Summary
The results of the histochemical stainings are summarised in Table 3a and b.
The histological examination of the dry eyes shows the thickening and keratinisation of the superficial flattened cell layer of the corneal and con-junctival epithelium. There is generalised hypertrophy of the epithelium but in some places hydropic degeneration of the cells and atrophy is seen. The cells are irregularly arranged, sometimes forming a “rosette”. There is intercellular and intracellular oedema of the epithelium.
A large number of Teng cells (Teng & Katzin, 1953; Teng, 1961, 1962) are seen in the corneal epithelium. These cells participate in the regeneration of the basement membrane of the epithelium. This membrane becomes irregular and wavy in keratitis sicca.
In the basal and middle layers of the corneal epithelium and the deeper layers of the conjunctiva increased RNA activity is found.
The histochemical stainings demonstrate intranuclear keratinisation and denaturation of DNA. These nuclei stain positive with alcian blue and PAS stains; negative or faintly positive with the Feulgen reaction; show ortho-chromasia instead of the metachromasia with toluidine blue metachromatic staining and give a positive reaction for the keratin.
The activity of the acid phosphatase is increased in the epithelium.
The cells of the corneal and conjunctival epithelium show intracytoplasmic deposits of heterogenous material composed of 0.1 μ elementary particles. These deposits show positive reactions for -SH groups and glycoproteins. This material presents an isotropic and anisotropic zones. Its density is variable and pleomorphic which progressively increases towards the superficial layers. These characteristics correspond to those of keratohyalin.
The superficial keratinised layers of the corneal and conjunctival epithelium are disposed in lamellar fashion and give positive stainings for -SH groups and -S-S- bridges.
In addition to the changes of keratinisation, progressive atrophy of the goblet cells is seen in the conjunctiva. These cells may entirely disappear in some areas. The submucosa shows subacute inflammatory cell infiltration and hyperaemia. In some cases it is found fragmented. Quite often a fibrinous deposit can be seen on the conjunctival surface.
Slight oedema of the superficial layers of the corneal stroma is found which explains the feable stainings for mucopolysaccharides.
Before discussing the implications of the histochemical and histological findings in relation to the clinical observations in keratoconjunctivitis sicca, we ought to take into account the results of electron microscopy. Discussion of the overall findings, therefore, follows in the section ‘General discussion and conclusions’'.
Similar content being viewed by others
References
Adler, F.H. Physiology of the Eye. The C.V. Mosby Company, St Louis (1965).
Alexander, L.E. X-Ray diffraction methods in polymar science. John Wiley and Sons, New York (1969).
Anderson, J.R., K.G. Gray, J.S. Beck & W.F. Kinnear. Precipitating autoantibodies in Sjögren's disease. Lancet 2: 456 (1961).
Appelmans, M. La keratoconjunctivite séche de Gougerot-Sjögren. Arch. Ophtal. 8: 577 (1948).
Beck, J.S., J.R. Anderson, K.J. Bloch, W.W. Buchanan & J.J. Bunim. Antinuclear and precipitating autoantibodies in Sjögren's syndrome. Ann. Rheum. Dis. 24: 16 (1965).
Ben-Porat, T. & A.S. Kaplan. Replication-Biochemical aspects. In: The Herpes Viruses. Ed. A.S. Kaplan. Academic Press, New York and London (1973).
Bertram, U., J.J. Pindborg, H.H. Seedorff & A. Videbaek. Sjögren's Syndrome, with special reference to oral findings. Ugeskr. Laeg. 123: 1085 (1961).
Bloch, K.J., W.W. Buchanan, M.J. Wohl & J.J. Bunim. Sjögren's syndrome. A clinical, pathological and serological study of sixty two cases. Medicine (Baltimore) 44: 187 (1965).
Bloch, K.J. & J.J. Bunim. Sjögren's syndrome and its relation to connective tissue diseases. J. Chr. Dis. 16: 915 (1963).
