ObjectiveTo observe the changes of peripapillary vessel density and retinal nerve fiber layer parameters (RNFL) in diabetic mellitus (DM) patients with early diabetic retinopathy (DR).MethodsA retrospective clinical study. From January to December 2018, twenty-eight DM patients (47 eyes, DM group) and 20 normal subjects (40 eyes, control group) in Eye Hospital of Wenzhou Medical University at Hangzhou were included in the study. There was no significant difference between the two groups in age (t=－1.397, P=0.169) and sex composition ratio (χ2=0.039, P=0.843). The optic nerve head was scanned by OCT angiography (OCTA) with HD 4.5 mm ×4.5 mm imaging scanning mode for all subjects. The peripapillary radial peripapillary capillaries vessel density (ppVD) and peripapillary retinal nerve fiber layer (pRNFL) thickness were measured. The changes of ppVD and pRNFL thickness between the two groups were observed. Pearson correlation analysis was used to analyze the correlation between ppVD and pRNFL in each quadrant.ResultsCompared with the control group, the mean ppVD and superior-hemi part, inferior-hemi part, superior, nasal, inferior and temporal quadrant ppVDs of DM group were all significantly lower than those of control group (t=5.107, 4.360, 3.713, 4.007, 2.806, 4.046, 2.214; P＜0.05). The mean and all quadrants pRNFL thickness were lower in eyes of DM group compared with the control, and the superior and inferior quadrant pRNFL thickness were statistically significant (t=2.117, 2.349; P＜0.05), while the mean pRNFL and superior-hemi, inferior-hemi part, nasal and temporal quadrant were not statistically significant (t=1.867, 1.717, 1.869, 0.720, 0.303; P＞0.05). Pearson correlation analysis showed that the significant high-positive correlation was found between ppVD and pRNFL thickness in the nasal quadrant (r=0.734, P＜0.001).ConclusionIn early DR patients, ppVD decreased and pRNFL thinned.
ObjectiveTo observe and analyze the clinical phenotype and genetic characteristics of COL2A1 and COL11A1 de novo mutation (DNM) related Stickler syndrome type I and II patients. MethodsA family-based cohort study. From December 2023 to November 2024, 4 patients (all probands) with Stickler syndrome diagnosed by clinical and genetic testing in Department of Ophthalmology of People's Hospital of Ningxia Hui Autonomous Region and their parents (8 cases) were included in the study. The patients came from 4 unrelated families. A detailed medical history was taken, and the patients underwent best-corrected visual acuity (BCVA), refraction, and fundus color photography examinations. Systemic examinations included the oral and facial regions, skeletal, joints, and hearing. Peripheral venous blood samples were collected from the patients and their parents, and genomic DNA was extracted. Whole-exome sequencing was used to screen for pathogenic genes and their loci, which were then validated by Sanger sequencing and combined with segregation analysis in the families to identify candidate gene mutation sites. The candidate variants were assessed for pathogenicity according to the American College of Medical Genetics and Genomics (ACMG) criteria and guidelines for the classification of genetic variants. Additionally, cross-species conservation analysis was performed to determine the evolutionary conservation of wild-type amino acids, and protein three-dimensional modeling techniques were used to characterize the spatial conformational changes of the variant proteins and the alterations in their local hydrogen bond networks. ResultsAmong the 4 patients, there were 2 males and 2 females; their ages ranged from 3 to 12 years. There were 2 cases of Stickler syndrome type I (proband of families 1 and 2) and 2 cases of type II (proband of families 3 and 4). The diopters ranged from －8.00 to－11.0 D. BCVA ranged from no light perception to 0.6-. There were 2 cases each of vitreous membrane-like and “bead-like” opacity. Three cases showed peripapillary atrophy arcs and leopard pattern changes in the retina; one case had bilateral retinal detachment with a large macular hole in the left eye, which had previously been treated with vitrectomy surgery. One case had bilateral sensorineural hearing loss. There were 3 cases of simple micrognathia; one case had a flat nasal bridge, short nose, midface depression, and micrognathia. Two cases had excessive elbow joint extension. The phenotypes of the parents of the 4 patients were normal. Genetic testing results revealed that the probands of families 1 and 2 carried COL2A1 gene c.85+1G>C (M1) splice site variant and c.3950_3951insA (p.M1317Ifs*48) (M2) frameshift variant, respectively; the probands of families 3 and 4 carried COL11A1 gene (NM_001854.4) c.2549 G>T (p.G850V) (M3) missense variant and c.3816+6T>C (M4) splice site variant, respectively. The parents did not carry the related gene variants. Among them, M2, M3, and M4 are newly reported DNM. According to the ACMG guidelines, they were all considered likely pathogenic. The cross-species conservation analysis results showed that the wild-type amino acid of the COL11A1 gene M3 missense variant was highly conserved across multiple different species. Protein local structure modeling analysis revealed that the COL2A1 gene M2 frameshift variant and the COL11A1 gene M3 missense variant significantly altered the tertiary structure conformation of the protein, leading to abnormal spatial arrangement and hydrogen bond network in the key functional domains ConclusionThe COL2A1 gene M1 splice site variant, M2 frameshift variant, and the COL11A1 gene M3 missense variant, M4 splice site variant are respectively the potential pathogenic genes for families 1, 2, and families 3, 4; leading to the onset of Stickler syndrome type I in families 1 and 2, and type II in families 3 and 4.