Skip to main content
SpringerLink
Log in

Pathology of the Cornea

  • Living reference work entry
  • First Online:
Albert and Jakobiec's Principles and Practice of Ophthalmology

Abstract

This chapter provides an overview of corneal pathology. In addition to reviewing the histologic features of the normal cornea, the following categories of corneal pathology are covered: (1) congenital and developmental anomalies, (2) dystrophies, (3) degenerations and ectatic disorders, (4) inflammation and infections, (5) injuries and wound healing, (6) systemic metabolic diseases, (7) pigmentations, and (8) tumors.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

References

  1. Yanoff M, Sassani JW. Ocular pathology. 7th ed. London: Elsevier; 2015.

    Google Scholar 

  2. Inoue Y, Inoue T, Ishii Y, Shimomura Y, Tano Y. Histology of microcornea complicated by bullous keratopathy. Acta Ophthalmol Scand. 2001;79:94–6.

    Article  CAS  PubMed  Google Scholar 

  3. Starck T, Hersh PS, Kenyon KR. Corneal dysgeneses, dystrophies, and degenerations. In: Albert DM, Jakobiec FA, Azar DT, Gragoudas ES, editors. Principles and practice of ophthalmology. 2nd ed. Philadelphia: W.B. Saunders Company; 2000. p. 695–6.

    Google Scholar 

  4. Meire FM. Megalocornea: clinical and genetic aspects. Doc Ophthalmol. 1994;87:1–121.

    Article  CAS  PubMed  Google Scholar 

  5. Wood WJ, Green WR, Marr WG. Megalocornea: a clinico-pathologic clinical case report. Md State Med J. 1974;23:57–60.

    CAS  PubMed  Google Scholar 

  6. Nischal KK. A new approach to the classification of neonatal corneal opacities. Curr Opin Ophthalmol. 2012;23:344–54.

    Article  PubMed  Google Scholar 

  7. Lesnik Oberstein SA, Kriek M, White SJ, Kalf ME, Szuhai K, den Dunnen JT, et al. Peters Plus syndrome is caused by mutations in B3GALTL, a putative glycosyltransferase. Am J Hum Genet. 2006;79:562–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Ozeki H, Shirai S, Nozaki M, Sakurai E, Mizuno S, Ashikari M, et al. Ocular and systemic features of Peters’ anomaly. Graefes Arch Clin Exp Ophthalmol. 2000;238:833–9.

    Article  CAS  PubMed  Google Scholar 

  9. Bhandari R, Ferri S, Whittaker B, Liu M, Lazzaro DR. Peters anomaly: review of the literature. Cornea. 2011;30:939–44.

    Article  PubMed  Google Scholar 

  10. Seifi M, Walter MA. Axenfeld-Rieger syndrome. Clin Genet. 2018;93:1123–30.

    Article  CAS  PubMed  Google Scholar 

  11. Pearce WG, Mielke BC, Kulak SC, Walter MA. Histopathology and molecular basis of iridogoniodysgenesis syndrome. Ophthalmic Genet. 1999;20:83–8.

    Article  CAS  PubMed  Google Scholar 

  12. Kivela T, Messmer EM, Rymgayllo-Jankowska B. Cornea. In: Heegaard S, Grossniklaus H, editors. Eye pathology. Berlin: Springer; 2015. p. 79–154.

    Google Scholar 

  13. Weiss J, Møller H, Aldave A, Seitz B, Bredrup C, Kivelä T, et al. IC3D classification of corneal dystrophies – edition 2. Cornea. 2015;34:117–59.

    Article  PubMed  Google Scholar 

  14. Weiss J, Moller HU, Lisch W, Kinoshita S, Aldave A, Belin M, et al. The IC3D classification of the corneal dystrophies. Cornea. 2008;27:S1–83.

    PubMed  PubMed Central  Google Scholar 

  15. Corden LD, Swensson O, Swensson B, Smith FJ, Rochels R, Uitto J. Molecular genetics of Meesmann’s corneal dystrophy: ancestral and novel mutations in keratin 12 (K12) and complete sequence of the human KRT12 gene. Exp Eye Res. 2000;70:41–9.

