Medically Reversible Limbal Stem Cell Disease: Clinical Features and 1 Management Strategies

Purpose: To describe the clinical features and management strategies in patients whose limbal stem cell (LSC) disease reversed with medical therapy. Design: Retrospective case series. Subjects: 22 eyes of 15 patients seen at 3 tertiary referral centers between 2007 and 2011 with greater than 3 months follow-up. Methods: Medical records of patients with medically reversible LSC disease were reviewed. Demographic data, etiologies, location and duration of disease and medical inventions were analyzed. Main Outcome Measures: Primary outcomes assessed included resolution of 62 signs of LSC disease and improvement in visual acuity. Results: Etiologies of the LSC disease included contact lens wear only (13 eyes), contact lens wear in the setting of ocular rosacea (3 eyes), benzalkonium chloride toxicity (2 eyes) and idiopathic (4 eyes). Ophthalmologic findings included loss of limbal architecture, a whorl-like epitheliopathy or an opaque epithelium arising from the limbus with late fluorescein staining. The superior limbus was the most common site of involvement (95%).The corneal epithelial phenotype returned to normal with only conservative measures including lubrication and discontinuing contact lens wear in 4 patients (4 eyes) while in 11 patients (18 eyes) additional interventions were required after at least 3 months of conservative therapy. Medical interventions included topical corticosteroids, topical cyclosporine, topical vitamin A, oral doxycycline, and/or punctal occlusion. All eyes achieved a stable ocular surface over a mean follow-up of 15 months (range, 4-60 months). Visual acuity improved from a mean of 20/42 to 20/26 (P <0.0184). Conclusions: Disturbances to the LSC function and/or niche may be potentially reversible by medical therapy. These cases, which represent a subset of patients with LSC deficiency, may be considered to have LSC niche dysfunction. PRECIS We demonstrate the reversibility of limbal stem cell disease through medical treatment and withdrawal of toxic and traumatic insults. This reversibility suggests the limbal disease may result from dysfunction of the limbal stem niche

Additional file 1: of Novel targeted therapies and immunotherapy for advanced thyroid cancers

Table S1. Ongoing clinical trials mentioned. (DOCX 16 kb

Comparison of HIV Incidence Curves Based on the Present Model and on Other Growth Models Published on the Literature.

<p>Growth 1 was based on the results from the HTPN 061 study based on all trial participants [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0123482#pone.0123482.ref053" target="_blank">53</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0123482#pone.0123482.ref055" target="_blank">55</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0123482#pone.0123482.ref056" target="_blank">56</a>]; Growth 2 was based on the results from the HTPN 061 study based on trial participants aged 30 years or less [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0123482#pone.0123482.ref053" target="_blank">53</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0123482#pone.0123482.ref055" target="_blank">55</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0123482#pone.0123482.ref056" target="_blank">56</a>]; Growth 3 was based on the results from the InvolveMENt study [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0123482#pone.0123482.ref054" target="_blank">54</a>]; Growth 4 was based on the average of the previous growth models; Growth 5 was based on this model’s predictions.</p

Results from the Univariate Sensitivity Analyses Based on the Percent Change in new HIV acquired infections (i.e. HIV Incidence) and Prevalence from the Status Quo Scenario; (A) Community, (B) Jail, and (C) Prison.

<p>This analysis assumed an increase of 20%, 40% and 60% in the rate of transmission through anal receptive (<i>ξ</i>_{<i>receptive</i>}) and insertive (<i>ξ</i>_{<i>insertive</i>})sex, in the probability of having unprotected receptive anal sex (<i>pr</i>), and in the product between the average number of anal sexual partners and anal sexual encounters (<i>np</i>*<i>ne</i>).</p

Results for the Model Calibration; (A) New Diagnosed Cases in the Community, and (B) Prevalent Cases in the Community.

<p>Actual data represents the new diagnoses (A) or prevalent (B) cases reported by the Georgia Department of Public Health [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0123482#pone.0123482.ref019" target="_blank">19</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0123482#pone.0123482.ref020" target="_blank">20</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0123482#pone.0123482.ref022" target="_blank">22</a>–<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0123482#pone.0123482.ref028" target="_blank">28</a>]. Data were compared using the two-sample Kolmogorov-Smirnov test.</p

Results from the Univariate Sensitivity Analyses Based on the Percent Change in new HIV acquired infections (i.e. HIV Incidence) and Prevalence from the Status Quo Scenario.

<p>This analysis assumed a decrease of 10%, 15% and 20% in condom efficacy (parameter <i>δ</i>).</p

Additional file 3: of Commensal microbiota modulate gene expression in the skin

Dataset S1. Results from differential expression analysis. Rows contain the 15,448 features analyzed. Columns contain Ensembl feature id, mean expression of GF samples, mean expression of SPF samples, the NOISeq differential expression statistic theta, the probability of differential expression (equal to 1-FDR-corrected p value when using NOISeqBio, DEGs defined as those with prob. > 0.9), the log2 fold change in expression (upregulated in GF > 0, downregulated in GF < 0), feature length, chromosome, feature start and end coordinates, feature biotype, and feature symbol. (XLSX 2289 kb

Additional file 2: Figure S1. of Commensal microbiota modulate gene expression in the skin

Quality control of RNA-sequencing data. (A) Mean quality score per base for each of the 16 samples. (B) Number of reads mapping to the mouse reference genome for each sample. (C) Relative abundance of reads mapping to each biotype. (D) Percentage of the genome covered by mapped reads per sample. (EPS 1354 kb

Additional file 7: Table S2. of Commensal microbiota modulate gene expression in the skin

WGCNA gene module characterization. Top 5 significantly enriched biological process gene ontology terms (Bonferroni p < 0.05) associated with each WGCNA module. (XLSX 47 kb

Additional file 9: Figure S4. of Commensal microbiota modulate gene expression in the skin

Analysis of skin immune cell populations supports gene expression findings. (A) Toluidine blue staining for mast cells. (B) Immunofluorescence staining of CD3, a pan T cell marker. Significance testing was performed on an aggregate of three experiments with n = 3 GF and SPF mice each. (C) Flow cytometry analysis of GF and SPF (n = 5 each) of IL-1α and IL-1β production by cell subset. Comparisons that are significantly different with a p value < 0.05 are denoted with * and those with a p value < 0.01 with **. (D) Barplots showing normalized gene expression values for IL-1α and IL-1β. Lines depict standard error and padj represents the FDR-corrected p value (1-prob) calculated by NOISeqBio. (E) Boxplot of normalized gene expression of terminal differentiation markers Krt1 and Krt14, with padj indicating the FDR-corrected p value (1-prob) calculated by NOISeqBio. (EPS 85855 kb