Abstract:AIM: To compare the potential protective effects of epi-gallocatechin gallate (EGCG) and ellagic acid (EA) in an experimental cataract model. METHODS: Twenty-eight Spraque-Dawley rat pups were assigned into four groups. All the rats, except for those in the control group, were injected subcutaneously sodium selenite to induce experimental cataract on the postpartum ninth day, and between 10th and 14th days. Rats in the sham, EGCG, and EA groups were intraperitoneally administered 50 mg/(kg·d) saline solution, 50 mg/(kg·d) EGCG and 200 mg/(kg·d) EA, respectively. The reduced glutathione (GSH) and malondialdehyde (MDA) levels, total antioxidant status (TAS) and total oxidant status (TOS) in lens supernatants were measured. RESULTS: The mean cataract gradings in EGCG and EA groups were found to be significantly lower than that in sham group (P<0.001). The mean GSH levels and TASs in EGCG and EA groups were significantly higher than that in sham group while mean MDA levels and TOSs in EGCG and EA groups were significantly lower than that in the sham group (P<0.001). CONCLUSION: EGCG and EA have protective effects on cataract development via the inhibition of oxidative stress.

Abstract:AIM: To investigate the cross-talk between oxidative stress and the epidermal growth factor receptor (EGFR)/AKT signaling pathway in retinal pigment epithelial (RPE) cells. METHODS: Human RPE cell lines (ARPE-19 cell) were treated with different doses of epidermal growth factor (EGF) and hydrogen peroxide (H2O2). Cell viability was determined by a methyl thiazolyl tetrazolium assay. Cell proliferation was examined by a bromodeoxyuridine (BrdU) incorporation assay. EGFR/AKT signaling was detected by Western blot. EGFR localization was also detected by immunofluorescence. In addition, EGFR/AKT signaling was intervened upon by EGFR inhibitor (erlotinib), PI3K inhibitor (A66) and AKT inhibitor (MK-2206), respectively. H2O2-induced oxidative stress was blocked by antioxidant N-acetylcysteine (NAC). RESULTS: EGF treatment increased ARPE-19 cell viability and proliferation through inducing phosphorylation of EGFR and AKT. H2O2 inhibited ARPE-19 cell viability and proliferation and also suppressed EGF-stimulated increase of RPE cell viability and proliferation by affecting the EGFR/AKT signaling pathway. EGFR inhibitor erlotinib blocked EGF-induced phosphorylation of EGFR and AKT, while A66 and MK-2206 only blocked EGF-induced phosphorylation of AKT. EGF-induced phosphorylation and endocytosis of EGFR were also affected by H2O2 treatment. In addition, antioxidant NAC attenuated H2O2-induced inhibition of ARPE-19 cell viability through alleviating reduction of EGFR, and phosphorylated and total AKT proteins. CONCLUSION: Oxidative stress affects RPE cell viability and proliferation through interfering with the EGFR/AKT signaling pathway. The EGFR/AKT signaling pathway may be an important target in oxidative stress-induced RPE cell dysfunction.

Abstract:AIM: To investigate the altering expression profiles of efflux transporters such as breast cancer-resistance protein (BCRP), lung resistance protein (LRP), and multidrug resistance protein 1 (MDR1) at the inner blood-retinal barrier (BRB) during the development of early diabetic retinopathy (DR) and/or aging in mice. METHODS: Relative mRNA and protein expression profiles of these three efflux transporters in the retina during the development of early DR and/or aging in mice were examined. The differing expression profiles of Zonula occludens 1 (ZO-1) and vascular endothelial growth factor-A (VEGFA) in the retina as well as the perfusion characterization of fluorescein isothiocyanate (FITC)-dextran and Evans blue were examined to evaluate the integrity of the inner BRB. RESULTS: There were significant alterations in these three efflux transporters’ expression profiles in the mRNA and protein levels of the retina during the development of diabetes mellitus and/or aging. The development of early DR was confirmed by the expression profiles of ZO-1 and VEGFA in the retina as well as the compromised integrity of the inner BRB. CONCLUSION: The expression profiles of some efflux transporters such as BCRP, LRP, and MDR1 in mice retina during diabetic and/or aging conditions are tested, and the attenuated expression of BCRP, LRP, and MDR1 along with the breakdown of the inner BRB is found, which may be linked to the pathogenesis of early DR.

