Abstract:AIM: To investigate how macrophage inducible C-type lectin (Mincle) influences inflammation in mice fungal keratitis induced by Aspergillus fumigatus (A. fumigatus). METHODS: C57BL/6 mice were infected with A. fumigatus after pretreated with Mincle agonist TDB or Mincle neutralizing antibody (MincleAb), taking DMSO or IgG as control group respectively. The cornea lesions were monitored with slit-lamp microscope and evaluated by clinical score. Mincle expression was assessed using reverse transcription-ploymerase chain reaction (RT-PCR) and immunostaining. The expression of cytokines (IL-1β, TNF-α and IL-6) chemokines (CXCL-1 and MIP-2) was determined by RT-PCR and ELISA. Neutrophil infiltration was observed by immunostaining. The levels of nitric oxide (NO) generated by corneas were tested by Griess reaction. RESULTS: Mincle mRNA and protein levels were higher in infected corneas than normal corneas of C57BL/6 mice, saving clinical scores revealed differences. When pretreated with Mincle agonist TDB, the mRNA and protein levels of IL-1β, TNF-α and IL-6 in infected corneas were significantly increased compared with the control group (P<0.01). Results of the counterpart in corneas pretreated with Mincle neutralizing antibody was decreased consistently (P<0.01). Expression of CXCL1 and MIP-2 mRNA levels were up-regulated in TDB group and down-regulated in MincleAb group (P<0.01), coincide with neutrophil aggregation degree in corneas showed by immunostaining. As for the concentration of NO, it was promoted in TDB group compared with DMSO control group, and decreased in MincleAb group compared with IgG control group. CONCLUSION: Mincle plays a dual role in mice fungal keratitis. It participates in the innate immune system by enhancing inflammation. What's more, Mincle can mediate cytotoxic effects by regulating the formation of NO.

Abstract:AIM: To investigate whether high-mobility group box 1 (HMGB1) Boxb exacerbates BALB/c mice corneal immune responses and inflammatory through the Toll-like receptor 4 (TLR4)/myeloid differentiation primary response 88 (MyD88)-dependent signaling pathway in Aspergillus fumigatus (A. fumigatus) keratitis. METHODS: The mice corneas were pretreated with phosphate buffer saline (PBS), Boxb before A. fumigatus infection. The abdominal cavity extracted macrophages were pretreated with PBS, Boxb, TLR4 inhibitor (CLI-095), Dimethyl sulfoxide (DMSO) separately before A. fumigatus hyphae stimulation. HMGB1 was detected in normal and infected mice corneas and macrophages by real-time reverse transcriptase polymerase chain reaction (RT-PCR), the TLR4, MyD88, interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) were detected by Western blot and PCR. RESULTS: In BALB/c mice corneas, the expressions of TLR4, HMGB1, IL-1β, TNF-α were increased after A. fumigatus infection. While pretreatment with Boxb significantly increased the expressions of TLR4, HMGB1, MyD88, IL-1β, TNF-α compared with PBS control after infection. In BALB/c mice abdominal cavity extracted macrophages, pretreatment with Boxb increased the expressions of TLR4, HMGB1, MyD88, IL-1β, TNF-α, while pretreatment with CLI-095 and Boxb significantly decreased the expressions of TLR4, HMGB1, MyD88, IL-1β, TNF-α. CONCLUSION: In A. fumigatus keratitis, Boxb play a pro-inflammatory role in corneal anti-fungi immune response through the HMGB1-TLR4-MyD88 signal pathway.

Abstract:AIM: To study the effect of senescence marker protein 30 (SMP30) on the proliferation and apoptosis of human lens epithelial cell (HLEC) SRA01/04. METHODS: SMP30 overexpression (OE) and knock down (KD) type cell lines were cultivated by using two groups regucalcin (RGN; SMP30) lentiviral vectors (LV-RGN, LV-RGN-RNAi) and the respective negative control virus infect SRA01/04 cells. Western blot and real-time quantitative polymerase chain reaction (q-PCR) analysis were used to determine RGN overexpression and knock down efficiency. We use cell counting kit-8 (CCK8) assay to measure cell viability and 5-bromodeoxyuridine (BrdU) assay to test cell proliferation. Cell cycle was measured by PI FACS assay and cell apoptosis was tested by Annexin V-APC assay through flow cytometry. We use Western blot to measure the content of caspase-3 in SRA01/04. RESULTS: We used PCR and Western blot techniques to determine the successful transfection of SMP30 OE and KD SRA01/04 cell lines. By CCK8, Brdu and PI FACS cell cycle assay, it was found that the SMP30 OE group promoted cell proliferation (P<0.05) compared with the control group, and the KD group inhibited cell proliferation (P<0.05). The results of Annexin V-APC signal staining detection indicated that compared with respective control group, the cell apoptosis rate was higher in KD group (P<0.05) but lower in OE group (P<0.01). The expression of caspase-3 was down-regulated in OE group through Western blot assay and up-regulated in KD group compared with respective control group. CONCLUSION: Proliferation of SRA01/04 was promoted by SMP30 OE and apoptosis was suppressed. Increasing the expression of SMP30 may protect HLEC SRA01/04 against apoptosis in cataract.

