Abstract
Microscopic evaluation of the ocular structures has always been a challenge for ophthalmic clinicians and researchers. In Vivo Confocal Microscopy utilized ophthalmologists and scientists to evaluate the anterior segment and revolutionized some aspects of diagnosis and management the patients. Nowadays confocal microscopy is becoming an indispensable tool for studying living cornea and other ocular surface structures at a cellular level. This technology provides fast and non-invasive images of different layers in both normal and pathologic eyes which are so helpful in studying of normal cornea, diagnosis of several disorders and monitoring the patients. The purpose of this chapter is to describe the principles of confocal microscopy and its different types and finally summarize several applications of confocal microscopy and characteristics findings in some of clinical states such as infectious keratitis, dry eye, ocular allergy and contact lens wearing.
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References
Minsky M. Memoir on inventing the confocal scanning microscope. Scanning. 1988;10(4):128–38.
Egger MD, Petran M. New reflected-light microscope for viewing unstained brain and ganglion cells. Science. 1967;157(3786):305–7.
Petroll WM, Jester JV, Cavanagh HD. In vivo confocal imaging. Int Rev Exp Pathol. 1996;36:93–129.
Petroll WM, Robertson DM. In vivo confocal microscopy of the cornea: new developments in image acquisition, reconstruction, and analysis using the HRT-Rostock corneal module. Ocular Surface. 2015;13(3):187–203.
Labbé A, Khammari C, Dupas B, Gabison E, Brasnu E, Labetoulle M, et al. Contribution of in vivo confocal microscopy to the diagnosis and management of infectious keratitis. Ocular Surface. 2009;7(1):41–52.
Jalbert I, Stapleton F, Papas E, Sweeney D, Coroneo M. In vivo confocal microscopy of the human cornea. Br J Ophthalmol. 2003;87(2):225–36.
Leduc C, Dupas B, Ott-Benoist A, Baudouin C. Advantages of the in vivo HRT2 corneal confocal microscope for investigation of the ocular surface epithelia. J Fr Ophtalmol. 2004;27(9 Pt 1):978–86.
Zhivov A, Stachs O, Kraak R, Stave J, Guthoff RF. In vivo confocal microscopy of the ocular surface. Ocular Surface. 2006;4(2):81–93.
Patel DV, McGhee CN. Quantitative analysis of in vivo confocal microscopy images: a review. Surv Ophthalmol. 2013;58(5):466–75.
Guthoff RF, Zhivov A, Stachs O. In vivo confocal microscopy, an inner vision of the cornea–a major review. Clin Exp Ophthalmol. 2009;37(1):100–17.
Efron N, Morgan PB, Makrynioti D. Chronic morbidity of corneal infiltrative events associated with contact lens wear. Cornea. 2007;26(7):793–9.
Vaddavalli PK, Garg P, Sharma S, Sangwan VS, Rao GN, Thomas R. Role of confocal microscopy in the diagnosis of fungal and Acanthamoeba keratitis. Ophthalmology. 2011;118(1):29–35.
Kobayashi A, Mawatari Y, Yokogawa H, Sugiyama K. In vivo laser confocal microscopy after Descemet stripping with automated endothelial keratoplasty. Am J Ophthalmol. 2008;145(6):977–85. e1.
Bouheraoua N, Jouve L, El Sanharawi M, Sandali O, Temstet C, Loriaut P, et al. Optical coherence tomography and confocal microscopy following three different protocols of corneal collagen-crosslinking in Keratoconus. Invest Ophthalmol Vis Sci. 2014;55(11):7601–9.
Petroll WM, Cavanagh HD, Jester JV. Clinical confocal microscopy. Curr Opin Ophthalmol. 1998;9(4):59–65.
Tervo T, Moilanen J. In vivo confocal microscopy for evaluation of wound healing following corneal refractive surgery. Prog Retinal Eye Res. 2003;22(3):339–58.
Kaufman SC, Kaufman HE. How has confocal microscopy helped us in refractive surgery? Curr Opin Ophthalmol. 2006;17(4):380–8.
Jester JV, Petroll WM, Cavanagh HD. Corneal stromal wound healing in refractive surgery: the role of Myofibroblasts. Prog Retinal Eye Res. 1999;18(3):311–56.
Villani E, Baudouin C, Efron N, Hamrah P, Kojima T, Patel SV, et al. In vivo confocal microscopy of the ocular surface: from bench to bedside. Curr Eye Res. 2014;39(3):213–31.
Ulrich M, Lange-Asschenfeldt S. In vivo confocal microscopy in dermatology: from research to clinical application. J Biomed Optics. 2013;18(6):061212.
Mazzotta C, Hafezi F, Kymionis G, Caragiuli S, Jacob S, Traversi C, et al. In vivo confocal microscopy after corneal collagen crosslinking. Ocular Surface. 2015;13(4):298–314.
Lemp MA, Dilly PN, Boyde A. Tandem-scanning (confocal) microscopy of the full-thickness cornea. Cornea. 1985;4(4):205–9.
Cavanagh HD, Jester JV, Essepian J, Shields W, Lemp MA. Confocal microscopy of the living eye. The CLAO J. 1990;16(1):65–73.
