piperidines and Central-Serous-Chorioretinopathy

Serous chorioretinopathy has been associated with MEK inhibitors, including cobimetinib. We describe the clinical features of serous retinopathy observed with cobimetinib in patients with BRAF. In the coBRIM study, 493 patients were treated in two randomly assigned treatment groups: cobimetinib and vemurafenib (n = 247) or vemurafenib (n = 246). All patients underwent prospective ophthalmic examinations at screening, at regular intervals during the study, and whenever ocular symptoms developed. Patients with serous retinopathy were identified in the study database using a group of relevant and synonymous adverse event terms.. Eighty-six serous retinopathy events were reported in 70 patients (79 events in 63 cobimetinib and vemurafenib-treated patients vs seven events in seven vemurafenib-treated patients). Most patients with serous retinopathy identified by ophthalmic examination had no symptoms or had mild symptoms, among them reduced visual acuity, blurred vision, dyschromatopsia, and photophobia. Serous retinopathy usually occurred early during cobimetinib and vemurafenib treatment; median time to onset was 1.0 month. Most events were managed by observation and continuation of cobimetinib without dose modification and resolved or were resolving by the data cutoff date (19 Sept 2014).. Cobimetinib treatment was associated with serous retinopathy in patients with BRAF

Topics: Adult; Aged; Azetidines; Central Serous Chorioretinopathy; Female; Humans; Indoles; Male; Melanoma; Middle Aged; Mutation; Piperidines; Proto-Oncogene Proteins B-raf; Recurrence; Skin Neoplasms; Sulfonamides; Time Factors; Vemurafenib

To investigate the clinical and morphologic characteristics of serous retinal disturbances in patients taking mitogen-activated protein kinase kinase (MEK) inhibitors.. A total of 313 fluid foci in 50 eyes of 25 patients receiving MEK inhibitors for treatment of their metastatic cancer, who had evidence of serous retinal detachments confirmed by optical coherence tomography (OCT).. Single-center, retrospective cohort study.. Clinical examination and OCT were used to evaluate MEK inhibitor-associated subretinal fluid. The morphology, distribution, and location of fluid foci were serially evaluated for each eye. Choroidal thickness was measured at each time point (baseline, fluid accumulation, and fluid resolution). Two independent observers performed all measurements. Statistical analysis was used to correlate interobserver findings and compare choroidal thickness and visual acuity at each time point.. Comparison of OCT characteristics of retinal abnormalities at baseline to fluid accumulation.. The majority of patients had fluid foci that were bilateral (92%) and multifocal (77%) and at least 1 focus involving the fovea (83.3%). All fluid foci occurred between the interdigitation zone and an intact retinal pigment epithelium. The 313 fluid foci were classified into 4 morphologies, as follows: 231 (73.8%) dome, 36 (11.5%) caterpillar, 31 (9.9%) wavy, and 15 (4.8%) splitting. Best-corrected visual acuity at fluid resolution was not statistically different from baseline; and no eye lost more than 2 Snellen lines from baseline at the time of fluid accumulation. There was no statistical difference in the choroidal thickness between the different time points (baseline, fluid accumulation, and fluid resolution). A strong positive interobserver correlation was obtained for choroidal thickness measurements (r = 0.97, P < 0.0001) and grading of foci morphology (r = 0.97, P < 0.0001).. The subretinal fluid foci associated with MEK inhibitors have unique clinical and morphologic characteristics, which can be distinguished from the findings of central serous chorioretinopathy. In this series, MEK inhibitors did not cause irreversible loss of vision or serious eye damage.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Azetidines; Benzimidazoles; Central Serous Chorioretinopathy; Female; Fluorescein Angiography; Humans; Male; Middle Aged; Mitogen-Activated Protein Kinase Kinases; Neoplasms; Piperidines; Protein Kinase Inhibitors; Pyridones; Pyrimidinones; Retinal Detachment; Retrospective Studies; Subretinal Fluid; Tomography, Optical Coherence; Visual Acuity; Young Adult

Topics: Antineoplastic Agents; Azetidines; Central Serous Chorioretinopathy; Drug Therapy, Combination; Humans; Indoles; Male; Melanoma; Middle Aged; Piperidines; Recurrence; Skin Neoplasms; Sulfonamides; Treatment Outcome; Vemurafenib