Contact lens-induced changes in the anterior eye as observed in vivo with the confocal microscope
Introduction
Complications of contact lens wear can arise as a result of mechanical insult, hypoxic or hypercapnic stress, immunological reactions to lens deposits or solutions, toxic reactions to solutions, or infection, and can be exacerbated by local ocular problems (e.g. dry eye) or general systemic disorders (e.g. diabetes) (Efron, 2004a). Contact lens practitioners rely upon the optical slit lamp biomicroscope (SLB) for the critical task of examining the anterior ocular structures before, during and after contact lens wear. This instrument is extremely flexible in that it offers a stereoscopic view over a range of magnifications. The cornea can be illuminated with a slit of light that can be tilted and rotated, varied in terms of brightness, width and height, and interposed with coloured and polarizing filters.
A fundamental limitation of the SLB is that the highest practicable magnification possible is around ×40, with a lateral resolution of 30 μm. In certain circumstances, this places a considerable constraint upon clinical decision-making. For example, it is not possible to identify the precise nature of infiltrates in a case of keratitis. The relatively new technique of confocal microscopy (CM) offers clinicians the opportunity to examine the living human cornea at a magnification of around ×500 to ×700. This technique, therefore, enables examination of tissue structures at a cellular level, and in relation to the example given above, extraneous matter such as infectious agents can be identified.
In this article, the optical principle of CM will be briefly reviewed, and the development of this instrument will be recounted up to the present point in time at which CM is a viable clinical technique. The design and construction of current instruments will be outlined. A qualitative and quantitative analysis of images obtained from normal human corneas using this technique will be presented, along with the results of research detailing the effects of contact lens wear on the cornea.
Section snippets
Confocal microscopy
In broad terms, the optical principle of the CM is that field of view is sacrificed for resolution. In the SLB, a broad beam of light is used to view a large section of cornea at relatively low magnification. This arrangement offers a large field of view, but resolution is limited. With the CM, a small spot of light is projected into the cornea, and the small illuminated region of corneal tissue is imaged via a confocal optical arrangement. This results in very high resolution but virtually no
The normal cornea as viewed with the confocal microscope
A number of qualitative and quantitative studies have been undertaken documenting the appearance of the normal cornea as viewed with the CM. Some studies have been designed as specific investigations of the normal human cornea, and others have provided details relating to normal control corneas as part of broader experiments. Much of this work has been conducted using earlier generation instruments, primarily the SSCM. The greater image brightness and contrast of the LSCM result in subtle
The normal limbus and conjunctiva as viewed with the confocal microscope
The LSCM allows the limbal region to be viewed with good clarity (Rong and Yan, 2006). Limbal palisades of Vogt are clearly discernable (Kobayashi and Sugiyama, 2005; Patel et al., 2006; Rong and Yan, 2006). Red blood cells can be seen within vessels at the limbus (Fig. 16). Limbal vessels and red blood cells can also be imaged using the SSCM (Makrynioti and Efron, 2004), but with less clarity. Rong and Yan (2006) observed that the surface epithelium at the limbus has a rather ‘loose’
The cornea during contact lens wear
The availability of the CM introduces the prospect of solving contact lens-related problems that have been difficult to investigate due to a lack of resolution and magnification available with existing instruments—primarily the SLB. The CM has allowed researchers and clinicians to (a) discover, or better understand, the reason for the appearance of certain contact lens related phenomena (e.g. stromal striae and folds), (b) verify the patho-physiology of certain conditions that are already
The limbus during contact lens wear
Limbal and conjunctival redness induced by contact lens wear has long been a topic of considerable interest because of both the pathophysiologic implications and the adverse cosmesis associated with a red eye. As described in Section 4, high-quality images of the limbus and conjunctiva can be obtained using LSCM. This technique has been used to examine the reaction of the limbus and conjunctiva to contact lens wear.
Summary and conclusions
The development of the CM has heralded the introduction of a new era in ocular science and medicine. It is now possible to view structures of the cornea at a cellular level, which means that phenomena that have previously only been imaged at low magnification and resolution can now be re-investigated to develop a better understanding of normal corneal structure and function and abnormal corneal conditions. The implications of this technology for generating a better understanding of corneal
Future directions
The image analysis software supplied with current CMs facilitates quantification of a limited number of tissue structures via a combination of semi- and fully automated tools. As the importance of various corneal features become apparent, efforts should be directed to developing software to assist researchers and clinicians in acquiring quantitative information from confocal images. Thus, there is a need to develop fully automated electronic tools that assist, for example, in determining the
Acknowledgements
I wish to thank friends and colleagues who have collaborated with me in the confocal microscopy studies described in this review, in particular Jo Hollingsworth, Panos Kallinikos, Dimitra Makrynioti, Phil Morgan, Haliza Mutalib, Laura Oliveira-Soto and Inma Perez-Gomez. I also wish to thank Nicola Pritchard for critically reviewing the manuscript.
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