In vivo confocal microscopy of human corneal nerves in health, in ocular and systemic disease, and following corneal surgery: a review

The exponential evolution of in vivo confocal microscopy (IVCM) has led to a significant enhancement in our knowledge of the living cornea in both its physiological and pathological states. Studies using white light and coherent light-based IVCM have enabled detailed quantitative analysis of sub-basal nerve parameters, and have also resulted in the elucidation of the two-dimensional architecture of the normal corneal sub-basal nerve plexus. However, accurate and repeatable methods for quantitative analysis of stromal nerves imaged by IVCM remain to be developed. The effect of corneal surgery on central corneal nerves has been well documented in many IVCM studies, and these studies provide an indication of the regenerative capacity of corneal nerves. IVCM has also clearly demonstrated the involvement of corneal nerves in diseases such as keratoconus, although it remains unclear whether these alterations are a cause of, or occur secondary to, the disease process. IVCM has also been proposed as non-invasive method of accurately diagnosing and assessing the progression of diabetic neuropathy, highlighting the potential application of this technique as an indicator of systemic disease. This review consolidates our knowledge of how IVCM has contributed significantly to our greater understanding of corneal nerves in the living human cornea in health and disease.

[1]  INMA PEREZ-GOMEZ,et al.  Change to Corneal Morphology after Refractive Surgery (Myopic Laser In Situ Keratomileusis) as Viewed with a Confocal Microscope , 2003, Optometry and vision science : official publication of the American Academy of Optometry.

[2]  W. Petroll,et al.  Effect of myopic LASIK on corneal sensitivity and morphology of subbasal nerves. , 2000, Investigative ophthalmology & visual science.

[3]  Nathan Efron,et al.  Corneal nerve tortuosity in diabetic patients with neuropathy. , 2004, Investigative ophthalmology & visual science.

[4]  Francesco Viola,et al.  The cornea in Sjogren's syndrome: an in vivo confocal study. , 2007, Investigative ophthalmology & visual science.

[5]  L. Hesse,et al.  Corneal reinnervation after photorefractive keratectomy and laser in situ keratomileusis: an in vivo study with a confocal videomicroscope. , 1996, German journal of ophthalmology.

[6]  I. Immonen,et al.  Corneal structure and sensitivity in type 1 diabetes mellitus. , 2000, Investigative ophthalmology & visual science.

[7]  Dipika V Patel,et al.  Mapping the corneal sub-basal nerve plexus in keratoconus by in vivo laser scanning confocal microscopy. , 2006, Investigative ophthalmology & visual science.

[8]  H. Matsuda Electron microscopic study on the corneal nerve with special reference to its endings , 1968 .

[9]  Oliver Stachs,et al.  In vivo three-dimensional confocal laser scanning microscopy of the epithelial nerve structure in the human cornea , 2007, Graefe's Archive for Clinical and Experimental Ophthalmology.

[10]  C. Baudouin,et al.  Evaluation of corneal stromal changes in vivo after laser in situ keratomileusis with confocal microscopy. , 2001, Ophthalmology.

[11]  C. McGhee,et al.  Laser scanning in vivo confocal microscopy and quantitative aesthesiometry reveal decreased corneal innervation and sensation in keratoconus , 2009, Eye.

[12]  Enrico Grisan,et al.  Automatic recognition of corneal nerve structures in images from confocal microscopy. , 2008, Investigative ophthalmology & visual science.

[13]  N. Efron,et al.  Morphology of corneal nerves in soft contact lens wear. A comparative study using confocal microscopy. , 2003, Ophthalmic & physiological optics : the journal of the British College of Ophthalmic Opticians.

[14]  T. Tervo,et al.  Long-term corneal morphology after PRK by in vivo confocal microscopy. , 2003, Investigative ophthalmology & visual science.

[15]  C. McGhee,et al.  Age-related differences in the normal human cornea: a laser scanning in vivo confocal microscopy study , 2007, British Journal of Ophthalmology.

[16]  T. Møller-Pedersen,et al.  Stromal wound healing explains refractive instability and haze development after photorefractive keratectomy: a 1-year confocal microscopic study. , 2000, Ophthalmology.

[17]  Sanjay V. Patel,et al.  Keratocyte density of central human cornea after laser in situ keratomileusis. , 2002, American journal of ophthalmology.

[18]  N. Efron,et al.  Subbasal Nerve Regeneration After Penetrating Keratoplasty , 2007, Cornea.

[19]  N Efron,et al.  Morphology of Corneal Nerves Using Confocal Microscopy , 2001, Cornea.

[20]  Hyman A. Carrel,et al.  Decreased density of corneal basal epithelium and subbasal corneal nerve bundle changes in patients with diabetic retinopathy. , 2006, American journal of ophthalmology.

[21]  J. McLaren,et al.  Reinnervation in the cornea after LASIK. , 2002, Investigative ophthalmology & visual science.

[22]  J. García-Sánchez,et al.  An in vivo confocal masked study on corneal epithelium and subbasal nerves in patients with dry eye. , 2004, Investigative ophthalmology & visual science.

