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Purpose To delineate anatomic and visual outcomes of injured eye globes with perforating, and to develop the prognostic indicators for perforating eyes. Methods The case series study, from a multicenter prospective cohort database. To the date of December 31st, 2018, of 63 perforating globes were selected. All cases underwent vitreoretinal surgeries or enucleations, and were followed up for at least 6 months. Demographic characteristics, basic examination for traumatized eyes, and intraocular tissue damages were recorded by surgery-in-chief. At the follow-up visit, best corrected VA, intraocular pressure, the intraocular tamponade material, retinal anatomic outcome of eye-globes, and phthisis or enucleation were evaluated. Results Fifty injured eyes (79%) were caused by sharp objects and 13 eyes (21%) were injured by a missiles. Twenty-two injured eyes can be anatomically restored with final vision of more than 4/200 through vitreoretinal surgery. The PVR-C (OR = 5.67, P = 0.01), area of retinectomy more than 2 times of optic disk (OR = 5.16, P = 0.04), and macular damage (OR = 6.38, P = 0.01) were correlated with unfavorable outcomes. Conclusion The injured eyes with perforation can be saved through vitreoretinal surgery, the PVR-C, retinectomy more than 2 times of optic disk, and macular damage were independent risk factors for poor long-term prognosis.

PurposeTo explore the long-term efficacy of novel choroidal suturing methods including trans-scleral mattress suturing (TSS) and intraocular suturing (IOS) in the treatment of choroidal avulsion.DesignProspective cohort, hospital-based study.MethodsA total of 24 patients who were diagnosed with choroidal avulsion were enrolled in this study. The demographic characteristics, baseline information of trauma, best-corrected visual acuity (BCVA), and intraocular pressure (IOP) were collected before surgery, and the anatomic abnormities of the globe were recorded before or during surgery. All patients were diagnosed with choroidal avulsion and underwent choroid suturing treatment during vitrectomy, postoperative functional variables including BCVA and IOP, anatomic variables including retinal and choroidal reattachment rate, and silicone oil migration rate, which were recorded at the regular follow-ups at least 1 year after surgery.ResultsAll patients with open globe injury involved zone III, 70.8% of the patients presented with two quadrants of the avulsed choroid, and 29.2% with one quadrant involved; moreover, all patients had complications with retinal detachment (RD), of which 58.3% of patients had closed funnel retinal detachment. TSS was applied in nineteen patients and IOS in five patients. Postoperatively, a significant improvement on LogMAR BCVA was observed at each follow-up from 3.57 ± 0.69 before surgery to 2.82 ± 0.98 at the last follow-up (p < 0.05), and the proportion of no light perception (NLP) was also reduced from 69.6 to 37.5%. IOP was markedly elevated from 6.4 ± 4.1 mmHg preoperatively to 11.3 ± 4.3 mmHg at the last follow-up (p < 0.05). Choroidal reattachment was achieved in 91.7% of patients; two patients were observed with silicone oil migration at 3 months after surgery and underwent drainage of suprachoroidal silicone oil and sclera buckling. Meanwhile, retinal attachment was observed in 95.8% of patients, only one patient developed partial RD due to postoperative proliferative vitreoretinopathy, and secondary vitrectomy was performed; all patients were observed with complete retinal and choroidal attachment at the last follow-up. Eventually, four patients were silicone oil-free, and 20 patients were silicone oil-dependent.ConclusionsChoroidal suturing proved to be an effective method to fix the avulsed choroid, which greatly improved the BCVA and maintained the IOP, and efficiently increased the choroidal and retinal reattachment rate and preservation of the eyeball.

