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Achromatopsia is the most common cone dysfunction syndrome, affecting 1 in 30,000 people. It is an autosomal recessive disorder with a heterogeneous genetic background with variants reported in CNGA3, CNGB3, GNAT2, PDE6C, PDE6H, and ATF6. Up to 90% of achromatopsia patients harbour mutations in CNGA3 or CNB3, which encode for the alpha and beta subunits of the cone cyclic nucleotide-gated (CNG) channel in cone-specific phototransduction. The condition presents at birth or early infancy with poor visual acuity, nystagmus, photophobia, and colour vision loss in all axes. Multimodal retinal imaging has provided insightful information to characterise achromatopsia patients based on their genotype. There is no FDA-approved treatment for achromatopsia; however, studies have reported several preclinical gene therapies with anatomical and functional improvements reported in vivo. There are currently five gene therapy clinical trials registered for human patients at the phase I/II stage and for CNGA3 or CNGB3 causing achromatopsia. This review aims to discuss the genetics of achromatopsia, genotypic and phenotypic correlations in multimodal retinal imaging, and the developments and challenges in gene therapy clinical trials. [ABSTRACT FROM AUTHOR]

Age-related macular degeneration (AMD) is a growing public health concern given the aging population and it is the leading cause of blindness in developed countries, affecting individuals over the age of 55 years. AMD affects the retinal pigment epithelium (RPE) and Bruch's membrane in the macula, leading to secondary photoreceptor degeneration and eventual loss of central vision. Late AMD is divided into two forms: neovascular AMD and geographic atrophy (GA). GA accounts for around 60% of late AMD and has been the most challenging subtype to treat. Recent advances include approval of new intravitreally administered therapeutics, pegcetacoplan (Syfovre) and avacincaptad pegol (Iveric Bio), which target complement factors C3 and C5, respectively, which slow down the rate of enlargement of the area of atrophy. However, there is currently no treatment to reverse the central vision loss associated with GA. Optogenetics may provide a strategy for rescuing visual function in GA by imparting lightsensitivity to the surviving inner retina (i.e., retinal ganglion cells or bipolar cells). It takes advantage of residual inner retinal architecture to transmit visual stimuli along the visual pathway, while a wide range of photosensitive proteins are available for consideration. Herein, we review the anatomical changes in GA, discuss the suitability of optogenetic therapeutic sensors in different target cells in pre-clinical models, and consider the advantages and disadvantages of different routes of administration of therapeutic vectors. [ABSTRACT FROM AUTHOR]

Background Chronic kidney disease (CKD) increases the risk of cardiovascular disease (CVD) and is more prevalent in older adults. Retinal age gap, a biomarker of aging based on fundus images, has been previously developed and validated. This study aimed to investigate the association of retinal age gap with CKD and subsequent CVD complications. Methods A deep learning model was trained to predict the retinal age using 19 200 fundus images of 11 052 participants without any medical history at baseline. Retinal age gap, calculated as retinal age predicted minus chronological age, was calculated for the remaining 35 906 participants. Logistic regression models and Cox proportional hazards regression models were used for the association analysis. Results A total of 35 906 participants (56.75 ± 8.04 years, 55.68% female) were included in this study. In the cross-sectional analysis, each 1-year increase in retinal age gap was associated with a 2% increase in the risk of CKD prevalence [odds ratio 1.02, 95% confidence interval (CI) 1.01–1.04, P = .012]. A longitudinal analysis of 35 039 participants demonstrated that 2.87% of them developed CKD in follow-up, and each 1-year increase in retinal age gap was associated with a 3% increase in the risk of CKD incidence (hazard ratio 1.03, 95% CI 1.01–1.05, P = .004). In addition, a total of 111 CKD patients (15.81%) developed CVD in follow-up, and each 1-year increase in retinal age gap was associated with a 10% increase in the risk of incident CVD (hazard ratio 1.10, 95% CI 1.03–1.17, P = .005). Conclusions We found that retinal age gap was independently associated with the prevalence and incidence of CKD, and also associated with CVD complications in CKD patients. This supports the use of this novel biomarker in identifying individuals at high risk of CKD and CKD patients with increased risk of CVD. [ABSTRACT FROM AUTHOR]

A 75-year-old woman was admitted to a regional hospital with an acute kidney injury (AKI) and nausea on a background of recent treatment for Staphylococcus aureus bacteraemia secondary to pneumonia. The treatment thereof resulted in a high anion gap metabolic acidosis (HAGMA). The pneumonia was initially treated with intravenous piperacillin and tazobactam and the patient transferred to a tertiary hospital. There, the diagnosis of S. aureus bacteraemia secondary to a pulmonary source was confirmed and treatment was changed to intravenous flucloxacillin and the patient was discharged to hospital in the home (HITH is a service that allows short-term healthcare at home to be provided to people who would otherwise need to be in hospital) to complete the antibiotic course. Five weeks after commencing flucloxacillin, the patient was referred back to hospital with nausea and worsening kidney function with an associated significant HAGMA. The patient has a background of chronic kidney disease and chronic back pain for which she was taking long-term paracetamol. The HAGMA was determined to be due to a pyroglutamic acidosis (PGA), deemed secondary to the combined use of paracetamol and flucloxacillin. This was subsequently confirmed with a plasma pyroglutamic acid concentration level of 7467 μmol/L (reference range 20–50 μmol/L) and a urinary level of 1700 mmol/mol creatinine (<110 mmol/mol creatinine). To our knowledge, this is the highest plasma and urinary levels published to date. Furthermore, considering the common use of paracetamol and penicillins, it is important to recognise HAGMA as a potential complication of co-administration of paracetamol and iso-oxylopenicillin. The HAGMA resolved after cessation of flucloxacillin despite the continuation of paracetamol and without administration of N-acetylcysteine. PGA-related HAGMA appears to be a unique potential side effect of iso-oxylopenicillin rather than other beta-lactams. [ABSTRACT FROM AUTHOR]