    Article  CAS  PubMed  Google Scholar 

  16. Pieramici SF, Afshari NA. Genetics of corneal dystrophies: the evolving landscape. Curr Opin Ophthalmol. 2006;17:361–6.

    Article  PubMed  Google Scholar 

  17. Boutboul S, Black GC, Moore JE, Sinton J, Menasche M, Munier FL, et al. A subset of patients with epithelial basement membrane corneal dystrophy have mutations in TGFBI/BIGH3. Hum Mutat. 2006;27:553–7.

    Article  CAS  PubMed  Google Scholar 

  18. Lisch W, Buttner A, Oeffner F, Boddeker I, Engel H, Lisch C, et al. Lisch corneal dystrophy is genetically distinct from Meesmann corneal dystrophy and maps to xp22.3. Am J Ophthalmol. 2000;130:461–8.

    Article  CAS  PubMed  Google Scholar 

  19. Lisch W, Steuhl KP, Lisch C, Weidle EG, Emmig CT, Cohen KL, et al. A new, band-shaped and whorled microcystic dystrophy of the corneal epithelium. Am J Ophthalmol. 1992;114:35–44.

    Article  CAS  PubMed  Google Scholar 

  20. Ide T, Nishida K, Maeda N, Tsujikawa M, Yamamoto S, Watanabe H, et al. A spectrum of clinical manifestations of gelatinous drop-like corneal dystrophy in Japan. Am J Ophthalmol. 2004;137:1081–4.

    Article  PubMed  Google Scholar 

  21. Uhlig CE, Groppe M, Busse H, Saeger W. Morphological and histopathological changs in gelatinous drop-like corneal dystrophy during a 15-year follow up. Acta Ophthalmol. 2010;88:e273–4.

    Article  PubMed  Google Scholar 

  22. Klintworth GK, Valnickova Z, Kielar RA, Baratz KH, Campbell RJ, Enghild JJ, et al. Familial subepithelial corneal amyloidosis – a lactoferrin-related amyloidosis. Invest Ophthalmol Vis Sci. 1997;38:2756–63.

    CAS  PubMed  Google Scholar 

  23. Ren Z, Lin PY, Klintworth GK, Iwata F, Munier FL, Schorderet DF, et al. Allelic and locus heterogeneity in autosomal recessive gelatinous drop-like corneal dystrophy. Hum Genet. 2002;110:568–77.

    Article  CAS  PubMed  Google Scholar 

  24. Kannabiran C, Klintworth GK. TGFBI gene mutations in corneal dystrophies. Hum Mutat. 2006;27:615–25.

    Article  CAS  PubMed  Google Scholar 

  25. Kuchle M, Green WR, Volcker HE, Barraquer J. Reevaluation of corneal dystrophies of Bowman’s layer and the anterior stroma (Reis–Bucklers and Thiel–Behnke types): a light and electron microscopic study of eight corneas and a review of the literature. Cornea. 1995;14:333–54.

    Article  CAS  PubMed  Google Scholar 

  26. Munier FL, Korvatska E, Djemai A, le Paslier D, Zografos L, Pescia G, et al. Keratoepithelin mutations in four 5q31-linked corneal dystrophies. Nat Genet. 1997;15:247–51.

    Article  CAS  PubMed  Google Scholar 

  27. Han KE, Choi SI, Chung WS, Jung SH, Katsanis N, Kim TI, et al. Extremely varied phenotypes in granular corneal dystrophy type 2 heterozygotes. Mol Vis. 2012;18:1755–62.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Klintworth GK, Smith CF, Bowling BL. CHST6 mutations in north American subjects with macular corneal dystrophy: a comprehensive molecular genetic review. Mol Vis. 2006;12:159–76.

    CAS  PubMed  Google Scholar 

  29. Ganesh A, Bruwer Z, Al-Thihli K. An update on ocular involvement in mucopolysaccharidoses. Curr Opin Ophthamol. 2013;24:379–88.