Abstract:AIM: To investigate the effect of HtrA1 on the proliferation, migration and apoptosis of human retinal pigment epithelium (RPE) cells in the light injured model, as well as the expression of the apoptosis related molecules. METHODS: The human RPE cell line ARPE-19 was exposed to blue light to establish the light injured model. The cells were transfected with HtrA1 siRNA to knockdown HtrA1 expression. Subsequent expression of HtrA1 was determined by real-time polymerase chain reaction (RT-PCR) and Western blot, respectively. Changes in cell proliferation, migration and apoptosis were assessed by cell counting kit-8 (CCK-8), Transwell assay and flow cytometry respectively, as well as changes in the mRNA and protein levels of Bax, Caspase-3 and Bcl-2 expression. RESULTS: HtrA1 was highly expressed in ARPE-19 cells after blue light irradiation. Knockdown of HtrA1 expression inhibited the proliferation, migration and apoptosis of the blue-light-irradiated ARPE-19 cells (P<0.05). Bax and Caspase-3 expression were significantly reduced both at mRNA and protein levels (P<0.05) after siRNA treatment. Bcl-2 expression significantly increased in blue-light-irradiated ARPE-19 cells after siRNA interference (P<0.05). CONCLUSION: Silence of HtrA1 may inhibit the proliferation, migration and apoptosis of ARPE-19 cells in light injured model. Moreover, HtrA1 suppression in blue-light-irradiated ARPE-19 cells may ameliorate cell apoptosis through down-regulation of Bax and Caspase-3, and up-regulation of Bcl-2 expression.

Abstract:AIM: To investigate the content of serum microRNA-126 (miR-126) and its role in screening retinal endothelial injury and early diagnosis of proliferative diabetic retinopathy. METHODS: The study included 184 serum samples, 59 samples from healthy individuals, 44 samples from diabetes mellitus (DM) patients without diabetic retinopathy (NDR), 42 from non-proliferative diabetic retinopathy (NPDR) patients and 39 samples from proliferative diabetic retinopathy (PDR) patients. The expression of miR-126 was evaluated using a real-time quantitative polymerase chain reaction. RESULTS: The serum content of miR-126 declined as the damage degree in the retina. There was significant difference between the two retinopathy groups (P<0.001). No difference was observed in miR-126 content between healthy individuals and NDR patients (P>0.05). Receiver operating characteristic curve (ROC) analyses indicated that serum miR-126 had significant diagnostic value for PDR. It yielded an area under the curve (AUC) of ROC of 0.976 with 81.21% sensitivity and 90.34% specificity in discriminating PDR from healthy controls, and an AUC of ROC of 0.919 with 84.75% sensitivity and 94.41% specificity in discriminating NDR and NPDR from healthy controls. When the diagnostic threshold was greater than or equal to 8.43, there was an increase in the possibility of NPDR. When the content of miR-126 was less than or equal to 5.02, the possibility of the occurrence of PDR increased. CONCLUSION: Serum miR-126 can serve as a non-invasive biomarker for screening retinal endothelial injury and early diagnosis PDR.

Abstract:AIM: To identify the effects of interleukin (IL)-13 on retinal pigment epithelial (RPE) cells and the IL-13 level in aqueous humor of age-related macular degeneration (AMD) patients. METHODS: IL-13 levels in aqueous humor specimens from AMD patients were detected with enzyme-linked immunosorbent assay (ELISA). ARPE-19 cells were treated with 10 ng/mL IL-13 for 12, 24, and 48h. The cell proliferaton was evaluated by the MTS method. The mRNA and protein levels of α-SMA and ZO-1 were evaluated with quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot respectively. The expression of tumor necrosis factor-α (TNF-α), transforming growth factor-β (TGF-β) and vascular endothelial growth factor (VEGF) were assessed by ELISA. RESULTS: IL-13 levels in the aqueous humor of patients with AMD were significantly higher than those in the control (167.33±17.64 vs 27.12±5.65 pg/mL; P<0.01). In vitro, IL-13 of high concentrations (10, 15, and 20 ng/mL) inhibited ARPE-19 cell proliferation. α-SMA mRNA in ARPE-19 cell were increased (1.017±0.112 vs 1.476±0.168; P<0.001) and ZO-1 decreased (1.051±0.136 vs 0.702±0.069; P<0.001) after treated with 10 ng/mL IL-13 for 48h. The protein expression of α-SMA and ZO-1 also showed the same tendency (α-SMA: P=0.038; ZO-1: P=0.008). IL-13 significantly reduced the level of TNF-α (44.70±1.67 vs 31.79±3.53 pg/mL; P=0.005) at 48h, but the level of TGF-β2 was significantly increased from 34.44±2.92 to 57.61±6.31 pg/mL at 24h (P=0.004) and from 61.26±1.11 to 86.91±3.59 pg/mL at 48h (P<0.001). While expressions of VEGF didn’t change after IL-13 treatment. CONCLUSION: IL-13 in vitro inhibit ARPE-19 cell proliferation and expression in the aqueous may be associated with AMD.

