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 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.
Objective To analyze the pathogenic gene and clinical phenotypes of a family affected with rare sector retinitis pigmentosa (sector RP). Methods A retrospective clinical study. A patient with sector RP diagnosed in Renmin Hospital of Wuhan University and his parents were included in the study. Detailed medical history was collected; best corrected visual acuity (BCVA), fundus color photography, autofluorescence (AF), visual field, optical coherence tomography (OCT), electroretinogram, fluorescein fundus angiography (FFA), indocyanine green angiography (ICGA) examination were performed. The peripheral venous blood of the patient and his parents were collected, and DNA was extracted. A whole exon sequencing was used for the proband. The mutations were verified by targeted Sanger sequencing and quantitative polymerase chain reaction. Bioinformatics analysis and cosegregation analysis were performed. ResultsThe proband, a 17-year-old male, had presented with gradually decreased vision in the past 2 years with BCVA of 0.4 in both eyes. Retinal vessels attenuation and macular dystrophy without obvious pigmentation on the fundus were observed. AF showed, in bilateral eyes, a symmetrical hypo-autofluorescent region only in the inferonasal quadrant and “petal-like” hyper-AF macula. The visual field examination showed defects in the superotemporal quadrant corresponding to the affected retina. OCT showed loss of the photoreceptor layer except for the foveal region. Electroretinogram examination presented reduced scotopic wave peaks and extinct photopic response. FFA and ICGA showed the atrophy retinal pigment epithelium around the optic disk and in the inferior retina. The clinical phenotypes of the parents were normal. The whole exon sequencing identified one mutation in SPATA7 gene, c.1112T>C (p.Ile371Thr) in exon10 and a copy number variation in trans. The missense mutation resulted in the change of isoleucine to threonine at amino acid 371 in the encoded SPATA7 protein, and the mother carried this heterozygous mutation c.1112T>C. According to the guidelines of the American College of Medical Genetics and Genomics (ACMG) criteria and guidelines for classification of genetic variants, the missense mutation was classified as the uncertain significance. The CNV, originating from his father, contributed to the loss of exon10 and was confirmed as the likely pathogenic variant. ConclusionsThe macula can be involved in sector RP, leading to the macular dystrophy. The missense variant in SPATA7 gene, c.1112T>C (p.Ile371Thr), might be a pathogenic mutation site in this pedigree.
Cilia are hair-like protuberance on cells of the human body that play a vital role in organs generation and maintenance. Abnormalities of ciliary structure and function affect almost every system of the body, such as the brain, eyes, liver, kidney, bone, reproductive system and so on. Retinal photoreceptor cells are one of sensory neurons which convert light stimuli into neurological responses. This process, called phototransduction, takes place in the outer segments (OS) of rod and cone photoreceptors. OS are specialized sensory cilia, and disruptions in cilia genes, which are causative in a growing number of non-syndromic retinal dystrophies, such as retinitis pigmentosa, Leber’s congenital amaurosis. These syndromes are genetically heterogeneous, involving mutations in a large number of genes. They show considerable clinical and genetic overlap. At present, there are few researches on retinal ciliopathies and clinical treatment strategy. This review shows a comprehensive overview of ciliary dysfunction and visual development related diseases, which contributes to understand the characteristics of these diseases and take early intervention in clinic.
Objective To observe the characteristics of fundus autofluorescence (AF) in short wavelength AF (SW-AF) and Near Infrared AF (NIR-AF), and their relationship with visual fields. Methods Twelve patients (24 eyes) with primary RP were enrolled in this study. The patients included nine males (18 eyes) and three females (six eyes). The patients aged from 15 to 69 years, with a mean age of (35.33plusmn;15.03) years. All the patients were examined for color photography, SW-AF, NIR-AF, visual fields and optical coherence tomography examination. Results There were hyper-AF ring of varying sizes in posterior pole by SW-AF and NIR-AF examinations. The area of hypo-AF which located in SW-AF hyper-AF ring had a positive correlation with the area of hyper-AF in the NIR-AF (r=0.662，P＜0.05). OCT showed that outside the hyper-AF ring, there were disconnected inner segment/outer segment (IS/OS) junction and external limiting membrane, and thinned outer nuclear layer and retinal pigment epithelium. Peripheral retinal osteocytes-like pigmentation showed non fluorescence in SW-AF and NIR-AF. The plaque-like area showed mottled and low fluorescence examined by SW-AF. SW-AF hyper-AF ring had a positive correlation with visual fields (r=0.492，P＜0.05). Conclusions The area of hypo-AF inside of the SW-AF hyper-AF ring is related to visual fields in RP patients. The retinal structures in the hypo-AF area inside of the SW-AF hyper-AF ring, and in the NIR-AF hyper-AF region are normal.
Retinitis pigmentosa (RP) is a group of hereditary blinding fundus diseases caused by abnormalities in photoreceptors of the retina. RP is highly heterogeneous in hereditary and cdinical phenotypes. It can be divided into simple type RP and syndrome type RP. The main inheritance patterns are autosomal dominant, autosomal recessive inheritance and X-linked inheritance. With the popularization and clinical application of gene sequencing technology, more and more disease-causing genes have been discovered, and these genes are mainly expressed in photoreceptor cells and retinal pigment epithelial cell. ln-depth understanding of RP pathogenic genes not only provides a theoretical basis for RP diagnosis and genetic counseling, but also provides guidance for RP gene therapy.