Petroll WM, Cavanagh HD, Jester J. Three-dimensional imaging of corneal cells using in vivo confocal microscopy. J Microsc. 1993;170(3):213–9.
Masters BR, Thaer AA. Real-time scanning slit confocal microscopy of the in vivo human cornea. Appl Opt. 1994;33(4):695–701.
Brakenhoff G, Visscher K. Confocal imaging with bilateral scanning and array detectors. J Microsc. 1992;165(1):139–46.
Erie EA, McLaren JW, Kittleson KM, Patel SV, Erie JC, Bourne WM. Corneal subbasal nerve density: a comparison of two confocal microscopes. Eye Contact Lens. 2008;34(6):322.
Zhivov A, Stachs O, Stave J, Guthoff RF. In vivo three-dimensional confocal laser scanning microscopy of corneal surface and epithelium. Br J Ophthalmol. 2009;93(5):667–72.
Wilson T. Confocal microscopy. Microanalysis of Solids: Springer; 1994. p. 219–32.
Guthoff RF, Baudouin C, Stave J. Atlas of confocal laser scanning in-vivo microscopy in ophthalmology: Springer Science & Business Media; 2007.
Eckard A, Stave J, Guthoff RF. In vivo investigations of the corneal epithelium with the confocal Rostock Laser Scanning Microscope (RLSM). Cornea. 2006;25(2):127–31.
del Castillo JMBt, Wasfy MA, Fernandez C, Garcia-Sanchez J. An in vivo confocal masked study on corneal epithelium and subbasal nerves in patients with dry eye. Investigative ophthalmology & visual science. 2004;45(9):3030–5.
Ceresara G, Fogagnolo P, De Cillà S, Panizzo V, Danelli PG, Orzalesi N, et al. Corneal involvement in Crohn’s disease: an in vivo confocal microscopy study. Cornea. 2011;30(2):136–42.
Patel D, Ku J, Johnson R, McGhee C. Laser scanning in vivo confocal microscopy and quantitative Aesthesiometry reveal decreased corneal innervation and sensation in Keratoconus. Eye. 2009;23(3):586.
Matsuda H. Electron microscopic study of the corneal nerve with special reference to the nerve endings. Nippon Ganka Gakkai Zasshi. 1968;72(7):880–93.
Ueda S, del Cerro M, LoCascio JA, Aquavella JV. Peptidergic and catecholaminergic fibers in the human corneal epithelium: an immunohistochemical and electron microscopic study. Acta Ophthalmol. 1989;67(S192):80–90.
Auran JD, Koester CJ, Kleiman NJ, Rapaport R, Bomann JS, Wirotsko BM, et al. Scanning slit confocal microscopic observation of cell morphology and movement within the normal human anterior cornea. Ophthalmology. 1995;102(1):33–41.
Oliveira-Soto L, Efron N. Morphology of corneal nerves using confocal microscopy. Cornea. 2001;20(4):374–84.
Patel DV, McGhee CN. Contemporary in vivo confocal microscopy of the living human cornea using white light and laser scanning techniques: a major review. Clin Exp Ophthalmol. 2007;35(1):71–88.
Jester JV, Moller-Pedersen T, Huang J, Sax CM, Kays WT, Cavangh HD, et al. The cellular basis of corneal transparency: evidence for ‘corneal crystallins.’ J Cell Sci. 1999;112(5):613–22.
Zhivov A, Stachs O, Kraak R, Guthoff R. Cellular laser microscopy of corneal ulcer and infiltrate. Klin Monatsbl Augenheilkd. 2008;225(1):86–90.
Mastropasqua L, Nubile M, Lanzini M, Carpineto P, Ciancaglini M, Pannellini T, et al. Epithelial dendritic cell distribution in normal and inflamed human cornea: in vivo confocal microscopy study. American journal of ophthalmology. 2006;142(5):736–44. e2.
Zhivov A, Stave J, Vollmar B, Guthoff R. In vivo confocal microscopic evaluation of Langerhans cell density and distribution in the normal human corneal epithelium. Graefe’s Arch Clin Exp Ophthalmol. 2005;243(10):1056–61.
Zhivov A, Stave J, Vollmar B, Guthoff R. In vivo confocal microscopic evaluation of langerhans cell density and distribution in the corneal epithelium of healthy volunteers and contact lens wearers. Cornea. 2007;26(1):47–54.
Thomas PA, Geraldine P. Infectious keratitis. Curr Opin Infect Dis. 2007;20(2):129–41.
Keay L, Edwards K, Naduvilath T, Taylor HR, Snibson GR, Forde K, et al. Microbial keratitis: predisposing factors and morbidity. Ophthalmology. 2006;113(1):109–16.
Pachigolla G, Blomquist P, Cavanagh H. A 5-year review of 132 cases of microbial keratitis at a major urban county hospital. Eye Contact Lens. 2007;33(4):207.
Chew S-J, Beuerman RW, Assouline M, Kaufman HE, Barron BA, Hill JM. Early diagnosis of infectious keratitis with in vivo real time confocal microscopy. The CLAO J. 1992;18(3):197–201.
Linna T, Mikkilä H, Karma A, Seppälä I, Petroll WM, Tervo T. In vivo confocal microscopy: a new possibility to confirm the diagnosis of Borrelia keratitis? Cornea. 1996;15(6):639.