Abstract:AIM: To determine whether gypenosides have protective effects in experimental autoimmune optic neuritis (EAON). METHODS: Mice were randomly divided into seven groups: control group, model group, three different density gypenosides monotherapy, methylprednisolone monotherapy, combination of gypenosides and methylprednisolone group. The control group was subcutaneously injected with oil emulsion adjuvant and all other groups were subcutaneously immunized with an emulsified mixture of myelin oligodendrocyte glycoprotein (MOG) 35-55 peptide to induce EAON. Mice in the gypenosides groups were administered injections daily with three concentrations (15 mg/kg, 30 mg/kg, 45 mg/kg) of gypenosides respectively. Mice in the methylprednisolone group and the combination treatment group were injected daily with methylprednisolone (20 mg/kg) or methylprednisolone (20 mg/kg) + gypenosides (30 mg/kg), respectively. After MOG immunization, visual evoked potential (VEP), optical coherence tomography (OCT), and histopathologic examination were performed at 14, 20, 30, and 40d post-inoculation (p.i.). All results were expressed as mean±SEM. The data were evaluated by one-way ANOVA followed by Tukey or Games-Howell test. RESULTS: Compared with the control group, p2 latency was prolonged in the model group (P=0.041). Combination treatment can alleviated the change in VEP at 20d p.i. (P=0.012). Average peripapillary retinal nerve fiber layer (RNFL) thickness was reduced in the model group (P= 0.000, 30d; P=0.000, 40d) and gypenosides treatment remarkably diminished the degree of RNFL degeneration at 30d and 40d p.i (P=0.000, 30d; P=0.000, 40d). The pathomorphological results showed a decrease in demye-lination (P=0.020) and inflammatory reactions in the combination group compared with the model group (20d p.i.). Gypenosides treatment also alleviated the degree of axonal loss (40d p.i.) (P=0.003). CONCLUSION: Treatment with gypenosides exerts protective effects on retinal nerve fibers and axons in EAON. When combined with gypenosides, methylprednisolone reduces demyelination in the acute stage of EAON.

Abstract:AIM: To study the expression of collagen I and transcription factor specificity protein 1 (Sp1), a transforming growth factor-β1 (TGF-β1) downstream target, and reveal the impact of the TGF-β1-Sp1 signaling pathway on collagen remodeling in myopic sclera. METHODS: Seventy-five 1-week-old guinea pigs were randomly divided into normal control, form deprivation myopia (FDM), and self-control groups. FDM was induced for different times using coverage with translucent latex balloons and FDM recovery was performed for 1wk after 4wk treatment; then, changes in refractive power and axial length were measured. Immunohistochemistry and reverse transcription-polymerase chain reaction were used to evaluate dynamic changes in collagen I and Sp1 expression in the sclera of guinea pigs with emmetropia and experimental myopia, and the relationship between collagen I and Sp1 levels was analyzed. RESULTS: In the FDM group, the refractive power was gradually changed (from 2.09±0.30 D at week 0 to -1.23±0.69 D, -4.17±0.59 D, -7.07±0.56 D, and -4.30±0.58 D at weeks 2, 4, 6, and 1wk after 4wk, respectively; P<0.05), indicating deepening of myopia. The axial length was increased (from 5.92±0.39 mm at week 0 to 6.62±0.36 mm, 7.30±0.34 mm, 7.99±0.32 mm, and 7.41±0.36 mm at weeks 2, 4, 6, and 1wk after 4wk; P<0.05). The mRNA and protein expression of Sp1 and collagen I in the sclera of the FDM group was lower than that of the control groups (P<0.05), and the reduction was eye-coverage time-dependent. Furthermore, correlation between Sp1 and collagen I down-regulation in the myopic sclera was observed. CONCLUSION: Our data indicate that transcription factor Sp1 may be involved in the regulation of type I collagen synthesis/degradation during myopic sclera remodeling, suggesting that TGF-β1 signaling plays a role in the development and progression of myopia.