[23]  C. McGhee,et al.  Corneal innervation and cellular changes after corneal transplantation: an in vivo confocal microscopy study. , 2007, Investigative ophthalmology & visual science.

[24]  Sanjay V. Patel,et al.  Keratocyte density and recovery of subbasal nerves after penetrating keratoplasty and in late endothelial failure. , 2007, Archives of ophthalmology.

[25]  N. Efron,et al.  Subbasal nerve regeneration after LASEK measured by confocal microscopy. , 2007, Journal of refractive surgery.

[26]  Mehmet Orhan,et al.  Morphologic Alterations of Both the Stromal and Subbasal Nerves in the Corneas of Patients with Diabetes , 2006, Cornea.

[27]  Nathan Efron,et al.  Surrogate Markers of Small Fiber Damage in Human Diabetic Neuropathy , 2007, Diabetes.

[28]  H. Lee,et al.  Comparison of corneal nerve regeneration and sensitivity between LASIK and laser epithelial keratomileusis (LASEK). , 2006, American journal of ophthalmology.

[29]  Y. Konttinen,et al.  Corneal innervation and morphology in primary Sjögren's syndrome. , 2003, Investigative ophthalmology & visual science.

[30]  Lihui Luo,et al.  Altered Corneal Nerves in Aqueous Tear Deficiency Viewed by In Vivo Confocal Microscopy , 2005, Cornea.

[31]  M. Cerro,et al.  Peptidergic and catecholaminergic fibers in the human corneal epithelium , 1989, Acta ophthalmologica. Supplement.

[32]  A. Thaer,et al.  Confocal microscopy reveals persisting stromal changes after myopic photorefractive keratectomy in zero haze corneas , 1998, The British journal of ophthalmology.

[33]  C. O'donnell,et al.  An evaluation of corneal nerve morphology and function in moderate keratoconus. , 2005, Contact lens & anterior eye : the journal of the British Contact Lens Association.

[34]  Sanjay V. Patel,et al.  Confocal microscopy in vivo in corneas of long-term contact lens wearers. , 2002, Investigative ophthalmology & visual science.

[35]  Dipika V Patel,et al.  Mapping of the normal human corneal sub-Basal nerve plexus by in vivo laser scanning confocal microscopy. , 2005, Investigative ophthalmology & visual science.

[36]  J. McLaren,et al.  The Effect of Age on the Corneal Subbasal Nerve Plexus , 2005, Cornea.

[37]  F. Varon Patients with diabetes. , 2009, Journal of the American Dental Association.

[38]  E. Varnell,et al.  Corneal healing after uncomplicated LASIK and its relationship to refractive changes: a six-month prospective confocal study. , 2004, Investigative ophthalmology & visual science.

[39]  C. McGhee,et al.  Assessing the sub‐basal nerve plexus of the living healthy human cornea by in vivo confocal microscopy , 2002, Clinical & experimental ophthalmology.

[40]  D. Patel,et al.  In vivo confocal microscopy of the cornea in health and disease , 2011 .

[41]  Dipika V Patel,et al.  Contemporary in vivo confocal microscopy of the living human cornea using white light and laser scanning techniques: a major review , 2007, Clinical & experimental ophthalmology.

[42]  N. Efron,et al.  Correlation of the Appearance of the Keratoconic Cornea In Vivo by Confocal Microscopy and In Vitro by Light Microscopy , 2005, Cornea.

[43]  R. A. Malik,et al.  Corneal confocal microscopy: a non-invasive surrogate of nerve fibre damage and repair in diabetic patients , 2003, Diabetologia.

[44]  R. Guthoff,et al.  Corneal reinnervation following penetrating keratoplasty--correlation of esthesiometry and confocal microscopy. , 1996, German journal of ophthalmology.

[45]  J. McLaren,et al.  Recovery of corneal subbasal nerve density after PRK and LASIK. , 2005, American journal of ophthalmology.

[46]  J. McLaren,et al.  Corneal reinnervation after LASIK: prospective 3-year longitudinal study. , 2004, Investigative ophthalmology & visual science.

[47]  D. Patel,et al.  In vivo laser scanning confocal microscopy confirms that the human corneal sub-basal nerve plexus is a highly dynamic structure. , 2008, Investigative ophthalmology & visual science.

[48]  A. Elhan,et al.  Morphology of corneal nerves and corneal sensation in dry eye: a preliminary study , 2005, Eye.

[49]  J. Auran,et al.  Scanning slit confocal microscopic observation of cell morphology and movement within the normal human anterior cornea. , 1995, Ophthalmology.

[50]  W. Wiegand,et al.  In vivo observation of corneal nerve regeneration after photorefractive keratectomy with a confocal videomicroscope. , 1996, German journal of ophthalmology.

[51]  G F Vrensen,et al.  Architecture of human corneal nerves. , 1997, Investigative ophthalmology & visual science.

[52]  N. Efron,et al.  Subbasal nerve fiber regeneration after LASIK and LASEK assessed by noncontact esthesiometry and in vivo confocal microscopy: Prospective study , 2007, Journal of cataract and refractive surgery.