Age-related macular degeneration (AMD) is the major cause of blindness in the elderly in developed countries and its prevalence is increasing with the aging population. AMD initially affects the retinal pigment epithelium (RPE) and gradually leads to secondary photoreceptor degeneration. Recent studies have associated mitochondrial damage with AMD, and we have observed mitochondrial and autophagic dysfunction and repressed peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α; also known as Ppargc1a) in native RPE from AMD donor eyes and their respective induced pluripotent stem cell-derived RPE. To further investigate the effect of PGC-1α repression, we have established a mouse model by feeding Pgc-1α+/− mice with a high-fat diet (HFD) and investigated RPE and retinal health. We show that when mice expressing lower levels of Pgc-1α are exposed to HFD, they present AMD-like abnormalities in RPE and retinal morphology and function. These abnormalities include basal laminar deposits, thickening of Bruch's membrane with drusen marker-containing deposits, RPE and photoreceptor degeneration, decreased mitochondrial activity, increased levels of reactive oxygen species, decreased autophagy dynamics/flux, and increased inflammatory response in the RPE and retina. Our study shows that Pgc-1α is important in outer retina biology and that Pgc-1α+/− mice fed with HFD provide a promising model to study AMD, opening doors for novel treatment strategies.

2064 Background: Recurrent glioblastoma (rGBM) following chemoradiation is associated with a poor prognosis. While bevacizumab is the most common salvage therapy, responses remain brief and without an associated survival benefit. Resistance may involve overexpression of Fatty Acid Synthase (FASN). Our institution is conducting a phase 2 study of bevacizumab with FASN inhibitor TVB-2640 in patients with GBM in first relapse. Methods: This is a prospective, phase 2 study of bevacizumab with TVB-2640 in patients with GBM in first relapse. Primary end point is progression free survival (PFS). Inclusion criteria are: age ≥ 18, ECOG 0 to 2, GBM progression following standard combined modality treatment. Randomization into two arms for the first 28 days is included for exploratory biochemical analysis: patients in arm 1 receive bevacizumab every 2 weeks in combination with TVB-2640; those in arm 2 receive bevacizumab alone every 2 weeks. MR-Spectroscopy (MRS) and serum sampling for exosome analysis are obtained on patients at day 1 and 28 of first cycle. Starting on cycle 2 day 1, all patients converge to a single arm and continue to receive bevacizumab in combination with TVB-2640. Results: We have enrolled 24 patients to date; 23 have started treatment. Of those 23 patients, 10 have died, 4 have progressed but are still alive, 2 withdrew, and 7 are still active on trial. The PFS6 is and OS9 are both currently 50%, which compares favorably with historical controls. There have been no reports of grade 4 or 5 treatment-related AEs (of note, 2 deaths were thought definitely unrelated to treatment, including 1 case of intracerebral hemorrhage, and 1 case of sepsis). There have been two cases of grade 3 hand-foot syndrome thought definitely related to treatment. Updated results will include PFS, response, and biomarker analysis (exosome, MRS). Conclusions: The combination of TVB2640 with bevacizumab appears be well tolerated. PFS6 and OS9 are both currently 50%. The study has completed accrual with final data expected later in 2019. Clinical trial information: NCT03032484.

Background: Central nervous system (CNS) neoplasms are relatively uncommon and potentially debilitating. From 1984-2012, there were around 200 new cases of malignant primary brain tumours each year in Hong Kong, and the trend has been static. To improve epidemiological reporting of CNS tumours in Hong Kong, the Hong Kong Cancer Registry (HKCaR) has established the brain and CNS tumour registry (BCTR) to collect all incident cases of primary malignant and non-malignant CNS tumours since 2013.Methods: The HKCaR is a population-based cancer registry in Hong Kong. Clinical records and pathology reports were obtained from public and private care providers with high coverage of 95%. These records were entered, cleansed and validated. Incidence of pathologically or clinically diagnosed CNS tumours with malignant, benign or uncertain behaviours were reported over the period of 2013-2017. The incidence were age-standardized with the 2000 US standard population and compared with US data from CBTRUS.Results: The age-standardised incidence of malignant and non-malignant brain tumours pooled over the period of 2013 to 2017 were 3/100,000 population and 8.6/ 100,000 population respectively. The top three most common types of malignant neoplasms were glioblastoma, other glial tumours and embryonal tumours; and in non-malignant neoplasms being meningioma, pituitary tumours and nerve sheath tumours. The incidence of both malignant and non-malignant tumours were around half of that in the US (7.08 and 16.33 per 100,000 population in the period of [2012][2013][2014][2015][2016]. The incidence of non-malignant and malignant brain tumours both increases significantly with age, with steep increment for non-malignant tumours starting from age of 45-64 and for malignant after the year of 65. The incidence rate in the whole population and in each age group has remained static over the reported years.Conclusions: Significant geographical differences in incidence of CNS tumours was observed between Hong Kong and the US. Under-diagnosis of brain tumour is unlikely due to easy access to public healthcare service and cross sectional imaging. The difference may be due to ethnic and environmental factors, which include higher rate of allergic conditions in Hong Kong which may confer protection. Further investigations are warranted.Legal entity responsible for the study: The authors.