A novel missense variant expands the phenotype and genotype of PAX6-associated foveal hypoplasia accompanied by various manifestations of anterior segment dysgenesis.

BACKGROUND: According to previous reports, PAX6-associated foveal hypoplasia (FH) could usually be accompanied by various anterior segment anomalies including variable iris changes. This study aims to exhibit unusual phenotypes of a novel missense variant of PAX6 from a Chinese pedigree. METHODS: Ophthalmic examinations including slit-lamp biomicroscopy, gonioscopy, ophthalmic ultrasound, ultrasonic biomicroscopy, optical coherence tomography, wide-field fundus imaging, and visual field test were performed to evaluate the clinical manifestations. Whole-exome sequencing (WES) and bioinformatics analysis were conducted in eight members from this pedigree to identify the causative mutation. RESULTS: WES revealed a novel heterozygous substitution of PAX6 (NM_000280.5:c.157G > A, p.(Val53Met) (chr11:31823309 C > T, hg19)), which cosegregated with the phenotype of this pedigree. All the three patients (a pair of fraternal twins and their mother) exhibited bilateral FH and anterior segment dysgenesis (ASD) including microcornea, sclerocornea, obvious symmetrical corectopia, iris stromal dysplasia, goniodysgenesis, and abnormal distribution of fundus blood vessels. The girl of the fraternal twins also demonstrated bilateral temporal deviation of lenses and abnormal tissue membrane connecting anterior chamber angle and lens anterior capsule in the right eye. The mother additionally showed apparent cataract bilaterally and cupping of the optic disc in her left eye. CONCLUSION: A novel missense variant in PAX6 gene was detected in a Chinese pedigree demonstrating bilateral FH and ASD. It is really distinctive that the ASD involves almost all parts of the anterior segment, and bilateral symmetrical corectopia is the most perceptible sign. This study expands the phenotypic and genotypic spectrum of PAX6-associated ocular diseases, and facilitates the understanding of the crucial role that PAX6 plays in the development of the eye. Meanwhile, PAX6 could be considered as a candidate pathogenic gene of bilateral symmetrical corectopia.

Analysis of Drug Clinical Trials for Eye Diseases in China.

Purpose: We systematically retrospected and analyzed the general characteristics of ophthalmic drug clinical trials (CTs) registered in China from January 2014 to December 2021. Methods: Data were retrieved from the Drug Trial Registration and Information Publication Platform and then standardized and statistically classified using bibliometric analysis. Results: We identified 201 drug CTs for eye diseases, including 24 international multicenter trials. The number of drug CTs for eye diseases has considerably increased since 2017 in parallel with new policies to encourage innovation in drugs and medical devices in China. The drug types consist of biologicals (48.26%), chemicals (45.77%), and traditional Chinese medicine/natural medicines (5.97%). The main indications were age-related macular degeneration (AMD; n = 47, 23.38%), macular edema (n = 32, 15.92%), and diabetic retinopathy (n = 19, 9.45%). The trials included those in phase I (n = 67, 33.33%), phase II (n = 33, 16.42%), and phase III (n = 72, 35.82%). The phase I trials comprised 24 innovative drug treatments for AMD and 6 novel drug treatments for neuromyelitis optica spectrum disorders, with 39 biologicals and 27 chemicals. The trials mostly followed a randomized (84.08%) or masked (67.16%) design, with 90.37% of the latter being double-masked trials. Conclusion: Research and development of ophthalmic drugs have substantially increased in recent years and are influenced by regulatory policies. Among these drugs, biologicals for AMD are the most prevalent, followed by biologicals for macular edema. Randomized double-masked research designs are often used and represent high-quality evidence.