Pax7 expressing cells contribute to dermal wound repair, regulating scar size through a ß-catenin mediated process.

During skin wound healing, fibroblast-like cells reconstitute the dermal compartment of the repaired skin filling the wound gap. A subset of these cells are transcriptionally active for ß-catenin/T-cell factor (TCF) signaling during the proliferative phase of the repair process, and ß-catenin levels control the size of the scar that ultimately forms by regulating the number of dermal fibroblasts. Here, we performed cell lineage studies to reveal a source of the dermal cells in which ß-catenin signaling is activated during wound repair. Using a reporter mouse, we found that cells in the early wound in which TCF-dependent transcription is activated express genes involved in muscle development. Using mice in which cells express Pax7 (muscle progenitors) or Mck (differentiated myocytes) are permanently labeled, we showed that one quarter of dermal cells in the healing wound are Pax7 expressing progeny, but none are Mck progeny. Removing one allele of ß-catenin in Pax7 expressing progeny resulted in a significantly smaller scar size with fewer Pax7 expressing progeny cell contributing to wound repair. During wound healing, ß-catenin activation causes muscle satellite cells to adopt a fibrotic phenotype and this is a source of dermal cells in the repair process.

Preservative exposure and surgical outcomes in glaucoma patients: The PESO study.

PURPOSE: To study the impact of benzalkonium chloride (BAK) exposure from eye drops on subsequent time to trabeculectomy failure. PATIENTS AND METHODS: Retrospective chart review of 128 glaucoma patients who had undergone a trabeculectomy between 2004 and 2006. The number and type of ophthalmic drops used preoperatively and relevant demographics were recorded. Surgical failure criteria included inadequate pressure lowering or need for postoperative ocular antihypertensives, laser trabeculoplasty, 5-fluorouracil needling, or repeated surgery. Patients were examined for these criteria over a minimum postoperative period of 2 years. Data were assessed using Kaplan-Meier and Cox regression models. RESULTS: Complete surgical success was achieved in 47.7% of patients. Patients received between 1 and 8 BAK-containing drops daily, with a median of 3. Time to surgical failure in patients receiving higher preoperative daily doses of BAK was shorter than in patients who had less BAK exposure (P=0.008). Proportional hazard modeling identified uveitic and neovascular glaucoma as significant confounders of the univariate model (P=0.024), although the main effect of BAK exposure was maintained with a hazard ratio of 1.21 (P=0.032). The number of different medications used to control intraocular pressure did not significantly affect survival time in a secondary Cox model (P=0.948). CONCLUSIONS: Increased preoperative exposure to ophthalmic solutions preserved with BAK is a risk factor for earlier surgical failure, independent of the number of medications used. This study extends earlier findings of potential adverse effects of ophthalmic preservatives on surgical outcomes to the modern pharmacopeia used in the medical management of glaucoma.

Evolving surgical techniques of and indications for corneal transplantation in Ontario from 2000 to 2009.

OBJECTIVE: To determine the changes in the leading indications for and the preferred surgical techniques of corneal transplantation in Ontario over a 9-year period. DESIGN: Retrospective review of Eye Bank of Canada (Ontario Division) records. PARTICIPANTS: Recipients of corneal transplants performed in Ontario between 2000 and 2009, totaling 6240 patients. METHODS: Records of all corneal tissues sent for transplantation in Ontario by the Eye Bank of Canada (Ontario Division) from July 1 2000 to June 30 2009 were reviewed. The records consist of recipient information forms completed by surgeons at the time of corneal transplant surgery. Of the 8186 available recipient information forms, 7755 (94.7%) were sufficiently complete to meet the inclusion criteria. RESULTS: The leading indications for corneal transplantation were pseudophakic corneal edema (28.3%), regraft (21.5%), Fuchs dystrophy (16.6%), and anterior keratoconus (13.8%). Beginning in 2006, there has been a shift in the proportion of corneal transplants performed using Descemet's stripping automated endothelial keratoplasty (DSAEK) and deep anterior lamellar keratoplasty, from 2.4% to 36.1% of all corneal transplants. Concomitantly, DSAEK has replaced penetrating keratoplasty (PKP) as the technique of choice when corneal transplantation is indicated for Fuchs' dystrophy (139 DSAEKs vs. 68 PKPs in 2009) and for pseudophakic corneal edema (118 DSAEKs vs. 115 PKPs in 2009). CONCLUSION: The indications for PKP in this study agree with the North American literature. In recent years, partial-thickness transplants have gained favor over PKP for select indications in Ontario. These changes reflect the future direction of corneal transplantation and will have implications on the supply of and demand for tissues.