Blümcke, S. & Jr. K. Morgenworth. The stereo ultrastructure of the external and internal surface of the cornea. J. Ultrastruct. Res. 18: 502 (1967).
Bonner, W.A. & A.J. Castro. Essentials of modern organic chemistry. Reinhold Publishing Corporation, New York (1965).
Bowers, D. Sjögren's syndrome: systemic lupus erythematosus and auto-immune haemolytic anaemia. Report of a case with long survival. Can. med. Ass. J. 100: 1148 (1969).
Brody, I. Different staining methods for the electron microscopic elucidation of the tonofibrillar differentiation in normal epidermis. In: The Epidermis. Ed. W. Montagna & W. Lobitz. Academic Press, New York and London (1964).
Bunim, J.J., W.W. Buchanan, P.T. Wertlake, L. Sokoloff, K.J. Bloch, J.S. Beck & antibodies in Sjögren's syndrome. Ann. N. Y. Acād. Sci. 124: 852 (1965).
Bunim, J.J., W.W. Buchanan, P.T. Wertlake, L. Sokoloff, K.J. Bloch, J.S. Beck & F.P. Alepa. Clinical, pathological and serological studies in Sjögren's syndrome. An. Intern. Med. 61: 509 (1964).
Coverdale, H. Sjögren's syndrome as a constitutional defect. N.Z. med. J. 54: 641 (1955).
Crews, S.J. & A.G.W. Whitfield. Sjögren's syndrome. Postgrad. Med. J. 39: 324 (1963).
De Haas, E.B.H. Deux complications oculaires rares de la maladie de Bernier-Boeck chez un même sujet. Kératoconjunctivite séche et calcification de la cornée et de la conjunctive. Ophthalmologica 123: 65 (1952).
De Robertis, E.D.P., W.W. Noxinski & F.A. Saez. Cell Biology. W.B. Saunders Company, Philadelphia (1970).
De Röth, A. Lacrimation in normal eyes. Arch. Ophth. 49: 185 (1953).
Darlington, R.W. & A. Granoff. Replication-Biological Aspects. In: The Herpes Viruses. Ed. A.S. Kaplan. Academic Press, New York and London (1973).
Denko, C.W. Antibodies in the Sicca Syndrome (Sjögren's syndrome). Arthr. and Rheum. 8: 970 (1965).
Denko, C.W. & D.M. Bergenstal. The Sicca Syndrome (Sjögren's syndrome). Arch. Intern. Med. 105: 849 (1960).
Dohlman, C.H. New concepts in xerophthalmia. Trans. Ophth. Soc. U.K. 91: 105 (1971).
Duff, R. & E. Doller. Cellular transformation by herpes simplex virus type 1 and 2. Virus Research. Ed. Fox, C.F. & W.S. Robinson. Academic Press, New York and London (1973).
Duke-Elder, S. & P.A. MacFaul. System of Ophthalmology, Vol. XIII. The Ocular Adenexa. Ed. Duke-Elder, S. Henry Kimpton, London (1974).
Eglitis, I. The Glands. In: The rabbit in eye research. Ed. Prince, J.H. Charles C. Thomas, Publisher. Springfield, Ill. (1964).
Ehlers, N. The precorneal film. Acta Ophth. Kbh. 81: 60 (1965).
Escande, J.P. & R. Degos. Les syndromes de Gougerot-Sjögren. Presse méd. 76: 1421 (1968).
Feltkamp, T.E.W. & A.L. van Rossum. Antibodies to salivary duct cells and other antibodies in patients with Sjögren's syndrome and other idiopathic autoimmune diseases. Clin. Expt. Immun. 3: 1 (1968).
Fernandez-Meijide, R.E., V. Victoria-Troncoso & E.S. Malbran. Determinación de la viabilidad endotelial en las queratoplastias perforantes. Arch. Oftal. Buenos Aires 45: 143 (1970).
Ferreira-Marques, J. A contribution to the study of the Sjögren syndrome. Acta dermato-venerol. (Stockh.) 40: 485 (1960).
