PSCs Reveal PUFA-Provoked Mitochondrial Stress as a Central Node Potentiating RPE Degeneration in Bietti's Crystalline Dystrophy.

Bietti's crystalline dystrophy (BCD) is an incurable retinal disorder caused by the polypeptide 2 of cytochrome P450 family 4 subfamily V (CYP4V2) mutations. Patients with BCD present degeneration of retinal pigmented epithelial (RPE) cells and consequent blindness. The lack of appropriate disease models and patients' RPE cells limits our understanding of the pathological mechanism of RPE degeneration. In this study, using CYP4V2 mutant pluripotent stem cells as disease models, we demonstrated that RPE cells with CYP4V2 mutations presented a disrupted fatty acid homeostasis, which were characterized with excessive accumulation of poly-unsaturated fatty acid (PUFA), including arachidonic acid (AA) and eicosapentaenoic acid (EPA). The PUFA overload increased mitochondrial reactive oxygen species, impaired mitochondrial respiratory functions, and triggered mitochondrial stress-activated p53-independent apoptosis in CYP4V2 mutant RPE cells. Restoration of the mutant CYP4V2 using adeno-associated virus 2 (AAV2) can effectively reduce PUFA deposition, alleviate mitochondria oxidative stresses, and rescue RPE cell death in BCD RPE cells. Taken together, our results highlight a role of PUFA-induced mitochondrial damage as a central node to potentiate RPE degeneration in BCD patients. AAV2-mediated gene therapy may represent a feasible strategy for the treatment of BCD.

RETINAL AND CHOROIDAL BLOOD PERFUSION IN PATIENTS WITH BIETTI CRYSTALLINE DYSTROPHY.

PURPOSE: To compare changes of chorioretinal blood perfusion between Bietti crystalline dystrophy (BCD) and typical retinitis pigmentosa and perform a staging and a longitudinal analysis of chorioretinal perfusion in BCD. METHODS: Twenty-eight patients with BCD (56 eyes), 28 patients with typical retinitis pigmentosa (56 eyes), and 28 healthy subjects (56 eyes) were enrolled. Macular structural parameters and subfoveal choroidal thickness were measured using optical coherence tomography. Retinal vessel and perfusion densities were calculated using optical coherence tomography angiography. Choroidal blood perfusion was assessed through indocyanine green angiography. The results of the BCD group were compared with those of the retinitis pigmentosa and control groups and followed by a staging and a longitudinal analysis of BCD. RESULTS: Macular structural and perfusion parameters were decreased less in the BCD group than those in the retinitis pigmentosa group. Subfoveal choroidal thickness was significantly thinner in the BCD group, with a remarkable choroidal perfusion deficit using indocyanine green angiography. The staging analysis revealed damage of both retinal and choroidal perfusion in BCD; however, the longitudinal analysis showed the impairment of choroidal perfusion outweighed retinal. CONCLUSION: Both retinal and choroidal blood perfusion are impaired in BCD, but choroidal perfusion deficit caused by CYP4V2 mutations may play a more vital pathologic role.

Ocular abnormalities in a large patient cohort with retinitis pigmentosa in Western China.

BACKGROUND: To report the prevalence of ocular abnormalities and investigate visual acuity in a large cohort of retinitis pigmentosa (RP) patients in Western China. METHODS: The medical records and ophthalmic examination reports of 2127 eyes of 1065 RP patients at one eye hospital were retrospectively reviewed to determined the prevalence of ocular abnormalities and the relationship between best corrected visual acuity (BCVA) and macular abnormalities. RESULTS: Nyctalopia (58.2%) and blurred vision (27.1%) were the leading reasons for RP patients to request an ophthalmic examination. BCVA measurements in the better eyes at first clinical presentation showed that 304 patients (28.5%) were categorised as blind and 220 patients (20.7%) as low vision. The most common ocular abnormalities were macular abnormalities (59.7%) and cataracts (43.1%). The macular abnormalities included epiretinal membranes (51.1%), cystoid macular edema (18.4%), vitreomacular traction syndrome (2.4%), macular holes (2.3%) and choroidal neovascular membranes (0.05%). Glaucoma was found in 35 eyes (1.6%). The proportions of epiretinal membranes (p = 0.001) and macular holes (p = 0.008) increased significantly with age. Cystoid macular edema was significantly associated with poorer visual acuity in RP patients with clear lens (p = 0.002). CONCLUSION: Cataracts and macular abnormalities are common in RP patients. Of the macular abnormalities, cystoid macular edema may have a negative effect on BCVA in RP patients with clear lens. Therefore, optical coherence tomography screening in RP patients is highly recommended for early detection and treatment of maculopathy.

