piperidines has been researched along with Retinal-Diseases* in 8 studies
2 trial(s) available for piperidines and Retinal-Diseases
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Characterization of Serous Retinopathy Associated with Cobimetinib: Integrated Safety Analysis of Four Studies.
Serous retinopathy can be associated with MEK inhibitors, including cobimetinib. We present results of an integrated safety analysis to further characterize ocular functional and structural changes due to serous retinopathy.. Four studies evaluating cobimetinib at the approved dose and schedule in combination with other oncology drugs were included. Study CO39721 incorporated standardized ophthalmologic assessments to fully characterize serous retinopathy events over time and was the primary study for analysis. Supporting information was provided by studies GO28141, WO29479, and GO30182.. In total, 655 patients received one or more doses of cobimetinib and comprised the safety-evaluable population. Overall, 117 patients (17.9%) had one or more serous retinopathy events, 24 (3.7%) had two or more events, and four (0.6%) had three or more events. Grade 3 events occurred in < 2.5% of patients. In CO39721, the median time to onset was 15 days (range 7-111); median time to resolution of first occurrence was 26 days (range 6-591 + days). Twelve of 25 patients (48.0%) recovered without a dose modification and 4/25 (16.0%) were recovered/recovering following a dose modification. The most frequent presentation of serous retinopathy was focal subretinal fluid on optical coherence tomography (62.8% of cases); in some instances (25.7% of cases), subretinal fluid was multifocal. There was no loss of visual function or visual acuity at serous retinopathy onset or resolution.. Results from this integrated safety analysis indicate that cobimetinib-associated serous retinopathy can be managed with or without a dose modification of cobimetinib at the discretion of the treating physician. No visual loss or permanent retinal damage was identified on comprehensive ophthalmologic assessments.. ClinicalTrials.gov identifiers: NCT03178851, NCT01689519, NCT02322814, and NCT02788279. Topics: Azetidines; Humans; Piperidines; Protein Kinase Inhibitors; Retinal Diseases | 2022 |
Sub-Tenon infiltration or classical analgesic drugs to relieve postoperative pain.
In a prospective randomized double-blind study, the analgesic effect produced by sub-Tenon infiltration was compared with classic analgesic drugs in patients scheduled for posterior segment surgery under general anaesthesia.. One hundred patients were randomized into two groups of 50. One group received sub-Tenon infiltration (group 1) with 3 mL of bupivacaine 0.50% by the surgeon before the end of the surgery and the other (group 2) received only classical analgesic drugs postoperatively. A visual analogue scale (VAS) (graded from 1 to 10) was used to assess pain. For both groups, when VAS was between 1 and 3 paracetamol (3 g/24 h) associated with ketoprofen (200 mg/24 h) was given; between 3 and 6 nalbuphine (0.2 mg/kg slowly intravenously repeated every 4 h if necessary) was given; and over 6 morphine was given. Morphine 1 mg was injected every 2 min until VAS below 3 was obtained.. All patients in group 2 (control) experienced pain in the recovery room period; however, no patient in group 1 required analgesic drugs in the first 6 h after the sub-Tenon infiltration. In the recovery room period, the VAS pain score in patients who received sub-Tenon infiltration (group 1) was 0.6 +/- 1.3 (mean +/- SD) compared to 3.4 +/- 2.2 in group 2. The difference was statistically significant (P = 0.000001). All patients in group 2 asked for analgesic drugs in the recovery room, some of whom required morphine. Despite the administration of drugs the pain score was statistically higher in group 2. Between the end of the recovery room period and the 6th hour, the VAS pain score in group 1 was statistically lower. From the 6th until the 24th hour, the pain score was not statistically significantly different between the groups. Regarding consumption of analgesic drugs from the recovery room until the 24th hour, the consumption of level 1 analgesic drugs (paracetamol, ketoprofen) and level 3 (morphine) was statistically lower in group 1 (P = 0.0009). The difference was not significant for level 2, probably because the number of patients was not sufficient.. Sub-Tenon infiltration with 3 mL of bupivacaine 0.50% offers excellent postoperative analgesia for about 6 h and is an excellent alternative to classical drugs. Furthermore, it is highly reliable and safe. Topics: Adult; Analgesia; Analgesics, Opioid; Anesthetics, Local; Bupivacaine; Connective Tissue; Double-Blind Method; Fascia; Female; Humans; Male; Middle Aged; Pain Measurement; Pain, Postoperative; Piperidines; Prospective Studies; Remifentanil; Retinal Diseases; Time Factors; Vitrectomy | 2004 |
6 other study(ies) available for piperidines and Retinal-Diseases
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En Face Widefield OCT Angiography of MEK Inhibitor-Associated Retinopathy.
