length (b), and IOP (c). Statistically significant correlation was found between the birefringence and the IOP (two-sided test using Pearson's correlation coefficient, r = −0.63, P = 0.002). The slope and intercept of the linear regression line were −2.4 × 10−2 deg/μm/mmHg and 1.5 deg/μm, respectively. The results did not show statistically significant correlations between birefringence and spherical equivalent refractive error or axial eye length.

Figure 5
Fig. 5 Plots of local birefringence of the porcine sclera and controlled IOP. Linear regression line of each porcine eye is also shown. Each color represents a different eye.
shows the plots of birefringence at the controlled IOP for each porcine eye. To determine the dependence of birefringence on the IOP, linear regression was applied for each eye. Mean slope was −9.9 × 10−4 deg/μm/mmHg.

Figure 6
Fig. 6 Scatter plot of the slope between scleral birefringence and IOP. Filled square and open squares show the results of in vivo human eyes and ex vivo porcine eyes, respectively.
shows the scatter plot of the slope between the scleral birefringence and IOP of in vivo human eyes (black rectangle) and ex vivo porcine eyes (white rectangles). The minimum slope of 16 porcine eyes was less than 15% of the average of 21 human eyes without controlled IOP.

Figure 7
Fig. 7 SHG microscopy images of the porcine sclera at the superior side of the cornea. Rows A, B, and C show the SHG images on the external surface, at the depth of 600 μm, and on the internal surface of the sclera, respectively. The numbers of the columns from 1 to 6 show IDs of porcine eyes.
shows the SHG images at the superior side of the cornea of porcine eyes ex vivo. On the external surface of the sclera (row A of Fig. 7), SHG images showed clear collagen bundles that roughly aligned in the horizontal direction, which were parallel to the limbus. At the depth of 600 μm, as shown in row B of Fig. 7, the contrast of collagen bundles was not as clear as at the external surface. This could be partly because the sliced plane was not parallel to the fiber. On the internal surface of the sclera (row C of Fig. 7), the contrast of collagen fiber was not clear, and the collagen fiber did not have a specific orientation of alignment. Because the detector gain was optimized for each SHG image, the contrasts of all images are nearly the same. However, the raw SHG intensity from the internal surfaces was significantly weaker than at the external surfaces.

Figure 8
Fig. 8 SHG images of the porcine sclera at the posterior pole. Rows A, B, and C show the SHG images on the external surface, at the depth of 600 μm, and on the internal surface of the sclera, respectively. The numbers of the columns from 1 to 6 show IDs of porcine eyes.
shows the SHG images of the porcine sclera at the posterior pole. On the external surface (row A of Fig. 8), SHG images clearly showed undulating thick bundles, which had a width of 20−50 μm. The bundles had interwoven structures with various orientations. There was no notable major orientation of the fiber bundles. At the depth of 600 μm (row B of Fig. 8), the contrast of collagen bundles was better than that observed near the limbus, as shown in Fig. 7. On the internal surface of the sclera (row C of Fig. 8), fine collagen bundles were observed in eyes 1 and 2. These bundles had a diameter of 3−5 μm and were frequently branched and intermingled. In the other eyes, the images looked fuzzy, and individual bundles were not as clear as in the other eyes.

4. Discussion

In the study of in vivo human eyes, we investigated the relationship between birefringence and biometric parameters. The IOP showed statistically significant correlation with the birefringence, while the spherical equivalent refractive error and axial eye length did not show these correlations in this small number of subjects. To further explain the relationship between the IOP and birefringence, several mechanisms can be hypothesized.

The first hypothesis is that the ultrastructure of the sclera has a role in regulating IOP. However, the sclera is not the main resistance component for both trabecular and uveoscleral outflow [33

33. A. Alm and S. F. Nilsson, “Uveoscleral outflow--a review,” Exp. Eye Res. 88(4), 760–768 (2009). [CrossRef] [PubMed]

], and it is unlikely that scleral ultrastructure affects the IOP directly, at least in the normal eyes.

Another hypothesis is that short-term alteration of IOP could affect the birefringence, because the alteration of IOP may change the density of collagen fibrils or the anisotropy of collagen fibers. For example, it was reported that the birefringence of human skin was altered by stretching [34

34. S. Sakai, M. Yamanari, Y. Lim, N. Nakagawa, and Y. Yasuno, “In vivo evaluation of human skin anisotropy by polarization-sensitive optical coherence tomography,” Biomed. Opt. Express 2(9), 2623–2631 (2011). [CrossRef] [PubMed]

]. To examine this hypothesis, the birefringence of the porcine sclera was measured under controlled IOP. The results disproved this hypothesis for the porcine sclera. The short-term alteration of IOP did not significantly affect the scleral birefringence in the case of porcine eyes ex vivo. Although it has been known that human and porcine eyes have similar properties of the sclera in some aspects [35

35. T. W. Olsen, S. Sanderson, X. Feng, and W. C. Hubbard, “Porcine sclera: Thickness and surface area,” Invest. Ophthalmol. Vis. Sci. 43(8), 2529–2532 (2002). [PubMed]

-38

38. S. Nicoli, G. Ferrari, M. Quarta, C. Macaluso, P. Govoni, D. Dallatana, and P. Santi, “Porcine sclera as a model of human sclera for in vitro transport experiments: histology, sem, and comparative permeability,” Mol. Vis. 15, 259–266 (2009). [PubMed]

], additional studies would be required to show whether the outcome of porcine eyes is interchangeable to human eyes. If it was exchangeable, our result would suggest that the short-term alteration of IOP does not explain the significant negative relationship between the IOP and scleral birefringence of human eyes in vivo. This validation is still left as a future work.

Assuming interchangeability between porcine and human eyes as discussed above and considering the structural source of the birefringent tissues, our results may indicate that because of unknown factors, the sclera of healthy eyes with relatively high IOP had low density collagen fibrils or irregular orientations of the collagen fibers. One possible but not proven hypothesis is that chronic elevation of IOP affects the tissue remodeling process of sclera [39

39. M. J. A. Girard, J.-K. F. Suh, M. Bottlang, C. F. Burgoyne, and J. C. Downs, “Biomechanical changes in the sclera of monkey eyes exposed to chronic iop elevations,” Invest. Ophthalmol. Vis. Sci. 52(8), 5656–5669 (2011). [CrossRef] [PubMed]

] and the scleral birefringence could have been gradually decreased over time.