Clinical and genetic characteristics of Stargardt disease in a large Western China cohort: Report 1.

Stargardt disease 1 (STGD1) is the most prevalent retinal dystrophy caused by pathogenic biallelic ABCA4 variants. Forty-two unrelated patients mostly originating from Western China were recruited. Comprehensive ophthalmological examinations, including visual acuity measurements (subjective function), fundus autofluorescence (retinal imaging), and full-field electroretinography (objective function), were performed. Next-generation sequencing (target/whole exome) and direct sequencing were conducted. Genotype grouping was performed based on the presence of deleterious variants. The median age of onset/age was 10.0 (5-52)/29.5 (12-72) years, and the median visual acuity in the right/left eye was 1.30 (0.15-2.28)/1.30 (0.15-2.28) in the logarithm of the minimum angle of resolution unit. Ten patients (10/38, 27.0%) showed confined macular dysfunction, and 27 (27/37, 73.7%) had generalized retinal dysfunction. Fifty-eight pathogenic/likely pathogenic ABCA4 variants, including 14 novel variants, were identified. Eight patients (8/35, 22.8%) harbored multiple deleterious variants, and 17 (17/35, 48.6%) had a single deleterious variant. Significant associations were revealed between subjective functional, retinal imaging, and objective functional groups, identifying a significant genotype-phenotype association. This study illustrates a large phenotypic/genotypic spectrum in a large well-characterized STGD1 cohort. A distinct genetic background of the Chinese population from the Caucasian population was identified; meanwhile, a genotype-phenotype association was similarly represented.

Oguchi disease caused by a homozygous novel SAG splicing alteration associated with the multiple evanescent white dot syndrome: A 15-month follow-up.

PURPOSE: We report a 15-month follow-up case on a Chinese patient with Oguchi disease associated with the multiple evanescent white dot syndrome (MEWDS). METHODS: The patient's clinical presentation and follow-up visits were documented via decimal best-corrected visual acuity, fundus photography, fundus autofluorescence (FAF) imaging, near-infrared FAF, spectral domain optical coherence tomography, Humphrey's visual fields, microperimetry, and multifocal electroretinography. We also performed whole exome sequencing for screening variation in the patient and her relatives. RESULTS: The patient had typical clinical characteristic of Oguchi disease, including night blindness, the Mizuo-Nakamura phenomenon (a golden yellow discoloration of the fundus that disappears in the prolonged dark adaptation [DA]) and typical full-field electroretinogram changes (nearly undetected b-wave in 0.01 and 0.03 ERGs that can partially recover only after prolonged DA). Aside from Oguchi disease, the patient was also diagnosed with the MEWDS based on clinical detections, including suddenly reduced visual acuity, appeared white dots, blurred ellipsoid zone and disrupted interdigitation zone, enlarged blind spot, and reduced macular sensitivity. A series of investigations revealed that along with the 15-month follow-up after onset, the visual acuity enhanced, the numerous white dots disappeared, and the macular structure returned to normal. Moreover, the novel homozygous splicing alteration c.181 + 1G > A was identified in the SAG gene. CONCLUSIONS: This work is the first long-term case study of a patient with Oguchi disease associated with the MEWDS. The recovery period of symptoms caused by the MEWDS was much longer than that in typical patients with MEWDS. Molecular genetics demonstrate that this is the first case of Oguchi disease caused by splicing alterations in the SAG gene.

