Hostname: page-component-cd9895bd7-dzt6s Total loading time: 0 Render date: 2024-12-25T06:08:25.416Z Has data issue: false hasContentIssue false
  • English
  • Français

Identification of Objective Morphometric Markers of Xerostomia in the Oral Mucosa Epithelium with In Vivo Confocal Microscopy

Published online by Cambridge University Press:  06 February 2017

Ida G. Fostad ,
Jon R. Eidet ,
Neil S. Lagali ,
Darlene A. Dartt ,
Sten Ræder ,
Edvard B. Messelt  and
Tor P. Utheim Open the ORCID record for Tor P. Utheim [Opens in a new window]
Ida G. Fostad*
Affiliation:
Department of Oral Biology, Faculty of Dentistry, University of Oslo, Sognsvannsveien 10, PO Box 1052, 0316 Oslo, Norway The Norwegian Dry Eye Clinic, Lille Grensen 7, 0159 Oslo, Norway
Jon R. Eidet
Affiliation:
The Norwegian Dry Eye Clinic, Lille Grensen 7, 0159 Oslo, Norway Department of Ophthalmology, Oslo University Hospital, Kirkeveien 166, PO Box 4956, Nydalen, Norway
Neil S. Lagali
Affiliation:
Department of Clinical and Experimental Medicine, Linköping University, SE-581 83 Linköping, Sweden
Darlene A. Dartt
Affiliation:
Schepens Eye Research Institute/Massachusetts Eye and Ear, Harvard Medical School, 20 Staniford Street, Boston, MA 02114, USA
Sten Ræder
Affiliation:
The Norwegian Dry Eye Clinic, Lille Grensen 7, 0159 Oslo, Norway
Edvard B. Messelt
Affiliation:
Department of Oral Biology, Faculty of Dentistry, University of Oslo, Sognsvannsveien 10, PO Box 1052, 0316 Oslo, Norway
Tor P. Utheim
Affiliation:
Department of Oral Biology, Faculty of Dentistry, University of Oslo, Sognsvannsveien 10, PO Box 1052, 0316 Oslo, Norway The Norwegian Dry Eye Clinic, Lille Grensen 7, 0159 Oslo, Norway Department of Medical Biochemistry, Oslo University Hospital, Kirkeveien 166, PO Box 4956, Nydalen, Norway Department of Ophthalmology, Vestre Viken Hospital Trust, Dronninggata 28, 3004 Drammen, Norway
*
* Corresponding author. [email protected]
Get access

Abstract

The purpose of this work was to determine whether the morphology of the oral mucosa epithelium (OME) of patients with xerostomia differ from patients without xerostomia. In total, 34 patients with dry eye disease (DED) with or without xerostomia were examined at The Norwegian Dry Eye Disease Clinic with in vivo confocal microscopy of the lower lip. In addition, age- and gender-matched healthy controls (HC) were included. DED patients with xerostomia had a higher superficial to deep backscatter ratio compared with DED patients without xerostomia (p=0.002) and HC (p=0.001). Regression analysis demonstrated that this ratio was related to xerostomia independently of gender and age (p<0.001). Sensitivity and specificity of detecting xerostomia were 0.78 and 0.85, respectively, when using a superficial to deep backscatter ratio cut-off value of 0.995 (p=0.004). The mean nucleus to cytosol backscatter ratio in the superficial OME was lower in patients with xerostomia than in those without xerostomia (p=0.034). In vivo confocal microscopy is a potential tool for evaluating the oral cavity and to assess changes in the OME associated with xerostomia, objectively and quantitatively. The cause of the increased backscatter in the superficial OME in xerostomia, however, remains to be elucidated.

