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Background:To evaluate whether better prognosis can be obtained from the continuous surgical treatment (CST) before fibrosis /scar formation in open anterior segment (AS) injury.Methods:Prospective cohort study.19 eyes of 19 patients were selected from the database of Eye Injury Vitrectomy Study, which is a multi-center prospective cohort study and began in 1990s, from January 1, 2020 to July 31, 2021. Of these, 9 patients who received CST were assigned to group 1, and 10 patients without continuous treatment after initial wound repairment were included in group 2. Comparison between two groups was conducted in final best corrected visual acuity (BCVA), presumably significant complications with X² test. Corneal leucoma area ratio, astigmatism and score of AS abnormalities were analyzed by Students’ t-test.Results:Gross appearance displays remarkable differences between two groups with observation on AS. The individually paradigm, such as corneal-scleral wound and intraocular abnormalities, can be noted over various post-traumatic time intervals. The final BCVA is better in group 1(P=0.011). The complications directly caused by AS injury, adhesive corneal leucoma, uneven anterior chamber, block of light pass through pupil and fibrosis/scar are more frequent in group 2 (P=0.011, 0.022, 0.037 and 0.040, respectively). Secondary glaucoma (three cases) and severe AS structure destruction (two cases) occurred only in group 2 (P=0.037 and 0.474, respectively).Conclusions:Relying on comprehensive evaluations, advantages of CST of initiating before fibrosis/scar formation in open AS injury show dominance over following nature course of wound healing after wound repairment.

Severe mechanical ocular trauma with no light perception (NLP) predicts a poor prognosis of visual acuity and enucleation of the eyeball. Since the innovative treatment concept of exploratory vitreoretinal surgery has developed and treatment technology has advanced, the outcomes of severe ocular trauma treatment in NLP patients have greatly improved. However, there remains a lack of unified standards for the determination, surgical indication, and timing of vitrectomy in NLP eye treatment. To address these problems, we aimed to create evidence-based medical guidelines for the diagnosis, treatment, and prognosis of mechanical ocular trauma with NLP. Sixteen relevant recommendations for mechanical ocular trauma with NLP were obtained, and a consensus was reached. Each recommendation was explained in detail to guide the treatment of mechanical ocular trauma associated with NLP.

To observe the ultrastructural outcomes of autologous transplantation of retinal pigment epithelium-partial-thickness choroidal (RPE-PTC) sheets in rabbits after 6 months.Eighteen pigmented rabbits were used in this study. Among them, nine rabbits were used for autologous transplantation of RPE-PTC sheets. Tissue sections were observed under a transmission electron microscope for one, three, and six months after transplantation, respectively.One, three, and six months after the autologous transplantation of RPE-PTC sheets, the inner and outer segments of photoreceptor cells were arranged regularly, and the connection between the inner and outer segments was normal. The inner structure of the RPE cells and tight junctions among them remained normal. Phagocytosis of outer segment of photoreceptor cells could also be observed in RPE cells. The structure of the Bruch's membrane appeared loose, rather than being dense as normal, and it was undulated after one and three months, while it became dense after six months. The graft and the bed were healed well, the boundary was unclear, and the graft was vascularized after one, three, and six months, respectively.Our findings revealed that the RPE-PTC sheets could quickly rebuild blood vessels, thereby maintaining the normal physiological functions of RPE cells, as well as the survival and functional status of photoreceptor cells for a long-time.

Background and Objective In smoking cessation clinical research and practice, objective validation of self-reported smoking status is crucial for ensuring the reliability of the primary outcome, that is, smoking abstinence. Speech signals convey important information about a speaker, such as age, gender, body size, emotional state, and health state. We investigated (1) if smoking could measurably alter voice features, (2) if smoking cessation could lead to changes in voice, and therefore (3) if the voice-based smoking status assessment has the potential to be used as an objective smoking cessation validation method. Methods A systematic review of the scientific literature was conducted to compile studies on smoking status assessment based on voice features. We searched nine scientific databases for original studies involving the effects of smoking on voice features, the effects of smoking cessation on voice features. Results A total of 34 studies were identified for review. We found that fundamental frequency, jitter, shimmer, harmonics to noise ratio, and other voice features are affected by smoking and could be used to assess smoking status. Conclusion Speech assessment of smoking status based on voice features has potential as a smoking status validation method, as it is simple, reliable, and less time-consuming. Furthermore, this study provides recommendations for future research on the objective speech assessment of smoking status based on voice features.

Background: Closure of traumatic macular hole (TMH) can be achieved spontaneously or by surgical intervention. Thus far, there exist no prospective comparative studies that have analyzed the difference between the two modalities. This study aimed to compare the anatomical and visual recovery of eyes with TMH following either an immediate vitrectomy or six-month observation. Methods: This was a multicenter prospective comparative study. Eight centers participated in the study. Patient data from 40 eyes with a recent history of blunt ocular trauma and newly formed full-thickness TMH were recruited in this study. The participating patients selected between an early vitrectomy or a six-month observation after a doctor explained the potential benefits and risks of both strategies in an unbiased manner. Twenty-five patients underwent an immediate vitrectomy, and 15 patients received six-month observation. Patients were assessed by spectral-domain optical coherence tomography (SD-OCT) and best-corrected visual acuity (BCVA). Results: Closure rates were 66.7% for the observational group, and 100% for the surgical group (P=0.002). There were no vision-threatening ocular complications in both groups. For the observational group, the mean closure time was 2.5±1.6 months, and 80% of the hole closure occurred within 3 months; cystic edema on the edge of the hole at baseline was significantly more frequent in the non-closed subgroup than in the closed subgroup (P=0.03). There were no significant differences in the foveal microstructure and in the final visual outcome between the spontaneously closed cases and the surgically closed cases. Conclusions: TMH had a moderately high incidence of spontaneous closure, but an immediate vitrectomy achieved an even higher closure rate. Vitrectomy was effective and safe to treat TMH, while a 3-month observation for spontaneous closure may be an alternative modality for TMH management. Cystic edema on the edge of the hole may be an unfavorable factor for the spontaneous closure of TMH.

