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References 221

Fig. 18.4  Ex vivo imaging of the photoreceptor mosaic in a human donor eye by two photon-excited fluorescence

the inflammatory response to laser damage was longer than previously thought.

Two major challenges for the further development of molecular imaging in eye disease are the improvement of current imaging methods and the design of reporting biomarkers. The introduction of the confocal scanning laser ophthalmoscope has allowed for recording images of the living retina with enhanced sensitivity and high contrast. It has already been proven to be useful for molecular imaging in ophthalmology in several studies as outlined above. However, as opposed to the reliable analysis of the topographic distribution of the signal over one image, an absolute quantification of fluorescence intensities has not yet been possible in a reliable manner [19]. Several new imaging technologies and new development in the field of optics are available, but must be translated to ophthalmology. For example, the advantages of twophoton excited fluorescence have been already demonstrated on human eye donor tissue ex vivo (Fig. 18.4) [20, 21]. Without any slicing or cutting, the photoreceptor mosaic could be imaged with high resolution through the complete neurosensory retina. This was achieved by using the femtosecond laser. Hereby, the excitation light is effectively concentrated both in space and time, resulting in overall relative low excitation energy and generating a low amount of scattered light. When compared with standard confocal imaging, the result is an improved sig- nal-to-noise ratio and better image contrast, permitting the visualization of more and deeper retinal structures.

Furthermore, promising target molecules for eye disease must be identified and coupled with fluorescent dyes in order to use them as biomarkers for molecular imaging. To be successful, these reporting molecules must be highly sensitive and recordable with available in vivo imaging methods. Not all substances will most likely find

the way to the patient. The tolerability, safety profile and – last but not the least – the drug licensure by authorities must not be neglected.

Summaries for the Clinician

“Molecular imaging” aims at in vivo identification of organic and cellular malfunction before the occurrence of morphological or functional changes.

Molecular imaging offers great perspectives for earlier diagnoses, monitoring, and individualizing therapies.

A growing understanding of disease mechanisms and their causes at the molecular level could lead to a transformation in our treatment approach.

In several animal models, molecular imaging has already been successfully applied in ophthalmo­ logy.

For the sustained development of this new field, multidisciplinary efforts and close cooperation of experts from the field of ocular imaging with specialists in the field of molecular biology and probe development appear to be essential.

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