Neovascular glaucoma in a pediatric patient with neurofibromatosis type 1: a case report.

BACKGROUND: To report a case of a young patient with neurofibromatosis type 1 (NF1). METHODS: Here we review the treatment administered to a 7-year-old NF1 patient with neovascular glaucoma as the primary diagnosis. CASE PRESENTATION: A 7-year-old boy developed visual loss in the right eye associated with periocular pain and ipsilateral headache that had persisted for 1 week. The patient's condition did not improve after treatment with topical or systemic glaucoma medications. Fundus examination of the right eye showed superotemporal retinal vasoproliferative tumors (RVPT). Near-infrared reflectance scans of the left eye's fundus revealed bright patchy regions, scattered across the posterior pole; systemic examination showed café-au-lait spots all over the patient's body. The patient had a clear family history. Genetic testing confirmed NF1. The right eye was treated with intravitreal ranibizumab injection, retinal lesion cryotherapy, and transscleral ciliary body photocoagulation. After treatment, RVPT scarring was observed. The patient's intraocular pressure remained within normal limits. CONCLUSIONS: We report a rare case of neurofibromatosis in a pediatric patient with neovascular glaucoma accompanied by RVPT. We suggest that evaluations of young patients with neovascular glaucoma should include careful attention to the overall condition of the patient and his/her parents, as well as family history. If necessary, NF1 molecular testing should be performed to avoid a missed diagnosis or misdiagnosis.

[Contributions of human rods and cones pathway to different components of oscillatory potentials in time and frequency domain].

OBJECTIVE: To investigate the contributions of human rods and cones pathway to different components of oscillatory potentials (OP) in time and frequency domain. METHODS: Case-control study. Twenty subjects were divided into two groups, normal groups (NG) and cones pathway abnormal groups (CAG). All eyes were investigated by dark-adapted (DA) and light-adapted (LA) 3.0 ERG recommended by ISCEV. Data were output into the computer and processed and analyzed by the software Matlab7.0. First, to extract the OP by filter, then to get the frequency-amplitude relationship by FFT, after that the relationship was fitted by equations and lastly we statistic and analyze the parameters gotten from the equations. RESULTS: Compared with normal group [(48.63 ± 4.29), (158.00 ± 32.75), (69.27 ± 30.31), (38.5 ± 15.28) µV], the amplitudes of the first two components of dark-adapted OP in the CAG [(4.12 ± 3.20), (71.25 ± 25.43), (48.96 ± 20.05), (36.84 ± 14.26) µV] were significant decreased (t = 16.68, 5.77, P < 0.01). Frequency domain of LA and DA OP in the two groups was comprised with two components (harmonic and subharmonic). Compared with normal group, harmonic components of CAG were dramatic decreased (t = 2.72, P < 0.05; Z = -2.24, P < 0.05). The value of subharmonic component in CAG was lowest in DA OP compared with NG (t = 4.20, P < 0.005). CONCLUSIONS: Cones and rods pathway all contributed to the DA and LA OP Cones pathway mainly contributes to the earlier and faster components of OP while the rods pathway to the later and slower components.

Application effect of diversified health-promoting models on rehabilitation exercises for cervical spondylotic myelopathy.

