Abstract:Pterygium, a common ocular surface disorder, has a complex pathophysiology that may mimic tumorigenesis. There is altered expression of cell cycle/proliferation-related factors in pterygium tissues. Therefore, similar to cancer treatments, the management of pterygium ought to be multifactorial based on the patient’s condition. Current therapeutic methods for pterygium are focused on surgical resection in conjunction with antimetabolite use, in addition tissue graft is usually performed in the context of the avoidance of bare sclera. However, future directions in the management of pterygia will likely focus on genetic approaches. This perspective views the pathogenesis of pterygium, its existing therapies as well as current and future challenges in its treatment.

Abstract:AIM: To elucidate the effect of rapamycin on regulating the production of interleukin (IL)-1β in Aspergillus fumigatus (A. fumigatus)-induced keratitis and to verify whether the expression of IL-1β in A. fumigatus keratitis is associated with the mammalian target of rapamycin (mTOR)/Toll-like receptor 4 (TLR4) signaling pathway. METHODS: Fungal keratitis mouse models of susceptible C57BL/6 mice were established using A. fumigatus. The mice were subsequently treated with rapamycin. The protein levels of p-mTOR, TLR4, and IL-1β in normal and infected corneal tissue were measured by Western blot. The TLR4 and IL-1β mRNA levels were determined by real-time polymerase chain reaction (PCR). RESULTS: In C57BL/6 mice, rapamycin treatment decreased the clinical scores and production of the pro-inflammatory cytokine, IL-1β. The expression of TLR4, stimulated by A. fumigatus, was reduced as well when the mTOR signaling pathway was suppressed by rapamycin. CONCLUSION: Rapamycin is beneficial for the outcome of fungal keratitis and has an inhibitory effect expression of the inflammatory cytokine IL-1β. The inhibitory effect on IL-1β expression can be associated with the mTOR/TLR4 signaling pathway in A. fumigatus infection in mice.

Abstract:AIM: To investigate if significant improvement of optic disc blood flow (ODBF) occurs after instillation of brinzolamide onto rabbit eyes. METHODS: Testing of bilateral intraocular pressure (IOP) and left ODBF in 10 male rabbits took place every 3h over a 24h period. Brinzolamide (1% ophthalmic solution, two drops at 9:00 and 21:00) was administered to the left eye. ODBF, assessed using laser speckle flowgraphy, was determined as the mean blur rate (MBR). Furthermore, the effect of brinzolamide on isolated rabbit ciliary arteries using isometric tension recording system was performed. RESULTS: After brinzolamide instillation, IOP was significantly decreased in the left eye. MBR-vessel was greater at 18:00 and 21:00 (P<0.05) than in the controls. MBR-tissue and MBR-average were greater at 18:00 (P<0.05) than in the controls. For isolated arteries pre-contracted with a high-K solution, brinzolamide induced concentration-dependent relaxation, reaching 46.1%±9% (n=21) at 1 mmol/L. In Ca2+-free solutions, incubation with brinzolamide suppressed 1 μmol/L histamine-induced contractions (P<0.05). CONCLUSION: Brinzolamide decreases IOP and increases ocular blood flow. The direct vasodilatory effect of brizolamide is mediated by suppression of Ca2+ release from intracellular calcium stores.

Abstract:AIM: To investigate the roles of integrins in choroidal neovascularization (CNV) and their associations with the stromal cell-derived factor-1 (SDF-1)/CXCR4 axis. METHODS: CNV lesions were induced in mice using laser photocoagulation. After CNV induction, all animals were randomly assigned to: control, SDF-1, SDF-1+age-related macular degeneration (AMD) 3100 (CXCR4 inhibitor), and SDF-1+ATN161 (integrin α5β1 inhibitor) groups; their effects on CNV progression were observed using hematoxylin eosin (HE) staining, fundus fluorescein angiography (FFA) grading and optical coherence tomography (OCT), and their effects on CXCR4/integrin α5 expression were evaluated using Western blot and double immunofluorescence staining. Hypoxia-exposed endothelial cells (ECs) were used to simulate CNV in vitro, they were treated with SDF-1, combined with CXCR4 siRNA/AMD3100 or ATN161, and expression of integrin α5, cell migration and tube formation were analyzed. RESULTS: Integrin subunit α5 increased at 3rd and 7th day and decreased at 14th day in CNV mice, with no significant change of β1-integrin. CXCR4 expression in CNV mice had persistent increase within 14d after induction. SDF-1 treatment significantly promoted the CNV progression during 3-14d. The mean CNV length in AMD3100 and ATN161 group at day 7 was 270.13 and 264.23 μm in HE images, significantly lower than the mean length in SDF-1 (345.70 μm) group. AMD3100 and ATN161 also significantly reduced thickness and leakage of CNV induced by SDF-1. Mean integrin α5 positive area in SDF-1 group reached 2.31×104 μm2, significantly higher than control (1.25×104 μm2), which decreased to 1.78×104 μm2 after AMD3100 treatment. About 61.36% of ECs in CNV lesions expressed α5 in SDF-1 group, which significantly decreased to 43.12% after AMD3100 treatment. In vitro, integrin α5 peaked by 6 folds after 6h of hypoxia exposure and CXCR4 gradually increased by up to 2.3 folds after 24h of hypoxia. Approximately 25.12% of ECs expressed integrin α5 after SDF-1 stimulation, which decreased to 7.2%-9.5% after si-CXCR4 or AMD3100 treatment. ATN161 exerted an inhibitory effect comparable to that of si-CXCR4 on EC migration and tube formation in the presence of SDF-1. CONCLUSION: SDF-1/CXCR4 signaling induces integrin α5β1 expression in ECs to promote CNV.

