The PPCD1 Mouse: Characterization of a Mouse Model for Posterior Polymorphous Corneal Dystrophy and Identification of a Candidate Gene

The PPCD1 mouse, a spontaneous mutant that arose in our mouse colony, is characterized by an enlarged anterior chamber resulting from metaplasia of the corneal endothelium and blockage of the iridocorneal angle by epithelialized corneal endothelial cells. The presence of stratified multilayered corneal endothelial cells with abnormal patterns of cytokeratin expression are remarkably similar to those observed in human posterior polymorphous corneal dystrophy (PPCD) and the sporadic condition, iridocorneal endothelial syndrome. Affected eyes exhibit epithelialized corneal endothelial cells, with inappropriate cytokeratin expression and proliferation over the iridocorneal angle and posterior cornea. We have termed this the “mouse PPCD1” phenotype and mapped the mouse locus for this phenotype, designated “Ppcd1”, to a 6.1 Mbp interval on Chromosome 2, which is syntenic to the human Chromosome 20 PPCD1 interval. Inheritance of the mouse PPCD1 phenotype is autosomal dominant, with complete penetrance on the sensitive DBA/2J background and decreased penetrance on the C57BL/6J background. Comparative genome hybridization has identified a hemizygous 78 Kbp duplication in the mapped interval. The endpoints of the duplication are located in positions that disrupt the genes Csrp2bp and 6330439K17Rik and lead to duplication of the pseudogene LOC100043552. Quantitative reverse transcriptase-PCR indicates that expression levels of Csrp2bp and 6330439K17Rik are decreased in eyes of PPCD1 mice. Based on the observations of decreased gene expression levels, association with ZEB1-related pathways, and the report of corneal opacities in Csrp2bptm1a(KOMP)Wtsi heterozygotes and embryonic lethality in nulls, we postulate that duplication of the 78 Kbp segment leading to haploinsufficiency of Csrp2bp is responsible for the mouse PPCD1 phenotype. Similarly, CSRP2BP haploinsufficiency may lead to human PPCD

Analysis of patient outcomes following proton radiation therapy for retinoblastoma

Purpose: Proton radiation therapy (PRT) is used to treat patients with retinoblastoma (RB) and has the potential to minimize exposure of normal tissue to radiation and thus decrease the risk of toxicity and second malignancies. However, comprehensive analyses of long-term patient outcomes are not available. Methods and materials: Patients with RB who were treated with PRT at our institution between 1986 and 2012 were invited to participate in a study that was designed to assess long-term outcomes. Patients who were enrolled in the study underwent a comprehensive analysis that included oncologic, ophthalmic, endocrine, cephalometric, and quality of life (QOL) assessments. Results: A total of 12 patients were enrolled in this study. The average length of follow-up was 12.9 years (range, 4.8-22.2 years). All study patients had bilateral disease, and the disease and visual outcomes were similar to the outcomes for all patients with RB who were treated with PRT over the same time period at our institution. An analysis of endocrine-related test results revealed no growth abnormalities or hormonal deficiencies across the cohort. Magnetic resonance imaging scans and external cephalometry showed that PRT was associated with less facial hypoplasia than enucleation. Patient and parent-proxy QOL assessments revealed that treatment for RB did not appear to severely affect long-term QOL. Conclusions: In addition to providing an opportunity for long-term disease control and functional eye preservation, PRT does not appear to be associated with unexpected late visual, endocrine, or QOL effects in this cohort of patients with RB

Boston Keratoprosthesis Type II: Indications, Techniques, Outcomes, and Management

Implantation of a keratoprosthesis device is indicated for the visual rehabilitation of patients with corneal blindness in whom a standard corneal allograft would likely fail. The Boston keratoprosthesis type I device is a collar button-shaped device, composed of polymethyl methacrylate and titanium, whereas the type II device has an additional anterior extension that allows for implantation through surgically closed eyelids. The type I device is used in patients with intact eyelids, normal blink, and adequate tear film. The type II device is reserved for patients with abnormal lid function and tear secretion, forniceal foreshortening, and ocular surface keratinization. Herein, we focus on the indications, preoperative assessment, surgical technique, and postoperative care for the Boston keratoprosthesis type II and provide advice on management of complications