The impact of preloaded intraocular lens implantation system (TECNIS iTec®) in routine cataract surgery in China: a time-motion analysis.

OBJECTIVE: To evaluate the impact on surgical efficiency and labor time cost of preloaded intraocular lens (IOL) implantation system compared with manual IOL implantation system in age-related cataract surgery in China. METHODS: This study was an observational, multicenter, prospective time-motion analysis. IOL preparation time, operation time, cleaning time, number and cost of cataract surgeries in eight participating hospitals were collected. The linear mixed model was used to explore factors associated with the difference in operation time between the preloaded IOL implantation system and the manual IOL implantation system. A time-motion model was constructed to convert the operation time cost saved by using preloaded IOL into economic benefits from hospital and social perspective, respectively. RESULTS: There were 2,591 cases included in the study (preloaded IOL: 1,591 cases; manual IOL: 1,000 cases). The preloaded IOL implantation system was significant time-saving in both preparation time and operation time compared to the manual IOL implantation system (25.48s vs. 47.04s, P < 0.001 and 353.84s vs. 367.46s, P = 0.004, respectively). An average total of 35.18s can be saved by using preloaded IOL per procedure. The results of linear mixed model showed that the type of IOL was the main factor leading to the difference in preparation time between preloaded IOL and manual IOL implantation system. By switching from manual IOL to preloaded IOL, the model projected additional 392 surgeries can be performed each year and an increase in revenue of $565,282 per hospital, a 9% increase from hospital perspective. And the annual productivity loss saved by using preloaded IOL was $3,006 in eight hospitals from perspective of society. CONCLUSION: Compared with manual IOL implantation system, the preloaded IOL implantation system reduces lens preparation time and operation time, which increases potential surgical volume and revenue, and reduces the loss of work productivity. This study provides real-world evidence to support the advantages of the preloaded IOL implantation system in improving efficiency of ophthalmic surgery in China.

[Clinical application of visual quality analysis in cataract patients].

Cataract is a major cause of blindness and vision impairment disease, and the main therapy for cataract is operation. For improving the postoperative efficiency, cataract surgery has gradually transformed from traditional restorative surgery to refractive surgery with modern technique. Visual quality is one of the crucial indicators for assessing imaging quality and surgical efficiency in cataract patients. Although several instruments are available, each has its advantage and disadvantage. In the clinic, the optimum visual quality analysis methods should be selected according to the principle, function and clinical significance to meet the practical needs of different cataract patients.

A Missense Mutation in GJA8 Encoding Connexin 50 in a Chinese Pedigree with Autosomal Dominant Congenital Cataract.

Congenital cataract is leading cause of visual impairment and blindness in children worldwide. Approximately one-third of congenital cataract cases are familial, whose genetic etiology can be distinguished by targeted exome sequencing. Here, a three-generation congenital cataract pedigree was recruited, and physical and ophthalmologic examinations were taken. Targeted exome sequencing of 139 cataract-related genes was performed on the proband III:1. Sanger sequencing was used to validate the presence of variation identified via exome sequencing in family members and 200 controls. Conservative and functional prediction was performed with bioinformatic tools. We, thus, found a heterozygous missense mutation c.10T>A (p.W4R) in gap junction protein alpha 8 (GJA8) in the patients. However, this mutation was not present in normal family members and 200 unrelated controls. The GJA8 gene encodes a gap junction protein, connexin 50 (Cx50), in lens fibers that provide channels for exchange of ions and small molecules between adjacent cells. Conservative and functional prediction suggests that the W-to-R substitution at codon 4 may impair the function of the human Cx50 protein. Accordingly, we analyzed the distribution of Flag-tagged mutant Cx50 protein in HeLa cervical cancer cells. Immunofluorescent staining showed that the W-to-R substitution impaired Cx50 trafficking to the plasma membrane to form the gap junction. In conclusion, c.10T>A (p.W4R) in GJA8 is the newly identified genetic cause of familial congenital cataract. The W-to-R substitution near the amino-terminus may alter the localization of mutant Cx50, thereby impairing gap junction formation, which is the molecular pathogenic mechanism of this mutation.

[Application of Icare rebound tonometer in children after congenital cataract surgery].