Purpose To investigate the frequency of primary angle closure (PAC) and primary angle closure glaucoma (PACG) in patients with retinal vein occlusion (RVO) based on a hospital population. Methods A total of 375 consecutive cases newly diagnosed with RVO by fluorescein fundus angiography at a single eye centre in Peking were reviewed. Gonioscopy was performed in all patients. Glaucoma was diagnosed according to the criteria of the International Society of Geographical and Epidemiological Ophthalmology. Retinal vein occlusion was classified as central retinal vein occlusion (CRVO), hemicentral retinal vein occlusion (HRVO), or branch retinal vein occlusion (BRVO), and as arteriovenous crossing RVO (AV-RVO), optic cup RVO (OC-RVO), optic nerve RVO without optical nerve head swelling (NONHS-RVO), or RVO with optical nerve head swelling (ONHS-RVO) based on the site of venous occlusion. Percentage of PAC or PACG for each type of RVO were calculated. Results PACG had a frequency of 4.1% [95% confidence interval (CI) 2.2-6.9%] in 317 RVO patients [5.3% (95% CI 2.0-11.2%) in CRVO, 8.8% (95% CI 1.9-23.7%) in HRVO, and 1.9% (95% CI 0.4-5.4%) in BRVO]. Primary angle closure (PAC) had a frequency of 2.9% (95% CI 1.4-5.5%) in RVO. PAC/PACG had a frequency of 11.5% (95% CI 6.3-18.9%) in CRVO, 8.8% (95% CI 1.9-23.7%) in HRVO and 3.1% (95% CI 1.0-7.1%) in BRVO. PAC/PACG was significantly more prevalent in NONHS-RVO [18.9% (95% CI 9.4-32.0%)] than in ONHS-RVO [6.5% (95% CI 2.1-14.5%)], AV-RVO [3.1% (95% CI 0.9-7.8%)], and OC-RVO [2.3% (95% CI 0.1-12.3%)]. Conclusion The overall frequency of PAC/PACG was much higher in patients with RVO (especially CRVO) than that in the general population. Eyes with PAC/PACG may undergo mechanical changes in the lamina cribrosa of the optic disc, resulting in RVO. Angle-closure conditions should be borne in mind when investigating Chinese patients with RVO.

A novel class of styryl sulfones were designed and synthesized as CAPE derivatives by our work team, which showed a multi-target neuroprotective effect, including antioxidative and anti-neuroinflammatory properties. However, the underlying mechanisms remain unclear. In the present study, the anti-Parkinson’s disease (PD) activity of 10 novel styryl sulfone compounds was screened by the cell viability test and the NO inhibition test in vitro. It was found that 4d exhibited the highest activity against PD among them. In a MPTP-induced mouse model of PD, the biological activity of 4d was validated through suppressing dopamine neurotoxicity, microglial activation, and astrocytes activation. With compound 4d, we conducted the mechanistic studies about anti-inflammatory responses through inhibition of p38 phosphorylation to protect dopaminergic neurons, and antioxidant effects through promoting nuclear factor erythroid 2-related factor 2 (Nrf2). The results revealed that 4d could significantly inhibit 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/1-methyl-4-phenylpyridinium (MPTP/MPP+)-induced p38 mitogen-activated protein kinase (MAPK) activation in both in vitro and in vivo PD models, thus inhibiting the NF-κB-mediated neuroinflammation-related apoptosis pathway. Simultaneously, it could promote Nrf2 nuclear transfer, and upregulate the expression of antioxidant phase II detoxification enzymes HO-1 and GCLC, and then reduce oxidative damage.

Purpose To report the results and complications of scleral buckling for the treatment of rhegmatogenous retinal detachment (RRD) using 25-gauge chandelier endoillumination. Methods A total of 61 patients (61 eyes) with RRD were treated with scleral buckling. For the sclera buckling procedure, a 25-gauge chandelier was inserted through the pars plana for intra-ocular illumination, and retinal tears were identified and treated with episcleral cryotherapy under surgical microscope. On postoperative days 1, 3 and 7, the intra-ocular pressure was measured by a non-contact tonometer. On postoperative months 1 and 3, ultrasound biomicroscopy was used to examine the pars plana incision. Results In the surgical procedure, there was no lenticular or retinal damage due to the chandelier insertion. There was no conjunctival bleb formation at pars plana incision and no incidence of endophthalmitis after surgery. The mean intra-ocular pressure was 15.74 ± 2.98, 15.83 ± 2.76 and 16.14 ± 2.52 mmHg on postoperative days 1, 3 and 7, respectively. The one-time retinal reattachment rate was 93.4%. No visible vitreous incarceration was found in the incision of the pars plana. Conclusion There was no complication found due to the chandelier insertion in early postoperative period. Chandelier endoillumination is a feasible method for retinal visualization under surgical microscope during scleral buckling.