Previously, we showed that birefringence and elasticity of sclera were positively correlated [13

13. M. Yamanari, K. Ishii, S. Fukuda, Y. Lim, L. Duan, S. Makita, M. Miura, T. Oshika, and Y. Yasuno, “Optical rheology of porcine sclera by birefringence imaging,” PLoS ONE 7(9), e44026 (2012). [CrossRef] [PubMed]

]. Considering this report and the results of our study, human eyes may have different scleral biomechanical properties depending on their inherent IOP. However, further studies are necessary to validate this hypothesis.

In our other recent paper [12

12. S. Nagase, M. Yamanari, R. Tanaka, T. Yasui, M. Miura, T. Iwasaki, H. Goto, and Y. Yasuno, “Anisotropic alteration of scleral birefringence to uniaxial mechanical strain,” PLoS ONE 8(3), e58716 (2013). [CrossRef] [PubMed]

], we reported that the birefringence of porcine sclera was altered by uniaxial strain in both meridional and equatorial directions. However, the alteration of birefringence in the inflation test in the current study was smaller than that with the uniaxial strain. The different results of these studies are likely to be explained by the different protocols of the applied pressure. Since one can assume that the inflation test imposes almost equibiaxial loading condition, only little reorganization of the collagen structure is occurred. This would explain why birefringence was not significantly altered with IOP for the porcine sclera. One additional thought is about strain at limbus. The IOP elevation would not always produce an equibiaxial loading at the limbus because of the abrupt change in curvature between the sclera and the cornea. It would be expected that the birefringence alteration at limbus under IOP alteration is not the same with the scleral region measured in the current study. It is an important future study and is potentially important for the computational models of the sclera, which assume that collagen fibers and matrix deforms according to the macroscopic deformation of the tissue [39

39. M. J. A. Girard, J.-K. F. Suh, M. Bottlang, C. F. Burgoyne, and J. C. Downs, “Biomechanical changes in the sclera of monkey eyes exposed to chronic iop elevations,” Invest. Ophthalmol. Vis. Sci. 52(8), 5656–5669 (2011). [CrossRef] [PubMed]

41

41. R. Grytz and G. Meschke, “A computational remodeling approach to predict the physiological architecture of the collagen fibril network in corneo-scleral shells,” Biomech. Model. Mechanobiol. 9(2), 225–235 (2010). [CrossRef] [PubMed]

].

Highly intertwined and interwoven structures of collagen fibers could have decreased total birefringence, because the birefringence of collagen fibers with different orientations partly cancels each other [14

14. R. Oldenbourg, E. D. Salmon, and P. T. Tran, “Birefringence of single and bundled microtubules,” Biophys. J. 74(1), 645–654 (1998). [CrossRef] [PubMed]

,50

50. M. C. van Turnhout, S. Kranenbarg, and J. L. van Leeuwen, “Modeling optical behavior of birefringent biological tissues for evaluation of quantitative polarized light microscopy,” J. Biomed. Opt. 14(5), 054018 (2009). [CrossRef] [PubMed]

]. Hence, the birefringence at the posterior region, where the randomness of fiber orientation of sclera is relatively high, would be lower than that of the region near the limbus. Further understanding of the relationship between the birefringence and ultrastructural properties of the sclera would be important to strengthen the use of PS-OCT for evaluating mechanical properties of tissues.

Although SHG microscopy has been frequently used for corneal imaging [55

55. N. Morishige, A. J. Wahlert, M. C. Kenney, D. J. Brown, K. Kawamoto, T.-i. Chikama, T. Nishida, and J. V. Jester, “Second-harmonic imaging microscopy of normal human and keratoconus cornea,” Invest. Ophthalmol. Vis. Sci. 48(3), 1087–1094 (2007). [CrossRef] [PubMed]

57

57. N. Morishige, N. Yamada, X. Zhang, Y. Morita, N. Yamada, K. Kimura, A. Takahara, and K.-H. Sonoda, “Abnormalities of stromal structure in the bullous keratopathy cornea identified by second harmonic generation imaging microscopy,” Invest. Ophthalmol. Vis. Sci. 53(8), 4998–5003 (2012). [CrossRef] [PubMed]

], there are only a few reports of its application to scleral imaging [58

58. M. Han, G. Giese, and J. Bille, “Second harmonic generation imaging of collagen fibrils in cornea and sclera,” Opt. Express 13(15), 5791–5797 (2005). [CrossRef] [PubMed]

,59

59. S.-W. Teng, H.-Y. Tan, J.-L. Peng, H.-H. Lin, K. H. Kim, W. Lo, Y. Sun, W.-C. Lin, S.-J. Lin, S.-H. Jee, P. T. C. So, and C.-Y. Dong, “Multiphoton autofluorescence and second-harmonic generation imaging of the ex vivo porcine eye,” Invest. Ophthalmol. Vis. Sci. 47(3), 1216–1224 (2006). [CrossRef] [PubMed]

]. As shown in Figs. 7 and 8, we demonstrated that SHG microscopy is useful in observing the orientation and anisotropy of collagen fibers that have regional differences in the sclera. Although it is difficult to resolve individual collagen fibrils by SHG microscopy, it has the advantage of observing collagen bundles in a wider field of view than scanning electron microscopy, and of enabling imaging of both stained and unstained samples in situ.

In summary, scleral birefringence of healthy human eyes was found to be correlated with IOP. Although this finding may indicate that the ultrastructure of collagen fibers in the sclera of healthy eyes is likely to be affected by IOP even in normal ranges as a long-term effect, further studies are required to validate the hypothesis. This study is the first to demonstrate the relationship between scleral birefringence and biometric parameters in vivo.

Acknowledgments

This study was supported in part by the Japan Science and Technology Agency under a program of development of systems and technology for advanced measurement and analysis and by Tomey Corporation.

References and links

1.

N. A. McBrien and A. Gentle, “Role of the sclera in the development and pathological complications of myopia,” Prog. Retin. Eye Res. 22(3), 307–338 (2003). [CrossRef] [PubMed]

2.

C. F. Burgoyne, J. C. Downs, A. J. Bellezza, J. K. Suh, and R. T. Hart, “The optic nerve head as a biomechanical structure: a new paradigm for understanding the role of IOP-related stress and strain in the pathophysiology of glaucomatous optic nerve head damage,” Prog. Retin. Eye Res. 24(1), 39–73 (2005). [CrossRef] [PubMed]

3.

J. A. Rada, S. Shelton, and T. T. Norton, “The sclera and myopia,” Exp. Eye Res. 82(2), 185–200 (2006). [CrossRef] [PubMed]

4.