OBJECTIVE: To compare the difference in intraocular pressure (IOP) readings as well as the tolerability between Icare rebound tonometer (Icare RBT) and Goldmann applanation tonometer (GAT), and to evaluate the application of Icare RBT in monitoring the intraocular pressure in children after congenital cataract surgery. METHODS: The IOP was measured with the Icare RBT and GAT respectively in 150 children (262 eyes) after congenital cataract surgery by two experienced ophthalmologists. Correlation and Bland-Altman analysis were used to assess the agreement in IOP readings between the two instruments. The influence of the central corneal thickness (CCT) adjusted for age on IOP readings was analyzed by linear regression analysis. The tolerance of the patients to Icare RBT and GAT measurement were surveyed. RESULTS: The mean age was (44.82 ± 11.56) months in 150 children, including 81 boys and 69 girls. The mean IOP readings by the Icare RBT and GAT were (16.08 ± 5.72) mmHg and (14.17 ± 5.05) mmHg, respectively. The mean difference between the Icare RBT and GAT was (1.91 ± 2.04) mmHg, which was significantly correlated with CCT (r=0.409, P<0.001). The IOP readings by Icare RBT was significantly correlated with that measured by GAT(r= 0.936, P<0.001). The 95% confidence interval of the difference between the two instruments was ?2.10 to 5.91 mmHg. The Icare RBT examination was well tolerated by the children compared to the GAT examination. CONCLUSION: The Icare RBT is easy to use and well tolerated by the children after congenital cataract surgery. Compared to GAT, the value measured by the IOPs trends to be overestimated. The difference in readings between the 2 tonometers will magnify with the increase in CCT.

[Ultraviolet radiation-induced apoptosis in human lens epithelial cells and its effect on Bcl-2 and Bax].

OBJECTIVE: To explore the apoptosis-inducing effect of ultraviolet(UV) radiation on human lens epithelial cells (HLEC), with particular focus on changes in Bcl-2 or Bax expression as possible mechanisms. METHODS: All experimental groups were exposed to the same UV light source. HLEC were divided into 6 groups according to duration of UV radiation : 0 min group (control group), 5 min group, 10 min group,15 min group, and 30 min group. Analysis on apoptosis of HLEC was performed by flow cytometry analysis (FCA, Annexin V + PI staining). Changes of Bax and Bcl-2 expression in HLEC were detected by hybridization in situ. RESULTS: Apoptosis in HLEC increased with UV exposure time. The expression level of Bax mRNA was increased with the increase of UV exposure time, whereas the expression level of Bcl-2 mRNA decreased with the increase of UV exposure time. The proportion of apoptotic cells was negatively correlated with ratio of Bcl-2/Bax (r=-0.874, P<0.05). CONCLUSION: UA radiation can induce apoptosis of HLEC in vitro. Bcl-2 and Bax genes may play an important role in regulating this apoptotic process.

[Effect of ultraviolet radiation on ALDH1 expression in human lens epithelial cells].

OBJECTIVE: To determine the apoptosis-inducing effect of ultraviolet light (UV) on human lens epithelial cell (HLEC) and to explore the involvement of changes in ALDH1 folowing UV radiation. METHODS: HLEC was exposed to the same UV light source and was subsequently divided into 6 groups according to UV radiation time of 0 (control group), 5, 10, 15, and 30 min. Apoptosis was detected by AO/EB staining. Changes of ALDH1 in HLEC were detected by immunohistochemical staining and Western blot. RESULTS: The intensity of immunohistochemical staining and the rate of positive cells decreased with increase of UV time (P<0.05). The rate of positive ALDH1 cells was negatively correlated with the rate of apoptosis (r= -0.92, P<0.05). Western blot showed the integrated absorbance values significantly decreased with the increase of UV time (P<0.05). CONCLUSION: ALDH1 in HLEC decreases with an increase of UV exposure, which may be related to UV induced apoptosis of HLEC.

Phacoemulsification with or without goniosynechialysis for angle-closure glaucoma: a global Meta-analysis based on randomized controlled trials.