Abstract:AIM: To observe the effect of exosomes derived from human umbilical cord blood mesenchymal stem cells (hUCMSCs) on the expression of vascular endothelial growth factor-A (VEGF-A) in blue light injured human retinal pigment epithelial (RPE) cells and laser-induced choroidal neovascularization (CNV) in rats. METHODS: Exosomes were isolated from hUCMSCs and characterized by transmission electron microscope and Western blot. MSCs-derived exosomes were cultured with RPE cells exposed to blue light. The mRNA and protein expression of VEGF-A were determined by real time-polymerase chain reaction (PCR) and Western blot, respectively. Immunofluorescence assay was used for the detection of the expression level of VEGF-A. We injected different doses of MSCs-derived exosomes intravitreally to observe and compare their effects in a mouse model of laser-induced retinal injury. The histological structure of CNV in rats was inspected by hematoxylin-eosin (HE) staining and fundus fluorescein angiography. The expression of VEGF-A was detected by immunohistochemistry. RESULTS: Exosomes exhibited the typical characteristic morphology (cup-shaped) and size (diameter between 50 and 150 nm). The exosomes marker, CD63, and hUCMSCs marker, CD90, showed a robust presence. In vitro, MSCs-derived exosomes downregulated the mRNA(Exo-L: t=6.485, 7.959, 9.286; Exo-M: t=7.517, 10.170, 13.413; Exo-H: t=10.317, 12.234, 14.592, P<0.05) and protein (Exo-L: t=2.945, 4.477, 6.657; Exo-M: t=4.713, 6.421, 8.836; Exo-H: t=6.539, 12.194, 12.783; P<0.05) expression of VEGF-A in RPE cells after blue light stimulation. In vivo, we found that the MSCs-derived exosomes reduced damage, distinctly downregulated VEGF-A (Exo-H: t=0.957, 1.382; P<0.05), and gradually improved the histological structures of CNV for a better visual function (Exo-L: 0.346, Exo-M: 3.382, Exo-H: 8.571; P<0.05). CONCLUSION: MSCs-derived exosomes ameliorate blue light stimulation in RPE cells and laser-induced retinal injury via downregulation of VEGF-A.

Abstract:AIM: To explore the state of autophagy and related mechanisms in the murine retinal microvascular endothelial cells (RMECs) under hypoxia stimulation. METHODS: The murine RMECs were primarily cultured and randomly divided into three groups: hypoxia group (cultured in 1% O2 environment), hypoxia+autophagy inhibition group [pretreated with 5 mmol/L 3-methyladenine (3-MA) for 4h followed by incubation in 1% O2] and control group (cultured under normoxic condition). The state of autophagy in RMECs was examined by assaying the turnover of light chain 3B (LC3BB) and expression of Beclin-1, Atg3 and Atg5 proteins with Western blotting, by detecting formation of autophagosomes with transmission electron microscopy (TEM) and by counting the number of GFP+ puncta in RMECs. The protein levels of AMPK, P-AMPK, Akt, P-Akt, m-TOR and P-mTOR were also assayed by Western blotting. RESULTS: Primary murine RMECs were successfully cultured. Under hypoxic conditions, the ratio of LC3BB-II/I and the expression of Beclin-1, Atg3 and Atg5 proteins were increased when compared with the control group. In addition, the numbers of autophagosome and the GFP+ puncta were also increased under hypoxia. However, pre-treatment with 3-MA obviously attenuated these changes in autophagy in RMECs under hypoxia. Protein expression of P-Akt and P-AMPK was increased but P-mTOR level was decreased in cells exposed to hypoxia. CONCLUSION: In murine RMECs autophagy is activated under hypoxia possibly through activation of the AMPK/mTOR signaling pathway.

Abstract:AIM: To compare the effects of intravitreal anti-vascular endothelial growth factor (VEGF) and dexamethasone in an experimental rabbit model of posterior penetrating ocular injury. METHODS: Thirty white New Zealand rabbits were included in the study. A posterior penetrating ocular injury was performed at the superotemporal quadrant. They were randomly divided into three groups. The rabbits in group 1 received intravitreal dexamethasone, in group 2 they received intravitreal bevacizumab and those in group 3 received intravitreal physiological saline solution in both eyes. All eyes were examined ophthalmologically on the 1st, 3rd, 7th, 14th and 28th days following the injury and the clinical findings were scored. On the day 28, the eyes were enucleated, evaluated and scored macroscopically, histopathologically and scanning electron microscopically. RESULTS: The median clinical score on the 14th and 28th days and the median macroscopic score of the dexamethasone group was significantly better than that of control (P=0.004, 0.018). Dexamethasone group was also better than that of bevacizumab group but the differences did not reach statistical significance. Retinal detachment rate was 8.3%, 16.6% and 12.5% in the dexamethasone group, bevacizumab group and control group, respectively (P=0.476). More extensive fibrocelluler proliferations were observed in controls compared with dexamethasone and bevacizumab groups. But these differences did not reach the statistical significance (P=0.538). In scanning electron microscopy all groups showed fibreous stalk and dense collagen fibrils in vitreous. CONCLUSION: This study shows that intravitreal injection of both dexamethasone and bevacizumab may reduce the intraocular fibrous proliferation after an experimental posterior penetrating ocular injury in rabbits.

