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3D Histomorphometric Reconstruction and Quantification of the Optic Nerve Head Connective Tissues

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Glaucoma

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1695))

Abstract

Accurately characterizing the 3D geometry of the optic nerve head neural and connective tissues has been the goal of a large and important body of scientific work. In the present report, we summarize our methods for the high-resolution, digital, 3D histomorphometric reconstruction of the optic nerve head tissues, including their visualization, parameterization, and quantification. In addition, we present our methods for between-eye comparisons of this anatomy, and their use to determine animal-specific and experiment-wide experimental glaucoma versus Control eye differences in the unilateral, monkey experimental glaucoma model. Finally, we demonstrate its application to finite element modeling, 3D optic nerve head reconstruction of other species, and 3D optic nerve head reconstructions using other imaging modalities.

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References

  1. Burgoyne CF, Downs JC, Bellezza AJ, Hart RT (2004) Three-dimensional reconstruction of normal and early glaucoma monkey optic nerve head connective tissues. Invest Ophthalmol Vis Sci 45(12):4388–4399. https://doi.org/10.1167/iovs.04-0022

    Article  PubMed  Google Scholar 

  2. Yang H, Downs JC, Bellezza A, Thompson H, Burgoyne CF (2007) 3-D histomorphometry of the normal and early glaucomatous monkey optic nerve head: prelaminar neural tissues and cupping. Invest Ophthalmol Vis Sci 48(11):5068–5084. https://doi.org/10.1167/iovs.07-0790

    Article  PubMed  Google Scholar 

  3. Yang H, Downs JC, Girkin C, Sakata L, Bellezza A, Thompson H, Burgoyne CF (2007) 3-D histomorphometry of the normal and early glaucomatous monkey optic nerve head: lamina cribrosa and peripapillary scleral position and thickness. Invest Ophthalmol Vis Sci 48(10):4597–4607. https://doi.org/10.1167/iovs.07-0349

    Article  PubMed  PubMed Central  Google Scholar 

  4. Yang H, Downs JC, Burgoyne CF (2009) Physiologic intereye differences in monkey optic nerve head architecture and their relation to changes in early experimental glaucoma. Invest Ophthalmol Vis Sci 50(1):224–234. https://doi.org/10.1167/iovs.08-2464

    Article  PubMed  Google Scholar 

  5. Yang H, Williams G, Downs JC, Sigal IA, Roberts MD, Thompson H, Burgoyne CF (2011) Posterior (outward) migration of the lamina cribrosa and early cupping in monkey experimental glaucoma. Invest Ophthalmol Vis Sci 52(10):7109–7121. https://doi.org/10.1167/iovs.11-7448

    Article  PubMed  PubMed Central  Google Scholar 

  6. Lockwood H, Reynaud J, Gardiner S, Grimm J, Libertiaux V, Downs JC, Yang H, Burgoyne CF (2015) Lamina cribrosa microarchitecture in normal monkey eyes part 1: methods and initial results. Invest Ophthalmol Vis Sci 56(3):1618–1637. https://doi.org/10.1167/iovs.14-15967

    Article  PubMed  PubMed Central  Google Scholar 

  7. Pazos M, Yang H, Gardiner SK, Cepurna WO, Johnson EC, Morrison JC, Burgoyne CF (2016) Expansions of the neurovascular scleral canal and contained optic nerve occur early in the hypertonic saline rat experimental glaucoma model. Exp Eye Res 145:173–186. https://doi.org/10.1016/j.exer.2015.10.014

    Article  CAS  PubMed  Google Scholar 

  8. Reynaud J, Lockwood H, Gardiner SK, Williams G, Yang H, Burgoyne CF (2016) Lamina cribrosa microarchitecture in monkey early experimental glaucoma: global change. Invest Ophthalmol Vis Sci 57(7):3451–3469. https://doi.org/10.1167/iovs.16-19474

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Roberts MD, Grau V, Grimm J, Reynaud J, Bellezza AJ, Burgoyne CF, Downs JC (2009) Remodeling of the connective tissue microarchitecture of the lamina cribrosa in early experimental glaucoma. Invest Ophthalmol Vis Sci 50(2):681–690. https://doi.org/10.1167/iovs.08-1792

