ObjectiveTo observe the clinical characteristics of primary retinitis pigmentosa (RP) complicated with glaucoma.MethodsA retrospective clinical study. From June 2008 to March 2020, the diagnosis of primary RP were included in the diagnosis confirmed by the eye examination of West China Hospital of Sichuan University included 4794 eyes of 2432 patients. Among them, 4679 eyes (97.2%, 2364/2432) were in 2364 cases with RP alone, and 115 eyes were in 68 cases with RP combined with glaucoma (2.80%, 68/2432). All affected eyes underwent best corrected visual acuity (BCVA) and intraocular pressure examination. The BCVA examination was carried out using the international standard visual acuity chart, which was converted into the logarithmic minimum angle of resolution (logMAR) visual acuity during statistics. The 67 eyes of 40 patients with RP and glaucoma with complete follow-up data were analyzed to observe the proportion of different glaucoma types, logMAR BCVA, intraocular pressure and other clinical characteristics, as well as treatment methods and post-treatment intraocular pressure control. After treatment, the intraocular pressure ≤21 mm Hg (1 mm Hg=0.133 kPa) was regarded as intraocular pressure (IOP) control; ＞21 mm Hg was regarded as uncontrolled IOP.ResultsAmong the 67 eyes of 40 cases with complete follow-up data, 5 cases (7 eyes) with primary open-angle glaucoma (10.45%, 7/67), 56 cases (58 eyes) with angle-closure glaucoma (ACG) (86.57%, 58/67), 4 cases (4 eyes) with neovascular glaucoma (5.97%, 4/67), 2 of them had both ACG and neovascular glaucoma. Among 58 ACG eyes, 17 eyes were acute ACG (25.37%, 17/67), 21 eyes were chronic ACG (31.34%, 21/67), and 2 eyes were suspicious angle closure (2.99%, 2/67), lens dislocation secondary to angle-closure glaucoma in 8 eyes (11.94%, 8/67), chronic angle-closure glaucoma after anti-glaucoma surgery, intraocular lens shift in 5 eyes (7.46%, 5/67), 5 eyes (7.46%, 5/67) secondary to glaucoma with true small eyeballs. The logMAR BCVA 3.50 of the affected eye,＜3.50-＞2.00, ≤2.00-≥1.30,＜1.30-＞1.00, ≤1.00-0.52,＜0.52 were 9 (13.43%, 9/67), 30 (44.78%, 30/ 67), 7 (10.45%, 7/67), 4 (5.97%, 4/67), 11 (16.42%, 11/67), 6 (8.96%, 6/67) eyes, which correspond to mean intraocular pressure were 32.31±11.67, 30.15±14.85, 28.17±13.19, 31.50±17.25, 18.71±8.85, 14.12±4.25 mm Hg. Among 67 eyes, 37eyes (55.22%, 37/67), 18eyes (26.86%, 18/67), and 6 (8.96%, 6/67) eyes underwent surgery, medication alone, and peripheral iris laser perforation treatment, respectively. The treatment of 6 eyes was abandoned (8.96%, 6/67). Malignant glaucoma occurred in 3 eyes (8.11%, 3/37) after the operation, all of which were after trabeculectomy of the ACG eye. After treatment, intraocular pressure was controlled in 37 eyes (55.22%, 37/67), 19 eyes were not controlled (28.36%, 19/67), and 11 eyes were lost to follow-up (16.42%, 11/67).ConclusionsThe incidence of glaucoma in patients with primary RP is 2.80%. ACG is more common, and the combined lens dislocation or intraocular lens shift is more common.