Abstract:AIM: To investigate the expression of matrix metalloproteinases 1 and 3 (MMP-1 and MMP-3) and their tissue inhibitors of metalloproteinases 1 and 3 (TIMP-1 and TIMP-3) in the conjunctiva of eyes with conjunctivochalasis (CCh). METHODS: The conjunctival tissue was obtained from the CCh patients and controls, the MMPs/TIMPs expression concentration was determined by enzyme-linked immuno-sorbent assay (ELISA) and immunofluorescence staining. The expression levels of MMPs/TIMPs in the CCh fibro-blasts were determined by analyzing its concentration in the cellular supernatant that was abstracted from the in vitro cultured CCh fibroblasts. RESULTS: MMP-1 and MMP-3 levels determined by ELISA were both significantly higher in the CCh group than that in the control group (P=0.042, 0.022, respectively), so was the levels of TIMP-1 (P=0.010). No significant difference in the expression of TIMP-3 in conjunctiva was found between the two groups (P=0.298). The expression of MMP-1 and MMP-3 were both up-regulated significantly in the CCh group (P=0.040, 0.001, respectively) on immuno-fluorescence staining. MMP-1 and MMP-3 expression in the fibroblasts were both significantly higher in the CCh group than that in the control group (P=0.027, 0.001, respectively), while neither the TIMP-1 nor TIMP-3 expression was significantly different between the two groups (P=0.421, 0.237, respectively). CONCLUSION: The overexpression of MMP-1 and MMP-3 in conjunctival tissue and fibroblasts may play an important role in the pathogenesis and development of CCh.

Abstract:AIM: To develop a new method to produce recombinant reprogramming proteins, cMyc, Klf4, Oct4, and Sox2, in soluble format with low cost for the generation of induced pluripotent stem cells (iPSCs). METHODS: A short polypeptide sequence derived from the HIV trans-activator of transcription protein (TAT) and the nucleus localization signal (NLS) polypeptide were fused to the N terminus of the reprogramming proteins and they were constructed into pCold-SUMO vector which can extremely improve the solubility of recombinant proteins. Then these vector plasmids were transformed into E. coli BL21 (DE3) Chaperone competent cells for amplification. The solubility of these recombinant proteins was determined by SDS-PAGE and Coomassie brilliant blue staining. The recombinant proteins were purified by Ni-NTA resin and identified by Western blot. The transduction of these proteins into HEK 293T cells were evaluated by immunofluorescence staining. RESULTS: These four reprogramming proteins could be produced in soluble format in pCold-SUMO expression vector system with the assistance of chaperone proteins in bacteria. The proteins were purified successfully with a purity of over 70% with a relative high transduction rate into 293 cells. CONCLUSION: The results in the present study indicate the four important reprogramming proteins, cMyc, Klf4, Oct4, and Sox2, can be produced in soluble format in bacteria with low cost. Our new method thus might be expected to greatly contribute to the future study of iPSCs.

Abstract:AIM: To determine the agreement and repeatability of the pupil measurement obtained with VIP-200 (Neuroptics), PowerRef II (Plusoptix), WAM-5500 (Grand Seiko) and study the effects of instrument design on pupillometry. METHODS: Forty patients were measured twice in low, mid and high mesopic. Repeatability was analyzed with the within-subject standard deviation (Sw) and paired t-tests. Agreement was studied with Bland-Altman plots and repeated measures ANOVA. Instrument design analysis consisted on measuring pupil size with PowerRef II simulating monocular and binocular conditions as well as with proximity cues and without proximity cues. RESULTS: The mean difference (±standard deviation) between test-retest for low, mid and high mesopic conditions were, respectively: -0.09 (±0.16), -0.05 (±0.18) and -0.08 (±0.23) mm for Neuroptics, -0.05 (±0.17), -0.12 (±0.23) and -0.17 (±0.34) mm for WAM-5500, -0.04 (±0.27), -0.13 (±0.37) and -0.11 (±0.28) mm for PowerRef II. Regarding agreement with Neuroptics, the mean difference for low, mid and high mesopic conditions were, respectively: -0.48 (±0.35), -0.83 (±0.52) and -0.38 (±0.56) mm for WAM-5500, -0.28 (±0.56), -0.70 (±0.55) and -0.61 (±0.54) mm for PowerRef II. The mean difference of binocular minus monocular pupil measurements was: -0.83 (±0.87) mm; and with proximity cues minus without proximity cues was: -0.30 (±0.77) mm. CONCLUSION: All the instruments show similar repeat-ability. In all illumination conditions, agreement of Neuroptics with WAM-5500 and PowerRef II is not good enough, which can be partially induced due to their open field design.

