Abstract:AIM: To explore the possibility of human umbilical cord mesenchymal stem cells (hUCMSCs), human umbilical vein endothelial cells (hUVECs), human dental pulp stem cells (hDPSCs) and human periodontal ligament stem cells (hPDLSCs) serving as feeder cells in co-culture systems for the cultivation of limbal stem cells. METHODS: Different feeder layers were cultured in Dulbecco’s modified Eagle’s medium (DMEM)/F12 and were treated with mitomycin C. Rabbits limbal stem cells (LSCs) were co-cultured on hUCMSCs, hUVECs, hDPSCs, hPDLSCs and NIH-3T3, and then comparative analysis were made between each group to see their respective colony-forming efficiency (CFE) assay and immunofluorescence (IPO13,CK3/12). RESULTS: The efficiency of the four type cells in supporting the LSCs morphology and its cellular differentiation was similar to that of NIH-3T3 fibroblasts as demonstrated by the immunostaining properties analysis, with each group exhibiting a similar strong expression pattern of IPO13, but lacking CK3 and CK12 expression in terms of immunostaining. But hUCMSCs, hDPSCs and hPDLSCs feeder layers were superior in promoting colony formation potential of cells when compared to hUVECs and feeder-cell-free culture. CONCLUSION: hUCMSCs, hDPSCs and hPDLSCs can be a suitable alternative to conventional mouse NIH-3T3 feeder cells, so that risk of zoonotic infection can be diminished.

Abstract:AIM: To investigate the toxicity of the E-prostanoid 2 (EP2) receptor agonist, butaprost against human subconjunctival (Tenon’s capsule) fibroblasts, and to determine the underlying mechanism. METHODS: We isolated Tenon’s fibroblasts from the subconjunctival area of healthy subjects and evaluated the types of EP receptors expressed using quantitative real-time reverse transcription polymerase chain reaction (RT-PCR). The toxicity of butaprost against the fibroblasts was evaluated using methyl thiazolyl tetrazolium and lactic dehydrogenase assays. The inhibition of conjunctival fibroblast proliferation by butaprost was assessed by measuring α-actin levels. The underlying mechanism was assessed by measuring intracellular cyclic adenosine monophosphate (cAMP) levels. Intergroup differences were statistically analyzed using an independent t-test. Densitometry of the Western blot bands was performed using the Image J software. RESULTS: Quantitative real-time RT-PCR revealed that the fibroblast EP2 receptor levels were higher than those of the other EP receptors. Butaprost did not show toxicity against Tenon’s tissue, but inhibited conjunctival fibroblast proliferation by reducing collagen synthesis. EP2 receptor activation enhanced the cAMP cascade, which might be an important mechanism underlying this effect. CONCLUSION: Butaprost effectively reduces the subconjunctival scarring response. Given the significance of wound healing modulation in blebs, butaprost’s inhibitory effect on subconjunctival Tenon’s fibroblasts may be beneficial in managing postoperative scarring in glaucoma surgery.

Abstract:AIM: To investigate the expression differences of transforming growth factor-β2 (TGF-β2), basic fibroblast growth factor (bFGF) and intercellular cell-adhesion molecule-1 (ICAM-1) in lens epithelial cells (LECs) of complicated cataract with silicone oil tamponade and age-related cataract. METHODS: Totally 150 eyes of 150 patients (aged 35 to 77y) were investigated, including 75 patients with complicated cataract after silicone oil tamponade and 75 patients with age-related cataract. The central piece of anterior capsules was collected during cataract surgery. TGF-β2, bFGF and ICAM-1 were detected in the 60 specimens of the two groups by immunohistochemistry. The expression levels of the three kinds of messenger ribonucleic acid (mRNA) were determined by real-time quantitative reverse transcription-polymerase chain reaction in the 90 specimens of the two groups. RESULTS: TGF-β2 was detected in the cytomembrane and cytoplasm of the LECs and bFGF was detected in the nucleus. ICAM-1 was positive in the cytomembrane of the LECs and the distribution of positive cells was uneven. The mRNA genes expression of the TGF-β2, bFGF and ICAM-1 was significant differences between the two groups and markedly increased in complicated cataract group (P<0.05). CONCLUSION: The up-regulated TGF-β2, bFGF and ICAM-1 maybe associate with the occurrence and development of complicated cataract with silicone oil tamponade.

