ABSTRACT
Congenital myasthenic syndromes-5 (CMS5) is a rare autosomal recessive heterogeneous disorder, caused by pathogenic variants in the COLQ that lead to skeletal muscle weakness and abnormal fatigability. The onset is usually from birth to childhood. Disease-causing variants in the collagen-like tail subunit are the most explained etiology in synaptic CMS, causing defected acetylcholinesterase. In this study whole-exome sequencing (WES) was performed in an affected boy with muscle weakness, ophthalmoplegia, and bilateral ptosis and gene expression assay by qRT-PCR was performed in entire family. A homozygous nonsense variant in the COLQ [NM_005677.4:c.679C>T], (p.Arg227Ter) was identified in the proband. Segregation analysis by Sanger sequencing confirmed the homozygous state in the proband and heterozygous state in his parents and four of the siblings. The mRNA expression level in the proband was 0.02 of a healthy person, and in the carriers were 0.42 of a healthy person. This study presents an Iranian family with two affected children and eight symptomatic carriers with attenuated mRNA expression. This study provides evidence that carriers of the COLQ disease-causing variants could become symptomatic with some yet unknown pathogenesis mechanism and underscore the importance of further investigations to elucidate this mechanism.
ABSTRACT
PURPOSE: To compare the effects of accelerated corneal collagen cross-linking (CXL) in progressive keratoconus (KCN) patients via epithelium removal and transepithelial techniques, using Daya Disruptor (Duckworth and Kent, Hertfordshire, UK). METHODS: This study is a double-blinded, randomized clinical trial. Patients with documented bilateral progressive KCN were randomized into two groups: one eye underwent epithelium removal (Group 1), and the fellow eye underwent epithelium disruption (Group 2). The primary outcomes were best corrected visual acuity (BCVA) and uncorrected visual acuity (UCVA), Scheimpflug-extracted keratometric indices, and anterior segment-optical coherence tomography-derived epithelial thickness profiles. These parameters were evaluated before and 12 months after CXL. RESULTS: Sixty-four eyes from 34 patients with progressive KCN (34 eyes in the epithelium-removal group and 30 eyes in the epithelium-disruption group) were included. The mean ± standard deviation (SD) of age was 23.4 ± 3.8 years in the epithelium-removal group and 23.2 ± 3.5 years in the epithelium-disruption group. The mean ± SD of the preoperative spherical equivalent (SE), front maximum keratometry (K-max), back K-max, thickness of thinnest point, and corneal apex thickness were - 2.9 ± 3.0 diopter (D) and - 3.7 ± 3.1 D (P = 0.183), 53.8 ± 5.15 D and 54.4 ± 5.53 D (P = 0.653), -6.63 ± 2.40 D and - 6.68 ± 2.48 D (P = 0.131), 459.2 ± 37.4 µm and 460.8 ± 32.7 µm (P = 0.708), 470.5 ± 37.7 µm and 469.7 ± 33.1 µm (P = 0.679), and 55.4 ± 4.97 µm and 54.6 ± 7.16 µm (P = 0.767) in the epithelium-removal and epithelium-disruption groups, respectively. The mean ± SD changes of the UCVA and BCVA 12 months after CXL were - 0.1 ± 0.11 and - 0.02 ± 0.18 and - 0.04 ± 0.12 and - 0.02 ± 0.14 in the epithelium-removal and epithelium-disruption groups, respectively. No statistically significant improvement was observed in the UCVA and BCVA between the two groups (P = 0.868 and P = 0.937, respectively). The mean ± SD changes of the SE, superior epithelial thickness, corneal apex thickness, and thickness of thinnest point 12 months after CXL were - 0.21 ± 1.1 D and + 0.32 ± 1.6 D (P = 0.0001), -0.08 ± 0.26 µm and + 0.03 ± 0.33 µm (P = 0.028), -23 ± 11 µm and - 2 ± 6 µm (P = 0.0001), and - 25 ± 8 µm and - 3 ± 7 µm (P = 0.0001) in the epithelium-removal and epithelium-disruption groups, respectively. CONCLUSIONS: This study showed that the epithelium-disruption CXL using Daya has a similar potential for halting KCN progression as the epithelium-removal CXL. However, regarding the 12-month changes, the epithelium-disruption CXL is superior to the epithelium-removal CXL in the SE and corneal pachymetry.
ABSTRACT
PURPOSE: To compare epithelium-removal and epithelium-disruption corneal crosslinking (CXL) methods in Fourier analysis of keratometric data and clinical outcomes. METHODS: In this double masked randomized clinical trial, each eye of 34 patients with bilateral keratoconus was randomly allocated to either the epithelium-removal or epithelium-disruption CXL treatment groups. Ocular examination, refraction, uncorrected and best spectacle-corrected visual acuity (UCVA and BSCVA, respectively) measurements, and Pentacam imaging (keratometry, pachymetry, and Fourier analysis) were performed at baseline and at six-month follow-up period. RESULTS: Patients' mean age was 23.3 ± 3.6 years. The preoperative thickness of the thinnest point was 459.20 ± 37.40 µm and 455.80 ± 32.70 µm in the epithelium-removal and epithelial-disruption CXL groups, respectively (P > 0.05). The corresponding figures were 433.50 ± 33.50 µm and 451.90 ± 39.70 µm, respectively, six months after the treatment (P = 0.0001). Irregularity component of the fourier analysis was 0.030 ± 0.016 µm in the epithelium-removal group and 0.028 ± 0.011 µm in the epithelium-disruption group preoperatively (P > 0.05). This measurement was 0.031 ± 0.016 µm and 0.024 ± 0.009 µm, respectively at month 6 (P = 0.04). The epithelium-disruption CXL group had better results in terms of the thickness of the thinnest point and the irregularity component as compared to the epithelium-removal group. The two study groups were comparable in spherical equivalent, mean keratometry, UCVA, BSCVA, or other Fourier analysis components (spherical R min, spherical eccentricity, central, peripheral regular astigmatism, and maximum decentration) (P > 0.05). CONCLUSION: This study shows that epithelium-disruption CXL is superior to epithelium-removal CXL regarding the short-term changes in pachymetry and corneal irregularity. Other evaluated parameters were comparable between the two techniques.
ABSTRACT
Pterygium is one of the most common eye conditions without any clear etiology. Some studies have suggested an association between sun exposure and pterygium, but others have proposed the role of genetic variations in its pathogenesis. To date, no study has investigated the association of inflammatory transcription factor, NFκB genes with pterygium in the Middle East. We examined the changes in expression of 3 inflammatory related NFκB1, NFκB2, and RELA genes in patients with pterygium. Thirty patients with pterygium and 30 age and sex-matched controls were enrolled in this case-control study. None of the participants showed any clinical signs of inflammation in their conjunctiva. Demographic information was obtained and the expression levels of three genes including NFκB1, NFκB2, and RELA were measured in their conjunctiva by real-time RT-PCR using gene-specific primers. Mean expression level of NFκB1, NFκB2 and RELA genes in patients were 2.4±0.3, 1.9± 0.5, and 1.8±0.4 times higher than normal subjects, respectively. Higher levels of gene expression were observed in individuals with more outdoor activity and sun exposure. Moreover, a significant correlation was observed between the expression levels of NFκB2 and RELA genes, suggesting a possible NFκB2- RELA heterodimer formation in patients with pterygium. This study has indicated a significant association between expressions of inflammatory-related NFκB1, NFκB2 and RELA genes, and pterygium. Further studies to verify the role of inflammation in the pathogenesis of pterygium, may provide new targets for managing pterygia.