Kaufman SC, Laird JA, Cooper R, Beuerman RW. Diagnosis of bacterial contact lens related keratitis with the white-light confocal microscope. The CLAO J. 1996;22(4):274–7.
Vaddavalli PK, Garg P, Sharma S, Thomas R, Rao GN. Confocal microscopy for Nocardia keratitis. Ophthalmology. 2006;113(9):1645–50.
Cavanagh HD, Petroll WM, Alizadeh H, He Y-G, McCulley JP, Jester JV. Clinical and diagnostic use of in vivo confocal microscopy in patients with corneal disease. Ophthalmology. 1993;100(10):1444–54.
Rosenberg ME, Tervo TM, Müller LJ, Moilanen JA, Vesaluoma MH. In vivo confocal microscopy after herpes keratitis. Cornea. 2002;21(3):265–9.
Dosso AA, Rungger-Brändle E. Clinical course of epidemic keratoconjunctivitis: evaluation by in vivo confocal microscopy. Cornea. 2008;27(3):263–8.
Asbell P, Stenson S. Ulcerative keratitis: survey of 30 years’ laboratory experience. Arch Ophthalmol. 1982;100(1):77–80.
Leck A, Thomas P, Hagan M, Kaliamurthy J, Ackuaku E, John M, et al. Aetiology of suppurative corneal ulcers in Ghana and south India, and epidemiology of fungal keratitis. Br J Ophthalmol. 2002;86(11):1211–5.
Upadhyay MP, Karmacharya PC, Koirala S, Tuladhar NR, Bryan LE, Smolin G, et al. Epidemiologic characteristics, predisposing factors, and etiologic diagnosis of corneal ulceration in Nepal. Am J Ophthalmol. 1991;111(1):92–9.
Liesegang TJ, Forster RK. Spectrum of microbial keratitis in South Florida. Am J Ophthalmol. 1980;90(1):38–47.
Patel A, Hammersmith K. Contact lens-related microbial keratitis: recent outbreaks. Curr Opin Ophthalmol. 2008;19(4):302–6.
Kanavi MR, Javadi M, Yazdani S, Mirdehghanm S. Sensitivity and specificity of confocal scan in the diagnosis of infectious keratitis. Cornea. 2007;26(7):782–6.
Winchester K, Mathers WD, Sutphin JE. Diagnosis of Aspergillus keratitis in vivo with confocal microscopy. Cornea. 1997;16(1):27–31.
Avunduk A, Beuerman R, Varnell E, Kaufman H. Confocal microscopy of Aspergillus fumigatus keratitis. Br J Ophthalmol. 2003;87(4):409–10.
Brasnu E, Bourcier T, Dupas B, Degorge S, Rodallec T, Laroche L, et al. In vivo confocal microscopy in fungal keratitis. Br J Ophthalmol. 2007;91(5):588–91.
Sagoo MS, Mehta JS, Hau S, Irion LD, Curry A, Bonshek RE, et al. Microsporidium stromal keratitis: in vivo confocal findings. Cornea. 2007;26(7):870–3.
Shah GK, Pfister D, Probst LE, Ferrieri P, Holland E. Diagnosis of microsporidial keratitis by confocal microscopy and the chromatrope stain. Am J Ophthalmol. 1996;121(1):89–91.
Kumar RL, Cruzat A, Hamrah P, editors. Current state of in vivo confocal microscopy in management of microbial keratitis. Semin Ophthalmol. 2010, Taylor & Francis.
Foulks GN. Acanthamoeba keratitis and contact lens wear: static or increasing problem? Eye Contact Lens. 2007;33(6):412–4.
Mathers WD. Acanthamoeba: a difficult pathogen to evaluate and treat. LWW. 2004.
Claerhout I, Goegebuer A, Van Den Broecke C, Kestelyn P. Delay in diagnosis and outcome of Acanthamoeba keratitis. Graefe’s Arch Clin Exp Ophthalmol. 2004;242(8):648–53.
Awwad ST, Petroll WM, McCulley JP, Cavanagh HD. Updates in Acanthamoeba keratitis. Eye Contact Lens. 2007;33(1):1–8.
Mathers WD, Nelson SE, Lane JL, Wilson ME, Allen RC, Folberg R. Confirmation of confocal microscopy diagnosis of Acanthamoeba keratitis using polymerase chain reaction analysis. Arch Ophthalmol. 2000;118(2):178–83.
Tu EY, Joslin CE, Sugar J, Booton GC, Shoff ME, Fuerst PA. The relative value of confocal microscopy and superficial corneal scrapings in the diagnosis of Acanthamoeba keratitis. Cornea. 2008;27(7):764–72.
Kobayashi A, Ishibashi Y, Oikawa Y, Yokogawa H, Sugiyama K. In vivo and ex vivo laser confocal microscopy findings in patients with early-stage Acanthamoeba keratitis. Cornea. 2008;27(4):439–45.
Auran JD, Starr MB, Koester CJ, LaBombardi VJ. In vivo scanning slit confocal microscopy of Acanthamoeba keratitis. A case report. Cornea. 1994;13(2):183–5.
Winchester K, Mathers WD, Sutphin JE, Daley TE. Diagnosis of Acanthamoeba keratitis in vivo with confocal microscopy. Cornea. 1995;14(1):10–7.