Flynn, F. & A. Schulmeister. Keratoconjunctivitis sicca and new techniques in its management. Med. J. Aust. 54: 33 (1967).
Fogel, D.H. Sjögren's syndrome with benign purpura hyperglobulinaemia. New Engl. J. Med. 261: 81 (1959).
Fox, Jr, J.T. Sjögren's syndrome and late-life myopathy. Arch. Neural. (Chic.) 15: 397 (1966).
François, J. & M. Rabaey, personal communication.
Fruton, J.S. & S. Simmonds. General Biochemistry. John Wiley and Sons. New York and London (1963).
Fukuyama, K. & W.L. Epstein. Ultrastructural autoradiographic studies of keratohyalin granule formation. J. Invest. Derm. 49: 595 (1967).
Gamp, A. Sjögren's syndrome. Rheumatism 14: 51 (1958).
Guillaine, J., D. Sterin & J.P. Menanteau. Cyroglobulinaemia with Gougerot-Sjögren's syndrome. Bull. Soc. Franç. Derm. Syph. 77: 757 (1970).
Haggis, G.H., D. Michie, A.R. Muir, K.B. Roberts & P.M.B. Walker. Introduction to molecular biology. Longmans, Green and Co, London (1967).
Hardsky, M., V. Herout, F. Cernik, L. Sazama, Z. Rondiakova & J. Kvasnicka. Das Gougerot-Houwer-Sjögren syndrom und die polyarteritis nodosa. Z. Ges. Inn. Med. 23: 25 (1968).
Hardy, M.H. Responses in embryonic mouse skin to excess vitamin A in organotypic cultures from the trunk, upper lip and lower jaw. Exp. Cell Res. 46: 376 (1967).
Haye, C.R. Calle & Cueto-Alvarez. Syndrome de Mikulicz par lymphoreticulo-sarcome. Bull. Soc. Belge Ophtal. 148: 390 (1968).
Heaton, J.M. Sjögren's syndrome and systemic lupus erythematosus. Brit. Med. J. 1: 466 (1959).
Heindle, E. Symptomatische Sjögren syndrome nach lymphosarkom. Derm. Wschr. 153: 536 (2967).
Henderson, J.W. Keratoconjunctivitis sicca. A review with a survey of 121 additional cases. Amer. J. Ophthal. 33: 797 (1950).
Henderson, J.W. & W.A. Prough. Influence of age and sex on flow of tears. Arch. Ophthal. 43: 224 (1950).
Hoffman, F. The surface of the epithelial cells of the cornea under the scanning electron microscope. Ophthal. Res. (Basel) 3: 207 (1972).
Hoffman, F. & L. Dumitrescu. Beobachtungen der Kaninchenhornhaut unter der Raster-Elektronenmikroskop. Beitr. Elektronenmikr. Direktabb. Oberfl. 3: 307 (1970).
Hoffman, F. & J.U. Schweichel. The microvilli structure of the corneal epithelium of the rabbit in relation to cell function. A transmission and scanning electron microscopic study. Ophthal Res. 4: 175 (1972/73).
Hood, J., G.A. Burns & R.E. Hodges. Sjögren's syndrome in scurvy. New Engl. J. Med. 282: 1120 (1970).
Horan, E.C. Ophthalmic manifestations of progressive systemic lupus erythematosus. Brit. J. Ophthal. 53: 388 (1969).
Hornbaker, Jr, J.H., E.A. Foster, G.S. Williams & J.S. Davis, IV. Sjögren's syndrome and nodular reticulum cell sarcoma. Arch. Intern. Med. 118: 449 (1966).
Hoyes, A.D. Acid mucopolysaccharides in human fetal epidermis. Br. J. Derm. 48: 598 (1967).
Jessen, H. Two types of keratohyalin granules. J. Ult. Res. 33: 95 (1970).
Jessen, H. Electron cytochemical demonstration of sulfhydryl groups in keratohyalin granules and in the peripheral envelope of cornified cells. Histochemie 33: 15 (1973).