J. T. Siegwart Jr and T. T. Norton, “Regulation of the mechanical properties of tree shrew sclera by the visual environment,” Vision Res. 39(2), 387–407 (1999). [CrossRef] [PubMed]

5.

N. A. McBrien, L. M. Cornell, and A. Gentle, “Structural and ultrastructural changes to the sclera in a mammalian model of high myopia,” Invest. Ophthalmol. Vis. Sci. 42(10), 2179–2187 (2001). [PubMed]

6.

J. K. Pijanka, B. Coudrillier, K. Ziegler, T. Sorensen, K. M. Meek, T. D. Nguyen, H. A. Quigley, and C. Boote, “Quantitative mapping of collagen fiber orientation in non-glaucoma and glaucoma posterior human sclerae,” Invest. Ophthalmol. Vis. Sci. 53(9), 5258–5270 (2012). [CrossRef] [PubMed]

7.

J. C. Downs, J.-K. F. Suh, K. A. Thomas, A. J. Bellezza, R. T. Hart, and C. F. Burgoyne, “Viscoelastic material properties of the peripapillary sclera in normal and early-glaucoma monkey eyes,” Invest. Ophthalmol. Vis. Sci. 46(2), 540–546 (2005). [CrossRef] [PubMed]

8.

B. Coudrillier, J. Tian, S. Alexander, K. M. Myers, H. A. Quigley, and T. D. Nguyen, “Biomechanics of the human posterior sclera: Age- and glaucoma-related changes measured using inflation testing,” Invest. Ophthalmol. Vis. Sci. 53(4), 1714–1728 (2012). [CrossRef] [PubMed]

9.

A. J. Bellezza, C. J. Rintalan, H. W. Thompson, J. C. Downs, R. T. Hart, and C. F. Burgoyne, “Deformation of the lamina cribrosa and anterior scleral canal wall in early experimental glaucoma,” Invest. Ophthalmol. Vis. Sci. 44(2), 623–637 (2003). [CrossRef] [PubMed]

10.

H. Yang, H. Thompson, M. D. Roberts, I. A. Sigal, J. C. Downs, and C. F. Burgoyne, “Deformation of the early glaucomatous monkey optic nerve head connective tissue after acute IOP elevation in 3-D histomorphometric reconstructions,” Invest. Ophthalmol. Vis. Sci. 52(1), 345–363 (2011). [CrossRef] [PubMed]

11.

H. A. Quigley, M. E. Dorman-Pease, and A. E. Brown, “Quantitative study of collagen and elastin of the optic nerve head and sclera in human and experimental monkey glaucoma,” Curr. Eye Res. 10(9), 877–888 (1991). [CrossRef] [PubMed]

12.

S. Nagase, M. Yamanari, R. Tanaka, T. Yasui, M. Miura, T. Iwasaki, H. Goto, and Y. Yasuno, “Anisotropic alteration of scleral birefringence to uniaxial mechanical strain,” PLoS ONE 8(3), e58716 (2013). [CrossRef] [PubMed]

13.

M. Yamanari, K. Ishii, S. Fukuda, Y. Lim, L. Duan, S. Makita, M. Miura, T. Oshika, and Y. Yasuno, “Optical rheology of porcine sclera by birefringence imaging,” PLoS ONE 7(9), e44026 (2012). [CrossRef] [PubMed]

14.

R. Oldenbourg, E. D. Salmon, and P. T. Tran, “Birefringence of single and bundled microtubules,” Biophys. J. 74(1), 645–654 (1998). [CrossRef] [PubMed]

15.

S. K. Nadkarni, M. C. Pierce, B. H. Park, J. F. de Boer, P. Whittaker, B. E. Bouma, J. E. Bressner, E. Halpern, S. L. Houser, and G. J. Tearney, “Measurement of collagen and smooth muscle cell content in atherosclerotic plaques using polarization-sensitive optical coherence tomography,” J. Am. Coll. Cardiol. 49(13), 1474–1481 (2007). [CrossRef] [PubMed]

16.

C. J. Doillon, M. G. Dunn, E. Bender, and F. H. Silver, “Collagen fiber formation in repair tissue: development of strength and toughness,” Coll. Relat. Res. 5(6), 481–492 (1985). [CrossRef] [PubMed]

17.

D. A. Parry, “The molecular and fibrillar structure of collagen and its relationship to the mechanical properties of connective tissue,” Biophys. Chem. 29(1-2), 195–209 (1988). [CrossRef] [PubMed]

18.

G. D. Pins, D. L. Christiansen, R. Patel, and F. H. Silver, “Self-assembly of collagen fibers. influence of fibrillar alignment and decorin on mechanical properties,” Biophys. J. 73(4), 2164–2172 (1997). [CrossRef] [PubMed]

19.

E. Götzinger, M. Pircher, M. Sticker, A. F. Fercher, and C. K. Hitzenberger, “Measurement and imaging of birefringent properties of the human cornea with phase-resolved, polarization-sensitive optical coherence tomography,” J. Biomed. Opt. 9(1), 94–102 (2004). [CrossRef] [PubMed]

20.

Y. Yasuno, M. Yamanari, K. Kawana, M. Miura, S. Fukuda, S. Makita, S. Sakai, and T. Oshika, “Visibility of trabecular meshwork by standard and polarization-sensitive optical coherence tomography,” J. Biomed. Opt. 15(6), 061705 (2010). [CrossRef] [PubMed]

21.

M. G. Ducros, J. D. Marsack, H. G. Rylander III, S. L. Thomsen, and T. E. Milner, “Primate retina imaging with polarization-sensitive optical coherence tomography,” J. Opt. Soc. Am. A 18(12), 2945–2956 (2001). [CrossRef]

22.

B. Cense, T. C. Chen, B. H. Park, M. C. Pierce, and J. F. de Boer, “Thickness and birefringence of healthy retinal nerve fiber layer tissue measured with polarization-sensitive optical coherence tomography,” Invest. Ophthalmol. Vis. Sci. 45(8), 2606–2612 (2004). [CrossRef] [PubMed]

23.

M. Yamanari, M. Miura, S. Makita, T. Yatagai, and Y. Yasuno, “Phase retardation measurement of retinal nerve fiber layer by polarization-sensitive spectral-domain optical coherence tomography and scanning laser polarimetry,” J. Biomed. Opt. 13(1), 014013 (2008). [CrossRef] [PubMed]

24.

M. Miura, M. Yamanari, T. Iwasaki, A. E. Elsner, S. Makita, T. Yatagai, and Y. Yasuno, “Imaging polarimetry in age-related macular degeneration,” Invest. Ophthalmol. Vis. Sci. 49(6), 2661–2667 (2008). [CrossRef] [PubMed]

25.

