Familial exudative vitreoretinopathy (FEVR) is a hereditary retinal vascular dysplasia. So far, 6 genes have been found to be associated with FEVR: Wnt receptor Frizzled Protein 4, Norrie's disease, co-receptor low-density lipoprotein receptor-related protein 5, tetraspanin 12, zinc finger protein 408, and kinesin family members 11 genes. Its clinical manifestations, pathological processes and genetic patterns are diverse, and it shows the relationship between gene polymorphism and clinical manifestation diversity. It is characterized by different symptoms between the same individual, the same family, and the same gene mutation; different clinical stages and gene mutation types of parents or unilateral genetic children; different clinical characteristics and gene mutation patterns of full-term and premature infant; combined with other eye disease and systemic diseases; double gene mutations and single gene mutations have different clinical manifestations and gene mutation characteristics. A comprehensive understanding of the different clinical manifestations and diverse genetics of FEVR can provide better guidance for the treatment of FEVR.
The fundus appearance of polypoidal choroidal vasculopathy (PCV) often demonstrates orange-red nodular lesions. ICGA reveals terminal dilation of the polyps with or without branching vascular networks. Currently, pachychoroid spectrum disease is a series of conditions included choroidal vasodilatation and increased permeability due to choroidal ischemia, choroidal thickening, retinal pigment epitheliopathy, and secondary pigment epithelial detachment, choroidal neovascularization and polyps included uncomplicated pachychoroid, pachychoroid pigment epitheliopathy, pachychoroid neovascularization, central serous chorioretinopathy, and PCV. These entities have the similar characteristics and prognosis, suggesting that they have the similar pathology. The recognition of PCV based on the pachychoroid spectrum disease can provide new ideas for the prevention and intervention of PCV.
ObjectiveTo observe and analyze the genotype and clinical phenotype in 34 families of familial exudative vitreoretinopathy associated with (FEVR) gene variation.MethodsCohort study. Thirty-four FEVR families, in which the patients and both of their parents were all found to have FEVR-related gene mutations (proband 34 cases, 67 eyes; parents 68 cases, 136 eyes), were included in the study. These patients were identifIed from 722 FEVR patients through genetic screening, which diagnosed in Department of Ophtalmology of Xinhua Hospital and Tianjin Medical University Eye Hospital from January 2010 to December 2018. The probands and their parents underwent a comprehensive ophthalmological examination appropriate to their age, including BCVA, intraocular pressure, axial length, slit lamp examination, indirect ophthalmoscopy, FFA or color fundus photography or wide field color fundus photography. According to the severity of the disease, the clinical manifestations were divided into severe phenotype and mild phenotype. Thirty-four normal healthy people over 40 years old were included as the control group. The peripheral blood samples of FEVR family members and control group members were collected, and the genes known to be involved in FEVR, such as FZD4, LRP5, NDP, TSPAN12, ZNF408 and KIF11, were analyzed by next generation sequencing molecular genetics. The data were statistically analyzed by SPSS. The counting data was expressed in numbers or rates, and tested by Kruskal-Wallis test and χ2 test to find out the existence of significant difference.ResultsIn 67 eyes of the 34 probands, 48 eyes (71.64%) were classified into severe phenotype and 19 eyes (28.36%) were mild phenotype. In 136 eyes of 68 parents of the proband patients, 76 eyes (55.88%) were normal, 60 eyes (44.12%) were classified into mild phenotype, and no severe phenotype was found. A total of 65 variants of FEVR-related genes were detected in the 34 probands, of which LRP5 mutation was the most common (64.61%), followed by FZD4 (12.31%), NDP (10.77%), TSPAN12 (6.15%), ZNF408 (4.62%) and KIF11 (1.54%). Missense mutations were the most common variant in FEVR-related genes. However, the results of correlation analysis indicated that there was no significant correlation between the type of mutation and the severity of clinical phenotype (H=1.775, P=0.620). Among the 65 mutation types, 21 types have been previously identified and 44 were novel in this study. Thirty-nine eyes of 20 cases had only one single pathogenic mutation gene but with multiple mutation sites, 26 eyes of 13 cases carried 2 relevant pathogenic mutation genes, and 2 eyes in one case had 3 pathogenic mutation genes. The mutation frequencies of LRP5, NDP, ZNF408, FZD4, TSPAN12 and KIF11 genes in probands were significantly higher than those in control group, and the difference was statistically significant. The total mutation frequencies of LRP5, NDP, ZNF408, FZD4, TSPAN12 and KIF11 genes in proband group were significantly higher than those in control group (χ2=64.702, P＜0.001).ConclusionsIn the FEVR families, the most frequent mutations were those in LRP5, followed by FZD4, NDP, TSPAN12,ZNF408 and KIF11. Missense mutation is the most common type of FEVR-related gene mutation, but there is no significant correlation between the clinical phenotype and gene variation type. Most of the probands were with severe clinical phenotype, while most of the parents with FEVR pathogenic gene mutation showed normal or mild manifestations.