AIM: To compare the benefits and potential harms of routine phacoemulsification (phaco) alone and combined surgery with goniosynechialysis (GSL) for angle-closure glaucoma (ACG) and coexisting lens opacity, as shown in different randomized controlled trials (RCTs). METHODS: A systematic review was conducted searching several databases including PubMed, Cochrane Library, EMBASE, ClinicalTrials.gov from the inception to September 2018 for RCTs with data published on the effects and safety of phaco and intraocular lens implantation combined with GSL or routine cataract surgery alone. Several studies were recruited which reported data at baselines and postoperative follow-up, including the mean values of postoperative intraocular pressure (IOP) and mean numbers of anti-glaucoma medications using postoperatively. The numbers of complications happening were also included. Fixed-effect and random-effect models were applied, and the quality of evidence was evaluated. RESULTS: Analysis of the seven included RCTs, with a total number of 321 participants (358 eyes) diagnosed with ACG and cataract, received a solo procedure (phaco group) or a combined surgery (phaco-GSL group) randomly, and follow-up periods ranging from 2 to 12mo postoperatively. The involved studies showed that the mean value of IOP between the two groups at 3 (four studies, one study follow-up at 2mo postoperative was included), 6, 12mo postoperative were not significantly different. Only two studies reported the change in IOP value at 12mo compared with baseline but showed no significant differences between the two interventions. Although three studies did not have the significant difference in the number of medications using to reduce IOP at 3mo postoperatively, two studies reported that the participants using fewer anti-glaucoma medications at 12mo postoperative in the phaco group than in the phaco-GSL surgery group. CONCLUSION: The analysis provides a low to moderate-quality evidence that phaco-GSL surgery lead to an equivalent IOP-lowering effect. The phaco-GSL surgery may not help patients to reduce the consumption of anti-glaucoma eyedrops in the long period. The results of this analysis suggested that additional GSL may not be necessary for primary angle closure glaucoma (PACG) patients. Further studies, especially RCTs with more participants and longer follow-up time were needed to provide more sufficient data.

LncRNA-MALAT1 promotes neovascularization in diabetic retinopathy through regulating miR-125b/VE-cadherin axis.

Background: Diabetic retinopathy (DR) is currently the leading cause of blindness and visual disability in adults with diabetes mellitus (DM). Neovascularization has been identified as an important clinical property in DR, however, the exact mechanisms in DR neovascularization are still unclear and need further elucidation.Methods: Quantitative real-time PCR (qRT-PCR) was conducted to detect the expression level of long non-coding RNA (lncRNA)-metastasis associated lung adenocarcinoma transcript 1 (MALAT1), miR-125b and vascular endothelial-cadherin (VE-cadherin) in human retina microvascular endothelial cells (hRMECs) treated with high glucose (HG). Luciferase assay was used to detect interaction of MALAT1 with miR-125b and miR-125b with VE-cadherin. MTT assay, transwell assay, tube formation assay and vascular permeability assay were conducted to detect the cell viability, migration tube formation ability and permeability of hRMECs, respectively. ELISA was used to examine the release of VE-cadherin and vascular endothelial growth factor (VEGF). Western blotting was used to access the protein expression of VE-cadherin, VEGF, ß-catenin, matrix metalloproteinase (MMP) 2 (MMP2) and MMP9.Results: MALAT1 and VE-cadherin were up-regulated while miR-125b was down-regulated in hRMECs treated with HG. MALAT1 could competitively bind to miR-125b against VE-cadherin at the site of 3'-untranslated region (3'-UTR), leading to the up-regulation of VE-cadherin. Knockdown of MALAT1 inhibited the proliferation, migration, tube formation and vascular permeability of hRMECs induced by HG through up-regulating miR-125b. Furthermore, we found the deletion of MALAT1 suppressed the VE-cadherin/ß-catenin complex and neovascularization related proteins expression, which was up-regulated by HG.Conclusion: Knockdown of MALAT1 inhibited cell proliferation, migration and angiogenesis of hRMECs via suppressing the VE-cadherin/ß-catenin complex through targeting miR-125b. Inhibition of MALAT1 may serve as a potential target for anti-angiogenic therapy for DR.

Attenuation of periostin in retinal Müller glia by TNF-α and IFN-γ.

AIM: To investigate the regulation and mechanisms of periostin expression in retinal Müller glia, and to explore the relevance to retinal neovascularization. METHODS: The oxygen-induced retinopathy (OIR) mouse model and the human Moorfield/Institute of Ophthalmology-Müller 1 (MIO-M1) cell line were used in the study. Immunofluorescence staining was used to determine the distribution and expression of periostin and a Müller glial cell marker glutamine synthetase (GS). Cytokines TNF-α and IFN-γ were added to stimulate the MIO-M1 cells. ShRNA was used to knockdown periostin expression in MIO-M1 cells. Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) was conducted to assess the mRNA expression of periostin. RESULTS: Immunofluorescence staining showed that periostin was expressed by MIO-M1 Müller glia. GS-positive Müller glia and periostin increased in OIR retinas, and were partially overlaid. The stimulation of TNF-α and IFN-γ reduced the mRNA expression of periostin significantly and dose-dependently in MIO-M1 cells. Knockdown of periostin reduced mRNA expression of vascular endothelial growth factor A (VEGFA) in MIO-M1 cells, while VEGFA expression was not changed in periostin knock-out OIR retinas. CONCLUSION: Müller glia could be one of the main sources of periostin in the retina, and might contribute to the pathogenesis of retinal neovascularization. Proinflammatory cytokines TNF-α and IFN-γ attenuate the periostin expression in retinal Müller glia, which provides a potential and novel method in treating retinal neovascular diseases.