Y. Yasuno, M. Yamanari, K. Kawana, T. Oshika, and M. Miura, “Investigation of post-glaucoma-surgery structures by three-dimensional and polarization sensitive anterior eye segment optical coherence tomography,” Opt. Express 17(5), 3980–3996 (2009). [CrossRef] [PubMed]

26.

Y. Lim, M. Yamanari, S. Fukuda, Y. Kaji, T. Kiuchi, M. Miura, T. Oshika, and Y. Yasuno, “Birefringence measurement of cornea and anterior segment by office-based polarization-sensitive optical coherence tomography,” Biomed. Opt. Express 2(8), 2392–2402 (2011). [CrossRef] [PubMed]

27.

M. Yamanari, S. Makita, and Y. Yasuno, “Polarization-sensitive swept-source optical coherence tomography with continuous source polarization modulation,” Opt. Express 16(8), 5892–5906 (2008). [CrossRef] [PubMed]

28.

M. Yamanari, Y. Lim, S. Makita, and Y. Yasuno, “Visualization of phase retardation of deep posterior eye by polarization-sensitive swept-source optical coherence tomography with 1- µm probe,” Opt. Express 17(15), 12385–12396 (2009). [CrossRef] [PubMed]

29.

M. Yamanari, S. Makita, Y. Lim, and Y. Yasuno, “Full-range polarization-sensitive swept-source optical coherence tomography by simultaneous transversal and spectral modulation,” Opt. Express 18(13), 13964–13980 (2010). [CrossRef] [PubMed]

30.

M. Miura, M. Yamanari, T. Iwasaki, M. Itoh, T. Yatagai, and Y. Yasuno, “Polarization-sensitive optical coherence tomography of necrotizing scleritis,” Ophthalmic Surg. Lasers Imaging 40(6), 607–610 (2009). [CrossRef] [PubMed]

31.

S. Makita, M. Yamanari, and Y. Yasuno, “Generalized jones matrix optical coherence tomography: performance and local birefringence imaging,” Opt. Express 18(2), 854–876 (2010). [CrossRef] [PubMed]

32.

L. Duan, S. Makita, M. Yamanari, Y. Lim, and Y. Yasuno, “Monte-carlo-based phase retardation estimator for polarization sensitive optical coherence tomography,” Opt. Express 19(17), 16330–16345 (2011). [CrossRef] [PubMed]

33.

A. Alm and S. F. Nilsson, “Uveoscleral outflow--a review,” Exp. Eye Res. 88(4), 760–768 (2009). [CrossRef] [PubMed]

34.

S. Sakai, M. Yamanari, Y. Lim, N. Nakagawa, and Y. Yasuno, “In vivo evaluation of human skin anisotropy by polarization-sensitive optical coherence tomography,” Biomed. Opt. Express 2(9), 2623–2631 (2011). [CrossRef] [PubMed]

35.

T. W. Olsen, S. Sanderson, X. Feng, and W. C. Hubbard, “Porcine sclera: Thickness and surface area,” Invest. Ophthalmol. Vis. Sci. 43(8), 2529–2532 (2002). [PubMed]

36.

B. K. Pierscionek, M. Asejczyk-Widlicka, and R. A. Schachar, “The effect of changing intraocular pressure on the corneal and scleral curvatures in the fresh porcine eye,” Br. J. Ophthalmol. 91(6), 801–803 (2007). [CrossRef] [PubMed]

37.

D. S. Schultz, J. C. Lotz, S. M. Lee, M. L. Trinidad, and J. M. Stewart, “Structural factors that mediate scleral stiffness,” Invest. Ophthalmol. Vis. Sci. 49(10), 4232–4236 (2008). [CrossRef] [PubMed]

38.

S. Nicoli, G. Ferrari, M. Quarta, C. Macaluso, P. Govoni, D. Dallatana, and P. Santi, “Porcine sclera as a model of human sclera for in vitro transport experiments: histology, sem, and comparative permeability,” Mol. Vis. 15, 259–266 (2009). [PubMed]

39.

M. J. A. Girard, J.-K. F. Suh, M. Bottlang, C. F. Burgoyne, and J. C. Downs, “Biomechanical changes in the sclera of monkey eyes exposed to chronic iop elevations,” Invest. Ophthalmol. Vis. Sci. 52(8), 5656–5669 (2011). [CrossRef] [PubMed]

40.

P. M. Pinsky, D. van der Heide, and D. Chernyak, “Computational modeling of mechanical anisotropy in the cornea and sclera,” J. Cataract Refract. Surg. 31(1), 136–145 (2005). [CrossRef] [PubMed]

41.

R. Grytz and G. Meschke, “A computational remodeling approach to predict the physiological architecture of the collagen fibril network in corneo-scleral shells,” Biomech. Model. Mechanobiol. 9(2), 225–235 (2010). [CrossRef] [PubMed]

42.

Collaborative Normal-Tension Glaucoma Study Group, “Comparison of glaucomatous progression between untreated patients with normal-tension glaucoma and patients with therapeutically reduced intraocular pressures,” Am. J. Ophthalmol. 126(4), 487–497 (1998). [CrossRef] [PubMed]

43.

Y. Suzuki, A. Iwase, M. Araie, T. Yamamoto, H. Abe, S. Shirato, Y. Kuwayama, H. K. Mishima, H. Shimizu, G. Tomita, Y. Inoue, and Y. KitazawaY. SuzukiA. IwaseM. AraieT. YamamotoH. AbeS. ShiratoY. KuwayamaH. K. MishimaH. ShimizuG. TomitaY. InoueY. KitazawaTajimi Study Group, “Risk factors for open-angle glaucoma in a japanese population: The tajimi study,” Ophthalmology 113(9), 1613–1617 (2006). [CrossRef] [PubMed]

44.

M. J. A. Girard, J. C. Downs, C. F. Burgoyne, and J.-K. F. Suh, “Peripapillary and posterior scleral mechanics--part i: Development of an anisotropic hyperelastic constitutive model,” J. Biomech. Eng. 131(5), 051011 (2009). [CrossRef] [PubMed]

45.

B. Coudrillier, C. Boote, H. A. Quigley, and T. D. Nguyen, “Scleral anisotropy and its effects on the mechanical response of the optic nerve head,” Biomech. Model. Mechanobiol. 12(5), 941–963 (2013). [CrossRef] [PubMed]

46.