    Article  PubMed  Google Scholar 

  10. Pazos M, Yang H, Gardiner SK, Cepurna WO, Johnson EC, Morrison JC, Burgoyne CF (2015) Rat optic nerve head anatomy within 3D histomorphometric reconstructions of normal control eyes. Exp Eye Res 139:1–12. https://doi.org/10.1016/j.exer.2015.05.011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Burgoyne CF (2015) The non-human primate experimental glaucoma model. Exp Eye Res 141:57–73. https://doi.org/10.1016/j.exer.2015.06.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Strouthidis NG, Yang H, Fortune B, Downs JC, Burgoyne CF (2009) Detection of optic nerve head neural canal opening within histomorphometric and spectral domain optical coherence tomography data sets. Invest Ophthalmol Vis Sci 50(1):214–223. https://doi.org/10.1167/iovs.08-2302

    Article  PubMed  Google Scholar 

  13. Jansonius NM, Nevalainen J, Selig B, Zangwill LM, Sample PA, Budde WM, Jonas JB, Lagreze WA, Airaksinen PJ, Vonthein R, Levin LA, Paetzold J, Schiefer U (2009) A mathematical description of nerve fiber bundle trajectories and their variability in the human retina. Vis Res 49(17):2157–2163. https://doi.org/10.1016/j.visres.2009.04.029

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Hood DC, Kardon RH (2007) A framework for comparing structural and functional measures of glaucomatous damage. Prog Retin Eye Res 26(6):688–710. https://doi.org/10.1016/j.preteyeres.2007.08.001

    Article  PubMed  PubMed Central  Google Scholar 

  15. Turpin A, Sampson GP, McKendrick AM (2009) Combining ganglion cell topology and data of patients with glaucoma to determine a structure-function map. Invest Ophthalmol Vis Sci 50(7):3249–3256. https://doi.org/10.1167/iovs.08-2492

    Article  PubMed  Google Scholar 

  16. Harwerth RS, Wheat JL, Fredette MJ, Anderson DR (2010) Linking structure and function in glaucoma. Prog Retin Eye Res 29(4):249–271. https://doi.org/10.1016/j.preteyeres.2010.02.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Jonas JB, Nguyen NX, Naumann GO (1989) The retinal nerve fiber layer in normal eyes. Ophthalmology 96(5):627–632

    Article  CAS  PubMed  Google Scholar 

  18. Patel NB, Wheat JL, Rodriguez A, Tran V, Harwerth RS (2012) Agreement between retinal nerve fiber layer measures from Spectralis and cirrus spectral domain OCT. Optom Vis Sci 89(5):E652–E666. https://doi.org/10.1097/OPX.0b013e318238c34e

    Article  PubMed  PubMed Central  Google Scholar 

  19. Garway-Heath DF, Poinoosawmy D, Fitzke FW, Hitchings RA (2000) Mapping the visual field to the optic disc in normal tension glaucoma eyes. Ophthalmology 107(10):1809–1815

    Article  CAS  PubMed  Google Scholar 

  20. Downs JC, Yang H, Girkin C, Sakata L, Bellezza A, Thompson H, Burgoyne CF (2007) Three-dimensional histomorphometry of the normal and early glaucomatous monkey optic nerve head: neural canal and subarachnoid space architecture. Invest Ophthalmol Vis Sci 48(7):3195–3208. https://doi.org/10.1167/iovs.07-0021

    Article  PubMed  PubMed Central  Google Scholar 

  21. He L, Ren R, Yang H, Hardin C, Reyes L, Reynaud J, Gardiner SK, Fortune B, Demirel S, Burgoyne CF (2014) Anatomic vs. acquired image frame discordance in spectral domain optical coherence tomography minimum rim measurements. PLoS One 9(3):e92225. https://doi.org/10.1371/journal.pone.0092225

