In vivo confocal microscopy of the ocular surface: from bench to bedside

Abstract

In vivo confocal microscopy (IVCM) is an emerging technology that provides minimally invasive, high resolution, steady-state assessment of the ocular surface at the cellular level. Several challenges still remain but, at present, IVCM may be considered a promising technique for clinical diagnosis and management. This mini-review summarizes some key findings in IVCM of the ocular surface, focusing on recent and promising attempts to move "from bench to bedside". IVCM allows prompt diagnosis, disease course follow-up, and management of potentially blinding atypical forms of infectious processes, such as acanthamoeba and fungal keratitis. This technology has improved our knowledge of corneal alterations and some of the processes that affect the visual outcome after lamellar keratoplasty and excimer keratorefractive surgery. In dry eye disease, IVCM has provided new information on the whole-ocular surface morphofunctional unit. It has also improved understanding of pathophysiologic mechanisms and helped in the assessment of prognosis and treatment. IVCM is particularly useful in the study of corneal nerves, enabling description of the morphology, density, and disease- or surgically induced alterations of nerves, particularly the subbasal nerve plexus. In glaucoma, IVCM constitutes an important aid to evaluate filtering blebs, to better understand the conjunctival wound healing process, and to assess corneal changes induced by topical antiglaucoma medications and their preservatives. IVCM has significantly enhanced our understanding of the ocular response to contact lens wear. It has provided new perspectives at a cellular level on a wide range of contact lens complications, revealing findings that were not previously possible to image in the living human eye. The final section of this mini-review provides a focus on advances in confocal microscopy imaging. These include 2D wide-field mapping, 3D reconstruction of the cornea and automated image analysis.

FIGURE 1

Laser IVCM appearance of (A) Acanthamoeba cysts demonstrating clustering of cysts, (B) Acanthamoeba cysts demonstrating linear alignment of cysts and (C and D) Acanthamoeba trophozoites.

FIGURE 2

Laser ICVM appearance of (A) Fusarium solani hyphae, (B) Paecilomyces lilacinus hyphae and (C) Candida parapsilosis.

FIGURE 3

Representative confocal microscopy of MGs scans of (A) normal control subject, (B) MGD patients and (C) SS patient. Please note the decreased density and the enlargement of acinar unit and the increased secretion reflectivity in MGD patient (B). SS patient shows small acinar units, with increased density of inflammatory cells and increased inhomogeneity of the periglandular interstice (C).

FIGURE 4

Representative impression cytology imprint and confocal microscopy scans of bulbar conjunctiva in (A and C) normal control subject and (B and D) SS patient. The squamous metaplasia was observed both in impression cytology and confocal microscopy examination.

FIGURE 5

IVCM appearance of microcysts of aqueous humor in the conjunctival epithelium over a filtering bleb after trabeculectomy.

FIGURE 6

Corneal epithelial changes in glaucoma patient, showing anisocytosis and inflammatory cells.

FIGURE 7

Extensive formation of microdots in the corneal stroma of a rigid lens wearer.

FIGURE 8

IVCM appearance of microcysts in the bulbar conjunctiva of an asymptomatic soft contact lens wearer.

FIGURE 9

Real-time mapping of (A) SNP structures and (B) results of automatic quantification of SNP structures using in house developed software.