Jezegabel, C, G. Duprey & C. Rossazza. Syndrome de Mikulicz et leucémie lymphoide. Rev. Otoneuroophtal. 38: 208 (1966).
Kaye, G.I. & G.D. Pappas. Studies on the cornea. I. The fine structure of the rabbit cornea and the uptake and transport of colloidal particles by the cornea in vivo. J. CellBiol. 12: 457 (1962).
Kirkham, T.H. Scleroderma and Sjögren's syndrome. Brit. J. Ophthal. 53: 131 (1969).
Kologlu, S. Un cas de syndrome de Gougerot-Houwer-Sjögren. Sem. Hôp. Paris. 34: 3227 (1958).
Kuczynski, A., R.J.C. Evans & M.J. Mitchinson. Sicca syndrome due to primary amyloidosis. Brit. Med. J. 2: 506 (1971).
Kuming, B.S. & W.M. Politzer. Xerophthalmia and protein malnutrition in Bantu children. Brit. J. Ophthal. 51: 649 (1967).
Lavker, R.M. & A.G. Matoltsy. Substructure of keratohyalin granules of the epidermis as revealed by high resolution microscopy. J. Ult. Res. 35: 575 (1971).
Lechner-Netsch, G., A. Barry & J.M. Delagy. Leucémies et maladie auto-immunes: syndrome de Sjögren et anémie hémolytique associes à la leucémies lymphoide chronique. Canad. Med. Ass. J. 24: 1151 (1969).
Leuenberger, P.M. Die stereo Ultrastrukture der Cornealoberflache bei der Ratte. A. V. Graefes Arch. Klin. Exp. Ophth. 180: 182 (1970).
Leventhal, B.C., D.S. Waldorf & N. Talal. Impaired lymphocyte transformation and delayed hypersensitivity in Sjögren's syndrome. J. Clin. Invest. 46: 1338 (1967).
Love, R. & P. Wildy. Cytochemical studies of the nucleoproteins of Hela cells infected with herpes virus. J. Cell Biology 17: 237 (1963).
Luft, J.H. Improvements in epoxyresin embedding methods. J. Bioph. Bioch. Cytol. 9: 409 (1961).
Matoltsy, A.G. & P.F. Parakkal. Membrane coating granules of keratinising epithelia. J. Cell Biol. 24: 297 (1965).
Matoltsy, A.G., R.M. Lavker & M.N. Matoltsy. Demonstration of cystine-containing protein in keratohyalin granules of the epidermis. J. Invest. Derm. 62: 406 (1974).
Matoltsy, A.G. Desmosomes, filaments, and keratohyaline granules: their role in the stabilization and keratinization of the epidermis. J. Invest. Derm. 65: 127 (1975).
Mercer, E.H., G.E. Rogers, B.L. Munger & S.I. Roth. A suggested nomenclature for fine-structural components of keratin and keratin-like products of cells. Nature 201: 367 (1964).
McLenachan, J. New aspects of the aetiology of Sjögren's syndrome. Trans. Ophthal. Soc. U.K. 76: 413 (1956).
McNair Scott, T.F. & T. Tokumaru. The herpes virus group. In: Viral and Rickettesial infections of man. Ed. Horsfall, Jr, F.L. & I. Tam. Pitman Medical Publ. Company, London, and J.B. Lippincott Co, Philadelphia (1965).
Montagna, W. & W. Lobitz. The Epidermis. Academic Press, New York and London (1964).
Mortelmans, R. & M. Sebruyns, personal communication.
Nagakura, M.M. & M. Nagakura. A case of Sjögren's syndrome (in Japanese). J. Otorhinolaryng. Soc. Jap. 67: 1338 (1964).
Naib, Z., A. Clepper & S. Elliot. Exfoliative cytology as an aid in the diagnosis of opthalmic lesions. Acta Cytol. 11: 295 (1967).
O'Neill, E.M. Sjögren's syndrome with onset at 10 years of age. Proc. Royal Soc. Med. 58: 689 (1965).
