The Corneoscleral Shell of the Eye: an Age-Related Analysis of Structural Biomechanical Properties. Literature review

Structural biomechanical properties of the ocular corneoscleral shell largely determine its anatomic and optical parameters and its supporting and protective function. Therefore, changes related to age restructuring processes may affect the state of the cornea and the sclera, which should be taken into account in diagnosing eye diseases, especially age-related. According to actual literary data, age-related changes of the corneoscleral shell affecting its biomechanical properties involve all connective tissue components of the extracellular matrix: fibrous proteins (collagen and elastin) and intermediate substance components (proteoglycans and glycosaminoglycans). Aged patients have a larger diameter of elastic fiber fibrils in the external part of the sclera and a lower density of fibrils in the center as compared to young patients, which is an evidence of elastin damage at the molecular level and fibril degeneration. Age-related changes of proteoglycans are primarily
manifested in hydration loss, which leads to an increase in corneal and sclera density and regional thinning of tissues. Agerelated changes of collagen are less expressed than those of elastin and proteoglycans. Yet, the distance between collagen fibrils in the cornea becomes smaller with age; they are subject to destruction, and small spaces devoid of collagen tend to appear in the posterior stroma. The most pronounced age-related degenerative changes of collagen in the deeper layers of the corneal stroma occur in the limb, which accumulates more cross striated collagen fibrils. Recent years of research have shown that the formation of cross-linked chemical bonds, i.e. intra- and intermolecular cross links of collagen is the most important structural factor. It is this particular process that is responsible for structural stability of the corneal and scleral tissue, which tends to change with age or due to certain eye diseases, such as keratoconus or progressive myopia. Obviously, we need clinical technologies that allow an adequate estimation of the biomechanical state of the fibrous shell of the eye.

1. Bailey A. J. Structure, function and ageing of the collagens of the eye. Eye (Lond). 1987;1 (Pt 2):175‑183.

2. Iomdina E. N., Bauer S. M., Kotlyar K. E. [Biomechanics of eyes: theoretical aspects and clinical applications]. Biomekhanika glaza: teoreticheskie aspekty i klinicheskie prilozheniya. Moscow: Real’noe vremya; 2015. (in Russ.).

3. Fung Y. C. Biomechanics. Mechanical Properties of Living Tissues. NewYork: Springer-Verlag; 1990.

4. Eysteinsson T., Jonasson F., Sasaki H., Arnarsson A., et al. Central corneal thickness, radius of the corneal curvature and intraocular pressure in normal subjects using non-contact techniques: Reykjavik Eye Study. Acta Ophthalmol Scand. 2002;80 (1):11‑15.

5. Lee P. P., Walt J. W., Rosenblatt L. C., Siegartel L. R., Stern L. S., Glaucoma Care Study G. Association between intraocular pressure variation and glaucoma progression: data from a United States chart review. Am J Ophthalmol. 2007;144 (6):901‑907.

6. Kaufmann C., Bachmann L. M., Robert Y. C., Thiel M. A. Ocular pulse amplitude in

7. Lee R. E., Davison P. F. The collagens of the developing bovine cornea. Exp Eye Res. 1984;39 (5):639‑652.

8. healthy subjects as measured by dynamic contour tonometry. Arch Ophthalmol. 2006;124 (8):1104‑1108.

9. Vannas S., Teir H. Observations on structures and age changes in the human sclera. Acta Ophthalmol (Copenh). 1960;38:268‑279.

10. Liu J. H., Kripke D. F., Twa M. D., Hoffman R. E., et al. Twenty-four-hour pattern of intraocular pressure in the aging population. Invest Ophthalmol Vis Sci. 1999;40 (12):2912‑2917.

11. Ben-Zvi A., Rodrigues M. M., Krachmer J. H., Fujikawa L. S. Immunohistochemical characterization of extracellular matrix in the developing human cornea. Curr Eye Res. 1986;5 (2):105‑117.

12. Buzard K. A. Introduction to biomechanics of the cornea. Refract Corneal Surg. 1992;8 (2): 127‑138.

13. Rucklidge G. J., Milne G., McGaw B. A., Milne E., Robins S. P. Turnover rates of different collagen types measured by isotope ratio mass spectrometry. Biochim Biophys Acta. 1992;1156 (1):57‑61.