BACKGROUND: With improving living standards, the incidence of cervical spondylotic myelopathy (CSM) has become increasingly high. OBJECTIVE: The study aims to explore the effect of diversified health-promoting models on rehabilitation exercises in patients with CSM after an operation. METHOD: This was a randomized controlled trial, wherein 107 patients with CSM treated by neurosurgery were selected as the subjects. Of those, 52 patients in the control group adopted the conventional health-promoting model, while the remaining 55 patients in the intervention group adopted diversified health-promoting models. The effect of rehabilitation exercises in the two groups was evaluated according to the self-efficacy rehabilitation outcome scale, grip strength measurement of the affected limb, and Barthel index. RESULTS: At Day 3 post-operation and before discharge, the self-efficacy management of rehabilitation exercises in the intervention group was better than that of the control group (P< 0.05). The grip strength measurement of the affected limb, Japanese Orthopedic Association score of the cervical vertebra, and Barthel index of the two groups at Day 3 post-operation were lower than before the intervention and were not statistically significant (P> 0.05). However, these three items before discharge were improved when compared with those of before intervention and were statistically significant (P< 0.05). CONCLUSION: Postoperative rehabilitation exercises guided by the diversified health-promoting models for patients with CSM can improve the patients' self-efficacy management ability in rehabilitation exercises, help improve grip strength, and promote the recovery of cervical vertebra function, thereby improving the patients' quality of life.

Clinical manifestation and long-term follow-up of presumed ocular tuberculosis in China.

Background: This study aimed to report the clinical manifestations of presumed ocular tuberculosis (OTB) and the treatment response after anti-tuberculosis therapy (ATT) in a Chinese population. Methods: Clinical data, including general characteristics, ocular lesions, visual acuity at baseline, and final follow-up of patients with presumed OTB from 2006 to 2022 in two eye clinics in China, were retrospectively analyzed. Results: The study included 84 eyes of 52 patients. The following ocular manifestations were observed: anterior uveitis (4.8%), posterior uveitis (34.5%), panuveitis (11.9%), retinal vasculitis (40.5%) and optic neuropathy (8.3%). After ATT, the vision improved by varying degrees in 48 eyes (57.1%), remained stable in 34 eyes (40.5%) and decreased in 2 eyes (2.4%). Conclusions: OTB is likely to be misdiagnosed as other infectious uveitis and optic neuropathy. Clinical features must be interpreted in conjunction with topical and general laboratory findings and in collaboration with other subspecialties to make a final diagnosis.

Construction and optimization of a polygenic risk model for venous thromboembolism in the Chinese population.

BACKGROUND: Venous thromboembolism (VTE) has both environmental and genetic risk factors. It is regulated by polygenes and multisites. The polygenic risk score (PRS) has been widely used because any single genetic biomarker failed to accurately predict the genetic risk of VTE. However, no polygenic risk model has been proposed for VTE in the Chinese population. Thus, we aimed to construct a PRS model for the first episode of VTE in the Chinese population. METHODS: First, single nucleotide polymorphisms (SNPs) associated with VTE in genome-wide association studies, meta-analyses, and candidate gene studies were screened as variables for the PRS. The logarithm of the odds ratio was used to weight the variables. Second, a training set with simulated data from 1000 cases of VTE and 1000 controls was created with different genotypes and frequencies. Finally, we calculated the area under the receiver operating characteristic curve (AUC) to evaluate the discriminatory ability of the PRS model. RESULTS: We screened 53 SNPs potentially associated with the first episode of VTE in the Chinese population. The AUC of the PRS-53 model (containing 53 SNPs) was 0.748 (95% confidence interval, 0.727-0.770) in the training set. From the largest weight to the smallest weight, SNPs were incrementally added to the model to calculate the AUC for model optimization. The AUC of the PRS-10 model (containing 10 SNPs) was 0.718 (95% confidence interval, 0.696-0.740), with no statistically significant difference from the AUC for the PRS-53 model. CONCLUSIONS: The PRS-10 and PRS-53 models showed similar predictive abilities and satisfactory discriminatory power and can be used to predict the genetic risk of the first episode of VTE in the Chinese population. The simplified PRS-10 model is more efficient in clinical practice.

Comprehensive analysis of UGT1A1 genetic polymorphisms in Chinese Tibetan and Han populations.