    Article  Google Scholar 

  30. Weiss JS. Schnyder’s dystrophy of the cornea. A Swede-Finn connection. Cornea. 1992;11:93–101.

    Article  CAS  PubMed  Google Scholar 

  31. Weiss JS, Wiaux C, Yellore V, Raber I, Eagle R, Mequio M, et al. Newly reported p.Asp240Asn mutation in UBIAD1 suggests central discoid corneal dystrophy is a variant of Schynder corneal dystrophy. Cornea. 2010;29:777–80.

    Article  PubMed  Google Scholar 

  32. Theendakara V, Tromp G, Kuivaniemi H, White PS, Panchal S, Cox J, et al. Fine mapping of the Schnyder’s crystalline corneal dystrophy locus. Hum Genet. 2004;114:594–600.

    Article  CAS  PubMed  Google Scholar 

  33. Weiss JS, Kruth HS, Kuivaniemi H, Tromp G, White PS, Winters RS, et al. Mutations in the UBIADi gene on chromosome short arm 1, region 36, cause Schnyder crystalline corneal dystrophy. Invest Ophthalmol Vis Sci. 2007;48:5007–12.

    Article  PubMed  Google Scholar 

  34. Orr A, Dube MP, Marcadier J, Jiang J, Federico A, George S, et al. PLoS One. 2007;8:e685.

    Article  CAS  Google Scholar 

  35. Weiss JS. Visual morbidity in 34 families with Schnyder crystalline corneal dystrophy. Trans Am Ophthalmol Soc. 2007;105:616–48.

    PubMed  PubMed Central  Google Scholar 

  36. Rodrigues MM, Kruth HS, Krachmer JH, Willis R. Unesterified cholesterol in Schnyder’s corneal crystalline dystrophy. Am J Ophthalmol. 1987;104:157–63.

    Article  CAS  PubMed  Google Scholar 

  37. Bredrup C, Knappskog PM, Majewski J, Rodahl E, Boman H. Congenital stromal dystrophy of the cornea caused by a mutation in the decorin gene. Invest Ophthalmol Vis Sci. 2005;46:420–6.

    Article  PubMed  Google Scholar 

  38. Purcell JJ Jr, Krachmer JH, Weingeist TA. Fleck corneal dystrophy. Arch Ophthalmol. 1977;95:440–4.

    Article  PubMed  Google Scholar 

  39. Kim MJ, Frausto RF, Rosenwasser GO, Bui T, Le DJ, Stone EM, et al. Posterior amorphous corneal dystrophy is associated with a deletion of small leucine-rich proteoglycans on chromosome 12. PLoS One. 2014;9:e95037.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  40. Grimm BB, Waring GO, Grimm SB. Posterior amorphous corneal dysgenesis. Am J Ophthalmol. 1995;120:448–55.

    Article  CAS  PubMed  Google Scholar 

  41. Sieck EA, Joyce NC. Genetic influences on differentiation mitosis and dystrophies of the corneal endothelium. Int Ophthalmol Clin. 1993;33:37–48.

    Article  CAS  PubMed  Google Scholar 

  42. Waring GO, Rodrigues MM, Laibson PR. Corneal dystrophies. II. Endothelial dystrophies. Surv Ophthalmol. 1978;23:147–68.

    Article  PubMed  Google Scholar 

  43. Waring GO, Rodrigues MM. Patterns of pathologic response in the cornea. Surv Ophthalmol. 1987;31:262–6.

    Article  PubMed  Google Scholar 

  44. Waring GO, Bourne WM, Edelhauser HF, Kenyon KR. The corneal endothelium. Normal and pathologic structure and function. Ophthalmology. 1982;89:531–90.

    Article  PubMed  Google Scholar 

  45. Aldave AJ, Han J, Fausto RF. Genetics of the corneal endothelial dystrophies: an evidence based review. Clin Genet. 2013;84:109–19.

