BackgroundMitogen-activated protein kinase kinase (MEK) inhibitor cobimetinib and V-raf murine sarcoma viral oncogene homolog B1 (BRAF) inhibitor vemurafenib have significantly improved the prognosis of BRAF-mutated metastatic melanoma. Some ocular symptoms and signs were recently recognized to follow this treatment. The study was aimed to investigate ocular toxicity in patients with metastatic melanoma treated with cobimetinib in combination with vemurafenib.Patients and methodsIn the prospective, observational study, patients with BRAF-mutated metastatic melanoma treated with cobimetinib in combination with vemurafenib at the Institute of Oncology Ljubljana were asked to participate. Ophthalmic examination was performed including measurement of visual acuity and intraocular pressure, slit lamp examination, funduscopy (CF), infrared-reflectance (IR) imaging and optical coherence tomography (OCT).ResultsFive out of 7 patients noticed changes in vision few days after starting the therapy with cobimetinib. In all patients, small circular lesions, described as MEKAR lesions, were documented in outer retinal layers demonstrated with OCT, IR, and CF. Changes were in the center and/or scattered over the retina almost symmetrical in both eyes in 6 patients, and asymmetrical in one patient, the latter presented also with unilateral anterior uveitis and cystoid macular edema.ConclusionsMultiple bilateral foveal and extrafoveal small retinal lesions in the outer retinal layers develop in patients treated with MEK inhibitor in combination with BRAF inhibitor. Ophthalmologists and oncologists need to be aware of this common, yet relatively benign and often transient ocular side effect to avoid needless intervention, including the discontinuance of a potentially life-prolonging therapy.

BackgroundStored red blood cells (RBCs) accumulate biochemical and biophysical changes, known as storage lesion. The aim of this study was to re-challenge current data that anaemia in chronically anaemic haematology patients is not associated with low skeletal muscle tissue oxygen (StO2), and that RBC storage age does not influence the tissue response after ischaemic provocation, using near-infrared spectroscopy.Patients and methodsTwenty-four chronic anaemic haematology patients were included. Thenar skeletal muscle StO2 was measured at rest (basal StO2), with vascular occlusion testing (upslope StO2, maximum StO2) before and after transfusion.ResultsBasal StO2 was low (53% ± 7%). Average RBC storage time was 10.5 ± 3.9 days. Effects of RBC transfusions were as follows: basal StO2 and upslope StO2 did not change significantly; maximum StO2 increased compared to baseline (64 ± 14% vs. 59 ± 10%, p = 0.049). Change of basal StO2, upslope StO2 and maximum StO2 was negatively related to age of RBCs. The decrease of maximum StO2 was predicted (sensitivity 70%, specificity 100%), after receiving RBCs ≥ 10days old.DiscussionResting skeletal muscle StO2 in chronic anaemic patients is low. RBC storage time affects skeletal muscle StO2 in the resting period and after ischaemic provocation.

Pars plana vitrectomy (PPV) is a surgical approach mainly chosen for complex rhegmatogenous retinal detachment (RRD) repair with highly variable functional results. The aim of this analysis was to evaluate the impact of preoperative factors and postoperative optical coherence tomography (OCT) macular findings on the functional outcome of patients undergoing primary PPV for RRD. A retrospective analysis was performed on 88 eyes of 88 patients with complex RRD managed by PPV. A swept source OCT was used to obtain images at the postoperative visit at least 6 months after PPV. Hierarchical linear regression model was used to evaluate the influence of preoperative factors related to patient, ocular clinical and postoperative OCT macular findings on functional outcomes of PPV for RRD. Duration of symptoms (p = 0.031) and discontinuity of the ellipsoid zone (EZ) on OCT (p = 0.024) showed statistically significant negative correlation, while preoperative best-corrected visual acuity (BCVA; p < 0.001) showed statistically significant positive correlation to postoperative BCVA. Preoperative BCVA and duration of symptoms can be used as prognostic factors for visual outcome in patients undergoing PPV for RRD. Discontinuity of the EZ was the only postoperative OCT variable related to worse postoperative visual outcome.