A STUDY OF OUTCOME OF ROSE K LENSES IN KERATOCONUS

Background: Cornea is affected by several distinct disorders that produce marked thinning without significant inflammation. They are keratoconus, posterior keratoconus, pellucid marginal degeneration, and keratoglobus. keratoconus and posterior keratoconus produces central and inferior thinning with ectasia. Materials and Methods: All patients of keratoconus in age group 15 to 60 years at various stages of progression were included this was a prospective study, 20 Eyes of 15 patients of keratoconus in age group of 15 to 60 years at various stages of progression were included in the study. Visual acuity, slit lamp Biomicroscopy was done, corneal topography and Fundus examination was done by both direct and indirect ophthalmoscopy with full dilatation when possible. Results: Subjective score of pre rose k eyes when compared to post rose k lens eye was highly significant, which signifies that the same patient was highly satisfied after wearing rose k lens. Conclusion: Present study observed that, Rose K lenses improved patient\u27s overall quality of life in moderate and advance cases of keratoconus. KEYWORDS: Keratoconus; Pellucid marginal degeneration; Keratoglobus; rose k lenses

A STUDY OF OUTCOME OF ROSE K LENSES IN KERATOCONUS

Background: Cornea is affected by several distinct disorders that produce marked thinning without significant inflammation. They are keratoconus, posterior keratoconus, pellucid marginal degeneration, and keratoglobus. keratoconus and posterior keratoconus produces central and inferior thinning with ectasia. Materials and Methods: All patients of keratoconus in age group 15 to 60 years at various stages of progression were included this was a prospective study, 20 Eyes of 15 patients of keratoconus in age group of 15 to 60 years at various stages of progression were included in the study. Visual acuity, slit lamp Biomicroscopy was done, corneal topography and Fundus examination was done by both direct and indirect ophthalmoscopy with full dilatation when possible. Results: Subjective score of pre rose k eyes when compared to post rose k lens eye was highly significant, which signifies that the same patient was highly satisfied after wearing rose k lens. Conclusion: Present study observed that, Rose K lenses improved patient's overall quality of life in moderate and advance cases of keratoconus. KEYWORDS: Keratoconus; Pellucid marginal degeneration; Keratoglobus; rose k lenses

High dose intermittent sorafenib shows improved efficacy over conventional continuous dose in renal cell carcinoma

<p>Abstract</p> <p>Background</p> <p>Renal cell carcinoma (RCC) responds to agents that inhibit vascular endothelial growth factor (VEGF) pathway. Sorafenib, a multikinase inhibitor of VEGF receptor, is effective at producing tumor responses and delaying median progression free survival in patients with cytokine refractory RCC. However, resistance to therapy develops at a median of 5 months. In an effort to increase efficacy, we studied the effects of increased sorafenib dose and intermittent scheduling in a murine RCC xenograft model.</p> <p>Methods</p> <p>Mice bearing xenografts derived from the 786-O RCC cell line were treated with sorafenib according to multiple doses and schedules: 1) Conventional dose (CD) continuous therapy; 2) high dose (HD) intermittent therapy, 3) CD intermittent therapy and 4) HD continuous therapy. Tumor diameter was measured daily. Microvessel density was assessed after 3 days to determine the early effects of therapy, and tumor perfusion was assessed serially by arterial spin labeled (ASL) MRI at day 0, 3, 7 and 10.</p> <p>Results</p> <p>Tumors that were treated with HD sorafenib exhibited slowed tumor growth as compared to CD using either schedule. HD intermittent therapy was superior to CD continous therapy, even though the total dose of sorafenib was essentially equivalent, and not significantly different than HD continuous therapy. The tumors exposed to HD sorafenib had lower microvessel density than the untreated or the CD groups. ASL MRI showed that tumor perfusion was reduced to a greater extent with the HD sorafenib at day 3 and at all time points thereafter relative to CD therapy. Further the intermittent schedule appeared to maintain RCC sensitivity to sorafenib as determined by changes in tumor perfusion.</p> <p>Conclusions</p> <p>A modification of the sorafenib dosing schedule involving higher dose intermittent treatment appeared to improve its efficacy in this xenograft model relative to conventional dosing. MRI perfusion imaging and histologic analysis suggest that this benefit is related to enhanced and protracted antiangiogenic activity. Thus, better understanding of dosing and schedule issues may lead to improved therapeutic effectiveness of VEGF directed therapy in RCC and possibly other tumors.</p