Age-related macular degeneration (AMD) is a major reason of blindness in the elderly. MicroRNAs are implicated in various pathological processes, including inflammation and apoptosis. In this study, we aim to investigate the biological functions of miR-21-3p in inflammation and apoptosis caused by lipopolysaccharide (LPS) in human retinal pigment epithelial (ARPE-19) cells. The miR-21-3p inhibitor and mimic were transfected into ARPE-19 cells for 48 hours, followed by exposed to LPS (10 μg/mL) for 24 hours. The mRNA and protein expression of IL-6 and MCP-1 were measured using real-time PCR (RT-PCR) and enzyme-linked immunosorbent assays. Cell viability, apoptosis, caspase 3 activity, cleaved caspase-3 and cleaved-PARP protein levels were detected to evaluate the effects of miR-21-3p on apoptosis. Additionally, the target relationship between miR-21-3p and regulator of G-protein signalling 4 (RGS4) was verified by dual luciferase reporter assay. RT-PCR analysis demonstrated that LPS induced miR-21-3p expression. Inhibition of miR-21-3p reduced the mRNA and protein levels of IL-6 and MCP-1. Apoptosis, caspase-3 activity, and cleaved-caspase 3 and cleaved PARP protein levels were repressed by the miR-21-3p inhibitor. However, overexpression of miR-21-3p showed the opposite results. Furthermore, we identified that miR-21-3p directly targeted the 3' untranslated region of RGS4. MiR-21-3p negatively regulated the expression of RGS4 both in mRNA and protein levels. Silencing RGS4 reduced the anti-inflammatory and anti-apoptotic effects of miR-21-3p inhibitor. Our results revealed that miR-21-3p inhibition targeted RGS4 to attenuate inflammatory responses and apoptosis caused by LPS in ARPE-19 cells.

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.

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.

"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."

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.

Objective The primary study hypothesis was that ranibizumab 0.5 mg monotherapy or combined with laser is superior to laser monotherapy based on mean average change in best-corrected visual acuity (BCVA) over 12 months in Asian patients with visual impairment resulting from diabetic macular edema (DME). Design A 12-month, randomized, double-masked, multicenter, laser-controlled, phase III study. Participants Three hundred ninety-six patients aged ≥18 years, with type 1 or 2 diabetes mellitus, BCVA of 78–39 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, and visual impairment resulting from DME. Methods Patients were randomized to ranibizumab + sham laser (n = 133), ranibizumab + active laser (n = 132), or sham injection + active laser (n = 131). Ranibizumab/sham injections were administered on day 1 and continued monthly. As of month 3, monthly injections were continued if stable vision was not reached. Treatment was reinitiated if BCVA decreased because of DME progression. Active/sham laser was administered on day 1 and thereafter according to ETDRS guidelines. Main Outcome Measures Average change in BCVA from baseline to months 1 through 12, central retinal subfield thickness (CRST), and safety over 12 months. Results Ranibizumab monotherapy or combined with laser was superior to laser in improving mean average change in BCVA from baseline to months 1 through 12 (+5.9 and +5.7 vs +1.4 letters). At month 12, greater proportion of patients gained ≥15 letters with ranibizumab and ranibizumab + laser compared with laser (18.8% and 17.8% vs 7.8%). Mean CRST reduced significantly from baseline to month 12 with ranibizumab (−134.6 μm) and ranibizumab + laser (−171.8 μm) versus laser (−57.2 μm). Patients received a mean of 7.8 and 7.0 ranibizumab injections in the ranibizumab and ranibizumab + laser arms, respectively, and 1.5–1.9 active laser across treatment arms over 12 months. Conjunctival hemorrhage was the most common ocular, whereas nasopharyngitis and hypertension were the most common nonocular adverse events. Ranibizumab was not associated with any cases of cerebrovascular hemorrhage and cerebrovascular ischemia. No death related to study treatment was reported. Conclusions Ranibizumab monotherapy or combined with laser showed superior BCVA improvements over laser treatment alone in Asian patients with visual impairment resulting from DME. No new ocular or nonocular safety findings were observed and treatment was well tolerated over 12 months.

Background The objective of the study was to delineate clinical characteristics, surgical interventions, anatomic and visual outcomes of ruptured eye balls after trauma, and establish the prognostic indicators, which can assist clinicians in making correct surgical decisions during globe exploration for ruptured eyes. Design The study design used was a multicentre prospective cohort study, including six university-affiliated tertiary hospitals. Participants We selected 242 cases of ruptured globe from the Eye Injury Vitrectomy Study database, until 31 December 2012. Methods All selected cases underwent vitreoretinal surgery, enucleation or evisceration, and were followed up for at least 6 months. Age, visual acuity (VA) after injury, ocular trauma zone, time to surgery, corneal laceration, scleral wound, extrusion of iris or lens, ciliary body damage, intraocular haemorrhage, retinal detachment or defect, proliferative vitreoretinopathy (PVR) and choroidal damage were the predisposing factors evaluated by logistic regression models. Main Outcome Measures We compared the pre-surgical indicators between cases of anatomically restored eyes with VA of 4/200 or better, or eyes with initial no light perception restored light perception or better, and cases of VA worse than 4/200, silicone oil-sustained eyes, phthisis or enucleation. Results Nearly 40% of cases with ruptured globe were anatomically restored through vitreoretinal surgery. The closed-funnel retinal detachment or extensive retinal loss (odds ratio [OR] = 3.38, P = 0.026), PVR-C (OR = 3.45, P = 0.008), and choroidal damage (OR = 4.20, P = 0.004) were correlated with poor outcomes. Conclusion The closed-funnel retinal detachment or extensive retinal loss, PVR-C, and choroidal damage are the risk factors for unfavourable outcomes in globe ruptures.