Objective To observe the surgical outcome of the modified transconjunctival technique for minimal segmental buckling on rhegmatogenous retinal detachment (RRD). Methods This is a retrospective case series. Seventy-six patients (78 eyes) with uncomplicated RRD who underwent the modified transconjunctival technique for minimal segmental buckling were enrolled in this study. There were 41 male (42 eyes) and 35 female (36 eyes). The average age was (33.9±15.6) years. Best corrected vision acuity (BCVA), fundus examination with three-mirrors lens, ocular B ultrasound, optical coherence tomography (OCT) were performed in all patients. BCVA was examined through Standard logarithmic visual acuity chart and transferred to logMAR vision for statistical analysis. The logMAR BCVA was 0.88±0.88. The technique was successfully performed in all 78 eyes. After transconjunctival location of the retinal break was made, a 5 to 6 mm radial conjunctival incision was performed corresponding to the retinal break without cutting the limbal conjunctiva–Tenon’s capsule. After cryopexy, a minimal explant was fixed with one to two sutures through the conjunctival opening, expanded by a pediatric speculum. BCVA, intraocular pressure, tear film stability, conjunctival recovery and retinal reattachment were collected 1 week, 1 month, 3 months, 6 months after surgery. Results One week after surgery, retinal reattachments were achieved in 77 of 78 (98.7%) eyes and 1 eye (1.3%) received vitrectomy. Compared before surgery, the logMAR BCVA improved to 0.44±0.41, with significant difference (t=3.092, P＜0.01). Conjunctival incision tear occurred in 1 eye. Subretinal hemorrhage occurred in 5 eyes during subretinal fluid drainage procedure. Subretinal hemorrhage occurred in 5 eyes during subretinal fluid drainage procedure. Hemorrhage was absorbed in 2 of the 5 eyes at 3 months after surgery and absorbed in all 5 eyes at 6 months after surgery. Subretinal fluid occurred in 10 eyes at 1 week after surgery and be absorbed completely at 6 months after surgery. Tear film stability improved to preoperative lever at 1 week after surgery. Less change in corneal and conjunctival sensitivity was observed in all eyes. No other surgical complications were observed within the follow-up period, such as scleral perforation, explant extrusion, diplopia or infection. Conclusions The modified transconjunctival technique for minimal segmental buckling minimizes the damage to conjunctiva without reducing the retinal reattachment rate. It can effectively treat uncomplicated RRD with preserving an intact limbal conjunctiva and rapid tear film stability recovery.