Cox-2 Inhibition Enhances the Activity of Sunitinib in Human Renal Cell Carcinoma Xenografts

Background: Sunitinib (Su), a tyrosine kinase inhibitor of VEGFR, is effective at producing tumour response in clear cell renal cell carcinoma (cRCC), but resistance to therapy is inevitable. As COX-2 is a known mediator of tumour growth, we explored the potential benefit of COX-2 inhibition in combination with VEGFR inhibition in attempts at delaying tumour progression on Su. Methods: COX-2 expression was compared with areas of hypoxia in tumours that progressed on Su vs untreated tumours. Mice bearing human cRCC xenografts were treated with Su and the COX-2 inhibitor, celecoxib, and the effects on tumour growth were assessed. Sequential vs concurrent regimens were compared. Results: COX-2 expression was increased in cRCC xenografts in areas of tumour hypoxia. The combination of Su and celecoxib achieved longer times to tumour progression compared to treatment with either agent alone or to untreated control animals in four models. This effect was seen with concurrent but not with sequential therapy. Conclusion: COX-2 inhibition can extend the effectiveness of VEGFR inhibition. This effect is dependent on the timing of therapy. Clinical trials combining Su and COX-2 inhibitors should be considered as a means delaying time to progression on sunitinib in patients with metastatic cRCC

Inhibition of ALK1 signaling with dalantercept combined with VEGFR TKI leads to tumor stasis in renal cell carcinoma

Treatment of metastatic renal cell carcinoma (mRCC) with agents that block signaling through vascular endothelial growth factor receptor 2 (VEGFR2) induces disease regression or stabilization in some patients; however, these responses tend to be short-lived. Therefore, development of combination therapies that can extend the efficacy of VEGFR antagonists in mRCC remains a priority. We studied murine xenograft models of RCC that become refractory to treatment with the VEGFR tyrosine kinase inhibitor (TKI) sunitinib. Dalantercept is a novel antagonist of Activin receptor-like kinase 1 (ALK1)/Bone morphogenetic protein (BMP) 9 signaling. Dalantercept inhibited growth in the murine A498 xenograft model which correlated with hyperdilation of the tumor vasculature and an increase in tumor hypoxia. When combined with sunitinib, dalantercept induced tumor necrosis and prevented tumor regrowth and revascularization typically seen with sunitinib monotherapy in two RCC models. Combination therapy led to significant downregulation of angiogenic genes as well as downregulation of endothelial specific gene expression particularly of the Notch signaling pathway. We demonstrate that simultaneous targeting of molecules that control distinct phases of angiogenesis, such as ALK1 and VEGFR, is a valid strategy for treatment of mRCC. At the molecular level, combination therapy leads to downregulation of Notch signaling

Resistance of Renal Cell Carcinoma to Sorafenib Is Mediated by Potentially Reversible Gene Expression