Pfister DR, Cameron JD, Krachmer JH, Holland EJ. Confocal microscopy findings of Acanthamoeba keratitis. Am J Ophthalmol. 1996;121(2):119–28.
Cho B-J, Holland EJ. In vivo tandem scanning confocal microscopy in Acanthamoeba keratitis. Korean J Ophthalmol. 1998;12(2):112–207.
Bourcier T, Dupas B, Borderie V, Chaumeil C, Larricart P, Baudouin C, et al. Heidelberg retina tomograph II findings of Acanthamoeba keratitis. Ocular Immunol Inflam. 2005;13(6):487–92.
Matsumoto Y, Dogru M, Sato EA, Katono Y, Uchino Y, Shimmura S, et al. The application of in vivo confocal scanning laser microscopy in the management of Acanthamoeba keratitis. Mol Vis. 2007;13(7):1319–26.
Mathers WD, Sutphin JE, Folberg R, Meier PA, Wenzel RP, Elgin RG. Outbreak of keratitis presumed to be caused by Acanthamoeba. Am J Ophthalmol. 1996;121(2):129–42.
Parmar DN, Awwad ST, Petroll WM, Bowman RW, McCulley JP, Cavanagh HD. Tandem scanning confocal corneal microscopy in the diagnosis of suspected Acanthamoeba keratitis. Ophthalmology. 2006;113(4):538–47.
Su P-Y, Hu F-R, Chen Y-M, Han J-H, Chen W-L. Dendritiform cells found in central cornea by in-vivo confocal microscopy in a patient with mixed bacterial keratitis. Ocular Immunol Inflam. 2006;14(4):241–4.
Nakano E, Oliveira M, Portellinha W, de Freitas D, Nakano K. Confocal microscopy in early diagnosis of Acanthamoeba keratitis. J Refract Surg. 2004;20(5):S737–40.
Tan DT, Mehta JS. Future directions in lamellar corneal transplantation. Cornea. 2007;26:S21–8.
McLaren JW, Patel SV. Modeling the effect of forward scatter and aberrations on visual acuity after endothelial keratoplasty. Invest Ophthalmol Vis Sci. 2012;53(9):5545–51.
Baratz KH, McLaren JW, Maguire LJ, Patel SV. Corneal haze determined by confocal microscopy 2 years after Descemet stripping with endothelial keratoplasty for Fuchs corneal dystrophy. Arch Ophthalmol. 2012;130(7):868–74.
Patel SV, Baratz KH, Hodge DO, Maguire LJ, McLaren JW. The effect of corneal light scatter on vision after Descemet stripping with endothelial keratoplasty. Arch Ophthalmol. (Chicago, Ill: 1960). 2009;127(2):153–60.
Patel SV, McLaren JW. In vivo confocal microscopy of Fuchs endothelial dystrophy before and after endothelial keratoplasty. JAMA Ophthalmol. 2013;131(5):611–8.
Van Der Meulen IJ, Patel SV, Lapid-Gortzak R, Nieuwendaal CP, McLaren JW, Van Den Berg TJ. Quality of vision in patients with Fuchs endothelial dystrophy and after Descemet stripping endothelial keratoplasty. Arch Ophthalmol. 2011;129(12):1537–42.
Patel SV, Erie JC, McLaren JW, Bourne WM. Keratocyte density and recovery of subbasal nerves after penetrating keratoplasty and in late endothelial failure. Arch Ophthalmol. 2007;125(12):1693–8.
Ahuja Y, Baratz KH, McLaren JW, Bourne WM, Patel SV. Decreased corneal sensitivity and abnormal corneal nerves in Fuchs endothelial dystrophy. Cornea. 2012;31(11):1257.
Al-Aqaba M, Alomar T, Lowe J, Dua HS. Corneal nerve aberrations in bullous keratopathy. Am J Ophthalmol. 2011;151(5):840–9. e1.
Patel SV, Baratz KH, Maguire LJ, Hodge DO, McLaren JW. Anterior corneal aberrations after Descemet’s stripping endothelial keratoplasty for Fuchs’ endothelial dystrophy. Ophthalmology. 2012;119(8):1522–9.
Raecker ME, McLaren JW, Kittleson KM, Patel SV. Endothelial image quality after descemet stripping with endothelial keratoplasty: a comparison of three microscopy techniques. Eye Contact Lens. 2011;37(1):6–10.
Seery LS, Nau CB, McLaren JW, Baratz KH, Patel SV. Graft thickness, graft folds, and aberrations after Descemet stripping endothelial keratoplasty for Fuchs dystrophy. Am J Ophthalmol. 2011;152(6):910–6.
Shortt AJ, Allan BD, Evans JR. Laser‐assisted in‐situ keratomileusis (LASIK) versus photorefractive keratectomy (PRK) for myopia. Cochrane Database Systemat Rev. 2013(1).
McLaren JW, Bourne WM, Patel SV. Stromal reflectance after photorefractive keratectomy: a paired comparison between epithelial removal by rotary brush and excimer laser-scrape. Invest Ophthalmol Visual Sci. 2012;53(14):1469.
McLaren JW, Bourne WM, Patel SV. Standardization of corneal haze measurement in confocal microscopy. Invest Ophthalmol Vis Sci. 2010;51(11):5610–6.
