OBJECTIVE: To develop a few-shot learning (FSL) approach for classifying optical coherence tomography (OCT) images in patients with inherited retinal disorders (IRDs). METHODS: In this study, an FSL model based on a student-teacher learning framework was designed to classify images. 2,317 images from 189 participants were included. Of these, 1,126 images revealed IRDs, 533 were normal samples, and 658 were control samples. RESULTS: The FSL model achieved a total accuracy of 0.974-0.983, total sensitivity of 0.934-0.957, total specificity of 0.984-0.990, and total F1 score of 0.935-0.957, which were superior to the total accuracy of the baseline model of 0.943-0.954, total sensitivity of 0.866-0.886, total specificity of 0.962-0.971, and total F1 score of 0.859-0.885. The performance of most subclassifications also exhibited advantages. Moreover, the FSL model had a higher area under curves (AUC) of the receiver operating characteristic (ROC) curves in most subclassifications. CONCLUSION This study demonstrates the effective use of the FSL model for the classification of OCT images from patients with IRDs, normal, and control participants with a smaller volume of data. The general principle and similar network architectures can also be applied to other retinal diseases with a low prevalence.
Humans ; Tomography, Optical Coherence ; Deep Learning ; Retinal Diseases/diagnostic imaging* ; Retina/diagnostic imaging* ; ROC Curve

Objective To investigate the ameliorative effect of salidroside on diabetes retinopathy (DR) rats and its mechanism. Methods Male SD rats were randomly divided into blank group, model group, low-dose and high-dose salidroside treatment groups. Except for the blank group, other groups were modeled by intraperitoneal injection of streptozotocin. After successful modeling, treatment groups were injected intraperitoneally with [50 mg/(kg.d)] and [100 mg/(kg.d)] salidroside respectively, for 4 weeks; the blank group and model group were injected with corresponding doses of saline. ELISA was used to measure the expression levels of antioxidant-related enzyme activity and inflammatory factors in blood glucose and serum of rats in each group. Retinal tissue lesions were detected by HE staining, and the expression of vascular endothelial growth factor (VEGF) and intercellular adhesion molecule 1 (ICAM-1) in retinal tissues were detected by immunohistochemical staining. Western blot analysis was used to detect the expression of phosphatidylinositol 3 kinase (PI3K) , nuclear factor κB p65 (NF-κB p65), phosphorylated p38 MAPK (p-p38 MAPK), and phosphorylated protein kinase B (p-AKT) proteins. Results Compared with model group, salidroside could significantly reduce blood glucose level and increase body mass in DR rats. The serum levels of superoxide dismutase (SOD) and catalase (CAT) were significantly increased, while the levels of malondialdehyde (MDA), tumor necrosis factor α (TNF-α), interleukin 6 (IL-6) and IL-1β were reduced. The protein expression of VEGF, ICAM-1, NF-κB p65 and p-p38 MAPK was significantly decreased, while the protein expression of PI3K and p-AKT was increased. Conclusion Salidroside can reduce DR in rats by inhibiting oxidative stress and immune inflammatory response, which may be related to the reduction of abnormal expression of VEGF and ICAM-1 and the activation of PI3K/AKT signaling pathway.
Animals ; Male ; Rats ; Blood Glucose ; Diabetes Mellitus ; Inflammation/metabolism* ; Intercellular Adhesion Molecule-1/metabolism* ; NF-kappa B/metabolism* ; Oxidative Stress ; Phosphatidylinositol 3-Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Rats, Sprague-Dawley ; Retinal Diseases ; Tumor Necrosis Factor-alpha/metabolism* ; Vascular Endothelial Growth Factor A/metabolism*

