Refractory Keratolimbal Allograft Rejection in Autoimmune Polyglandular Syndrome-Associated Keratopathy Treated With Intravenous Immunoglobulin.

PURPOSE: The aim of this study was to describe the use of intravenous immunoglobulin (IVIG) in the management of a 20-year-old woman with autoimmune polyglandular syndrome-associated keratopathy who developed acute transplant rejection after keratolimbal allograft (KLAL) surgery. CASE: Nine weeks after KLAL surgery, a 20-year-old woman with autoimmune polyglandular syndrome-related limbal stem cell deficiency presented with graft injection, hemorrhage, and an epithelial rejection line. This was concerning for acute rejection in the setting of triple-agent systemic immunosuppression (albeit nonadherence at times). There was initial reversal of the rejection process with a sub-Tenon's injection of triamcinolone, frequent topical corticosteroids, increase in oral prednisone, and optimization of systemic immunosuppression medications; however, recurrence of the epithelial rejection line and symptoms were noted whenever the prednisone dose was tapered. This was accompanied by ocular surface decompensation (late staining, neovascularization, and persistent epithelial defects). She was found to have weakly positive HLA Class 1 antibodies. The patient was treated with a pulsed corticosteroid infusion and 2 monthly IVIG infusions. This led to resolution of the acute rejection. However, there was a subsequent rejection episode 4 months later after tapering the prednisone. Monthly IVIG for 6 more months led to final resolution with successful prednisone tapering and no further rejection. CONCLUSIONS: Treatment with prolonged IVIG showed better improvement in a case of acute rejection refractory to traditional treatments, especially in the setting of HLA antibodies. The case demonstrates that close follow-up with a corneal specialist and collaboration with a transplant specialist is important to monitor for postoperative KLAL rejection.

Phialophora chinensis fungal keratitis: An initial case report and species identification.

Purpose: To report the initial case of microbial keratitis caused by Phialophora chinensis, a rare cause of fungal keratitis. Observations: A 66-year-old gentleman with a complex right eye (OD) ocular history including herpes simplex virus infectious epithelial keratitis with subsequent neurotrophic keratopathy, and prior combined Candida albicans and parapsilosis fungal keratitis presented with pain OD in the absence of an antecedent trauma. The patient was found to have a filamentous fungal keratitis, which was subsequently cultured and identified as Phialophora chinensis by the laboratory. Despite topical and oral antifungal treatment based on sensitivities determined by the lab, the patient ultimately required intrastromal and subconjunctival antifungal injections, corneal crosslinking, and superficial keratectomy with amniotic membrane to clinically improve. The fungal keratitis recurred twice, with each occurrence rapidly progressing to corneal perforation. Months after the second penetrating keratoplasty, the patient's mental status declined due to multiorgan failure. An occult pulmonary malignancy was discovered during this hospital stay, and the patient was lost to follow-up after entering hospice. Conclusions and Importance: We report a unique case of fungal keratitis caused by Phialophora chinensis and the subsequent management, including both medical and surgical interventions. Despite a multimodal treatment regimen, this case demonstrates the recalcitrant and potentially recurrent nature of fungal keratitis caused by P. chinensis.

The PTIP-Associated Histone Methyltransferase Complex Prevents Stress-Induced Maladaptive Cardiac Remodeling.

Pressure overload induces stress-induced signaling pathways and a coordinated transcriptional response that begets concentric cardiac hypertrophy. Although concentric hypertrophy initially attenuates wall stress and maintains cardiac function, continued stress can result in maladaptive cardiac remodeling. Cardiac remodeling is orchestrated by transcription factors that act within the context of an epigenetic landscape. Since the epigenetic landscape serves as a molecular link between environmental factors (stress) and cellular phenotype (disease), defining the role of the epigenome in the development and progression of cardiac remodeling could lead to new therapeutic approaches. In this study, we hypothesized that the epigenetic landscape is important in the development of cardiac hypertrophy and the progression to maladaptive remodeling. To demonstrate the importance of the epigenome in HF, we targeted the PTIP-associated histone methyltransferase complex in adult cardiac myocytes. This complex imparts histone H3 lysine 4 (H3K4) methylation marks at actively expressed genes. We subjected PTIP null (PTIP-) mice to 2 weeks of transverse aortic constriction, a stress that induces concentric hypertrophy in control mice (PTIP+). PTIP- mice have a maladaptive response to 2wk of transverse aortic constriction (TAC)-induced pressure overload characterized by cardiac dilatation, decreased LV function, cardiac fibrosis, and increased cell death. PTIP deletion resulted in altered stress-induced gene expression profiles including blunted expression of ADRA1A, ADRA1B, JUN, ATP2A2, ATP1A2, SCN4B, and CACNA1G. These results suggest that H3K4 methylation patterns and the complexes that regulate them, specifically the PTIP-associated HMT, are necessary for the adaptive response to TAC.