Paczesniak, R. A case of Sjögren's syndrome (in Polish). Klin. Oczna 27: 289 (1957).
Pangrati, D. Sindrom Sjögren-Gougerot. Oftalmologica (Buc.) 8: 231 (1964).
Payrau, O., Y. Pouliquen, J.P. Faure & G. Offret. La transparence de la cornée. Le mècanisme de ses altérations. Masson et Cie. Ed. Paris (1967).
Pearse, G.A.E. Histochemistry. Theoretical and applied. Ed. Churchill Livingstone, Edinburgh and London. Part I (1968). Part II (1972).
Pedler, C. The fine structure of the corneal epithelium. Exp. Eye Res. 1: 286 (1962).
Pittman, F.E. & D.A. Holub. Sjögren's syndrome and adult coeliac disease. Gastroenterology 48: 869 (1965).
Plotkin, J., A. Reynaud & M. Okumoto. Cytological study of herpetic keratitis. Arch. Ophth. 85: 597 (1971).
Radnot, M. & E. Wallner. Keratoconjunctivitis sicca in Kindersalter. Ophthalmologica (Basel) 128: 355 (1954).
Ramage, J.H. & W.F. Kinnear. Keratoconjunctivitis sicca and the collagen diseases. Brit. J. Ophth. 40: 416 (1956).
Remolar, J.M., A. Roisenblit & L.N. Brown. Syndrome de Sjögren asociado a tiroiditis cronica. Rev. Asoc. mèd. Argent. 79: 106 (1965).
Rogers, G. E. The structure and biochemistry of keratin. In: The Biological Basis of Medicine. Eds. Bittar, E.E. & N. Bittar. Vol. 6. Academic Press, New York and London (1969).
Roizman, B. The programming of herpes virus multiplication in mammalian cells. Viruses, Nucleic acids and Cancer. Seventeenth annual symposium on fundamental cancer research. The Williams and Wilkins Co, Baltimore (1963).
Roizman, B., P.G. Spear & E.D. Kieff. Herpes simplex virus I and II: A biochemical definition. In: Persistent virus infections-Perspectives in Virology. VIII. Ed. M. Pollard. Academic Press, New York and London (1973).
Rozenblit, J. & I. Tenczynska. A borderline case of Feltys' syndrome and Sjögren's syndrom (in Polish). Wiad. Lek. 18: 1261 (1965).
Rudall, K.M. Intercellular fibrous proteins and keratins. In: Comprehensive Biochemistry. Eds. Florkin, M. &E.H. Stotz Elsevier Publishing Co., Amsterdam (1968).
Seifter, S. & P.M. Gallop. The structure of proteins. VI-Keratins. In: The Proteins. Ed. H. Neurath. Academic Press, New York and London (1966).
Shearn, M.A. & W.H. Tu. Nephrogenic diabetes insipidus and other defects of renal tubular function in Sjögren's syndrome. Amer. J. Med. 39: 312 (1965).
Shioji, R., T. Furuyama, S. Onodera, H. Saito, H. Ito & Y. Sasaki. Sjögren's syndrome and renal tubular acidosis. Amer. J. Med. 48: 456 (1970).
Sjögren, H. A new conception of keratoconjunctivitis sicca (Translated by J. B. Hamilton). Australian Medical Publishing Company (1943).
Sood, N.N. Sjögren's syndrome (a clinico-pathological study). J. All India Ophthal. Soc. 16: 19 (1968).
Stanworth, A. Keratoconjunctivitis sicca. Brit. J. Ophthal. 35: 317 (1951).
Steinberg, A.D. & N. Talal. The co-existence of Sjögren's syndrome and systemic lupus erythematosus. Ann. Intern. Med. 74: 55 (1971).
Stevens, T.R. & J.O. Oh. Comparison of type 1 and 2 herpes virus hominis infection of rabbit eyes. II. Histopathologic and virologic studies. Arch. Ophthal. 90(6): 477 (1973).