Retinitis pigmentosa (RP) comprises a group of incurable inherited retinal degenerations. Targeting common processes, instead of mutation-specific treatment, has proven to be an innovative strategy to combat debilitating retinal degeneration. Growing evidence indicates that melatonin possesses a potent activity against neurodegenerative disorders by mitigating cell damage associated with apoptosis and inflammation. Given the pleiotropic role of melatonin in central nervous system, the aim of the present study was to investigate whether melatonin would afford protection against retinal degeneration in autosomal recessive RP (arRP). Rd10, a well-characterized murine model of human arRP, received daily intraperitoneal injection of melatonin (15 mg/kg) between postnatal day (P) 13 and P30. Retinas treated with melatonin or vehicle were harvested for analysis at P30 and P45, respectively. The findings showed that melatonin could dampen the photoreceptors death and delay consequent retinal degeneration. We also observed that melatonin weakened the expression of glial fibrillary acidic protein (GFAP) in Muller cells. Additionally, melatonin could alleviate retinal inflammatory response visualized by IBA1 staining, which was further corroborated by downregulation of inflammation-related genes, such as tumor necrosis factor alpha (Tnf-α), chemokine (C-C motif) ligand 2 (Ccl2), and chemokine (C-X-C motif) ligand 10 (Cxcl10). These data revealed that melatonin could ameliorate retinal degeneration through potentially attenuating apoptosis, reactive gliosis, and microglial activation in rd10 mice. Moreover, these results suggest melatonin as a promising agent improving photoreceptors survival in human RP.

The purpose of this study was to compare the efficacy of intravitreal bevacizumab (IVB) in the treatment of acute (3 months [mo]. duration) macular edema (ME), with or without subretinal hemorrhage (SRH), resulting from branch retinal vein occlusion (BRVO).We conducted a retrospective review of 33 consecutive patients (n = 33 eyes) with ME caused by acute BRVO. All patients received an injection of IVB at baseline examination. All patients were followed monthly, with administration of additional IVB injections if there was persistent or recurrent ME. Specific patterns of ME were investigated using spectral-domain optical coherence tomography (SD-OCT).SD-OCT revealed serous retinal detachments in the fovea of 15 eyes, 10 of which had accompanying foveal SRH. Based on initial detection of foveal SRH, patients were divided into SRH-negative (n = 23 eyes) or SRH-positive (n = 10 eyes) groups. Initial best-corrected visual acuity (BCVA) did not differ between the two groups. In the SRH-negative group, both BCVA and central macular thickness (CMT) improved significantly after IVB injections (mean, 2.3 injections) at the 6-mo. follow-up examination. In the SRH-positive group, there was no significant improvement in BCVA after IVB injections (mean, 2.0 injections), although there was a significant decrease in CMT. The final BCVA of the SRH-positive group was significantly poorer than that of the SRH-negative group (p = 0.001).The presence of foveal SRH may be a negative predictor of IVB treatment outcomes for BRVO patients with ME.

Purpose: To identiy the disease causing mutation in a Chinese family presenting with early-onset cataract and dental anomalies.Materials and Methods: A specific Hereditary Eye Disease Enrichment Panel (HEDEP) (personalized customization by MyGenostics, Baltimore, MD) based on targeted exome capture technology was used to collect the protein coding regions of 30 early-onset cataract associated genes, and high throughput sequencing was done with Illumina HiSeq 2000 platform. The identified variant was confirmed with Sanger sequencing.Results: A novel deletion in exon 4 (c.852delG) of NHS gene was identified; the identified 1 bp deletion altered the reading frame and was predicted to result in a premature stop codon after the addition of twelve novel amino acid (p.S285PfsX13). This mutation co-segregated in affected males and obligate female carriers, but was absent in 100 matched controls.Conclusions: Our findings broaden the spectrum of NHS mutations causing Nance-Horan syndrome and phenotypic spec...