Erie JC, McLaren JW, Hodge DO, Bourne WM. Recovery of corneal subbasal nerve density after PRK and LASIK. Am J Ophthalmol. 2005;140(6):1059–64. e1.
Patel SV, McLaren JW, Kittleson KM, Bourne WM. Subbasal nerve density and corneal sensitivity after laser in situ keratomileusis: femtosecond laser vs mechanical microkeratome. Arch Ophthalmol. 2010;128(11):1413–9.
Calvo R, McLaren JW, Hodge DO, Bourne WM, Patel SV. Corneal aberrations and visual acuity after laser in situ keratomileusis: femtosecond laser versus mechanical microkeratome. Am J Ophthalmol. 2010;149(5):785–93.
Klingler KN, McLaren JW, Bourne WM, Patel SV. Corneal endothelial cell changes 5 years after laser in situ keratomileusis: femtosecond laser versus mechanical microkeratome. J Cataract Refract Surg. 2012;38(12):2125–30.
Patel SV, Bourne WM. Corneal endothelial cell loss 9 years after excimer laser keratorefractive surgery. Arch Ophthalmol. 2009;127(11):1423–7.
Lee SJ, Kim JK, Seo KY, Kim EK, Lee HK. Comparison of corneal nerve regeneration and sensitivity between LASIK and laser epithelial keratomileusis (LASEK). Am J Ophthalmol. 2006;141(6):1009–15. e1.
Lee BH, McLaren JW, Erie JC, Hodge DO, Bourne WM. Reinnervation in the cornea after LASIK. Invest Ophthalmol Vis Sci. 2002;43(12):3660–4.
Kallinikos P, Berhanu M, O’Donnell C, Boulton AJ, Efron N, Malik RA. Corneal nerve tortuosity in diabetic patients with neuropathy. Invest Ophthalmol Vis Sci. 2004;45(2):418–22.
Stapleton F, Hayward KB, Bachand N, Trong PH, Teh DW, Deng KM, et al. Evaluation of corneal sensitivity to mechanical and chemical stimuli after LASIK: a pilot study. Eye Contact Lens. 2006;32(2):88–93.
Stachs O, Zhivov A, Kraak R, Hovakimyan M, Wree A, Guthoff R. Structural-functional correlations of corneal innervation after LASIK and penetrating keratoplasty. J Refract Surg. 2010;26(3):159–67.
Tuisku IS, Lindbohm N, Wilson SE, Tervo TM. Dry eye and corneal sensitivity after high myopic LASIK. J Refract Surg. 2007;23(4):338–42.
Ambrósio R Jr, Tervo T, Wilson SE. LASIK-associated dry eye and neurotrophic epitheliopathy: pathophysiology and strategies for prevention and treatment. J Refract Surg. 2008;24(4):396–407.
Rosenthal P, Baran I, Jacobs DS. Corneal pain without stain: is it real? Ocular Surface. 2009;7(1):28–40.
Nettune GR, Pflugfelder SC. Post-LASIK tear dysfunction and dysesthesia. Ocular Surface. 2010;8(3):135–45.
Hamrah P, Cruzat A, Dastjerdi MH, Zheng L, Shahatit BM, Bayhan HA, et al. Corneal sensation and subbasal nerve alterations in patients with herpes simplex keratitis: an in vivo confocal microscopy study. Ophthalmology. 2010;117(10):1930–6.
Hamrah P, Cruzat A, Dastjerdi MH, Prüss H, Zheng L, Shahatit BM, et al. Unilateral herpes zoster ophthalmicus results in bilateral corneal nerve alteration: an in vivo confocal microscopy study. Ophthalmology. 2013;120(1):40–7.
Rosenberg ME, Tervo TM, Immonen IJ, Müller LJ, Grönhagen-Riska C, Vesaluoma MH. Corneal structure and sensitivity in type 1 diabetes mellitus. Invest Ophthalmol Vis Sci. 2000;41(10):2915–21.
Martone G, Alegente M, Balestrazzi A, Nuti E, Traversi C, Pichierri P, et al. In vivo confocal microscopy in bilateral herpetic keratitis: a case report. London, UK: SAGE Publications; 2008.
Patel DV, McGhee CN. Laser scanning in vivo confocal microscopy demonstrating significant alteration of human corneal nerves following herpes zoster ophthalmicus. Arch Neurol. 2010;67(5):640–1.
Hamrah P, Schrems W, Hoesl L, Dastjerdi M, Dana R, Pavan-Langston D. Corneal epithelial and stromal changes in patients with herpes simplex keratitis: An in vivo confocal microscopy study. Invest Ophthalmol Visual Sci. 2009;50(13):2389.
Patel DV, Tavakoli M, Craig JP, Efron N, McGhee CN. Corneal sensitivity and slit scanning in vivo confocal microscopy of the subbasal nerve plexus of the normal central and peripheral human cornea. Cornea. 2009;28(7):735–40.
Mocan MC, Yilmaz PT, Irkec M, Orhan M. In vivo confocal microscopy for the evaluation of corneal microstructure in keratoconus. Curr Eye Res. 2008;33(11–12):933–9.