Abstract:AIM: To compare three kinds of fluorescent probes for in vitro labeling and in vivo tracking of endothelial progenitor cells (EPCs) in a mouse model of laser-induced retinal injury. METHODS: EPCs were isolated from human umbilical cord blood mononuclear cells and labeled with three different fluorescent probes: 5-(and-6)-carboxyfluorescein diacetate succinimidyl ester (CFSE), 1,1′-dilinoleyl-3,3,3′,3′-tetramethylindo-carbocyanine perchlorate linked acetylated low-density lipoprotein (DiI-AcLDL), and green fluorescent protein (GFP). The fluorescent intensity of EPCs was examined by confocal microscopy. Survival rate of labeled EPCs was calculated with trypan blue staining, and their adhesive capability was assessed. A mouse model of retinal injury was induced by laser, and EPCs were injected into the vitreous cavity. Frozen section and fluorescein angiography on flat-mounted retinal samples was employed to track the labeled EPCs in vivo. RESULTS: EPCs labeled with CFSE and DiI-AcLDL exhibited an intense green and red fluorescence at the beginning; the fluorescence intensity decreased gradually to 20.23% and 49.99% respectively, after 28d. On the contrary, the florescent intensity of GFP-labeled EPCs increased in a time-dependent manner. All labeled EPCs showed normal morphology and no significant change in survival and adhesive capability. In the mouse model, transplantation of EPCs showed a protective effect against retinal injury. EPCs labeled with CFSE and DiI-AcLDL were successfully tracked in mice during the development of retinal injury and repair; however, GFP-labeled EPCs were not detected in the laser-injured mouse retina. CONCLUSION: The three fluorescent markers used in this study have their own set of advantages and disadvantages. CFSE and DiI-AcLDL are suitable for short-term EPC-labeling, while GFP should be used for long-term labeling. The choice of fluorescent markers should be guided by the purpose of the study.

Abstract:AIM: To investigate the association between ocular demodex folliculorum infestation and ocular surface manifestations in meibomian gland dysfunction (MGD). METHODS: Eight-six patients with MGD were enrolled. All enrolled subjects were tested in the following sequence: ocular surface disease index (OSDI), slit-lamp biomicroscope examination, corneal surface regularity index (SRI) and surface asymmetry index (SAI), tear fluid collection, fluorescein tear film break-up time (F-BUT), corneal fluorescein staining (CFS), Schirmer I test (SIT) and demodex folliculorum counting. Tear matrix metalloproteinase (MMP)-9 activity was assessed using MMP-9 activity assay kit. RESULTS: Among 86 MGD patients, 40 were positive for demodex. The ocular demodex-positive group showed significantly increased scores of OSDI (25.96±13.74 vs 18.07±11.55, P=0.01), lid margin abnormality (2.38±0.87 vs 1.98±0.91, P=0.04) and CFS (1.28±2.00 vs 0.94±1.36, P=0.01) compared to the ocular demodex-free group. The tear MMP-9 activity was higher in the ocular demodex-positive group (102.9±32.4 ng/mL) than the ocular demodex-free group (46.2±19.2 ng/mL, P=0.03). There was no significant difference in meibum quality and expressibility, SRI, SAI, F-BUT and SIT between the two groups (P>0.05 for each). No significant correlation was noted between the number of demodex and ocular surface parameters in demodex-positive MGD group (P>0.05 for each). CONCLUSION: Ocular demodex folliculorum infestation may be associated with ocular discomfort and ocular surface damage in MGD.

Abstract:AIM: To investigate the efficacy of combined topical 0.05% cyclosporine A (CsA; Restasis®, Allergan pharmaceuticals, USA) and 0.1% sodium hyaluronate treatment in dry eyes with meibomian gland dysfunction (MGD). METHODS: In a retrospective analysis, 53 patients (106 eyes) with MGD were enrolled and performed lid warm massage for 10min daily and be instilled preservative free sodium hyaluronate 0.1% eye drops 4 times daily. Patients were divided into subjects treated with topical 0.05% CsA and preservative free sodium hyaluronate vehicle (experimental group, n=74 eyes) and subjects treated with the preservative free sodium hyaluronate vehicle (control group, n=32 eyes). They were evaluated at baseline and 1, 2, and 3mo for subjective symptoms and objective signs including tear film break-up time (tBUT), Schirmer test, corneal staining (CS) score, lid margin telangiectasia (LMT), meibomian gland secretion (MGS), and conjunctival injection (CI). RESULTS: In the short-term treatment, the experimental group showed a statistically significant improvement in the ocular surface disease index (OSDI; P<0.001), tBUT (P=0.004), Schirmer test score (P=0.008) and LMT (P=0.021) by repeated measure ANOVA. Additionally, mean changes from baseline in OSDI (P<0.001), tBUT (P=0.001), Schirmer test score (P=0.029), CS score (P=0.047), LMT (P=0.002), CI (P=0.030) were improved better in the experimental group than in the control group at 3mo. However, there was no significant difference between the two groups in MGS (P=0.67). CONCLUSION: In dry eyes with MGD, 0.05% CsA improves the tear film stability as well as subjective ocular discomfort, and is effective in controlling lid margin inflammation.