The study of polymorphism of the UGT1A1 gene has not been reported in the Chinese Tibetan population, and there are no comparisons of genetic polymorphism in the gene between Chinese Han and Tibetan populations. In this study, we directly sequenced the functional regions of the UGT1A1 gene in 200 unrelated healthy Chinese volunteers, detecting 20 variations (including five novel ones). The distributions of allele and genotype frequencies differ between the two groups. UGT1A1*6 is the major reduced functional variant in the populations, and the *27 allele was detected only in the Han group. Differences in the frequencies of the UGT1A1*6/*63 genotype between the Tibetan and Han populations were statistically significant (P = 0.009). Our genetic data might provide fundamental information for the advance of personalized medicine and will facilitate genotype-phenotype studies in larger populations.

Effect of Alginate Gelatin Hydrogel Composited with Nano-Zinc on Cesarean Section Wound Healing.

The Surgical procedure of cesarean section (CS) causes a large wound that any delay in its healing could increase the rate of stress, inconvenience, and dissatisfaction among the women who underwent CS procedure about six weeks after childbirth. The present study is trying to evaluate the effect of alginate and gelatin hydrogel composited with nanozinc effective extensibility and compressibility as a wound dressing nursing care after CS. The number of participants was 700 individuals enrolled all who underwent C-sections at Medical College in the Second Affiliated Hospital of Xi'an Jiaotong University (from September 2017 until September 2020). Patients were divided into two groups of case and control consist of 350 cases. The case group was treated with alginate gelatin hydrogel-nZnO+antibacterial wound dress and the control group was treated with wound healing ordinary creams+antibacterial. Three and four weeks following CS, the healing process of the wound was evaluated using REEDA wound scale. In the current study, there was not any significant difference between the studied case and control group in respect to individual's demographical characteristics such as economic status, educational level, BMI, and age. (P > 0.05). Also, we observed that patients treated with alginate gelatin hydrogel-nZnO would experience a significantly lower score for redness, ecchymosis, edema, and approximation of CS wound in comparison to the control group (P < 0.05). Also, slope analysis showed that the healing process was significantly quicker in patients treated with alginate gelatin hydrogel-nZnO in comparison to the control group. Finally, it was observed that more than 80% of patients did not represent any major sign of CS after three weeks, however, in the control case this issue was estimated at 50.6%. No allergic reaction has been observed. Our results showed that using alginate gelatin hydrogel-nZnO wound dress could be a novel treatment in a nursing care setting to decrease the CS wound complication and increase the healing process without any allergic reaction.

Quantitative assessment of visual pathway function in blind retinitis pigmentosa patients.

OBJECTIVE: The current methods used to assess visual function in blind retinitis pigmentosa (RP) patients are mostly subjective. We aimed to identify effective, objective methods. METHODS: We enrolled patients diagnosed with blindness associated with RP; we finally selected 26 patients (51 eyes) with a visual field radius less than 10 degrees and divided them into the following 4 groups by best-corrected visual acuity (BCVA): group 1, no light perception (NLP, 4 eyes); group 2, light perception (LP, 12 eyes); group 3, hand movement or finger counting (faint form perception, FFP, 22 eyes); and group 4, BCVA from 0.1 to 0.8 (form perception, FP, 13 eyes). All patients underwent optometry, optical coherence tomography (OCT), color fundus photography, fundus autofluorescence (FAF), full field electroretinography (ffERG), pattern electroretinography (PERG), multifocal electroretinography (mf-ERG), pattern visual evoked potential (PVEP), flash visual evoked potential (FVEP), and pupillary light response (PLR) assessments. Five patients in groups 1, 2, and 3 (1, 2, and 2 subjects, respectively) underwent functional magnetic resonance imaging (fMRI) scans and were compared with five healthy subjects. RESULTS: The outer plexiform layer was thinner in group 1, and the outer nuclear layer was thinner in groups 1 and 2. The ffERG, PERG, and mf-ERG findings were unrecordable in all four groups. The P2 amplitude of the FVEP was significantly lower in groups 1 and 2, while the P100 amplitude of the PVEP was higher in groups 2, 3 and 4 than in group 1. After white- and blue-light stimuli, the PLR thresholds in the patients without form perception were significantly higher. The threshold of the PLR stimulated by blue and white light was negatively correlated with the amplitudes of P2 and P100. Moreover, the fMRI findings showed that some RP patients have significant visual cortex activation in response to certain types of stimulation. However, statistical analysis was not performed because of the small number of cases. CONCLUSIONS: OCT, VEP, PLR and fMRI assessments can evaluate residual visual pathway function in blind RP patients. SIGNIFICANCE: Our study may have clinical significance for the potential prediction of RP patient prognoses and the effects after clinical trials.