M. J. Hogan, J. A. Alvarado, and J. E. Weddell, Histology of the human eye: an atlas and textbook (Saunders, 1971).

47.

H. A. Quigley, E. M. Addicks, W. R. Green, and A. E. Maumenee, “Optic nerve damage in human glaucoma. Ii. the site of injury and susceptibility to damage,” Arch. Ophthalmol. 99(4), 635–649 (1981). [CrossRef] [PubMed]

48.

Y. Lim, Y.-J. Hong, L. Duan, M. Yamanari, and Y. Yasuno, “Passive component based multifunctional jones matrix swept source optical coherence tomography for doppler and polarization imaging,” Opt. Lett. 37(11), 1958–1960 (2012). [CrossRef] [PubMed]

49.

T. Torzicky, S. Marschall, M. Pircher, B. Baumann, M. Bonesi, S. Zotter, E. Götzinger, W. Trasischker, T. Klein, W. Wieser, B. Biedermann, R. Huber, P. Andersen, and C. K. Hitzenberger, “Retinal polarization-sensitive optical coherence tomography at 1060 nm with 350 khz a-scan rate using an fourier domain mode locked laser,” J. Biomed. Opt. 18(2), 026008 (2013). [CrossRef] [PubMed]

50.

M. C. van Turnhout, S. Kranenbarg, and J. L. van Leeuwen, “Modeling optical behavior of birefringent biological tissues for evaluation of quantitative polarized light microscopy,” J. Biomed. Opt. 14(5), 054018 (2009). [CrossRef] [PubMed]

51.

P. Watson and B. Hazleman, The Sclera and Systemic Disorders (Jp Medical Pub, 2012).

52.

R. H. Newton and K. M. Meek, “The integration of the corneal and limbal fibrils in the human eye,” Biophys. J. 75(5), 2508–2512 (1998). [CrossRef] [PubMed]

53.

D. Yan, S. McPheeters, G. Johnson, U. Utzinger, and J. P. Vande Geest, “Microstructural differences in the human posterior sclera as a function of age and race,” Invest. Ophthalmol. Vis. Sci. 52(2), 821–829 (2011). [CrossRef] [PubMed]

54.

M. J. A. Girard, A. Dahlmann-Noor, S. Rayapureddi, J. A. Bechara, B. M. E. Bertin, H. Jones, J. Albon, P. T. Khaw, and C. R. Ethier, “Quantitative mapping of scleral fiber orientation in normal rat eyes,” Invest. Ophthalmol. Vis. Sci. 52(13), 9684–9693 (2011). [CrossRef] [PubMed]

55.

N. Morishige, A. J. Wahlert, M. C. Kenney, D. J. Brown, K. Kawamoto, T.-i. Chikama, T. Nishida, and J. V. Jester, “Second-harmonic imaging microscopy of normal human and keratoconus cornea,” Invest. Ophthalmol. Vis. Sci. 48(3), 1087–1094 (2007). [CrossRef] [PubMed]

56.

J. M. Bueno, E. J. Gualda, A. Giakoumaki, P. Pérez-Merino, S. Marcos, and P. Artal, “Multiphoton microscopy of ex vivo corneas after collagen cross-linking,” Invest. Ophthalmol. Vis. Sci. 52(8), 5325–5331 (2011). [CrossRef] [PubMed]

57.

N. Morishige, N. Yamada, X. Zhang, Y. Morita, N. Yamada, K. Kimura, A. Takahara, and K.-H. Sonoda, “Abnormalities of stromal structure in the bullous keratopathy cornea identified by second harmonic generation imaging microscopy,” Invest. Ophthalmol. Vis. Sci. 53(8), 4998–5003 (2012). [CrossRef] [PubMed]

58.

M. Han, G. Giese, and J. Bille, “Second harmonic generation imaging of collagen fibrils in cornea and sclera,” Opt. Express 13(15), 5791–5797 (2005). [CrossRef] [PubMed]

59.

S.-W. Teng, H.-Y. Tan, J.-L. Peng, H.-H. Lin, K. H. Kim, W. Lo, Y. Sun, W.-C. Lin, S.-J. Lin, S.-H. Jee, P. T. C. So, and C.-Y. Dong, “Multiphoton autofluorescence and second-harmonic generation imaging of the ex vivo porcine eye,” Invest. Ophthalmol. Vis. Sci. 47(3), 1216–1224 (2006). [CrossRef] [PubMed]

60.

A. Miyazawa, M. Yamanari, S. Makita, M. Miura, K. Kawana, K. Iwaya, H. Goto, and Y. Yasuno, “Tissue discrimination in anterior eye using three optical parameters obtained by polarization sensitive optical coherence tomography,” Opt. Express 17(20), 17426–17440 (2009). [CrossRef] [PubMed]

61.

L. Duan, M. Yamanari, and Y. Yasuno, “Automated phase retardation oriented segmentation of chorio-scleral interface by polarization sensitive optical coherence tomography,” Opt. Express 20(3), 3353–3366 (2012). [CrossRef] [PubMed]

62.

T. Torzicky, M. Pircher, S. Zotter, M. Bonesi, E. Götzinger, and C. K. Hitzenberger, “Automated measurement of choroidal thickness in the human eye by polarization sensitive optical coherence tomography,” Opt. Express 20(7), 7564–7574 (2012). [CrossRef] [PubMed]

63.

J. Liu and C. J. Roberts, “Influence of corneal biomechanical properties on intraocular pressure measurement,” J. Cataract Refract. Surg. 31(1), 146–155 (2005). [CrossRef] [PubMed]

OCIS Codes
(170.4470) Medical optics and biotechnology : Ophthalmology
(170.4500) Medical optics and biotechnology : Optical coherence tomography
(050.2555) Diffraction and gratings : Form birefringence
(180.4315) Microscopy : Nonlinear microscopy

ToC Category:
Ophthalmology Applications

History
Original Manuscript: January 13, 2014
Revised Manuscript: March 26, 2014
Manuscript Accepted: March 31, 2014
Published: April 3, 2014

Citation
Masahiro Yamanari, Satoko Nagase, Shinichi Fukuda, Kotaro Ishii, Ryosuke Tanaka, Takeshi Yasui, Tetsuro Oshika, Masahiro Miura, and Yoshiaki Yasuno, "Scleral birefringence as measured by polarization-sensitive optical coherence tomography and ocular biometric parameters of human eyes in vivo," Biomed. Opt. Express 5, 1391-1402 (2014)
http://www.opticsinfobase.org/boe/abstract.cfm?URI=boe-5-5-1391