    Article  CAS  PubMed  Google Scholar 

  46. Borboli S, Colby K. Mechanisms of disease: Fuchs’ endothelial dystrophy. Ophthalmol Clin N Am. 2002;15:17–25.

    Article  Google Scholar 

  47. Moroi SE, Gokhale PA, Schteingart MT, Sugar A, Downs CA, Shimizu S, et al. Clinicopathologic correlation and genetic analysis in a case of posterior polymorphous corneal dystrophy. Am J Ophthalmol. 2003;135:461–70.

    Article  PubMed  Google Scholar 

  48. Bakhtiari P, Frausto RF, Roldan AN, Wang C, Yu F, Aldave A. Exclusion of pathogenic promoter region variants and identification of novel nonsense mutations in the zinc finger E-box binding homeobox 1 gene in posterior polymorphous corneal dystrophy. Mol Vis. 2013;19:575–80.

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Aldave AJ, Ann LB, Frausto RF, Nguyen CK, Yu F, Raber IM. Classification of posterior polymorphous corneal dystrophy as a corneal Ectatic disorder following confirmation of associated significant corneal steepening. JAMA Ophthalmol. 2013;131:1583–90.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Jiao X, Sultana A, Garg P, Ramamurthy B, Vemuganti GK, Gangopadhyay N, et al. Autosomal recessive corneal endothelial dystrophy (CHED2) is associated with mutations in SLC4A11. J Med Genet. 2007;44:64–8.

    Article  CAS  PubMed  Google Scholar 

  51. Schmid E, Lisch W, Philipp W, Lechner S, Gottinger W, Schlotzer-Schrehardt U, et al. A new, X-linked endothelial corneal dystrophy. Am J Ophthalmol. 2006;141:478–87.

    Article  PubMed  Google Scholar 

  52. Cursino JW, Fine BS. A histologic study of calcific and noncalcific band keratopathies. Am J Ophthalmol. 1976;82:395–404.

    Article  CAS  PubMed  Google Scholar 

  53. Das S, Link B, Seitz B. Salzmann’s nodular degeneration of the cornea: a review and case series. Cornea. 2005;24:772–7.

    Article  PubMed  Google Scholar 

  54. Aldave AJ, Rayner SA, King JA. No pathogenic mutations identified in the TGFBI gene in polymorphic corneal amyloid deposition. Cornea. 2006;25:413–5.

    Article  PubMed  Google Scholar 

  55. Waring GO. Making sense of keratospeak IV. Arch Ophthalmol. 1992;110:1385–91.

    Article  PubMed  Google Scholar 

  56. Johnson DH, Bourne WM, Campbell RT. The ultrastructure of Descemet’s membrane II. Aphakic bullous keratopathy. Arch Ophthalmol. 1982;100:1948–51.

    Article  CAS  PubMed  Google Scholar 

  57. Rabinowitz YS. Keratoconus. Surv Ophthalmol. 1998;42:297–319.

    Article  CAS  PubMed  Google Scholar 

  58. Dawson CR, Hanna L, Togni B. Adenovirus type 8 infections in the U.S. IV. Observations on the pathogenesis of lesions in severe eye disease. Arch Ophthalmol. 1972;87:258–68.

    Article  CAS  PubMed  Google Scholar 

  59. Sharma S. Keratitis. Biosci Rep. 2001;21:419–44.

    Article  CAS  PubMed  Google Scholar 

  60. Starr CE, Pavan-Langston D. Varicella-zoster virus: mechanisms of pathogenicity and corneal disease. Ophthalmol Clin N Am. 2002;15:7–15.

    Article  Google Scholar 

  61. Kaye S, Choudhary A. Herpes simplex keratitis. Prog Retin Eye Res. 2006;25:355–80.

    Article  PubMed  Google Scholar 

  62. Grossniklaus HE, Waring GO 4th, Akor C, Castellano-Sanchez AA, Bennett K. Evaluation of hematoxylin and eosin and special stains for the detection of acanthamoeba keratitis in penetrating keratoplasties. Am J Ophthalmol. 2003;136:520–6.