Comparative Study of a Modified Sub-Tenon's Capsule Injection of Triamcinolone Acetonide and the Intravenous Infusion of Umbilical Cord Mesenchymal Stem Cells in Retinitis Pigmentosa Combined With Macular Edema.

Retinitis pigmentosa (RP) is a hereditary retinal degenerative disease leading to eventual blindness. When RP is combined with macular edema (ME), the visual impairment further worsens. We compared a modified sub-Tenon's capsule injection of triamcinolone acetonide (TA) and the intravenous infusion of umbilical cord mesenchymal stem cells (UCMSCs) in the treatment of RP combined with ME (RP-ME) to assess their safety and efficacy in eliminating ME and restoring visual function. A phase I/II clinical trial enrolled 20 patients was conducted. All patients were followed up for 6 months. There were no severe adverse effects in both groups. In retinal morphological tests, the central macular thickness (CMT) in TA group significantly decreased at first week, first and second month after injection (p < 0.05). The CMT in UCMSCs group significantly decreased at first month after infusion. The rate of reduction of CMT in TA group was significantly greater than that in UCMSCs group at second month (p < 0.05). Reversely, the rate of reduction of CMT in UCMSCs group was significantly greater than that in TA group at sixth month (p < 0.05). In visual functional test, although there were no significant differences in visual acuity or visual fields within each group or between groups, but the amplitude of P2 wave of flash visual evoked potential (FVEP) showed significant increasing in TA group at second month in UCMSCs group at sixth month (p < 0.05). At 6th month, the rate of growth in the amplitude of P2 wave in USMCSs group was significantly greater than that in TA group (p < 0.05). This study suggests both modified sub-Tenon's capsule injection of TA and intravenous infusion of UCMSCs are safe for RP-ME patients. TA injection is more effective at alleviating ME while improving visual function in a short term. UCMSC intravenous infusion shows slow but persistent action in alleviating ME, and can improve the visual function for a longer time. These approaches can be applied separately or jointly depending on the disease condition for patients to benefit maximumly. Clinical Trial Registration: http://www.chictr.org.cn, identifier ChiCTR-ONC-16008839.

Ocular Characteristics of Patients With Bardet-Biedl Syndrome Caused by Pathogenic BBS Gene Variation in a Chinese Cohort.

Bardet-Biedl syndrome (BBS; OMIM 209900) is a rare genetic disease causing damage to multiple organs and affecting patients' quality of life in late adolescence or early adulthood. In this study, the ocular characteristics including morphology and function, were analyzed in 12 BBS patients from 10 Chinese families by molecular diagnostics. A total of five known and twelve novel variants in four BBS genes (BBS2, 58.33%; BBS4, 8.33%; BBS7, 16.67%; and BBS9, 16.67%) were identified in 10 Chinese families with BBS. All patients had typical phenotypes of retinitis pigmentosa with unrecordable or severely damaged cone and rod responses on full-field flash electroretinography (ffERG). Most of the patients showed unremarkable reactions in pattern visual evoked potential (PVEP) and multifocal electroretinography (mfERG), while their flash visual evoked potentials (FVEP) indicated display residual visual function. Changes in the fundus morphology, including color fundus photography and autofluorescence (AF) imaging, were heterogeneous and not consistent with the patients' functional tests. Overall, our study expands the variation spectrum of the BBS gene, showing that the ocular characteristics of BBS patients are clinically highly heterogeneous, and demonstrates the usefulness of a combination of the ffERG and FVEP assessments of visual function in the advanced stage of retinopathy in BBS.

