Surgical Outcomes of Primary RRD With and Without Concurrent Full-Thickness Macular Hole (PRO Study Report No. 7).

BACKGROUND AND OBJECTIVE: Non-causal macular holes (MHs) can occur concurrently with rhegmatogenous retinal detachments (RRDs). The visual outcomes and surgical approach for these eyes are variable. PATIENTS AND METHODS: This was a multi-institutional, retrospective review of all primary retinal detachment surgeries from January 1, 2015, through December 31, 2015. Pre-, intra-, and postoperative metrics were recorded. RESULTS: There were 2,242 eyes that had pars plana vitrectomy for primary RRD, 43 (1.9%) of which had a MH at the time of surgery. The mean postoperative logMAR visual acuity (VA) for the MH cohort was 0.87 ± 0.64 (20/148) and for eyes without a MH was 0.47 ± 0.63 (20/59; P < .0001). The single-surgery re-attachment rate for the MH cohort and no MH cohort was 86.1% and 84.9%, respectively (P = 1.0000). CONCLUSIONS: Patients with noncausal MHs and RRD had significantly worse VA than patients without a MH. Preoperative counseling is imperative in patients with both RRD and MH. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:500-505.].

Combination therapy with vemurafenib (PLX4032/RG7204) and metformin in melanoma cell lines with distinct driver mutations.

BACKGROUND: A molecular linkage between the MAPK and the LKB1-AMPK energy sensor pathways suggests that combined MAPK oncogene inhibition and metabolic modulation of AMPK would be more effective than either manipulation alone in melanoma cell lines. MATERIALS AND METHODS: The combination of the BRAF inhibitor vemurafenib (formerly PLX4032) and metformin were tested against a panel of human melanoma cell lines with defined BRAF and NRAS mutations for effects on viability, cell cycle and apoptosis. Signaling molecules in the MAPK, PI3K-AKT and LKB1-AMPK pathways were studied by Western blot. RESULTS: Single agent metformin inhibited proliferation in 12 out of 19 cell lines irrespective of the BRAF mutation status, but in one NRASQ61K mutant cell line it powerfully stimulated cell growth. Synergistic anti-proliferative effects of the combination of metformin with vemurafenib were observed in 6 out of 11 BRAFV600E mutants, including highly synergistic effects in two BRAFV600E mutant melanoma cell lines. Antagonistic effects were noted in some cell lines, in particular in BRAFV600E mutant cell lines resistant to single agent vemurafenib. Seven out of 8 BRAF wild type cell lines showed marginally synergistic anti-proliferative effects with the combination, and one cell line had highly antagonistic effects with the combination. The differential effects were not dependent on the sensitivity to each drug alone, effects on cell cycle or signaling pathways. CONCLUSIONS: The combination of vemurafenib and metformin tended to have stronger anti-proliferative effects on BRAFV600E mutant cell lines. However, determinants of vemurafenib and metformin synergism or antagonism need to be understood with greater detail before any potential clinical utility of this combination.