Patel DV, McGhee CN. Mapping the corneal sub-basal nerve plexus in keratoconus by in vivo laser scanning confocal microscopy. Invest Ophthalmol Vis Sci. 2006;47(4):1348–51.
Niederer RL, Perumal D, Sherwin T, McGhee CN. Laser scanning in vivo confocal microscopy reveals reduced innervation and reduction in cell density in all layers of the keratoconic cornea. Invest Ophthalmol Vis Sci. 2008;49(7):2964–70.
Mannion LS, Tromans C, O’Donnell C. An evaluation of corneal nerve morphology and function in moderate keratoconus. Contact Lens and Anterior Eye. 2005;28(4):185–92.
Spoerl E, Huhle M, Seiler T. Induction of cross-links in corneal tissue. Exp Eye Res. 1998;66(1):97–103.
Wollensak G, Spoerl E, Seiler T. Riboflavin/ultraviolet-A–induced collagen crosslinking for the treatment of keratoconus. Am J Ophthalmol. 2003;135(5):620–7.
Al-Aqaba M, Calienno R, Fares U, Otri AM, Mastropasqua L, Nubile M, et al. The effect of standard and transepithelial ultraviolet collagen cross-linking on human corneal nerves: an ex vivo study. Am J Ophthalmol. 2012;153(2):258–66. e2.
Spadea L, Salvatore S, Paroli MP, Vingolo EM. Recovery of corneal sensitivity after collagen crosslinking with and without epithelial debridement in eyes with keratoconus. J Cataract Refract Surg. 2015;41(3):527–32.
Dyck PJ, Overland CJ, Low PA, Litchy WJ, Davies JL, Dyck PJB, et al. Signs and symptoms versus nerve conduction studies to diagnose diabetic sensorimotor polyneuropathy: Cl vs. NPhys Trial. Muscle Nerve. 2010;42(2):157–64.
Petropoulos IN, Green P, Chan AW, Alam U, Fadavi H, Marshall A, et al. Corneal confocal microscopy detects neuropathy in patients with type 1 diabetes without retinopathy or microalbuminuria. PLoS ONE. 2015;10(4):e0123517.
Misra SL, Craig JP, Patel DV, McGhee CN, Pradhan M, Ellyett K, et al. In vivo confocal microscopy of corneal nerves: an ocular biomarker for peripheral and cardiac autonomic neuropathy in type 1 diabetes mellitus. Invest Ophthalmol Vis Sci. 2015;56(9):5060–5.
Bitirgen G, Ozkagnici A, Malik R, Kerimoglu H. Corneal nerve fibre damage precedes diabetic retinopathy in patients with type 2 diabetes mellitus. Diabet Med. 2014;31(4):431–8.
Palejwala NV, Walia HS, Yeh S. Ocular manifestations of systemic lupus erythematosus: a review of the literature. Autoimmune Dis. 2012;2012.
Marsovszky L, Resch MD, Németh J, Toldi G, Medgyesi E, Kovács L, et al. In vivo confocal microscopic evaluation of corneal Langerhans cell density, and distribution and evaluation of dry eye in rheumatoid arthritis. Innate Immun. 2013;19(4):348–54.
Mohsenin A, Huang JJ. Ocular manifestations of systemic inflammatory diseases. Conn Med. 2012;76(9):533–44.
Villani E, Beretta S, De Capitani M, Galimberti D, Viola F, Ratiglia R. In vivo confocal microscopy of meibomian glands in Sjögren’s syndrome. Invest Ophthalmol Vis Sci. 2011;52(2):933–9.
Hong J, Zhu W, Zhuang H, Xu J, Sun X, Le Q, et al. In vivo confocal microscopy of conjunctival goblet cells in patients with Sjögren’s syndrome dry eye. Br J Ophthalmol. 2010;94(11):1454–8.
Enríquez-de-Salamanca A, Bonini S, Calonge M. Molecular and cellular biomarkers in dry eye disease and ocular allergy. Curr Opin Allergy Clin Immunol. 2012;12(5):523–33.
Kari O, Saari KM. Diagnostics and new developments in the treatment of ocular allergies. Curr Allergy Asthma Rep. 2012;12(3):232–9.
Miljanović B, Dana R, Sullivan DA, Schaumberg DA. Impact of dry eye syndrome on vision-related quality of life. Am J Ophthalmol. 2007;143(3):409–15. e2.
Matsumoto Y, Sato EA, Ibrahim OM, Dogru M, Tsubota K. The application of in vivo laser confocal microscopy to the diagnosis and evaluation of meibomian gland dysfunction. Mol Vision. 2008;14:1263.
Ibrahim OM, Matsumoto Y, Dogru M, Adan ES, Wakamatsu TH, Goto T, et al. The efficacy, sensitivity, and specificity of in vivo laser confocal microscopy in the diagnosis of meibomian gland dysfunction. Ophthalmology. 2010;117(4):665–72.
Villani E, Ceresara G, Beretta S, Magnani F, Viola F, Ratiglia R. In vivo confocal microscopy of meibomian glands in contact lens wearers. Invest Ophthalmol Vis Sci. 2011;52(8):5215–9.
Matsumoto Y, Shigeno Y, Sato EA, Ibrahim OM, Saiki M, Negishi K, et al. The evaluation of the treatment response in obstructive meibomian gland disease by in vivo laser confocal microscopy. Graefe’s Arch Clin Exp Ophthalmol. 2009;247(6):821–9.