Younger patients who underwent vitrectomy for proliferative diabetic retinopathy (PDR) display more aggressive nature distinguished from the older patients. Preoperative anti-VEGF therapy has been widely used as an adjunct for PDR surgery. However, the effect of anti-VEGF administration in young diabetics has rarely been evaluated in previous studies. The purpose of this study was to evaluate the effects of ranibizumab pretreatment on vitrectomy surgery in young patients with PDR.This was a prospective nonrandomized comparative study. Young patients (40 years old) undergoing diabetic vitrectomy with or without ranibizumab pretreatment (25 eyes in each group) were analyzed in this study. The use of the drug was determined by the patients' own preference. The two surgical groups were matched according to a complexity score. Intravitreal injection of ranibizumab (IVR) was performed 3-5 days prior to the vitrectomy surgery in the IVR group. Intraoperative records including total surgical time, intraoperative bleeding, the use of endodiathermy, the frequency of relaxing retinotomies, the incidence of iatrogenic retinal breaks, and the use of perfluorocarbon liquid (PFCL) and silicone oil tamponade, and postoperative indices regarding recurrent vitreous hemorrhage (VH), neovascular glaucoma (NVG), recurrent retinal detachment, and visual outcome were evaluated between the two groups. All patients were followed up for one year after surgery.In young PDR patients, the severity of intraoperative bleeding was significantly lower in the IVR group than in the control group (P=0.04). The total surgical time was shorter in the IVR group than in the control group. However, the rate of relaxing retinotomy, the incidence of iatrogenic retinal breaks and the use of PFCL and silicone oil tamponade were not affected by IVR pretreatment but affected by the complexity score of the case. Early postvitrectomy hemorrhage occurred less frequently in the IVR group than in the control group (P0.001), Early visual recovery was better in the IVR group than in the control group (P=0.03). However, there were no significant differences in the development of late recurrent VH, NVG, recurrent retinal detachment, and final visual outcome.IVR pretreatment is a safe and effective adjunct to vitrectomy in reducing intraoperative and early postvitrectomy bleeding and should be suggested in young PDR patients. However, IVR does not reduce the incidence of intraoperative and late postoperative complications in these patients. The risk of iatrogenic retinal breaks and silicone oil use are closely correlated with the complexity score of the surgical cases.

Purpose To characterize the classification, incidence, diagnosis and prognosis of traumatic choroidal injuries. Methods Subjects were selected from the database of the Eye Injury Vitrectomy Study (EIVS) and were examined for occurrences of different categories of choroidal injuries. Standard photographs were collected. Anatomical and visual outcomes were assessed in patients with greater than 1 year of follow-up. Eyes that had no light perception (NLP) and/or phthisis bulbi were defined as having had unfavourable outcomes. The percentage of eyes with an unfavourable outcome was analysed for different types of choroidal injuries. Results Nine categories of choroidal injuries with distinctive features were identified in the EIVS database. The incidence and the percentage of eyes with an unfavourable outcome in each injury category were as follows: suprachoroidal effusion, 21.2% (7.2%); suprachoroidal haemorrhage, 12.8% (11.2%); massive suprachoroidal haemorrhage, 4.0% (64.9%); choroidal avulsion, 4.2% (92.2%); traumatic chorioretinal rupture, 1.8% (13.3%); choroidal rupture, 4.8% (6.8%); choroidal loss, 1.6% (79.3%); choroidal hole, 1.1% (5.3%); and choroidal damage at the wound site, 39.2% (17.7%). Conclusions Ocular trauma can cause a variety of choroidal injuries that have distinctive features, some of which are associated with a high frequency of unfavourable prognoses.

"AIM: To describe the complex, overlapping phenotype of four Chinese patients with inherited retinal dystrophies (IRDs) who harbored two pathogenic genes simultaneously. METHODS: This retrospective study included 4 patients affected with IRDs. Medical and ophthalmic histories were obtained, and clinical examinations were performed. A specific Hereditary Eye Disease Enrichment Panel (HEDEP) based on exome capture technology was used for genetic screening. RESULTS: Four patients were identified to harbor disease-causing variants in two different genes. Patient retinitis pigmentosa (RP) 01-II:1 exhibited both classical ABCA4 -induced Stargardt disease (STGD) 1 and USH2A-associated RP, patient RP02-III:2 exhibited both classical ABCA4-induced STGD1 and CDH23-associated RP, patient RP03-II:1 exhibited both USH2A-induced autosomal recessive retinitis pigmentosa (arRP) syndrome and SNRNP200-induced autosomal dominant retinitis pigmentosa (adRP), and patient RP04- II:2 exhibited USH2A-induced arRP syndrome and EYS-induced arRP at the same time. CONCLUSION: Our study demonstrates that genotype–phenotype correlations and comprehensive genetic screening is crucial for diagnosing IRDs and helping family planning for patients suffering from the disease."