ObjectiveTo investigate and analyze the relationship between genotype and phenotype in patients with early-onset high myopia (eoHM) associated with hereditary eye diseases. MethodsA family-based study was conducted among 30 families diagnosed with eoHM at Department of Ophthalmology of People's Hospital of Ningxia Hui Autonomous Region from January 2022 to June 2023. Seven families (23.3%, 7/30), all probands, and their 14 parents were included. These seven families were unrelated. Detailed patient and family histories were collected. All participants underwent comprehensive ophthalmic examinations, including best-corrected visual acuity, color vision testing, fundus color photography, optical coherence tomography, fluorescein fundus angiography, and fundus autofluorescence imaging. Full-field electroretinography was performed in four cases. Peripheral venous blood samples were collected from patients and their parents for whole-genome DNA extraction and whole-exome sequencing. Potential pathogenic variants were identified, and their pathogenicity was analyzed and confirmed by Sanger sequencing. The pathogenicity of newly discovered gene variants was evaluated according to the guidelines of the American College of Medical Genetics and Genomics (ACMG). Literature on previously reported eoHM associated with hereditary eye diseases was reviewed to analyze the relationship between variant genes and clinical phenotypes. ResultsAmong the seven families, three exhibited X-linked inheritance, two showed autosomal recessive inheritance, and two demonstrated autosomal dominant inheritance. All the patients were male. Among the seven patients, one case each was identified with congenital stationary night blindness (CSNB), Bornholm eye disease, X-linked retinitis pigmentosa (XL-RP), cone-rod dystrophy, Knobloch syndrome, familial exudative vitreoretinopathy (FEVR), and Stickler syndrome. Genetic testing revealed nine gene variants highly correlated with the observed phenotypes. The genetic testing results revealed that all patients were found to carry nine gene variants highly associated with the phenotype, including: a hemizygous missense variant NYX c.647A>T (p.N216I) (M1), an OPN1LW LIAVA haplotype variant (M2), a hemizygous frameshift variant RPGR c.3096_3097del (p.E1033RfsTer45) (M3), compound heterozygous variants TTLL5 c.1588_1589del (p.L531EfsTer24) and c.850G>C (p.D284H) (M4, M5), compound heterozygous variants COL18A1 c.2118dup (p.G707RfsTer23) and c.3523_3524del (p.L1175VfsTer72) (M6, M7), a heterozygous missense mutation FZD4 c.1499C>T (p.T500I) (M8), and a heterozygous frameshift variant COL11A2 c.966dup (p.T323HfsTer19) (M9). Among them, M2, M4, M5, M8 and M9 were newly discovered mutation sites, and M1, M3, M6 and M7 were known mutation sites. According to the classification standards and guidelines of genetic variation issued by ACMG, M2, M3, M4, M6, M7, and M9 were judged to be pathogenic variants, while M1, M5, and M8 were of unknown clinical significance. Through literature review, it was found that eoHM was more common among the clinical phenotypes of 4 types of hereditary retinal diseases, including CSNB, Stickler syndrome, FEVR and XL-RP. ConclusioneoHM is intricately associated with inherited eye diseases and may serve as the earliest indicator of such conditions.
Retinitis pigmentosa is a hereditary disease which is characterized by damage in retinal photoreceptor cells and retinal pigment epithelium. Its main clinical features include low vision with night blindness, progressive visual field defects, and abnormal electroretinograms. The development of gene sequencing, the diagnosis and treatment methods of retinitis pigmentosa update year by year, including gene therapy, stem cell therapy, optogenetic therapy, etc. However, there is still a big gap in these treatments from laboratory technology into effective clinical treatment drugs. Some problems which include immune response, potential mutagenesis and tumorigenesis of the inserted region, genetic toxicity, quality and stability of gene technology and stem cell technology, mass production and promotion of clinical grade drugs, and optimization of the effectiveness of drugs and surgery, etc, remain to be solved by researchers.
