Paul Dubord

Mutations in the UBIAD1 Gene, Encoding a Potential Prenyltransferase, Are Causal for Schnyder Crystalline Corneal Dystrophy

Schnyder crystalline corneal dystrophy (SCCD, MIM 121800) is a rare autosomal dominant disease characterized by progressive opacification of the cornea resulting from the local accumulation of lipids, and associated in some cases with systemic dyslipidemia. Although previous studies of the genetics of SCCD have localized the defective gene to a 1.58 Mbp interval on chromosome 1p, exhaustive sequencing of positional candidate genes has thus far failed to reveal causal mutations. We have ascertained a large multigenerational family in Nova Scotia affected with SCCD in which we have confirmed linkage to the same general area of chromosome 1. Intensive fine mapping in our family revealed a 1.3 Mbp candidate interval overlapping that previously reported. Sequencing of genes in our interval led to the identification of five putative causal mutations in gene UBIAD1, in our family as well as in four other small families of various geographic origins. UBIAD1 encodes a potential prenyltransferase, and is reported to interact physically with apolipoprotein E. UBIAD1 may play a direct role in intracellular cholesterol biochemistry, or may prenylate other proteins regulating cholesterol transport and storage.

Evolving indications for and trends in keratoplasty in British Columbia, Canada, from 2002 to 2011: a 10-year review.

Purpose: The aim of this study was to report the evolving indications for keratoplasty and the shift in the type of keratoplasty performed in British Columbia, Canada, over a 10-year period from 2002 to 2011. Methods: This was a retrospective database review of all the records of corneal transplant tissues at the Eye Bank of British Columbia, Canada, from January 2002 to December 2011. The patient demographics, indications, and types of transplant performed were analyzed. Results: A total of 4843 corneal transplants were performed in 3742 patients (1968 male and 1774 female) from January 2002 to December 2011. The number of keratoplasties performed ranged from 420 in 2008 to 578 in 2011. The top 4 indications over the 10-year period were Fuchs endothelial dystrophy (FED; 18.9%), aphakic/pseudophakic bullous keratopathy (17.4%), regraft (17.1%), and keratoconus (15.5%). Penetrating keratoplasty (PKP) accounted for 86.5% (4191 transplants) of all keratoplasties performed. Since the introduction of Descemet stripping automated endothelial keratoplasty (DSAEK) in 2007, there was a significant increase in the number of DSAEKs (P < 0.0001) performed and a statistical decline in the number of PKPs (P < 0.0001) performed. Despite only 30 deep anterior lamellar keratoplasties being performed, an increasing trend was observed after 2008 (P = 0.0087). A decreasing trend in PKPs and an increasing trend in DSAEKs were observed for surgeries performed for FED, aphakic/pseudophakic bullous keratopathy, and regraft. Conclusions: FED has become the top indication for performing a keratoplasty over the 10-year period. There was a shift from PKP to DSAEK performed for endothelial failure. Although the number of deep anterior lamellar keratoplasty surgeries was small, there was a significant increasing trend.

Panstromal Schnyder corneal dystrophy. A clinical pathologic report with quantitative analysis of corneal lipid composition.

BACKGROUND The pathogenesis of Schnyder dystrophy is thought to be a primary abnormality of corneal lipid metabolism resulting in opacification secondary to lipid accumulation. Histochemical investigations have suggested the accumulated lipid includes unesterified cholesterol; however, quantitative analysis has not been done. METHODS Quantitative biochemical analysis was performed on a corneal button obtained from a patient with clinically and pathologically proven Schnyder dystrophy. Results were compared with four age-, sex-, and size-matched corneal buttons obtained from cadaveric eyes. RESULTS Corneal lipid accumulated in Schnyder dystrophy predominantly is composed of phospholipid, free cholesterol, and cholesterol ester. These constituents were markedly elevated in the Schnyder cornea when compared with cadaveric control corneas as follows: (1) phospholipid, 23.6 versus 4.05 mg/g; (2) unesterified cholesterol, 6.99 versus 0.52 mg/g; and (3) cholesterol ester, 3.16 versus 0.26 mg/g. CONCLUSION Phospholipid, unesterified cholesterol and cholesterol ester are the predominant lipids in Schnyder dystrophy. The pathogenesis may be a primary disorder of corneal lipid metabolism.