Abstract:AIM: To explore the roles of phospholipids and sphingolipids in the inflammatory process of uveitis. METHODS: Aqueous humor (AH) and the retina were obtained from endotoxin-induced uveitis (EIU) rats during the acute inflammation stage (24h after endotoxin injection). Lipids were extracted using a modified Bligh and Dyer method and subjected to mass spectrometric identification using class-specific lipid standards and ratiometric quantification. Relative intensity analysis was performed to evaluate the amount change of common lipids between the EIU and control groups. RESULTS: Unique lipid species encompassing all five phospholipid classes were found in both control and the EIU AH and retina. Commensurate with the significantly increased level of lysophospholipids in the EIU AH and retina, we found that the ratio of lysophospholipids to total phospholipids was significantly increased too. We also detected a significant increase in 18:0 lysophosphatidylcholine levels in the EIU group (fold change =6.4 in AH and 3.8 in retina). Cer240, Cer241, and SM240 levels remarkably increased in the EIU AH. Enhanced C12 ceramide-1-phosphate (C12 C-1-P), C16 C-1-P, C24 C-1-P, and upregulated Cer160, Cer240, SM120, and SM240 were found in EIU retina. C-1-P was believed to restore homeostasis by inhibiting nuclear factor kappa B (NF-κB) activation. However, we still found elevated NF-κB levels in the EIU retina. CONCLUSION: A variety of lipids might have played a critical role in EIU inflammation. Exogenous topical application of these protective lipids or inhibition of these pro-inflammatory lipids may be useful therapeutic strategies for the resolution of EIU.

Abstract:AIM: To identify the pathological role of amyloid beta (Aβ) deposition in retinal degeneration, and explore Aβ deposition on the retinal pigment epithelium cells (RPE) layer and the associated structural and functional changes in Alzheimer’s disease transgenic mice. METHODS: RPE changes in the eyes of APPswe/PS1 transgenic and none transgenic (NTG) mice over 20 months old were examined. Histological changes were investigated via hematoxylin and eosin (H&E) staining and transmission electron microscopy (TEM) examination, whereas the expression of amyloid precursor protein (APP), Aβ, Zonula occludens-1 (ZO-1) and Ionized calcium binding adaptor molecule-1 (IBA-1) were investigated using immunohistochemistry and immunofluorescence techniques. All of the obtained results were quantitatively and statistically analyzed. RESULTS: In aged transgenic mice, an APP-positive immunoreaction and Aβ deposition were detected on the RPE layer but were undetectable in NTG mice. The RPE demonstrated some vacuole changes, shortened basal infoldings and basal deposition in histopathological examination and TEM tests, wherein irregular shapes were indicated by ZO-1 disorganization through fluorescence. Furthermore, IBA-1 positive cells were observed to have accumulated and infiltrated into the RPE layer and localized beneath the RPE/Bruch’s membrane (BrM) complex, which was accompanied by an increase in BrM thickness in aged transgenic mice in comparison to NTG mice. The IBA-1 positive cells were found to be co-stained with Aβ deposition on the RPE flat mounts. CONCLUSION: The observed Aβ deposition in the RPE layer may cause RPE dysfunction, which is associated with microglia cells infiltration into the retina of aged transgenic mice, suggesting that Aβ deposition probably plays a significant role in RPE-related degenerative disease.