OBJECTIVES: To study the protective effect of melatonin (Mel) against oxygen-induced retinopathy (OIR) in neonatal mice and the role of the HMGB1/NF-κB/NLRP3 axis. METHODS: Neonatal C57BL/6J mice, aged 7 days, were randomly divided into a control group, a model group (OIR group), and a Mel treatment group (OIR+Mel group), with 9 mice in each group. The hyperoxia induction method was used to establish a model of OIR. Hematoxylin and eosin staining and retinal flat-mount preparation were used to observe retinal structure and neovascularization. Immunofluorescent staining was used to measure the expression of proteins and inflammatory factors associated with the HMGB1/NF-κB/NLRP3 axis and lymphocyte antigen 6G. Colorimetry was used to measure the activity of myeloperoxidase. RESULTS: The OIR group had destruction of retinal structure with a large perfusion-free area and neovascularization, while the OIR+Mel group had improvement in destruction of retinal structure with reductions in neovascularization and perfusion-free area. Compared with the control group, the OIR group had significant increases in the expression of proteins and inflammatory factors associated with the HMGB1/NF-κB/NLRP3 axis, the expression of lymphocyte antigen 6G, and the activity of myeloperoxidase (P<0.05). Compared with the OIR group, the OIR+Mel group had significant reductions in the above indices (P<0.05). Compared with the control group, the OIR group had significant reductions in the expression of melatonin receptors in the retina (P<0.05). Compared with the OIR group, the OIR+Mel group had significant increases in the expression of melatonin receptors (P<0.05). CONCLUSIONS Mel can alleviate OIR-induced retinal damage in neonatal mice by inhibiting the HMGB1/NF-κB/NLRP3 axis and may exert an effect through the melatonin receptor pathway.
Animals ; Mice ; HMGB1 Protein ; Melatonin/therapeutic use* ; Mice, Inbred C57BL ; NF-kappa B ; NLR Family, Pyrin Domain-Containing 3 Protein ; Oxygen/adverse effects* ; Peroxidase ; Receptors, Melatonin ; Retinal Diseases/drug therapy*

OBJECTIVE: We wanted to investigate the radial peripapillary capillary (RPC) network in patients with Bietti crystalline dystrophy (BCD). METHODS: We compared RPC densities in the disk and different peripapillary regions, obtained using optical coherence tomography angiography in 22 patients with BCD (37 eyes) and 22 healthy subjects (37 eyes). The BCD group was then divided into Stage 2 and Stage 3 subgroups based on Yuzawa staging, comparing the RPC densities of the two. RESULTS: The disk area RPC density was 38.8% ± 6.3% in the BCD group and 49.2% ± 6.1% in the control group ( P < 0.001), and peripapillary region RPC density was significantly lower in the BCD group than in the control group (49.1% ± 4.7% and 54.1% ± 3.0%, respectively, P < 0.001). There were no significant RPC density differences between the tempo quadrant and inside disk of Stages 2 and 3 subgroups; the other areas showed a significantly lower RPC density in Stage 3 than in Stage 2 BCD. CONCLUSION The BCD group RPC density was significantly lower than the control group. The reduction of RPC density in the tempo quadrant occurred mainly in the Stage 1 BCD. In contrast, the reduction of RPC density in superior, inferior, and nasal quadrants occurred mainly in Stage 2.
Adult ; Aged ; Angiography ; Corneal Dystrophies, Hereditary/physiopathology* ; Female ; Humans ; Male ; Microvascular Density ; Microvessels/physiopathology* ; Middle Aged ; Retinal Diseases/physiopathology* ; Retinal Vessels/physiopathology* ; Tomography, Optical Coherence

OBJECTIVE: To build bridges between anti-α enolase antibody (anti-enolase 1 antibody, anti-ENO1 antibody) and common clinical and laboratory characteristics of systemic lupus erythematosus (SLE) and to analyze the role of anti-ENO1 antibody in the evaluation of SLE disease activity. METHODS: The SLE patients with retinopathy and without retinopathy were enrolled in the study, as well as healthy individuals whose gender and age matched with those of the SLE patients. Serum anti-ENO1 antibodies were measured using enzyme-linked immunosorbent assay (ELISA), presenting as intra-group positive rate and arbitrary units (AU) value. Clinical and laboratory data were obtained from medical records. RESULTS: The SLE retinopathy patients represented various fundus abnormalities. Ranked by percentage, the top three retinopathies were retinal hemorrhage (14/32, 43.75%), cotton-wool spots (8/32, 25.00%) and retinal vein occlusion (3/32, 9.38%). Among the 32 SLE retinopathy patients, 13 (40.63%) suffered from two or more fundus abnormalities. The positive rate and AU value of the SLE patients were higher than of the SLE patients without retinopathy (68.75% vs. 46.00%, P=0.043; 16.11%±10.35% vs. 12.06%±6.47%, P=0.045). Besides, the positive rate and AU value of the two SLE groups were both significantly higher than those of the healthy control group (P < 0.001). Compared with the SLE-without-retinopathy group, the systemic lupus erythematosus disease activity index (SLEDAI)-2000 of the SLE retinopathy patients were significantly higher than those of the SLE patients without retinopathy (17.41±4.25 vs. 9.48±5.35, P < 0.001). Dividing all the SLE patients into an anti-ENO1-positive group and an anti-ENO1-negative group, we found that anti-ENO1-positive was more likely to be correlated to developing fever and positive result of urine occult blood (P=0.011, P=0.042). Comparing with the patients with negative anti-ENO1 antibodies, the patients with positive anti-ENO1 antibodies had significantly higher erythrocyte sedimentation rate (ESR) [the median (range) was 29.50 (1.52-110.00) mg/L vs. 12.00 (4.00-101.00) mg/L, P=0.001], higher immunoglobulin G (IgG) [the median (range) was 14.30 (4.02-37.80) g/L vs. 10.46 (2.50-25.73) g/L, P=0.000 3], and higher blood platelet count (PLT) [(205.87×10⁹±67.98×10⁹) /L vs. (164.57×10⁹±69.57×10⁹) /L, P=0.008], as well as higher immunoglobulin A (IgA) [the median (range) was 2.85 (0.07-27.00) g/L vs. 2.05 (0.42-4.36) g/L, P=0.014]. CONCLUSION The positive rate and AU value of anti-ENO1 antibody suggested higher SLE disease activity and they were elevated in SLE and SLE retinopathy.
Humans ; Autoantibodies ; Lupus Erythematosus, Systemic ; Enzyme-Linked Immunosorbent Assay ; Retinal Diseases/etiology* ; Immunoglobulin G