Stoltze, C.A., D.G. Hanlon, G.L. Pease & J.W. Henderson. Keratoconjunctivitis sicca and Sjögren's syndrome. Systemic manifestations and haematologic and protein abnormalities. Arch. Intern. Med. (Chic.) 106: 513 (1960).
Suzuki, H., K. Kurosumi.& C. Miyata. Electron microscopy of spherical keratohyalin granules. J. Invest. Derm. 60: 279 (1973).
Talal, N. & J.J. Bunim. The development of malignant lymphoma in the course of Sjögren's syndrome. Amer. J. Med. 36: 529 (1964).
Teng, C.C. & M. Katzin. The basement membrane of corneal epithelium. Amer. J. Ophthal. 36: 895 (1953).
Teng, C.C. The fine structure of the corneal epithelium and basement membrane of the rabbit. Amer. J. Ophthal. 51: 278 (1961).
Teng, C.C. Fine structure of the human corneal epithelium and stroma. Amer. J. Ophthal. 54: 969 (1962).
Threadgold, L.T. The ultrastructure of the animal cells. Pergamon Press, Oxford (1969).
Thygeson, P. Cytologic observations on herpetic keratitis. Amer. J. Ophthal. 45: 240 (1958).
Ugel, A.R. & W. Idler. Further characterisation of bovine keratohyaline. J. Cell Biol. 52: 453 (1972).
Ugel, A.R. Studies on isolated aggregating oligoribonucleoproteins of the epidermis with histochemical and morphological characteristics of keratohyalin. J. Cell Biol. 49: 405 (1971).
Van Bijsterveld, O.P. Diagnostic tests in the sicca syndrome. Arch. Ophthal. 82: 10 (1969).
Vanselow, N.A., V.N. Dodson, D.C. Angell & I.F. Duff. A clinical study of Sjögren's syndrome. Ann. intern. Med. 58: 124 (1963).
Vrabec, F. Age changes of the inner surface of the trabecular meshwork shown by the replica technique. Invest. Ophthal. 13/12: 950 (1974).
Vrabec, F. Plastic histology: study of surfaces of wet tissues by means of replicas. Amer. J. Ophthal. 69: 111 (1970).
Vrabec, F. The inner surface of the trabecular meshwork studied by a replica technique. Amer. J. Ophthal. 44: 7 (1957).
Vrabec, F. Sur la question de l'endothélium de la surface antérieure de l'iris humain. Ophthalmologica 123: 20 (1952).
Walser, A., I. Ivankovic & M. Baur. Sjögren-syndrome und struma lymphomatosa Hashimoto. Schweiz. med. Wschr. 95: 765 (1965).
Watson, D.H. Replication of the viruses-morphological aspects. In: The Herpes Viruses. Ed. A.S. Kaplan. Academic Press, New York and London (1973).
Wegelius, O., F. Fyhrquist & P.L. Ander. Sjögren's syndrome associated with vitamin B12 deficiency. Acta rheum, Scand. 16: 184 (1970).
Whaley, K., J. Williamson, W.C. Dick & W.W. Buchanan. Sjögren's syndrome: its clinical manifestations and associations.
Williamson, J., R.W.W. Paterson, D.D.M. McGavin, W.R. Greig &K. Whaley. Sjögren's syndrome in relation to pernicious anaemia and idiopathic Addisonian disease. Brit. J. Ophthal. 54: 31 (1970).
Williamson, J., T. Wilson, J. Wallace & K. Whaley. Studies of the bacterial flora in keratoconjunctivitis sicca. Eye, Ear, Nose, Throat Monthly 50: 257 (1971).
Author information
Authors and Affiliations
Additional information
This paper was originally submitted as a Doctor's Thesis to the Department of Ophthalmology, University of Leuven (Faculty of Medicine) in 1976.
Rights and permissions
About this article
Cite this article
Maudgal, P.C. The epithelial response in keratitis sicca and keratitis herpetica (an experimental and clinical study). Doc Ophthalmol 45, 223–327 (1978). https://doi.org/10.1007/BF00161670
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF00161670