Keywords

xerostomiadry mouthin vivo confocal microscopyoral mucosa epithelium
Type
Biological Applications
Information
Microscopy and Microanalysis , Volume 23 , Issue 1 , February 2017 , pp. 88 - 96
Copyright
© Microscopy Society of America 2017 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Akpek, E.K., Klimava, A., Thorne, J.E., Martin, D., Lekhanont, K. & Ostrovsky, A. (2009). Evaluation of patients with dry eye for presence of underlying Sjogren syndrome. Cornea 28(5), 493–497.Google Scholar
Alhatem, A., Cavalcanti, B. & Hamrah, P. (2012). In vivo confocal microscopy in dry eye disease and related conditions. Semin Ophthalmol 27(5–6), 138–148.Google Scholar
Baruchin, A.M., Lustig, J.P., Nahlieli, O. & Neder, A. (1991). Burns of the oral mucosa. Report of 6 cases. J Craniomaxillofac Surg 19(2), 94–96.Google Scholar
Berardesca, E., Maibach, H. & Wilhelm, K.P. (2014). Non Invasive Diagnostic Techniques in Clinical Dermatology. Berlin: Springer.Google Scholar
Billings, M., Dye, B.A., Iafolla, T., Baer, A.N., Grisius, M. & Alevizos, I. (2016). Significance and implications of patient-reported xerostomia in Sjogren’s syndrome: Findings from the National Institutes of Health Cohort. EbioMedicine 12, 270–279.Google Scholar
Cardesa, A. & Slootweg, P.J. (2006). Pathology of the Head and Neck. Dordrecht: Springer.Google Scholar
Chaudhury, N.M., Shirlaw, P., Pramanik, R., Carpenter, G.H. & Proctor, G.B. (2015). Changes in saliva rheological properties and mucin glycosylation in dry mouth. J Dent Res 94(12), 1660–1667.CrossRefGoogle ScholarPubMed
Cinotti, E., Gergele, L., Perrot, J.L., Domine, A., Labeille, B., Borelli, P. & Cambazard, F. (2014). Quantification of capillary blood cell flow using reflectance confocal microscopy. Skin Res Technol 20(3), 373–378.Google Scholar
Davies, A. & Hall, S. (2011). Salivary gland dysfunction (dry mouth) in patients with advanced cancer. Int J Palliat Nurs 17(10), 477–482.CrossRefGoogle ScholarPubMed
Dawes, C., Pedersen, A.M., Villa, A., Ekstrom, J., Proctor, G.B., Vissink, A., Aframian, D., McGowan, R., Aliko, A., Narayana, N., Sia, Y.W., Joshi, R.K., Jensen, S.B., Kerr, A.R. & Wolff, A. (2015). The functions of human saliva: A review sponsored by the World Workshop on Oral Medicine VI. Arch Oral Biol 60(6), 863–874.Google Scholar
Delli, K., Spijkervet, F.K., Kroese, F.G., Bootsma, H. & Vissink, A. (2014). Xerostomia. Monogr Oral Sci 24, 109–125.Google Scholar
Drezek, R., Guillaud, M., Collier, T., Boiko, I., Malpica, A., Macaulay, C., Follen, M. & Richards-Kortum, R. (2003). Light scattering from cervical cells throughout neoplastic progression: Influence of nuclear morphology, DNA content, and chromatin texture. J Biomed Opt 8(1), 7–16.Google Scholar
Drezek, R.A., Collier, T., Brookner, C.K., Malpica, A., Lotan, R., Richards-Kortum, R.R. & Follen, M. (2000). Laser scanning confocal microscopy of cervical tissue before and after application of acetic acid. Am J Obstet Gynecol 182(5), 1135–1139.CrossRefGoogle ScholarPubMed
Duong, S., Youssef, J., Pimenta, P., Aguigam, H., Zhang, J., Calantog, A., Pilch, S., Masters, J.G. & Wilder-Smith, P. (2012). An imaging-based approach to the evaluation of xerostomia. Lasers Surg Med 44(6), 482–489.Google Scholar
Eidet, J.R., Pasovic, L., Maria, R., Jackson, C.J. & Utheim, T.P. (2014). Objective assessment of changes in nuclear morphology and cell distribution following induction of apoptosis. Diagn Pathol 9, 92.CrossRefGoogle ScholarPubMed
Ekberg, O. (2012). Dysphagia Diagnosis and Treatment. Dordrecht: Springer-Verlag Berlin Heidelberg.CrossRefGoogle Scholar