ObjectiveTo observe and analyze the multimodal imaging characteristics of fundus in patients with sympathetic ophthalmia (SO). Methods A retrospective study. From October 2012 to December 2021, 28 patients (36 eyes) diagnosed SO in the Department of Ophthalmology, Beijing Tongren Hospital were inclued in the study. There were 19 males (25 eyes) and 9 females (11 eyes), with the mean age of 51.61±12.02 years. There were 8 exciting eyes and 28 sympathizing eyes. The time to onset after trauma or surgery was 46.10±107.98 months. All patients underwent examinations including vision test, color fundus photograph, optical coherence tomography (OCT), fundus fluorescence angiography (FFA), indocyanine green angiography (ICGA). Angio-OCT (OCTA) was performed on 3 eyes and fundus autofluorescence (AF) was performed on 8 eyes. The early and late phase were defined respectively as ≤2 months and ＞2 months. Their multimodal imaging characteristics were summarized. ResultsIn 8 exciting eyes, subretinal fibrosis with mutifocal retinal atrophy and pigmentation was noted in 5 eyes (62.50%, 5/8), the other 3 eyes showed sunset glow fundus (37.50%, 3/8). In 28 sympathizing eyes, in the early phase, the fundus photograph showed shallow retinal detachment with optic disc edema in 9 eyes (32.14%, 9/28); in the late phase, peripapillary yellowish-white subretinal lesions in 11 eyes (39.29%, 11/28). In the late course of the disease, there were yellow-white lesions around the optic disc (peridisc) and peripheral subretinal area in 11 eyes (39.29%, 11/28). Dalen-Fuchs nodules were found in 10 eyes (35.71%, 10/28). On OCT, multiple serous retinal detachment and irregular choroidal folds were noted in the early phase; hill-like subretinal hyperreflective elevation was noted in peripapillary area and subfovea with presence of cystic spaces in the intraretina in the late phase. FFA examination showed "pinpoint-like" strong fluorescence in the early stage, and "multi-lake-like" fluorescein accumulation and leakage in the late stage; "map-like" weak fluorescence around the disc in the early stage of the disease, dot-like strong fluorescence lesions in each quadrant of the peripheral retina, and fluorescence in the late stage of the disease course. enhanced. ICGA examination showed that the FFA strong fluorescence lesions in the middle and late stages were weak fluorescence. FAF examination, point-like strong and weak autofluorescence lesions with unclear boundaries. Nine sympathizing eyes with subretinal yellow-white lesions has vision without light-0.1 (significantly decreased vison), while 8 eyes with sunset glow fundus was 0.5-1.0 (mildly decreased vison). ConclusionsSO could not only show the semblable features of acute phases of Vogt-Koyanagi-Harada syndrome, but also the yellowish-white lesions in the peripapillary area, macula and periphery. Most of the eyes with peripapillary lesions has a significantly decreased vison, while the eyes with sunset glow fundus has a mildly decreased vison.
The incidence of myopia is increasing year by year and the trend of younger age is obvious. The situation of myopia prevention and control is very serious. The sclera is the target organ for the development of myopia. When myopia occurs and develops, the ultrastructure of the sclera tissue will undergo pathological changes, resulting in a decrease in its tensile strength, then progressive axial growth and posterior sclera expansion. Scleral collagen cross-linking can effectively increase the hardness and tensile strength of scleral tissue, which may have great potential in the prevention and control of myopia, especially pathological myopia. At present, the effectiveness of scleral collagen cross-linking technology in the prevention and treatment of pathological myopia researches are still in the stage of animal experiments, and there are a lot of controversies on the safety. The development of any new technology to ensure safety is the primary condition. A comprehensive understanding of the safety of scleral collagen crosslinking in the prevention and control of myopia can provide more basis and guidance for the further study of scleral collagen crosslinking.
Objective To investigate the clinical manifestations and gene mutation of a pedigree with retinal lattice degeneration and granular corneal dystrophy (GCD) type 2. Methods Ten members in 3 generations of a pedigree with retinal lattice degeneration and GCD2 were included in the study, including 6 patients (3 males and 3 females) and 4 healthy family members. All members underwent visual acuity, slit lamp microscope, three-mirror lens, fundus color photography, optical coherence tomography, and corneal endothelial cells counting. Genomic DNA was extracted from peripheral venous blood (2 ml) from all the subjects and their spouses, who had no related inherited diseases. The next generation sequencing method was used to detect the mutation sites of transforming growth factor β (TGFBI), and all results underwent Sanger verification. Results Among the 12 eyes of 6 patients, the visual acuity was FC/20 cm-1.0. In the superficial central corneal stroma, snowflake-like deposits were observed in three cases (6 eyes), and a small amount of granular deposits were observed in three cases (6 eyes). Corneal endothelial cell counts were normal. Retinal lattice degeneration were observed in 3 cases, 6 eyes (including 3 cases of rhegmatogenous retinal detachment in 4 eyes); retinal thinning without obvious lattice degeneration in 4 eyes of 2 patients. Nystagmus in 1 patient and fundus examination showed no significant abnormalities. DNA sequencing results showed that the proband and 4 patients had missense mutation of TGFBI gene in exon 4 c.371G＞ A, the mutation site corresponding to the amino acid change encoded by TGFBI gene No. 124 Amino acids, from arginine to histidine (p.R124H). Patients with this mutation have varying degrees of clinical phenotype. Conclusions The mutation of c.701G＞ A (p.R124H) in TGFBI gene is the causative gene of GCD in this pedigree. The patients with this mutation have different clinical phenotypes.