Online survey on healthcare skin reactions for wearing medical-grade protective equipment against COVID-19 in Hubei Province, China.

With the spread of Coronavirus Disease 2019 globally, more than 40,000 healthcare staff rushed to Wuhan, Hubei Province to fight against this threatening disease. All staff had to wear personal protective equipment (PPE) for several hours when caring for patients, which resulted in adverse skin reactions and injuries. In this study, we used an online questionnaire to collect the self-reported skin damages among the first-line medical staff in the epidemic. The questionnaire was designed by four front-line wound care nurses and then revised through Delphi consultants. Items mainly focused on the adverse skin reactions and preventive strategies. The survey was distributed through phone application from March 15th to March 20th and received 275 responses in total. The prevalence of skin reactions (212, 77.09%) was high in both head and hands. The common clinical symptoms of skin reactions were redness, device-like mark, and burning pain in face; and dryness, dermatitis, and itch/irritation in hands. Three risk factors included gender, level of protection, and daily wearing time of PPE were identified that caused skin reactions among medical staff. 150 of 275 (54.55%) participants took preventive strategies like prophylactic dressings, however, more than 75% users had little knowledge about dressings. We suggest the frontline staff strengthened the protection of skin integrity and reduced the prevalence of adverse skin reactions after professional education.

Molecular genetics with clinical characteristics of Leber congenital amaurosis in the Han population of western China.

Purpose: Leber congenital amaurosis (LCA) is one of the earliest inherited retinal dystrophies (IRD) that leads to blindness. To date, there have been 25 LCA-associated genes reported in China as well as other countries. The current study aimed to present the dominant molecular genetics and clinical features of LCA in the Han population of western China.Methods: Our study comprised 37 patients with strictly defined Leber congenital amaurosis in a cohort of IRD (2009-2019). The mutations were detected by targeted next-generation sequencing (NGS), Sanger sequencing, and segregation analysis. The patients underwent comprehensive clinical examinations, analysis of phenotypes and genotypes.Results: Out of the 37 patients, 34 harbored known LCA genes; the detection rate of mutations was 91.9%. Forty-seven different alleles incorporated 21 novel mutations; 8 were known LCA-associated genes. The three most frequently mutated genes included CRB1 (27.0%), RDH12 (24.3%), and RPGRIP1 (18.9%). The CRB1-associated LCA showed a pigmented fundus; the RDH12-associated LCA featured macular atrophy. Our results revealed that CRB1 and RPGRIP1 genes occupied a greater proportion in the western Chinese population. The proportion of these two genes was similar in other regions of China as well. The difference existed in a larger proportion of RDH12-associated LCA in the western Chinese population.Conclusions: The new findings in our study group polished the spectrum of the novel mutations and phenotypes of LCA with regional and ethnic variations. This comprehensive database can provide essential information for gene therapies.

Ocular Characteristics of Patients with Leber Congenital Amaurosis 6 Caused by Pathogenic RPGRIP1 Gene Variation in a Chinese Cohort.