Abstract:AIM: To evaluate the rotational stability and visual outcomes of a single-piece hydrophilic acrylic toric intraocular lenses (IOL) over a 1.5-year follow-up period. Data from the 6-month follow-up study have been previously reported. METHODS: Forty eyes of 26 cataract patients (mean age: 72.8±7.9y) with pre-existing corneal astigmatism of 1.0 to 2.6 D were enrolled in the study. Mean axial length was 23.17±0.88 mm. Main outcome measures after implantation of the Torica-aA IOL (HumanOptics) were IOL rotational stability, subjective refraction, astigmatism correction, uncorrected and corrected distance visual acuity (UDVA, CDVA). RESULTS: There was no significant change in the parameters evaluated between the 6-month and 1.5-year follow-ups. At last visit, mean absolute IOL rotation (objective method) was 1.81°±1.87° (range 0.00° to 7.20°) with 78.6% of eyes having IOL rotation <3°, 92.9% of eyes <5° and 100% of eyes <8°. No patient required secondary IOL repositioning during the course of the study. Mean residual refractive cylinder was -0.60±0.40 D. There was a significant reduction in the magnitude of the J0 vector postoperatively (P<0.0001) with a mean absolute change of 0.76±0.40 D. The mean J45 vector was close to zero preoperatively and postoperatively and didn’t change significantly (P=0.28). Mean monocular UDVA and CDVA was 0.09±0.12 logMAR and -0.01±0.12 logMAR, respectively. No treatment with Nd:YAG laser was required. CONCLUSION: The Torica-aA IOL shows good and stable visual performance and rotational stability over a 1.5-year follow-up period.

Abstract:AIM: To study the effects of intraocular lens (IOL) explantation and demographic characteristics. METHODS: Retrospective non-comparative case series. Clinical data recorded from patient charts included the following: demographic, preoperative and postoperative characteristics; complications; surgical methods, and changes in visual acuity. RESULTS: A total of 69 eyes in 67 Chinese patients who received IOL explants were studied. The patients’ mean age at the time of explantation was 46.1 years old [SD 22.5 (6-85)], and 37 patients were female (55.2%). Regarding employment, 47.8% were farmers, 23.9% were retired, 16.4% were students, 4.5% were unemployed, 3% were workers, and 4.5% were other (including staff members, teachers and officers). The main reasons for explantation were dislocation/decentration in 41 cases (59.4%) and retinal detachment in 10 cases (14.5%). The third most prevalent cause was incorrect lens power in 7 eyes (10.1%). The remaining reasons were endophthalmitis in 6 cases (8.7%), posterior capsular opacity in 3 eyes (4.3%), and impacting retinal surgery operation in 2 cases (2.9%). The main comorbidities were high myopia in 18 eyes (26.1%), trauma in 8 eyes (11.6%), retinal detachment in 6 eyes(8.7%), congenital cataracts in 8 eyes (11.6%), and Marfan’s syndrome in 2 eyes (2.9%). The mean time from implantation to explantation was 4.0y [SD 4.2 (0.005-15)]. Treatment after explantation included posterior chamber IOL implantation in 44 eyes (63.8%) and aphakia in 25 eyes (36.2%). After surgery, the best corrected visual ability (BCVA) was improved in 50 cases (72.5%), including 28 patients (40.6%) in whom visual ability was improved by more than two lines. CONCLUSION: Dislocation/decentration is the main cause for explantation, and high myopia is a main risk factor. Posterior chamber IOL implantation remains the most elected treatment after explantation.

Abstract:AIM: To assess the relation between nutrient patterns and cataract risk. METHODS: This is a hospital-based case-control study with 97 cataract patients and 198 matched controls. Dietary consumption was collected through a valid food frequency questionnaire (FFQ). Nutrient patterns were detected by applying factor analysis. Unconditional logistic regression models were used to estimate odds ratio (ORs) and 95%CIs. RESULTS: We extracted 5 main nutrient patterns. Factor 1 included niacin, thiamin, carbohydrates, protein, zinc, vitamin B6 and sodium (sodium pattern). Factor 2 was characterized by oleic acid, monounsaturated fats, polyunsaturated fats, linoleic acid, trans fatty acid, linolenic acid, vitamin E and saturated fats (fatty acid pattern). The third factor represented high intake of vitamin B12, vitamin D, cholesterol and calcium (mixed pattern). The 4th pattern was high in intake of beta and alpha carotene, vitamin A and vitamin C (antioxidant pattern). Finally, the 5th pattern loaded heavily on docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) (omega-3 pattern). In crude and multivariate analysis, the sodium pattern was associated with increased risk of cataract (OR=1.97, 95%CI: 1.09-3.96). The fatty acid pattern elevated the risk of cataract (OR=1.94, 95%CI: 1.1-3.86). Antioxidant pattern was associated with a significant 79% reduced risk (2nd category compared with the 1st). Omega-3 pattern was significantly negatively associated with risk of cataract (P=0.04). CONCLUSION: These findings imply that nutrient patterns reflecting a combined consumption of nutrients might be important in the etiology of cataract. Additional studies with more efficient designs are warranted to confirm our findings.