Farnetani, F., Scope, A., Braun, R.P., Gonzalez, S., Guitera, P., Malvehy, J., Manfredini, M., Marghoob, A.A., Moscarella, E., Oliviero, M., Puig, S., Rabinovitz, H.S., Stanganelli, I., Longo, C., Malagoli, C., Vinceti, M. & Pellacani, G. (2015). Skin cancer diagnosis with reflectance confocal microscopy: Reproducibility of feature recognition and accuracy of diagnosis. JAMA Dermatol 151(10), 1075–1080.Google Scholar
Fostad, I.G., Eidet, J.R., Utheim, T.P., Raeder, S., Lagali, N.S., Messelt, E.B. & Dartt, D.A. (2016). Dry eye disease patients with xerostomia report higher symptom load and have poorer meibum expressibility. PLoS One 11(5), e0155214.Google Scholar
Garcia-Hernandez, A., Roldan-Marin, R., Iglesias-Garcia, P. & Malvehy, J. (2013). In vivo noninvasive imaging of healthy lower lip mucosa: A correlation study between high-definition optical coherence tomography, reflectance confocal microscopy, and histology. Dermatol Res Pract 2013, 205256.Google Scholar
Gilvetti, C., Porter, S.R. & Fedele, S. (2010). Traumatic chemical oral ulceration: A case report and review of the literature. Br Dent J 208(7), 297–300.Google Scholar
Guthoff, R.F., Baudouin, C. & Stave, J. (2006). Atlas of Confocal Laser Scanning In-Vivo Microscopy in Ophthalmology. Dordrecht: Springer.Google Scholar
Hofmann-Wellenhof, R., Pellacani, G., Malvehy, J. & Soyer, H.P. (2012). Reflectance Confocal Microscopy for Skin Diseases. Dordrecht: Springer.Google Scholar
Humphrey, S.P. & Williamson, R.T. (2001). A review of saliva: Normal composition, flow, and function. J Prosthet Dent 85(2), 162–169.CrossRefGoogle ScholarPubMed
Kullaa, A.M., Asikainen, P., Herrala, M., Ukkonen, H. & Mikkonen, J.J. (2014). Microstructure of oral epithelial cells as an underlying basis for salivary mucosal pellicle. Ultrastruct Pathol 38(6), 382–386.Google Scholar
Lagali, N., Bourghard, P.B, Germundsson, J., Eden, U., Danyali, R., Rinaldo, M. & Fagerholm, P. (2013). Laser-scanning in vivo confocal microscopy of the cornea: Imaging and analysis methods for preclinical and clinical applications. In Confocal Laser Microscopy - Principles and Applications in Medicine, Biology, and the Food Sciences, Neil Lagali (Ed.), InTech, DOI: 10.5772/55216. Available at http://www.intechopen.com/books/confocal-laser-microscopy-principles-and-applications-in-medicine-biology-and-the-food-sciences/laser-scanning-in-vivo-confocal-microscopy-of-the-cornea-imaging-and-analysis-methods-for-preclinica.Google Scholar
Lin, H., Li, W., Dong, N., Chen, W., Liu, J., Chen, L., Yuan, H., Geng, Z. & Liu, Z. (2010). Changes in corneal epithelial layer inflammatory cells in aqueous tear-deficient dry eye. Invest Ophthalmol Vis Sci 51(1), 122–128.CrossRefGoogle ScholarPubMed
Lourenco, S.V., Kos, E., Borguezan Nunes, T., Bologna, S.B., Sangueza, M. & Nico, M.M. (2015). In vivo reflectance confocal microscopy evaluation of cheilitis glandularis: A report of 5 cases. Am J Dermatopathol 37(3), 197–202.Google Scholar
Maddox, P., Szarewski, A., Dyson, J. & Cuzick, J. (1994). Cytokeratin expression and acetowhite change in cervical epithelium. J Clin Pathol 47(1), 15–17.CrossRefGoogle ScholarPubMed
Maitland, K.C., Gillenwater, A.M., Williams, M.D., El-Naggar, A.K., Descour, M.R. & Richards-Kortum, R.R. (2008). In vivo imaging of oral neoplasia using a miniaturized fiber optic confocal reflectance microscope. Oral Oncol 44(11), 1059–1066.Google Scholar
Narhi, T.O., Meurman, J.H. & Ainamo, A. (1999). Xerostomia and hyposalivation: Causes, consequences and treatment in the elderly. Drugs Aging 15(2), 103–116.Google Scholar