Abstract:AIM: To investigate the roles of PKC-α/ezrin signals in phagocytosis crisis of retinal pigment epithelium (RPE) cells in light damage model. METHODS: Light induced mice RPE injury model was established by continuously irradiating cool white light at different exposure time (0, 4, 8h light intensity: 4.18×10-6 J/cm2). In vitro, human ARPE-19 cells treated with the doses and intensity (1.57×10-6 J/cm2) of laser irradiation. Histology analysis was evaluated by hematoxylin and eosin (HE) staining. In vivo RPE phagocytosis was quantified by measuring the accumulation of photoreceptor outer segments in the sub-retinal space. In vitro RPE phagocytosis was assessed by calculating the relative fluorescence intensity of FITC-labeled microspheres in ARPE-19 cells. To further investigate the molecular mechanism, the activation of PKC-α/ezrin signal was evaluated by Western blot in vivo and in vitro. RESULTS: HE staining revealed that the thickness of outer nuclear layer decreased significantly after 4 and 8h light exposure. By immunostaining with rhodopsin, a significant greater accumulation of photoreceptor outer segment was noticed after light injury. In vitro, light injured RPE cells had less phagocytic activity in a dose dependent manner than that of the normal control (P<0.01). Western blot suggested the activation of PKC-α/ezrin signaling was down-regulated in a dose-dependent manner after light exposure. CONCLUSION: Our data suggest that light induced phagocytic crisis of RPE cells may result from the down-regulation of PKC-α/ezrin signaling.

Abstract:AIM: To investigate the potential of pigment epithelium-derived factor (PEDF) to protect the immortalized rat retinal ganglion cells-5 (RGC-5) exposed to CoCl2-induced chemical hypoxia. METHODS: After being differentiated with staurosporine (SS), RGC-5 cells were cultured in four conditions: control group cells cultured in Dulbecco 's modified eagle medium (DMEM) supplemented with 10% fetal bovine serum, 100 μmol/mL streptomycin and penicillin (named as normal conditions); hypoxia group cells cultured in DMEM containing 300 μmol/mL CoCl2; cells in the group protected by PEDF were first pretreated with 100 ng/mL PEDF for 2h and then cultured in the same condition as hypoxia group cells; and PEDF group cells that were cultured in the presence of 100 ng/mL PEDF under normal conditions. The cell viability was assessed by MTT assay, the percentage of apoptotic cells was quantified using Annexin V-FITC apoptosis kit, and intra-cellar reactive oxygen species (ROS) was measured by dichloro-dihydro-fluorescein diacetate (DCFH-DA) probe. The mitochondria-mediated apoptosis was also examined to further study the underlying mechanism of the protective effect of PEDF. The opening of mitochondrial permeability transition pores (mPTPs) and membrane potential (Δψm) were tested as cellular adenosine triphosphate (ATP) level and glutathione (GSH). Also, the expression and distribution of Cyt C and apoptosis inducing factor (AIF) were observed. RESULTS: SS induced differentiation of RGC-5 cells resulting in elongation of their neurites and establishing contacts between outgrowths. Exposure to 300 μmol/mL CoCl2 triggered death of 30% of the total cells in cultures within 24h. At the same time, pretreatment with 100 ng/mL PEDF significantly suppressed the cell death induced by hypoxia (P<0.05). The apoptosis induced by treatment of CoCl2 was that induced cell death accompanied with increasing intra-cellar ROS and decreasing GSH and ATP level. PEDF pre-treatment suppressed these effects (P<0.05). Additionally, PEDF treatment inhibited the opening of mPTPs and suppressed decreasing of Δψm in RGC-5 cells, resulting in blocking of the mitochondrial apoptotic pathway. CONCLUSION: Pretreatment of RGC-5 cells with 100 ng/mL PEDF significantly decreases the extent of apoptosis. PEDF inhibits the opening of mPTPs and suppresses decreasing of Δψm. Moreover, PEDF also reduces ROS production and inhibits cellular ATP level’s reduction. Cyt C and AIF activation in PEDF-pretreated cultures are also reduced. These results demonstrate the potential for PEDF to protect RGCs against hypoxic damage in vitro by preventing mitochondrial dysfunction.

