Evidence of toxic side effects of perfluorohexyloctane after vitreoretinal surgery as well as in previously established in vitro models with ocular cell types.
BACKGROUND
Cases of ocular irritation have been observed after early clinical trials using perfluorohexyloctane (F6H8) as endotamponade. In our clinic two of three eyes developed severe inflammatory-like reactions after intermediate-term tamponade. These cases will be depicted, serving as background for the experimental study. To elucidate possible toxic effects of F6H8 on different ocular cell types and corneal tissue we applied our previously established in vitro models to investigate effects of F6H8 on cultured ocular cells in comparison with perfluorodecaline.


METHODS
Vitality and proliferation of cultured human corneal endothelial cells (HCEC) and human retinal pigment epithelial cells (RPE) were measured after incubation with F6H8 or perfluorodecaline for up to 5 days. Vitality was evaluated using the Live/Dead assay, and proliferation was determined according to BrdU incorporation. Additionally the endothelium of donor corneas was incubated with F6H8 for 5 days and endothelial cell morphology was documented.


RESULTS
After 5 days incubation with F6H8, cultures of RPE and HCEC showed significantly lower extinctions for vital cells as well as a non-significant decrease in proliferation compared with controls. Analysis by means of fluorescence microscopy after treatment with F6H8 or perfluorodecaline revealed decreased cell densities (F6H8 > perfluorodecaline) within contact areas. The endothelium of donor corneas incubated in presence of F6H8 developed circumscribed necrotic areas.


CONCLUSIONS
Decreased amounts of vital cells cannot be explained solely by mechanical effects or nutritional deficit due to direct contact, since F6H8 has a lower specific weight than perfluorodecaline. The ability of the remaining cells to proliferate revealed that they were not irreversibly damaged. Due to the high lipophilicity of F6H8 interactions with cellular lipoprotein membranes as well as other toxic effects have to be considered and should further be investigated prior to clinical use.
Mertens
Sylvia
S
Klinik und Poliklinik für Augenheilkunde des Universitätsklinikums Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany. smertens@uke.uni-hamburg.de
Bednarz
Jürgen
J
Engelmann
Katrin
K
D000368:Aged; D000369:Aged, 80 and over; D002452:Cell Count; D018929:Cell Culture Techniques; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003131:Combined Modality Therapy; D004728:Endothelium, Corneal / Q000187:drug effects* / Q000473:pathology; D005260:Female; D005466:Fluorocarbons / Q000009:adverse effects* / Q000494:pharmacology; D006801:Humans; D017075:Laser Coagulation / Q000379:methods; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009924:Organ Culture Techniques; D010857:Pigment Epithelium of Eye / Q000187:drug effects* / Q000473:pathology; D011183:Postoperative Complications / Q000139:chemically induced* / Q000473:pathology; D012163:Retinal Detachment / Q000473:pathology / Q000628:therapy*; D014821:Vitrectomy / Q000379:methods
D005466:Fluorocarbons; C008805:perfluorodecalin; C118616:perfluorohexyl-octan