Abstract:AIM: To study the effects of curcumin on the secretion of interleukin (IL) -6 and IL-8 by corneal limbus epithelial cells. METHODS: Human corneal limbus epithelial cells were isolated and cultured from donor eyes and irradiated by UVB at different dosages with or without curcumin. MTT test was used for studying the effects of UVB and curcumin on the cell viability. The role of mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) pathways on the UVB-induced secretion of IL-6 and IL-8 were tested by addition of their inhibitors to the culture with or without UVB-radiation. Levels of various signal pathways, IL-6 and IL-8 in the cells and in the conditioned culture medium were measured by ELISA analysis. RESULTS: UVB at 20 mJ/cm2 or less and curcumin at 20 μmol/L or less did not affect the cell viability of cultured limbus epithelial cells (P>0.05). UVB irradiation at 10 and 20 mJ/cm2 induced a significant increase of secretion of IL-6 and IL-8 and upregulated NF-κB and phosphorylated MAPK pathways of cultured limbus epithelial cells (P<0.05). Various signal pathway inhibitors, including SP600125 (JNK inhibitor), SB203580 (p38 MAPK inhibitor) and BAY11-7082 (NF-κB inhibitor) significantly decreased the UVB-induced secretion of IL-6 and IL-8 secretion (P<0.05). Curcumin at 5-20 μmol/L significantly inhibited UVB-induced secretion of IL-6 and IL-8 by limbus epithelial cells in a dose-dependent manner; while curcumin alone did not affect the secretion of IL-6 and IL-8. The upregulation of NF-κB and MAPK pathways induced by UVB treatment was significantly inhibited by curcumin, suggesting that NF-κB and MAPK pathways are involved in the inhibitory effect of curcumin on UVB-induced production of IL-6 and IL-8. CONCLUSION: Curcumin may be a promising agent to be explored for the prevention and treatment of pterygium.

Abstract:AIM: To evaluate the effect of sorafenib in murine high risk keratoplasty model. METHODS: Graft survival, corneal neovascularization, and corneal lymphangiogenesis were compared among the sorafenib, dexamethasone, dimethyl sulfoxide (DMSO), and phosphate buffered saline (PBS) groups following subconjunctival injection in mice that underwent high risk penetrating keratoplasty (HRPK). Real-time polymerase chain reaction was performed to quantify the expression of inflammatory cytokines and vascular endothelial growth factor (VEGF)-A, VEGF-C, vascular endothelial growth factor receptor (VEGFR)-2, VEGFR-3. RESULTS: The two-month graft survival rate for HRPK was 42.86% in sorafenib group, 37.50% in dexamethasone group, 0 in DMSO group, and 0 in PBS group. Sorafenib significantly increased graft survival compared to the DMSO and PBS group (P<0.05). The sorafenib didn’t show significant effect in decreasing neovascularization compared with dexamethsone, DMSO, and PBS group. The sorafenib showed less total lymphangiogenesis than the dexamethasone, DMSO, and PBS group (P=0.011, P<0.001, P<0.001, respectively). The sorafenib group showed reduced expression of VEGF-C, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, VEGFR-2 and VEGFR-3 compared with DMSO group and PBS group (all P<0.05). The sorafenib group didn’t show difference in the expression of VEGF-A compared with DMSO, neither with PBS. The sorafenib group showed reduced expression of VEGFR-3 compared with dexamethasone (P=0.051). CONCLUSION: The subconjunctivally administered sorafenib shows significant anti-lymphangiogenic effect, resulting in increased transplant survival in a murine high risk keratoplasty model. We suggest that a close linkage between decreased VEGF-C/VEGFR-2 and -3 signaling and increased corneal graft survival by sorafenib seems to exist.

Abstract:AIM: To investigate the changes in vitreous gel structure after lens extirpation combined with anterior vitrectomy in rabbit eyes. METHODS: Twenty-eight chinchilla rabbits were divided into three groups. The control group (Group I) included 16 eyes from eight rabbits who did not receive any treatment. Group II included 20 eyes from 10 rabbits that underwent lens aspiration only. Group III included 20 eyes from 10 rabbits that underwent lens aspiration combined with posterior capsulotomy and anterior vitrectomy. Eyes were harvested on the 30th and 60th day postoperatively, respectively. Changes in vitreous gel stretch length due to gravity and the rate of vitreous liquefaction were observed. The collagen content in the vitreous body was examined using the L-hydroxyproline test. Electronic microscopic images were obtained from each eyeball. RESULTS: On both the 30th and 60th day postoperatively, the vitreous gel length of group III was significantly shorter than group I and group II (P<0.05), while the rate of liquefaction of the vitreous body in group III was significantly higher than group I and group II (P<0.05). The collagen content in group III was also higher than that in group I and group II (P<0.05). CONCLUSION: Loss of vitreous gel mass is more likely to occur in the eyes of rabbits receiving anterior vitrectomy. Lensectomy combined with anterior vitrectomy may damage the stable three-dimensional mesh structure of collagen, which could aggravate vitreous gel liquefaction.

