Ocular endotamponade

The particularity of the use of highly fluorinated liquids as ocular endotamponades Biocompatibility... 

Evaluation of undesirable local effects of ocular endotamponades 2.4.1. Effects of the high density Oxygen content... 

In different medical disciplines, highly fluorinated liquids are directly used, like in the case of ocular endotamponades in ophthalmology, of gas carriers in liquid ventilation, or of preservation and transport media in transplantation medicine. For these applications, the highly fluorinated liquids are used in a purified form or as mixtures. The extraordinary... 

This chapter presents the state of the art of the use of highly fluorinated liquids in ophthalmology and perspectives of future applications in the eye. In different medical disciplines, the characteristics of these fluids are directly used, like in the case of ocular endotamponades in ophthalmology, of gas carriers in liquid ventilation, or of preservation and transport media in transplantation medicine [1-3]. For these applications, the highly fluorinated liquids are used in a purified form or as mixtures. The intended effect is created by the physicochemical characteristics themselves. The extraordinary behaviour of the fluorocarbon liquids (FCLs) requires specialised biocompatibility testing, adjusted to this class of components. 

Finally, an outlook into the possible future of highly fluorinated compounds as drug-delivering ocular endotamponades will be given. 

The demonstration of the potential of this stable and obviously excellently tolerated compound has inspired a great number of scientists to develop PFCLs as special tools for medical applications and to introduce therapies using the outstanding behaviours of PFCLs, like the well-known concepts of complete and partial liquid ventilation [4], oxygen support of the skin, wound treatment [5], artificial tears [6], and ocular endotamponade media [1], to name only a few. Until now, the mouse submersed in PFCLs is often used as an eye-catcher for the demonstration of the biocompatibility of PFCLs even in cases where the topic of the presentation is not reflected by this experiment. 

Table 1. Perfluorocarbons used as ocular endotamponade and their behaviour...

An ocular endotamponade has to fulfil the related requirements of the particularities for this special application. 

From a classification point of view, ocular endotamponades are classical medical devices. Their application inside the human eye requires, besides ultra-purity, special controls during the manufacturing as well as for the release of finished products. They must be non-toxic and sterile and have to meet the general requirements of the European Medical Device Directive (MDD). 

Table 1 shows the products used and tested as ocular endotamponades and their characteristics. In addition to the specific density, the interfacial tension against water is also an important parameter for the use. The drainage of subret-inal fluids is achieved, but the interfacial tension prevents the passage of the PFCL into the subretinal space. 

Developments to improve ocular endotamponades were focused initially on lower-density FCLs as alternatives to the PFCLs [23-25]. 

The new ocular endotamponades extend the portfolio of available intraoperative tools, but they do not overcome the side effects already described for the established products. 

For FCLs as a short-term ocular endotamponade, the following tests must be performed ... 

The following test procedures reflect the experiences with the characterisation of perfluorinated and partially fluorinated compounds used as ocular endotamponades but should also be used for other, similar applications. A risk assessment shows that toxic effects from a completely water-insoluble substance can be caused by... 

Evaluation of undesirable local effects of ocular endotamponades... 

These findings should have two consequences. First, the development of potential long-term ocular endotamponades should consider harmonising viscosity and density to avoid mechanically induced side effects. And secondly, the evaluation of the biocompatibility should include effects not directly related to classic toxic phenomena. 

The introduction of the heavier than water tamponades into the market was a milestone in the development of long-term ocular endotamponades (vitreous substitute). 

All these parameters are very close to the requirements which a long-term ocular endotamponade has to fulfil. Also the in vivo tests in a rabbit eye model were extremely promising no emulsification, no changes in the vascular structure of the retina and no increase of the intra-ocular pressures. All negative side effects, seen with the monomeric FCLs, seemed to be eliminated. In addition, some additional advantages could be claimed reduced tissue penetration and the potential to dissolve drugs [44,45]. 

Ocular endotamponades based on FCL are and will be interoperative tools. They have to be removed after use. The risk-benefit analysis must be the base for defining the maximum treatment period. The mean task of these devices is space filling/maintaince. 

The ocular endotamponades of the future could be a combination of tampo-nading and drug delivery device. Vitrectomy removes the natural vitreous after it has become opaque, inflamed, or unable to keep the retina in place. In many cases, the necessity to remove it is the result of retinal disorders, which are still existent after vitrectomy [50]. In equivalence to the blood-brain barrier, there is also a blood-retina barrier, with the effect that it is difficult to treat retinal disorders systemically. Therefore, the delivery of appropriate drugs via the vitreous cavity would open new treatment options. 

All existing ocular endotamponades have a neglectable dissolution potential for approved drug substances. This situation could be significantly improved by... 

D.H. Menz, Side effects of ocular endotamponades caused by surface behaviors of fluorocarbons. Poster presentation 14th European Symposium on Fluorine Chemistry, Poznan, Pologne, 11-16 juillet, (2004). 

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