Abstract:AIM: To investigate the role of oxidative stress in regulating the functional expression of P-glycoprotein (P-gp) in mitochondria of D407 cells. METHODS: D407 cells were exposed to different ranges of concentrations of H2O2. The mitochondrial location of P-gp in the cells subjected to oxidative stress was detected by confocal analysis. Expression of P-gp in isolated mitochondria was assessed by Western blot. The pump activity of P-gp was evaluated by performing the efflux study on isolated mitochondria with Rhodamine 123 (Rho-123) alone and in the presence of P-gp inhibitor (Tariquidar) using flow cytometry analysis. The cells were pretreated with 10 mmol/L N-acetylcysteine (NAC) for 30min before exposing to H2O2, and analyzed the mitochondrial extracts by Western blot and flow cytometry. RESULTS: P-gp was co-localized in the mitochondria by confocal laser scanning microscopy, and it was also detected in the mitochondria of D407 cells using Western blot. Exposure to increasing concentrations of H2O2 led to gradually increased expression and location of P-gp in the mitochondria of cells. Rho-123 efflux assay showed higher uptake of Rho-123 on isolated mitochondria in the presence of Tariquidar both in normal and oxidative stress state. H2O2 up-regulated P-gp in D407 cells, which could be reversed by NAC treatment. CONCLUSION: H2O2 could up-regulate the functional expression of P-gp in mitochondria of D407 cells, while antioxidants might suppress oxidative-stress-induced over-expression of functional P-gp. It is indicative that limiting the mitochondrial P-gp transport in retinal pigment epithelium cells would be to improve the effect of mitochondria-targeted antioxidant therapy in age-related macular degeneration-like retinopathy.

Abstract:AIM: To investigate the mechanism underlying the loss of responsiveness to anti-vascular endothelial growth factor (VEGF) treatment after repeated injections for choroidal neovascularization, VEGF and VEGF receptor (VEGFR) expressions were evaluated following repeated bevacizumab treatments in hypoxic human umbilical vein endothelial cells (HUVECs) in vitro. METHODS: HUVECs were incubated under hypoxic conditions in two media of different bevacizumab concentrations (1.0 or 2.5 mg/mL) for 17h, and then in a new medium without bevacizumab for 7h. This procedure was repeated twice more. A culture with an identical volume of excipients served as the control. Cytotoxicity and cell proliferation were assessed using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide and Ki-67 assays, respectively. Levels of VEGF and VEGFR were assessed using enzyme-linked immunosorbent assay and Western blot respectively. RESULTS: Cytotoxic effects were not reported for either bevacizumab concentration. Cell proliferation was not reduced after anti-VEGF treatments. VEGF level after single treatment was significantly higher than that of the control and after repeated treatments. Phosphorylated VEGFR-2 expression increased significantly after single and repeated bevacizumab treatments compared with the control. The 1.0 mg/mL bevacizumab induced significantly higher expressions of VEGFR-2 than the 2.5 mg/mL in single and repeated treatment groups. CONCLUSION: Bevacizumab treatment of HUVECs elevated VEGFR expression in both single and repeated treatments, indicating a mechanism for the reduced efficacy of anti-VEGF therapy in ocular neovascular disorders.

Abstract:AIM: To investigate whether single-dose intravitreal injections of bevacizumab and ranibizumab transfer into milk. METHODS: This study included lactating 12 sheep and a single 3-month old suckling lamb of each sheep. Two groups consisting of 6 sheep and their lambs were constituted; the ranibizumab group and the bevacizumab group before the administration of intravitreal injections, blood and milk samples were obtained from all sheep and, following the injections, blood and milk samples of all sheep and blood samples of all lambs were collected at regular time points. Serum and milk concentrations of bevacizumab and ranibizumab were measured using an enzyme-linked immunosorbent assay (ELISA) kit. The limit of determination was 0.9 ng/mL for bevacizumab and 0.62 ng/mL for ranibizumab. RESULTS: At 6h after intravitreal injections, bevacizumab concentration was above the limit of determination in the blood of all sheep. At 3wk, when the study was terminated, bevacizumab concentrations were high in 4 sheep. Even though bevacizumab concentrations in milk showed fluctuations, the drug transferred into the milk of all sheep at detectable concentrations. Ranibizumab drug concentrations in the blood and milk of sheep and those in the blood of lambs were below the limit of determination by the ELISA kit. CONCLUSION: This sheep model study demonstrate that intravitreal injection of ranibizumab, which did not transfer into the milk of sheep and suckling lambs, is safer than bevacizumab during lactation period.