Clinical application of accommodating intraocular lens.

The present review describes recent advances in application of accommodating intraocular lenses (AIOLs). Standard monofocal intraocular lenses (MIOLs) only correct distance vision, while AIOLs are designed to allow both good distance vision and near vision, which is achieved through the contraction and relaxation of ciliary muscles by providing transformation of the axial movement or curvature of the lens. Thus, AIOLs may be a better choice for those patients who demand a higher level of visual performance. Since techniques to analyze the performance of AIOLs have not been standardized, and there is a variety of both subjective and objective methods, it is hard to measure the performance of these intraocular lenses. By evaluating advantages and disadvantages of various AIOLs, and introducing techniques for measurement the performance postoperative, this paper can provide some relative information on choosing the type of AIOLs in the clinic.

New options for uveitis treatment.

Uveitis is one of the most important causes of blindness worldwide. Its etiology and pathogenesis are complicated and have not been well understood. The treatment for uveitis is predominantly based on steroids and immunosuppressants. However, systemic side effects limit their clinical application. With the advancement of molecular biology, some intravitreal implants and biologic agents have been used for the treatment of uveitis. Additionally, novel techniques such as gene therapy and RNA interference are being studied for using as uveitis therapy. This paper reviews recent advances in uveitis treatment.

Alpha lipoic acid protects lens from H(2)O(2)-induced cataract by inhibiting apoptosis of lens epithelial cells and inducing activation of anti-oxidative enzymes.

OBJECTIVE: To determine whether alpha lipoic acid (LA) can effectively protect lenses from hydrogen peroxide (H2O2)-induced cataract. METHODS: Lens from adult Sprague-Dawley rats were cultured in 24-well plates and treated without or with 0.2 mM of H2O2, 0.2 mM of H2O2 plus 0.5 mM, 1.0 mM, or 2.0 mM of LA for 24 h. Cataract was assessed using cross line grey scale measurement. Superoxide dismutase (SOD), glutathione (GSH-Px), lactate dehydrogenase (LDH), and malondialdehyde (MDA) activity or level in lens homogenates was measured. Apoptosis of lens epithelial cells in each group were detected by Terminal Deoxynucleotidyl Transferase dUTP Nick End Labeling (TUNEL) Assay. RESULTS: A total of 0.2 mM of H2O2 induced obvious cataract formation and apoptosis in lens' epithelial cells, but 0.5-2.0 mM of LA could block the effect of 0.2 mM H2O2 in inducing cataract and apoptosis. Furthermore, 0.2 mM of H2O2 significantly decreased SOD, GSH-Px, and LDH activity and significant increased MDA level in the lens, but 0.5-2.0 mM of LA blocked the effect of 0.2 mM H2O2. One mM of LA was found to be the most effective. CONCLUSIONS: LA can protect lens from H2O2-induced cataract. LA exerts protective effects through inhibition of lens' epithelial cell apoptosis and activation of anti-oxidative enzymes.

Comparison of the Icare tonometer and the hand-held goldmann applanation tonometer in pediatric aphakia.

PURPOSE: To compare the intraocular pressure (IOP) measurements obtained by the Icare and the hand-held Goldmann applanation tonometer (also called Perkins) in aphakic children after congenital cataract surgery. METHODS: We investigated 125 children with aphakia after congenital cataract surgery in this study. A younger group (3 to 30 mo) and an elder group (31 to 72 mo) were divided in those patients by their age. In the younger group, all measurements were performed under sedation using chloral hydrate. Axial length of the eye and central corneal thickness (CCT) were also measured from all patients. RESULTS: Significant correlation was found on IOP readings obtained by the Icare and the Perkins tonometers (r=0.943, P<0.001). After establishing a Bland-Altman plot, we found that 95% limit of the agreement between the 2 methods distributed between -1.6 to 5.6 mm Hg. The IOPs recorded from the Icare increased faster than that from the Perkins tonometer with the increase of the CCT thickness; a significant association relationship was found on the IOP difference between the 2 measurements (r=0.408, P<0.001). However, no statistical correlation was identified between the axial length and the IOPs recorded by either tonometer. CONCLUSIONS: Most of the young patients accepted the Icare tonometer under unsedated conditions. This significant advantage indicated that the Icare tonometer will be overall better tolerated in pediatric aphakia population, although it could overestimate the IOPs compared with the measurements obtained from the Perkins tonometer. Differences in readings between the 2 tonometers become bigger as the CCT increase.

Selective laser trabeculoplasty.