Abstract:AIM: To evaluate the effectiveness of autologous conjunctival flap surgery for repairing the late-onset filtering bleb leakage after trabeculectomy. METHODS: This study retrospectively reviewed 106 eyes from 106 patients with late-onset filtering bleb leakage after trabeculectomy who received autologous conjunctival flap surgery at the Zhongshan Ophthalmic Centre from 2005 to 2015. The basic information was recorded, and the interval time between trabeculectomy and autologous conjunctival flap surgery as well as related risk factors, intraocular pressure (IOP), anterior chamber depth (ACD) and best corrected visual acuity (BCVA) were analysed. Moreover, 41 patients who completed the 1-year follow up were analysed to determine the IOP and BCVA changes and long-term success rates. RESULTS: The 50 male and 56 female subjects (average age 39.13±17.96y) included 47 (44.34%) and 33 (31.13%) cases of primary open angle and primary angle-closure glaucoma. The mean interval between trabeculectomy and repair surgery was 60.60±56.92 (3-264)mo. The mean mitomycin (MMC) concentration during trabeculectomy was 0.27±0.04 (0.12-0.4) mg/mL in the fornix-based conjunctival flap group (68 patients) and 0.28±0.04 (0.20-0.33) mg/mL in the limbal-based conjunctival flap group (11 patients). After bleb leakage, the patients' vision remained stable while the IOP decreased from 10.25±4.76 (3-20.86) to 9.44±4.33 (2-21) mm Hg (P<0.01). In the 41 analysed patients, the IOP was controlled at 15.68±5.11 (7-40) mm Hg in the 1st year after autologous conjunctival flap surgery and recurrence was not observed, for a long-term success rate of 100%. CONCLUSION: Autologous conjunctival flap repairing surgery is an effective technique for sealing filtering bleb leakages and controlling IOP postoperatively.

Abstract:AIM: To evaluate the complications and outcomes of descemet stripping automated endothelial keratoplasty (DSAEK) combined with artisan aphakia intraocular lens (IOL) implantation in severely damaged eyes without capsular support. METHODS: DSAEK combined with artisan iris claw IOL implantation was performed on 29 eyes. All eyes were of abnormal structure due to complications from prior intraocular surgeries and ocular trauma. Ocular complications observed included graft dislocations, high intraocular pressure (IOP), IOL dislocations, macular edema and hyphema. Best corrected visual acuity (BCVA), IOP and mean central endothelial cell density (ECD) were recorded. RESULTS: Thirteen eyes had a history of ocular trauma, 10 eyes had an anterior chamber IOL, 16 eyes had prior vitrectomy. The iris was abnormal in 22 cases. Graft dislocation occurred in 5 (17.2%) of 29 eyes. IOL dislocation occurred in 2 eyes (6.9%). High IOP was found in 9 eyes and was controlled with treatment. The preoperative mean BCVA was 20/286. The 6mo postoperative mean BCVA was 20/42. The average center ECD was 1965.3 cells/mm2 at 6mo, and the rate of the donor cell loss was 34.7%. CONCLUSION: DSAEK combined with artisan aphakia IOL implantation is an alternative option for resolving endothelial and lens disorders in aphakic eyes without capsular support. However, it should be performed cautiously for eyes with severe iris defects.

Abstract:AIM: To evaluate the efficacy and safety of the excimer laser correction of the residual refractive errors after cataract extraction with intraocular lens (IOL) implantation in uncommon cases. METHODS: Totally 24 patients with high residual refractive error after cataract surgery with IOL implantation were examined. Twenty-two patients had a history of phacoemulsification and IOL implantation, and two had extra-capsular cataract extraction with IOL implantation. Detailed examination of preoperative medical records was done to explain the origin of the post-cataract refractive errors. All patients underwent photorefractire keratectomy (PRK) enhancement. The mean outcome measures were refraction, uncorretted visual acuity (UCVA), best corrected visual acuity (BCVA) and corneal transparency and follow up ranged from 1 to 8y. RESULTS: The principal causes of residual ametropia was inexact IOL calculation in abnormal eyes with high myopia and congenital lens abnormalities, followed by corneal astigmatism both suture induced and preexisting. After cataract surgery and before the laser enhancement the mean spherical equivalent (SE) was -0.56±3 D ranging from -4.62 to +2.25 D in high myopic patients, instead it was -1±1.73 D ranging from -3.25 to +3.75 D in the astigmatic eyes, with a mean cylinder of -3.75±0 ranging from -3 to +5.50 D. After laser refractive surgery the mean SE was 0.1±0.73, ranging from -0.50 to +1.50 in the myopic group, and it was -0.50±0.57 ranging from -1.25 to +0.50 in astigmatic patients, with a mean cylinder of -0.25±0.75. In myopic patients the mean UCVA and BCVA were 0.038±0.072 logMAR and 0.018±0.04 respectively, both ranging from 0.10 to 0.0. In astigmatic patients, the mean UCVA and BCVA were 0.213±0.132 and 0.00±0.0 respectively, UCVA ranging from 0.50 to 0.22 and BCVA was 0.00. All patients presented normal corneal transparency. No ocular hypertension was detected and no corneal haze was observed. All registered values remained stable also at the end line evaluation. CONCLUSION: The excimer laser treatment of residual refractive errors after cataract surgery with IOL implantation in abnormal eyes resulted in satisfactory and stable visual outcome with good safety and efficacy.