    Article  PubMed  PubMed Central  Google Scholar 

  22. Reis AS, Sharpe GP, Yang H, Nicolela MT, Burgoyne CF, Chauhan BC (2012) Optic disc margin anatomy in patients with glaucoma and normal controls with spectral domain optical coherence tomography. Ophthalmology 119(4):738–747. https://doi.org/10.1016/j.ophtha.2011.09.054

    Article  PubMed  PubMed Central  Google Scholar 

  23. Anderson DR, Hoyt WF (1969) Ultrastructure of intraorbital portion of human and monkey optic nerve. Arch Ophthalmol 82(4):506–530

    Article  CAS  PubMed  Google Scholar 

  24. Elschnig A (1928) Über Glaukom. Albrecht von Græfes Archiv für Ophthalmologie 120(1–2):94–116. https://doi.org/10.1007/bf01852791

    Article  Google Scholar 

  25. Reis AS, O'Leary N, Yang H, Sharpe GP, Nicolela MT, Burgoyne CF, Chauhan BC (2012) Influence of clinically invisible, but optical coherence tomography detected, optic disc margin anatomy on neuroretinal rim evaluation. Invest Ophthalmol Vis Sci 53(4):1852–1860. https://doi.org/10.1167/iovs.11-9309

    Article  PubMed  PubMed Central  Google Scholar 

  26. Yang H, Thompson H, Roberts MD, Sigal IA, Downs JC, Burgoyne CF (2011) 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. https://doi.org/10.1167/iovs.09-5122

    Article  PubMed  PubMed Central  Google Scholar 

  27. Yang H, Ren R, Lockwood H, Williams G, Libertiaux V, Downs C, Gardiner SK, Burgoyne CF (2015) The connective tissue components of optic nerve head cupping in monkey experimental glaucoma part 1: global change. Invest Ophthalmol Vis Sci 56(13):7661–7678. https://doi.org/10.1167/iovs.15-17624

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Grau V, Downs JC, Burgoyne CF (2006) Segmentation of trabeculated structures using an anisotropic Markov random field: application to the study of the optic nerve head in glaucoma. IEEE Trans Med Imaging 25(3):245–255. https://doi.org/10.1109/TMI.2005.862743

    Article  PubMed  Google Scholar 

  29. Dougherty RP, Kunzelmann K-H 2007 Computing local thickness of 3D structures with ImageJ. In: Microscopy & microanalysis meeting, Fort. Lauderdale, FL, 5–9 August 2007

    Google Scholar 

  30. Saito T, Toriwaki J-I (1994) New algorithms for euclidean distance transformation of an n-dimensional digitized picture with applications. Pattern Recogn 27(11):1551–1565. https://doi.org/10.1016/0031-3203(94)90133-3

    Article  Google Scholar 

  31. Hildebrand T, Rüegsegger P (1997) A new method for the model-independent assessment of thickness in three-dimensional images. J Microsc 185(1):67–75. https://doi.org/10.1046/j.1365-2818.1997.1340694.x

    Article  Google Scholar 

  32. Carolynne AK (2014) Chapter III: two parameter gamma distribution. In: Carolynne AK (ed) Gamma and related distributions. Books on Demand, Norderstedt, Germany, pp 6–27

    Google Scholar 

  33. Quigley HA, Hohman RM, Addicks EM, Massof RW, Green WR (1983) Morphologic changes in the lamina cribrosa correlated with neural loss in open-angle glaucoma. Am J Ophthalmol 95(5):673–691

    Article  CAS  PubMed  Google Scholar 

  34. Minckler DS, Spaeth GL (1981) Optic nerve damage in glaucoma. Surv Ophthalmol 26(3):128–148

    Article  CAS  PubMed  Google Scholar 

  35. Quigley H, Anderson DR (1976) The dynamics and location of axonal transport blockade by acute intraocular pressure elevation in primate optic nerve. Investig Ophthalmol 15(8):606–616

    CAS  Google Scholar 

  36. Minckler DS (1986) Correlations between anatomic features and axonal transport in primate optic nerve head. Trans Am Ophthalmol Soc 84:429–452

