On the 21st of November, the 3rd Heavy Tamponade (HEATAM-3) meeting was held in Amsterdam attended by 80 international delegates. The first meeting was held because the semi-fluorinated alkenes and alkanes were introduced; there was genuine excitement that these new substances might serve as heavy tamponades. Proliferative vitreoretinopathy (PVR) is one the main causes of surgical failure for the repair of retinal detachment and PVR has a propensity for the inferior fundus. Therefore, a heavier-than-water long-term tamponade has long been sought, especially after the disappointment of several previous false dawns. Substances like fluorosilicone oils and the perfluorocarbon liquids (PFCL) proved toxic when left in the eye for extended periods.

Is it toxic?

Figure 1

The first meeting was held in Telf, Austria back in 2003. The big issue at the time was whether any of the fluorinated alkanes / alkenes could be used; the main concern was that the substances could be toxic (like previous heavier-than-water tamponade agents). There were several groups working separately on different compounds. The first group, led by Professors Kirchhof, Wong and van Meurs (of Germany, UK and Holland respectively), conducted a multicentre clinical trial of perfluorohexyloctane or F6H8. A second group included Professors Hoerauf, Roider and Gabel investigated the semifluorinated alkanes perfluorobutylbutane (O(44)), perfluorohexylethan (O(62)) and the oligomer OL(62HV). Sebastian Wolf already had the clinical experience of the first available mixture of silicone and semifluorinated alkene, namely Oxane HD, which was marketed by Bausch and Lomb. It was clear from the cumulated experience of several groups that the partially fluorinated alkanes and alkenes can be toxic and induced inflammation in the eye. Several new observations were made including proteinaceous deposits on the retina and the retrolental space; additionally the low viscosity tamponades emulsified quickly into droplets. Even back in 2003, it was speculated that the adverse effect may either be directly toxic (as in the case of O62 or the oligomer) or indirectly, simply as a result of emulsification into small droplets that set up macrophage / foreign body giant cell reaction. Of the several substances, probably the least toxic was F6H8. A strategy was agreed upon to take heavy tamponade forward. This involved introducing a solution of F6H8 and silicone oil. As a solution, the viscosity can be increased and thus the propensity for emulsification be decreased (hopefully, the tendency to induce inflammation be diminished).

Which heavy oil?

The second meeting was held in Viareggio, Italy 2006. Several new concepts were introduced. The Italians have been using "double tamponade", mixing F6H8 and silicone oil hoping to provide support for the superior and inferior fundus. This was highly controversial as the physicists and the model eye chamber studies indicated that double tamponade might not be possible; the resultant mixture acted as a single bubble. Another controversial aspect concerned Oxane HD. Nuclear magnetic resonance studies indicated that the agent may in fact not be a solution, in the sense that the mixture is not homogenous. The low solubility of alkene, RMN3 is such that the heavy oil solution probably readily separates into its constituent components. More worryingly, a new phenomenon that was not observed previously became apparent. Heavy oil can be sticky! This was very much the case with Oxane HD. Dr Dresp speculated that it might be due to the interaction of PFCL with the Oxane HD that led to the oil sticking. A straw poll was taken at this meeting asking who would use heavy oil? Having heard all of the presentation, half of the delegates indicated they would use Densiron and none of the delegates would choose Oxane HD. Both double tamponade and Oxane HD focused our minds as to how tamponade work. Previously, it has always been assumed for a tamponade agent to be effective, it needs to be lighter (or heavier) than aqueous. The fact that double tamponade and Oxane HD with its uncertain specific gravity both seemed to effective and acceptable, called into question our whole understanding of the tamponade effect. It is clear in some circumstances, a near total fill with oil was sufficient and compatible with anatomical success.

Two additional concepts dominated the meeting. Firstly, Prof Joussen's group did further work on other alkanes including F4H5, F4H6 and F4H8. To everyone's surprise, although the chemical structure of the substances were similar, the biocompatibility varied tremendously. It was concluded that the ratio between the number of carbon atoms with attached fluorine atoms to the number of carbon atoms with attached hydrogen atoms probably mattered. Equally, the size of the molecule might also be important. F4H5 is much better tolerated that F6H8. Secondly, Prof Kirchhof explained his concept of treating PVR with heavy tamponade. The intention is not so much to provide support for the inferior retina and close breaks located in the lower half of the fundus, but primarily to displace the proliferative milieu or the aqueous with its contained cytokines and growth factors to the superior retina where the retina is less affected by epiretinal membranes and where there may not be any retinal breaks present. This is very much the hypothesis and the basis for the multi-centre randomized trial of heavy silicone oil (Densiron-68) versus conventional silicone oil. The assumption is that Densiron would be more effective than conventional silicone oil for treating such cases of PVR with no retinal breaks within the top 4 clock hours of the fundus. Cologne was the initiating centre and Prof Joussen was the lead in this clinical trial.