Sort:  Author  |  Year  |  Journal  |  Reset  

References

  1. N. A. McBrien and A. Gentle, “Role of the sclera in the development and pathological complications of myopia,” Prog. Retin. Eye Res.22(3), 307–338 (2003). [CrossRef] [PubMed]
  2. C. F. Burgoyne, J. C. Downs, A. J. Bellezza, J. K. Suh, and R. T. Hart, “The optic nerve head as a biomechanical structure: a new paradigm for understanding the role of IOP-related stress and strain in the pathophysiology of glaucomatous optic nerve head damage,” Prog. Retin. Eye Res.24(1), 39–73 (2005). [CrossRef] [PubMed]
  3. J. A. Rada, S. Shelton, and T. T. Norton, “The sclera and myopia,” Exp. Eye Res.82(2), 185–200 (2006). [CrossRef] [PubMed]
  4. J. T. Siegwart and T. T. Norton, “Regulation of the mechanical properties of tree shrew sclera by the visual environment,” Vision Res.39(2), 387–407 (1999). [CrossRef] [PubMed]
  5. N. A. McBrien, L. M. Cornell, and A. Gentle, “Structural and ultrastructural changes to the sclera in a mammalian model of high myopia,” Invest. Ophthalmol. Vis. Sci.42(10), 2179–2187 (2001). [PubMed]
  6. J. K. Pijanka, B. Coudrillier, K. Ziegler, T. Sorensen, K. M. Meek, T. D. Nguyen, H. A. Quigley, and C. Boote, “Quantitative mapping of collagen fiber orientation in non-glaucoma and glaucoma posterior human sclerae,” Invest. Ophthalmol. Vis. Sci.53(9), 5258–5270 (2012). [CrossRef] [PubMed]
  7. J. C. Downs, J.-K. F. Suh, K. A. Thomas, A. J. Bellezza, R. T. Hart, and C. F. Burgoyne, “Viscoelastic material properties of the peripapillary sclera in normal and early-glaucoma monkey eyes,” Invest. Ophthalmol. Vis. Sci.46(2), 540–546 (2005). [CrossRef] [PubMed]
  8. B. Coudrillier, J. Tian, S. Alexander, K. M. Myers, H. A. Quigley, and T. D. Nguyen, “Biomechanics of the human posterior sclera: Age- and glaucoma-related changes measured using inflation testing,” Invest. Ophthalmol. Vis. Sci.53(4), 1714–1728 (2012). [CrossRef] [PubMed]
  9. A. J. Bellezza, C. J. Rintalan, H. W. Thompson, J. C. Downs, R. T. Hart, and C. F. Burgoyne, “Deformation of the lamina cribrosa and anterior scleral canal wall in early experimental glaucoma,” Invest. Ophthalmol. Vis. Sci.44(2), 623–637 (2003). [CrossRef] [PubMed]
  10. H. Yang, H. Thompson, M. D. Roberts, I. A. Sigal, J. C. Downs, and C. F. Burgoyne, “Deformation of the early glaucomatous monkey optic nerve head connective tissue after acute IOP elevation in 3-D histomorphometric reconstructions,” Invest. Ophthalmol. Vis. Sci.52(1), 345–363 (2011). [CrossRef] [PubMed]
  11. H. A. Quigley, M. E. Dorman-Pease, and A. E. Brown, “Quantitative study of collagen and elastin of the optic nerve head and sclera in human and experimental monkey glaucoma,” Curr. Eye Res.10(9), 877–888 (1991). [CrossRef] [PubMed]
  12. S. Nagase, M. Yamanari, R. Tanaka, T. Yasui, M. Miura, T. Iwasaki, H. Goto, and Y. Yasuno, “Anisotropic alteration of scleral birefringence to uniaxial mechanical strain,” PLoS ONE8(3), e58716 (2013). [CrossRef] [PubMed]
  13. M. Yamanari, K. Ishii, S. Fukuda, Y. Lim, L. Duan, S. Makita, M. Miura, T. Oshika, and Y. Yasuno, “Optical rheology of porcine sclera by birefringence imaging,” PLoS ONE7(9), e44026 (2012). [CrossRef] [PubMed]
  14. R. Oldenbourg, E. D. Salmon, and P. T. Tran, “Birefringence of single and bundled microtubules,” Biophys. J.74(1), 645–654 (1998). [CrossRef] [PubMed]
  15. S. K. Nadkarni, M. C. Pierce, B. H. Park, J. F. de Boer, P. Whittaker, B. E. Bouma, J. E. Bressner, E. Halpern, S. L. Houser, and G. J. Tearney, “Measurement of collagen and smooth muscle cell content in atherosclerotic plaques using polarization-sensitive optical coherence tomography,” J. Am. Coll. Cardiol.49(13), 1474–1481 (2007). [CrossRef] [PubMed]
  16. C. J. Doillon, M. G. Dunn, E. Bender, and F. H. Silver, “Collagen fiber formation in repair tissue: development of strength and toughness,” Coll. Relat. Res.5(6), 481–492 (1985). [CrossRef] [PubMed]
  17. D. A. Parry, “The molecular and fibrillar structure of collagen and its relationship to the mechanical properties of connective tissue,” Biophys. Chem.29(1-2), 195–209 (1988). [CrossRef] [PubMed]
  18. G. D. Pins, D. L. Christiansen, R. Patel, and F. H. Silver, “Self-assembly of collagen fibers. influence of fibrillar alignment and decorin on mechanical properties,” Biophys. J.73(4), 2164–2172 (1997). [CrossRef] [PubMed]
  19. E. Götzinger, M. Pircher, M. Sticker, A. F. Fercher, and C. K. Hitzenberger, “Measurement and imaging of birefringent properties of the human cornea with phase-resolved, polarization-sensitive optical coherence tomography,” J. Biomed. Opt.9(1), 94–102 (2004). [CrossRef] [PubMed]
  20. Y. Yasuno, M. Yamanari, K. Kawana, M. Miura, S. Fukuda, S. Makita, S. Sakai, and T. Oshika, “Visibility of trabecular meshwork by standard and polarization-sensitive optical coherence tomography,” J. Biomed. Opt.15(6), 061705 (2010). [CrossRef] [PubMed]
  21. M. G. Ducros, J. D. Marsack, H. G. Rylander, S. L. Thomsen, and T. E. Milner, “Primate retina imaging with polarization-sensitive optical coherence tomography,” J. Opt. Soc. Am. A18(12), 2945–2956 (2001). [CrossRef]