Sustainability of Routine Notification and Request legislation on eye bank tissue supply and corneal transplantation wait times in Canada.

OBJECTIVE: To assess whether provinces with Routine Notification and Request (RNR) legislation have sustained increases in corneal tissue supply and decreases in wait times for corneal transplantation surgery. DESIGN: Cross-sectional survey of Canadian corneal transplant (CT) surgeons and eye banks. PARTICIPANTS: Canadian CT surgeons and representatives from the 10 Canadian eye banks. METHODS: Voluntary and anonymous surveys were distributed between July and October 2009. Eligible CT surgeons were defined as ophthalmologists who practice in Canada; currently perform Penetrating keratoplasty (PKP), Deep anterior lamellar keratoplasty (DALK), Deep lamellar endothelial keratoplasty (DLEK), Descemet stripping endothelial keratoplasty (DSEK), or Descemet membrane endothelial keratoplasty (DMEK); and have obtained tissues from a Canadian eye bank. RESULTS: From 2006 to 2009, for provinces with RNR legislation and where data are available, mean wait times from date of diagnosis to date of CT surgery have increased: in Ontario, from 31 ± 34 weeks to 36 ± 27 weeks; in British Columbia, from 39 ± 20 weeks to 42 ± 35 weeks; in Manitoba, from 32 ± 23 weeks to 49 ± 36 weeks. In addition, the amount of corneal tissue in RNR provinces suitable for transplant, with the exception of British Columbia, has declined between 2006 and 2008: in Ontario, 1186 tissues to 999 tissues (16% decline); in Manitoba, 92 tissues to 83 tissues (10% decline); in New Brunswick, 129 tissues to 98 tissues (24% decline). CONCLUSION: Although initially effective, RNR legislation has not sustained an increase in corneal tissue availability nor has it shortened wait times in most provinces. Incorporation of community hospitals into the RNR catchment, improved enforcement, and continued education of hospital staff regarding the RNR process may be effective in making this legislation more sustainable in the long term.

Management of recurrent pterygium with intraoperative mitomycin C and conjunctival autograft with fibrin glue.

PURPOSE: To evaluate the safety and efficacy of using fibrin glue in cases of recurrent pterygium treated with pterygium excision and conjunctival autograft combined with mitomycin C. DESIGN: Retrospective, interventional case series. METHODS: The charts of 28 patients with recurrent pterygium who had undergone pterygium excision and conjunctival autograft using fibrin glue to secure the graft combined with intraoperative mitomycin C at a corneal service in a university teaching hospital were reviewed. Inclusion criteria were recurrent pterygium that had undergone at least 1 previous surgical excision and patients who had completed a regular postoperative follow-up of at least 12 months. Outcome measures included mean best-corrected visual acuity (BCVA) and intraoperative and postoperative complications. RESULTS: The mean age of the cohort was 49.7 years. There were no intraoperative complications. Early postoperative total graft dehiscence developed in 1 eye that underwent repositioning with glue and sutures. One eye had mild graft dehiscence and required no surgical intervention. One eye had a conjunctival cyst on the graft that did not require intervention. No significant change was observed in BCVA. At a mean follow-up of 26.5 months, there was 1 case of recurrence. CONCLUSIONS: Pterygium excision and conjunctival autograft using fibrin glue to secure the graft combined with intraoperative mitomycin C seems to be a safe and effective surgical option for treating recurrent pterygium. However, a larger cohort with longer follow-up may be required to assess the recurrence rate of this method.