Abstract:AIM: To analyze the clinical factors influencing the human vision corrections via the changing of ocular components of human eye in various applications; and to analyze refractive state via a new effective axial length. METHODS: An effective eye model was introduced by the ocular components of human eye including refractive indexes, surface radius (r1, r2, R1, R2) and thickness (t, T) of the cornea and lens, the anterior chamber depth (S1) and the vitreous length (S2). Gaussian optics was used to calculate the change rate of refractive error per unit amount of ocular components of a human eye (the rate function M). A new criterion of myopia was presented via an effective axial length. RESULTS: For typical corneal and lens power of 42 and 21.9 diopters, the rate function Mj (j=1 to 6) were calculated for a 1% change of r1, r2, R1, R2, t, T (in diopters) M1=+0.485, M2=-0.063, M3=+0.053, M4=+0.091, M5=+0.012, and M6=-0.021 diopters. For 1.0 mm increase of S1 and S2, the rate functions were M7=+1.35, and M8=-2.67 diopter/mm, respectively. These rate functions were used to analyze the clinical outcomes in various applications including laser in situ keratomileusis surgery, corneal cross linking procedure, femtosecond laser surgery and scleral ablation for accommodation. CONCLUSION: Using Gaussian optics, analytic formulas are presented for the change of refractive power due to various ocular parameter changes. These formulas provide useful clinical guidance in refractive surgery and other related procedures.

Abstract:AIM: To determine the incidence of cystoid macular edema (CME) after Descemet’s stripping automated endothelial keratoplasty (DSAEK). METHODS: This study included all consecutive patients operated in a Spanish tertiary reference hospital over a period of four years. A total of 55 eyes from 47 patients matched the selection criteria. CME was diagnosed clinically at the slit-lamp and confirmed by optical coherence tomography. RESULTS: Six cases of CME were diagnosed postoperatively, which represented an incidence of 11%. Three patients had previously undergone DSAEK alone (7%; 3/41) and the other three, DSAEK combined with phacoemulsification (21%; 3/14). Five out of six patients with CME responded to standard therapy. CONCLUSION: CME is a possible complication after DSAEK and can be treated with standard therapy. CME appears more frequently when DSAEK is combined with phacoemulsification and posterior chamber (PC) intraocular lens (IOL) implantation. Intraoperative damage to the corneal endothelial cells might play a role in the pathogenesis of CME. As long as the causes remain unclear, we recommend administering prophylaxis when risk factors are present or when combined surgery is planned.

Abstract:AIM: To use the cumulative sum analysis score (CUSUM) to construct objectively the learning curve of phacoemulsification competency. METHODS: Three second-year residents and an experienced consultant were monitored for a series of 70 phacoemulsification cases each and had their series analysed by CUSUM regarding posterior capsule rupture (PCR) and best-corrected visual acuity. The acceptable rate for PCR was <5% (lower limit h) and the unacceptable rate was >10% (upper limit h). The acceptable rate for best-corrected visual acuity worse than 20/40 was <10% (lower limit h) and the unacceptable rate was >20% (upper limit h). The area between lower limit h and upper limit h is called the decision interval. RESULTS: There was no statistically significant difference in the mean age, sex or cataract grades between groups. The first trainee achieved PCR CUSUM competency at his 22nd case. His best-corrected visual acuity CUSUM was in the decision interval from his third case and stayed there until the end, never reaching competency. The second trainee achieved PCR CUSUM competency at his 39th case. He could reach best-corrected visual acuity CUSUM competency at his 22nd case. The third trainee achieved PCR CUSUM competency at his 41st case. He reached best-corrected visual acuity CUSUM competency at his 14th case. CONCLUSION: The learning curve of competency in phacoemulsification is constructed by CUSUM and in average took 38 cases for each trainee to achieve it.