ObjectiveTo investigate the changes in the nerve fiber layer of the cornea in patients with demyelinating optic neuritis (DON) and its correlation with visual acuity. MethodsA cross-sectional study. From March 2021 to July 2022, 27 cases (39 eyes) of DON patients diagnosed in the Department of Neurology and Ophthalmology of Beijing Tongren Hospital Affiliated to Capital Medical University were enrolled in this study. According to the serological test results, the patients were divided into aquaporin 4 antibody associated optic neuritis (AQP4-ON group) and myelin oligodendrocyte glycoprotein antibody associated optic neuritis (MOG-ON group), with 15 cases (19 eyes) and 12 cases (20 eyes) respectively. According to previous history of glucocorticoid treatment, the patients were divided into glucocorticoid treated group and non-glucocorticoid treated group, with 17 cases (27 eyes) and 10 cases (12 eyes) respectively. Twenty healthy volunteers (20 eyes) with age- and gender-matched were selected as the control group. All eyes underwent best corrected visual acuity (BCVA) and in vivo confocal microscopy (IVCM) examinations. BCVA was performed using Snellen's standard logarithmic visual acuity chart, which was converted into logarithmic minimum angle resolution (logMAR) visual acuity during statistics. The corneal nerve fiber length (CNFL), corneal nerve fiber density (CNFD), corneal nerve fiber branch length (CNBL), corneal nerve fiber branch density (CNBD) and the density of corneal dendritic cells (DC) were detected by IVCM examination. Parameter comparison between groups by t-test and Kruskal-Wallis rank sum test. The correlation between logMAR BCVA and pamameters of corneal nerve fibers were analyzed using Spearman analysis. ResultsThe CNFL, CNFD, and CNBL of the DON group and the control group were (10.67±2.55) mm/mm2, (57.78±12.35) root/mm2, (3.27±1.34) mm/mm2, and (13.74±3.05) mm/mm2, (70.95±13.14) root/mm2, and (4.22±1.03) mm/mm2, respectively; the difference in CNFL, CNFD, and CNBL between the two groups were statistically significant (t=4.089, 3.795, 2.773; P＜0.05). The CNFL, CNBL, and CNBD of the affected eyes in the MOG-ON group and AQP4-ON group were (12.02±2.13) mm/mm2, (3.80±1.19) mm/mm2, (47.97±8.86) fibers/mm2, and (9.25±2.19) mm/mm2, (2.72±1.19) mm/mm2, (39.43±13.86) fibers/mm2, respectively; the differences in CNFL, CNBL, and CNBD between the two groups were statistically significant (t=－4.002, －2.706, －2.306; P＜0.05). The corneal DC density of the patients in the hormone treated group and the non-hormone treated group was (24.43±8.32) and (41.22±9.86) cells/mm2, respectively. The difference in corneal DC density between the two subgroups was statistically significant (P＜0.001). Correlation analysis showed that there was a significant negative correlation between logMAR BCVA and CNBL and CNFL in patients with DON (r=－0.422, －0.456; P＜0.05). ConclusionsThere are different degrees of corneal nerve fiber damage in patients with different types of DON. There was a negative correlation between BCVA and the length of corneal nerve fibers.