14. D. M. M. The cornea and the sclera. In: Davson Y, ed The Eye: Vegetative Physiology and Biochemistry. Orlando, Florida: AcademicPress; 1984. p. 1‑58.

15. Ihanamaki T., Salminen H., Saamanen A. M., Pelliniemi L. J., et al. Age-dependent changes in the expression of matrix components in the mouse eye. Exp Eye Res. 2001;72 (4):423‑431.

16. Boote C., Dennis S., Huang Y., Quantock A. J., Meek K. M. Lamellar orientation in human cornea in relation to mechanical properties. J Struct Biol. 2005;149 (1):1‑6.

17. Manschot W. A. Senile scleral plaques and senile scleromalacia. Br J Ophthalmol.

18. Borcherding M. S., Blacik L. J., Sittig R. A., Bizzell J. W., Breen M., Weinstein

19. 1978;62 (6):376‑380.

20. H. G. Proteoglycans and collagen fibre organization in human corneoscleral tissue. Exp Eye Res. 1975;21 (1):59‑70.

21. Sorsby A., Wilcox K., Ham D. The Calcium Content of the Sclerotic and Its Variation with Age. Br J Ophthalmol. 1935;19 (6):327‑337.

22. Komai Y., Ushiki T. The three-dimensional organization of collagen fibrils in the human cornea and sclera. Invest Ophthalmol Vis Sci. 1991;32 (8):2244‑2258.

23. Hogan M. J., Alvarado J. Ultrastructure of the deep corneolimbal region. Doc Ophthalmol. 1969;26:9‑30.

24. Olsen T. On the calculation of power from curvature of the cornea. Br J Ophthalmol. 1986;70 (2):152‑154.

25. Hirano K., Nakamura M., Kobayashi M., Kobayashi K., Hoshino T., Awaya S. Longspacing collagen in the human corneal stroma. Jpn J Ophthalmol. 1993;37 (2):148‑155.

26. Shimmyo M., Orloff P. N. Corneal thickness and axial length. Am J Ophthalmol. 2005;139 (3):553‑554.

27. Yan D., McPheeters S., Johnson G., Utzinger U., Vande Geest J. P. Microstructural differences in the human posterior sclera as a function of age and race. Invest Ophthalmol Vis Sci. 2011;52 (2):821‑829.

28. Olsen T. W., Aaberg S. Y., Geroski D. H., Edelhauser H. F. Human sclera: thickness and surface area. Am J Ophthalmol. 1998;125 (2):237‑241.

29. Girard M. J., Suh J. K., Bottlang M., Burgoyne C. F., Downs J. C. Scleral biomechanics in the aging monkey eye. Invest Ophthalmol Vis Sci. 2009;50 (11):5226‑5237.

30. Haider K. M., Mickler C., Oliver D., Moya F. J., Cruz O. A., Davitt B. V. Age and racial variation in central corneal thickness of preschool and school-aged children. J Pediatr Ophthalmol Strabismus. 2008;45 (4):227‑233.

31. Sheppard J., Hayes S., Boote C., Votruba M., Meek K. M. Changes in corneal collagen architecture during mouse postnatal development. Invest Ophthalmol

32. Aghaian E., Choe J. E., Lin S., Stamper R. L. Central corneal thickness of Caucasians, Chinese, Hispanics, Filipinos, African Americans, and Japanese in a glaucoma clinic. Ophthalmology. 2004;111 (12):2211‑2219.

33. Vis Sci. 2010;51 (6):2936‑2942.

34. Chen M. J., Liu Y. T., Tsai C. C., Chen Y. C., Chou C. K., Lee S. M. Relationship between central corneal thickness, refractive error, corneal curvature, anterior chamber depth and axial length. J Chin Med Assoc. 2009;72 (3):133‑137.

35. Boote C., Hayes S., Young R. D., Kamma-Lorger C. S., et al. Ultrastructural changes in the retinopathy, globe enlarged (rge) chick cornea. J Struct Biol. 2009;166 (2):195‑204.

36. Harper C. L., Boulton M. E., Bennett D., Marcyniuk B., et al. Diurnal variations in human corneal thickness. Br J Ophthalmol. 1996;80 (12):1068‑1072.

37. McBrien N. A., Cornell L. M., Gentle A. Structural and ultrastructural changes to the sclera in a mammalian model of high myopia. Invest Ophthalmol Vis Sci. 2001;42 (10):2179‑2187.