Abstract:AIM: To evaluate the intrinsic excitability of retinal ganglion cells (RGCs) in degenerated retinas. METHODS: The intrinsic excitability of various morphologically defined RGC types using a combination of patch-clamp recording and the Lucifer yellow tracer in retinal whole-mount preparations harvested from Royal College of Surgeons (RCS) rats, a common retinitis pigmentosa (RP) model, in a relatively late stage of retinal degeneration (P90) were investigated. Several parameters of RGC morphologies and action potentials (APs) were measured and compared to those of non-dystrophic control rats, including dendritic stratification, dendritic field diameter, peak amplitude, half width, resting membrane potential, AP threshold, depolarization to threshold, and firing rates. RESULTS: Compared with non-dystrophic control RGCs, more depolarizations were required to reach the AP threshold in RCS RGCs with low spontaneous spike rates and in RCS OFF cells (especially A2o cells), and RCS RGCs maintained their dendritic morphologies, resting membrane potentials and capabilities to generate APs. CONCLUSION: RGCs are relatively well preserved morphologically and functionally, and some cells are more susceptible to decreased excitability during retinal degeneration. These findings provide valuable considerations for optimizing RP therapeutic strategies.

Abstract:AIM: To investigate the effect of the overexpression of C-X-C chemokine receptor type 4 (CXCR4) on homing of mesenchymal stem cells (MSCs) in vitro and therapeutic effects of diabetic retinopathy (DR) in vivo. METHODS: MSCs were infected by lentivirus constructed with CXCR4. The expression of CXCR4 was examined by immunofluorescence, Western blot, and quantitative polymerase chain reaction. CXCR4-overexpressing MSCs were cultured in vitro to evaluate their chemotaxis, migration, and apoptotic activities. CXCR4-overexpressing MSCs were intravitreally injected to observe and compare their effects in a mouse model of DR. The histological structure of DR in rats was inspected by hematoxylin and eosin staining. The expression of rhodopsin, neuron-specific enolase (NSE), and inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α was examined by Western blot and immunohistochemical analyses. RESULTS: The transduction of MSCs by lentivirus was effective, and the transduced MSCs had high expression levels of CXCR4 gene and protein. Improved migration activities were observed in CXCR4-overexpressing MSCs. Further, reduced retinal damage, upregulation of rhodopsin and NSE protein, and downregulation of inflammatory cytokines IL-6 and TNF-α were observed in CXCR4-overexpressing MSCs in vivo. CONCLUSION: The homing of MSCs can be enhanced by upregulating CXCR4 levels, possibly improving histological structures of DR. CXCR4-overexpressing MSCs can be a novel strategy for treating DR.

Abstract:AIM: To reveal the role of miRNAs in retinopathy of prematurity (ROP) by bioinformatics analysis. METHODS: The raw data of this study came from the researches of Wang et al and Zhao et al who analyzed the microRNA (miRNA) expression profile between ROP and controls. Based on the identified differentially expressed miRNAs, the related target genes, lncRNA and circRNA were predicted. Then we performed functional enrichment analysis to further analyze the functions of target genes. RESULTS: Hsa-miRNA-128-3p and hsa-miRNA-9-5p showed significantly different expression in both studies. LncRNA of POLDIP2, GAS5, NEFL and UHRF1, circRNA of ZNF280C_hsa_circ_001211 and SIAE_hsa_circ_002083, tar-get gene of QKI showed meaningful differential expression in ROP. Enrichment analysis showed that TGF-β signaling pathway, PI3K-Akt signaling pathway and MAPK signaling pathway might play important roles in the prog-ress of ROP. CONCLUSION: This research may provide a comprehensive bioinformatics analysis of differentially expressed miRNAs which are possibly involved in ROP.

Abstract:AIM: To determine the effects of Rutin on methanol induced optic neuropathy and compare the results with the effects of ethanol. METHODS: Totally 30 rats were divided into 5 groups, with 6 rats in each group as follows: healthy controls (C), methotrexate (MTX), methotrexate+methanol (MTM), methotrexate+methanol+ethanol (MTME) and methotrexate+ methanol+Rutin (MTMR). In all rabbits except those of the control group, MTX, diluted in sterile serum physiologic, 0.3 mg/kg per oral was applied for 7d by the aid of a tube. After this procedure to the rats of MTM, MTME and MTMR groups, 20% methanol with a dose of 3 g/kg per oral was given by the aid of a tube. In MTME group, 4h after the application of methanol, 20% ethanol was applied by the same way with a dose of 0.5 g/kg. On the other hand, in MTMR group 4h after the application of methanol, Rutin, which was dissolved in distilled water, was applied by the same way with a dose of 50 mg/kg. RESULTS: There were statistically significant differences in tissue 8- hydroxy-2 deoxyguanine (8-OHdG), interleukin-1β (IL-1β), tumor necrosis factor-alpha (TNF-α), malondialdehyde (MDA), myeloperoxidase (MPO). glutathione peroxidase (tGSH) and superoxide dismutase (SOD) levels between groups (P<0.001). In MTMR group tissue 8-OHdG, IL-1β, MDA, and MPO levels were similar with the healthy controls but significantly different than the other groups. In histopathological evaluations, in MTX group there was moderate focal destruction, hemorrhage and decrease in number of astrocytes and oligodendrocytes; in MTM group there was severe destruction and edema with decrease in number of astrocytes and oligodendrocytes; in MTME group there was mild hemorrhage, mild edema, mildly dilated blood vessels with congestion while in MTMR group, optic nerve tissue was resembling the healthy controls. CONCLUSION: Rutin may prevent methanol-induced optic neuropathy via anti-inflammatory effects and decreasing the oxidative stress. New treatment options are warranted in this disease to avoid loss of vision in patients.