Abstract:AIM: To assess the level of glutathione, thioltransferase, and argpyrimidine in nuclear and cortical cataractous lenses as well as in the clear lenses in the north Indian population. METHODS: Human cataractous lenses were collected from the patients who underwent extracapsular cataract extraction surgery; clear lenses were collected from the freshly donated eye bank eyes. Antioxidant molecules such as glutathione and thioltransferase enzyme activity were measured; simultaneously in these lenses a blue fluorophore argpyrimidine, an advanced glycation end (AGE) product level was assessed using high performance liquid chromatography (HPLC). RESULTS: The protein concentration was found to be present at higher levels in the control lenses compared to cataract lenses. A significant decrease in the glutathione level was observed in the nuclear cataractous lenses compared to cortical cataractous (P=0.004) and clear lenses (P≤0.005), but no significant change in the level of antioxidant enzyme thioltransferase was observed. Further, argpyrimidine a blue fluorophore (AGE) was found to be significantly higher in the nuclear cataract (P=0.013) compared to cortical cataract lenses. CONCLUSION: Antioxidants such as glutathione significantly decrease in age-related nuclear and cortical cataract and an AGE, argpyrimidine are present at significantly higher levels in nuclear cataract.

Abstract:AIM: To determine the levels of aquaporin-1 (AQP-1) in the lens epithelial cells (LECs) of primary glaucoma and to clarify its correlation with lens thickness. METHODS: This study comprised 64 eyes of 64 patients with primary glaucoma, who were divided into 3 groups: 25 eyes of 25 patients with acute primary angle-closure glaucoma (APACG), 19 eyes of 19 patients with chronic primary angle-closure glaucoma (CPACG) and 20 eyes of 20 patients with primary open angle glaucoma (POAG). This study also included 12 eyes of 12 patients with senile cataract as controls. The levels of AQP-1 in LECs were examined by real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry. The lens thickness was measured by A-scan ultrasonography. RESULTS: The AQP-1 mRNA levels of LECs were 0.84±0.27, 0.69±0.34, 0.44±0.19 and 0.51±0.21 in APACG, CPACG, POAG and senile cataract group, respectively. The levels of AQP-1m RNA were significantly higher in PACG groups compared with those in senile cataract and POAG group (all P<0.05). The immunohistochemistry showed the AQP-1 expression were strong-positive in PACG groups, but weak-positive in senile cataract and POAG group. A positive correlation was found between AQP-1 mRNA levels and the lens thickness (r=0.645, P<0.001). CONCLUSION: These findings show that the higher expression of AQP-1 in LECs may contribute to increased lens thickness, which might be associated with the occurrence and development of PACG.

Abstract:AIM: To evaluate and compare the diagnostic capabilities of peripapillary retinal nerve fiber layer (p-RNFL) parameters of Spectralis optical coherence tomography (OCT) versus Stratus OCT to detect glaucoma in patients with high myopia. METHODS: This is a retrospective, cross-sectional study. Sixty highly myopic eyes of 60 patients were enrolled, with 30 eyes in the glaucoma group and 30 eyes in the control group. All eyes received peripapillary imaging of the optic disc using Stratus and Spectralis OCT. Areas under the receiver operating characteristic curve (AUROC) and the sensitivity at specificity of >80% and >95% for p-RNFL parameters obtained using the two devices to diagnose glaucoma were analysed and compared. RESULTS: In Spectralis OCT, p-RNFL thickness parameters with the largest AUROC were the temporal-inferior sector (0.974) and the inferior quadrant (0.951), whereas in Stratus OCT, the best parameters were the 7-o’clock sector (0.918) and the inferior quadrant (0.918). Compared to the Stratus OCT parameters, the Spectralis OCT parameters demonstrated generally higher AUROC; however, the difference was not statistically significant. CONCLUSION: The best p-RNFL parameters for diagnosing glaucoma in patients with high myopia were the temporal-inferior sector on Spectralis OCT and the 7-o’clock sector on Stratus OCT. There were no significant differences between the AUROCs for Spectralis OCT and Stratus OCT, which suggest that the glaucoma diagnostic capabilities of these two devices in patients with high myopia are similar.