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.

A novel class of (E)-3,4-dihydroxy styryl sulfonamides and their 3,4-diacetylated derivatives as caffeic acid phenethyl ester (CAPE) analogs was designed and prepared for improving stability and solubility of the lead compound. Their neuroprotective properties were assessed by several models. The results showed that target compounds displayed positive free radical quenching abilities, superior to that of CAPE. Compounds 6j-k and 7j-k demonstrated remarkable protection effects against damage induced by hydrogen peroxide which were apparently stronger than that of CAPE. Most of target compounds could inhibit nitric oxide production. Additionally, target compounds showed high blood-brain barrier permeability.

Purpose To investigate potential risk factors for development of proliferative vitreoretinopathy (PVR) post trauma and evaluate the effect of PVR on anatomical and visual outcomes in injured eyes. Methods Overall, 179 eyes with PVR and 221 eyes without PVR after injury were selected from the database of the Eye Injury Vitrectomy Study, a multicenter cohort study launched in 1997. Multivariate logistic regression was used to ascertain the independent risk factors for development of PVR and to evaluate the influence of PVR on anatomical and visual outcomes. Results An interval of injury and vitrectomy of more than 28 days (odds ratio, 139.25; confidence interval, 50.09-387.10), severe vitreous hemorrhage (odds ratio, 2.72; confidence interval, 1.13-6.52), and total retinal detachment (odds ratio, 12.67; confidence interval, 3.96-40.52) were important independent risk factors for PVR. One hundred and fifteen eyes (52.0%) and 49 eyes (27.4%) without and with PVR, respectively, were anatomically restored with ambulant visual acuity (≥4/200). Proliferative vitreoretinopathy, poor initial visual acuity, relative afferent pupillary defect, total retinal detachment, and retinal tear or retinal defect were unfavorable prognostic indicators. Conclusion Proliferative vitreoretinopathy occurs frequently in injured eyes and is associated with poor outcomes. Its onset depends on interval of injury and vitrectomy, wound location, vitreous hemorrhage, and retinal detachment. Early vitrectomy (before 2 weeks) and aggressive therapy should be considered for specific high-risk cases.

E-3,4-Dihydroxy styryl aralkyl ketones as well as their 3,4-diacetylated derivatives as the analogues of neuroprotective agent CAPE were designed and synthesized for improving stability and lipid solubility. The neuroprotective activities of target compounds 10a-g and 11a-g were tested by three models in vitro, including 1,1-diphenyl-2-picrylhydrazyl radical scavenging capacity, neuronal protecting effect against damage induced by H2O2 in PC12 cells and nitric oxide suppression effect in BV2 microglial cells. The results demonstrated that compounds 10f and 11f exhibited the most potent neuroprotective effect against oxidative stress and inflammation, which is higher than that of the lead compound CAPE.

To determine the phases of traumatic proliferative vitreoretinopathy after open globe injury by assessing cellular components, extracellular matrix constituents of proliferative vitreoretinopathy membranes, and intraretinal changes over time. Twenty-one epiretinal and/or subretinal membrane specimens were obtained from 21 patients with open globe injuries. The patients were divided into Groups A (≤28 days), B (29-120 days), and C (>120 days) according to the interval between injury and vitrectomy. The staining intensity and percentage of positive cells in membranes were compared among the groups, and proliferative indices for Ki-67 and proliferating cell nuclear antigen were assessed. Intraretinal changes were evaluated through histology and immunohistochemistry. Fundus photography was performed during vitrectomy. The proliferating cell nuclear antigen proliferative index was significantly higher in Group B (P = 0.002) than in Group A, and lower in Group C (P < 0.001) than in Group B. α-smooth muscle actin expression increased from day 29 to 120 after injury. Meanwhile, intraretinal gliosis and fibrosis developed. Active proliferation and contraction in proliferative vitreoretinopathy membranes continue until 120 days after injury, and are accompanied by the initiation of intraretinal gliosis and fibrosis. These findings provide further insight into the optimal timing of vitrectomy after trauma.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

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.