Abstract:AIM: To compare the efficacy of selective laser trabeculoplasty (SLT) in replacing medical therapy in pseudophakic and phakic eyes. METHODS: Subgroup of a prospective randomized clinical trial including patients with primary open angle glaucoma or ocular hypertension controlled with medication. Of 38 pseudophakic eyes were matched with 38 phakic eyes. SLT was offered as a way to decrease medication while maintaining the same low eye pressure. SLT was performed over 360°, at 3ns, spotsize 400 µm, 100 spots. Data [intraocular pressure (IOP), number of medications needed] were measured at 1h, 1wk, 1, 3, 6 and 12mo. An independent-samples t-test was performed to compare baseline characteristics of the phakic and the pseudophakic group and differences in evolution of mean IOP and number of used medications. Chi-squared analysis was performed to investigate proportions of fast, slow and non-responders. RESULTS: The mean IOP measurement was 13.00± 2.88 mm Hg in the phakic group (38 eyes) and 13.51± CONCLUSION: IOP lowering effect of SLT is comparable between phakic and pseudophakic eyes.

Abstract:AIM: To compare the diagnostic performance of isolated-check visual evoked potential (icVEP) and standard automated perimetry (SAP), for evaluating the application values of icVEP in the detection of early glaucoma. METHODS: Totally 144 subjects (288 eyes) were enrolled in this study. icVEP testing was performed with the Neucodia visual electrophysiological diagnostic system. A 15% positive-contrast (bright) condition pattern was used in this device to differentiate between glaucoma patients and healthy control subjects. Signal-to-noise ratios (SNR) were derived based on a multivariate statistic. The eyes were judged as abnormal if the test yielded an SNR≤1. SAP testing was performed with the Humphrey Field Analyzer II. The visual fields were deemed as abnormality if the glaucoma hemifield test results outside normal limits; or the pattern standard deviation with P<0.05; or the cluster of three or more non-edge points on the pattern deviation plot in a single hemifield with P<0.05, one of which must have a P<0.01. Disc photographs were graded as either glaucomatous optic neuropathy or normal by two experts who were masked to all other patient information. Moorfields regression analysis (MRA) used as a separate diagnostic classification was performed by Heidelberg retina tomograph (HRT). RESULTS: When the disc photograph grader was used as diagnostic standard, the sensitivity for SAP and icVEP was 32.3% and 38.5% respectively and specificity was 82.3% and 77.8% respectively. When the MRA Classifier was used as the diagnostic standard, the sensitivity for SAP and icVEP was 48.6% and 51.4% respectively and specificity was 84.1% and 78.0% respectively. When the combined structural assessment was used as the diagnostic standard, the sensitivity for SAP and icVEP was 59.2% and 53.1% respectively and specificity was 84.2% and 84.6% respectivlely. There was no statistical significance between the sensitivity or specificity of SAP and icVEP, regardless of which diagnostic standard was based on. CONCLUSION: The diagnostic performance of icVEP is not better than that of SAP in the detection of early glaucoma.

Abstract:AIM: To evaluate the potential role of hyperreflective foci (HF) as a prognostic indicator of visual outcome in patients with macular edema (ME) due to retinal vein occlusion (RVO). METHODS: We retrospectively reviewed 50 eyes of 50 patients with ME due to ischemic central retinal vein occlusion (CRVO), non-ischemic CRVO and branch retinal vein occlusion (BRVO) who were treated with anti-vascular endothelial growth factor (anti-VEGF) at Beijing Tongren Eye Center from January 2013 to July 2016. All patients underwent best-corrected visual acuity (BCVA), spectral domain optical coherence tomography (SD-OCT) at baseline and follow-up. Such factors were evaluated and compared among three groups as baseline and final BCVA, central retinal thickness (CRT), external limiting membrane (ELM) status and the numbers of HF in different position. Multiple linear regression analysis was employed to analyze the relationship between baseline HF and final BCVA. Changes of HF before and after treatment were evaluated too. RESULTS: Among three groups, HF could be located in each retinal layers, as well as in vitreous cavity. The mean HF in outer retinal layer (ORL) at baseline was 5.29±8.48 in ischemic CRVO with intact ELM, 1.93±2.76 in non-ischemic CRVO, and 1.75±2.05 in BRVO. With disrupted ELM, the mean HF in ORL increased. There was statistically difference of HF in ORL between intact and disrupted ELM. The numbers of HF in ORL were associated with poor visual outcome among three groups. However, HF in inner retinal layer (IRL) and vitreous cavity were not associated with poor visual outcome. Meanwhile, the baseline HF in ORL and vitreous cavity reduced significantly in non-ischemic CRVO and BRVO after anti-VEGF treatment. CONCLUSION: The numbers of HF in ORL are prognostic factors associated with the final BCVA in patients with ME due to RVO after anti-VEGF treatment.