Abstract:AIM: To evaluate the efficacy of prophylactic administration of topical non-steroidal anti-inflammatory drugs (NSAIDs) on macular edema following cataract surgery in diabetic patients, and to compare between types of NSAIDs (ketorolac tromethamine 0.4% and nepafenac 0.1%). METHODS: Group 1 (control) received artificial tears substitute as a placebo group, group 2 (nepafenac) received topical nepafenac 0.1%, and group 3 (ketorolac) received topical ketorolac tromethamine 0.4%. Patients were examined postoperatively after completing one week, one month, two months and three months' intervals for evaluating cystoid macular edema (CME) development. The main study outcomes were achieving the best corrected visual acuity (BCVA) and change in the central macular thickness (CMT) measured with optical coherence topography (OCT). RESULTS: Eighty eyes of 76 patients were included in this study. BCVA showed a statistically significant difference at the third month postoperative follow up between the control group and the NSAIDs groups (P=0.04). There was an increase in the CMT in all cases starting from postoperative first week until third month. CMT showed a statistically significant difference between control group and NSAIDs groups from postoperative first month until third month (P=0.008, 0.027, 0.004). There was no statistically significant difference between nepafenac and ketorolac groups in BCVA and OCT CMT. CONCLUSION: Prophylactic preoperative and postoperative NSAIDs may have a role in reducing the frequency and severity of CME in diabetic eyes following cataract surgery.

Abstract:AIM: To analyze and compare five different variables over one year follow-up (1wk, 1, 3, 6 and 12mo): anterior capsule (AC), and posterior capsule (PC) area densitometry values, AC and PC linear densitometry values, and AC opening area reduction ratio after femtosecond laser-assisted cataract surgery. METHODS: This was a prospective comparative study. Seventy-one patients underwent femtosecond laser-assisted cataract surgery on single eye between June 2014 and December 2015. A 5.0 mm diameter laser assisted anterior capsulotomy was performed on all eyes. In every post-surgery evaluation, AC opacificaction (ACO) and PC opacification (PCO) density levels were provided by Oculus Pentacam®HR using area and linear densitometry methods. Digital images were captured with a slit-lamp Topcon photographic camera and IMAGEnet® 5 software. The AC opening area on the digital images was measured using the Sketchandcalc area calculator and converted to reduction ratio levels. RESULTS: Using Pearson correlation coefficient (PCC), we found no correlation (r=-0.091, P=0.46) in the twelfth month assessment between the evolution of ACO area densitometry values and PCO area densitometry values considered as independent variables. We found no correlation, using PCC (r=-0.096, P=0.43) between the evolution of ACO linear densitometry values and PCO linear densitometry values, in the twelfth month visit, working both as independent variables. AC linear densitometry levels and AC area densitometry levels continued to grow strongly from sixth to twelfth months. Analysis of the values of AC opening area reduction ratio (1wk, 1, 3, 6, 12mo) revealed statistically significant differences between the values of successive examinations but the magnitude of the change decreased. In the final period of monitoring between six and twelve months the magnitude of change was low. CONCLUSION: Our results show strong increases of Scheimpflug ACO densitometry values from the sixth to the twelfth month while capsulorhexis area reduction ratio levels displayed a considerable decrease. We found no correlation between ACO area and linear densitometry values and PCO area and linear densitometry values, in the twelfth month examination, working as independent variables.

Abstract:AIM: To report long-term outcomes of secondary glaucoma due to uveitis treated with Ahmed glaucoma valve (AGV) implantation in a series of Chinese patients. METHODS: The retrospective study included 67 eyes from 56 patients with uveitic glaucoma who underwent AGV implantation. Success of the treatment was defined as patients achieving intraocular pressure (IOP) levels between 6 and 21 mm Hg with or without additional anti-glaucoma medications and/or a minimum of 20% reduction from baseline IOP. The main outcome measurements included IOP, the number of glaucoma medications at 1, 3, 6, 12, 24, 36, 48 and 60mo after surgery, surgical complications, final best-corrected vision acuity (BCVA), visual field (VF) and retinal nerve fiber layer (RNFL). RESULTS: The mean follow-up was 53.3±8.5 (range 48 to 60)mo. The cumulative probability of success rate was 98.5%, 95.5%, 89.6%, 83.6%, 76.1%, 70.1%, 65.7% and 61.2% at 1, 3, 6, 12, 24, 36, 48 and 60mo, respectively. IOP was reduced from a baseline of 30.8±6.8 to 9.9±4.1, 10.1±4.2, 10.9±3.7, 12.9±4.6, 13.8±3.9, 13.2±4.6, 12.3±3.5 and 13.1±3.7 mm Hg at 1, 3, 6, 12, 24, 36, 48 and 60mo, respectively (P<0.01). The number of postoperative glaucoma medications was significantly decreased compared with baseline at all time points during the study period (P<0.05). There was no significant difference between preoperative and postoperative BCVA. Remarkable surgical complications were not found after surgery. The VF and RNFL of the patients were stable after the surgery. CONCLUSION: AGV implantation is safe and effect in terms of reducing IOP, decreasing the number of glaucoma medications, and preserving vision for patients with uveitic glaucoma.