The aim of this study was to provide data on the dose dependence of manganese-enhanced MRI (MEMRI) in the visual pathway of experimental rats and to study the toxicity of MnCl₂ to the retina. Sprague-Dawley rats were intravitreally injected with 2 μL of 0, 10, 25, 50, 75, 100, 150 and 300 mM MnCl₂, respectively. The contrast-to-noise ratio (CNR) of MEMRI for optic nerve enhancement was measured at different concentrations of MnCl₂. Simultaneously, the toxicity of manganese was evaluated by counting retinal ganglion cells and by retinal histological examination using light microscopy and transmission electron microscopy. The CNR increased with increasing concentration of MnCl₂ up to 75 mM. Retinal ganglion cell densities were reduced significantly when the concentration of MnCl₂ in the intravitreal injection was equal to or greater than 75 mM. Increasing numbers of ribosomes in retinal ganglion cells were first detected at 25 mM of MnCl₂. The retinal toxicity of MnCl₂ at higher concentration also included mitochondrial pathology and cell disruption of retinal ganglion cells, as well as abnormalities of photoreceptor and retinal pigment epithelium cells. It can be concluded that intravitreal injection of MnCl₂ induces retinal cell damage that appears to start from 25 mM. The concentration of MnCl₂ should not exceed 25 mm through intravitreal injection for visual pathway MEMRI in the rat.

PURPOSE: To examine the carbohydrate sulfotransferase 6 (CHST6) gene in Chinese patients with macular corneal dystrophy (MCD). METHODS: Nineteen unrelated Chinese families with MCD, including 24 patients and 3 unaffected relatives, were examined. Genomic DNA was extracted from peripheral blood leukocytes. The coding region of the CHST6 gene was amplified by the polymerase chain reaction, and the DNA fragments were directly sequenced. Fifty unrelated normal Chinese volunteers served as the controls. RESULTS: Eighteen different mutations in the CHST6 gene (including 15 novel mutations) were identified, of which 12 were missense mutations, 5 were nonsense mutations, and 1 was a frameshift mutation. Six families had homozygous mutation, and 13 families had compound heterozygous mutation. None of these mutations were detected in the normal controls. CONCLUSIONS: CHST6 mutations may be responsible for the pathogenesis of MCD in Chinese patients. The Q298X mutation detected in 5 of 19 families (6 of 38 alleles, 15.8%) may be the founder mutation in Chinese patients. However, our findings also indicate a high level of allelic heterogeneity of the CHST6 gene in Chinese patients and in other ethnic groups.

To investigate serum inflammatory factors in patients with idiopathic choroidal vascularization (CNV), including vascular endothelial growth factor (VEGF), tumor necrosis factor alpha (TNFα), Interleukin1-beta (IL1-β), IgG, IgA, IgM, IgE, 50% hemolytic unit of complement (CH50), complement C3, complement C4 and C reactive protein (CRP).21 patients and 20 normal individuals were recruited. They received comprehensive ophthalmic examinations. Serous concentrations of VEGF, TNFα, IL1-β were assayed by ELISA, and the concentrations of other serum factor were assayed by immunonephelometry.The mean serum VEGF level in the CNV group was significantly greater than that in the control group (p=0.025). The median level of IgE in the CNV group was significantly lower than that in the control group (p=0.006). Statistical analysis revealed no significant difference in the levels of TNFα, IL1-β, IgG, IgA, IgM, CH50, C3, C4 or CRP between the two groups.The possible roles of these factors and mechanisms of idiopathic CNV formation were analyzed. Serum VEGF and IgE levels may play an important role in the formation of idiopathic CNV.

Purpose The purpose of this study was to investigate the dynamic course of experimental thrombosis and thrombolysis of the retinal veins. Methods Dynamic changes in the blood flow in the retinal veins were documented on a digital recorder through a microscope-mounted video camera and were analyzed on a monitor by video playback. Photochemical thrombus formation was induced by intravenous injection of 30% Rose Bengal followed by endoillumination of individual branch retinal veins of the eyes of 20 anesthetized pigmented rabbits. Subsequently, 10 rabbits were treated with an infusion in an ear vein of 3 mg/kg recombinant tissue plasminogen activator, whereas 10 control rabbits were administered with similar volumes of normal saline solution. Occlusion and recanalization were confirmed histologically and assessed by video microscopy. Results At the site exposed to light, photochemical injury resulted in the formation of a white thrombus, stagnation of blood flow, and subsequent complete venous occlusion in 20 rabbits. In this study, of the 10 animals in the recombinant tissue plasminogen activator treatment group, 9 (90%) showed evident thrombolysis, whereas none of the control group animals showed evident thrombolysis. The video showed that the massive thrombus disrupted into nonuniform fragments, which were quickly washed away by the blood flow, and the circulation was reestablished with no recurrence of secondary obstruction. Conclusion In vivo data suggest that video microscopy may provide a visual approach for observing the dynamic changes occurring during experimental thrombus formation and lysis by the early administration of recombinant tissue plasminogen activator; this approach may assist in future investigation of thrombus research of ocular fundus.