Abstract:AIM: To describe a Chinese family affected by a severe form of Axenfeld-Rieger syndrome (ARS) and characterize the molecular defect in PITX2 in the family. METHODS: Patients presented with typical ARS from a Chinese family were investigated. We performed genome-wide linkage scan and exome sequencing to identify the pathogenic mutations. Candidate mutations were verified for co-segregation in the whole pedigree using Sanger sequencing. Real-time polymerase chain reaction (RT-PCR) and Western blotting were performed to verify the expression of the pathogenic gene. RESULTS: Genome-wide linkage and exome sequencing analyses showed PITX2 as the disease candidate gene. A>G substitution at position -11 of 3’ss of exon 5 (IVS5-11A>G) that co-segregated with the disease phenotype was discovered in the family. The PITX2 messenger ribonucleic acid and protein levels were about 50% lower in patients with ARS than in unaffected family members in the family. CONCLUSION: Our findings implicate the first intronic mutation of the PITX2 gene in the pathogenesis of a severe form of ARS in a Chinese family. This study highlights the importance of a systematic search for intronic mutation in ARS cases for which no mutations in the exons of PITX2 have been found.

Abstract:AIM: To explore if ischemic preconditioning (IPC) can enhance the survival of retinal ganglion cells (RGCs) after optic nerve axotomy. METHODS: Twenty-four hours prior to retinal ischemia 60min or axotomy, IPC was applied for ten minutes in groups of (n=72) animals. The survival of RGCs, the cellular expression of heat shock protein 27 (HSP27) and heat shock protein 70 (HSP70) and the numbers of retinal microglia in the different groups were quantified at 7 and 14d post-injury. The cellular expression of HSP27 and HSP70 and changes in the numbers of retinal microglia were quantified to detect the possible mechanism of the protection of the IPC. RESULTS: Ten minutes of IPC promoted RGC survival in both the optic nerve injury (IPC-ONT) and the retinal ischemia 60min (IPC-IR60) groups, examined at 7d and 14d post-injury. Microglial proliferation showed little correlation with the extent of benefit effects of IPC on the rescue of RGCs. The number of HSP27-positive RGCs was significantly higher in the IPC-ONT group than in the sham IPC-ONT group, although the percentage of HSP27-positive RGCs did not significantly differ between groups. For the IPC-IR60 group, neither the number nor the percentage of the HSP27-positive RGCs differed significantly between the IPC and the sham-operated groups. The number of HSP70-positive RGCs was significantly higher for both the IPC-ONT and the IPC-IR60 experimental groups, but the percentages did not differ. CONCLUSION: The induction of IPC enhances the survival of RGCs against both axotomy and retinal ischemia.

Abstract:AIM: To investigate the role of CCR7/p-ERK1/2/VEGF signaling in the mouse model of oxygen-induced retinopathy (OIR). METHODS: Neonatal C57BL/6J mice were evenly randomized into four groups: normoxia, OIR, OIR control (treated with scramble siRNA), and OIR treated (treated with CCR7 siRNA). Normoxia group was not specially handled. Postnatal day 7 (P7) mice in the OIR group were exposed to 75%±5% oxygen for 5d (P7-P12) and then maintained under normoxic conditions for 5d (P12-P17). Mice in the OIR control and OIR treated groups were given injections of scramble or CCR7 siRNA plasmid on P12 before returning to normoxic conditions for 5d (P12-P17). Retina samples were collected from all mice on P17, stained with adenosine diphosphatase (ADPase), and retinal neovascularization (RNV) was assessed. Retinas were also stained with hematoxylin and eosin (H&E) for RNV quantitation. The distribution and expression of CCR7, p-ERK1/2 and vascular endothelial growth factor (VEGF) were assessed via immunohistochemistry, Western blot, and quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: High oxygen promoted retinal neovascularization (P<0.05) and increased the number of endothelial nuclei in new vessels extending from the retina to the vitreous body; CCR7 promoted this process (P<0.05). CCR7 and VEGF mRNA were expressed at higher levels in the OIR and OIR control groups than in the normoxia and OIR treated groups. CCR7, p-ERK1/2, and VEGF protein were expressed in the retinas of mice in the OIR and OIR control groups. Intravitreal injection of CCR7 siRNA significantly reduced CCR7, p-ERK1/2, and VEGF expression in the OIR mouse model (all P<0.05). CCR7 significantly enhanced the neovascularization and non-perfusion areas in the OIR group (P<0.05). CCR7 siRNA significantly reduced levels of p-ERK1/2 and VEGF as compared to OIR controls (P<0.05). CONCLUSION: These results suggest that CCR7/p-ERK 1/2/VEGF signaling plays an important role in OIR. CCR7 may be a potential target for the prevention and treatment of retinopathy of prematurity.

