Long-term outcomes of anti-VEGF treatment with 5+PRN regimen for macular edema due to central retinal vein occlusion.

AIM: To assess the long-term outcomes of treating macular edema (ME) associated with central retinal vein occlusion (CRVO) with a regimen of "5+pro re nata (PRN)". METHODS: This retrospective study included 27 eyes of 27 patients with ME associated with non-ischemic CRVO (non-iCRVO group, n=15) and ischemic CRVO (iCRVO group, n=12). The eyes were treated with five consecutive intravitreal injections of conbercept or ranibizumab, followed by reinjections as needed or PRN. Retinal laser photocoagulation or intravitreal dexamethasone implants (DEX) were implemented in both groups when necessary. The best-corrected visual acuity (BCVA, logMAR) and central retinal thickness (CRT) were recorded at baseline, at 1, 2, 3, 4, 5, 6, and 12mo, and at the final visit. The efficacy rates of BCVA and CRT before and after treatment were calculated. The number of injections at each visit and the incidence of adverse events were also recorded. RESULTS: The patients, aged 59.4±15.1y, were followed up for 24.7±8.8mo (range: 15-42mo). After treatment, BCVA improved significantly from 1.04±0.56 logMAR at baseline to 0.59±0.36 logMAR (P=0.038) at the final visit in all patients. Both the non-iCRVO and the iCRVO groups achieved improved BCVA compared to the baseline at all visit points, but there was no statistical significance (P=0.197 and 0.33, respectively). The mean CRT was statistically reduced compared to baseline at all visit points in all the eyes and in both groups (all P<0.001). The apparent effective rate was 22.22% for BCVA and 37.04% for CRT after the first injection, 48.15% for BCVA and 62.96% for CRT after 5 consecutive injections, and 74.08% for BCVA and 100% for CRT at the end of follow up. The average number of injections in all patients was 9.0±2.4 at 12mo and 14.9±8.1 finally with no statistical significance between both groups (P>0.05). Laser treatment was applied to all eyes in the iCRVO group, while only 5 patients in the non-iCRVO group. Six patients in the non-iCRVO group and 3 patients in the iCRVO group had a drug switch. DEX was applied to 4 eyes in the non-iCRVO group and 5 eyes in the iCRVO group. CONCLUSION: The 5+PRN anti-vascular endothelial growth factor (VEGF) regimen is found to be safe and effective for both iCRVO and non-iCRVO, especially in the iCRVO group. The best regimen for such patients needs to be further investigated. Adjuvant laser therapy and DEX are necessary in some cases.

5-ALA-PDT induced ferroptosis in keloid fibroblasts via ROS, accompanied by downregulation of xCT, GPX4.

Keloids display many cancerous properties, including uncontrolled and invasive growth, high rates of recurrence as well as similar bioenergetics. 5-aminolevulinic acid-based photodynamic therapy (5-ALA-PDT) is an effective treatment that performs cytotoxic effects by producing reactive oxygen species (ROS), which is linked to lipid peroxidation and ferroptosis. Herein, we explored underlying mechanisms of 5-ALA-PDT against keloids. We identified that 5-ALA-PDT led to elevated levels of ROS and lipid peroxidation in keloid fibroblasts, accompanied by downregulation of xCT and GPX4, which are associated with anti-oxidation effects and ferroptosis inhibition. These results may indicate that 5-ALA-PDT treatment increases ROS while inhibiting xCT and GPX4, thus promoting lipid peroxidation to induce ferroptosis in keloid fibroblasts.

ALA-PDT regulates macrophage M1 polarization via ERK/MAPK-NLRP3 pathway to promote the early inflammatory response.

BACKGROUND: Photodynamic therapy (PDT) is a promising new approach to promote wound healing and its effectiveness has been demonstrated in both clinical and animal studies. Macrophages are the key cells in wound healing and inflammatory response. However, the mechanism of action of PDT on macrophages in promoting wound healing is still unclear. METHODS: In this study, RAW264.7 cells were used. We analyzed the expression levels of macrophage markers arginase 1 (Arg-1), CD206, iNOS, CD86, and inflammatory factors IL-6, TNF-α, and IL-1ß by reverse transcription-polymerase chain reaction and Western blot, Milliplex microtubule-associated protein multiplex assay was performed to analyze the expression of inflammatory factors in the supernatant. Live cell Imaging System to observe the dynamic process of macrophage phagocytosis. Western blot was performed to observe the activation of extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) and NOD-like receptor protein 3 (NLRP3) inflammasome. RESULTS: 5-Aminolevulinic acid (ALA)-PDT increased the expression of M1 marker iNOS/CD86 and decreased the expression of Arg-1/CD206 in RAW264.7 cells, while, proinflammatory factors IL-6, TNF-α, and IL-1ß expression was enhanced and macrophage phagocytosis was increased. We also found that these phenomena were associated with activation of the ERK/MAPK-NLRP3 pathway. CONCLUSION: ALA-PDT promotes early inflammatory responses by regulating macrophage M1 polarization through the ERK/MAPK-NLRP3 pathway. It also promotes macrophage phagocytosis.

Long-term outcomes of drusenoid pigment epithelium detachment in intermediate AMD treated with 577 nm subthreshold micropulse laser: a preliminary clinical study.

AIM: To evaluate the long-term anatomical and visual outcomes of drusenoid pigment epithelial detachment (D-PED) in intermediate age-related macular degeneration (AMD) eyes treated with 577 nm yellow subthreshold micropulse laser (SML). METHODS: In this retrospective study, 21 eyes of 16 patients with D-PED in intermediate AMD were consecutively included and assessed. All the eyes were treated with 577 nm SML in several sessions according to D-PED growth status. The logarithm of the minimum angle of resolution (logMAR) best-corrected visual acuity (BCVA) were assessed at the initial visit and after treatment. Spectral-domain optical coherence tomography (SD-OCT) was performed to evaluate the D-PED lifecycle by volumetric calculations. Regression analysis was used to determine the breakpoint, growth, and collapse rate of the D-PED lesions. The progression to advanced AMD was also documented. RESULTS: All the eyes were treated with SML for 2.9±1.0 sessions. The mean follow-up period was 25.3±12.6mo. The BCVA was stable from the baseline to final visit. All the eyes were categorized into two groups according to the anatomical changes of the D-PED lesion: the collapse group (n=6, 28.6%) and non-collapse group (n=15, 71.4%). The change in logMAR BCVA did not differ significantly between the collapse group 0.00 (-0.31, 0.85) and non-collapse group 0.00 (0.00, 0.00; P=1). Regression analysis showed that the growth rate was significantly higher in the collapse group (0.090±0.095 mm3/mo) than in the non-collapse group (0.025±0.035 mm3/mo; P<0.001). One eye (4.8%) developed macular neovascularization at 11mo after SML treatment in the non-collapse group. Three eyes (14.3%) developed geographic atrophy (GA) in the collapse group. CONCLUSION: Compared to the natural course of D-PED reported by previous studies, our results preliminarily show that SML can alleviate visual loss and possibility of progression to advanced AMD in eyes with D-PED in intermediate AMD. A controlled clinical trial needs to further verify the benefit of the intervention.