Prospective cholestanol screening of cerebrotendinous xanthomatosis among patients with juvenile-onset unexplained bilateral cataracts.

BACKGROUND: Cerebrotendinous xanthomatosis (CTX) is a rare genetic disorder related to CYP27A1 biallelic mutations, leading to decreased synthesis of bile acids and increased cholestanol. Juvenile bilateral cataracts are one of the most common findings in the disease, frequently occurring before the onset of neurological manifestations. While early treatment with chenodeoxycholic acid can prevent the onset of neurological impairment, poor awareness of CTX accounts for a markedly delayed diagnosis. The objective of this study was to evaluate the utility of plasma cholestanol analysis at the moment of cataract diagnosis and before the onset of neurological impairment in CTX. METHODS: Multicenter prospective cohort study of patients with juvenile-onset unexplained bilateral cataracts recruited from seven French ophthalmology departments. Plasma cholestanol analysis was performed at diagnosis from January 2018 to January 2020. CYP27A1 genetic testing was performed at the ophthalmologist's discretion. Cholestanol levels were compared with those of a similar population of patients without cataracts (control cohort). RESULTS: 30 patients were finally recruited, with a mean age at cataract diagnosis of 7.1 years (± 4.8 SD, range 1-19 years). One patient had a very high cholestanol level (68 µmol/L, reference < 10) and carried two pathogenic heterozygous mutations in CYP27A1 confirming CTX. This patient was a 19-year-old female, reporting chronic diarrhea only in childhood, and diagnosed with bilateral posterior cataracts with cortical fleck-like opacities. Therefore, the incidence of CTX in our cohort of patients was 3.3%. Five further patients (5/29; 17.2%) had moderate elevations of cholestanol level (between 10.3 and 16.5 µmol/L), compared to 12/286 (4.2%) in the control cohort (p = 0.014) after adjustment for age. CONCLUSION: Our study argue for the relevance of plasma cholestanol CTX screening in all patients with juvenile-onset unexplained cataracts, even without other CTX identified manifestations. Whether moderate elevations of plasma cholestanol unrelated to CTX may be a risk factor for bilateral cataracts occurrence needs further examination.

Diagnostic accuracy of Quantitative Colour Doppler Flow imaging in distinguishing Persistent Fetal Vasculature from Retinal Detachment.

PURPOSE: Distinguishing posterior persistent fetal vasculature (PFV) from retinal detachment (RD) may be very challenging clinically and ultrasonographically, as they share common morphological features. However, it is crucial, considering their substantially distinct management and treatment. We aimed to assess the relevance of quantitative colour Doppler flow imaging to distinguish PFV from RD in children. METHODS: This retrospective bi-centre study included 66 children (30 females and 36 males, mean age: 244 ± 257 days) with a clinically suspected diagnosis of RD or posterior PFV. All children underwent systematic and standardized conventional ultrasonography and colour Doppler flow imaging under general anaesthesia with a qualitative and quantitative analysis of the retrolental tissue's vascularization. Peak systolic velocity, end-diastolic velocity and resistive index were recorded for analysis. Whenever available, surgical findings were deemed gold standard for diagnosis. A Mann-Whitney U-test was used to compare quantitative colour Doppler flow imaging data. RESULTS: Peak systolic velocity and end-diastolic velocity were significantly lower in children with PFV versus RD: 2.7 (IQR: 0.5) versus 5.1 (IQR: 2.8), p < 0.001, and 0.0 (IQR: 0.0) versus 2.0 (IQR: 1.2), p < 0.001, respectively. Resistive index was significantly higher in children with PFV versus RD: 1 (IQR: 0) versus 0.6 (IQR: 0.1), p < 0.001. Area under curves (AUCs) were of 0.94, 0.99 and 1, respectively. No differences between PFV and RD were observed on structural ultrasound or qualitative analysis of colour Doppler. CONCLUSION: Quantitative colour Doppler flow imaging has an excellent accuracy in distinguishing PFV from RD in children. It may help to improve management and treatment.

Clinical, Meibographic, and Interferometric Evaluation in Children With Ocular Rosacea.

PURPOSE: To describe clinical, meibographic, and interferometric signs in children with ocular rosacea. DESIGN: Prospective case-control study. METHODS: This single-center study at the Fondation Ophtalmologique Rothschild (Paris, France) included 42 children with ocular rosacea and 44 healthy volunteers (median ages of 10 and 11 years old, respectively) who had infrared meibography images of their lower lids and tear lipid layer thickness measurements taken with the LipiView II device (Tearscience). Clinical severity was graded on a 0 to 4 scale and compared with meiboscores (range 0-4) and tear film lipid layer thickness (range 0-100 nm). RESULTS: Seven patients presented with unilateral disease and 29 had an asymmetrical form. Twenty-four patients had associated cutaneous rosacea. Ten of 84 eyes presented with a loss of vision <20/25. The mean clinical severity grade was 2.5 ± 1.4. Meibographic abnormalities were significantly more important in children with ocular rosacea (mean meiboscore 2.1 ± 1.36) than in healthy volunteers (0.61 ± 0.78, P < .001). Clinical severity (r = 0.44, P < .001), duration of disease (r = 0.28, P = .011), and a history of chalazia (r = 0.30, P = .006) were correlated to meibographic severity. Mean lipid layer thickness was not significantly different between cases and controls (74.4 ± 18.7 nm and 76.6 ± 18 nm, respectively, P = .47). CONCLUSION: Meibomian structural alterations in children can be severe and are correlated to ocular rosacea severity. Meibography is an essential tool for diagnosis and follow-up, whereas the contribution of tear film interferometry is uncertain.