Retinitis pigmentosa (RP) is a clinically and genetically heterogeneous disorder characterized by night blindness, visual field constriction, and severely reduced visual acuity. Despite a number of genes being implicated in RP pathogenesis, the genetic etiology of the disease remains unknown in many patients. In this study, our aim was to identify the disease-causing mutation of a large Chinese family with autosomal dominant RP (adRP). Targeted exon capture sequencing was initially performed to screen mutations in known disease-causing genes, followed by exome sequencing. In doing so, a heterozygous mutation in ADIPOR1 (c.929A > G) that results in an amino acid substitution (p.Y310C) was identified to co-segregate with the disease phenotype in this family. Adipor1 is wildly expressed throughout the body, but appears to be enriched in the photoreceptor inner and outer segments. The p.Y310C mutation, predicted to affect the structure and function of the protein, was confirmed to affect protein folding and its subcellular localization in vitro. In addition, knockdown of adipor1 expression in a zebrafish model with morpholino (MO) preferentially reduced the number of rod photoreceptors, with no effect on the number of cones, a phenotype that is characteristic of RP. Furthermore, the knockdown phenotype was partially rescued by injecting wild-type, but not mutant, human ADIPOR1 mRNA. We conclude that ADIPOR1 is a novel adRP-causing gene and plays an important role in rod development and maintenance.

Purpose To compare the outcome after choroidal neovascular (CNV) membrane excision and retinal pigment epithelium (RPE) transplantation and make further evaluation of two types of RPE grafts on the visual function in patients with neovascular age-related macular degeneration (AMD), complicated by massive subretinal haemorrhage. Methods We retrospectively reviewed 80 patients who underwent CNV membrane excision with or without RPE transplantation. Two types of RPE grafts were adopted, RPE–Bruch's membrane complex graft (subgroup 1) and RPE monolayer sheet graft (subgroup 2). Outcome measures included pre- and postoperative visual acuity score (VAS), clinical findings, complications and recurrence rates. Results The mean VAS [Early Treatment of Diabetic Retinopathy Study (ETDRS)] in the CNV membrane excision group was 11.06 ± 18.28 at baseline and 14.41 ± 16.86 at follow-up (p = 0.12) in a mean follow-up period of 24.35 ± 9.31 months. While in subgroup 1, VAS increased from 22.62 ± 23.72 to 35.50 ± 24.46 (p = 0.02) in a mean period of 20.63 ± 6.25 months. The percentage of visual acuity (VA) improvement (at least two or more lines changed) in subgroup 1 is 62.5%, which is significantly higher than that in CNV excision group (23.5%), p = 0.02. In subgroup 2, VAS increased from 16.61 ± 27.98 to 29.16 ± 23.80 (p = 0.02) in a mean period of 21.72 ± 11.09 months. The percentage of VA improvement in subgroup 2 is 58.0%, which is also significantly higher than that in CNV excision group (23.5%), p = 0.02. Postoperative VA elevation was comparable between the two subgroups (p = 0.05). Complications including retinal detachment, proliferative vitreal retinopathy and CNV recurrence occurred in both techniques. Central fixation stability was observed in eight eyes in subgroup 1 and five eyes in subgroup 2. Conclusions The autologous RPE transplantation can increase the vision of patients with haemorrhagic AMD. Two types of autologous RPE grafts were both effective and comparable in restoring visual function and central fixation stability.

Axonal tracing is useful for detecting optic nerve injury and regeneration, but many commonly used methods cannot be used to observe axoplasmic flow and synaptic transmission in vivo. Manganese (Mn(2+))-enhanced magnetic resonance imaging (MEMRI) can be used for in vivo longitudinal tracing of the visual pathway. Here, we explored the dose response and time course of an intravitreal injection of MnCl2 for tracing the visual pathway in rabbits in vivo using MEMRI. We found that 2 mM MnCl2 enhanced images of the optic nerve but not the lateral geniculate body or superior colliculus, whereas at all other doses tested (5-40 mM), images of the visual pathway from the retina to the contralateral superior colliculus were significantly enhanced. The images were brightest at 24 hours, and then decreased in brightness until the end of the experiment (7 days). No signal enhancement was observed in the visual cortex at any concentration of MnCl2. These results suggest that MEMRI is a viable method for temporospatial tracing of the visual pathway in vivo. Signal enhancement in MEMRI depends on the dose of MnCl2, and the strongest signals appear 24 hours after intravitreal injection.

Directed differentiation of human induced pluripotent stem cells (iPSCs) into retinal pigmented epithelium (RPE) holds great promise in cell replacement therapy for patients suffering from degenerative eye diseases, including age-related macular degeneration (AMD). In this study, we generated iPSCs from human dermal fibroblasts (HDFs) by electroporation with episomal plasmid vectors encoding OCT4, SOX2, KLF4, L-MYC together with p53 suppression. Intriguingly, cell reprogramming resulted in a metastable transcriptional activation and selective demethylation of neural and retinal specification-associated genes, such as OTX2, RX1 and SIX3. In contrast, RPE progenitor genes were transcriptionally silent in HDFs and descendant iPSCs. Overexpression of OCT4 and SOX2 directly stimulated the expression of OTX2, RX1 and SIX3 in HDFs and iPSCs. Luciferase and chromatin immunoprecipitation (ChIP) assays further identified an OCT4- and two SOX2-binding sites located in the proximal promoter of OTX2. Histone acetylation and methylation on the local promoter also participated in the reactivation of OTX2. The transcriptional conversion of RX1 and SIX3 genes partially attributed to DNA demethylation. Subsequently, iPSCs were induced into the RPE cells displaying the characteristics of polygonal shapes and pigments, and expressing typical RPE cell markers. Taken together, our results establish readily efficient and safe protocols to produce iPSCs and iPSC-derived RPE cells, and underline that the reactivation of anterior neural transcription factor OTX2, eye field transcription factor RX1 and SIX3 in iPSCs is a feature of pluripotency acquisition and predetermines the potential of RPE differentiation.

