pyrimidinones and Central-Serous-Chorioretinopathy

Inhibitors of the mitogen-activated protein kinase (MAPK) signal pathway have decisively improved the prognosis of metastatic cutaneous melanoma in patients with an activating mutation in position V600 of the BRAF gene. We report on a patient who was regularly examined in our clinic while participating in a randomized blinded clinical trial. The aim of this trial was to examine the effectiveness and tolerability of a combination of the BRAF inhibitor dabrafenib and the MAPK kinase (MEK) inhibitor trametinib compared with a monotherapy with dabrafenib (plus placebo). During therapy the patient developed a diffuse neuroretinal detachment which could not be completely reversed after discontinuation of the study medication.

Topics: Antineoplastic Combined Chemotherapy Protocols; Central Serous Chorioretinopathy; Diagnosis, Differential; Female; Humans; Imidazoles; Melanoma; Middle Aged; Oximes; Pyridones; Pyrimidinones; Single-Blind Method; Skin Neoplasms; Treatment Outcome

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