Purpose: To describe the principles, capabilities, and applications of confocal microscopy in vivo in ophthalmology. Design: Perspective, literature review, and commentary. Methods: Review and synthesis of selected recent literature, with interpretation and perspective. Results: Confocal microscopy imaging has led to a better understanding of the cellular microstructure in the normal, postsurgical, and diseased cornea by enabling quantitative analysis of the cellular response in the human cornea in vivo. At present, the major role of confocal microscopy is in research of corneal surgery and disease. Clinical applications are limited to facilitating the diagnosis of Acanthamoeba and deep fungal keratitis, measuring residual bed thickness after laser in situ keratomileusis, and measuring endothelial cell density in high-light-scattering situations. Conclusions: In addition to providing qualitative data, confocal microscopy is valuable for quantitative analysis of the cornea and will enable the investigation of pharmacologic and surgical modifications of corneal wound healing, nerve regeneration, and cellular responses. Prospective, quantitative analyses require individual calibration of confocal microscopes for lateral and axial dimensions of images, for image depth, and for light intensity.
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