Age-related macular degeneration (AMD) is an expanding problem as longevity increases worldwide. While inflammation clearly contributes to vision loss in AMD, the mechanism remains controversial. Here we show that neutrophils are important in this inflammatory process. In the retinas of both early AMD patients and in a mouse model with an early AMD-like phenotype, we show neutrophil infiltration. Such infiltration was confirmed experimentally using ribbon-scanning confocal microscopy (RSCM) and IFNλ− activated dye labeled normal neutrophils. With neutrophils lacking lipocalin-2 (LCN-2), infiltration was greatly reduced. Further, increased levels of IFNλ in early AMD trigger neutrophil activation and LCN-2 upregulation. LCN-2 promotes inflammation by modulating integrin β1 levels to stimulate adhesion and transmigration of activated neutrophils into the retina. We show that in the mouse model, inhibiting AKT2 neutralizes IFNλ inflammatory signals, reduces LCN-2-mediated neutrophil infiltration, and reverses early AMD-like phenotype changes. Thus, AKT2 inhibitors may have therapeutic potential in early, dry AMD.
Purpose:To study the utility and predictive ability of newer macular hole (MH) indices for closure following surgery.Methods:In this retrospective study, pre- and post-operative optical coherence tomography images of 49 eyes with idiopathic full-thickness MH were reviewed and analysed. Various quantitative parameters of MH like maximum outer diameter (OD), minimum diameter between edges, height, nasal and temporal arm lengths, macular hole angle were noted. Indices including hole form factor, Macular Hole Index, (MHI), Diameter Hole Index (DHI) and Tractional Hole Index (THI) were calculated. Newer area indices like macular hole area index (MAI), cystoid space area index (MCSAI) and tissue area index (MTAI) were calculated using Image J (Ver. 1.51). Receiver operating characteristic (ROC) curves and cut-off values were derived for indices predicting type 1 or type 2 closure. Stepwise regression analysis and binary logistic regression analysis were carried out to predict the chances of hole closure.Results:ROC curve analysis showed indices like MHI, THI and MCSAI were capable of successfully predicting type 1 closure while OD, DHI and MAI predicted type 2 closure. On stepwise regression analysis, MAI was identified as the most important index in predicting the type of hole closure. Using the binary logistic regression analysis, the predictive ability of the model to identify success or failure following MH surgery was 89.7% and 80% respectively.Conclusion:MAI measurement could be used as a single important index in predicting hole closure in idiopathic MH. Further research is required to study this area index in detail.
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