Abstract:AIM: To assess the correlation between choroidal thickness (CT) and the early stages of diabetic retinopathy (DR) in type 2 diabetic patients. METHODS: We divided 83 diabetic patients (51-80 years of age; 50 females) into non diabetic retinopathy group (NDR) and mild/moderate nonproliferative diabetic retinopathy (NPDR) group, and compared them with 26 non-diabetic control subjects (51-78 years of age; 16 females). Subfoveal choroidal thickness (SFCT) and parafoveal choroidal thickness (PFCT) were measured using enhanced depth imaging spectral-domain optical coherence tomography (EDI-OCT). Ocular health status, disease duration, body mass index, and hemoglobin A1c (HbA1c) were recorded. RESULTS: The mean ages of the NDR, NPDR, and control groups were 68.0±6.9y, 67.8±6.4y, and 65.1±6.3y, respectively (P=0.17). Pearson correlation of the right and left eyes for the control subjects was 0.95 and for the NDR subjects was 0.93. SFCT for the right eyes of the controls was 252.77± 41.10 μm, which was significantly thicker than that of the right eyes in NDR group (221.51±46.56 μm) and the worse eyes of the NPDR group (207.18±61.87 μm; ANOVA, P<0.01). In the diabetic patients pooled together, age was the only variable significantly associated with SFCT (multiple linear regression analysis, P=0.01). CONCLUSION: CT decreased significantly in the NDR and mild/moderate NPDR eyes compared with the control eyes. Age is significantly associated with SFCT in the diabetic patients. Diabetic choroidopathy may be present before clinical retinopathy.

Abstract:AIM: To evaluate the clinical outcomes of V4c implantable collamer lens (Hole ICL) implantation with regard to the optical quality assessed according to different degrees of decentering. METHODS: This included 49 eyes that received conventional ICL and 94 eyes that received Hole ICL. The eyes that received Hole ICL were divided into three groups according to the degree of decentering: group 1, central hole within 1 hole diameter (HD) from the pupil center; group 2, central hole within 1 HD to 2 HD; and group 3, central hole within 2 HD to 3 HD. Visual acuity (VA), intraocular pressure (IOP), and spherical equivalent (SE) values were assessed at 1wk, 1 and 3mo after surgery. The ocular modulation transfer function, Strehl ratio, objective scattering index, and higher order aberrations (HOAs) were measured for 4-mm pupils at 3mo after surgery. RESULTS: There were no significant differences in VA, IOP, and SE among the conventional and Hole ICL groups. With regard to HOAs, values for coma and spherical aberrations showed no differences. The total HOA and trefoil values were significantly higher in group 2 than in group 1 (P=0.02, 0.03, respectively). There were no significant differences among groups with regard to other optical quality parameter at 3mo after surgery. CONCLUSION: Our results suggest that Hole ICL implantation provides satisfactory visual quality that is equivalent to that provided by conventional ICL, regardless of the presence of central hole and degree of decentering.

Abstract:AIM: To compare visual quality after femtosecond laser in situ keratomileusis (FS-LASIK), between the coaxially sighted corneal light reflex (CSCLR) group and conventional ablation line of sight (LOS) group. METHODS: In total, 243 eyes (122 patients) were treated with centration on the CSCLR (visual axis) and 238 eyes (119 patients) treated with centration on the pupil center (LOS). Postoperative outcomes [uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA)], safety index, efficacy index, refractive outcome, ablation center distance from the visual axis, corneal high-order aberrations, subjective discomfort glare and shadowing incidence rate, and contrast sensitivity at 1, 3, and 6mo were measured and compared. RESULTS: The mean age was 27.77±7.1y in the CSCLR group and 26.03±7.70y in the LOS group. Preoperatively, the manifest refraction spherical equivalent (MRSE) was -6.68±2.60 D in the CSCLR group and -6.65±2.68 D in the LOS group. The postoperative UCVA, BSCVA, MRSE (-0.03±0.263 D in the CSCLR group, -0.05±0.265 D in the LOS group), efficacy index (1.04, 1.03), and safety index (1.09, 1.08) were not significantly different between the groups (all P>0.05). In total, 3% lost one line and more of BSCVA in the CSCLR group, as 9% in the LOS group postoperatively (P<0.05). The ablation center deviation was 0.20±0.15 mm from the visual axis (Pentacam system default setting; range, 0-0.75 mm) in the CSCLR group, and 0.43±0.22 mm (range, 0-1.32 mm) in the LOS group (P<0.0001). Statistically significant greater augmentation of total corneal higher-order aberrations (0.15±0.10 µm and 0.20±0.12 µm respectively, P=0.03) and vertical and horizontal coma (P<0.0001) were noted in the LOS group. Subjective discomfort glare and shadowing incidence rates were 8.59% and 17.5% in the CSCLR and LOS groups, respectively (P<0.05). The 1-month postoperative contrast sensitivity visual acuity in the CSCLR group was significantly higher than that in the LOS group on contrast (100%, 25%, 10%) with a dark background, but there was no significant difference between the groups at 3 or 6m. CONCLUSION: Myopic LASIK centered on the CSCLR achieves significantly lower induction of loss of BSCVA, corneal high-order aberrations, and lower risk of subjective discomfort glare and shadowing, and lower decline in early contrast sensitivity by comparison with centration on the LOS, giving advantages in visual quality postoperatively.

