Retro-orbital injection of FITC-dextran combined with isolectin B4 in assessing the retinal neovascularization defect.

BACKGROUND: A reliable and effective method is required to deliver agent that can aid the in vivo imaging of retinal vessels. The aim of the present study was to evaluate retro-orbital (RO) injection of fluorescein-labeled isothiocyanate dextran (FITC-dextran) as a method of demonstrating retinal neovascularization (NV) and avascular areas in oxygen-induced retinopathy (OIR) mice. METHODS: Different concentrations of FITC-dextran were used to compare the efficacy of this agent in perfusing the retinal vessels. Hematoxylin-eosin (HE) staining was used to evaluate the safety of RO injection. The vitreous blood vessels and extent of NV were assessed in P17 OIR mice using FITC-dextran and compared with the corresponding measurements obtained following isolectin B4 staining or the combination of both methods. RESULTS: The fluorescence of small vessels and neovascular tufts could be observed clearly following RO injection of 0.05 ml of 25 mg/ml or 50 mg/ml FITC-dextran. No visible damage to tissues adjacent to the injection site was discovered. Vitreous blood flow was gradually reduced from P0 to P5 and eventually disappeared in P17 OIR mice, as demonstrated by FITC-dextran perfusion. The retinal NV areas assessed by isolectin B4 were larger than those assessed by FITC-dextran, but the retinal avascular areas were smaller. The combination of both methods could conduce to distinguish non-functional blood vessels. CONCLUSIONS: RO injection of FITC-dextran combined with isolectin B4 is an effective, optimal method for assessing the NV area and avascular area.

Clinical and genetic features of retinoschisis in 120 families with RS1 mutations.

BACKGROUND/AIMS: X-linked retinoschisis (XLRS), associated with RS1, is the most common type of X-linked retinopathy in children. This study aimed to identify clinical and genetic features of retinoschisis in 120 families with RS1 variants in China. METHODS: RS1 variants were collected from our in-house exome data and were predicted by multiple-step bioinformatics analysis. Clinical data of 122 patients from 120 families with potential pathogenic RS1 variants were analysed and summarised, respectively. RESULT: Totally, 79 hemizygous variants (53 missense, 25 truncation and 1 indel), were detected. All except one (78/79, 98.7%), including 22 novels, were classified as potential pathogenic and detected exclusively in 120 families with retinoschisis. Clinical data demonstrated an average age of presentation at 5 years (1 month-41 years). Macular changes were classified as macular schisis (87.5%), macular atrophy (10.7%), normal (0.9%) and unclassified (0.9%). Patients with macular atrophy had older age but similar visual acuity compared with macular schisis. Peripheral retinal changes included flat retinoschisis (52.4%), bullous retinoschisis (BRS) (10.7%) and normal-like (36.9%) patients. Spontaneous regression was observed in two patients with BRS on follow-up examination. Visual acuity in the peripheral retinoschisis group was worse than that without peripheral retinoschisis. CONCLUSION: Almost all rare RS1 variants were potential pathogenic. All patients with RS1 pathogenic variants showed detectable characteristics in the macula and/or peripheral retina. Our data on RS1 variants and associated clinical phenotypes may be of value for clinical diagnosis and genetic test of retinoschisis.

Clinical and Genetic Features of NR2E3-Associated Retinopathy: A Report of Eight Families with a Longitudinal Study and Literature Review.

(1) Background: NR2E3 encodes a nuclear receptor transcription factor that is considered to promote cell differentiation, affect retinal development, and regulate phototransduction in rods and cones. This study aimed to analyze the clinical characteristics and observe the prognosis of autosomal dominant retinopathy (ADRP) and autosomal recessive retinopathy (ARRP) associated with NR2E3; (2) Methods: NR2E3 variants were collected from our exome sequencing data and identified per the American College of Medical Genetics and Genomics criteria. Data from our cohort and a systemic literature review were conducted to explore the NR2E3 variants spectrum and potential genotype-phenotype correlations; (3) Results: Nine pathogenic variants/likely pathogenic variants in NR2E3, including five novel variants, were detected in eight families (four each with ADRP and ARRP). Follow-up data showed schisis/atrophy in the macula and retinal degeneration initiation around the vascular arcades with differences in ADRP and ARRP. A systemic literature review indicated patients with ADRP presented better visual acuity (p < 0.01) and later onset age (p < 0.0001) than did those with ARRP; (4) Conclusions: Macular schisis and retinal degeneration around vascular arcades may present as the prognosis of NR2E3-retinopathy, dominant, or recessive. Our data might further enrich our understanding of NR2E3 variants and associated inherited retinopathy.