Topics: Azetidines; Craniopharyngioma; Female; Fluorescein Angiography; Fundus Oculi; Humans; MAP Kinase Kinase 1; Middle Aged; Piperidines; Pituitary Neoplasms; Protein Kinase Inhibitors; Retinal Diseases; Tomography, Optical Coherence; Vemurafenib | 2021 |
Sudden Onset of Multiple Green Spots in the Eyes of a Woman With Breast Cancer.
Topics: Aged; Antineoplastic Agents; Azetidines; Breast Neoplasms; Female; Fluorescein Angiography; Humans; MAP Kinase Kinase 1; Neoplasm Staging; Piperidines; Retinal Diseases; Tomography, Optical Coherence; Visual Acuity | 2020 |
MEK Retinopathy. Clinical case reports.
Three clinical cases are presented of MEK retinopathy associated with the combination of cobimetinib and vemurafenib characterised by alteration of the retinal pigment epithelium and neurosensory detachment. Two of the cases conserved the vision of the unit, and the third developed a large bilateral neurosensory detachment with final visual acuity of 0.6 for the right eye and 0.1 for the left one.. The new therapeutic strategies against metastatic cutaneous melanoma condition the appearance of alterations of the pigmentary epithelium of the retina with serous detachments, leading to close monitoring with macular optical coherence tomography. Topics: Antineoplastic Agents; Azetidines; Female; Humans; Male; Melanoma; Middle Aged; Mitogen-Activated Protein Kinases; Piperidines; Retinal Diseases; Vemurafenib | 2018 |
The cKit Inhibitor, Masitinib, Prevents Diabetes-Induced Retinal Vascular Leakage.
Stem cell factor (SCF) has recently demonstrated activity as a novel endothelial permeability factor that contributes to the development of diabetes-induced hyperpermeable retinal vasculature. This study investigated the therapeutic potential of masitinib, a pharmacologic inhibitor of the SCF receptor cKit, for prevention of diabetes-induced breakdown of blood retinal barrier (BRB).. Permeability assays were performed with human retinal microvascular endothelial cells (HRMECs) and murine retinal vasculature. Localization of vascular endothelial (VE)-cadherin and activation of SCF signaling pathway was determined by immunofluorescence and Western blotting assays. Mice and rats with streptozotocin (STZ)-induced diabetes were used to investigate the role of cKit and masitinib in diabetes-induced retinal vascular hyperpermeability.. Masitinib substantially blocked SCF-induced phosphorylation of cKit in HRMECs. In vitro and in vivo vascular permeability assays showed that masitinib significantly inhibited SCF-induced endothelial hyperpermeability and junctional loss of VE-cadherin. Streptozotocin-induced diabetes was induced in cKit-mutant mice with low cKit expression in their endothelial cells. Although diabetic wild-type mice exhibited enhanced retinal vascular leakage, diabetic cKit-mutant mice showed no increase in retinal vascular leakage or alteration in the distribution of VE-cadherin; this indicates the crucial role of cKit in diabetes-induced breakdown of BRB. Moreover, in vivo prevention experiments showed that an intravitreal injection of masitinib substantially inhibited the development of hyperpermeable retinal vasculature.. These results provide the first demonstration that cKit inhibitors, such as masitinib, might be promising therapeutics for prevention of diabetes-induced breakdown of the BRB. Topics: Animals; Benzamides; Blood-Retinal Barrier; Blotting, Western; Capillary Permeability; Cells, Cultured; Diabetes Mellitus, Experimental; Diabetic Retinopathy; Endothelium, Vascular; Gene Expression Regulation; Humans; Immunohistochemistry; Intravitreal Injections; Male; Mice; Mice, Inbred C57BL; Piperidines; Protein Kinase Inhibitors; Pyridines; Rats; Rats, Sprague-Dawley; Retinal Diseases; Retinal Vessels; Reverse Transcriptase Polymerase Chain Reaction; RNA; Signal Transduction; Stem Cell Factor; Thiazoles; Vascular Resistance | 2016 |
Neuroprotective effects of topical CB1 agonist WIN 55212-2 on retinal ganglion cells after acute rise in intraocular pressure induced ischemia in rat.