Abstract:AIM: To analyze indications and reasons for failure of anterior lamellar keratoplasty (ALK). METHODS: The clinical records were retrospectively reviewed. Main outcome measures included indications for ALK and reasons for failure of ALK. RESULTS: A total of 434 patients (462 eyes) were treated with ALK at Qingdao Eye Hospital, Shandong Eye Institute from June 1, 2009 to May 31, 2016. The main indications were infectious keratitis (33.3%), keratoconus (23.6%), corneal dystrophy and degeneration (9.8%), Mooren’s ulcer (8.4%), corneal neoplasm (7.8%), viral keratitis (6.5%) and regrafting (3.7%). Fungal keratitis accounted for 73.4% in the infectious keratitis cases. ALKs were failed in 36 patients, with the major causes being recurrence of primary diseases (63.9%). The leading causes of graft failure was Mooren’s ulcer (36.1%), followed by infectious keratitis (30.6%). Recurrence of fungal keratitis accounted for 81.8% in the failed cases after ALK for infectious keratitis cases. CONCLUSION: Infectious keratitis and keratoconus are the main indications for ALK, of which fungal keratitis was the major cause of corneal infections. Recurrence of primary disease is the main reason of graft failure after ALK, in which the main primary diseases associated with graft failure are Mooren’s ulcer and fungal keratitis.

Abstract:AIM: To evaluate the ability of macular ganglion cell complex (GCC) thickness using Fourier domain optical coherence tomography (FD-OCT) to detect glaucoma in highly myopic eyes. METHODS: Cross-sectional study. A total of 114 participants, consecutively were enrolled. Macular GCC thickness and peripapillary retinal nerve fiber layer (RNFL) thickness were obtained with RTVue FD-OCT. Receiver operating characteristics curves were constructed for each measurement parameter, and areas under the curves (AUCs) were compared. RESULTS: Both the average GCC and average RNFL thickness showed negative correlations with axial length (rGCC=-0.404, P=0.001; rRNFL=-0.561, P<0.001). The largest AUCs from GCC, and RNFL parameters were 0.968 [global loss volume (GLV)], and 0.855 (average RNFL), respectively. GLV was significantly better for detecting high myopic glaucoma than average RNFL (P<0.001). CONCLUSION: Macular GCC thickness has higher diagnostic power than peripapillary RNFL thickness to discriminate glaucoma patients from non-glaucoma subjects in high myopia.

Abstract:AIM: To evaluate the effect (clinically, histopathologically and immunohistochemically) and safety of a single intra-pterygium injection of bevacizumab. METHODS: Prospective interventional study comprised 40 eyes of 40 patients with primary fleshy pterygia who attended the Outpatient Clinic of Department of Ophthalmology, Assiut University Hospitals, Egypt from May 2015 to May 2016. Patients were randomly classified into 2 groups: the first group received a single intralesional injection of bevacizumab (Avastin; Genentech, San Francisco, CA, USA); the second group comprised patients who did not receive subconjunctival bevacizumab. Excision of pterygium and conjunctival auto graft was done in both groups. The excised pterygium tissues were subjected to histopathological and immunohistochemical evaluation. RESULTS: The study comprised 40 eyes of 40 patients (33 men, 7 women) of age range from 31-58y. The study group included 22 eyes. The control group included 18 eyes. A decrease in the vascularity of the pterygium was noted in all injected cases. The mean vessel count was higher in non-injected pterygia than that in injected pterygia and the difference was statistically significant (P=0.001). Also, the mean vessel count in both groups was significantly higher than normal conjunctive (P=0.005 and 0.001). A statistically significant difference in vascular endothelial growth factor (VEGF) expression between injected and non-injected cases was detected in the epithelial, stromal and endothelial cells (P=0.0001, 0.016, 0.014). No serious intraoperative complications occurred in both groups. CONCLUSION: The use of single intra lesional injection of Avastin in pterygium decreased vascularity and decreased VEGF expression in injected pterygium after one month. Our study proved the effect of single intra lesional injection of Avastin on pterygium. Further studies may enable limiting the need for surgery and improve quality of life for patients with pterygia.