The introduction of selective laser trabeculoplasty (SLT) provided a new choice for the reduction of intraocular pressure (IOP) in eyes with open angle glaucoma (OAG) and ocular hypertension (OHT). SLT was demonstrated equally as effective as topical medical therapy and argon laser trabeculoplasty (ALT) to lower IOP. It is a potentially repeatable procedure because of the lack of coagulation damage to the trabecular meshwork (TM) and also effect in patients with previously failed ALT. SLT can be used to treat patients with OAG, pseudoexfoliation glaucoma, pigmentary glaucoma, normal-tension glaucoma, OHT, juvenile glaucoma, pseudophakic and aphakic glaucoma. Furthermore, SLT can be considered as a primary treatment option in patients who cannot tolerate or are noncompliant with medications, while not interfering with the success of future surgery. Its safety profiles include mild and transient inflammation, ocular pain and a small risk of moderate IOP elevations after the procedure. SLT is a safe and effective means of IOP reduction in eyes with OAG and OHT.

Descemet membrane detachment after trabeculectomy.

Descemet's membrane detachment (DMD) can be a potentially serious complication of intraocular surgery or ocular trauma. The cause is not very clear. We are trying to remind an awareness of the spectrum of DMD resulting from trabeculectomy by presenting a case of extensive DMD after trabeculectomy which was successfully repaired.

Involvement of the PI3K/Akt signaling pathway in platelet-derived growth factor-induced migration of human lens epithelial cells.

PURPOSE: Posterior capsular opacification (PCO) is caused partially by the migration of lens epithelial cells. To date, the mechanism of the migration is largely unknown. The purpose of this study was to investigate the effect of platelet-derived growth factor (PDGF)-triggered signaling pathways and its downstream effectors in the migration of lens epithelial cells. METHODS: In vitro scratch-wound healing and transwell migration assays were used to measure the migration of lens epithelial cells. The activation of PDGFR beta, phosphatidylinositol 3-kinas (PI3K)/protein kinase B (Akt) and mitogen activation protein kinase (MAPK) pathways, the impact of PDGF stimulation on the expression of cell protrusion molecules, and the stabilization of beta-catenin were measured by western blotting. The translocation of beta-catenin was detected using indirect immunofluorescence. RESULTS: PDGF was found to enhance cell migration, which depended on the PI3K/Akt pathway. The activation of the PI3K/Akt pathway by the PDGF/PDGFR beta axis induced the up regulation of cell protrusion molecules and stabilization and translocation of beta-catenin, contributing to enhanced cell migration. CONCLUSION: Data from this study directly linked the central PI3K/Akt pathway to lens epithelial cell migration and pointed to new avenues for therapeutic intervention in PCO.

[Correlation between secretion of VEGF and proliferation of cultured bovine retinal pigment epithelium cells under hypoxic condition].

PURPOSE: To investigate the effect of hypoxia on bovine retinal pigment epithelial (RPE) cell secreting vascular endothelial growth factor (VEGF) and the correlation between VEGF and proliferation of the cultured bovine retinal pigment epithelial cell. METHODS: Cells we harvested were divided into different groups with or without anti-VEGF monoclonal antibody (VEGF MAb), and then grew under hypoxic and normal (as a control) condition. After 24 h, cell supernatants were collected and used for ELISA VEGF protein assay. The proliferation of cells grown under different conditions was detected by MTT colorimetric assay. RESULTS: Cell proliferation and concentration of VEGF protein: The hypoxia with VEGF MAb group (Group A) was (1.812 +/- 0.068), (55.07 +/- 19.18) pg/ml; the hypoxia without VEGF MAb group (Group B) was (2.292 +/- 0.197), (171.61 +/- 16.02) pg/ml; the normal with VEGF MAb group (Group C) was (1.350 +/- 0.185), (43.92 +/- 21.39) pg/ml; the normal without VEGF MAb group (Group D) was (1.435 +/- 0.157), (48.51 +/- 24.73) pg/ml. Group A was lower than Group B on cell proliferation and concentration of VEGF protein. There is obvious difference between the two groups on both sides (P < 0.05). Group A was higher than Group D on cell proliferation. There is obvious difference between them on cell proliferation (P < 0.05). Group B is higher than Group D on cell proliferation and concentration of VEGF protein. There is obvious difference between them on both sides (P < 0.05). There is a linear association between the concentration of VEGF protein and the proliferation of RPE cell under hypoxic condition by Pearson Correlation (r = 1.000, P < 0.05). CONCLUSION: Hypoxia stimulates the secretion of vascular endothelium growth factor of bovine RPE cell, which contributes to the proliferation of bovine RPE cell.