38. Dubbelman M., Weeber H. A., van der Heijde R. G., Volker-Dieben H. J. Radius and asphericity of the posterior corneal surface determined by corrected Scheimpflug photography. Acta Ophthalmol Scand. 2002;80 (4):379‑383.

39. McBrien N. A., Gentle A. Role of the sclera in the development and pathological complications of myopia. Prog Retin Eye Res. 2003;22 (3):307‑338.

40. Katsube N., Wang R., Okuma E., Roberts C. Biomechanical response of the cornea to phototherapeutic keratectomy when treated as a fluid-filled porous material. J Refract Surg. 2002;18 (5):593‑597.

41. Daxer A., Misof K., Grabner B., Ettl A., Fratzl P. Collagen fibrils in the human

42. Roberts C. Biomechanics of the cornea and wavefront-guided laser refractive surgery. J Refract Surg. 2002;18 (5):589‑592.

43. corneal stroma: structure and aging. Invest Ophthalmol Vis Sci. 1998;39 (3):644‑648.

44. Avetisov E. S. [Miopia]. Blizorukost’. Moscow: Meditsina; 1999. (in Russ.).

45. Fratzl P. Collagen. Potsdam: Springer; 2008.

46. Doughty M. J., Jonuscheit S. An assessment of regional differences in corneal thickness in normal human eyes, using the Orbscan II or ultrasound pachymetry. Optometry. 2007;78 (4):181‑190.

47. Malik N. S., Meek K. M. Vitamins and analgesics in the prevention of collagen ageing. Age Ageing. 1996;25 (4):279‑284.

48. Olsen T. W., Sanderson S., Feng X., Hubbard W. C. Porcine sclera: thickness and

49. surface area. Invest Ophthalmol Vis Sci. 2002;43 (8):2529‑2532.

50. Vurgese S., Panda-Jonas S., Jonas J. B. Scleral thickness in human eyes. PLoS One. 2012;7 (1):e29692.

51. Nesterov A. P., Bunin A. Ya., Katsnel’son L. A. [Intraocular pressure. Physiology and pathology]. Vnutriglaznoe davlenie. Fiziologiya i patologiya. Moscow: Nauka; 1974. (in Russ.).

52. Strakhov V. V., Alekseev V. V. [Dynamic rigidometriya] Dinamicheskaya rigidometriya. [Annals of Ophthalmology]. Vestnik oftal’mologii. 1995;1:18‑20. (in

53. Russ.).

54. Pallikaris I. G., Kymionis G. D., Ginis H. S., Kounis G. A., Tsilimbaris M. K. Ocular rigidity in living human eyes. Invest Ophthalmol Vis Sci. 2005;46 (2):409‑414.

55. Friedman E., Ivry M., Ebert E., Glynn R., Gragoudas E., Seddon J. Increased scleral rigidity and age-related macular degeneration. Ophthalmology. 1989;96

56. (1):104‑108.

57. Akpatrov A. I., Kustov V. N. [The relation between the coefficient of rigidity and the volume of the eye] O zavisimosti mezhdu koeffitsientom rigidnosti i ob»emom glaza. [Annals of Ophthalmology]. Vestnik oftal’mologii. 1978;6:15‑17. (in Russ.).

58. Pinter L. A. [Active and passive components of the rigidity of the eye] Aktivnyi

59. i passivnyi komponenty rigidnosti glaza. [Annals of Ophthalmology]. Vestnik oftal’mologii. 1978;3:9‑10. (in Russ.).

60. 30. Faragher R. G., Mulholland B., Tuft S. J., Sandeman S., Khaw P. T. Aging and the cornea. Br J Ophthalmol. 1997;81 (10):814‑817.

61. Sarvazyan A. P., Lyrchikov A. G. [Communication volume-elastic properties of soft biological tissues having a water content, protein and fat] Svyaz’ ob»emno-uprugikh svoistv myagkikh biologicheskikh tkanei s soderzhaniem vody, belka i zhira. In: Medical biomechanics. Riga. p. 75‑77. (in Russ.).

62. Dische Z. Biochemistry of connective tissue of the vertebrate eye. Int Rev Connect Tissue Res. 1970;5:209‑279.

63. Vo T. D., Blumenfeld O. O., Coleman D. J. The biochemical composition of the human sclera and its relationship to the pathogenesis of degenerative myopia. Proc of 3rd Intern Conference on Myopia. 1987. p. 206‑214.