  22. B. Cense, T. C. Chen, B. H. Park, M. C. Pierce, and J. F. de Boer, “Thickness and birefringence of healthy retinal nerve fiber layer tissue measured with polarization-sensitive optical coherence tomography,” Invest. Ophthalmol. Vis. Sci.45(8), 2606–2612 (2004). [CrossRef] [PubMed]
  23. M. Yamanari, M. Miura, S. Makita, T. Yatagai, and Y. Yasuno, “Phase retardation measurement of retinal nerve fiber layer by polarization-sensitive spectral-domain optical coherence tomography and scanning laser polarimetry,” J. Biomed. Opt.13(1), 014013 (2008). [CrossRef] [PubMed]
  24. M. Miura, M. Yamanari, T. Iwasaki, A. E. Elsner, S. Makita, T. Yatagai, and Y. Yasuno, “Imaging polarimetry in age-related macular degeneration,” Invest. Ophthalmol. Vis. Sci.49(6), 2661–2667 (2008). [CrossRef] [PubMed]
  25. Y. Yasuno, M. Yamanari, K. Kawana, T. Oshika, and M. Miura, “Investigation of post-glaucoma-surgery structures by three-dimensional and polarization sensitive anterior eye segment optical coherence tomography,” Opt. Express17(5), 3980–3996 (2009). [CrossRef] [PubMed]
  26. Y. Lim, M. Yamanari, S. Fukuda, Y. Kaji, T. Kiuchi, M. Miura, T. Oshika, and Y. Yasuno, “Birefringence measurement of cornea and anterior segment by office-based polarization-sensitive optical coherence tomography,” Biomed. Opt. Express2(8), 2392–2402 (2011). [CrossRef] [PubMed]
  27. M. Yamanari, S. Makita, and Y. Yasuno, “Polarization-sensitive swept-source optical coherence tomography with continuous source polarization modulation,” Opt. Express16(8), 5892–5906 (2008). [CrossRef] [PubMed]
  28. M. Yamanari, Y. Lim, S. Makita, and Y. Yasuno, “Visualization of phase retardation of deep posterior eye by polarization-sensitive swept-source optical coherence tomography with 1- µm probe,” Opt. Express17(15), 12385–12396 (2009). [CrossRef] [PubMed]
  29. M. Yamanari, S. Makita, Y. Lim, and Y. Yasuno, “Full-range polarization-sensitive swept-source optical coherence tomography by simultaneous transversal and spectral modulation,” Opt. Express18(13), 13964–13980 (2010). [CrossRef] [PubMed]
  30. M. Miura, M. Yamanari, T. Iwasaki, M. Itoh, T. Yatagai, and Y. Yasuno, “Polarization-sensitive optical coherence tomography of necrotizing scleritis,” Ophthalmic Surg. Lasers Imaging40(6), 607–610 (2009). [CrossRef] [PubMed]
  31. S. Makita, M. Yamanari, and Y. Yasuno, “Generalized jones matrix optical coherence tomography: performance and local birefringence imaging,” Opt. Express18(2), 854–876 (2010). [CrossRef] [PubMed]
  32. L. Duan, S. Makita, M. Yamanari, Y. Lim, and Y. Yasuno, “Monte-carlo-based phase retardation estimator for polarization sensitive optical coherence tomography,” Opt. Express19(17), 16330–16345 (2011). [CrossRef] [PubMed]
  33. A. Alm and S. F. Nilsson, “Uveoscleral outflow--a review,” Exp. Eye Res.88(4), 760–768 (2009). [CrossRef] [PubMed]
  34. S. Sakai, M. Yamanari, Y. Lim, N. Nakagawa, and Y. Yasuno, “In vivo evaluation of human skin anisotropy by polarization-sensitive optical coherence tomography,” Biomed. Opt. Express2(9), 2623–2631 (2011). [CrossRef] [PubMed]
  35. T. W. Olsen, S. Sanderson, X. Feng, and W. C. Hubbard, “Porcine sclera: Thickness and surface area,” Invest. Ophthalmol. Vis. Sci.43(8), 2529–2532 (2002). [PubMed]
  36. B. K. Pierscionek, M. Asejczyk-Widlicka, and R. A. Schachar, “The effect of changing intraocular pressure on the corneal and scleral curvatures in the fresh porcine eye,” Br. J. Ophthalmol.91(6), 801–803 (2007). [CrossRef] [PubMed]
  37. D. S. Schultz, J. C. Lotz, S. M. Lee, M. L. Trinidad, and J. M. Stewart, “Structural factors that mediate scleral stiffness,” Invest. Ophthalmol. Vis. Sci.49(10), 4232–4236 (2008). [CrossRef] [PubMed]
  38. S. Nicoli, G. Ferrari, M. Quarta, C. Macaluso, P. Govoni, D. Dallatana, and P. Santi, “Porcine sclera as a model of human sclera for in vitro transport experiments: histology, sem, and comparative permeability,” Mol. Vis.15, 259–266 (2009). [PubMed]
  39. M. J. A. Girard, J.-K. F. Suh, M. Bottlang, C. F. Burgoyne, and J. C. Downs, “Biomechanical changes in the sclera of monkey eyes exposed to chronic iop elevations,” Invest. Ophthalmol. Vis. Sci.52(8), 5656–5669 (2011). [CrossRef] [PubMed]
  40. P. M. Pinsky, D. van der Heide, and D. Chernyak, “Computational modeling of mechanical anisotropy in the cornea and sclera,” J. Cataract Refract. Surg.31(1), 136–145 (2005). [CrossRef] [PubMed]
  41. R. Grytz and G. Meschke, “A computational remodeling approach to predict the physiological architecture of the collagen fibril network in corneo-scleral shells,” Biomech. Model. Mechanobiol.9(2), 225–235 (2010). [CrossRef] [PubMed]
  42. Collaborative Normal-Tension Glaucoma Study Group, “Comparison of glaucomatous progression between untreated patients with normal-tension glaucoma and patients with therapeutically reduced intraocular pressures,” Am. J. Ophthalmol.126(4), 487–497 (1998). [CrossRef] [PubMed]
  43. Y. Suzuki, A. Iwase, M. Araie, T. Yamamoto, H. Abe, S. Shirato, Y. Kuwayama, H. K. Mishima, H. Shimizu, G. Tomita, Y. Inoue, Y. Kitazawa, and Tajimi Study Group, “Risk factors for open-angle glaucoma in a japanese population: The tajimi study,” Ophthalmology113(9), 1613–1617 (2006). [CrossRef] [PubMed]