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Quigley HA, Addicks EM (1981) Regional differences in the structure of the lamina cribrosa and their relation to glaucomatous optic nerve damage. Arch Ophthalmol 99(1):137–143

    Article  CAS  PubMed  Google Scholar 

  38. Radius RL, Gonzales M (1981) Anatomy of the lamina cribrosa in human eyes. Arch Ophthalmol 99(12):2159–2162

    Article  CAS  PubMed  Google Scholar 

  39. Bellezza AJ, Hart RT, Burgoyne CF (2000) The optic nerve head as a biomechanical structure: initial finite element modeling. Invest Ophthalmol Vis Sci 41(10):2991–3000

    CAS  PubMed  Google Scholar 

  40. Sigal IA, Yang H, Roberts MD, Downs JC (2010) Morphing methods to parameterize specimen-specific finite element model geometries. J Biomech 43(2):254–262. https://doi.org/10.1016/j.jbiomech.2009.08.036

    Article  PubMed  Google Scholar 

  41. Sigal IA, Yang H, Roberts MD, Grimm JL, Burgoyne CF, Demirel S, Downs JC (2011) IOP-induced lamina cribrosa deformation and scleral canal expansion: independent or related? Invest Ophthalmol Vis Sci 52(12):9023–9032. https://doi.org/10.1167/iovs.11-8183

    Article  PubMed  PubMed Central  Google Scholar 

  42. Girard MJ, Suh JK, Bottlang M, Burgoyne CF, Downs JC (2009) Scleral biomechanics in the aging monkey eye. Invest Ophthalmol Vis Sci 50(11):5226–5237. https://doi.org/10.1167/iovs.08-3363

    Article  PubMed  PubMed Central  Google Scholar 

  43. Fazio MA, Grytz R, Bruno L, Girard MJ, Gardiner S, Girkin CA, Downs JC (2012) Regional variations in mechanical strain in the posterior human sclera. Invest Ophthalmol Vis Sci 53(9):5326–5333. https://doi.org/10.1167/iovs.12-9668

    Article  PubMed  PubMed Central  Google Scholar 

  44. Grytz R, Meschke G (2010) 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. https://doi.org/10.1007/s10237-009-0173-2

    Article  PubMed  Google Scholar 

  45. Coudrillier B, Pijanka JK, Jefferys JL, Goel A, Quigley HA, Boote C, Nguyen TD (2015) Glaucoma-related changes in the mechanical properties and collagen micro-architecture of the human sclera. PLoS One 10(7):e0131396. https://doi.org/10.1371/journal.pone.0131396

    Article  PubMed  PubMed Central  Google Scholar 

  46. Srinivasan VJ, Adler DC, Chen Y, Gorczynska I, Huber R, Duker J, Schuman JS, Fujimoto JG (2008) Ultrahigh-speed optical coherence tomography for three-dimensional and en face imaging of the retina and optic nerve head. Invest Ophthalmol Vis Sci 49(11):5103–5110. https://doi.org/10.1167/iovs.08-2127

    Article  PubMed  PubMed Central  Google Scholar 

  47. Lee EJ, Kim TW, Weinreb RN, Park KH, Kim SH, Kim DM (2011) Visualization of the lamina cribrosa using enhanced depth imaging spectral-domain optical coherence tomography. Am J Ophthalmol 152(1):87–95. e81. https://doi.org/10.1016/j.ajo.2011.01.024

    Article  PubMed  Google Scholar 

  48. Girard MJ, Tun TA, Husain R, Acharyya S, Haaland BA, Wei X, Mari JM, Perera SA, Baskaran M, Aung T, Strouthidis NG (2015) Lamina cribrosa visibility using optical coherence tomography: comparison of devices and effects of image enhancement techniques. Invest Ophthalmol Vis Sci 56(2):865–874. https://doi.org/10.1167/iovs.14-14903

    Article  PubMed  Google Scholar 

  49. Reynaud J, Cull G, Wang L, Fortune B, Gardiner S, Burgoyne CF, Cioffi GA (2012) Automated quantification of optic nerve axons in primate glaucomatous and normal eyes—method and comparison to semi-automated manual quantification. Invest Ophthalmol Vis Sci 53(6):2951–2959. https://doi.org/10.1167/iovs.11-9274

