Retinopathy of prematurity is a devastating vascular disease of premature infants. A number of studies indicate that retinal function is affected in this disease. Using the rat model of oxygen-induced retinopathy, it is possible to explore more fully the complex relationship between neuronal, glial and vascular pathology in this condition. This review examines the structural and functional changes that occur in the rat retina following oxygen-induced retinopathy. We highlight that vascular pathology in rats is characterized by aberrant growth of blood vessels into the vitreous at the expense of blood vessel growth into the body of the retina. Moreover, amino acid neurochemistry, a tool for examining neuronal changes in a spatially complete manner reveals widespread changes in amacrine and bipolar cells. In addition, neurochemical anomalies within inner retinal neurons are highly correlated with the absence of retinal vessels. The key cell types that link blood flow with neuronal function are macroglia. Macroglia cells, which in the retina include astrocytes and Müller cells, are affected by oxygen-induced retinopathy. Astrocyte loss occurs in the peripheral retina, while Müller cells show signs of reactive gliosis that is highly localized to regions that are devoid of intraretinal blood vessels. Finally, we propose that treatments, such as blockade of the renin-angiotensin system, that not only targets pathological angiogenesis, but that also promotes re-vascularization of the retina are likely to prove important in the treatment of those with retinopathy of prematurity.

Background Heart failure (HF) is a major cause of morbidity and mortality. Sacubitril/valsartan has demonstrated reductions in HF hospitalisation, and all‐cause mortality in patients with heart failure with reduced ejection fraction. Aims To assess the tolerability and efficacy of sacubitril/valsartan in an intention to treat patient cohort. Methods Sixty‐five patients who were commenced on sacubitril/valsartan in 2017 at a major metropolitan centre in Victoria were retrospectively audited. Clinical outcomes and quality of life scores were obtained pre and post sacubitril/valsartan commencement through phone and regular clinic follow up, 6–12 months after commencement of sacubitril/valsartan. Results Fourteen percent of patients were able to achieve maximal dose (97/103 mg twice daily) whilst 37% remained on 49/51 mg and 23% on 24/26 mg. The mean systolic blood pressure reduced from 118 ± 18 mmHg to 109 ± 15 mmHg with symptomatic hypotension (30%) being the most common side‐effect leading to dose reduction or drug cessation. Left ventricular ejection fraction improved from 29.1 ± 9.7% to 33.8 ± 9.9% (P < 0.05) on drug. There was also a significant improvement in quality of life scores; EQ5D‐VAS 40 pre versus 67 post sacubitril/valsartan (P < 0.05), and New York Heart Association class (P < 0.05). Importantly, 10 patients lost an existing indication for device based therapy after treatment with sacubitril/valsartan. Conclusions Sacubitril/valsartan is a much needed therapeutic advancement in the treatment of HF. Our study indicates it is well tolerated with improvements in cardiac function and symptoms. Sacubitril/valsartan could redefine the definition of ‘optimal medical therapy’ when assessing patients for device based therapies.

No abstract

No abstract