Inherited retinal dystrophies (IRDs) are a group of clinically and genetically heterogeneous diseases involving more than 280 genes and no less than 20 different clinical phenotypes. In this study, our aims were to identify the disease-causing gene variants of 319 Chinese patients with IRD, and compare the pros and cons of targeted panel sequencing and whole exome sequencing (WES). Patients were assigned for analysis with a hereditary eye disease enrichment panel (HEDEP) or WES examination based on time of recruitment. This HEDEP was able to capture 441 hereditary eye disease genes, which included 291 genes related to IRD. As RPGR ORF15 was difficult to capture, all samples were subjected to Sanger sequencing for this region. Among the 163 disease-causing variants identified in this study, 73 had been previously reported, and the other 90 were novel. Genes most commonly implicated in different inheritances of IRDs in this cohort were presented. HEDEP and WES achieved diagnostic yield with 41.2% and 33.0%, respectively. In addition, nine patients were found to carry pathogenic mutations in the RPGR ORF15 region with Sanger sequencing. Our study demonstrates that HEDEP can be used as a first-tier test for patients with IRDs.

Compared to the doubly fed induction machine (DFIM), the brushless doubly fed induction machine (BDFIM) has higher reliability by virtue of the absence of a brush gear. Recent research on structure optimization design and control strategy of BDFIM has made remarkable progress. BDFIM indirect stator-quantities control (ISC) is a new control strategy, which, in comparison to vector control strategy, requires fewer parameters and does not need rotating coordinate transformation. This paper further develops the dynamic control of reactive power for the BDFIM with ISC scheme. Detailed theoretical analysis is done to show the controller structure of the reactive power. The experimental results of the prototype show the feasibility of the proposed scheme. As a result, the proposed ISC controllers have been able to control not only speed and torque, but also the reactive power.

Purpose: To study the microsurgical anatomy of the lacrimal drainage system and to provide anatomical evidence for transnasal endoscopic lacrimal drainage system bypass surgery by autogenous tissue grafting. Materials and Methods: A total of 20 Chinese adult cadaveric heads in 10% formaldehyde, comprising 40 lacrimal ducts were used. The middle third section of the specimens were examined for the following features: the thickness of the lacrimal fossa at the anterior lacrimal crest, vertical middle line, and posterior lacrimal crest; the cross section of the upper opening, middle part, and lower opening of the nasolacrimal canal; the horizontal, 30° oblique, and 45° oblique distances from the lacrimal caruncle to the nasal cavity; the distance from the lacrimal caruncle to the upper opening of the nasolacrimal duct; and the included angle between the lacrimal caruncle-nasolacrimal duct upper opening junction and Aeby's plane. Results: The middle third of the anterior lacrimal crest was significantly thicker than the vertical middle line and the posterior lacrimal crest ( P > 0.05). The horizontal distance, 30° oblique distance, and 45° oblique distance from the lacrimal caruncle to the nasal cavity exhibited no significant differences ( P > 0.05). The included angle between the lacrimal caruncle and the lateral wall middle point of the superior opening line of the nasolacrimal duct and Aeby's plane was average (49.9° ± 1.8°). Conclusion: The creation of the bony tunnel should start from the middle or posterior middle part of the lacrimal fossa, extending toward the anterior inferior region with an optimal downward oblique angle of 45°.

Context: Severe pediatric ocular injury remains a frequent and difficult problem. Vitrectomy is a major technique that has been used to manage severely damaged eyes. However, limited follow-up studies exist currently. Aims: To evaluate the clinical features and predictive factors of visual and anatomic outcomes in Eye Injury Vitrectomy Study (EIVS). Settings and Design: Retrospective, consecutive, interventional case series. Materials and Methods: Reviewing and analyzing records of children, aged 15 years or younger, who had undergone vitrectomy for eye injuries in EIVS database between January 1997 and December 2009. Statistical analysis used: Descriptive analyses and multiple Logistic regressions were employed for all variables using SPSS software (version 17.0, SPSS Inc.). Results: Eighty-seven children (89 eyes) with more than 6 months follow-up and complete records identified in EIVS were included in this study. Average follow-up was 12.7 months. The mean age was 9.4 ± 3.8 years. Seventy-seven eyes (86.5%) had open globe injuries, and 12 (13.5%) had closed globe injuries. Seventeen eyes (19.3%) presented with endophthalmitis. Seventy-five eyes (88.2%) presented with visual acuity of 4/200 or worse; however, 42 eyes (47.7%) achieved 4/200 or better vision with anatomical restoration after vitrectomy. Multiple analysis showed that choroidal damage, large scleral wound, and endophthalmitis were significantly associated with unfavorable outcome, the OR values were 16.7 (95% CI: 2.7-102.4, P = 0.002), 10.9 (95% CI: 1.7-71.6, P = 0.013), and 6.6 (95% CI: 1.0-42.4, P = 0.048), respectively. Conclusions: Vitrectomy intervention resulted in favorable visual and anatomic outcomes in almost half of the injured eyes. Choroidal damage, large scleral wound, and endophthalmitis were the prognostic indicators of unfavorable outcome.