Pu-erh tea is believed to possess many beneficial health effects since it is a natural source of cardioprotective lipid lowering and antioxidant compounds, although, the major constituents putatively responsible for these beneficial effects remain unknown. In this study, we examined the effects of two commonly consumed forms of Pu-erh tea, fermented and unfermented, on weight gain, serum levels of lipids and lipoprotein, lipid oxidation, and blood antioxidant enzymes in a rat hyperlipidemia model. Hyperlipidemic rats were treated with water extracts of either 0.5, 1.5 or 3.0 mg/kg fermented or unfermented Pu-erh tea. Serum low density lipoprotein-cholesterol (LDL-C) and triglyceride levels were significantly lowered by tea extract compared to the control group. (p < 0.05) and in most cases were indistinguishable from rats fed normal chow, basal diet. Conversely, levels of high density lipoprotein-cholesterol (HDL-C) were elevated in the groups given daily doses of tea extract (p < 0.05). Compared to the hyperlipidemic control group, activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in serum were significantly elevated in Pu-erh tea-treated groups while levels of malondiadehyde (a byproduct of lipid peroxidation) decreased in the same groups. These effects were most pronounced in the groups treated with the highest dose of fermented Pu-erh tea extract. Our results suggest that Pu-erh tea exerts strong antioxidative and lipid-lowering effects and therefore can be used to reduce the risk of cardiovascular disorders.

The objective of this study was to develop an efficient vasculature-targeted liposomal combretastatin A4 (CA4), by the modification of the sterically stabilized liposomes (SSL) with a ligand of integrins and to explore the possibility of such system for the treatment of choroidal neovascularization (CNV).CA4-loaded liposomes were prepared by thin-film dispersion method. The linear arginine-glycine-aspartic acid tripeptide (RGD) with affinity for integrins such as alphavbeta3 expressed on rapidly proliferative vascular endothelial cells was coupled to the distal end of polyethylene glycol (PEG) connected on the surface of SSL. The liposome delivery system was characterized in terms of size and size distribution profiles by dynamic light scattering method, entrapment efficiency, and leakage properties by high-performance liquid chromatography (HPLC). The uptake efficiency by human umbilical vein endothelial cells (HUVECs) was evaluated by confocal microscopy. The therapeutic efficacy was quantitatively assessed by choroidal flat mounts.CA4-loaded RGD-SSL (RGD-SSL-CA4) was obtained with an entrapment efficiency over 70% and an average diameter of approximately 120 nm. The leakage property of RGD-SSL-CA4 was similar with SSL-CA4, both were slower than CA4 ethanol solution. Confocal microscopy studies revealed that RGD-SSL could facilitate the liposomes' uptake into HUVECs. Rats treated with two intravenous injections of 7 mg/kg RGD-SSL-CA4 resulted in a significant reduction in the area of CNV compared with control group (P0.05).RGD-modified SSL loaded with CA4 can be successfully prepared, and the vasculature-targeted liposome system would increase the uptake of HUVECs and improve the therapeutic efficacy of CA4 on CNV compared with the control formulations.

Caffeic acid phenethyl ester (CAPE) is an active component of propolis obtained from honeybee hives and is found to have the following properties: anti-mitogenic, anti-carcinogenic, anti-inflammatory, immunomodulatory, and antioxidant. Recent reports suggest that CAPE also has a neuronal protective property against ischemic injury. Since excitotoxicity may play an important role in ischemia, in this study, we investigated whether CAPE could directly protect neurons against excitotoxic insult. We treated cultured rat cerebellar granule neurons (CGNs) with excitotoxic concentrations of glutamate in the presence or absence of CAPE and found that CAPE markedly protected neurons against glutamate-induced neuronal death in a concentration-dependent fashion. Glutamate-induced CGNs death is associated with time-dependent activation of caspase-3 and phosphorylation of p38, both events of which can be blocked by CAPE. Treating CGNs with specific inhibitors of these two enzymes together exerts a synergistic neuroprotective effect, similar to the neuroprotective effect of CAPE exposure. These results suggest that CAPE is able to block glutamate-induced excitotoxicity by inhibiting phosphorylation of p38 and caspase-3 activation. This finding may further help understanding of the mechanism of glutamate-induced neuronal death and CAPE-induced neuroprotection against excitotoxicity.

