Rare single nucleotide variants in COL5A1 promoter do not play a major role in keratoconus susceptibility associated with rs1536482.

BACKGROUND: Keratoconus is a chronic degenerative disorder of the cornea characterized by thinning and cone-shaped protrusions. Although genetic factors play a key role in keratoconus development, the etiology is still under investigation. The occurrence of single-nucleotide polymorphisms (SNPs) associated with keratoconus in Russian patients is poorly studied. The purpose of this study was to validate whether three reported keratoconus-associated SNPs (rs1536482 near the COL5A1 gene, rs2721051 near the FOXO1 gene, rs1324183 near the MPDZ gene) are also actual for a Russian cohort of patients. Additionally, we investigated the COL5A1 promoter sequence for single-nucleotide variants (SNVs) in a subgroup of keratoconus patients with at least one rs1536482 minor allele (rs1536482+) to assess the role of these SNVs in keratoconus susceptibility associated with rs1536482. METHODS: This case-control study included 150 keratoconus patients and two control groups (main and additional, 205 and 474 participants, respectively). We performed PCR targeting regions flanking SNVs and the COL5A1 promoter, followed by Sanger sequencing of amplicons. The additional control group was genotyped using an SNP array. RESULTS: The minor allele frequency was significantly different between the keratoconus and control cohorts (main and combined) for rs1536482, rs2721051, and rs1324183 (p-value < 0.05). The rare variants rs1043208782 and rs569248712 were found in the COL5A1 promoter in two out of 94 rs1536482+ keratoconus patients. CONCLUSION: rs1536482, rs2721051, and rs1324183 were associated with keratoconus in a Russian cohort. SNVs in the COL5A1 promoter do not play a major role in keratoconus susceptibility associated with rs1536482.

Anterior vitreous detachment: risk factor for intraoperative complications during phacoemulsification.

PURPOSE: To confirm the presence of incomplete vitreolenticular adhesion via microscope-integrated intraoperative optical coherence tomography (iOCT) during cataract surgery and via diagnostic spectral-domain OCT (SD-OCT) postoperatively. SETTING: S. Fyodorov Eye Microsurgery Complex State Institution, Moscow, Russia. DESIGN: Prospective noninterventional single-center study. METHODS: Clinical characteristics and surgical videos of 27 patients (28 eyes) who had cataract surgery were documented. Real-time iOCT integrated into the surgical microscope was directed to view the retrolenticular anatomy at the end of the surgery. Postoperatively, SD-OCT was also performed. RESULTS: This study comprised 28 eyes of 27 patients. Berger space was identified in 21 cases (75%) intraoperatively via iOCT and in 23 cases (82%) postoperatively via stationary OCT. Depth dimensions varied from 33.5 ± 87.0 µm to 383.1 ± 226.3 µm. Hyperreflective dots and particles of different shapes and sizes were documented within Berger space in 16 cases (57%) intraoperatively and in 9 cases (32%) postoperatively. Capsular rupture occurred in 1 case due to excessive posterior capsular movement anteriorly. The posterior capsular rupture was converted into a posterior capsulorhexis, leaving the anterior hyaloid membrane intact. CONCLUSIONS: iOCT confirmed the penetration of crystalline lens microfragments, cellular material, or medical suspension (triamcinolone) into the space between the posterior lens capsule and the anterior hyaloid membrane. This occurs due to discontinuity of both lenticular zonules and Wieger ligament attachment. A Wieger ligament rupture can also allow excessive Berger space hydration during phacoemulsification leading to anterior displacement of the posterior lens capsule increasing the risk of instrument touch and posterior capsule rupture.

Dataset on transcriptome profiling of corneal endothelium from patients with Fuchs endothelial corneal dystrophy.

Fuchs endothelial corneal dystrophy (FECD) is a bilateral inherited eye disease with advanced forms only treatable by corneal transplantation. The pathogenesis of FECD has not been worked out yet, however, trinucleotide repeat polymorphism CTG18.1 in the TCF4 gene has recently been associated with late-onset FECD. Gene expression profiling of corneal endothelium with and without this expansion can help elucidate molecular mechanisms of the disease development. Current data article represents whole transcriptome profiles of corneal endothelium obtained from 12 patients with FECD and 6 control tissues from eye bank donors. RNA sequencing data is available at NCBI Sequence Read Archive under Accession No. PRJNA524323. In addition, each patient and donor were genotyped for CTG18.1 expansion and the corresponding numbers of CTG repeats in the TCF4 gene are provided within this article. The dataset includes samples from FECD patients both with and without CTG18.1 expansion.

CTG18.1 Expansion is the Best Classifier of Late-Onset Fuchs' Corneal Dystrophy Among 10 Biomarkers in a Cohort From the European Part of Russia.

Purpose: To assess the occurrence and diagnostic performance of nine single-nucleotide variants (SNVs) in the TCF4, SLC4A11, LOXHD1, and AGBL1 genes and the CTG18.1 trinucleotide repeat expansion in a Russian cohort of Fuchs' endothelial corneal dystrophy (FECD) patients. Methods: This retrospective case-control study included 100 patients diagnosed with FECD (cases) and 100 patients with cataracts (controls). Blood DNA was used to perform PCR and subsequent Sanger sequencing of rs613872 and rs17595731 in TCF4, c.99-100delTC, rs267607065, rs267607064, and rs267607066 in SLC4A11, rs113444922 in LOXHD1, and rs181958589 and rs185919705 in AGBL1. The number of CTG18.1 trinucleotide repeats was determined by a combination of conventional PCR or triplet primed PCR with fragment analysis. Results: At least one rs613872 marker allele was found in 78% of FECD patients and 21% of controls, and at least one rs17595731 marker allele was found in 14% and 2%, respectively. CTG18.1 trinucleotide expansion (>40 repeats) was detected in 72% of FECD patients and 5% of controls. Marker alleles of the tested SNVs in SLC4A11, LOXHD1, and rs185919705 in AGBL1 were not found in our FECD cohort. One FECD patient carried the marker allele of the rs181958589 SNV. Analysis of the diagnostic performance of individual markers in TCF4 and their combinations showed that the CTG18.1 repeat expansion was the best classifier for FECD (AUC = 0.84). Conclusions: Patients carrying CTG18.1 repeat expansion constituted a high proportion of the Russian FECD cohort; therefore, this marker is suitable for development of diagnostic and therapeutic approaches.