METHODS: We utilized a combination of chromosome microarray, exome sequencing, and genome sequencing with structural variant and trio analysis to investigate a cohort of 41 predominantly sporadic cases.
RESULTS: We identified likely causative variants in 54% (22/41) of cases, including 51% (19/37) of sporadic cases and 75% (3/4) of cases initially referred as familial ASD. Two-thirds of sporadic cases were found to have heterozygous variants, which in most cases were de novo. Approximately one-third (7/22) of genetic diagnoses were found in rarely reported or recently identified ASD genes including PXDN, GJA8, COL4A1, ITPR1, CPAMD8, as well as the new phenotypic association of Axenfeld-Rieger anomaly with a homozygous ADAMTS17 variant. The remainder of the variants were in key ASD genes including FOXC1, PITX2, CYP1B1, FOXE3, and PAX6.
CONCLUSIONS: We demonstrate the benefit of detailed phenotypic, genomic, variant, and segregation analysis to uncover some of the previously "hidden" heritable answers in several rarely reported and newly identified ocular ASD-related disease genes.
METHODS: This is a double-blind randomized controlled hospital-based study involving diabetic patients with postoperative corneal epithelial defects after vitreoretinal surgery. Diabetic patients were randomized into 2 different groups and received either 0.5 units of topical insulin (DTI) or artificial tears (Vismed, sodium hyaluronate 0.18%; DAT). The primary outcome measured was the rate of corneal epithelial wound healing (mm 2 /h) over a preset interval and time from baseline to minimum size of epithelial defect on fluorescein-stained anterior segment digital camera photography. The secondary outcome measured was the safety of topical insulin 0.5 units and artificial tears (Vismed, sodium hyaluronate 0.18%). Patients were followed up until 3 months postoperation.
RESULTS: A total of 38 eyes from 38 patients undergoing intraoperative corneal debridement during vitreoretinal surgery with resultant epithelial defects (19 eyes per group) were analyzed. DTI was observed to have a significantly higher healing rate compared with the DAT group at rates over 36 hours ( P = 0.010), 48 hours ( P = 0.009), and 144 hours ( P = 0.009). The rate from baseline to closure was observed to be significantly higher in the DTI group (1.20 ± 0.29) (mm 2 /h) compared with the DAT group (0.78 ± 0.20) (mm 2 /h) as well ( P < 0.001). No adverse effect of topical insulin and artificial tears was reported.
CONCLUSIONS: Topical insulin (0.5 units, 4 times per day) is more effective compared with artificial tears (Vismed, sodium hyaluronate 0.18%, 4 times per day) for the healing of postoperative corneal epithelial defects induced during vitreoretinal surgery in diabetic patients, without any adverse events.