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Precis: As new glaucoma treatments arise, including minimally invasive glaucoma surgeries and new classes of glaucoma medications, it is important to examine the prescription trends of current topical glaucoma medications and how they may change. Purpose: To determine the prescribing trends of topical glaucoma medications in Australia from 2001 to 2017. Methods and Analysis: Pharmaceutical Benefits Scheme (PBS) item numbers were used to determine glaucoma medication prescribing rates from 2001 to 2017. All data were adjusted for population (/100,000) as per the Australian Bureau of Statistics (ABS) population data. Results: Overall prescription rates for glaucoma medications ranged between 67,904 and 86,936 per 100,000 from 2001 to 2017. An upward trend was noted from 2001 to 2015, with the exception of a notable decline in 2013 by 14.7%, before then increasing by 13.7% in 2014. After 2015, prescribing rates were seen to decrease over the subsequent years in the study period. Latanoprost remained the most prescribed medication and prostaglandin the most prescribed class. Prescribing rates of single-agent beta-blockers were noted to decrease during the 17-year period, particularly with the introduction of combination agents, which note an upward trend. Brinzolamide/brimonidine has increased by 50.0% from 2016 to 2017. Conclusions: Total rates of prescriptions have remained relatively stable from 2001 to 2017. The number of medications prescribed when considering combination agents separately was seen to be increasing from 2001 to 2015. From 2015 to 2017, a downward trend was noted in the number of medications prescribed. Prostaglandins remain the most prescribed class throughout the study period.

Retinal neovascularization, or pathological angiogenesis in the retina, is a leading cause of blindness in developed countries. Pathological angiogenesis occurs through the complex activation of pro-inflammatory and pro-angiogenic pathways. Transforming growth factor-β-activated kinase 1 (TAK1) is a mitogen-activated protein kinase kinase kinase (MAPKKK) activated by TGF-β1 and other pro-inflammatory cytokines such as tumor necrosis factor α (TNFα) and interleukin-1 (IL-1). TAK1 is a key mediator of inflammation, innate immune responses, apoptosis and tissue homeostasis and plays an important role in physiological angiogenesis. Its role in pathological angiogenesis, particularly in retinal neovascularization, remains unclear. We investigated the regulatory role of TAK1 in pathological angiogenesis in the retina. Transcriptome analysis of human retina featuring retinal neovascularization revealed enrichment of known TAK1-mediated signaling pathways. Genetic or pharmacological inhibition of TAK1 activation in human endothelial cells induced by TNFα or IL-1 stimulation led to inhibition of phosphorylation of major kinases, including nuclear factor kappa B (NFκB) and mitogen-activated protein kinase (MAPK) signaling pathways. Suppression of this signaling, in turn, decreased expression of downstream genes associated with inflammation and angiogenesis, suggesting that TAK1 is required for these pathological processes. Transcriptome analysis of endothelial cells revealed that TAK1 knockout prevented inflammatory and immune responses induced by TNFα stimulation, mainly via cytokine and chemokine activity. Selective inhibition of TAK1 by 5Z-7-oxozeaenol in vitro ameliorated pro-angiogenic activity, including endothelial cell proliferation, migration and tube formation. Moreover, 5Z-7-oxozeaenol attenuated aberrant retinal angiogenesis in rats following oxygen-induced retinopathy. Our finding shows that TAK1 plays a key role in pathological angiogenesis in the retina. Selective inhibition of TAK1 prevents pathological angiogenesis, suggesting that TAK1 could be a potential therapeutic target for retinal neovascularization.GRAPHICAL ABSTRACT