Elsevier

Survey of Ophthalmology

Volume 51, Issue 5, September–October 2006, Pages 482-500
Survey of Ophthalmology

Diagnostic and Surgical Techniques
Clinical Corneal Confocal Microscopy

https://doi.org/10.1016/j.survophthal.2006.06.010Get rights and content

Abstract

Confocal microscopy allows non-invasive in vivo imaging of the ocular surface. Its unique physical properties enable microscopic examination of all layers of the cornea and have been used to investigate numerous corneal diseases: epithelial changes, numerous stromal degenerative or dystrophic diseases, endothelial pathologies, corneal deposits, infections, and traumatic lesions. It offers a new approach to study the physiological reactions of the cornea to different stimuli and the pathophysiologic events leading to corneal dysfunction in certain diseases. Confocal microscopy proves to be a powerful diagnostic tool and is especially of value in certain corneal diseases by allowing straightforward and non-invasive recognition of the pathologic conditions.

Introduction

Over the past decades, the clinical application of confocal microscopy in ophthalmology has expanded in a progressive and consistent manner. The present review aims to summarize the current knowledge of this technology in corneal sciences and to provide the basis to interpret and analyze corneal confocal images.

Section snippets

Physical Principles

When examining the cornea using light biomicroscopy, the resolution is decreased by interference of light reflected from structures above and below the plane of examination. For instance, when examining a corneal lesion located at a certain stromal depth using a slit-lamp, light reflection from the stroma proximal and distal to the lesion, the epithelium, the tear film, and the endothelium is also perceived by the examiner. By using a condensor to focus the light source within a small area of

The Normal Cornea

Recognition of the normal appearance of the different corneal layers42, 84, 94, 113, 136, 155, 193, 203, 208 is crucial in order to allow identification of abnormal elements.

In the superficial layers, roundish epithelial cells (Fig. 1) demonstrate hyperreflective nuclei. Basal epithelial cells appear without nuclei reflectivity (Fig. 2). Harrison et al found that the average basal cell density was 5,274 ± 575 cells/mm2, the average cell area was 192 ± 19.6 μm2, and the average number of cell

Epithelial Diseases

Several reports have documented the confocal appearances of epithelial or subepithelial deposits, including amiodarone, amyloid, chloroquine, ciprofloxacin, gold, and iron deposits. Findings in amiodarone-induced keratopathy are characterized by high reflective, bright intracellular inclusions in the corneal epithelial cells. Furthermore, other corneal layers may be involved: bright microdots within the anterior and posterior stroma and on the endothelial cell layer in more advanced cases,

Stromal Abnormalities

Stromal dystrophies usually are readily identified upon slit-lamp examination. However, their confocal microscopic appearance198, 218 should be recognized, in order to avoid misinterpretation and erroneous diagnosis. In lattice dystrophy (Fig. 15),28, 187, 222 linear and branching hyperreflective structures with changing reflectivity and poorly demarcated margins are visualized in the stroma. In Meretoja syndrome, hyperreflective amyloid deposits may also be observed.191 In fleck dystrophy (

Endothelial Pathologies

Conventional techniques to examine the endothelium include specular microscopy and light or electron microscopy. While specular microscopy is often ineffective in visualizing the endothelium in cases of corneal edema, light or electron microscopy may only be used for ex vivo examination. Confocal microscopy, on the other hand, enables in vivo examination of the endothelium, even in cases of moderate corneal edema.

In cases of cornea guttata or Fuchs endothelial dystrophy, cornea guttae appear as

Infections

One of the first clinical applications of confocal microscopy consisted of its use in cases of corneal infections. Although this technology does not allow identification of small infectious agents such as viruses, it may allow visualization of larger infectious agents such as fungus, acanthamoeba, or microsporidium. Fungal infections are characterized by the presence of hyperreflective, branching filaments in the affected corneal layers (Fig. 27).4, 5, 27, 31, 61, 106, 226 Acanthamoeba appears

Miscellaneous

In patients with diabetes,64, 99, 132, 188 confocal microscopic findings are consistent with previous findings of corneal epithelial thinning and endothelial polymorphism. In some patients, abnormal stromal nerves and a reduction of long nerve fiber bundles may be noted. Interestingly, the severity of diabetic retinopathy correlates with measurement of corneal light scattering by confocal microscopy.152 The same phenomenon was described by Nagel et al in contact lens–associated corneal

Further Developments

Confocal microscopy may benefit from improvements such as increased resolution or an eye tracking capability. Increased resolution may eventually allow direct identification of bacterial agents. Eye tracking systems may enable precise three-dimensional localization of corneal structures or pathologies within the cornea and, coupled to a memory system, may allow the confocal microscope to be focused at the some area at different examination sessions or with different users. An interesting aspect

Method of Literature Search

Literature selection of this review article was based on a MEDLINE search covering the past 35 years using the key words confocal microscopy and cornea. Searches included English, French, and German literature. We included reports documenting the use of confocal microscopy in clinical conditions involving the cornea. Articles related to in vitro experiments or animal studies were selected if they could highlight the clinical use of the technique.

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