OBJECTIVE: The CYP4V2 gene of two pedigrees affected with Bietti crystalline corneoretinal dystrophy was analyzed to indentify the cause of the disease and provide a basis for clinical diagnosis. METHODS: The probands were subjected to next generation sequencing (NGS). Suspected variants were verified by Sanger sequencing. Pathogenicity of the variants were searched through relevant databases and PubMed by following the ACMG guidelines. RESULTS: A homozygous variant in the CYP4V2 gene c. (802-8) _810delTCATACAGGTCATCGCTinsGC was detected in proband from pedigree 1, parents did not detect; CYP4V2 genes c. (802-8)_810delTCATACAGGTCATCGCTinsGC and c. 958 C>T (p.Arg320X) compound heterozygous variants existed in the proband of pedigree 2,both parents were variant carriers. The results of Sanger sequencing showed that the variant of CYP4V2 gene in the two families was consistent with the NGS sequencing. The c. (802-8)_810delTCATACAGGTCATCGCTinsGC of CYP4V2 gene was splicing variant, and both splicing variant and nonsense variant could produce truncated nonfunctional protein products. Based on standards and guidelines by American College of Medical Genetics and Genomics, the CYP4V2 genes c. (802-8)_810del TCATACAGGTCATCGCTinsGC and c. 958 C>T (p.Arg320X) were predicted to be pathogenic variants (PVS1+PS1+PM2+PM3). CONCLUSION The homozygous variant c. (802-8) _810delTCATACAGGTCATCGCTinsGC and the complex heterozygous variants c. (802-8) _810delTCATACAGGTCATCGCTinsGC and c.958C>T (p.Arg320X) in CYP4V2 gene are the cause of the disease in the probands of two pedigrees , respectively.
Corneal Dystrophies, Hereditary/pathology* ; Cytochrome P450 Family 4/genetics* ; Genetic Variation ; Humans ; Mutation ; Pedigree ; Phenotype ; Retinal Diseases/pathology*

Clinical ophthalmologists consider each retinal disease as a completely unique entity. However, various retinal diseases, such as uveitis, age-related macular degeneration, diabetic retinopathy, and primary open-angle glaucoma, share a number of common pathogenetic pathways. Whether a retinal disease initiates from direct injury to the blood-retinal barrier (BRB) or a defect/injury to retinal neurons or glia that impairs the BRB secondarily, the BRB is a pivotal point in determining the prognosis as self-limiting and recovering, or developing and progressing to a clinical phenotype. The present review summarizes our current knowledge on the physiology and cellular and molecular pathology of the BRB, which underlies its pivotal role in the initiation and development of common retinal diseases.
Blood-Retinal Barrier ; Diabetic Retinopathy ; Humans ; Macular Degeneration ; Phenotype ; Retinal Diseases

OBJECTIVE: To detect mutation of NDP gene in a pedigree affected with Norrie disease. METHODS: Sanger sequencing was used to analyze the NDP gene at Xp11.3. Prenatal diagnosis was performed on amniotic fluid sample after the causative gene was detected. RESULTS: Sanger sequencing has revealed a c.2T>C (p.M1T) missense mutation of the NDP gene in the proband and the fetus. The same variation was not found in ClinVar and HGMD database. CONCLUSION The c.2T>C mutation of the NDP gene probably underlies the Norrie disease in this pedigree.
Blindness ; congenital ; Eye Proteins ; Female ; Genetic Diseases, X-Linked ; Humans ; Nerve Tissue Proteins ; Nervous System Diseases ; Pedigree ; Pregnancy ; Prenatal Diagnosis ; Retinal Degeneration ; Spasms, Infantile