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.

Bietti crystalline corneoretinal dystrophy (BCD) is an inherited eye disease that is most common in the Chinese. It is caused by a mutation in the CYP4V2 gene. In this study, 43 Chinese BCD families were recruited; most patients manifested the characteristic phenotype of BCD, with 2 families initially misdiagnosed with retinitis pigmentosa. Five patients in our cohort presented with BCD and choroidal neovascularization (CNV), and 1 patient presented with typical BCD and abnormality in the terminals of both fingers and toes. A total of 17 pathogenic mutations involving 68 alleles were identified from 36 families using targeted exon sequencing and Sanger sequencing; we achieved a diagnostic rate of approximately 84%. Fifteen families were found to carry homozygous mutations, 17 families carried compound heterozygous mutations, and 4 families carried a single heterozygous mutation. Of the mutations identified, four variants c.802-8_810del17bpinsGC, c.802-8_810del17bpinsGT, c.992A > C (p.H331P), and c.1091-2A > G accounted for 71% of the mutations identified in CYP4V2. These mutations were hotspots in Chinese populations for BCD. Five among them were novel and predicted to be disease-causing, including c.65T > A (p.L22H), c.681_4delTGAG (p.S227Rfs*1), c.802-8_810del17bpinsGT, c.965_7delAAG (p.321delE), and c.994G > A (p.D332N). No apparent correlation between genotype and phenotype was identified. Our findings broaden the spectrum of CYP4V2 mutations that cause BCD and the phenotypic spectrum of the disease in Chinese families. These results will be useful for the genetic diagnosis of BCD, genetic consultation, and gene therapy in the future.

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.

Neurotoxicity induced by 6-hydroxydopamine (6-OHDA) is believed to be due, in part, to the production of reactive oxygen species (ROS). Antioxidants protect neurons against 6-OHDA-induced neurotoxicity by inhibiting free radical generation. In this study, we investigated whether or not caffeic acid phenethyl ester (CAPE) could protect neurons against 6-OHDA-induced neurotoxicity in cultured rat rostral mesencephalic neurons (RMN) and cerebellar granule neurons (CGN). We now report that exposure of RMN and CGN to 6-OHDA (40 microM for RMN and 70 microM for CGN) resulted in significant increases in free radical production and death of both neuron types. Pretreatment with CAPE (10 microM) for 2 h prevented both 6-OHDA-induced free radical generation and neurotoxicity. Furthermore, CAPE also attenuated H(2)O(2)-induced neurotoxicity. Our results strongly suggest that CAPE blocks 6-OHDA-induced neuronal death possibly by inhibiting 6-OHDA-induced free radical generation and blocking free radical-induced neurotoxicity in neurons. Both the antioxidative and neuroprotective effects of CAPE may be beneficial in the therapy for Parkinson's disease and other neurodegenerative diseases.

This study was undertaken to investigate the therapeutic efficacy and the toxicity of the intravitreal biodegradable poly(dl-lactide-co-glycolide)co-polymer microspheres containing cyclosporin A (CsA-PLGA-MS) on experimental uveitis in rabbits.CsA-PLGA-MS that had been prepared by a solvent evaporation approach were characterized for morphology, particle size, entrapment efficiency, and in vitro release profile of CsA-PLGA-MS. Therapeutic efficacy of the CsA-PLGA-MS was evaluated by scoring of the inflammation, aqueous leukocyte counting, aqueous protein determination, and histological examination in the experimental rabbits with artificial uveitis induced by the injection of lipopolysaccharide. The toxicity was investigated by slit-lamp examination, indirect ophthalmoscopy, and electroretinography (ERG) in the noninflamed rabbit eye.The CsA-PLGA-MS were spherical in shape, with an average particle size of nearly 50 microm and an entrapment efficiency of more than 80%. The compositions of the formulation that was most effective in the in vivo studies included CsA, PLGA, and 3% Pluronic F68. In vitro released cyclosporine A from the optimized microspheres was approximately 25% during the 60-day incubation at 37 degrees C. It was demonstrated that the intravitreal injection of the optimized CsA-PLGA-MS decreased significantly the severity of the inflammatory signs, cellular infiltrate, aqueous leukocyte counts, and protein levels in the eyes of experimental rabbits with uveitis, compared to other formulations. Also, the preparation did not cause obvious toxicity in the noninflamed eyes of rabbits, except that the ERG b-wave amplitude for the test eyes was reversibly depressed, compared to those of the control eyes at 2 weeks, which almost recovered at the end of 6 weeks.The CsA-PLGA-MS preparation might be useful in the treatment of patients with severe chronic posterior uveitis who cannot tolerate systemic or periocular therapy.

