Low-dose oral imatinib in the treatment of systemic sclerosis interstitial lung disease unresponsive to cyclophosphamide: a phase II pilot study

Introduction: Pulmonary involvement represents a major cause of death of systemic sclerosis (SSc) patients. Recent data suggest that tyrosine kinase inhibitors, such as imatinib, may be a therapeutic option for SSc patients. However, preliminary published clinical trials were inconclusive about imatinib efficacy and showed side effects. The purpose of this study was to verify efficacy and tolerability of low-dose imatinib on interstitial lung disease in a cohort of SSc patients unresponsive to cyclophosphamide therapy.Methods: Thirty consecutive SSc patients with active pulmonary involvement, unresponsive to cyclophosphamide, were treated with imatinib 200 mg/day for 6 months followed by a 6-month follow-up. A "good response" was defined as an increase of forced vital capacity (FVC) by more of 15% and/or increase of diffusing capacity of carbon monoxide (DLCO) > 15% and PaO2 > 90% of initial value and high-resolution computed tomography (HRCT)-scan pattern unchanged or improved.Results: Twenty-six patients completed the study. Three patients died and one patient was lost to follow-up. Four patients (15.32%) had a good response, 7 worsened and 15 had a stabilized lung disease. Overall, 19 (73.07%) patients had an improved or stabilized lung disease. After a 6-month follow-up, 12 (54.5%) of the 22 patients showed an improved or stabilized lung disease.Conclusions: Lung function was stabilized in a large proportion of patients unresponsive to cyclophosphamide therapy and a beneficial outcome emerged from the analysis of HRCT lung scans. There was no significant improvement of skin involvement, and the low dose was well tolerated. These data provide useful suggestions to design future randomized clinical trials for SSc therapeutics

Impact of corneal collagen cross-linking on vision-related quality of life measured with the keratoconus outcomes research questionnaire (KORQ) in patients with keratoconus

Purpose To assess the impact of corneal collagen cross-linking on self-reported vision-related quality of life (VR-QoL) in keratoconus patients by means of the Keratoconus Outcomes Research Questionnaire (KORQ), a new disease-specific patient reported outcomes measures (PROMs) tool. Methods Patients with progressive keratoconus undergoing corneal collagen cross-linking were consecutively enrolled. Patients completed the KORQ before and after the treatment, at 1, 3 and 6 months. Data were collected regarding the visual acuity and the topographic, aberrometric and pachymetric parameters of both eyes. Patients were also asked to quantify their eye rubbing behavior on a Visual Analogue Scale (VAS) from 0 to 10, before and 6 months after treatment. The KORQ scores were associated with the visual acuity, topographic, aberrometric and pachymetric data by means of the Spearman correlation coefficient. Results The Activity Limitation (AL) subscale score was higher after surgery. Preoperatively, negative correlations were observed between the KORQ AL score and Best Corrected Visual Acuity (logMAR), maximum keratometry, flattest keratometry, steepest keratometry, symmetry index front and higher order aberrations (HOA) of the treatment eye. Postoperatively, we observed a shift toward the fellow eye, with stronger correlation of the KORQ scores with the fellow eye parameters. The Symptoms subscale score correlated with the aberrometric parameters of both eyes at various time points. Statistically significant correlations were observed between the change in KORQ scores and the change in aberrometric parameters. A statistically significant reduction in the eye rubbing behavior was detected (p < 0,0001). Conclusions These results suggest that the corneal cross-linking treatment is effective both in improving the subjective perception of the disease by the patient and in stabilizing the objective indicators of disease progression. Keratometric, aberrometric and visual acuity values showed a significant impact on self-reported VR-QoL. Corneal cross-linking, by halting the worsening of these parameters, may bear a beneficial effect on VR-QoL

Biological parameters determining the clinical outcome of autologous cultures of limbal stem cells

Aim: Limbal cultures restore the corneal epithelium in patients with ocular burns. We investigated the biological parameters instrumental for their clinical success. Methods: We report a long-term multicenter prospective study on 152 patients carrying corneal destruction due to severe ocular burns, treated with autologous limbal cells cultured on fibrin and clinical-grade 3T3-J2 feeder cells. Clinical results were statistically evaluated both by parametric and nonparametric methods. Results: Clinical outcomes were scored as full success, partial success and failure in 66.05, 19.14 and 14.81% of eyes, respectively. The total number of clonogenic cells, colony size, growth rate and presence of conjunctival cells could not predict clinical results. Instead, the clinical data provided conclusive evidence that graft quality and likelihood of a successful outcome rely on an accurate evaluation of the number of stem cells detected before transplantation as holoclones expressing high levels of the p63 transcription factor. No adverse effects related to the feeder layer have been observed and the regenerated epithelium was completely devoid of any 3T3-J2 contamination. Conclusion: Cultures of limbal stem cells can be safely used to successfully treat massive destruction of the human cornea. We emphasize the importance of a discipline for defining the suitability and the quality of cultured epithelial grafts, which are relevant to the future clinical use of any cultured cell type

The Management of Dry Eye Disease: Proceedings of Italian Dry Eye Consensus Group Using the Delphi Method

Dry eye disease (DED) is a highly prevalent, chronic and progressive condition that affects 5-33% of the world's adult population [...]