PURPOSE: To investigate the risk factors of diabetic nephropathy in patients with diabetic retinopathy requiring panretinal photocoagulation (PRP) and the visual prognosis. METHODS: A retrospective review of electronic medical records was conducted at Seoul St. Mary's Hospital, comprising 103 patients with type 2 diabetes mellitus and diabetic retinopathy who underwent PRP from 1996 to 2005. Patients with type 1 diabetes mellitus, non-diabetic renal disease, non-diabetic retinal disease, visually significant ocular disease, high-risk proliferative diabetic retinopathy, and advanced diabetic retinopathy were excluded. The patients were divided into three groups: no nephropathy (group 1, n = 45), microalbuminuria (group 2, n = 16), and advanced nephropathy (group 3, n = 42). Duration of diagnosis of retinopathy and nephropathy, glycosylated hemoglobin, visual acuity, complications, and treatment history were investigated. RESULTS: The mean glycosylated hemoglobin of group 3 (8.4 ± 1.2) was higher than that of group 1 (7.7 ± 1.0) or group 2 (7.7 ± 1.0) (p = 0.04). Mean interval from PRP to diagnosis of nephropathy was 8.8 ± 6.0 years in group 2 and 8.7 ± 4.9 years in group 3. The significant decrease in visual acuity in group 3 (28 eyes, 35.9%) was significantly higher than that in group 1 (15 eyes, 18.1%, p = 0.01) or group 2 (6 eyes, 20.7%, p = 0.03). Only vitreous hemorrhage showed a significantly higher incidence in groups 2 and 3 than in group 1 (p = 0.02). Multivariate regression analysis revealed that female sex and lower glycosylated hemoglobin were significantly associated with a protective effect on development of nephropathy. CONCLUSIONS: In the clinical setting, many patients with PRP-requiring diabetic retinopathy develop nephropathy an average of 8 to 9 years after PRP. Male sex and higher glycosylated hemoglobin could be risk factors of nephropathy.
Diabetes Mellitus, Type 1 ; Diabetes Mellitus, Type 2 ; Diabetic Nephropathies ; Diabetic Retinopathy ; Diagnosis ; Electronic Health Records ; Female ; Hemoglobin A, Glycosylated ; Humans ; Incidence ; Light Coagulation ; Male ; Prognosis ; Retinal Diseases ; Retrospective Studies ; Risk Factors ; Seoul ; Visual Acuity ; Vitreous Hemorrhage

BACKGROUND: Because of genetically and phenotypically heterogenous features, identification of causative genes for inherited retinal diseases (IRD) is essential for diagnosis and treatment in coming gene therapy era. To date, there are no large-scale data of the genes responsible for IRD in Korea. The aim of this study was to identify the distribution of genetic defects in IRD patients in Korea. METHODS: Medical records and DNA samples from 86 clinically diagnosed IRD patients were consecutively collected between July 2011 and May 2015. We applied the next-generation sequencing strategy (gene panel) for screening 204 known pathogenic genes associated with IRD. RESULTS: Molecular diagnoses were made in 38/86 (44.2%) IRD patients: 18/44 (40.9%) retinitis pigmentosa (RP), 8/22 (36.4%) cone dystrophy, 6/7 (85.7%) Stargardt disease, 1/1 (100%) Best disease, 1/1 (100%) Bardet-Biedl syndrome, 1/1 (100%) congenital stationary night blindness, 1/1 (100%) choroideremia, and 2/8 (25%) other macular dystrophies. ABCA4 was the most common causative gene associated with IRD and was responsible for causing Stargardt disease (n = 6), RP (n = 1), and cone dystrophy (n = 1). In particular, mutations in EYS were found in 4 of 14 autosomal recessive RP (29%). All cases of Stargardt disease had a mutation in the ABCA4 gene with an autosomal recessive trait. CONCLUSION: This study provided the distribution of genetic mutations responsible for causing IRD in the Korean patients. This data will serve as a reference for future genetic screening and treatment for Korean IRD patients.
Bardet-Biedl Syndrome ; Choroideremia ; Diagnosis ; DNA ; Genetic Testing ; Genetic Therapy ; Humans ; Korea ; Macular Degeneration ; Mass Screening ; Medical Records ; Night Blindness ; Retinal Diseases ; Retinaldehyde ; Retinitis Pigmentosa ; Vitelliform Macular Dystrophy