Encephalopathy induced by hyperbilirubinemia in infants has been described in the medical literature for over a century but neither the cellular nor molecular mechanisms underlying bilirubin neurotoxicity are well understood. In this study, we have demonstrated that minocycline potently protects primary cultured rat cerebellar granule neurons against bilirubin neurotoxicity (IC50 approximately 2 microm) and almost completely blocks cerebellar hypoplasia and the profound loss of Purkinje and granule neurons observed in homozygous Gunn rats, a genetic model of hyperbilirubinemia-induced neurotoxicity. Minocycline-treated newborn Gunn rats had nearly equivalent numbers of viable Purkinje and granule neurons in the cerebellum as did control animals. Moreover, minocycline inhibits the bilirubin-induced phosphorylation of p38 mitogen-activated protein kinase both in vivo as well as in vitro. Taken together our data demonstrate that minocycline is able to greatly reduce bilirubin-induced neurotoxicity and suggest that minocycline's neuroprotective effects may be due in part to an inhibition of p38 mitogen-activated protein kinase activity. Our findings may lead to novel approaches for treating bilirubin-induced encephalopathy.

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 study the luminal characteristics of the central retinal vessels of young humans where the vessels pass through the anterior optic nerve. METHODS Serial sections of nine central retinal arteries (CRAs) and 13 central retinal veins (CRVs) from 12 eyes of 12 young donors (aged 20-29 years) without known ocular disease or anatomic malformation were examined by image analysis to determine their luminal dimensional differences right at, anterior to, and posterior to the lamina cribrosa. RESULTS The average values of the mean area of the CRAs in the prelaminar, laminar, and retrolaminar portions were 16.5 x 10(3) microm2, 17.2 x 10(3) microm2, and 15.2 x 10(3) microm2, and mean perimetric lengths were 541 microm, 528 microm, and 492 microm, respectively. Differences were detected in perimetric length and theoretical luminal area between the laminar and retrolaminar portions, but not the prelaminar and laminar portions. The average values of the mean area of the CRVs in the prelaminar, laminar, and retrolaminar portions were 24.6 x 10(3) microm2, 13.3 x 10(3) microm2, and 7.8 x 10(3) microm2, and mean perimetric lengths were 689 microm, 544 microm, and 411 microm, respectively. There were marked differences between the prelaminar and laminar values and between the laminar and retrolaminar values in terms of the perimetric lengths and theoretical luminal areas. CONCLUSIONS The results suggest that the resistance of blood flow in CRAs decreases when the blood enters the eye. The gradual constriction of CRVs from the prelaminar to the retrolaminar portion may act as a throttle mechanism in controlling the outflow of the blood and in maintaining the patency of the retinal venules and capillaries.

This study sought to analyze the changes to clots and retinal tissue following direct infusion of tissue plasminogen activator (tPA) at different rates to the obstructed area of the retinal vein in an experimental animal model of retinal vein occlusion.The miniature pigs, which underwent unilateral retinal vein thrombosis generated by a combination of light illumination of the retinal vein and I.V. administration of rose Bengal, were randomly divided into two groups. In the experimental group (n = 45), balanced salt solutions + tPA were infused into the obstructed retinal vein at different rates (30,60, and 80 ml/h) for 20 minutes (15 pigs in each subgroups). In the control group (n = 5), balanced salt solutions without tPA were infused. Retinal tissue and clots were evaluated by fundus photographic and histopathologic analysis.Clot lysis occurred in 2/15, 9/15, and 10/15 pigs respectively following the 30, 60, and 80 ml/h tPA infusion. Exudative retinal detachment appeared in 12/15 pigs after infusion of tPa at a rate of 80 ml/h. Retinal histopathology and transmission electron microscopy showed that endothelial cell tight junctions of retinal vein and capillaries were injured in pigs receiving the 80 ml/h tPA infusion.Experiments with our pig model suggests that the optimal infusion rate for the treatment of retinal vein thrombosis by direct tPA infusion is 60 ml/h for 20 minutes.