Abstract:AIM: To evaluate the clinical and tomographic outcomes after implantation of a new intrastromal corneal ring segment (ICRS) with 140-degrees of arc in eyes with corneal ectasia. METHODS: We evaluated patients with corneal ectasia implanted with Ferrara 140° ICRS from April 2010 to February 2015. Outcome measures included preoperative and postoperative corrected distance visual acuity (CDVA), keratometry simulated (K) reading, tomographic astigmatism and asphericity. All patients were evaluated using the Pentacam Scheimpflug system. RESULTS: The study evaluated 58 eyes. The mean follow-up was 16.81±10.8mo. The CDVA (logMAR) improved from 0.5±0.20 (20/60) to 0.3±0.21 (20/40) (P<0.01). The average K reduced from 49.87±7.01 to 47.34±4.90 D (P<0.01). The asphericity changed from -0.60±0.86 to -0.23±0.67 D (P<0.01). The mean preoperative tomographic astigmatism decreased from -8.0±3.45 to -4.53±2.52 D (P<0.01). CONCLUSION: The new ICRS model with 140-degrees of arc effectively improve the visual acuity and reduce the high astigmatism usually found in patients with corneal ectasia.

Abstract:AIM: To compare the functional and anatomic results of femtosecond laser (FSL)-assisted deep anterior lamellar keratoplasty (DALK) associated with phototherapeutic keratectomy (PTK) and FSL-assisted DALK performed using the big-bubble technique in keratoconus. METHODS: During the first phase of the study, an electron microscopy histopathology pilot study was conducted that included four unsuitable donor corneas divided into two groups: in FSL group, FSL lamellar cuts were performed on two corneas and in FSL+PTK group, PTK was performed at the stromal beds of two corneas after FSL lamellar cuts were made. During the second phase of the study, a randomized clinical trial was conducted that included two treatment groups of patients with keratoconus: group 1 (n=14 eyes) underwent FSL-assisted DALK associated with PTK and group 2 (n=12 eyes) underwent FSL-assisted DALK associated with the big-bubble technique. The main outcome measures were the postoperative visual acuity (VA) and optical coherence tomography (OCT) measurements, confocal microscopic findings, and contrast sensitivity. RESULTS: In the pilot study, histopathology showed a more regular stromal bed in the FSL+PTK group. In the clinical trial, group 1 had significantly worse best spectacle-corrected VA and contrast sensitivity (P<0.05 for both comparisons). The residual stromal bed measured by OCT was significantly (P<0.05) thicker in group 1. Confocal microscopy detected opacities only at the donor-receptor interface in group 1. CONCLUSION: Patients with keratoconus treated with FSL-assisted DALK performed using the big-bubble technique fare better than treated with FSL-assisted DALK associated with PTK.

Abstract:AIM: To evaluate the prevalence, clinical features, and the factors affecting onset of strabismus and nystagmus in patients with bilateral congenital cataracts. METHODS: This study evaluated 116 eyes of 58 patients who underwent lens removal for the treatment of bilateral congenital cataracts between January 1999 and January 2011. The presence and type of strabismus and nystagmus were determined before and after surgery. Type of strabismus and final visual acuity were compared in patients with and without nystagmus. Patients were divided into three groups (orthotropia/orthotropia, orthotropia/strabismus, and strabismus/strabismus) according to their preoperative and postoperative ocular alignment. Age at cataract surgery and associations of nystagmus and primary intraocular lens (IOL) implantation with strabismus were analyzed. RESULTS: Six patients (10.3%) had strabismus preoperatively and an additional 11 (19.0%) developed postoperative strabismus. Exotropia was more common than esotropia both preoperatively and postoperatively. Eighteen patients (31.0%) had postoperative nystagmus, with sensory nystagmus being the most common type. Of the 18 patients with nystagmus, 10 had strabismus, with exotropia being more common than esotropia. Postoperative visual acuity was poor in patients with nystagmus. Age at cataract surgery and rate of primary IOL implantation were significantly lower, and postoperative nystagmus was more common, in the orthotropia/strabismus group than in the other two groups. CONCLUSION: Exotropia and sensory nystagmus are common in patients with bilateral congenital cataracts. Age at cataract surgery and rate of IOL implantation are lower and nystagmus more common in patients with postoperative onset of strabismus. Nystagmus is associated with poor visual prognosis.

