Photodynamic therapy combined with antivascular endothelial growth factor treatment for recalcitrant chronic central serous chorioretinopathy.

PURPOSE: To determine whether combination photodynamic therapy (PDT) and antivascular endothelial growth factor (VEGF) therapy is effective in the management of chronic central serous chorioretinopathy (CSC) recalcitrant to conventional therapy. METHODS: This was a retrospective analysis of eight patients with chronic CSC unresponsive to topical nonsteroidal anti-inflammatory drugs, focal photocoagulation, anti-VEGF alone, or PDT alone. All patients were evaluated with a full ophthalmic examination, spectral-domain optical coherence tomography (OCT), fluorescein angiography (FA), and most with indocyanine green angiography (ICGA) followed by treatment with half-fluence PDT and intravitreal anti-VEGF injection (seven bevacizumab, one aflibercept). Patients were seen in follow-up 1 month after treatment. RESULTS: All eight patients achieved complete resolution in subretinal fluid following combination treatment. Average duration of CSC prior to initiation of combination therapy was 7.5 months. Mean central macular thickness on OCT decreased significantly from 401.2±52.7 µm to 297.9±18.2 µm (p=0.0010) by 4 months after treatment (1.63±1.18 months). Seven of eight patients were followed up for an average of 13 months with no recurrence during that time. One case recurred at 8 months and was treated with repeat combination at that time. Frank choroidal neovascularization (CNV) was not identified in these cases on FA or ICGA studies. Eight of eight patients showed significant improvement in vision from a logMAR of 0.1125±0.099 to 0.0125±0.064 (p=0.019). CONCLUSION: Combination PDT and anti-VEGF is effective for chronic CSC which has failed conventional therapy. Associated CNV and/or inflammation may be reasons for greater success in patients treated with combination therapy.

Dynamic changes in intracellular ROS levels regulate airway basal stem cell homeostasis through Nrf2-dependent Notch signaling.

Airways are exposed to myriad environmental and damaging agents such as reactive oxygen species (ROS), which also have physiological roles as signaling molecules that regulate stem cell function. However, the functional significance of both steady and dynamically changing ROS levels in different stem cell populations, as well as downstream mechanisms that integrate ROS sensing into decisions regarding stem cell homeostasis, are unclear. Here, we show in mouse and human airway basal stem cells (ABSCs) that intracellular flux from low to moderate ROS levels is required for stem cell self-renewal and proliferation. Changing ROS levels activate Nrf2, which activates the Notch pathway to stimulate ABSC self-renewal and an antioxidant program that scavenges intracellular ROS, returning overall ROS levels to a low state to maintain homeostatic balance. This redox-mediated regulation of lung stem cell function has significant implications for stem cell biology, repair of lung injuries, and diseases such as cancer.