Investing in vision: Innovation in retinal therapeutics and the influence on venture capital investment.

Since the groundbreaking approval of the first anti-VEGF therapy in 2004, the retinal therapeutics field has undergone a remarkable transformation, witnessing a surge in novel, disease-modifying therapeutics for a broad spectrum of retinal diseases, extending beyond exudative VEGF-driven conditions. The surge in scientific advancement and the pressing, unmet, medical need have captured the attention of venture capital investors, who have collectively invested close to $10 billion in research and development of new retinal therapeutics between 2004 and 2023. Notably, the field of exudative diseases has gradually shifted away from trying to outcompete anti-VEGF therapeutics towards lowering the overall treatment burden by reducing injection frequency. Simultaneously, a new era has emerged in the non-exudative field, targeting prevalent conditions like dry AMD and rare indications such as Retinitis pigmentosa. This has led to promising drug candidates in development, culminating in the landmark approval of Luxturna for a rare form of Retinitis pigmentosa. The validation of new mechanisms, such as the complement pathway in dry AMD has paved the way for the approvals of Syvovre (Apellis) and Izervay (Iveric/Astellas), marking the first two therapies for this condition. In this comprehensive review, we share our view on the cumulative lessons from the past two decades in developing retinal therapeutics, covering both positive achievements and challenges. We also contextualize the investments, strategic partnering deals, and acquisitions of biotech companies, pharmaceutical companies venture capital investors in retinal therapeutics, respectively. Finally, we provide an outlook and potentially a forward-looking roadmap on novel retinal therapeutics, highlighting the emergence of potential new intervention strategies, such as cell-based therapies, gene editing, and combination therapies. We conclude that upcoming developments have the potential to further stimulate venture capital investments, which ultimately could facilitate the development and delivery of new therapies to patients in need.

Paediatric outcomes and timing of admission.

Studies of adult patients have demonstrated that weekend admissions compared with weekday admissions had a significantly higher hospital mortality rate. We have reviewed the literature to determine if the timing of admission, for example, weekend or weekday, influenced mortality and morbidity in children. Seventeen studies reported the effect of timing of admission on mortality, and only four studies demonstrated an increase in those admitted at the weekend. Meta-analysis of the results of 15 of the studies demonstrated there was no significant weekend effect. There was, however, considerable heterogeneity in the studies. There were two large UK studies: one reported an increased mortality only for planned weekend admissions likely explained by planned admissions for complex conditions and the other showed no significant weekend effect. Two studies, one of which was large (n=2913), reported more surgical complications in infants undergoing weekend oesophageal atresia and trachea-oesophageal repair. Medication errors have also been reported to be more common at weekends. Five studies reported the effect of length of stay, meta-analysis demonstrated a significantly increased length of stay following a weekend admission, the mean difference was approximately 1 day. Those data, however, should be interpreted with the caveat that there was no adjustment in all of the studies for differences in disease severity. We conclude that weekend admission overall does not increase mortality but may be associated with a longer length of stay and, in certain conditions, with greater morbidity.