Ban Y, Ogawa Y, Ibrahim OM, Tatematsu Y, Kamoi M, Uchino M, et al. Morphologic evaluation of meibomian glands in chronic graft-versus-host disease using in vivo laser confocal microscopy. Mol Vis. 2011;17:2533.
Villani E, Canton V, Magnani F, Viola F, Nucci P, Ratiglia R. The aging Meibomian gland: an in vivo confocal study. Invest Ophthalmol Vis Sci. 2013;54(7):4735–40.
Villani E, Galimberti D, Papa ND, Nucci P, Ratiglia R. Inflammation in dry eye associated with rheumatoid arthritis: cytokine and in vivo confocal microscopy study. Innate Immun. 2013;19(4):420–7.
Alhatem A, Cavalcanti B, Hamrah P, editors. In vivo confocal microscopy in dry eye disease and related conditions. Semin Ophthalmol. 2012, Taylor & Francis.
Cruzat A, Witkin D, Baniasadi N, Zheng L, Ciolino JB, Jurkunas UV, et al. Inflammation and the nervous system: the connection in the cornea in patients with infectious keratitis. Invest Ophthalmol Vis Sci. 2011;52(8):5136–43.
Tuominen IS, Konttinen YT, Vesaluoma MH, Moilanen JA, Helintö M, Tervo TM. Corneal innervation and morphology in primary Sjogren’s syndrome. Invest Ophthalmol Vis Sci. 2003;44(6):2545–9.
Villani E, Galimberti D, Viola F, Mapelli C, Ratiglia R. The cornea in Sjogren’s syndrome: an in vivo confocal study. Invest Ophthalmol Vis Sci. 2007;48(5):2017–22.
Zhang X, Chen Q, Chen W, Cui L, Ma H, Lu F. Tear dynamics and corneal confocal microscopy of subjects with mild self-reported office dry eye. Ophthalmology. 2011;118(5):902–7.
Efron N. Contact lens-induced changes in the anterior eye as observed in vivo with the confocal microscope. Prog Retinal Eye Res. 2007;26(4):398–436.
Villani E, Viola F, Sala R, Salvi M, Mapelli C, Curro N, et al. Corneal involvement in Graves’ orbitopathy: an in vivo confocal study. Invest Ophthalmol Vis Sci. 2010;51(9):4574–8.
Lin H, Li W, Dong N, Chen W, Liu J, Chen L, et al. Changes in corneal epithelial layer inflammatory cells in aqueous tear–deficient dry eye. Invest Ophthalmol Vis Sci. 2010;51(1):122–8.
Matsumoto Y, Ibrahim OM. Application of in vivo confocal microscopy in dry eye disease. Invest Ophthalmol Visual Sci. 2018;59(14):DES41–DES7.
Benítez-del-Castillo JM, Acosta MC, Wassfi MA, Díaz-Valle D, Gegúndez JA, Fernandez C, et al. Relation between corneal innervation with confocal microscopy and corneal sensitivity with noncontact esthesiometry in patients with dry eye. Invest Ophthalmol Vis Sci. 2007;48(1):173–81.
Villani E, Galimberti D, Viola F, Mapelli C, Del Papa N, Ratiglia R. Corneal involvement in rheumatoid arthritis: an in vivo confocal study. Invest Ophthalmol Vis Sci. 2008;49(2):560–4.
Wakamatsu TH, Sato EA, Matsumoto Y, Ibrahim OM, Dogru M, Kaido M, et al. Conjunctival in vivo confocal scanning laser microscopy in patients with Sjögren syndrome. Invest Ophthalmol Vis Sci. 2010;51(1):144–50.
Iaccheri B, Torroni G, Cagini C, Fiore T, Cerquaglia A, Lupidi M, et al. Corneal confocal scanning laser microscopy in patients with dry eye disease treated with topical cyclosporine. Eye. 2017;31(5):788.
Levy O, Labbé A, Borderie V, Hamiche T, Dupas B, Laroche L, et al. Increased corneal sub-basal nerve density in patients with Sjögren syndrome treated with topical cyclosporine A. Clin Exp Ophthalmol. 2017;45(5):455–63.
Messmer E, Torres ES, Mackert M, Zapp D, Kampik A. In vivo confocal microscopy in blepharitis. Klin Monatsbl Augenheilkd. 2005;222(11):894–900.
Irkec MT, Bozkurt B. Molecular immunology of allergic conjunctivitis. Curr Opin Allergy Clin Immunol. 2012;12(5):534–9.
Hu Y, Matsumoto Y, Adan ES, Dogru M, Fukagawa K, Tsubota K, et al. Corneal in vivo confocal scanning laser microscopy in patients with atopic keratoconjunctivitis. Ophthalmology. 2008;115(11):2004–12.
Le Q, Hong J, Zhu W, Sun X, Xu J. In vivo laser scanning confocal microscopy of vernal keratoconjunctivitis. Clin Exp Ophthalmol. 2011;39(1):53–60.
Leonardi A, Lazzarini D, Bortolotti M, Piliego F, Midena E, Fregona I. Corneal confocal microscopy in patients with vernal keratoconjunctivitis. Ophthalmology. 2012;119(3):509–15.
