Genetics behind Cerebral Disease with Ocular Comorbidity: Finding Parallels between the Brain and Eye Molecular Pathology.

Cerebral visual impairments (CVIs) is an umbrella term that categorizes miscellaneous visual defects with parallel genetic brain disorders. While the manifestations of CVIs are diverse and ambiguous, molecular diagnostics stand out as a powerful approach for understanding pathomechanisms in CVIs. Nevertheless, the characterization of CVI disease cohorts has been fragmented and lacks integration. By revisiting the genome-wide and phenome-wide association studies (GWAS and PheWAS), we clustered a handful of renowned CVIs into five ontology groups, namely ciliopathies (Joubert syndrome, Bardet-Biedl syndrome, Alstrom syndrome), demyelination diseases (multiple sclerosis, Alexander disease, Pelizaeus-Merzbacher disease), transcriptional deregulation diseases (Mowat-Wilson disease, Pitt-Hopkins disease, Rett syndrome, Cockayne syndrome, X-linked alpha-thalassaemia mental retardation), compromised peroxisome disorders (Zellweger spectrum disorder, Refsum disease), and channelopathies (neuromyelitis optica spectrum disorder), and reviewed several mutation hotspots currently found to be associated with the CVIs. Moreover, we discussed the common manifestations in the brain and the eye, and collated animal study findings to discuss plausible gene editing strategies for future CVI correction.

Latanoprostene Bunod 0.024% in the Treatment of Open-Angle Glaucoma and Ocular Hypertension: A Meta-Analysis.

Latanoprostene bunod (LBN) 0.024%, a newly approved glaucoma eye drop, is metabolized into latanoprost acid and a nitric oxide (NO)-donating moiety, thus increasing the outflow of aqueous humor through the uveoscleral and trabecular routes, respectively. This study aimed to evaluate the intraocular pressure (IOP)-lowering effect of LBN among patients with open-angle glaucoma (OAG) and ocular hypertension (OHT). The effectiveness of LBN was also compared with timolol maleate 0.5% and latanoprost 0.005%. We searched PubMed and Embase between 1 January 2010, and 31 March 2022 and adopted only peer-reviewed clinical studies in our meta-analysis. A total of nine studies (2389 patients with OAG or OHT) assessing the IOP-reduction effect of LBN were included. Standardized mean differences (SMDs) of IOP between post-treatment time points (2 weeks, 6 weeks, 3 months, 6 months, 9 months, and 12 months) and baseline were calculated. The pooled analysis according to each time point revealed a significant IOP drop after LBN treatment (all p values for SMD < 0.05). In addition, LBN revealed a significantly stronger efficacy in decreasing IOP than timolol maleate 0.5% and latanoprost 0.005% during the follow-up period of three months. No serious side effects of LBN 0.024% were reported. Our study concluded that LBN could achieve good performance for IOP reduction in patients with OAG and OHT. The safety was favorable with no severe side effects.

Risk of inflammatory bowel disease in uveitis patients: a population-based cohort study.

OBJECTIVES: To investigate the potential association between uveitis and an increased risk of developing inflammatory bowel disease (IBD). METHODS: We conducted a retrospective cohort study by interrogating data from the Taiwan National Health Insurance Research Database entered between January 1, 2001 and December 31, 2013 to identify uveitis patients and age- and gender-matched controls. The cumulative incidence rates of subsequent IBD in the two groups were compared. The adjusted hazard ratio (HR) of IBD related to uveitis was generated by a multivariate cox regression model after adjustment for hypertension, diabetes, hyperlipidaemia, obesity and smoking. Furthermore, the HRs of the Crohn's disease (CD) and ulcerative colitis (UC) IBD subtypes were calculated separately. RESULTS: A total of 198,923 subjects with uveitis and 397,846 controls were enroled. The mean age of the cohort was 47.7 ± 18.9 years. A significantly higher cumulative incidence of IBD was found in the uveitis group than in controls (4.13% vs. 1.48%, p < 0.0001). Under univariate cox regression analysis, uveitis patients had a significantly higher risk of IBD (HR = 1.47; 95% confidence interval (CI): 1.43-1.52, p < 0.0001). The association remained significant in the multivariate regression model, with an adjusted HR of 1.44 (95% CI: 1.39-1.49, p < 0.0001). Moreover, in subgroup analysis, uveitis was significantly associated with an increased risk of Crohn's disease (adjusted HR = 1.49; 95% CI: 1.44-1.54), but not with ulcerative colitis (adjusted HR = 1.03; 95% CI: 0.92-1.15). CONCLUSIONS: Patients with uveitis are at significantly greater risk of developing IBD than individuals without uveitis.

The risk of psoriasis in patients with uveitis: A nationwide population-based cohort study.

OBJECTIVE: To evaluate whether the risk of subsequent psoriasis and psoriatic arthritis development is increased in patients with uveitis. METHODS: In Taiwan's national health insurance research database, we identified 195,125 patients with new-onset uveitis between 2001 and 2013. We randomly selected 390,250 individuals without uveitis who were matched 2:1 to uveitis cases based on age, sex and year of enrolment. The characteristics of the two groups were compared. Using multivariate Cox regression, hazard ratios (HRs) for psoriasis or psoriatic arthritis corresponding to uveitis were computed after adjustment for age, sex, insurance cost and comorbidities. In subgroup analyses, separate HRs for mild psoriasis, severe psoriasis and psoriatic arthritis were calculated. RESULTS: The mean age of the study cohort was 50.2 ± 17.2 years. Hypertension, diabetes, hyperlipidaemia and obesity were more prevalent in the uveitis group (all p < 0.0001). The hazard of psoriasis or psoriatic arthritis development was significantly greater in the uveitis group than in the non-uveitis group (p < 0.0001); this increased risk persisted after adjustment for confounders [adjusted HR = 1.41; 95% confidence interval (CI), 1.33-1.48]. Adjusted HRs showed an increasing trend from mild psoriasis (1.35; 95% CI, 1.28-1.44) to severe psoriasis (1.59; 95% CI, 1.30-1.94) and psoriatic arthritis (1.97; 95% CI, 1.60-2.42). CONCLUSIONS: This nationwide population-based cohort study revealed that patients with uveitis have an increased risk of subsequent psoriasis or psoriatic arthritis development.

Ocular and Systemic Manifestations in Paediatric Multisystem Inflammatory Syndrome Associated with COVID-19.

This study aimed to achieve a better understanding of the epidemiological and clinical characteristics of multisystem inflammatory syndrome in children (MIS-C) following coronavirus disease 2019 (COVID-19). We searched PubMed and Embase between December 2019 and March 2021 and included only peer-reviewed clinical studies or case series. The proportions of patients who had conjunctivitis, systemic symptoms/signs (s/s), Kawasaki disease (KD), and exposure history to suspected/confirmed COVID-19 cases were obtained. Moreover, positive rates of the nasopharyngeal real-time reverse transcriptase polymerase chain reaction (RT-PCR) and serum antibody for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were recorded. Overall, 32 studies with 1458 patients were included in the pooled analysis. Around half of the patients had conjunctivitis. The five most common systemic manifestations were fever (96.4%), gastrointestinal s/s (76.7%), shock (61.5%), rash (57.1%), and neurological s/s (36.8%). Almost one-third presented complete KD and about half had exposure history to COVID-19 cases. The positivity of the serology (82.2%) was higher than that of the nasopharyngeal RT-PCR (37.0%). MIS-C associated with COVID-19 leads to several features similar to KD. Epidemiological and laboratory findings suggest that post-infective immune dysregulation may play a predominant role. Further studies are crucial to elucidate the underlying pathogenesis.