Limbal Basal Cell Density Decreases in Limbal Stem Cell Deficiency.

PURPOSE: To investigate changes in limbal basal epithelial cell density in eyes with limbal stem cell deficiency (LSCD) using in vivo confocal laser scanning microscopy. DESIGN: Retrospective observational comparative study. METHODS: A total of 43 eyes of 30 patients diagnosed with LSCD were included in the study. Ten eyes from normal subjects were included as control. Confocal imaging of the central cornea, and the superior, nasal, inferior and temporal limbus were collected using the Heidelberg Retina Tomograph III Rostock Corneal Module. Basal cell density in all locations was measured by 2 independent observers. RESULTS: The mean basal cell density of the normal group was 9264 ± 598 cells/mm(2) in the cornea and 7120 ± 362 cells/mm(2) in the limbus. In the LSCD group, the mean basal cell density in the cornea decreased 31.0% (6389 ± 1820 cells/mm(2), P < .001) and in the limbus decreased 23.6% (5440 ± 1123 cells/mm(2), P < .001) compared to that in the control. There was a trend of basal cell density decline in more advanced stages of LSCD. The basal cell density declined in the unaffected regions at a similar degree as that in the affected region in sectoral LSCD (P > .05). The basal cell diameter increased by 24.6% in the cornea (14.7 µm) and by 15.7% in the limbus (15.5 µm) compared to the control. CONCLUSIONS: Basal cell density in both central cornea and limbus decreases in LSCD. Limbal stem cells (LSCs) are affected globally and basal cell density could be used as a parameter to measure LSC function at the early stages of the disease process.

Epithelial Thinning in Limbal Stem Cell Deficiency.

PURPOSE: To investigate the epithelial thickness in the cornea and limbus in limbal stem cell deficiency (LSCD) by using in vivo laser scanning confocal microscopy. DESIGN: Cross-sectional comparative study. METHODS: Confocal images of 48 eyes of 35 patients with LSCD collected by the Heidelberg Retina Tomograph III Rostock Corneal Module Confocal Microscope from 2010 to 2014 were analyzed. Volume Z-scans of the central cornea and the superior, nasal, inferior, and temporal limbus were included in the analysis. Eleven normal eyes served as control. Epithelial thickness in all locations was measured by 2 independent observers. RESULTS: The mean epithelial layer thickness was 48.6 ± 2.3 µm in the central cornea and 63.7 ± 11.3 µm in the limbus in the control. Compared with the epithelial thickness in normal control, the epithelial thickness in LSCD patients was reduced by an average of 20.2% in the central cornea and 38.5% in the limbus (all P < .05). The mean corneal epithelial thickness in patients with LSCD reduced 7.6%, 20.8%, and 61.3% in the early, intermediate, and late stage, respectively, compared to the control. In the limbus, the overall epithelial thickness decreased 30.0%, 39.7%, and 62.8% in the early, intermediate, and late stage of LSCD, respectively (all P < .05). Epithelial thinning correlated with the severity of LSCD in both cornea and limbus. In eyes with sectoral LSCD, a similar degree of epithelial thinning was also detected in the clinically unaffected limbal regions. CONCLUSIONS: Both corneal and limbal epithelia become progressively thinner in LSCD. Epithelial thickness could be used as a diagnostic measure of LSCD.

Systemic treatment for inoperable pancreatic adenocarcinoma: review and update.

There have been many clinical trials conducted to evaluate novel systemic regimens for unresectable pancreatic cancer. However, most of the trial results were negative, and gemcitabine monotherapy has remained the standard systemic treatment for years. A number of molecular targeted agents, including those against epidermal growth factor receptor and vascular endothelial growth factor receptors, have also been tested. In recent years, there have been some breakthroughs in the deadlock: three regimens, namely gemcitabine-erlotinib, FOLFIRINOX, and gemcitabine-nab-paclitaxel, have been shown to prolong the overall survival of patients when compared with gemcitabine monotherapy. In addition, emerging data suggested that the membrane protein human equilibrative nucleotide transporter 1 is a potential biomarker with which to predict the efficacy of gemcitabine. Here we review the literature on the development of systemic agents for pancreatic cancer, discuss the current choices of treatment, and provide future directions on the development of novel agents.