Background: Manganese-enhanced magnetic resonance imaging (MEMRI) for visual pathway imaging via topical administration requires further research. This study investigated the permeability of the corneal epithelium and corneal toxicity after topical administration of Mn 2+ to understand the applicability of MEMRI. Methods: Forty New Zealand rabbits were divided into 0.05 mol/L, 0.10 mol/L, and 0.20 mol/L groups as well as a control group ( n = 10 in each group). Each group was further subdivided into epithelium-removed and epithelium-intact subgroups ( n = 5 in each subgroup). Rabbits were given 8 drops of MnCl 2 in 5 min intervals. The Mn 2+ concentrations in the aqueous and vitreous humors were analyzed using inductively coupled plasma-mass spectrometry at different time points. MEMRI scanning was carried out to image the visual pathway after 24 h. The corneal toxicity of Mn 2+ was evaluated with corneal imaging and pathology slices. Results: Between the aqueous and vitreous humors, there was a 10 h lag for the peak Mn 2+ concentration times. The intraocular Mn 2+ concentration increased with the concentration gradients of Mn 2+ and was higher in the epithelium-removed subgroup than that in the epithelium-intact subgroup. The enhancement of the visual pathway was achieved in the 0.10 mol/L and 0.20 mol/L epithelium-removed subgroups. The corresponding peak concentrations of Mn 2+ were 5087 ± 666 ng/ml, 22920 ± 1188 ng/ml in the aqueous humor and 884 ± 78 ng/ml, 2556 ± 492 ng/ml in the vitreous body, respectively. Corneal injury was evident in the epithelium-removed and 0.20 mol/L epithelium-intact subgroups. Conclusions: The corneal epithelium is a barrier to Mn 2+ , and the iris and lens septum might be another intraocular barrier to the permeation of Mn 2+ . An elevated Mn 2+ concentration contributes to the increased permeation of Mn 2+ , higher MEMRI signal, and corneal toxicity. The enhancement of the visual pathway requires an effective Mn 2+ concentration in the vitreous body.

Hypertension is one of the most important, preventable causes of premature morbidity and mortality in the developed world. Aldosterone is a major mineralocorticoid hormone that plays a key role in the regulation of blood pressure and is implicated in the pathogenesis of hypertension and heart failure. Aldosterone synthase (AS, cytochrome P450 11B2, cyp11B2) is the sole enzyme responsible for the production of aldosterone in humans. To determine the effects of increased expression of human aldosterone synthase (hAS) on blood pressure (BP), we established transgenic mice carrying the hAS gene (cyp11B2). We showed that hAS overexpression increased levels of aldosterone in hAS+/− mice. On high salt diet (HS), BPs of hAS+/− mice were significantly increased compared with WT mice. Fadrozole (an inhibitor of aldosterone synthase) treatment significantly reduced BPs of hAS+/− mice on HS. This is the first time overexpression of AS in a transgenic mouse line has shown an ability to induce HP. Specifically inhibiting AS activity in these mice is a promising therapy for reducing hypertension. This hAS transgenic mouse model is therefore an ideal animal model for hypertension therapy studies.

To investigate the influence of the S447X variant in lipoprotein lipase (LPL) gene on the response rate to therapy with the thiazolidinedione pioglitazone. A total of 113 diabetic patients were treated with pioglitazone 30 mg for 10 weeks. Response to the pioglitazone treatment was defined by either a >10% relative reduction in fasting blood glucose (FBG) or a more than 1% decrease in glycosylated haemoglobin (HbA1c) values after 10 weeks of pioglitazone treatment. The genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism method. Using the criteria >10% relative reduction in FBG after 10 weeks of pioglitaone treatment, responder frequency to pioglitazone treatment in S447S genotype group is significantly higher than S447X genotype group. Meanwhile, the S447X genotype conferred a statistically significant 0.538-fold reduction in response rate to pioglitazone treatment relative to the S447S genotype. Moreover, pioglitazone treatment has significantly beneficial effects on serum lipid profile and blood pressure in S447S genotype carriers. The S447X variant in LPL gene may be a cause for therapy modification by pioglitazone.

Retinitis pigmentosa (RP) is the most common inherited retinal disease. It is a clinically and genetically heterogeneous disorder, which is why it is particularly challenging to diagnose. The aim of this study was to establish a targeted next-generation sequencing (NGS) approach for the comprehensive, rapid, and cost-effective clinical molecular diagnosis of RP. A specific hereditary eye disease enrichment panel (HEDEP) based on exome capture technology was used to collect the protein coding regions of 371 targeted hereditary eye disease genes, followed by high-throughput sequencing on the Illumina HiSeq2000 platform. From a cohort of 34 Chinese RP families, 13 families were successfully diagnosed; thus, the method achieves a diagnostic rate of approximately 40%. Of 16 pathogenic mutations identified, 11 were novel. Our study demonstrates that targeted capture sequencing offers a rapid and effective method for the molecular diagnosis of RP, which helps to provide a more accurate clinical diagnosis and paves the way for genetic counseling, family planning, and future gene-targeted treatment.

The accumulation of beta-amyloid (A beta) in neuritic plaques is thought to be causative for the progression of Alzheimer's disease (AD). Recently, both active immunization and passive administration of A beta antibodies dramatically attenuated amyloid plaque deposition, neuritic dystrophy, astrogliosis and behaviour deficits in transgenic animals. In addition, we and others have found that titres of naturally occurring anti-A beta antibodies in the CSF of AD patients are significantly lower than those in age-matched controls. Treatment with intravenous immunoglobulins (a preparation that contained anti-A beta antibodies) significantly lowered CSF levels of A beta in non-demented patients. In this study, anti-A beta antibodies were isolated from immunoglobulin preparations and these anti-A beta antibodies strongly block fibril formation or disrupt formation of fibrilar structures. Furthermore, these antibodies almost completely prevented neurotoxicity of A beta. In contrast, immunoglobulins depleted of anti-A beta antibodies had little effect on A beta fibril formation or protection of neuronal cells. This study supports the findings that human anti-A beta antibodies may interfere with the pathogenesis of AD by more than one mechanism, and administration of polyclonal human anti-A beta antibodies isolated from plasma is a potential therapeutic agent to prevent or slow down disease progression.