Abstract:AIM: To observe the attenuation of ethanol extract of Herba Scutellaria barbata (SE) against diabetic retinopathy (DR) and its engaged mechanism. METHODS: C57BL/6J mice were intraperitoneally injected with streptozotocin (STZ, 55 mg/kg) for 5 consecutive days to induce diabetes. The diabetic mice were orally given with SE (100, 200 mg/kg) for 1mo at 1mo after STZ injection. Blood-retinal barrier (BRB) breakdown was detected by using Evans blue permeation assay. Real-time polymerase chain reaction (RT-PCR), Western blot and immunofluorescence staining were used to detect mRNA and protein expression. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum contents of tumor necrosis factor-α (TNF-α) and interleukin (IL)-1β. RESULTS: SE (100, 200 mg/kg) reversed the breakdown of BRB in STZ-induced diabetic mice. The decreased expression of retinal claudin-1 and claudin-19, which are both tight junction (TJ) proteins, was reversed by SE. SE decreased the increased serum contents and retinal mRNA expression of TNF-α and IL-1β. SE also decreased the increased retinal expression of intercellular cell adhesion molecule-1 (ICAM-1). SE reduced the increased phosphorylation of nuclear factor kappa B (NFκB) p65 and its subsequent nuclear translocation in retinas from STZ-induced diabetic mice. Results of Western blot and retinal immunofluorescence staining of ionized calcium-binding adapter molecule 1 (Iba1) demonstrated that SE abrogated the activation of microglia cells in STZ-induced diabetic mice. CONCLUSION: SE attenuates the development of DR by inhibiting retinal inflammation and restoring the decreased expression of TJ proteins including claudin-1 and claudin-19.

Abstract:AIM: To identify the underlying cellular and molecular changes in retinitis pigmentosa (RP). METHODS: Label-free quantification-based proteomics analysis, with its advantages of being more economic and consisting of simpler procedures, has been used with increasing frequency in modern biological research. Dystrophic RCS rats, the first laboratory animal model for the study of RP, possess a similar pathological course as human beings with the diseases. Thus, we employed a comparative proteomics analysis approach for in-depth proteome profiling of retinas from dystrophic RCS rats and non-dystrophic congenic controls through Linear Trap Quadrupole - orbitrap MS/MS, to identify the significant differentially expressed proteins (DEPs). Bioinformatics analyses, including Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation and upstream regulatory analysis, were then performed on these retina proteins. Finally, a Western blotting experiment was carried out to verify the difference in the abundance of transcript factor E2F1. RESULTS: In this study, we identified a total of 2375 protein groups from the retinal protein samples of RCS rats and non-dystrophic congenic controls. Four hundred thirty-four significantly DEPs were selected by Student’s t-test. Based on the results of the bioinformatics analysis, we identified mitochondrial dysfunction and transcription factor E2F1 as the key initiation factors in early retinal degenerative process. CONCLUSION: We showed that the mitochondrial dysfunction and the transcription factor E2F1 substantially contribute to the disease etiology of RP. The results provide a new potential therapeutic approach for this retinal degenerative disease.