Abstract:AIM: To investigate the effect of internal limiting membrane transplantation and autologous blood on treating refractory giant macular hole. METHODS: Thirty-seven eyes with giant macular hole of the smallest hole diameter >700 μm, the maximum diameter of the substrate >1000 μm and hole formation factor <0.6 underwent surgical treatment. The patients were randomly divided into two groups. Nineteen eyes with surgical flip of the internal limiting membrane in group A, 18 eyes with internal limiting membrane transplantation in group B who underwent the tamponade of internal limiting membrane into the hole, autologous plasma was used to seal the hole. The patients were followed up for 3mo, optical coherence tomography and best corrected visual acuity (BCVA) were recorded before and after operation, and the results were statistically analyzed. RESULTS: At 3mo after operation, BCVA of the two groups was significantly improved compared with that before operation (tA=4.192, tB=4.374, P<0.05). But there was no significant difference in visual acuity between the two groups (χ2=0.128, P>0.05). At 3mo after operation, the closure rate of group A was 68.4%, and 100% in group B. (χ2=5.628, P<0.05). The defect diameter of inner segment/outer segment at 3mo after the operation was significantly lower than that before operation (tA=12.287, tB=15.481, P<0.05), and the difference was statistically significant (t=2.552, P<0.05). CONCLUSION: Internal limiting membrane transplantation combined with autologous whole blood can improve the postoperative closure rate of the refractory large aperture, and can effectively improve the postoperative visual acuity.

Abstract:AIM: To investigate the levels of ghrelin (Gh), acylated ghrelin (AGh) and AGh/Gh ratio in the humor aqueous (HA) of cases with pseudoexfoliation syndrome (PXS), pseudoexfoliation glaucoma (PXG), primary open angle glaucoma (POAG) and to compare these with control subjects. METHODS: A prospective examination was made of the total Gh, and AGh levels in HA of 67 patients undergoing cataract surgery. Patients were divided into 4 groups. HA samples were aspirated at the beginning of the surgery, stored at -70oC. Gh and AGh quantification was performed with ELISA kits and the AGh/total-Gh ratios were calculated. ANOVA, Kruskal-Wallis, Chi-square and post-hoc tests were used for statistical analysis. RESULTS: Total Gh levels in HA were 189.2±45.6 pg/mL in the control group, 199.2±32.9 pg/mL in PXS, 180.6±20.9 pg/mL in PXG and 176.8±21.4 pg/mL in POAG groups (P>0.05). AGh levels in HA were 23.09±5.01 pg/mL in the control group, 24.13±5.22 pg/mL in PXS, 22.29±1.55 pg/mL in PXG and 19.69±2.93 pg/mL in POAG groups (P>0.05). The ratio of AGh/Gh was 10.3%±2.34% in the control group, 13.03%±2.58% in PXS, 12.3%±1.54% in PXG and 11.79%±1.41% in POAG groups (P=0.044). The difference between the PXS and control groups was significant (P=0.03). CONCLUSION: In spite of statistically insignificant results, the HA total Gh levels were lower than those of the control subjects but not parallel with the AGh levels in glaucoma patients. The relative increase in the AGh/Gh ratio in glaucoma cases supports the view that proportional increases of AGh might play a role in the pathogenesis of glaucoma.

Abstract:AIM: To determine the Bruch’s membrane opening-minimum rim width (BMO-MRW) tipping point where corresponding visual field (VF) damages become detectable. METHODS: A total of 85 normal subjects and 83 glaucoma patients (one eye per participant) were recruited for the study. All of the patients had VF examinations and spectral-domain optical coherence tomography to measure the BMO-MRW. Total deviation values for 52 VF points were allocated to the corresponding sector according to the Garway-Heath distribution map. To evaluate the relationship between VF loss and BMO-MRW measurements, a “broken-stick” statistical model was used. The tipping point where the VF values started to sharply decrease as a function of BMO-MRW measurements was estimated and the slopes above and below this tipping point were compared. RESULTS: A 25.9% global BMO-MRW loss from normative value was required for the VF loss to be detectable. Sectorally, substantial BMO-MRW thinning in inferotemporal sector (33.1%) and relatively less BMO-MRW thinning in the superotemporal sector (8.9%) were necessary for the detection of the VF loss. Beyond the tipping point, the slopes were close to zero throughout all of the sectors and the VF loss was unrelated to the BMO-MRW loss. The VF loss was related to the BMO-MRW loss below the tipping point. The difference between the two slopes was statistically significant (P≤0.002). CONCLUSION: Substantial BMO-MRW loss appears to be necessary for VF loss to be detectable in patients with open angle glaucoma with standard achromatic perimetry.