Purpose To identify disease-causing mutations in Chinese families who presented with retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA). Methods The pathogenic variant in a Chinese family with autosomal dominant RP was investigated with a specific hereditary eye disease enrichment panel (HEDEP) based on targeted exome capture technology. The identified variant was confirmed with Sanger sequencing. CRB1 mutations in 67 patients with sporadic retinal dystrophy were examined with Sanger sequencing. Results Compound heterozygous mutations were identified in a family who had undergone HEDEP analysis. After complete sequence analysis of the CRB1 gene was performed in 67 patients with sporadic retinal dystrophy, other compound heterozygous mutations were detected in three families. The mutations included three novel heterozygous mutations: c.3059delT (p.M1020SfsX1), c.3460T>A (p.C1154S), and c.4207G>C (p.E1403Q). The mutation frequency of CRB1 in this study was 5.9% (8/136). Conclusions Our findings broaden the spectrum of CRB1 mutations and the phenotypic spectrum of the disease in Chinese patients. The results from this study show that patients with LCA carry CRB1 null mutations more frequently than patients with RP.

Objectives To identify disease-causing mutations in two Chinese families with autosomal dominant retinitis pigmentosa (adRP). Design Prospective analysis. Patients Two Chinese adRP families underwent genetic diagnosis. A specific hereditary eye disease enrichment panel (HEDEP) based on targeted exome capture technology was used to collect the protein coding regions of targeted 371 hereditary eye disease genes; high throughput sequencing was done with the Illumina HiSeq 2000 platform. The identified variants were confirmed with Sanger sequencing. Setting All experiments were performed in a large laboratory specialising in genetic studies in the Department of Ophthalmology, Peking University Third Hospital. Results Two novel mutations, including one splice site mutation (Int10 c.1074-2 A>T; p.Y359SfsX29) and one insertion (c.824_825insA; p.Y275X) of PRPF31 were identified in the two families. The two mutations segregated with the disease phenotype in their respective families. Conclusions Our findings broaden the spectrum of PRPF31 mutations causing adRP and the phenotypic spectrum of the disease in Chinese patients. The HEDEP based on targeted exome capture technology is an efficient method for molecular diagnosis in adRP patients.

Purpose To explore the possibility of the PEGylated liposome-protamine-hyaluronic acid nanoparticles (PEG-LPH-NP) loaded with siRNA (PEG-LPH-NP-S) in ARPE19 cells and a laser-induced rat model for the treatment of choroidal neovascularization (CNV). Methods PEG-LPH-NP-S was characterized by dynamic light scattering and transmission electron microscopy (TEM). The encapsulation efficiency of siRNA in PEG-LPH-NP was analyzed by ultracentrifugation, whereas the protection of siRNA by PEG-LPH-NP was evaluated by electrophoresis. Human RPE cells (ARPE19) were used as the cell model for the studies of cellular uptake and the inhibition of VEGFR1 expression, visualized by a laser scanning confocal microscope. The area of CNV in the laser-induced rat model after intravitreous injection was measured. The distribution of the lipid nanoparticles in the retina after intravitreous administration was investigated by fluorescence microscopy. Finally, the TUNEL test and morphologic observation of the retina were conducted. Results It was indicated that PEG-LPH-NP-S was approximately 132 nm in particle size with a positive charge of approximately 20 mV, whereas the encapsulation efficiency of siRNA in PEG-LPH-NP was >95%. PEG-LPH-NP could protect the siRNA load and could facilitate the intracellular delivery of fluorescein-labeled siRNA to ARPE19 cells. VEGFR1 expression in ARPE19 cells could be inhibited, and the CNV area in the murine model could be reduced more effectively by PEG-LPH-NP-S compared with naked siRNA and by PEG-LPH-NP with negative siRNA. It seems that the toxicity of PEG-LPH-NP-S on the rat retina is low, based on the results of TUNEL testing and morphologic observation. Conclusions PEG-LPH-NP may be a promising lipid nanoparticle system for the siRNA treatment of CNV.

Purpose Macular telangiectasia type 2 (MT2) is a condition of uncertain etiology characterized by retinal vascular abnormalities, depletion of luteal pigment, and photoreceptor loss. To model this condition, the authors recently used a purportedly glial-selective toxin, DL-α-aminoadipic acid (DL-α-AAA), to test the effect of Muller cell disruption on the blood-retinal barrier in rats. In this study, they investigated macular changes after subretinal injection of DL-α-AAA in monkeys. Methods Various doses of DL-α-AAA were injected beneath the macula in eight monkey eyes. Eyes were examined by multifocal electroretinography (mfERG), optical coherence tomography (OCT), fundus autofluorescence, color photography, and fluorescein angiography. Five months after injection, eyes were examined by histology and immunohistochemistry for changes in photoreceptors and the retinal glia. In vitro studies evaluated the effect of DL-α-AAA on 661W cone photoreceptor viability. Results Subretinal injection of DL-α-AAA resulted in virtually complete ablation of photoreceptors in the injected area, as shown by OCT and histology, and severely impaired mfERG responses. Muller cells, albeit activated, survived the injury. Macular pigment remained unchanged in the central fovea. Subretinal injection of DL-α-AAA did not induce vascular leakage, though it increased the fundus autofluorescence. DL-α-AAA had a dose-dependent toxic effect on 661W photoreceptors. Conclusions Submacular injection of DL-α-AAA induced severe damage to photoreceptors but failed to eliminate Muller cells in monkeys. Central macular pigment persisted despite loss of photoreceptors, and the retinal vasculature was unaffected. These observations may have significance in studying the roles of different cellular components in the pathogenesis of MT2.