    Article  PubMed  Google Scholar 

  63. Sridhar MS, Sharma S. Microsporidial keratoconjunctivitis in a HIV-seronegative patient treated with debridement and oral itraconazole. Am J Ophthalmol. 2003;136:745–6.

    Article  CAS  PubMed  Google Scholar 

  64. Davis RM, Font RL, Keisler MS, Shadduck JA. Corneal microsporidiosis: a case report including ultrastructural observations. Ophthalmology. 1990;97:953–7.

    Article  CAS  PubMed  Google Scholar 

  65. Kessel A, Vadasz Z, Toubi E. Cogan Syndrome – pathogenesis, clinical variants, and treatment approaches. Autoimmun Rev. 2014;13:351–4.

    Article  PubMed  Google Scholar 

  66. Jester JV, Rodrigues MM, Herman IM. Characterization of avascular corneal wound healing fibroblasts: new insights into the myofibroblast. Am J Pathol. 1987;127:140–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Kremer I, Rapuano CJ, Cohen EJ, Laibson PR, Eagle RC Jr. Retrocorneal fibrous membranes in failed corneal grafts. Am J Ophthalmol. 1993;115:478–83.

    Article  CAS  PubMed  Google Scholar 

  68. Goldberg MF, Maumenee AE, McKusick VA. Corneal dystrophies associated with abnormalities of mucopolysaccharide metabolism. Arch Ophthalmol. 1965;74:516–20.

    Article  CAS  PubMed  Google Scholar 

  69. Schwartz MF, Werblin TO, Green WR. Occurrence of mucopolysaccharide in corneal grafts in the Maroteaux-Lamy syndrome. Cornea. 1985;4:58–66.

    PubMed  Google Scholar 

  70. Palmer M, Green WR, Maumenee IH, Valle DL, Singer HS, Morton SJ, et al. Niemann-Pick disease type C: ocular histopathologic and electron microscopic studies. Arch Ophthalmol. 1985;103:817–22.

    Article  CAS  PubMed  Google Scholar 

  71. Cogan DG, Kruth HS, Datilis MB, Martin N. Corneal opacity in LCAT disease. Cornea. 1992;11:595–9.

    Article  CAS  PubMed  Google Scholar 

  72. Sanderson PO, Kuwabara T, Stark WJ, Wong VG, Collins EM. Cystinosis: a clinical, histopathologic, and ultrastructural study. Arch Ophthalmol. 1974;91:270–4.

    Article  CAS  PubMed  Google Scholar 

  73. Slansky HH, Kuwabara T. Intranuclear urate crystals in corneal epithelium. Arch Ophthalmol. 1968;80:338–44.

    Article  CAS  PubMed  Google Scholar 

  74. Rodrigues MM, Krachmer JH, Miller S, Newsome DA. Posterior corneal crystalline deposits in benign monoclonal gammopathy. Arch Ophthalmol. 1979;97:124–8.

    Article  CAS  PubMed  Google Scholar 

  75. Klintworth GK, Bredehoeft SJ, Reed JW. Analysis of corneal crystalline deposits in multiple myeloma. Am J Ophthalmol. 1978;86:303–13.

    Article  CAS  PubMed  Google Scholar 

  76. Milman T, Kao AA, Chu D, Gorski M, Steiner A, Simon CZ, et al. Paraproteinemic keratopathy: the expanding diversity of clinical and pathologic manifestations. Ophthalmology. 2015;122:1748–56.

    Article  PubMed  Google Scholar 

  77. Lisch W, Saikia P, Pitz S, Pleyer U, Lisch C, Jaeger M, et al. Chameleon-like appearance of immunotactoid keratopathy. Cornea. 2012;31:55–8.

    Article  PubMed  Google Scholar 

  78. Stiefel HC, Sandhu RK, Miller AK, Wilson DJ, Chamberlain WD. Characterization of corneal deposition keratopathy in the setting of blood cell dyscrasia and a minimally invasive technique to clear the cornea in a single case. Am J Ophthalmol Case Rep. 2018;13:83–8.