Neuroprotection in retinal experimental work consists primarily of preventing retinal ganglion cell (RGC) loss after exposure to a hostile event. We have studied the neuroprotective effect on RGCs in an ischemia-reperfusion model by activation of the cannabinoid receptor CB1 using topical application of WIN 55212-2. Intraocular pressure (IOP) was increased by continuous infusion of phosphate buffer saline (PBS) into the anterior chamber of the eye. Mean intraocular pressure was increased up to 88.5 ± 0.29 mm Hg (control normal IOP 15.1 ± 0.25 mm Hg), for 35 min. Animals were distributed in 3 groups. Left eyes underwent acute rise in intraocular pressure. First group was treated with topical Tocrisolve™ 100 in both eyes. Second group was treated with 1% solution of CB1 agonist WIN 55212-2 in both eyes. Third group was treated with WIN 55212-2 1% and CB1 antagonist AM 251 1% solutions in both eyes. Subsequently, RGCs were immunolabeled with Brn3a and automated quantification of retinal mosaics of RGCs were performed. The ischemic damage led to a mean loss in RGC density of 12.33%. After topic administration of WIN 55212-2, mean loss of RGCs was of 2.45%. Co-treatment with CB1 antagonist AM 251 abolished almost completely the neuroprotective effect of WIN 55212-2. Topic 1% WIN 55212-2 showed a neuroprotective effect on RGC degeneration after ischemia-reperfusion without pre-activation of CB1 receptors. Topics: Administration, Topical; Animals; Benzoxazines; Cell Count; Disease Models, Animal; Female; Intraocular Pressure; Morpholines; Naphthalenes; Neuroprotective Agents; Ocular Hypertension; Piperidines; Pyrazoles; Rats; Rats, Sprague-Dawley; Receptor, Cannabinoid, CB1; Reperfusion Injury; Retinal Diseases; Retinal Ganglion Cells; Tonometry, Ocular | 2013 |
Involvement of the endocannabinoid system in retinal damage after high intraocular pressure-induced ischemia in rats.
To evaluate whether high intraocular pressure (IOP)-induced ischemia is associated with modifications in the retinal endocannabinoid metabolism and to ascertain whether drugs that interfere with the endocannabinoid system may prevent retinal damage due to ischemic insult.. Anandamide (AEA) synthesis, transport, hydrolysis, and AEA endogenous levels were assessed by means of high-performance liquid chromatography in the retinas of rats undergoing 45 minutes of ischemia followed by 12 hours of reperfusion. Under these experimental conditions, binding to cannabinoid (CB1R) and vanilloid (TRPV1) receptor was assessed with rapid-filtration assays. AEA-hydrolase (FAAH, fatty acid amide hydrolase), CB1R and TRPV1 protein content was determined by enzyme-linked immunosorbent assay. Finally, to characterize the neuroprotective profile of drugs that interfere with the endocannabinoid system, cell counting in the retinal ganglion cell (RGC) layer and real-time polymerase chain reactions for Thy-1 mRNA expression were used.. In rat retina, ischemic insult followed by reperfusion resulted in enhanced FAAH activity and protein expression paralleled by a significant decrease in the endogenous AEA tone, whereas the AEA-membrane transporter or the AEA-synthase NAPE-PLD (N-acyl-phosphatidylethanolamine-hydrolyzing-phospholipase-d) were not affected. Retinal ischemia-reperfusion decreased the expression of cannabinoid (CB1) and vanilloid (TRPV1) receptors. Systemic administration of a specific FAAH inhibitor (e.g., URB597) reduced enzyme activity and minimized the retinal damage observed in ischemic-reperfused samples. Similarly, intravitreal injection of the AEA stable analogue, R(+)-methanandamide, reduced cell loss in the RGC layer, and this was prevented by systemic administration of a CB1 or TRPV1 selective antagonist (e.g., SR141716 and capsazepine, respectively).. The original observation that retinal ischemia-reperfusion reduces endogenous AEA via enhanced expression of FAAH supports the deduction that this is implicated in retinal cell loss caused by high IOP in the RGC layer. Topics: Amidohydrolases; Animals; Arachidonic Acids; Benzamides; Cannabinoid Receptor Modulators; Capsaicin; Carbamates; Cell Count; Chromatography, High Pressure Liquid; Endocannabinoids; Enzyme Inhibitors; Enzyme-Linked Immunosorbent Assay; Hydrolysis; Intraocular Pressure; Male; Ocular Hypertension; Piperidines; Polyunsaturated Alkamides; Pyrazoles; Rats; Rats, Sprague-Dawley; Receptor, Cannabinoid, CB1; Reperfusion Injury; Retinal Diseases; Retinal Ganglion Cells; Retinal Vessels; Reverse Transcriptase Polymerase Chain Reaction; Rimonabant; RNA, Messenger; Thy-1 Antigens; TRPV Cation Channels | 2007 |