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

Prompt versus delayed amniotic membrane application in a patient with acute Stevens-Johnson syndrome

Jessica B Ciralsky, Kimberly C SippelDepartment of Ophthalmology, Weill Cornell Medical College, New York, NY, USABackground: Stevens-Johnson syndrome is often associated with blinding ocular surface cicatricial sequelae. Recent reports have described markedly improved clinical outcomes with the application of amniotic membrane to the ocular surface during the acute phase. Here we describe the clinical outcome of a patient with acute Stevens-Johnson syndrome and severe ocular surface involvement in whom the evolving medical condition and family consent resulted in amniotic membrane application to each eye at differing intervals from disease onset.Methods: We undertook a retrospective chart review of a woman with Stevens-Johnson syndrome who presented within hours of disease onset. She underwent application of amniotic membrane to the ocular surface of the left eye during the hyperacute phase (<72 hours after disease onset) and to the right eye at a later time point during the acute phase (six days after disease onset). The clinical outcomes of the two eyes, as well as associated ocular symptoms, were compared over a one-year postoperative period.Results: The right eye, treated later in the course of the disease, required additional surgical procedures and ultimately exhibited significantly more advanced ocular surface pathology than the left. Further, the patient reported more pronounced issues of chronic eye pain and visual difficulties in the right eye.Conclusion: Earlier intervention with application of amniotic membrane to the ocular surface in this patient with severe ocular involvement secondary to Stevens-Johnson syndrome proved superior. Application of amniotic membrane as soon as possible after disease onset, preferably in the hyperacute phase, appears to result in a significantly better clinical outcome than application later in the disease course.Keywords: Stevens-Johnson syndrome, toxic epidermal necrolysis, amniotic membran

Boston type I keratoprosthesis-donor cornea interface evaluated by high-definition spectral-domain anterior segment optical coherence tomography

Ana G Alzaga Fernandez,* Nathan M Radcliffe,* Kimberly C Sippel, Mark I Rosenblatt, Priyanka Sood, Christopher E Starr, Jessica B Ciralsky, Donald J D&amp;#39;Amico, Szil&amp;aacute;rd KissDepartment of Ophthalmology, Weill Cornell Medical College, New York-Presbyterian Hospital, New York, NY, USA*These authors contributed equally to this work and both are considered principal authorsBackground: The purpose of this study was to assess whether the resolution offered by two different, recently commercially available high-resolution, spectral-domain anterior segment optical coherence tomography (AS-OCT) instruments allows for detailed anatomic characterization of the critical device-donor cornea interface in eyes implanted with the Boston type I permanent keratoprosthesis.Methods: Eighteen eyes of 17 patients implanted with the Boston type I keratoprosthesis were included in this retrospective case series. All eyes were quantitatively evaluated using the Cirrus HD-OCT while a subset (five eyes) was also qualitatively imaged using the Spectralis Anterior Segment Module. Images from these instruments were analyzed for evidence of epithelial migration onto the anterior surface of the keratoprosthesis front plate, and presence of a vertical gap between the posterior surface of the front plate and the underlying carrier donor corneal tissue. Quantitative data was obtained utilizing the caliper function on the Cirrus HD-OCT.Results: The mean duration between AS-OCT imaging and keratoprosthesis placement was 29 months. As assessed by the Cirrus HD-OCT, 83% of eyes exhibited epithelial migration over the edge of the front plate. Fifty-six percent of the keratoprosthesis devices displayed good apposition of the device with the carrier corneal donor tissue. When a vertical gap was present (44% of eyes), the mean gap was 40 (range 8&amp;ndash;104) microns. The Spectralis Anterior Segment Module also displayed sufficient resolution to allow for similar characterization of the device-donor cornea interface.Conclusion: Spectral-domain AS-OCT permits high resolution imaging of the keratoprosthesis device-donor cornea interface. Both the Cirrus HD-OCT and the Spectralis Anterior Segment module allowed for visualization of epithelial coverage of the device-donor cornea interface, as well as identification of physical gaps. These imaging modalities, by yielding information in regard to integration of the keratoprosthesis with surrounding corneal tissue, may help identify those at risk for keratoprosthesis-related complications, such as extrusion and endophthalmitis, and hence guide clinical management.Keywords: keratoprosthesis, anterior segment optical coherence tomography, epithelializatio