    Article  PubMed  PubMed Central  Google Scholar 

  79. McDonnell PJ, Green WR, Stevens RE, Bargeron CB, Riquelme JL. Blood staining of the cornea: light microscopic and ultrastructural features. Ophthalmology. 1985;92:1668–74.

    Article  CAS  PubMed  Google Scholar 

  80. Barraquer-Somers E, Chan CC, Green WR. Corneal epithelial iron deposition. Ophthalmology. 1983;90:729–34.

    Article  CAS  PubMed  Google Scholar 

  81. Johnson RE, Campbell RJ. Electron microscopic, x-ray energy spectroscopic, and atomic absorption spectroscopic studies of corneal copper deposition and distribution. Lab Investig. 1982;46:564–9.

    CAS  PubMed  Google Scholar 

  82. Spencer WH, Garron LK, Contreras F, Hayes TL, Lai C. Endogenous and exogenous ocular and systemic silver deposition. Trans Ophthalmol Soc UK. 1980;100:171–8.

    CAS  PubMed  Google Scholar 

  83. Kincaid MC, Green WR, Hoover RE, Schenck PH. Ocular chrysiasis. Arch Ophthalmol. 1982;100:1791–4.

    Article  CAS  PubMed  Google Scholar 

  84. D’Amico DJ, Kenyon KR, Ruskin JN. Amiodarone keratopathy: drug-induced lipid storage disorder. Arch Ophthalmol. 1981;99:257–61.

    Article  PubMed  Google Scholar 

  85. Cameron JA, Hidayat AA. Squamous cell carcinoma of the cornea. Am J Ophthalmol. 1991;111:571–4.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Ophthalmology, Casey Eye Institute, Oregon Health and Science University, Portland, OR, USA

    Hillary C. Stiefel

  2. Department of Ophthalmology, Oregon Health and Science University, Portland, OR, USA

    Daniel Albert

  3. Ophthalmology and Pathology, Wills Eye Hospital and Jefferson University Hospital, Philadelphia, PA, USA

    Tatyana Milman

Authors
  1. Hillary C. Stiefel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Daniel Albert
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tatyana Milman
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hillary C. Stiefel .

Editor information

Editors and Affiliations

  1. Department of Ophthalmology, Oregon Health & Science University Department of Ophthalmology, Portland, OR, USA

    Daniel Albert

  2. Massachusetts Eye and Ear, Boston, MA, USA

    Joan Miller

  3. Department of Ophthalmology, University of Illinois at Chicago Department of Ophthalmology, Chicago, IL, USA

    Dimitri Azar

  4. Department of Ophthalmology, Harvard Medical School, Boston, MA, USA

    Lucy H. Young

Section Editor information

  1. Anatomic Pathology, Massachusetts General Hospital, Boston, USA

    Anna M. Stagner

  2. Ophthalmic Pathology and Ophthalmic Plastic and Reconstructive Surgery, Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, USA

    Natalie Wolkow

  3. David Glendenning Cogan Laboratory of Pathology, Harvard Medical School, Boston, USA

    Thaddeus Dryja

  4. David Glendenning Cogan Laboratory of Ophthalmic Pathology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, USA

    Frederick A. Jakobiec

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this entry

Check for updates. Verify currency and authenticity via CrossMark

Cite this entry

Stiefel, H.C., Albert, D., Milman, T. (2020). Pathology of the Cornea. In: Albert, D., Miller, J., Azar, D., Young, L.H. (eds) Albert and Jakobiec's Principles and Practice of Ophthalmology. Springer, Cham. https://doi.org/10.1007/978-3-319-90495-5_129-1

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-90495-5_129-1

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-90495-5

  • Online ISBN: 978-3-319-90495-5

  • eBook Packages: Springer Reference MedicineReference Module Medicine

Publish with us

Policies and ethics

Search

Navigation