Ocular manifestations of CHARGE syndrome in a pediatric cohort with genotype/phenotype analysis.

CHARGE syndrome is a rare multi-system condition associated with CHD7 variants. However, ocular manifestations and particularly ophthalmic genotype-phenotype associations, are not well-studied. This study evaluated ocular manifestations and genotype-phenotype associations in pediatric patients with CHARGE syndrome. A retrospective chart review included pediatric patients under 20 years-old with clinical diagnosis of CHARGE syndrome and documented ophthalmic examination. Demographics, genetic testing, and ocular findings were collected. Comprehensive literature review enhanced the genotype-phenotype analysis. Forty-two patients (20 male) underwent eye examination at an average age of 9.45 ± 6.52 years-old. Thirty-nine (93%) had ophthalmic manifestations in at least one eye. Optic nerve/chorioretinal colobomas were most common (38 patients), followed by microphthalmia (13), cataract (6), and iris colobomas (4). Extraocular findings included strabismus (32 patients), nasolacrimal duct obstructions (11, 5 with punctal agenesis), and cranial nerve VII palsy (10). Genotype-phenotype analyses (27 patients) showed variability in ocular phenotypes without association to location or variant types. Splicing (10 patients) and frameshift (10) variants were most prevalent. Patients with CHARGE syndrome may present with a myriad of ophthalmic manifestations. There is limited data regarding genotype-phenotype correlations and additional studies are needed.

Self-Reported Visual Disability and Unemployment: Findings from the National Health Interview Survey.

PURPOSE: To investigate the association between visual impairment and employment status due to disability, utilizing data from the 2022 National Health Interview Survey (NHIS). METHODS: Adults 18 years of age and older were extracted from the 2022 NHIS dataset. A multivariable logistic regression model was created to evaluate the odds of unemployment ("laid off" and "looking for work"). Persons over the age of 65, as well as persons retired, going to school, self-employed, seasonal, or contract workers were excluded. Independent variables for the model included gender, race, Hispanic ethnicity, urban residency, level of education, citizenship, and self-reported vision. The latter variable was categorized as seeing with "some" difficulty, with "severe" difficulty, "can't see at all," and "a lot of difficulty." Outcomes were reported as odds ratios (OR) with 95% confidence intervals (CI). RESULTS: Associations with unemployment included education less than high school (OR 6.05, 95% CI: 3.98-9.18) and high school (OR 3.80, 95% CI 2.78-5.21); severe vision difficulty (OR 3.68 95% CI 1.73-7.86); Asian race (OR 2.53, 95% CI 1.64-3.89); and Black race (OR 1.78, 95% CI 1.31-2.41). The odds of unemployment were marginally elevated for those living in large metropolitan areas, while being born in the United States had a modest protective effect (OR 0.53, 95% CI 0.42-0.66). CONCLUSION: The degree of visual impairment in this post-COVID-19 pandemic survey substantially affects employment, which is consistent with historical studies. Education among those with impaired vision is an important and modifiable variable that can positively influence the chances of employment.

Predictors of Therapy Success in Weekly Adalimumab for Refractory Uveitis: A Retrospective Cohort Study.

PURPOSE: To determine predictors of treatment success after dose escalation of adalimumab, including measurement of anti-adalimumab antibodies as a predictor of success DESIGN: Retrospective clinical cohort study SETTING: Single-center academic institution STUDY POPULATION: Patients with noninfectious uveitis who were inadequately controlled or developed recurrent disease on biweekly adalimumab and required dose escalation or therapy modification OBSERVATION PROCEDURES: Patients who had anti-adalimumab antibodies checked with resultant low to intermediate levels were compared to patients who had no testing performed prior to adalimumab dose escalation. Of note, patients with testing and resultant high levels of anti-adalimumab antibodies were not escalated. Predictors of escalation success and utility of antibody testing prior to escalation were analyzed using Kaplan Meier survival analysis and Cox proportional hazard models. MAIN OUTCOME MEASURES: Treatment success defined as anterior chamber grade ≤0.5+ cell, topical corticosteroids ≤1 drop/day, oral prednisone ≤5 mg/day, resolution of macular edema, and resolution of angiographic signs of inflammation without any addition or escalation of therapy. RESULTS: 24 patients had antibodies tested with low to intermediate levels (average: 32.3 ng/mL, range: 0 - 154), while 41 did not have antibody testing. A greater treatment success rate post escalation was observed among the "low antibody" group compared to the "no testing" group (HR: 2.63, standard error: 1.19, p=0.031, 95% CI 1.09 - 6.37). Among the entire cohort, patients with panuveitis (n = 14) had a lower treatment success rate compared to the reference of anterior uveitis (n = 26) (HR: 0.09, standard error: 0.11, p = 0.05, 95% CI 0.01 - 0.99). CONCLUSIONS: Patients with low anti-adalimumab antibodies had a greater treatment success compared to patients in whom antibodies were not checked. This suggests a utility to checking antibodies prior to dose escalation and that low levels of antibodies may confer a success advantage. Overall, patients with panuveitis had a lower rate of success after escalation while patients with anterior uveitis patients had a very high rate of success suggesting that certain disease characteristics may guide clinicians when determining who to escalate versus changing therapy.

Cardiovascular disease: extraintestinal manifestation of inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a spectrum of diseases characterized by the interplay of the aberrant immune system, genetic factors, environmental factors, and intestinal microbiota, resulting in relapsing inflammation of the gastrointestinal tract. Underlying pro-inflammatory state and immune dysregulation act as a catalyst for increasing the likelihood of developing extraintestinal manifestations, including cardiovascular diseases (CVD) like atherosclerosis, pericarditis, myocarditis, venous and arterial thromboembolism, arrhythmias, despite a lower prevalence of classic CVD risk factors, like high body mass index or dyslipidemia compared to the general population. Chronic inflammation damages endothelium resulting in the recruitment of inflammatory cells, which induce cytotoxicity, lipoprotein oxidation, and matrix degradation, which increases the risk of atherosclerosis. Additionally, intestinal dysbiosis disrupts the intestinal mucosal barrier, releasing endotoxins and lipopolysaccharides into circulation, further exaggerating the atherosclerotic process. Abnormal collagen metabolism and alteration of nitric oxide-mediated vasodilation lead to blood pressure dysregulation in patients with IBD. Therefore, it is essential to make lifestyle modifications like smoking cessation, dietary changes, and increasing physical activity with adherence to medication to mitigate the risk of developing CVD in patients with IBD. This article reviews the potential links between IBD and the increased risk of CVD in such individuals.