Abstract:AIM: To evaluate the therapeutic effect of fluorofenidone on disrupted blood-retinal barrier in the diabetic mice and uncover its underlying mechanism. METHODS: db/db mice were randomly chosen for treatment with daily doses of fluorofenidone or placebo at 5-week-old, treatment continued until mice reach 24-week-old. Then, expression of transcriptiona factor insulin gene enhancer binding protein-1 (Islet-1) and vascular endothelial growth factor (VEGF) in murine retinas were evaluated. Retinal vascular permeability was assessed by examining the level of albumin in db/db murine retinas. Furthermore, the retinal vessel tight junction was estimated by checking the level of occludin in the murine retinal tissues. RESULTS: After occurrence of diabetic retinopthy in db/db mice, expressions of transcritpional factor Islet-1 was found to be upregulated in db/db murine retinas compared with non-diabetic controls. Similar to expression pattern of Islet-1, VEGF were also demonstrated to be increased in retinas of db/db mice, which was accompanied by increased retinal vascular leakage and decreased tight junction protein level. Systemetic administration of fluorofenidone repaired broken retinal vascular tight junction by restoring occludin expression in db/db retinal tissue. Consequently, retinal vascular premeability were indicated to be reduced by examining the transudative albumin level in diabetic retinal tissues. Both Islet-1 and VEGF expression were inhibited in the retinas of db/db mice after treatment with fluorofenidone. CONCLUSION: Fluorofenidone significantly protectes retinal tight junction and reduces retinal vascular leakage. The phenomenon can be partially attributed to reducing overexpression of Islet-1 and VEGF in diabetic retinal tissues.

Abstract:AIM: To investigate the effect of angiotensin II type 1 receptor blocker (ARB) and angiotensin converting enzyme inhibitor (ACEI) on intraocular growth factors and their receptors in streptozotocin-induced diabetic rats. METHODS: Forty Sprague-Dawley rats were divided into 4 groups: control, diabetes mellitus (DM), candesartan-treated DM, and enalapril-treated DM (each group, n=10). After the induction of DM by streptozotocin, candesartan [ARB, 5 mg/(kg·d)] and enalapril [ACEI, 10 mg/(kg·d)] were administered to rats orally for 4wk. Vascular endothelial growth factor (VEGF) and angiotensin II (Ang II) concentrations in the vitreous were measured using enzyme-linked immunosorbent assays, and VEGF receptor 2 and angiotensin II type 1 receptor (AT1R) levels were assessed at week 4 by Western blotting. RESULTS: Vitreous Ang II levels were significantly higher in the DM group and candesartan-treated DM group than in the control (P=0.04 and 0.005, respectively). Vitreous AT1R increased significantly in DM compared to the other three groups (P<0.007). Candesartan-treated DM rats showed higher vitreal AT1R concentration than the enalapril-treated DM group and control (P<0.001 and P=0.005, respectively). No difference in vitreous Ang II and AT1R concentration was found between the enalapril-treated DM group and control. VEGF and its receptor were below the minimum detection limit in all 4 groups. CONCLUSION: Increased Ang II and AT1R in the hyperglycemic state indicate activated the intraocular renin-angiotensin system, which is inhibited more effectively by systemic ACEI than systemic ARB.

Abstract:AIM: To investigate the epidemiology and surgical outcomes of old canalicular laceration and analyze the variables impacting on the prognosis of reparation. METHODS: A retrospective review of all old canalicular laceration repairs from Jan. 1, 2008 to Dec. 30, 2015 was performed. Analyzed data included demographics, mechanisms of injury, the time from injury to repair, causes for delayed repair, old associated injuries, the types of surgery, and the effects of repair using canaliculus anastomosis combined with bicanalicular stent intubation. RESULTS: Totally 148 patients with old canalicular laceration received surgical repair and were enrolled. The mean age at presentation was 32.52 years old (ranged from 3 to 63 years old). The 110 patients (74.32%) were male and 127 patients (85.81%) were adults (≥18 years old). The old upper, lower, and bicanalicular lacerations were found in 5 (3.38%), 39 (26.35%), and 104 patients (70.27%), respectively. The mechanism of old injury was primarily due to motor vehicle accidents (n=53, 35.81%). The mean time from injury to repair was 43.61mo (ranged from 1 to 360mo). Associated old ocular and orbit injuries were found in 65 patients (43.92%), and chronic dacryocystitis in 18 patients (12.16%). The main cause of delayed repair was that doctors or patients didn’t pay attention to the canalicular laceration because of the concurrent severe injuries (n=71, 47.97%). Totally 136 patients (91.89%) with old canalicular laceration underwent canaliculus anastomosis combined with bicanalicular stent intubation. In all of them, 20 patients (13.51%) were combined with dacryocystorhinostomy. In these cases, 132 patients (97.06%) attained anatomic success, 121 patients (88.97%) reported no epiphora (functional success), 11 patients (8.09%) reported significant epiphora anesis (functional improvement), and 4 (2.94%) reported no significant anesis (functional failure). Rates of anatomic success and functional success were significantly correlated with different canaliculus involved. However, rates of anatomic success and functional success were not significantly affected by the time from injury to repair. CONCLUSION: The canalicular anastomosis combined with bicanalicular stent intubation could act as an effective therapeutics for old canalicular laceration.