ObjectiveTo identify the causative genes of the posterior microphthalmia-retinal pigment degeneration family. MethodsA retrospective clinical study. One child (proband) and 3 family members of a family with posterior microphthalmia-retinitis pigmentosa diagnosed by clinical and genetic examination at Henan Provincial People's Hospital in July 2019 were included in the study. Medical history and family history, and draw pedigree of the patients was collected. Visual acuity, visual field, fundus color photography, optical coherence tomography and electroretinogram (ERG) were examined. The peripheral venous blood of the proband, his parents and sister, and extract the whole genome DNA was collected. Whole-exome sequencing was used to detect genetic variations, the suspected pathogenic variations were verified by Sanger sequencing, and the pathogenicity was determined by bioinformatics analysis. ResultsThe parents discovered the proband was poor vision at the age of 10 months. At the age of 3, the best corrected visual acuity of the right eye and the left eye were 0.3 and 0.4, respectively. No abnormality was found in anterior segment. Extremely high hyperopia in both eyes. The axial length was 14.47 mm and 15.78 mm, respectively. The optic disc of both eyes was relatively small and flushed, retinal folds can be observed in macular area, and no obvious pigment deposition was found. ERG examination showed that the rod system response and the maximal combined response of both eyes decreased slightly to moderately, and the single-flash cone response and the 30 Hz flicker response decreased moderately to severely. Genetic analysis revealed two novel mutations in the membrane frizzled-related protein (MFRP) gene in the proband: c.363delC/p.Thr121Thrfs*16, c.1627C＞T/p .Gln543Stop,37 in exon 4 and 13, the former was a frameshift mutation, encoding 16 amino acids and then terminated, and the latter was an nonsense mutation, truncated 37 amino acids, both which were predicted to be pathogenic and segregate with disease. The mother and sister carried c.363delC, and the father carried c.1627C＞T. ConclusionMFRP gene c.363delC/p.Thr121Thrfs*16, c.1627C＞T/p.Gln543Stop, 37 compound heterozygous mutation may be the pathogenic gene of this family.
ObjectiveTo analyze the subfoveal choroidal thickness in retinitis pigmentosa (RP) patients and to evaluate the correlation between the subfoveal choroidal thickness (SCT) and visual function. MethodsTotally 42 RP patients (84 eyes) and 49 age and diopter-matched normal controls (98 eyes) were enrolled in this study. All the patients were taken the enhanced depth imaging technique of optical coherence tomography (EDI-OCT) examination for the measurement of the SCT. The covariate analysis was used to analyze the interaction effect between age and group. Then the SCT was amended. The RP patients were examined by 30°visual field test (T32 or LVC program) and electroretinogram (ERG) test. 32 eyes examined by T32 program, 52 eyes examined by LVC program. The waveform of ERG, mean sensitivity (MS) and mean defect (MD) were recorded. The relationship of SCT, MS and MD were analyzed by Pearson correlation analysis. ResultsThe SCT of RP patients and controls were (223.12±69.59), (288.29±52.36) μm. The covariate analysis of covariance with different age group interaction was not statistically significant (F=1.619, P=0.205), as amended SCT of RP patients and controls were (217.34±6.60), (293.20±6.00) μm, respectively. The SCT was decreased in RP patients (t=7.042, P < 0.001). Among 84 eyes, bright cone response weaken in 35 eyes, scotopic rod response weaken in 31 eyes. The difference of SCT in different ERG waveform was not significant (t=-0.976, -1.584; P=0.332, 0.117). The MS and MD of 32 eyes using T32 program were (9.05±6.42), (18.84±6.30) dB, the SCT was (209.83±71.48) μm; the MS and SCT of 52 eyes using LVC program were (7.14±5.03) dB and (228.32±66.32) μm. The SCT was related to MS (r=0.494, P=0.003) and MD (r=-0.448, P=0.009) in eyes using T32 program. There was no correlation between SCT and MD in eyes using LVC program (r=-0.232, P=0.095). ConclusionsThe SCT of RP patients is thinner than that of normal controls. The SCT of RP patients is related to MS and MD of T32 program, but not correlated to ERG waveform and MS of LVC program.
