Evaluation of an opthalmic viscosurgical device utilizing a glycosaminoglycan

Abstract

Background An ophthalmic viscosurgical device (OVD) is a clear gel like chemical substance that has viscous and elastic properties and is biocompatible. It is used in ophthalmic surgery to create and maintain space, to protect the delicate corneal endothelial cells as well as to assist the surgeon in manipulating the ocular tissues during the course of the surgery. OVD's are made from various sources which include hyaluronic acid, chondroitin sulphate and hydroxypropylmethylcellulose. Hyaluronic acid OVD's are the most popular and its chemical composition lends it to have several favorable characteristics making it very successful as an OVD. These include being a non-Newtonian fluid enabling the change of its viscosity with various pressures as required while being injected through a thin cannula in the eye as well as being stationary in the anterior chamber of the eye. Its elastic properties ensure the protection of the corneal endothelial cells by absorbing the mechanical trauma created by the surgical instruments during the operation. It can either be a cohesive device, used for space creation and maintenance, or a dispersive device, used to protect the corneal endothelial cells, depending on the molecular weight of the OVD. A transient rise in the intraocular pressure (IOP) is expected with the use of an OVD but should return to normal within 24 hours after surgery. A cohesive OVD was developed and the scope of this thesis included the various preclinical tests in order to ensure its safety for human use. Aims The aim of this study was to test and evaluate a buffered hyaluronic acid (BHA) in order to determine its effect on in vivo and in vitro systems as part of preclinical testing as required by ISO 15798 for OVD's. Firstly the cytotoxic potential of the BHA was determined by exposing human dermal fibroblasts to different concentrations of the test substance. Next, the sensitization potential was determined by the Guinea pig Maximization test followed by the determination of the IOP pattern that can be expected postoperatively in comparison to a currently existing OVD on the market. Lastly, an eye irritation test was conducted on New Zealand white rabbits in order to determine the eye irritation potential of the OVD. Materials and Methods Human dermal fibroblasts were used in order to determine the cytotoxic potential of the BHA at various concentrations and cells were subjected to the test substance for 1 and 24 hours. The colorimetric MTT and Neutral red assays were performed as well as the qualitative Crystal violet assay. For the skin sensitization test intradermal injections of the test substance were made into the dorsal skin region of thirty Hartley Guinea pigs. The animals were left for 14 days after which the skin was challenged with the test substance again. The IOP pattern was determined by the injection of the test and control substance into the right and left eyes of six New Zealand white rabbits, and the IOP was then evaluated at different time intervals. For the eye irritation test, 0.1ml of the test substance was instilled into the lower conjunctival sac of six New Zealand white rabbits and was allowed to spread over the surface of the eye. The eyes were then evaluated with a slit lamp and a handheld ophthalmoscope. Results and Conclusion The test substance was seen to promote cell proliferation rather than cell damage. The overall test results indicated that the test substance was not cytotoxic. The test substance produced a 5.3% incidence in the skin sensitization test and is therefore not regarded as a skin sensitizer. A similar intraocular pressure pattern was seen in both the test and control OVD when injected into the eyes of white New Zealand rabbits and the peak IOP rise was found to be at 4 hours ± 1 hour for both substances. No positive scores were seen in the eye irritation test and it was concluded that the test substance is not an eye irritant. Copyright