64. Iomdina E. N. [Biomechanical and biochemical disturbances in the sclera of progressive myopia and methods of their correction]. Biomekhanicheskie i biokhimicheskie narusheniya sklery pri progressiruyushchei blizorukosti i metody ikh

65. korrektsii. In: Avetisov S. E., Kashchenko T. P., Shamshinova A. M. Visual functions and their correction in children. Moscow: Meditsina; 2006. p. 163‑183. (in Russ.).

66. Brown C. T., Vural M., Johnson M., Trinkaus-Randall V. Age-related changes of scleral hydration and sulfated glycosaminoglycans. Mech Ageing Dev. 1994;77

67. (2):97‑107.

68. Watson P. G., Young R. D. Scleral structure, organisation and disease. A review.

69. Exp Eye Res. 2004;78 (3):609‑623.

70. Rada J. A., Achen V. R., Penugonda S., Schmidt R. W., Mount B. A. Proteoglycan composition in the human sclera during growth and aging. Invest Ophthalmol Vis Sci. 2000;41 (7):1639‑1648.

71. Kanai A., Kaufman H. E. Electron microscopic studies of corneal stroma: aging

72. changes of collagen fibers. Ann Ophthalmol. 1973;5 (3):285‑287 passim. 39. Malik N. S., Moss S. J., Ahmed N., Furth A. J., Wall R. S., Meek K. M. Ageing of the human corneal stroma: structural and biochemical changes. Biochim Biophys Acta. 1992;1138 (3):222‑228.

73. Scott J. E., Orford C. R., Hughes E. W. Proteoglycan-collagen arrangements in developing rat tail tendon. An electron microscopical and biochemical investigation. Biochem J. 1981;195 (3): 573‑581.

74. Chakravarti S., Zhang G., Chervoneva I., Roberts L., Birk D. E. Collagen fibril assembly during postnatal development and dysfunctional regulation in the lumican- deficient murine cornea. Dev Dyn. 2006;235 (9):2493‑2506.

75. Koga T., Inatani M., Hirata A., Inomata Y., et al. Expression of a chondroitin sulfate proteoglycan, versican (PG-M), during development of rat cornea. Curr Eye Res. 2005;30 (6):455‑463.

76. Zatulina N. I., Sennova L. G. [On the elastic fibers of the drainage system of the human eye] Ob elasticheskikh voloknakh drenazhnoi sistemy glaza cheloveka. [Ophthalmological Journal] Oftal’mologicheskii zhurnal. 1983;8:497‑499. (in Russ.).

77. Marshall G. E. Human scleral elastic system: an immunoelectron microscopic study. Br J Ophthalmol. 1995;79 (1):57‑64.

78. Moses R. A., Grodzki W. J., Jr., Starcher B. C., Galione M. J. Elastin content of the scleral spur, trabecular mesh, and sclera. Invest Ophthalmol Vis Sci. 1978;17

79. (8):817‑818.

80. Weale R. A. A biography of the eye. Development, growth, age. London: H. K. Lewis Co. LTD; 1982.

81. Hassan A. U., Hassan G., Rasool Z., Hassan S. Clinical outcomes of elastin fibre

82. defects. Journal of Cytology and Histology 2013;4 (1):166‑169.

83. Iomdina E. N., Ignat’eva N. Yu., Arutyunyan L. L., Shekhter A. B. et al. [The study of collagen and elastic structures of the eye sclera in glaucoma using nonlinear optical (multiphoton) microscopy and histology (preliminary report)]. Izuchenie kollagenovykh i elasticheskikh struktur sklery glaz pri glaukome s pomoshch’yu nelineino-opticheskoi (mul’tifotonnoi) mikroskopii i gistologii (predvaritel’noe soobshchenie). [Russian Ophthalmological Journal] Rossiiskii oftal’mologicheskii zhurnal. 2015;8 (1):50‑58. (in Russ.).

84. Keeley F. W., Morin J. D., Vesely S. Characterization of collagen from normal human sclera. Exp Eye Res. 1984;39 (5): 533‑542.

85. Serov V. V., Paukov V. S. [Ultrastructural pathology]. Ul’trastrukturnaya patologiya. Moscow: Meditsina; 1975. (in Russ.).

86. Serov V. V., Shekhter A. B. [Connective tissue: functional morphology and general pathology]. Soedinitel’naya tkan’: funktsional’naya morfologiya i obshchaya patologiya. Moscow: Meditsina; 1981. (in Russ.).