Abstract:AIM: To assess the efficacy and safety of patterned laser trabeculoplasty (PLT) as an adjunctive treatment in open angle glaucoma (OAG) or ocular hypertension (OHT) patients who were under antiglaucoma medical treatment. METHODS: This study was a retrospective review of primary or secondary OAG patients and OHT patients with medically uncontrolled (≥18 mm Hg) intraocular pressure (IOP) who underwent 360o PLT from June 2016 to August 2016. Follow-up visits at week 1, and 1, 3 and 6mo were performed. IOP, best corrected visual acuity (BCVA), complications and eye drop glaucoma medication were recorded at each follow-up visit. Success was defined as IOP reduction ≥20% from baseline. RESULTS: Forty-one eyes of 25 patients were included in this study. Pre-treatment mean IOP was 20.2±1.6 mm Hg. After PLT, IOP was 19.3±5.2, 16.1±2.7, 17.1±3.7 and 16.3±3.5 mm Hg, at 1wk, 1, 3 and 6mo, respectively. IOP reduction from baseline was statistically significant from the first month, remaining stable at 6mo (P<0.001). PLT success at 6mo of follow-up was 48.78%. The number of glaucoma medication per eye (P=0.10) and the mean BCVA both remained constant (P=0.37). Complications included transient IOP spikes in 4 eyes (9.8%) and peripheral anterior synechiae in 7 eyes (17.1%). CONCLUSION: PLT is an effective and safe method for the management of patients with OHT or OAG as an adjunctive therapy. Additional larger studies should be designed to verify the long-term stability of IOP reduction with this laser technology.

Abstract:AIM: To evaluate the effect of intravitreal ranibizumab injection for retinopathy of prematurity (ROP) in Zone II Stage 3+. METHODS: Data was collected for ROP patients with Zone II Stage 3+ who received intravitreal ranibizumab injections between October 2014 and Janu-ary 2017 at the Department of Ophthalmology in our hospital. No prior laser or other intravitreal treatment was done. Prior to the intervention and at each follow-up visit, fundus examination was performed. Gestational age at birth, sex, birth weight, ROP zone, ROP stage, post menstrual age (PMA) at treatment, and follow-up pe-riod were recorded. The final clinical status of the retina was evaluated for each patient. The primary outcome mea-sures included ROP recurrences requiring re-treatment, complete or incomplete peripheral vascularization. RESULTS: Eighty-six eyes of 46 premature infants with Zone II Stage 3+ ROP were enrolled in the study. The mean gestational age at birth was 28.18±1.67 (range: 25 to 33)wk and the mean birth weight was 1070.57±226.85 (range: 720.00 to 1650.00) g. The mean PMA at treatment was 38.32±2.99 (range: 32.29 to 46.00)wk. Seventy-one eyes (82.56%) were treated success-fully with intravitreal ranibizumab as monotherapy. Fifteen eyes (17.44%) developed recurrent disease. The mean interval between the treatment and retreatment was 5.96±3.22 (range: 1.86 to 11.71)wk. All eyes vascularized into zone III at the end of the study and among them 62 eyes (72.09%) achieved complete vascu-larization. CONCLUSION: Intravitreal ranibizumab injection is an effective treatment in Zone II Stage 3+ ROP patients. More patients with longer follow-up duration are necessary to confirm the safety and efficacy of this treatment.

Abstract:AIM: To investigate the long-term visual and anatomical outcomes of patients who underwent intravitreal ranibizumab monotherapy to treat neovascular age-related macular degeneration (AMD) and followed-up for at least 2y. METHODS: A total of 74 eyes of 74 patients who underwent ranibizumab monotherapy for neovascular AMD were included in this retrospective study. RESULTS: The average patient age was 72.1±6.5 (range, 57-85)y, the average follow-up time 46.2±13.1 (range, 24-75)mo, and the average number of visits 24.1±9.5 (range, 8-48). The mean number of injections in year 1 was 4.5, 1.6 in year 2, 0.9 in year 3, 0.4 on year 4, and 0.1 in the following years. Within the entire follow-up period, the mean number of injections was 7.6±4.4 (range, 2-21). The mean visual acuity was 48.1±15 (range, 15-76) letters at baseline and 45.7±19 (range, 7-75) at year 5. The mean central macular thickness was 303±78 (range, 178-552) μm at baseline and 251±51 (range, 138-359) μm at year 5. Scars developed in 47 (63.5%) eyes at the end of the follow-up period, and atrophy was evident in 6 (8.1%) eyes. CONCLUSION: Ranibizumab monotherapy can stabilize visual acuity for a mean period of 4y in patients with neovascular AMD.

Abstract:AIM: To compare clinical results between toric and spherical periphery design orthokeratology (ortho-k) in myopic children with moderate-to-high corneal astigmatism. METHODS: This retrospective study enrolled 62 eyes of 62 subjects using toric ortho-k lenses. These subjects were assigned to the toric group. Based on the one-to-one match principle (same age, proximate spherical equivalence and corneal astigmatism), 62 eyes of 62 subjects were enrolled and included in the spherical group. At one-year follow-up visit, visual acuity, corneal astigmatism, treatment zone decentration, axial elongation and adverse reaction were compared between these two groups. RESULTS: At the one-year visit, corneal astigmatism was significantly lower in the toric group (1.22±0.76 D) than in the spherical group (2.05±0.85 D) (P=0.012). The mean magnitude of the treatment zone decentration was 0.62±0.42 mm in the toric group and 1.07±0.40 mm in the spherical group (P=0.004). Axial elongation was significantly slower in the toric group (0.04±0.13 mm) than in the spherical group (0.09±0.13 mm) (P=0.001). The one-year axial elongation was significantly correlated with initial age (r=-0.487, P<0.001) and periphery design of ortho-k lens (r=0.315, P<0.001). The incidence of corneal staining was lower in the toric group (8.1%) than in the spherical group (19.4%) (P<0.001). CONCLUSION: Toric periphery design ortho-k lenses may provide lower corneal astigmatism, better centration, slower axial elongation and lower incidence of corneal staining in myopic children with moderate-to-high corneal astigmatism.