Abstract:AIM: To appraise the effect of treatment for diabetic macular edema (DME) in proliferative stage with sufficient panrentinal photocoagulation (PRP) therapy and intravitreal injections (IV) Conbercept and posterior subtenon’s triamcinolone acetonide (STTA) sequential therapy. METHODS: This prospective clinical randomized controlled trial of cross-over design was conducted in three phases. The participants included cases of DME in proliferative stage. They were divided into two groups and treated with PRP before enrollment. Group A were treated with IV-Conbercept 0.5 mg for one month in the 1st phase. Group B were treated with STTA 40 mg (twice per two weeks). The interventions were exchanged in the second phase (2mo) between the two groups. In the third phase (3-6mo) no other treatment was given. Best corrected visual acuity (BCVA), central macular thickness (CMT) measured by OCT and complications were compared. RESULTS: After phase I: in Group A, BCVA improved from 0.201±0.17 to 0.37±0.24 (F=5.88, P=0.004). CMT changed from 449±155.10 to 304.1±84.70 μm (F=14.9, P<0.01). In Group B, BCVA changed from 0.195±0.19 to 0.26±0.20 (F=0.76, P=0.41) while CMT changed from 463.82±152.92 to 366.00±115.40 μm (F=3.70, P<0.03). The improvement of BCVA was better in Group A (P<0.05). After phase II: in Group A, BCVA raised to 0.47±0.27 (F=0.26, P<0.01), CMT reduced to 260.67±62.97 μm (F=-188.3, P<0.01); in Group B, BCVA raised to 0.51±0.26 (F=0.31, P<0.01), CMT reduced to 261.93±50.15 μm (F=-201.9, P<0.01). But there were no difference between two groups (P>0.05). After phase III: in Group A, BCVA maintained 0.42±0.25 (F=0.22, P=0.001), CMT maintained 267.8±58.34 μm, (F=-0.27, P<0.01); in Group B, BCVA was 0.47±0.25 (F=-0.27, P<0.01), CMT was 272.71±49.16 μm (F=-191.1, P<0.01). No serious complications happened in all phases. CONCLUSION: PRP+Conbercept is better than PRP+STTA in DME with proliferative stage but PRP+Conbercept+STTA sequential therapy may be a wiser choice for persistent effectiveness on anatomical as well as functional status.

Abstract:AIM: To study the factors affecting residual exotropia (>10 PD) at 4-6wk postoperative visit following two rectus muscle surgery for intermittent exotropia [bilateral lateral rectus (LR) recession or unilateral recess resect procedure]. METHODS: A retrospective chart review of patients with intermittent exotropia ≤50 PD who underwent two rectus muscle surgery in between Jan. 2011 to Dec. 2013 was performed. Possible factors were compared between patients with residual exotropia (>10 PD) and successful outcome (within 10 PD of orthotropia) at the 4-6wk postoperative visit. Effect/dose ratio was calculated by dividing the effect of surgery by the total amount (mm) of muscle surgery done. RESULTS: One hundred and fifty-seven patients with mean age of 14y (range 3-53y) were included. Twenty-seven patients (17.2%) had residual exotropia at 4-6wk postoperative follow up. Age at surgery (P=0.009) and preoperative deviation for distance (P≤0.001) and near (P=0.001) were identified as important predictors of unsuccessful outcome. The occurrence of residual exotropia was not affected by amblyopia, anisometropia, lateral incomitance, pattern deviation, vertical deviation, type of exotropia or type of surgery done (recess-resect or bilateral LR recession). The effect/dose ratio was more in deviations >40 PD in the both recess-resect and bilateral LR recession type of surgery. The effect/dose ratio was less in patients with residual exotropia as compared to the successful outcome group (1.36 PD/mm vs 2.05 PD/mm in the bilateral LR recession surgery and 1.93 PD/mm vs 2.63 PD/mm in the unilateral recess-resect surgery). CONCLUSION: Residual exotropia is seen in 17% of patients after two muscle surgery for intermittent exotropia. Patients with older age and larger preoperative deviation have greater chances of developing failure of two muscle strabismus surgery for intermittent exotropia.

Abstract:AIM: To evaluate the clinical effect of bevacizumab in pterygium treatment. METHODS: A systematic review and quantitative Meta-analysis was performed. PubMed, EMBASE, Web of Science and Cochrane database were searched for eligible literatures published in English until June 2016. The endpoint was recurrence rate and pooled risk ratio (RR) was calculated. RESULTS: Nine eligible studies were included and Meta-analysis results showed no significantly difference in patients treated with bevacizumab in short term follow-up [3mo: RR=0.70 (0.34, 1.45); 6mo: RR=0.55 (0.23, 1.32)] compared with control groups. No significant effects were observed in favor of bevacizumab in subgroup analyses: patients with subconjunctival injection of bevacizumab [3mo: RR=0.95 (0.70, 1.29); 6mo: RR=0.83 (0.55, 1.28)], primary pterygium [3mo: RR=0.59 (0.23, 1.54; 6mo: RR=0.59 (0.23, 1.53)], simple pterygium excision [3mo: 0.32 (0.05, 2.04), P=0.23; 6mo: 0.27 (0.05, 1.53)] and excision with conjunctival autograft [3mo: 1.51 (0.25, 9.15); 6mo: 1.11 (0.06, 21.69)]. CONCLUSION: In this Meta-analysis, we did not found the significant effect of bevacizumab in pterygium treatment, at least in short term follow-up (3mo and 6mo).