ObjectiveTo observe and analyze the pathogenic genes and clinical phenotype characteristics of retinitis pigmentosa sinepigmento(RPSP). MethodsA retrospective clinical study. Two patients (proband) and five family members from two RPSP families admitted to Xiamen Eye Center of Xiamen University in December 2022 and Shenzhen Eye Hospital in July 2023 were included in the study. Two families have no blood relationship and were both Han Chinese. Detailed ocular and systemic medical history and specialized examinations were performed for all members, including color fundus photography, fundus autofluorescence (FAF), and full field electroretinogram (ff-ERG) examination. The peripheral venous blood of all members was collected, and genomic DNA was extracted. Pathogenic genes and their loci were screened using whole exome high-throughput sequencing technology. Sanger sequencing was used to verify the pathogenic genes in the two pedigrees. The pathogenicity of candidate variants was evaluated according to the American Society for American College of Medical Genetics and Genomics (ACMG) classification criteria and guidelines for genetic variants. ResultsThe two probands were male, aged 9 and 7 years, respectively. The main complaint was poor binocular vision for 6 and 3 years and poor treatment effect of amblyopia. The proband (Ⅱ2) in family 1 had a pale red color on the optic disc, with leopard-like changes in the posterior pole and thinner retinal arteries. FAF showed mottled fluorescence attenuation outside the macular vascular arch. There was no significant waveform in both bright and dark visual responses of ff-ERG. He also had 6-toed deformity of both feet, renal cysts, and a slightly overweight body. The clinical diagnosis was non-pigmentary retinitis pigmentosa. The proband of family 2 (Ⅱ1) had poor binocular vision in a dark environment and had atrophy lesions on the nasal side of the optic disc and leopard print like changes in the fundus. FAF showed uneven enhancement in the fovea. ff-ERG showed severe abnormalities in dark and light response, with significant decrease and delay in b-wave amplitude and latency. He had no other systemic abnormalities. The clinical diagnosis was binocular RPSP. There were no abnormal ocular and systemic manifestations in the two family members. Gene sequencing revealed a homozygous mutation (c.534+1G>T) of BBS2 gene, which was inherited from the mother and father respectively. Based on clinical manifestations and genetic testing results, the final diagnosis was Bardet Biedl syndrome. The genetic sequencing results confirmed a novel compound heterozygous mutation (c.950T>G: p. Leu317Arg missense mutation and c.849+1G>C splicing mutation) of BBS7 gene. His father (Ⅰ1) and mother (Ⅰ2) carried M1 heterozygous variants. Combined with the clinical manifestations and genetic testing results, the final diagnosis was Bardet-Biedl syndrome (BBS). Family 2 proband (Ⅱ1) carried the BBS7 gene C.950T>G (p.Leu317Arg) (M2) missense variation and C.849 +1G>C (M3) splice site variation. His father (Ⅰ1) and mother (Ⅰ2) carried M3 shear site variation and M2 missense variation, respectively. The two families all fit the autosomal recessive inheritance pattern, and the genotype and clinical phenotype were coseparated. According to ACMG guidelines, M1, M2 and M3 were all identified as possible pathogenic variants. ConclusionsBBS2 gene M1 homozygous variation and BBS7 gene M2, M3 complex heterozygous variation are the possible pathogenic genes in family 1 and family 2, respectively. Two families are affected by BBS and RPSP, respectively.
Retinitis pigmentosa (RP) is a genetic disorder of photoreceptor cell apoptosis and retinal pigment epithelium (RPE) cell atrophy caused by gene mutation. The clinical manifestations are night blindness, peripheral visual field loss and progressive vision loss. RPE cell apoptosis plays an important role in the progression of RP, and exogenous implantation of RPE cells as an alternative therapy has shown certain efficacy in animal experiments and clinical trials. With the diversification of cell sources, the update of surgical techniques and the continuous emergence of biological materials, more possibilities and hopes are provided for cell therapy. To further promote the development of this field in the future, it is still necessary to strengthen the cooperation between medicine, bioengineering and other disciplines in the future to jointly promote the innovation and development of therapeutic methods. It is believed that RPE cell transplantation therapy will show a brighter prospect in the future