Abstract:AIM: To compare the optical quality after implantation of implantable collamer lens (ICL) and wavefront-guided laser in situ keratomileusis (WG-LASIK). METHODS: The study included 40 eyes of 22 patients with myopia who accepted ICL implantation and 40 eyes of 20 patients with myopia who received WG-LASIK. Before surgery and three months after surgery, the objective scattering index (OSI), the values of modulation transfer function (MTF) cutoff frequency, Strehl ratio, and the Optical Quality Analysis System (OQAS) values (OVs) were accessed. The higher order aberrations (HOAs) data including coma, trefoil, spherical, 2nd astigmatism and tetrafoil were also obtained. For patients with pupil size <6 mm, HOAs data were analyzed for 4 mm-pupil diameter. For patients with pupil size ≥6 mm, HOAs data were calculated for 6 mm-pupil diameter. Visual acuity, refraction, pupil size and intraocular pressures were also recorded. RESULTS: In both ICL and WG-LASIK group, significant improvements in visual acuities were found postoperatively, with a significant reduction in spherical equivalent (P< 0.001). After the ICL implantation, the OSI decreased slightly from 2.34±1.92 to 2.24±1.18 with no statistical significance (P=0.62). While in WG-LASIK group, the OSI significantly increased from 0.68±0.43 preoperatively to 0.91±0.53 postoperatively (Wilcoxon signed ranks test, P=0.000). None of the mean MTF cutoff frequency, Strehl ratio, OVs showed statistically significant changes in both ICL and WG-LASIK groups. In the ICL group, there were no statistical differences in the total HOAs for either 4 mm-pupil or 6 mm-pupil. In the WG-LASIK group, the HOA parameters increased significantly at 4 mm-pupil. The total ocular HOAs, coma, spherical and 2nd astigmatism were 0.12±0.06, 0.06±0.03, 0.00±0.03, 0.02±0.01, respectively. After the operation, these values were increased into 0.16±0.07, 0.08±0.05, -0.04±0.04, 0.03±0.01 respectively (Wilcoxon signed ranks test, all P<0.05). At 6 mm-pupil, the induction of total HOAs was not statistically significant in the WG-LASIK group. CONCLUSION: ICL implantation has a less disturbance to optical quality than WG-LASIK. The OQAS is a valuable complementary measurement to the wavefront aberrometers in evaluating the optical quality.

Abstract:AIM: To evaluate and compare the uniformity of angle Kappa adjustment between Oculyzer and Topolyzer Vario topography guided ablation of laser in situ keratomileusis (LASIK) by EX500 excimer laser for myopia. METHODS: Totally 145 cases (290 consecutive eyes )with myopia received LASIK with a target of emmetropia. The ablation for 86 cases (172 eyes) was guided manually based on Oculyzer topography (study group), while the ablation for 59 cases (118 eyes) was guided automatically by Topolyzer Vario topography (control group). Measurement of adjustment values included data respectively in horizontal and vertical direction of cornea. RESULTS: Horizontally, synclastic adjustment between manually actual values (dxmanu) and Oculyzer topography guided data (dxocu) accounts 35.5% in study group, with mean dxmanu/dxocu of 0.78±0.48; while in control group, synclastic adjustment between automatically actual values (dxauto) and Oculyzer topography data (dxocu) accounts 54.2%, with mean dxauto/dxocu of 0.79±0.66. Vertically, synclastic adjustment between dymanu and dyocu accounts 55.2% in study group, with mean dymanu/dyocu of 0.61±0.42; while in control group, synclastic adjustment between dyauto and dyocu accounts 66.1%, with mean dyauto/dyocu of 0.66±0.65. There was no statistically significant difference in ratio of actual values/Oculyzer topography guided data in horizontal and vertical direction between two groups (P=0.951, 0.621). CONCLUSION: There is high consistency in angle Kappa adjustment guided manually by Oculyzer and guided automatically by Topolyzer Vario topography during corneal refractive surgery by WaveLight EX500 excimer laser.

Abstract:AIM: To evaluate the differences in the functional connectivity (FC) of the primary visual cortex (V1) between the youth comitant exotropia (CE) patients and health subjects using resting functional magnetic resonance imaging (fMRI) data. METHODS: Totally, 32 CEs (25 males and 7 females) and 32 healthy control subjects (HCs) (25 males and 7 females) were enrolled in the study and underwent the MRI scanning. Two-sample t-test was used to examine differences in FC maps between the CE patients and HCs. RESULTS: The CE patients showed significantly less FC between the left brodmann area (BA17) and left lingual gyrus/cerebellum posterior lobe, right middle occipital gyrus, left precentral gyrus/postcentral gyrus and right inferior parietal lobule/postcentral gyrus. Meanwhile, CE patients showed significantly less FC between right BA17 and right middle occipital gyrus (BA19, 37). CONCLUSION: Our findings show that CE involves abnormal FC in primary visual cortex in many regions, which may underlie the pathologic mechanism of impaired fusion and stereoscopic vision in CEs.

