A randomised clinical study comparing the effect of Steareth 30 and SLS containing toothpastes on oral epithelial integrity (desquamation).

OBJECTIVE: To compare the clinical effect of toothpastes containing Steareth 30 and SLS (sodium lauryl sulphate) surfactants on oral epithelial integrity (desquamation) using a new Oral Mucosal Sloughing Index (OMSI). METHODS: 30 volunteers participated in a single centre, double-blind, randomised, crossover clinical study. After a lead-in, subjects were allocated to the first test toothpaste, which was applied to the maxilla via a cap splint, followed by whole mouth brushing with the respective toothpaste and rinsing with the toothpaste slurry. Soft desquamation (lesion status) was assessed using a novel Oral Mucosal Sloughing Index (OMSI). Soft tissue status was measured at baseline (prior to test product use), 30 min following test product application and 4 days later following "at home" use of test toothpaste. After a wash out period, soft tissue assessment and product use were repeated for the remaining toothpaste. RESULTS: Using the OMSI, 30 min post-application, significantly fewer lesion counts (all sites) were observed for the Steareth 30 toothpaste compared to SLS toothpaste (p < 0.0001). Additionally, 30 min after toothpaste use, the average lesion severity score was significantly lower for the Steareth 30 toothpaste compared to SLS toothpaste (p < 0.0001). There were no significant differences in lesion status at baseline or following 4 days of "at home" use of the toothpastes. No product related adverse events were reported. CONCLUSION: Using an Oral Mucosal Sloughing Index for assessment, application of a toothpaste containing Steareth 30 generated significantly less transient soft tissue desquamation (fewer lesion counts and lower severity) than a toothpaste containing SLS. CLINICAL SIGNIFICANCE: Treatment with a toothpaste containing Steareth 30 surfactant generated fewer transient soft tissue lesions (lower desquamation) compared to a toothpaste containing SLS surfactant.

Development and clinical assessment of an artificial cornea.

Keratoprosthesis research has been a gradual, rather fragmentary process with advances being made by isolated groups of researchers. This has arisen partly because of poor funding in the area; research groups which have achieved commercial support have often had constraints upon the full disclosure of their findings. Despite these difficulties there has been real progress over the last decade by several independent groups. This article concentrates upon our own development of a hydrogel core-and-skirt keratoprosthesis, the Chirila KPro, in order to illustrate the scientific and clinical problems common to keratoprosthesis research. Pilot data from a clinical trial is presented and the priorities for future research are discussed.

The modulation of corneal keratocyte and epithelial cell responses to poly(2-hydroxyethyl methacrylate) hydrogel surfaces: phosphorylation decreases collagenase production in vitro.

We examined the regulation of collagenase production by rabbit keratocyte, epithelial and mixed keratocyte/epithelial cell cultures which were exposed to poly(2-hydroxyethyl methacrylate) (PHEMA) hydrogel surfaces with different chemistries and morphologies (sponge and homogeneous gels). Tissue culture modified polystyrene (TCP), used as a control surface, induced the maximum collagenase response with all cell culture types. Copolymer homogeneous gels containing 2-ethoxyethyl methacrylate (EEMA) or methyl methacrylate (MMA) induced a high response in keratocyte cultures, whilst PHEMA hydrogels induced a moderate response and the phosphorylated PHEMA (phos-PHEMA) hydrogel induced no response. Epithelial cells cultured on PHEMA, copolymer and phos-PHEMA hydrogels produced less collagenase activity than the keratocyte cells. The profile of collagenases produced by epithelial cells in response to phos-PHEMA was different to that for the other hydrogels. Co-cultured cells produced higher levels of collagenase (relative to the TCP) in response to hydrogels than did either the keratocytes or epithelial cells alone, but the response of phos-PHEMA was still the lowest. The overall enzyme response to the sponge hydrogels was lower than that to the homogeneous hydrogels, although this effect was less prominent in the keratocyte cultures. The markedly reduced and alternative collagenase responses to phosphorylated surfaces was not a consequence of cell death, and may be a phenomenon related to changes in cell surface charge and morphology.

The modulation of cellular responses to poly(2-hydroxyethyl methacrylate) hydrogel surfaces: phosphorylation decreases macrophage collagenase production in vitro.

We examined the regulation of collagenase production by the monocyte/macrophage THP-1 cell line when these cells were exposed to poly(2-hydroxyethyl methacrylate) (PHEMA) hydrogel surfaces with different chemistries and morphologies. Tissue culture modified polystyrene (TCP), used as a control surface, induced the maximum collagenase response. Copolymer hydrogels containing 2-ethoxyethyl methacrylate (EMA) or methyl methacrylate (MMA) also induced a high response, while PHEMA hydrogels induced a low level response and the phosphorylated hydrogel induced no response. This pattern was altered when the morphology of the hydrogels was changed to that of a sponge. The overall enzyme response to the sponge hydrogels was lower than that to the homogeneous hydrogels. Sponges containing EMA and MMA produced low level response relative to the TCP control. PHEMA and phosphorylated sponges produced little and no response respectively. The dramatically reduced enzyme response to phosphorylated surfaces was not a consequence of cell death, and may be a phenomenon related to changes in cell surface charge.