Ibrahim OM, Matsumoto Y, Dogru M, Adan ES, Wakamatsu TH, Shimazaki J, et al. In vivo confocal microscopy evaluation of meibomian gland dysfunction in atopic-keratoconjunctivitis patients. Ophthalmology. 2012;119(10):1961–8.
Ladage PM, Petroll WM, Jester JV, Fisher S, Bergmanson JP, Cavanagh HD. Spherical indentations of human and rabbit corneal epithelium following extended contact lens wear1. Eye Contact Lens. 2002;28(4):177–80.
Craig JP, Sherwin T, Grupcheva CN, McGhee CN. An evaluation of mucin balls associated with high-DK silicone-hydrogel contact lens wear. Springer: Lacrimal Gland, Tear Film, and Dry Eye Syndromes 3; 2002. p. 917–23.
Millar TJ, Papas EB, Ozkan J, Jalbert I, Ball M. Clinical appearance and microscopic analysis of mucin balls associated with contact lens wear. Cornea. 2003;22(8):740–5.
Ladage PM, Yamamoto K, Ren DH, Li L, Jester JV, Petroll WM, et al. Effects of rigid and soft contact lens daily wear on corneal epithelium, tear lactate dehydrogenase, and bacterial binding to exfoliated epithelial cells. Ophthalmology. 2001;108(7):1279–88.
Sindt CW, Grout TK, Critser DB, Kern JR, Meadows DL. Dendritic immune cell densities in the central cornea associated with soft contact lens types and lens care solution types: a pilot study. Clin Ophthalmol (Auckland, NZ). 2012;6:511.
Böhnke M, Masters BR. Long-term contact lens wear induces a corneal degeneration with microdot deposits in the corneal stroma. Ophthalmology. 1997;104(11):1887–96.
Hollingsworth JG, Efron N. Confocal microscopy of the corneas of long-term rigid contact lens wearers. Contact Lens Anterior Eye. 2004;27(2):57–64.
Ma X, He L, He D, Xu J. Chloroquine keratopathy of rheumatoid arthritis patients detected by in vivo confocal microscopy. Curr Eye Res. 2012;37(4):293–9.
Sbeity Z, Palmiero PM, Tello C, Liebmann JM, Ritch R. Non-contact in vivo confocal scanning laser microscopy in exfoliation syndrome, exfoliation syndrome suspect and normal eyes. Acta Ophthalmol. 2011;89(3):241–7.
Mocan MC, Eldem B, Irkec M. In vivo confocal microscopic findings of two siblings with Maroteaux-Lamy syndrome. Cornea. 2007;26(1):90–3.
Efron N, Mutalib HA. Confocal microscopy observations of the cornea in response to contact lens wear. Die Kontaktlinse. 2001;35(1):4–16.
Nagel S, Wiegand W, Thaer A, Geyer O. Light scattering study of the cornea in contact lens patients. In vivo studies using confocal slit scanning microscopy. Der Ophthalmologe: Zeitschrift der Deutschen Ophthalmologischen Gesellschaft. 1996;93(3):252–6.
Rong B, Yan X. Changes of corneal limbus in long-term soft contact lens wearers by using laser confocal microscope. [Zhonghua yan ke za zhi] Chin J Ophthalmol. 2007;43(6):514–8.
Efron N, Al-Dossari M, Pritchard N. Confocal microscopy of the bulbar conjunctiva in contact lens wear. Cornea. 2010;29(1):43–52.
Labbé A, Dupas B, Hamard P, Baudouin C. In vivo confocal microscopy study of blebs after filtering surgery. Ophthalmology. 2005;112(11):1979. e1–e9.
Guthoff R, Klink T, Schlunck G, Grehn F. In vivo confocal microscopy of failing and functioning filtering blebs: results and clinical correlations. J Glaucoma. 2006;15(6):552–8.
Messmer EM, Zapp DM, Mackert MJ, Thiel M, Kampik A. In vivo confocal microscopy of filtering blebs after trabeculectomy. Arch Ophthalmol. 2006;124(8):1095–103.
Amar N, Labbé A, Hamard P, Dupas B, Baudouin C. Filtering blebs and aqueous pathway: an immunocytological and in vivo confocal microscopy study. Ophthalmology. 2008;115(7):1154–61. e4.
Martone G, Frezzotti P, Tosi GM, Traversi C, Mittica V, Malandrini A, et al. An in vivo confocal microscopy analysis of effects of topical antiglaucoma therapy with preservative on corneal innervation and morphology. American journal of ophthalmology. 2009;147(4):725–35. e1.
Baratz KH, Nau CB, Winter EJ, McLaren JW, Hodge DO, Herman DC, et al. Effects of glaucoma medications on corneal endothelium, keratocytes, and subbasal nerves among participants in the ocular hypertension treatment study. Cornea. 2006;25(9):1046–52.
Acknowledgement
I would like to express my special thanks to Dr. Kasra CHeraqpour for his effort in preparation of this chapter.
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Soleimani, M. (2021). Confocal Scan. In: Mohammadpour, M. (eds) Diagnostics in Ocular Imaging. Springer, Cham. https://doi.org/10.1007/978-3-030-54863-6_10
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