ObjectiveTo investigate the relationship between genotype and phenotype in children with CRB1 mutated Leber congenital amaurosis (LCA) and early onset retinal dystrophy (EOSRD).MethodsA retrospective clinical study. From January 2013 to December 2019, 10 children with CRB1 mutated LCA/EOSRD were enrolled in the study. The patients were identified as CRB1 mutation by the second generation targeted capture sequencing, Sanger sequencing and the family segregation analysis. All children underwent electroretinogram (ERG) and fundus examination. At the same time, 6 cases were examined by optical coherence tomography (OCT); 1 case was examined by fluorescein fundus angiography (FFA), 7 cases were examined by wide-angle laser scanning ophthalmoscope (UWF SLO).ResultsThere were 6 cases of LCA and 4 cases of EOSRD in 10 patients with CRB1 gene mutations. The average age of first visit was 3.61 years old. The light and dark wave of ERG was flat in 6 cases, and decreased in 4 cases. A total of 19 pathogenic mutations were detected. There were 1 homozygous mutation and 9 compound heterozygous mutations. There were 4, 2 and 1 cases of “copper-coin” like, “salt and pepper” like and “osteocyte” like pigment changes in retina, 1 case of “crystalline pigment” change and 2 cases of macular pigment scar. In 7 cases of UWF SLO examination, different degrees of para-arteriolar pigment epithelium retention (PPRPE) were found in the middle and peripheral fundus. In 6 cases examined by OCT, the outer layer of retina atrophied and the band of ellipsoid disappeared. Symmetrical cystoid macular edema, splitting cystoid macular degeneration and adhesion of epi-macular membrane to optic disc and macular area were found in 1 case, respectively, the retinal structure was rough and thickened, and the fovea became thinner in 3 cases. In FFA examination, 1 case showed uveitis-like changes with late optic disc fluorescein staining, macular fluorescence accumulation, strong fluorescence diffusing along the blood vessels in each quadrant, peripheral PPRPE of “frost-branch” like strong fluorescence.ConclusionThe relationship between genotype and phenotype of CRB1 mutation is complex, and PPRPE is a common characteristic change.
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 observe the efficacy of dexamethasone intravitreal implant (DEX) combined with pars plana vitrectomy (PPV) in eyes with severe idiopathic epimacular membrane (IMEM). MethodsA prospective clinical case study. From December 2018 to May 2021, 24 patients with 25 eyes of severe IMEM diagnosed in Tianjin Medical University Eye Hospital were included in the study. Among them, 7 males had 7 eyes, 17 females had 18 eyes. Age was 57 to 84 years old. The IMEM stage was 3 to 4 examined by spectral domain optical coherence tomography (SD-OCT). All eyes were performed best corrected visual acuity (BCVA) and central macular thickness (CMT) by SD-OCT. The patients were randomly divided into PPV group (11 eyes) and PPV+DEX group (14 eyes). Standard PPV by three-channel 25G was performed. Phacoemulsification, membrane stripping and intraocular lens implantation were combined during the operation. Patients received vitreous injection of 0.7 mg DEX in PPV+DEX group at the end of the operation. At 1 week, 1 month, 3 months and 6 months after operation, the same equipments and methods were used to perform relevant examinations. The changes of BCVA and CMT were compared between the two groups by t test. ResultsCompared with before operation, at 1, 3 and 6 months after operation, the BCVA of the eyes in the PPV+DEX group was significantly improved (t=3.974, 4.639, 4.453), CMT was significantly decreased (t=2.955, 3.722, 4.364), the differences were statistically significant (P＜0.05); at 3 and 6 months after surgery, the BCVA of the eyes in the PPV group was significantly improved (t=2.983, 4.436), CMT was significantly decreased (t=2.983, 3.461), the differences were statistically significant (P＜0.05). ConclusionIn the treatment of severe IMEM, DEX can accelerate the early postoperative visual recovery and reduce CMT.