Abstract:AIM: To analyze childhood glaucoma regarding its demographics, presentations, different causes and surgical modalities used among patients in Dakahelia and to apply the Childhood Glaucoma Research Network (CGRN) classification retrospectively to evaluate its convenience. METHODS: A retrospective study in which the medical files of all glaucoma patients <16 years old presented to Mansoura Ophthalmic Center, Mansoura University from 2014 to 2017, were retrieved and analyzed. Collected data included: age, gender, laterality, visual acuity (VA), refraction, intraocular pressure (IOP), corneal diameter, cup-disc ratio, types and number of surgeries and antiglaucomatous drugs (AGD) at the first and last visit. Prevalence of different subtypes was calculated and means of clinical features were compared. RESULTS: A total of 305 eyes of 207 patients were included classified into 6 groups: primary congenital glaucoma (PCG), juvenile open angle glaucoma (JOAG), glaucoma associated with systemic disease, glaucoma associated with ocular anomalies, acquired glaucoma and glaucoma following cataract surgery. PCG was the predominant type (55.1%) followed by acquired glaucoma (29.5%). Males represented 63.8% of the whole studied patients. Glaucoma associated with ocular anomaly group showed the youngest age at diagnosis (21.9±30.0mo). The shortest corneal diameter was recorded in post cataract group (10.4±0.5 mm). Highest cup-disc ratio was found in the PCG group (P<0.0005). Glaucoma associated with systemic disease presented with the highest baseline IOP (34.5±5.0 mm Hg). All the cases with PCG were treated surgically with 21.8% required more than one surgery. The majority of the patients (74.2%) in the acquired group were treated medically. Combined trabeculotomy-trabeculectomy was the most frequent operation done, accounting for 34.5% of all primary surgeries. Ahmed valve implantation comprised 87% of the secondary surgeries. Acquired glaucoma group had the highest percent of eyes with good final Snellen's VA (69.4%), while glaucoma associated with ocular anomaly group had poorest final VA. CONCLUSION: PCG is the most prevalent type of childhood glaucoma, followed by acquired glaucoma especially traumatic hyphema. Combined trabeculotomy-trabeculectomy and Ahmed valve implantation are the most common surgical interventions. CGRN classification is found to provide a consensus skeleton and is recommended to be integrated in our routine ongoing clinical practice.

Abstract:AIM: To evaluate choroidal thickness, medium choroidal vessel thickness (MCVT) and large choroidal vessel thickness (LCVT) in normal children and adult subjects. METHODS: Manual measurements of subfoveal choroidal thickness (SFCT), MCVT and LCVT at subfoveal and 750 μm nasal and temporal to fovea locations were completed on enhanced-depth imaging optical coherence tomography (EDI-OCT) scans of normal children and adult subjects. RESULTS: Fifty adult and fifty-seven child subjects were included in the study (including 80 adult and 103 child eyes). Mean (±SD) SFCT of adult and children eyes in the study was 309.3±95.7 μm and 279.3±50.4 μm respectively. SFCT and subfoveal MCVT in adult eyes were significantly more than children (P=0.01 and P≤0.0001 respectively). CONCLUSION: There is choroidal thickening with associated thickening of medium choroidal vessels in adults, suggesting that there is alteration in choroidal vasculature with ageing.

Abstract:Corneal cross-linking (CXL) is a noninvasive therapeutic procedure for keratoconus that is aimed at improving corneal biomechanical properties by induction of covalent cross-links between stromal proteins. It is accomplished by ultraviolet A (UVA) radiation of the cornea, which is first saturated with photosensitizing riboflavin. It has been shown that standard epithelium-off CXL (S-CXL) is efficacious, and it has been recommended as the standard of care procedure for keratoconus. However, epithelial removal leads to pain, transient vision loss, and a higher risk of corneal infection. To avoid these disadvantages, transepithelial CXL was developed. Recently, iontophoresis has been adopted to increase riboflavin penetration through the epithelium. Several clinical observations have demonstrated the safety and efficacy of iontophoresis-assisted epithelium-on CXL (I-CXL) for keratoconus. This review aimed to provide a comprehensive summary of the published studies regarding I-CXL and a comparison between I-CXL and S-CXL. All articles used in this review were mainly retrieved from the PubMed database. Original articles and reviews were selected if they were related to the I-CXL technique or related to the comparison between I-CXL and S-CXL.

Abstract:The formation of neovascularization is a common pathological feature of many ocular vascular diseases, and is an important cause of vision loss in patients. Neovascularization can cause retinal hemorrhage, vitreous hemorrhage, and other serious complications, leading to loss of vision. The treatment of intraocular neovascularization is the focus of ophthalmology research. In recent years, some studies have found that autophagy is closely related to vascular endothelial growth factor and the formation of neovascularization. Autophagy is expected to become a new target for the treatment of intraocular neovascularization. Therefore, this article reviews the research on autophagy and the formation of intraocular neovascularization.

Abstract:This study aimed to evaluate the outcomes and described the recovery process of cryopreserved limbal lamellar keratoplasty (CLLK) for peripheral corneal and limbal diseases. Thirteen eyes of 12 patients with a mean age of 41±23.9y were included. The average follow-up was 12.1±5.6mo. Stable ocular surface was achieved in all eyes at last follow-up. Epithelialization originated from both recipient and graft in 9 eyes. We conclude that CLLK compensates for the shortage of donor corneas and cryopreserved limbal grafts provide epithelialization sources in ocular surface reconstruction.

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