Implantation of PHEMA keratoprostheses after alkali burns in rabbit eyes.

PURPOSE: We have previously examined histologically the healing of a PHEMA core-and-skirt keratoprosthesis (the Chirila KPro) as a full-thickness implant in healthy animal corneas. The present study was carried out to determine whether a diseased cornea could also generate biocolonization of the skirt region of a KPro. METHODS: Ten KPros were placed as full-thickness corneal implants under conjunctival flaps in 10 alkali-burned rabbit corneas. Histological findings at intervals from 2 weeks to 6 months postoperatively were compared with earlier findings in 10 rabbits that had received identical KPros without prior alkali injury. RESULTS: Despite severe corneal injury and the reduced keratocyte population present, there were no clinically detected complications in 60%. Histological findings established that, compared with healthy host tissue, skirt biocolonization and KPro-cornea healing after an alkali burn were impaired, with evidence of epithelial downgrowth in 40%. One animal required euthanasia earlier than the planned end point, but no KPro extrusions occurred. CONCLUSION: Biocolonization of a KPro skirt is reduced but not prevented in an alkali-induced corneal inflammation model. Although no extrusions occurred, close follow-up and anticollagenolytic medication would be required to minimize the complication rate.

Clinical results of implantation of the Chirila keratoprosthesis in rabbits.

AIMS/BACKGROUND: An ideal keratoprosthesis (KPro) would closely resemble a donor corneal button in terms of its surgical handling, optics, and capacity to heal with host tissue in order to avoid many of the complications associated with the KPros which are currently in clinical use. This study was carried out to assess the long term clinical outcomes on implantation of the core and skirt poly(2-hydroxyethyl methacrylate) KPro in animals. METHODS: 20 KPros were made and implanted as full thickness corneal replacements into rabbits and followed for up to 21 months to date. RESULTS: 80% of the prostheses have been retained, with a low incidence of complications such as cataract, glaucoma, and retroprosthetic membrane formation which are frequently associated with KPro surgery. CONCLUSIONS: KPros of this type may offer promise in the treatment of patients for whom penetrating keratoplasty with donor material carries a poor prognosis. Refinement of the KPro and further animal trials, including implantation into abnormal corneas, are however mandatory before human implantation could be planned.

Keratoprosthesis results in animals: an update.

BACKGROUND: The report presented is an update on continuing development work on modified PHEMA core-and-shirt KPros in animals. METHODS: Two variations (improved wet-eye, and dry-eye) of a prototype core-and-skirt Chirila KPro are described. The clinical success rate on implantation of these versions of the Chirila KPro was assessed. RESULTS: It was found that a significant improvement in retention rate was shown in the improved model but that the dry-eye model failed early in two of the three implanted. CONCLUSIONS: The significance of the improved strength and the reasons for disappointing results with the early dry-eye KPros are discussed. Ongoing work is briefly outlined.

Histologic evaluation during healing of hydrogel core-and-skirt keratoprostheses in the rabbit eye.

PURPOSE: We developed two models that are modifications of our original poly(2-hydroxyethyl methacrylate) (PHEMA) core-and-skirt keratoprosthesis. In these keratoprostheses, the mechanical strength of the skirt has been considerably increased with divinyl glycol (DVG) as a cross-linking agent during polymerization. In one (KPro I), methyl methacrylate (MMA) was added as comonomer to increase cell adhesion, and in the other (KPro II), HEMA was polymerized with DVG without comonomer. The aim of this study was to evaluate the process of healing and biocolonization and to ascertain whether KPro I demonstrates better ingrowth than the mechanically stronger KPro II, after implantation in rabbit eyes. METHODS: Ten rabbits were used for each model and studied at five predetermined end points up to 26 weeks. The device was implanted as a full-thickness keratoprosthesis covered with a conjunctival flap. RESULTS: Neither prosthesis demonstrated extrusion or retroprosthetic membrane formation. There was no significant difference between the two types of prosthesis with respect to tissue ingrowth and surrounding tissue melting. Histologically, inflammation was not severe, but calcification was seen in most specimens. Evidence of biodegradation of the prosthesis also was seen. CONCLUSION: In our original keratoprosthesis, fibrovascular invasion had occurred into the prosthetic skirt, but wound dehiscence and low mechanical strength resulted in an unfavorable outcome. In this series, the mechanical properties were improved, and KPro II was stronger than KPro I. Therefore KPro II would be the preferred polymer combination for surgical manipulation. However, biodegradation and calcification require further investigation into the degree and significance of these adverse reactions.