Abstract:AIM: To assess the corneal sensitivity and the incidences of dry eye after small incision lenticule extraction (SMILE) and femtosecond laser-assisted in situ keratomileusis (FS-LASIK). METHODS: The Meta-analysis was performed using RevMan 5.3. We searched on PubMed from inception to March 2016. Summary weighted mean difference (WMD) and 95% confidence intervals (CIs) were used to analyze the datum. Random-effects or fixed-effects models were chosen up to between-study heterogeneity. The main outcomes were composed of the Ocular Surface Disease Index (OSDI) scores, tear film break-up time (TBUT), Schirmer Test and corneal sensitivity. RESULTS: Eight eligible studies including 772 eyes (386 in SMILE group and 386 in FS-LASIK group) were identified. The parameters have no significiant difference heterogeneity between SMILE and FS-LASIK group preoperatively. There were significant differences between the two groups in OSDI scores at one and three months postoperatively, in TBUT at one and three months postoperatively, in corneal sensitivity at one week, about one month and three months postoperatively. However, there was no significant difference observed in Schirmer Test at the follow-up periods. CONCLUSION: Compare to FS-LASIK, dry eye and the corneal sensitivity recover better in the SMILE group, in first three months after the surgery.

Abstract:AIM: To investigate the association of Manganese superoxide dismutase (MnSOD) Val16Ala polymorphism with diabetic retinopathy (DR). METHODS: PubMed, Embase, China National Knowledge Infrastructure, and Wanfang databases were searched. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the association. Subgroup, sensitivity, and cumulative analyses were performed. Publication bias was also analyzed. RESULTS: Eight studies were included in the pooled analysis. The MnSOD Val16Ala polymorphism was associated with the risk of DR under the dominant model (OR=0.66, 95%CI=0.48-0.91, P<0.0001), this result was demonstrated to be relatively stable in cumulative analysis. No significant publication bias was found. This polymorphism was also associated with the risk of DR in Caucasians under the dominant model (OR=0.64, 95%CI=0.42-0.97, P=0.04,) and in Asians under the recessive model (OR=0.31, 95%CI=0.11-0.88, P=0.03). CONCLUSION: These findings suggest that the MnSOD Val16Ala polymorphism is a risk factor for DR, and that more attention should be paid to carriers of these susceptibility genes.

Abstract:Gene therapy is a potentially effective treatment for retinal degenerative diseases. Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system has been developed as a new genome-editing tool in ophthalmic studies. Recent advances in researches showed that CRISPR/Cas9 has been applied in generating animal models as well as gene therapy in vivo of retinitis pigmentosa (RP) and leber congenital amaurosis (LCA). It has also been shown as a potential attempt for clinic by combining with other technologies such as adeno-associated virus (AAV) and induced pluripotent stem cells (iPSCs). In this review, we highlight the main points of further prospect of using CRISPR/Cas9 in targeting retinal degeneration. We also emphasize the potential applications of this technique in treating retinal degenerative diseases.

Abstract:This study evaluated the clinical outcomes in keratoconus corneas following accelerated transepithelial corneal collagen cross-linking (CXL) (Avedro KXL® system, Waltham, MA, USA) over one year of follow-up. The mean depth of the demarcation line measured by optical coherence tomography (OCT) was 205.19 µm. One month after surgery, a non-statistically significant change was noted in sphere (P=0.18) and in spherical equivalent (P=0.17), whereas a significant improvement was observed in corrected distance visual acuity (P=0.04). A significant change was observed in topographic astigmatism (P=0.03) and posterior corneal a sphericity (P=0.04). Accelerated transepithelial CXL may be a useful technique for the management of progressive keratoconus.

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