PURPOSE: To delineate the clinical and genetic characteristics of Chinese patients with RPGRIP1-associated Leber congenital amaurosis 6 (LCA6). METHODS: After screening 352 unrelated families with clinically diagnosed RP, five LCA6 patients with RPGRIP1 variations from unrelated Chinese families were identified. Full ophthalmology examinations, including decimal best-corrected visual acuity (BCVA), fundus photography, fundus autofluorescence imaging, spectral-domain optical coherence tomography (SD-OCT), full-field electroretinography (ffERG), multifocal electroretinography (mfERG), perimetry, and flash visual evoked potential (FVEP), were performed. Target next-generation sequencing (NGS) and Sanger sequencing were performed for the five patients to identify and to validate candidate disease-causing variants. RESULTS: Five patients were molecularly diagnosed as the LCA6 associated with RPGRIP1 variation, with typical clinical characteristics including congenital night blindness, nystagmus, and visual defect, at an early age. Interestingly, LCA6 exhibited extensive clinical heterogeneity and the changes in the morphology and function were not completely consistent in the five LCA6 patients. Case 1 showed extensive inferior-nasal retinal atrophy with a corresponding area of hypofluorescence in fundus autofluorescence, and the fundus photograph was nearly normal in cases 2 and 3. The ERG results displayed a moderately reduced rod-system response in cases 1 and 2 and a significant reduced rod-system response in case 3. Both case 4 and case 5 showed mottled pigmentation in fundi and an unrecordable rod and cone-system response in ERG. Moreover, we identified eight compound variants and one homozygous variant in the five patients with RPGRIP1. CONCLUSIONS: This is the largest report focused on the clinical electrophysiological features of patients with associated LCA6 caused by the variation in the RPGRIP1 gene in the Chinese population with an enriched phenotypic and genotypic background of LCA6 to improve future gene therapies.

Long-term follow-up of a Chinese patient with KCNV2-retinopathy.

Purpose: To characterize and monitor the clinical and electrophysiological features of a Chinese patient with KCNV2 retinopathy.Methods: A 17-year-old Chinese male with the diagnosis of cone dystrophy with supernormal rod response (CDSRR) was followed-up for 5 years, with full ophthalmological examinations, including decimal best corrected visual acuity (BCVA), fundus photography, fundus autofluorescence (FAF) imaging, spectral-domain optical coherence tomography (SD-OCT), and full-field electroretinogram (ERG). Genetic screening was performed to detect the sequence variations in the retinal dystrophy associated genes in the patient and his parents.Results: The patient demonstrated the characteristic full-field electroretinography (ERG) features of CDSRR, namely a profound enlargement of the dark-adapted ERG b-wave amplitude with increasing flash strength and a broadened a-wave trough; this case also had undetectable light-adapted ERGs. A BCVA of 0.15 was maintained over 5 years in both eyes; while progressive macular atrophy was identified. Molecular genetic analyses revealed two novel disease-causing KCNV2 variants in compound heterozygous state: c.1408 G > C (p.Gly470Arg) and c.1500 C > G (p.Tyr500Ter).Conclusions: This is the first long-term case study of an East Asian patient with molecularly confirmed CDSRR. The progressive atrophy with maintained VA demonstrated in this case will be valuable for increasing the understanding of the natural course of KCNV2 retinopathy and it will help in counselling patients with this disease.

A phase I clinical trial of human embryonic stem cell-derived retinal pigment epithelial cells for early-stage Stargardt macular degeneration: 5-years' follow-up.

OBJECTIVES: To evaluate the long-term biosafety and efficacy of transplantation of human embryonic stem cells-derived retinal pigment epithelial (hESC-RPE) cells in early-stage of Stargardt macular degeneration (STGD1). MATERIALS AND METHODS: Seven patients participated in this prospective clinical study, where they underwent a single subretinal transplantation of 1 × 105 hESC-RPE cells in one eye, whereas the fellow eye served as control. These patients were reassessed for a 60-month follow-up through systemic and ophthalmic examinations. RESULTS: None of the patients experienced adverse reactions systemically or locally, except for two who had transiently high intraocular pressure post-operation. Functional assessments demonstrated that all of the seven operated eyes had transiently increased or stable visual function 1-4 months after transplantation. At the last follow-up visit, two of the seven eyes showed visual function loss than the baseline; however, one of them showed a stable visual acuity when compared with the change of fellow eye. Obvious small high reflective foci in the RPE layer were displayed after the transplantation, and maintained until the last visit. Interestingly, three categories of patients who were classified based on autofluorescence, exhibited distinctive patterns of morphological and functional change. CONCLUSIONS: Subretinal transplantation of hESC-RPE in early-stage STGD1 is safe and tolerated in the long term. Further investigation is needed for choosing proper subjects according to the multi-model image and function assessments.