87. Avetisov E. S., Khoroshilova-Maslova I. P., Andreeva L. D. [The ultrastructural changes of sclera in myopia] Ul’trastrukturnye izmeneniya sklery pri miopii. [Annals of Ophthalmology]. Vestnik oftal’mologii. 1980;6:36‑42. (in Russ.).

88. Bailey A. J. Structure, function and ageing of the collagens of the eye. Eye (Lond). 1987;1 (Pt 2):175‑183.

89. Fung Y. C. Biomechanics. Mechanical Properties of Living Tissues. NewYork: Springer-Verlag; 1990.

90. Lee P. P., Walt J. W., Rosenblatt L. C., Siegartel L. R., Stern L. S., Glaucoma Care Study G. Association between intraocular pressure variation and glaucoma progression: data from a United States chart review. Am J Ophthalmol. 2007;144 (6):901‑907.

91. Lee R. E., Davison P. F. The collagens of the developing bovine cornea. Exp Eye Res. 1984;39 (5):639‑652.

92. Vannas S., Teir H. Observations on structures and age changes in the human sclera. Acta Ophthalmol (Copenh). 1960;38:268‑279.

93. Ben-Zvi A., Rodrigues M. M., Krachmer J. H., Fujikawa L. S. Immunohistochemical characterization of extracellular matrix in the developing human cornea. Curr Eye Res. 1986;5 (2):105‑117.

94. Rucklidge G. J., Milne G., McGaw B. A., Milne E., Robins S. P. Turnover rates of different collagen types measured by isotope ratio mass spectrometry. Biochim Biophys Acta. 1992;1156 (1):57‑61.

95. Ihanamaki T., Salminen H., Saamanen A. M., Pelliniemi L. J., et al. Age-dependent changes in the expression of matrix components in the mouse eye. Exp Eye Res. 2001;72 (4):423‑431.

96. Manschot W. A. Senile scleral plaques and senile scleromalacia. Br J Ophthalmol.

97. 1978;62 (6):376‑380.

98. Sorsby A., Wilcox K., Ham D. The Calcium Content of the Sclerotic and Its Variation with Age. Br J Ophthalmol. 1935;19 (6):327‑337.

99. Hogan M. J., Alvarado J. Ultrastructure of the deep corneolimbal region. Doc Ophthalmol. 1969;26:9‑30.

100. Hirano K., Nakamura M., Kobayashi M., Kobayashi K., Hoshino T., Awaya S. Longspacing collagen in the human corneal stroma. Jpn J Ophthalmol. 1993;37 (2):148‑155.

101. Yan D., McPheeters S., Johnson G., Utzinger U., Vande Geest J. P. Microstructural differences in the human posterior sclera as a function of age and race. Invest Ophthalmol Vis Sci. 2011;52 (2):821‑829.

102. Girard M. J., Suh J. K., Bottlang M., Burgoyne C. F., Downs J. C. Scleral biomechanics in the aging monkey eye. Invest Ophthalmol Vis Sci. 2009;50 (11):5226‑5237.

103. Sheppard J., Hayes S., Boote C., Votruba M., Meek K. M. Changes in corneal collagen architecture during mouse postnatal development. Invest Ophthalmol

104. Vis Sci. 2010;51 (6):2936‑2942.

105. Boote C., Hayes S., Young R. D., Kamma-Lorger C. S., et al. Ultrastructural changes in the retinopathy, globe enlarged (rge) chick cornea. J Struct Biol. 2009;166 (2):195‑204.

106. McBrien N. A., Cornell L. M., Gentle A. Structural and ultrastructural changes to the sclera in a mammalian model of high myopia. Invest Ophthalmol Vis Sci. 2001;42 (10):2179‑2187.

107. McBrien N. A., Gentle A. Role of the sclera in the development and pathological complications of myopia. Prog Retin Eye Res. 2003;22 (3):307‑338.

108. Daxer A., Misof K., Grabner B., Ettl A., Fratzl P. Collagen fibrils in the human

109. corneal stroma: structure and aging. Invest Ophthalmol Vis Sci. 1998;39 (3):644‑648.

110. Fratzl P. Collagen. Potsdam: Springer; 2008.

111. Malik N. S., Meek K. M. Vitamins and analgesics in the prevention of collagen ageing. Age Ageing. 1996;25 (4):279‑284.