Predicting miRNA-disease association through combining miRNA function and network topological similarities based on MINE.

Predicting associations between microRNAs (miRNAs) and diseases from the viewpoint of function modules has become increasingly popular. However, existing methods obtained the relations between diseases and miRNAs only through the construction of similarity networks and neglected the complex network characteristic. In this paper, a new method named combining miRNA function similarities and network topology similarities based on module identification in networks (ComSim-MINE) was developed. Combined similarity is calculated from the harmonic mean between miRNA function similarities and network topology similarities. Experimental results showed that ComSim-MINE can compete with several state-of-the-art weighted function module algorithms, such as ClusterONE, MCODE, NEMO, and SPICi, and achieved the satisfactory results in terms of the composite score of F-measure, sensitivity, and accuracy based on the generated miRNA function interaction network. From the analysis of case studies, some new findings obtained from our proposed method provide clinicians new clues for epidemic diseases, such as COVID-19.

Preoperative laser reduces silicone oil use in primary diabetic vitrectomy.

AIM: To identify the predictive factors and laser photocoagulation associated with the use of silicone oil as endotamponade during primary diabetic vitrectomy. METHODS: The medical and surgical records of 690 patients (798 eyes) who underwent primary diabetic vitrectomy at a tertiary eye hospital in China from January 2018 to December 2018 were reviewed in this retrospective cohort study. The patients' baseline characteristics and preoperative treatments were recorded. The binary Logistic regression model was used to evaluate the risk factors for the use of silicone oil as endotamponade agent during primary vitrectomy for proliferative diabetic retinopathy (PDR)-related complications. RESULTS: Among 690 patients with mean age of 52.1±10.5y (range: 18-85y), 299/690 (43.3%) were female. The 31.6% of the eyes received preoperative laser treatment, and 72.4% of the eyes received preoperative anti-VEGF adjuvant therapy. Non-clearing vitreous haemorrhage (VH) alone or combined with retinal detachment was the main surgical indication (89.5%) for primary vitrectomy. Silicone oil was used as endotamponade in 313 (39.2%) eyes. Lack of preoperative laser treatment [odds ratio (OR) 0.66, 95% confidence interval (CI): 0.48-0.92; P=0.015] and older age (OR 0.96, 95%CI: 0.95-0.98; P<0.001) were predictors of silicone oil tamponade during primary vitrectomy for PDR. CONCLUSION: The lack of preoperative laser treatment is a significant predictor of silicone oil tamponade during primary vitrectomy for PDR. However, the severity of PDR relevant to silicone oil use should be further evaluated.

Microinvasive pars plana vitrectomy versus panretinal photocoagulation in the treatment of severe non-proliferative diabetic retinopathy (the VIP study): study protocol for a randomised controlled trial.

INTRODUCTION: Diabetic retinopathy (DR) is the main cause of adult visual impairment worldwide. Severe non-proliferative DR (sNPDR) is an important clinical intervention stage. Currently, panretinal photocoagulation (PRP) is the standard treatment for sNPDR. However, PRP alone cannot completely prevent NPDR progression. One explanation might be that PRP does not remove the detrimental vitreous that plays an important role in DR progression. Microinvasive pars plana vitrectomy (PPV) was shown to be a safe and effective method to treat late-stage proliferative DR (PDR) by completely removing the pathological vitreous. However, whether PPV is effective in controlling sNPDR remains unknown. In this trial, we aim to compare the effectiveness of microinvasive PPV with that of PRP for sNPDR progression control. METHODS AND ANALYSIS: This single centre, parallel group, randomised controlled trial aims to evaluate the clinical efficacy of microinvasive PPV in preventing the progression of sNPDR compared with PRP. A total of 272 adults diagnosed with sNPDR will be randomised 1:1 to the microinvasive PPV and PRP groups. The primary outcome is the disease progression rate, calculated as the rate of sNPDR progressed to PDR from baseline to 12 months after treatment. The secondary outcomes include the change in best-corrected visual acuity, re-treatment rate, diabetic macular oedema occurrence, change in central retinal thickness, change in the visual field, cataract occurrence and change in the quality of life. ETHICS AND DISSEMINATION: The Ethics Committee of Zhongshan Ophthalmic Center approved this study (2019KYPJ108). The results will be presented at scientific meetings and submitted for publication to peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04103671.