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Research efforts to clarify its pathophysiology are leading to a better understanding of DED, demonstrating that inflammation, in addition to many other factors, plays a relevant role.

Ocular stem cell transplantation derived from either autologous or allogeneic donor corneoscleral junction is a functional cell therapy to manage extensive and/or severe limbal stem cell deficiencies that lead to corneal epithelial failure. Mesenchymal stem cells have been properly tested in animal models of this ophthalmic pathology, but never in human eyes despite their potential advantages. We conducted a 6-to 12month proof-of-concept, randomized, double-masked pilot trial to test whether allogeneic bone marrow-derived mesenchymal stem cell transplantation (MSCT, n=17) was as safe and as equally efficient as allogeneic cultivated limbal epithelial transplantation (CLET, n=11) to improve corneal epithelial damage due to limbal stem cell deficiency. Primary endpoints demanded combination of symptoms, signs, and the objective improvement of the epithelial phenotype in central cornea by in-vivo confocal microscopy. This proof-of-concept trial showed that MSCT was as safe and efficacious as CLET. Global success at 6-12 months was 72.7%-77.8% for CLET cases and 76.5%-85.7% for MSCT cases (not significant differences). Central corneal epithelial phenotype improved in 71.4% and 66.7% of MSCT and CLET cases, respectively at 12 months (p=1.000). There were no adverse events related to cell products. This trial suggests first evidence that MSCT facilitated improvement of a diseased corneal epithelium due to lack of its stem cells as efficiently as CLET. Consequently, not only CLET but also MSCT deserves more preclinical investigational resources before the favorable results of this proof-of-concept trial could be transformed into the larger numbers of the multicenter trials that would provide stronger evidence. (ClinicalTrials.gov number, NCT01562002.) 5 of 44 Key words: clinical trial, corneal blindness, corneal epithelial stem cells, human proof-of-concept, in vivo confocal microscopy, limbal stem cell deficiency, mesenchymal stem cell, stem cell transplantation of 44

The data strongly suggest that the expression levels of MUC1 may be used as a diagnostic test in DES for investigational and selective clinical trials.

Anti-TNF-α therapy is effective and relatively safe in refractory BD uveitis.

During retrospective and prospective studies, we attempted to determine the clinical characteristics, treatment, and visual outcome of patients with pars planitis and to evaluate the association between pars planitis and multiple sclerosis (MS). The retrospective study included 44 patients with pars planitis, who had been examined between October 1986 and January 1999. We analyzed age, sex, visual acuity (VA), median follow-up time, and medical and surgical treatments. The prospective study, which included 21 consecutive patients with pars planitis, was performed to determine the presence of MS. In the retrospective study, the mean patient age was 22.4 years (SD +/- 11.5) and the median follow-up was 34.9 months (SD +/- 27.2). Complications included macular edema (47.7%), vitreous opacities (38.6%), papillitis (38.6%), vasculitis (36.4%), and cataract (20.5%). Forty patients (90.9%) had a final bilateral VA better than 20/40. In the prospective study, magnetic resonance imaging (MRI) was performed. Demyelinating lesions were found in 10 (47.6%) of the 21 patients and relapsing-remitting clinically definite MS was diagnosed in seven (33.3%). With the exception of age, no significantly statistical differences were observed when the visual prognosis and the clinical and epidemiologic characteristics were compared between the two groups of patients with and without associated MS; a diagnosis of MS was more frequently made in patients over 25 years of age. With appropriate treatment, patients with pars planitis have a good visual prognosis. Because the presence of demyelinating lesions seems to be high among patients with pars planitis, MRI should be considered, especially in patients over 25 years of age.

Objective. To evaluate outcomes of cultivated limbal epithelial transplantation (CLET) for management of ocular surface failure due to limbal stem cell deficiency (LSCD). Design. Prospective, noncomparative, interventional case series and extensive comparison with recent similar studies. Participants. Twenty eyes with LSCD underwent CLET (11 autologous; 9 allogeneic) and were followed up for 3 years. Etiologies were divided into 3 prognostic categories: Group 1, chemical injuries (7 eyes); Group 2, immune-based inflammation (4 eyes); and Group 3, noninflammatory diseases (9 eyes). Intervention. Autologous and allogeneic limbal epithelial cells were cultivated on amniotic membranes and transplanted. Evaluations were based on clinical parameters, survival analysis, and in vivo confocal microscopy (IVCM). European Union Tissues/Cells Directive and good manufacturing procedures were followed. Main Outcome Measures. Improved clinical parameters, absence of epithelial defects, and improved central corneal epithelial phenotype. Results. Success rate was 80% at 1-2 years and 75% at 3 years. Autografts and allografts had similar survival. Success rate was significantly lower in prognostic Group 1 (42.9%) than in Groups 2-3 (100% each). All clinical parameters improved substantially. By IVCM, 80% of cases improved in epithelial status. Conclusions. CLET improved corneal epithelium quality, with subsequent improvement in symptoms, quality of life, and vision. These results confirm that CLET is a valid therapy for ocular surface failure.