  44. M. J. A. Girard, J. C. Downs, C. F. Burgoyne, and J.-K. F. Suh, “Peripapillary and posterior scleral mechanics--part i: Development of an anisotropic hyperelastic constitutive model,” J. Biomech. Eng.131(5), 051011 (2009). [CrossRef] [PubMed]
  45. B. Coudrillier, C. Boote, H. A. Quigley, and T. D. Nguyen, “Scleral anisotropy and its effects on the mechanical response of the optic nerve head,” Biomech. Model. Mechanobiol.12(5), 941–963 (2013). [CrossRef] [PubMed]
  46. M. J. Hogan, J. A. Alvarado, and J. E. Weddell, Histology of the human eye: an atlas and textbook (Saunders, 1971).
  47. H. A. Quigley, E. M. Addicks, W. R. Green, and A. E. Maumenee, “Optic nerve damage in human glaucoma. Ii. the site of injury and susceptibility to damage,” Arch. Ophthalmol.99(4), 635–649 (1981). [CrossRef] [PubMed]
  48. Y. Lim, Y.-J. Hong, L. Duan, M. Yamanari, and Y. Yasuno, “Passive component based multifunctional jones matrix swept source optical coherence tomography for doppler and polarization imaging,” Opt. Lett.37(11), 1958–1960 (2012). [CrossRef] [PubMed]
  49. T. Torzicky, S. Marschall, M. Pircher, B. Baumann, M. Bonesi, S. Zotter, E. Götzinger, W. Trasischker, T. Klein, W. Wieser, B. Biedermann, R. Huber, P. Andersen, and C. K. Hitzenberger, “Retinal polarization-sensitive optical coherence tomography at 1060 nm with 350 khz a-scan rate using an fourier domain mode locked laser,” J. Biomed. Opt.18(2), 026008 (2013). [CrossRef] [PubMed]
  50. M. C. van Turnhout, S. Kranenbarg, and J. L. van Leeuwen, “Modeling optical behavior of birefringent biological tissues for evaluation of quantitative polarized light microscopy,” J. Biomed. Opt.14(5), 054018 (2009). [CrossRef] [PubMed]
  51. P. Watson and B. Hazleman, The Sclera and Systemic Disorders (Jp Medical Pub, 2012).
  52. R. H. Newton and K. M. Meek, “The integration of the corneal and limbal fibrils in the human eye,” Biophys. J.75(5), 2508–2512 (1998). [CrossRef] [PubMed]
  53. D. Yan, S. McPheeters, G. Johnson, U. Utzinger, and J. P. Vande Geest, “Microstructural differences in the human posterior sclera as a function of age and race,” Invest. Ophthalmol. Vis. Sci.52(2), 821–829 (2011). [CrossRef] [PubMed]
  54. M. J. A. Girard, A. Dahlmann-Noor, S. Rayapureddi, J. A. Bechara, B. M. E. Bertin, H. Jones, J. Albon, P. T. Khaw, and C. R. Ethier, “Quantitative mapping of scleral fiber orientation in normal rat eyes,” Invest. Ophthalmol. Vis. Sci.52(13), 9684–9693 (2011). [CrossRef] [PubMed]
  55. N. Morishige, A. J. Wahlert, M. C. Kenney, D. J. Brown, K. Kawamoto, T.-i. Chikama, T. Nishida, and J. V. Jester, “Second-harmonic imaging microscopy of normal human and keratoconus cornea,” Invest. Ophthalmol. Vis. Sci.48(3), 1087–1094 (2007). [CrossRef] [PubMed]
  56. J. M. Bueno, E. J. Gualda, A. Giakoumaki, P. Pérez-Merino, S. Marcos, and P. Artal, “Multiphoton microscopy of ex vivo corneas after collagen cross-linking,” Invest. Ophthalmol. Vis. Sci.52(8), 5325–5331 (2011). [CrossRef] [PubMed]
  57. N. Morishige, N. Yamada, X. Zhang, Y. Morita, N. Yamada, K. Kimura, A. Takahara, and K.-H. Sonoda, “Abnormalities of stromal structure in the bullous keratopathy cornea identified by second harmonic generation imaging microscopy,” Invest. Ophthalmol. Vis. Sci.53(8), 4998–5003 (2012). [CrossRef] [PubMed]
  58. M. Han, G. Giese, and J. Bille, “Second harmonic generation imaging of collagen fibrils in cornea and sclera,” Opt. Express13(15), 5791–5797 (2005). [CrossRef] [PubMed]
  59. S.-W. Teng, H.-Y. Tan, J.-L. Peng, H.-H. Lin, K. H. Kim, W. Lo, Y. Sun, W.-C. Lin, S.-J. Lin, S.-H. Jee, P. T. C. So, and C.-Y. Dong, “Multiphoton autofluorescence and second-harmonic generation imaging of the ex vivo porcine eye,” Invest. Ophthalmol. Vis. Sci.47(3), 1216–1224 (2006). [CrossRef] [PubMed]
  60. A. Miyazawa, M. Yamanari, S. Makita, M. Miura, K. Kawana, K. Iwaya, H. Goto, and Y. Yasuno, “Tissue discrimination in anterior eye using three optical parameters obtained by polarization sensitive optical coherence tomography,” Opt. Express17(20), 17426–17440 (2009). [CrossRef] [PubMed]
  61. L. Duan, M. Yamanari, and Y. Yasuno, “Automated phase retardation oriented segmentation of chorio-scleral interface by polarization sensitive optical coherence tomography,” Opt. Express20(3), 3353–3366 (2012). [CrossRef] [PubMed]
  62. T. Torzicky, M. Pircher, S. Zotter, M. Bonesi, E. Götzinger, and C. K. Hitzenberger, “Automated measurement of choroidal thickness in the human eye by polarization sensitive optical coherence tomography,” Opt. Express20(7), 7564–7574 (2012). [CrossRef] [PubMed]
  63. J. Liu and C. J. Roberts, “Influence of corneal biomechanical properties on intraocular pressure measurement,” J. Cataract Refract. Surg.31(1), 146–155 (2005). [CrossRef] [PubMed]

Cited By

Alert me when this paper is cited

OSA is able to provide readers links to articles that cite this paper by participating in CrossRef's Cited-By Linking service. CrossRef includes content from more than 3000 publishers and societies. In addition to listing OSA journal articles that cite this paper, citing articles from other participating publishers will also be listed.


« Previous Article  |  Next Article »

OSA is a member of CrossRef.

CrossCheck Deposited