Abstract:AIM: To evaluate whether optical coherence tomography angiography (OCTA) can detect altered vessel density (VD) at the optic nerve head (ONH) in glaucoma patients. Special attention is paid to the accuracy of the OCTA technique for distinguishing healthy from glaucomatous eyes. METHODS: A total of 171 eyes were examined by the OCTA system AngioVue? (Optovue): 97 eyes diagnosed with glaucoma and 74 healthy control eyes. The papillary and peripapillary VD was measured. Furthermore, the VD was correlated with different structural and functional measurements. In order to test the accuracy of differentiation between eyes with and without glaucoma, we calculated the receiver operating characteristic curve (ROC) and the area under the curve (AUC). RESULTS: The papillary and peripapillary VD in glaucomatous eyes was significantly lower than in healthy eyes (P<0.05). The VD of the nasal peripapillary sector was significantly lower than in the other sectors. The further the disease had progressed [measured by determining the thickness of the ganglion cell complex (GCC) and the retinal nerve fiber layer (RNFL)] the greater the VD reduction. The AUC discriminated well between glaucomatous and normal eyes (consensus classifier 94.2%). CONCLUSION: OCTA allows non-invasive quantification of the peripapillary and papillary VD, which is significantly reduced in glaucomatous eyes and accurately distinguishes between healthy and diseased eyes. OCTA expands the spectrum of procedures for detecting and monitoring glaucoma.

Abstract:AIM: To evaluate the influence of age and axial length (AL) on the position of the fovea in patients with high myopia (HM). METHODS: In this prospective study, 96 patients (186 eyes) with HM were consecutively recruited from the Third Affiliated Hospital of Nanchang University. DRI-OCT Atlantis, fundus imaging, and IOL Master were used in this study. Three indices were measured: the distance between the fovea and the optic nerve head (ONH) center (DFO), the vertical distance between the fovea and the horizontal line pass of the ONH center (VDFO), and the horizontal distance between the fovea and the vertical line pass of the ONH center (HDFO). These measurements were used to analyze the effects of different age groups (A1, A2, A3 groups) and AL (AL1, AL2, AL3, AL4 groups) on these indices. RESULTS: The results showed that there was no statistical significance in DFO among the age and AL groups (F=0.46, 0.37; P=0.62, 0.76, respectively). In HDFO, there was also no statistical significance among the age and AL groups (F=0.10, 0.48; P=0.90, 0.69, respectively). In VDFO, however, the difference in the age and AL groups was statistically significant (F=3.21, 3.12; P=0.04, 0.02, respectively). Thus, VDFO were correlated with age and AL (r=0.21, 0.23, all P<0.01), while HDFO and DFO were not correlated with age and AL (r=0.30, P>0.05). CONCLUSION: In high myopia, the foveal position changes mainly in the vertical direction along with factors of age and AL.

Abstract:AIM: To survey ophthalmologists (who have participated previously in clinical research) and ophthalmic industry professionals (who have been involved in ocular research and development) to indicate perceived needs for new pharmaceuticals in various ophthalmic subspecialties. METHODS: A prospective, industry-based survey was sent to ophthalmologists and ophthalmic industry professionals about the perceived needs for new pharmaceutical products. RESULTS: This survey was sent to 559 ophthalmic pharma professionals and ophthalmologists. We received 82 (15%) responses. The results showed that the most commonly perceived need for new pharmaceuticals were dry and wet age-related macular degeneration, glaucoma, diabetic macular edema and dry eye. There was a statistical difference found between response groups (P<0.0001). Respondents indicated they would express their commitment to a new product they perceived as needed by recommending to colleagues (63%), prescribing (60%), participating as principle investigator in a related clinical trial (52%), advising the company (52%), lecturing on behalf of the product (43%), investing in the product (38%), taking no action (7%) or obtain a position in the company (1%). CONCLUSION: Ophthalmic pharma professionals and ophthalmologists perceive the greatest need for new medicines in ophthalmology to be in dry and wet age-related macular degeneration, glaucoma, diabetic macular edema and dry eye.

