Bilateral Acute Proptosis With Papilledema and Sub-retinal Fluid As Initial Manifestations of Acute Lymphoblastic Leukemia in a Child.

A five-year-old boy presented with bilateral acute proptosis, papilledema, and sub-retinal fluid. Notably, choroidal thickening exceeded 600 microns. These ocular findings were the initial manifestations of acute lymphoblastic leukemia. This case underscores the importance of recognizing uncommon ocular presentations in pediatric leukemia for timely diagnosis and management.

Using computational approaches to enhance the interpretation of missense variants in the PAX6 gene.

The PAX6 gene encodes a highly-conserved transcription factor involved in eye development. Heterozygous loss-of-function variants in PAX6 can cause a range of ophthalmic disorders including aniridia. A key molecular diagnostic challenge is that many PAX6 missense changes are presently classified as variants of uncertain significance. While computational tools can be used to assess the effect of genetic alterations, the accuracy of their predictions varies. Here, we evaluated and optimised the performance of computational prediction tools in relation to PAX6 missense variants. Through inspection of publicly available resources (including HGMD, ClinVar, LOVD and gnomAD), we identified 241 PAX6 missense variants that were used for model training and evaluation. The performance of ten commonly used computational tools was assessed and a threshold optimization approach was utilized to determine optimal cut-off values. Validation studies were subsequently undertaken using PAX6 variants from a local database. AlphaMissense, SIFT4G and REVEL emerged as the best-performing predictors; the optimized thresholds of these tools were 0.967, 0.025, and 0.772, respectively. Combining the prediction from these top-three tools resulted in lower performance compared to using AlphaMissense alone. Tailoring the use of computational tools by employing optimized thresholds specific to PAX6 can enhance algorithmic performance. Our findings have implications for PAX6 variant interpretation in clinical settings.

The Royal College of Paediatrics and Child Health Retinopathy of Prematurity Screening Guidelines (2022): a series of treated infants falling outside the updated criteria.

BACKGROUND/OBJECTIVES: Screening for retinopathy of prematurity (ROP) is a core healthcare intervention in premature babies to avoid preventable sight loss. A variety of screening criteria are in place globally for this purpose. The Royal College of Paediatrics and Child Health recently updated the United Kingdom ROP screening guidelines (March 2022). A key change was the reduction in the gestational age (GA) to warrant retinal screening (from 32 to 31 weeks). SUBJECTS/METHODS: In the course of informal national surveillance during guideline development (2017-2022) and soon after, babies under our care falling outside the updated screening criteria who underwent treatment for ROP were identified. A retrospective case review was carried out. RESULTS: Six babies were identified as having undergone screening and treatment, prior to implementation of the new guidance. Screening and treatment would have been forfeited as per the March 2022 guidelines. All six had numerous systemic risk factors for developing ROP. Specifically, all had documented poor postnatal weight gain. CONCLUSIONS: We present this case series to bring forth an urgent discussion amongst key stakeholders as to whether the new guidance, as it stands, is safe and fit for purpose.