Purpose: Resistance to antiangiogenic therapy is an important clinical problem. We examined whether resistance occurs at least in part via reversible, physiologic changes in the tumor, or results solely from stable genetic changes in resistant tumor cells. Experimental Design: Mice bearing two human RCC xenografts were treated with sorafenib until they acquired resistance. Resistant 786-O cells were harvested and reimplanted into naïve mice. Mice bearing resistant A498 cells were subjected to a 1 week treatment break. Sorafenib was then again administered to both sets of mice. Tumor growth patterns, gene expression, viability, blood vessel density, and perfusion were serially assessed in treated vs control mice. Results: Despite prior resistance, reimplanted 786-O tumors maintained their ability to stabilize on sorafenib in sequential reimplantation steps. A transcriptome profile of the tumors revealed that the gene expression profile of tumors upon reimplantation reapproximated that of the untreated tumors and was distinct from tumors exhibiting resistance to sorafenib. In A498 tumors, revascularization was noted with resistance and cessation of sorafenib therapy and tumor perfusion was reduced and tumor cell necrosis enhanced with re-exposure to sorafenib. Conclusions: In two RCC cell lines, resistance to sorafenib appears to be reversible. These results support the hypothesis that resistance to VEGF pathway therapy is not solely the result of a permanent genetic change in the tumor or selection of resistant clones, but rather is due to a great extent to reversible changes that likely occur in the tumor and/or its microenvironment

A comparative study of stromal reaction in Epi-on & Epi-off techniques post- C3R in Keratoconus patients with OCT.

TITLE: A patient study of Stromal Reaction after C3R with OCT and comparing Epi-On & Epi-Off techniques in Keratoconus patients. PURPOSE: To report a study of 20 patients of keratoconus showing the effect on the corneal structure and stromal reaction in post Corneal Collagen Cross Linking (C3R), through the Anterior Segment imaging technique- OCT METHODS: A Study was done from 15.7.2014 to 30.9.2014 of 20 patients having keratoconus, progressive type, where Collagen Cross linking was decided as the method of management (10 each of Epi-on and Epi-off technique). In the Epi-off technique, the epithelium was removed prior to corneal soakage of a dextran-based 0.1% photo sensitizer riboflavin solution for 30 minutes, followed by exposure of ultraviolet-A (typically 365-370 μm) light for 30 min with an intensity of 3 mW/cm 2 and 5.4 J/cm 2 of energy. In the Epi-on technique, a special dextran-trometamol EDTA based 0.1% riboflavin solution is used without scrapping the cornea, rest of the method is same. One week after the C3R procedure, the anterior segment OCT was done. RESULTS: In the first few weeks after cross-linking, a faint hyper reflectivity is noted in the anterior stroma, a distinct demarcation between the cross-linked and non-cross-linked areas of the cornea, the depth of demarcation line and the change in the corneal thickness was noted. CONCLUSION: In both the Epi-on and Epi-off technique, the change in the stromal thickness and demarcation line is same. Hence we conclude that both the techniques are equally effective

A Phase 2 Pilot Trial of Low-Dose, Continuous Infusion, or Metronomic Paclitaxel and Oral Celecoxib in Patients With Metastatic Melanoma

BACKGROUND: Tumor angiogenesis has been associated with poor prognosis in patients with metastatic melanoma (MM). Microtubule stabilizers and cyclooxygenase (COX)-2 inhibitors, alone and in combination, have shown inhibitory effects on endothelial cells and tumor angiogenesis. Angiogenesis, the growth of new blood vessels, is necessary for tumor growth and progression. Thus, we tested the safety and efficacy of a low dose of paclitaxel and celecoxib in patients with MM. METHODS: Patients received paclitaxel 10mg/m2 for 96 hours weekly by CIV and celecoxib 400 mg po/bid. Systemic tumor response was assessed at 6 week intervals. Tumor measurements at the end of Cycle 1 were used as the baseline for assessment of tumor progression. Patients with unacceptable toxicity or disease progression after Cycle 2 relative to the end of Cycle 1 were taken off study. RESULTS: Twenty patients were enrolled. Twelve (60%) had received 2 or more prior systemic therapies. Three patients did not receive treatment due to rapid disease progression. Treatment related grade 3–4 toxicities were limited to catheter-related complications. One patient achieved a partial response and 3/20 (15%) patients had stable disease for greater than 6 months. Median time to progression was 57 days (95% CI: 43–151) and median overall survival was 212 days (95% CI: 147–811 days. CONCLUSIONS: Low-dose, CIV paclitaxel and oral celecoxib can produce disease stabilization in a significant proportion of heavily pre-treated patients with MM. These findings support a role for metronomic therapy in this disease