Abstract:AIM: To compare the therapeutic effect and safety of laser photocoagulation along with intravitreal ranibizumab (IVR) versus laser therapy in treatment of diabetic macular edema (DME). METHODS: Pertinent publications were identified through comprehensive searches of PubMed, EMBASE, Web of Science, Cochrane Library, and ClinicalTrials.gov to identify randomized clinical trials (RCTs) comparing IVR+laser to laser monotherapy in patients with DME. Therapeutic effect estimates were determined by weighted mean differences (WMD) of change from baseline in best corrected visual acuity (BCVA) and central retinal thickness (CRT) at 6, 12, or 24mo after initial treatment, and the risk ratios (RR) for the proportions of patients with at least 10 letters of improvement or reduction at 12mo. Data regarding major ocular and nonocular adverse events (AEs) were collected and analyzed. The Review Manager 5.3.5 was used. RESULTS: Six RCTs involving 2069 patients with DME were selected for this Meta-analysis. The results showed that IVR+laser significantly improved BCVA compared with laser at 6mo (WMD: 6.57; 95% CI: 4.37-8.77; P<0.00001), 12mo (WMD: 5.46; 95% CI: 4.35-6.58; P<0.00001), and 24mo (WMD: 3.42; 95% CI: 0.84-5.99; P=0.009) in patients with DME. IVR+laser was superior to laser in reducing CRT at 12mo from baseline with statistical significance (WMD: -63.46; 95% CI: -101.19 to -25.73; P=0.001). The pooled RR results showed that the proportions of patients with at least 10 letters of improvement or reduction were in favor of IVR+laser arms compared with laser (RR: 2.13; 95% CI: 1.77-2.57; P<0.00001 and RR: 0.37; 95% CI: 0.22-0.62; P=0.0002, respectively). As for AEs, the pooled results showed that a significantly higher proportion of patients suffering from conjunctival hemorrhage (study eye) and diabetic retinal edema (fellow eye) in IVR+laser group compared to laser group (RR: 3.29; 95% CI: 1.53-7.09; P=0.002 and RR: 3.02; 95% CI: 1.24-7.32; P=0.01, respectively). The incidence of other ocular and nonocular AEs considered in this Meta-analysis had no statistical difference between IVR+laser and laser alone. CONCLUSION: The results of our analysis show that IVR+laser has better availability in functional (improving BCVA) and anatomic (reducing CRT) outcomes than laser monotherapy for the treatment of DME. However, the patients who received the treatment of IVR+laser may get a higher risk of suffering from conjunctival hemorrhage (study eye) and diabetic retinal edema (fellow eye).

Abstract:AIM: To gain a better understanding of possible factors that may influence the decision of diabetes persons to participate in annual eye screening in an urban community setting of China. METHODS: A structured interview including questions on attendance of eye screening, knowledge and awareness of diabetic retinopathy was conducted. The presence and degree of retinopathy were assessed using two field non-mydriatic retinal photography. RESULTS: Totally 720 diabetes persons were recruited and 519 were enrolled in this cross-sectional study. In this urban setting of Beijing, among diabetes patients of average of 10y duration, 77% confirmed having undergone at least one eye examination and 61% reported having at least one eye examination with dilated pupil. As for the last 12mo, the number decreased to 210 (47%) and 131 (30%) separately. Most of the participants (95%) were aware that diabetes could affect their vision and that regular eye examination was necessary. Very few of them (12%) however were aware that the early stages of diabetic retinopathy presented without symptoms of vision loss. Having attended patient education on diabetes was effective in building awareness about diabetic eye disease and was a significant positive predictor for attending eye screening [education in a year, Adj. OR=0.47 (0.29-0.74), P<0.001, education years ago, Adj. OR=0.56 (0.33-0.96), P=0.036]. The duration of disease also increased the likelihood of having undergone eye screening (Adj. OR=0.96, P<0.05). CONCLUSION: Being exposed to education about the complications of diabetes increases the probability of attending diabetic eye screening. An appropriate patient knowledge building strategy should be made available to patients from the time of diagnosis.