Purpose To evaluate a surgical procedure for patients with hemorrhagic age-related macular degeneration (AMD). Methods This procedure consisted of excision of the choroidal neovascular membrane and transplantation of autologous retinal pigment epithelium (RPE)-Bruch's membrane complex. The RPE-Bruch's membrane complex for transplantation was surgically developed by dissecting Bruch's membrane with the choriocapillaris from the medium size choroidal vessel layer at the midperipheral region of the choroid. Twenty-one eyes of 21 patients had this surgical procedure. Visual function tests included best corrected visual acuity (BCVA), multifocal (mf)ERG, and microperimetry. Optical coherence tomography (OCT), fluorescein angiography, and autofluorescence examinations were performed to study the status of the transplanted graft. Results Among the 21 eyes, 17 with complete clinical data and qualified follow-up durations, which were 20.35 +/- 10.31 months on average, were analyzed in this series. On the last follow-up visit, the mean for the ETDRS scores increased from 28.65 +/- 23.99 before surgery to 47.76 +/- 17.22 after surgery. Microperimetry showed that after surgery, seven eyes gained central fixation at the 12-month follow-up examination. However, two eyes lost their central fixation on the last follow-up visit. Fourteen (82.35%) of the transplanted patches preserved normal color without depigmentation. Among the 21 eyes, proliferative vitreoretinopathy (PVR) occurred in 3 (14.29%), and a recurrent neovascular membrane was observed in one eye (4.76%). Conclusions The transplantation of the autologous RPE-Bruch's membrane complex can increase the visual acuity of patients with hemorrhagic AMD. The surviving transplanted graft with functional overlying retina was observed after surgery.

Purpose An improved translocation technique for autologous retinal pigment epithelium (RPE) transplantation is presented. The graft consists of a sheet of a partial-thickness choroid with RPE attached. Methods Twenty-seven pigmented rabbits were used in this study. After mechanical debridement of Bruch membrane, partial-thickness RPE-choroid sheets were transplanted onto the subretinal space in 25 rabbits. The animals were examined by fundus photographs and fluorescein angiographs and were killed postoperatively at 1, 2, 4, 12, and 24 weeks. Eyecups containing the grafts were examined by light microscopy and immunohistochemistry. In addition, two partial-thickness RPE-choroid sheets were analyzed by transmission electron microscopy (TEM). Results TEM revealed that the partial-thickness RPE-choroid graft consisted of retinal pigment epithelial cells, Bruch membrane, choriocapillaris, and ruptured middle vessels. The thickness of the graft was approximately 50 to 60 microm. Fluorescein angiography revealed neither fluorescein leakage nor staining in the graft at early or late phase. Light microscopy revealed that in 17 experiments in which the graft survived, the neural retina remained intact; however, in eight experiments with unsuccessful grafts, the neural retina degenerated. The surviving graft showed revascularization and monolayered retinal pigment epithelial cells. Furthermore, in sections in which the neural retina over the graft remained intact, all retinal pigment epithelial cells in the graft and rhodopsin in photoreceptor outer segments were positively labeled with anticellular retinaldehyde-binding protein antibodies and anti-opsin antibodies, respectively. Conclusions A partial-thickness RPE-choroid graft showed improved integration with the host choroid and photoreceptors. This technique has the potential to be a treatment for age-related macular degeneration.

PURPOSE. To observe the changes in N-cadherin expression in the retina after experimental retinal detachment (RD) and reattachment in the rat and to explore the role N-cadherin might play after RD. METHODS. Forty rat retinas were detached by transscleral injection of 1.4% sodium hyaluronate into the subretinal space. The eyes were enucleated at different time intervals (n = 5), followed by fixation, embedding, and sectioning. The differences in N-cadherin expression in the normal retina, detached retina, and spontaneously reattached retina were determined. Furthermore, an N-cadherin antagonist was injected in combination with 1.4% sodium hyaluronate into the subretinal space in another 10 eyes, in an attempt to demonstrate the role N-cadherin plays after RD. RESULTS. N-cadherin was not expressed in the RPE layer of the normal rat retina. After RD, intense immunolabeling of N-cadherin was seen in the RPE cells, the photoreceptors, and the outer limiting membrane (OLM). An increasing number of cytokeratin (CK>positive cells likely to be RPE cells was found attached to the outer surface of the detached neural retina. Where the retina was reattached, the N-cadherin immunolabeling rapidly decreased. In eyes treated with an N-cadherin antagonist, the retinas appeared thinner than that in eyes without treatment, and the photoreceptor nuclei showed significantly loss. Moreover, CK-positive cells attached to the outer surface of the detached retina were markedly fewer in number. CONCLUSIONS. Increased expression of N-cadherin in the RPE cells, the photoreceptor cells, and the OLM of the retina after RD may contribute to RPE cell migration and photoreceptor survival. These changes could be reversed by retinal reattachment.