    Article  PubMed  PubMed Central  Google Scholar 

  50. Johnstone J, Fazio M, Rojananuangnit K, Smith B, Clark M, Downs C, Owsley C, Girard MJ, Mari JM, Girkin CA (2014) Variation of the axial location of Bruch's membrane opening with age, choroidal thickness, and race. Invest Ophthalmol Vis Sci 55(3):2004–2009. https://doi.org/10.1167/iovs.13-12937

    Article  PubMed  PubMed Central  Google Scholar 

  51. He L, Yang H, Gardiner SK, Williams G, Hardin C, Strouthidis NG, Fortune B, Burgoyne CF (2014) Longitudinal detection of optic nerve head changes by spectral domain optical coherence tomography in early experimental glaucoma. Invest Ophthalmol Vis Sci 55(1):574–586. https://doi.org/10.1167/iovs.13-13245

    Article  PubMed  PubMed Central  Google Scholar 

  52. Yang H, He L, Gardiner SK, Reynaud J, Williams G, Hardin C, Strouthidis NG, Downs JC, Fortune B, Burgoyne CF (2014) Age-related differences in longitudinal structural change by spectral-domain optical coherence tomography in early experimental glaucoma. Invest Ophthalmol Vis Sci 55(10):6409–6420. https://doi.org/10.1167/iovs.14-14156

    Article  PubMed  PubMed Central  Google Scholar 

  53. Ivers KM, Yang H, Gardiner SK, Qin L, Reyes L, Fortune B, Burgoyne CF (2016) In vivo detection of laminar and peripapillary scleral hypercompliance in early monkey experimental glaucoma. Invest Ophthalmol Vis Sci 57(9):OCT388–OCT403. https://doi.org/10.1167/iovs.15-18666

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgment

Supported in part by USPHS grants R01EY011610 (CFB) from the National Eye Institute, National Institutes of Health, Bethesda, Maryland; a grant from the American Health Assistance Foundation (now known as Bright Focus), Rockville, Maryland (CFB); a grant from The Whitaker Foundation, Arlington, Virginia (CFB); a Research to Prevent Blindness Career Development Award (CFB); The Alcon Research Institute; The Legacy Good Samaritan Foundation, Portland, Oregon; and the Sears Trust for Biomedical Research, Mexico, Missouri.

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Authors and Affiliations

  1. Optic Nerve Head Research Laboratory, Legacy Research Institute, Devers Eye Institute, 1225 NE 2nd Ave., Portland, OR, 97232, USA

    Hongli Yang, Juan Reynaud, Howard Lockwood, Galen Williams, Christy Hardin, Luke Reyes & Claude F. Burgoyne M.D.

  2. Discoveries in Sight Research Laboratories, Legacy Research Institute, Devers Eye Institute, Portland, OR, USA

    Hongli Yang, Juan Reynaud, Howard Lockwood, Galen Williams, Christy Hardin, Luke Reyes, Stuart K. Gardiner & Claude F. Burgoyne M.D.

Authors
  1. Hongli Yang
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  2. Juan Reynaud
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  3. Howard Lockwood
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  4. Galen Williams
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  5. Christy Hardin
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  6. Luke Reyes
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  7. Stuart K. Gardiner
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  8. Claude F. Burgoyne M.D.
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Corresponding author

Correspondence to Claude F. Burgoyne M.D. .

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Editors and Affiliations

  1. Department of Ophthalmology, Massachusetts Eye and Ear Infirmary/Schepens Eye, Research Institute, Harvard Medical School, Boston, Massachusetts, USA

    Tatjana C. Jakobs

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Yang, H. et al. (2018). 3D Histomorphometric Reconstruction and Quantification of the Optic Nerve Head Connective Tissues. In: Jakobs, T. (eds) Glaucoma. Methods in Molecular Biology, vol 1695. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7407-8_17

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  • DOI: https://doi.org/10.1007/978-1-4939-7407-8_17

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  • Publisher Name: Humana Press, New York, NY

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