Osailan, S.M., Pramanik, R., Shirlaw, P., Proctor, G.B. & Challacombe, S.J. (2012). Clinical assessment of oral dryness: Development of a scoring system related to salivary flow and mucosal wetness. Oral Surg Oral Med Oral Pathol Oral Radiol 114(5), 597–603.CrossRefGoogle ScholarPubMed
Peppelman, M., Wolberink, E.A., Gerritsen, M.J., van de Kerkhof, P.C. & van Erp, P.E. (2014). Application of leukotriene B4 and reflectance confocal microscopy as a noninvasive in vivo model to study the dynamics of skin inflammation. Skin Res Technol 21(2), 232–240.Google Scholar
Plemons, J.M., Al-Hashimi, I. & Marek, C.L, . & American Dental Association Council on Scientific, A (2014). Managing xerostomia and salivary gland hypofunction: Executive summary of a report from the American Dental Association Council on Scientific Affairs. J Am Dent Assoc 145(8), 867–873.Google Scholar
Rajadhyaksha, M., Menaker, G., Flotte, T., Dwyer, P.J. & Gonzalez, S. (2001). Confocal examination of nonmelanoma cancers in thick skin excisions to potentially guide mohs micrographic surgery without frozen histopathology. J Invest Dermatol 117(5), 1137–1143.CrossRefGoogle ScholarPubMed
Richards-Kortum, R.R., Zuluaga, A.F., Smithpeter, C., Collier, T. & Drezek, R. (2001). Enhancing contrast in biological imaging. Google Patents. Available at https://www.google.com/patents/US6593101Google Scholar
Scully, C. & Felix, D.H. (2005). Oral medicine — update for the dental practitioner: Oral white patches. Br Dent J 199(9), 565–572.Google Scholar
Selkin, B., Rajadhyaksha, M., Gonzalez, S. & Langley, R.G. (2001). In vivo confocal microscopy in dermatology. Dermatol Clin 19(2), 369–377. ix-x.CrossRefGoogle ScholarPubMed
Swindells, K., Burnett, N., Rius-Diaz, F., Gonzalez, E., Mihm, M.C. & Gonzalez, S. (2004). Reflectance confocal microscopy may differentiate acute allergic and irritant contact dermatitis in vivo. J Am Acad Dermatol 50(2), 220–228.CrossRefGoogle ScholarPubMed
Villa, A., Connell, C.L. & Abati, S. (2015a). Diagnosis and management of xerostomia and hyposalivation. Ther Clin Risk Manag 11, 45–51.Google Scholar
Villa, A., Wolff, A., Aframian, D., Vissink, A., Ekstrom, J., Proctor, G., McGowan, R., Narayana, N., Aliko, A., Sia, Y.W., Joshi, R.K., Jensen, S.B., Kerr, A.R., Dawes, C. & Pedersen, A.M. (2015b). World Workshop on Oral Medicine VI: A systematic review of medication-induced salivary gland dysfunction: Prevalence, diagnosis, and treatment. Clin Oral Investig 19(7), 1563–1580.Google Scholar
Von Bultzingslowen, I., Sollecito, T.P., Fox, P.C., Daniels, T., Jonsson, R., Lockhart, P.B., Wray, D., Brennan, M.T., Carrozzo, M., Gandera, B., Fujibayashi, T., Navazesh, M., Rhodus, N.L., & Schiodt, M. (2007). Salivary dysfunction associated with systemic diseases: systematic review and clinical management recommendations. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 103(Suppl), S57 e51–15.Google Scholar
White, W.M., Rajadhyaksha, M., Gonzalez, S., Fabian, R.L. & Anderson, R.R. (1999). Noninvasive imaging of human oral mucosa in vivo by confocal reflectance microscopy. Laryngoscope 109(10), 1709–1717.Google Scholar
Wolberink, E.A., Peppelman, M., van de Kerkhof, P.C., van Erp, P.E. & Gerritsen, M.J. (2014). Establishing the dynamics of neutrophil accumulation in vivo by reflectance confocal microscopy. Exp Dermatol 23(3), 184–188.Google Scholar
Zuluaga, A.F., Drezek, R., Collier, T., Lotan, R., Follen, M. & Richards-Kortum, R. (2002). Contrast agents for confocal microscopy: How simple chemicals affect confocal images of normal and cancer cells in suspension. J Biomed Opt 7(3), 398–403.Google Scholar