Abstract:AIM: To determine age norms in the first three years of life for grating visual acuity and contrast sensitivity obtained with Lea grating test and Hiding Heidi low contrast face test. METHODS: Lea grating test was used to estimate binocular grating acuity and Hiding Heidi low contrast face test was used to estimate contrast sensitivity in 600 healthy infants and children. Age ranged from 3 to 36mo subdivided into 12 groups subjected for full ophthalmologic and pediatric examinations. RESULTS: The grating acuity developed along the first three years of life. It ranged from 1.88±0.32 c/d at 3mo to 30.95±0.77 c/d at 36mo. The most rapid development was during the first 12mo and the slowest development was from 30 to 36mo. The contrast sensitivity showed rapid development in the first two years of life. Its mean value ranged from 4.23±1.17 at 3mo to 78.26±8.21 at 24mo. It was constant at the highest score (80) thereafter. CONCLUSION: Age norms for grating acuity along with contrast sensitivity offer a more comprehensive measure of spatial vision and should be incorporated in clinical practice for better visual assessment in preverbal and nonverbal children.

Abstract:According to World Health Organization, the global prevalence of blindness in 2010 was 39 million people, among which 4% were due to corneal opacities. Often, the sole resort for visual restoration of patients with damaged corneas is corneal transplantation. However, despite rapid developments of surgical techniques, instrumentations and immunosuppressive agents, corneal blindness remains a prevalent global health issue. This is largely due to the scarcity of good quality corneal grafts. In this review, the causes of corneal blindness, its major treatment options, and the major contributory factors of corneal graft scarcity with potential solutions are discussed.

Abstract:Sleep accounts for a third of one’s lifetime, partial or complete deprivation of sleep could elicit sever disorders of body function. Previous studies have reported the higher prevalence of sleep disorders in glaucoma patients, but the definite mechanism for this phenomenon is unknown. On the other hand, it is well known by us that the intrinsically photosensitive retinal ganglion cells (ipRGCs) serve additional ocular functions, called non-image-forming (NIF) functions, in the regulation of circadian rhythm, melatonin secretion, sleep, mood and others. Specifically, ipRGCs can directly or indirectly innervate the central areas such as suprachiasmatic nucleus (SCN), downstream pineal gland (the origin of melatonin), sleep and wake-inducing centers and mood regulation areas, making NIF functions of ipRGCs relate to sleep. The more interesting thing is that previous research showed glaucoma not only affected visual functions such as the degeneration of classical retinal ganglion cells (RGCs), but also affected ipRGCs. Therefore, we hypothesize that higher prevalence of sleep disorders in glaucoma patients maybe result from the underlying glaucomatous injuries of ipRGCs leading to the abnormalities of diverse NIF functions corresponding to sleep.

Abstract:This study aims to evaluate and to compare three different approaches of cataract surgery to patients with previous radial keratotomy (RK), and to analyze the mechanical properties of the cornea after cataract surgery. Three groups of patients, each one including 8 eyes of patients with 16 RK incisions. The first group includes eyes with the first cataract incision superiorly, the second group in the temporal area, the third group in temporal area and a precautionary stabilizing suture across the RK incision adjacent to the main tunnel. In the first group intraoperative dehiscence occurred in three eyes (37.5%): it required immediate application of a suture. In the second group dehiscence occurred intraoperatively in two radial scars (20%): it required immediate application of a suture. In the third group, no intraoperative dehiscences were observed. The stabilizing suture of the RK incision works safer, with a lower risk of dehiscences and less post-operative astigmatism.

Abstract:In the paper a referral system to assist the medical experts in the screening/referral of diabetic retinopathy is suggested. The system has been developed by a sequential use of different existing mathematical techniques. These techniques involve speeded up robust features (SURF), K-means clustering and visual dictionaries (VD). Three databases are mixed to test the working of the system when the sources are dissimilar. When experiments were performed an area under the curve (AUC) of 0.9343 was attained. The results acquired from the system are promising.

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