Eye banking and corneal transplantation communicable adverse incidents: current status and project NOTIFY.

Purpose: Evidence of the transmission of disease via donor ocular tissue has been demonstrated for adenocarcincoma, rabies, hepatitis B virus, cytomegalovirus, herpes simplex virus, Creutzfeldt-Jakob disease, and a variety of bacterial and fungal infections. Methods: Although there is no evidence to date of disease transmission for HIV infection, syphilis, hepatitis C, hepatitis A, tuberculosis, HTLV-1 and -2 infection, active leprosy, active typhoid, smallpox, and active malaria, these entities remain contraindications for transplantation for all eye banks nationally and internationally. The potential sources of contamination include infected donors, during the process of removing tissue from cadaveric donors, the processing environment, and contaminated supplies and reagents used during processing. The transmissions of Herpes simplex virus and HSV via corneal graft have been shown to be responsible for primary graft failure. HSV-1 may also be an important cause of PFG. Results: The long latency period of some diseases, the emergence of new infectious disease, and the reemergence of others emphasize the need for long-term record maintenance and effective tracing capabilities. Conclusions: The standardization of definitions for adverse events and reactions will be necessary to support the prevention and transmission of disease. International classification of a unique identification system for donors will be increasingly important for vigilance and traceability in cross-national exportation of human cells, tissues, and cellular- and tissue-based products. Opportunities for continuous improvement exist as does the need for constant vigilance and surveillance.

Corneal Cross-Linking in Pediatric Patients With Progressive Keratoconus.

Purpose: To evaluate corneal cross-linking (CXL) in the treatment of keratoconus in pediatric patients. Specifically, this study investigates the impact of CXL on uncorrected distance visual acuity (UDVA), best-corrected distance visual acuity (BDVA), manifest refraction, keratometry (K) measurements, and higher order aberrations. Methods: This is a retrospective, observational case series of patients 18 years old or younger with progressive keratoconus who underwent CXL from January 2009 to August 2013. Preoperative and 1-year postoperative data including BDVA, manifest refraction, mean K readings, and corneal aberration measurements were extracted from clinical charts and topographical imaging. Visual acuity was converted to logarithm of the minimum angle of resolution (logMAR) scale, and mean refractive spherical equivalent (MRSE) was calculated from manifest refraction. Results: The group consisted of 39 eyes from 28 patients, including 21 males and 7 females (mean age = 16.3 years, range: 11–18, standard deviation [SD] = 1.81). UDVA did not change significantly (preoperative UDVA = 1.20 logMAR, SD = 0.57, and postoperative UDVA = 0.90 logMAR, SD = 0.67, P = 0.19). BDVA did not change significantly (preoperative BDVA = 0.34 logMAR, SD = 0.27, and postoperative BDVA = 0.34 logMAR, SD = 0.23, P = 0.50). There was no significant change in mean K (preoperative K = 48.49, SD = 5.44, and postoperative K = 48.25, SD = 4.74, P = 0.34). Mean MRSE did not change significantly (preoperative MRSE = −3.29 D, SD = 4.04, and postoperative MRSE = −3.53 D, SD = 4.07, P = 0.31). Corneal aberration measurements were available for 10 eyes, and stability of measurements was demonstrated. There were no complications noted. Conclusions: This study suggests that CXL is a safe and effective procedure that halts the progression of keratoconus in pediatric patients at 1-year follow-up. To validate these findings, longer follow-up is required.

Double bubble with the big-bubble technique during deep anterior lamellar keratoplasty

PurposeTo report a case of intraoperative double bubble that formed during big-bubble DALK surgery in a patient with corneal scarring secondary to herpetic stromal keratitis.MethodsCase report.ResultsA 22 year old woman presented with a large corneal scar, likely secondary to previous herpetic stromal keratitis. She underwent big-bubble DALK surgery for visual rehabilitation. Intraoperatively, a mixed bubble with persistent type 2 bubble postoperatively was noted. The second bubble resorbed with clearance of the graft and good visual outcome after 6 weeks.ConclusionsThis case report describes the unusual development of a mixed bubble during big-bubble DALK surgery. This graft cleared with resolution of the second bubble postoperatively without further surgical intervention.