Abstract:AIM: To evaluate the association between visual impairment (VI) and mental health or social engagement in older adults living in rural Thailand. METHODS: Data for this cross-sectional study were drawn from a community survey conducted in 2015 in Saraburi Province, Thailand. Participants were 327 adults aged ≥50y. VI was assessed using presenting distance visual acuity. Mental health and social engagement were evaluated in face-to-face interviews using validated questionnaires. After determining the prevalence of VI and relevant sociodemographic characteristics, multivariate regression analysis was used to evaluate the impact of VI on mental health and social engagement. RESULTS: The prevalence of VI was 18.3%. Major causes were refractive error (58.3%) and cataract (35%). Factors associated with VI in the crude analysis were: older age [odds ratio (OR) 8.08], unemployment (OR 2.72), widowhood (OR 2.47), being divorced/separated (OR 3.27), smoking (OR 2.09) and disability in activities of daily living (OR 2.35). Protective factors were undergoing eye screening at least once a year (P=0.029) and obesity (P=0.005). VI was significantly associated with low social engagement (adjusted OR 4.13) but not with poor mental health (P>0.05). CONCLUSION: Although VI older adults reported less participation in social activities, there is no significant association between VI and poor mental health. Annual eye examinations may prevent VI in older adults. Information about employment and anti-smoking should be targeted to older adults with VI.

Abstract:Retinopathy of prematurity (ROP) is a retinal vascular disorder frequently found in premature infants. Different therapeutic strategies have been developed to treat ROP. However, there are still many children with ROP suffering by severe limitations in vision or even blindness. Recently, ROP has been suggested to be caused by abnormal development of the retinal vasculature, but not simply resulted by retinal neovascularization which takes about 4 to 6wk after birth in premature infants. Thus, instead of focusing on how to reduce retinal neovascularization, understanding the pathological changes and mechanisms that occur prior to retinal neovascularization is meaningful, which may lead to identify novel target(s) for the development of novel strategy to promote the healthy growth of retinal blood vessels rather than passively waiting for the appearance of retinal neovascularization and removing it by force. In this review, we discussed recent studies about, 1) the pathogenesis prior to retinal neovascularization in oxygen-induced retinopathy (OIR; a ROP in animal model) and in premature infants with ROP; 2) the preclinical and clinical research on preventive treatment of early OIR and ROP. We will not only highlight the importance of the mechanisms and signalling pathways in regulating early stage of ROP but also will provide guidance for actively exploring novel mechanisms and discovering novel treatments for early phase OIR and ROP prior to retinal neovascularization in the future.

Abstract:Myopia, a worldwide condition, is a multifactorial disease resulting in many ocular complications. Early onset of myopia has a great tendency to develop high myopia and pathological myopia later in life. The pathophysiology and progression of myopia is still unclear. Owing to its involving in visual function, optic disc and peripapillary change in high myopia can’t be neglected, and it may help in better understanding of the pathophysiology or mechanism of myopia progression. Recently, advanced imaging techniques have been developed, such as optical coherence tomography (OCT), allowing for better detecting of optic disc and peripapillary change. OCT is a high-resolution and noninvasive measurement for detection of ocular structure. Herein, we provide an updated review of optic disc and peripapillary change in OCT image, including its characteristics and clinical significance. We also propose some problems needed further investigation.

Abstract:Age-related macular degeneration (AMD) is a leading cause of blindness and is becoming a global crisis since affected people will increase to 288 million by 2040. Genetics, age, diabetes, gender, obesity, hypertension, race, hyperopia, iris-color, smoking, sun-light and pyroptosis have varying roles in AMD, but oxidative stress-induced inflammation remains a significant driver of pathobiology. Eye is a unique organ as it contains a remarkable oxygen-gradient that generates reactive oxygen species (ROS) which upregulates inflammatory pathways. ROS becomes a source of functional and morphological impairments in retinal pigment epithelium (RPE), endothelial cells and retinal ganglion cells. Reports demonstrated that hydrogen sulfide (H2S) acts as a signaling molecule and that it may treat ailments. Therefore, we propose a novel hypothesis that H2S may restore homeostasis in the eyes thereby reducing damage caused by oxidative injury and inflammation. Since H2S has been shown to be a powerful antioxidant because of its free-radicals’ inhibition properties in addition to its beneficial effects in age-related conditions, therefore, patients may benefit from H2S salubrious effects not only by minimizing their oxidant and inflammatory injuries to retina but also by lowering retinal glutamate excitotoxicity.

Abstract:This cohort study included 36 eyes of 21 patients with high myopia treated with angle supported phakic intraocular lens (pIOL). Endothelial cell density (ECD) at baseline, 6mo and 3y were 3017±296, 2775±265 and 2558±299 cells/mm2 respectively. ECD loss at 6mo was 7.2% and annual ECD loss was 3% over 36mo. Corrected distance visual acuity at 36mo was 0.4 logMAR or better in 32 (88.9%) eyes. Intraocular pressure did not change (P=0.9). No eyes developed cataract, retinal detachment or pupillary distortion. Angle supported pIOL gives good visual outcome. Endothelial cell loss should be monitored.

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