Abstract:AIM: To analyze the concentration-dependent effects of autologous serum (AS) and fetal bovine serum (FBS) on human corneal epithelial cell (HCEC) viability, migration and proliferation. METHODS: AS was prepared from 13 patients with non-healing epithelial defects Dulbecco's modified eagle medium/Ham’s F12 (DMEM/F12) with 5% FBS, 0.5% dimethyl sulphoxide (DMSO), 10 ng/mL human epidermal growth factor, 1% insulin-transferrin-selenium, then were incubated in serum media: DMEM/F12 supplemented by 5%, 10%, 15% or 30% AS or FBS. HCEC viability was analyzed using cell proliferation kit XTT, migration using a wound healing assay, proliferation by the cell proliferation enzyme-linked immunosorbent assay (ELISA) BrdU kit. Statistical analysis was performed using the generalized linear model, the values at 30% AS or 30% FBS were used as the baselines. RESULTS: HCEC viability was the highest at 30% AS or 15% FBS and the lowest at 10% AS or 30% FBS application. HCEC migration was the quickest through 30% AS or 30% FBS and the slowest through 5% AS or 5% FBS concentrations. Proliferation was the most increased through 15% AS or 5% FBS and the least increased through 30% AS or 30% FBS concentrations. HCEC viability at 10% and 15% AS was significantly worse (P=0.001, P=0.023) compared to baseline and significantly better at 15% FBS (P=0.003) concentrations. HCEC migration was significantly worse (P≤0.007) and HCEC proliferation significantly better (P<0.001) in all concentration groups compared to baseline. CONCLUSION: For the best viability of HCEC 30% AS or 15% FBS, for HCEC migration 30% AS or 30% FBS, for proliferation 15% AS or 5% FBS should be used. Therefore, we suggest the use of 30% AS in clinical practice.

Abstract:AIM: To evaluate the impact of spherical and aspherical intraocular lenses on the postoperative visual quality of age-related cataract patients using Optical Quality Analysis System (OQAS). METHODS: Seventy-four eyes with age-related cataracts were randomly divided into spherical and aspherical lens implantation groups. Best-corrected visual acuity (BCVA) was measured preoperatively, one day, one week, two weeks, one month and two months after surgery. A biometric systems analysis using the OQAS objective scattering index (OSI) was performed. RESULTS: There were no significant differences in visual acuity (P>0.05) before and after spherical and aspheric lens implantation. There was a negative linear correction between the OSI value and BCVA (r=-0.634, P=0.000), and positive corrections between the OSI value and the lens LOCUS III value of nucleus color (NC), nucleus opacity (NO), cortex (C) and posterior lens capsular (P) (r=0.704, P=0.000; r=0.514, P=0.000; r=0.276, P=0.020; r=0.417, P=0.000, respectively). OSI values of spherical vs aspherical lenses were 11.5±3.6 vs 11.8±3.4, 4.1±0.9 vs 3.3±0.8, 3.5±0.9 vs 2.7±0.7, 3.3±0.8 vs 2.6±0.7, 3.2±0.7 vs 2.5±0.8, and 3.2±0.8 vs 2.5±0.8 before and 1d, 1, 2wk, 1 and 2mo after surgery, respectively. All time points varied significantly (P<0.01) between the two groups. CONCLUSION: Aspherical IOLs does not significantly affect visual acuity compared with spherical IOLs. The OSI value, was significantly lower in the aspherical lens group compared with the spherical lens. This study shows that objective visual quality of aspheric IOLs is better than that of the spherical lens by means of OQAS biological measurement method.

Abstract:AIM: To evaluate the long-term outcome of viscocanalostomy combined with trabeculotomy and mitomycin C in the treatment of primary congenital glaucoma. METHODS: This is a retrospective study. Forty-two eyes of 26 patients with primary congenital glaucoma were enrolled. Intraocular pressure (IOP), corneal diameter (mm) and cup/disc (C/D) were measured before and after the surgery respectively. Follow-up period was 30mo. RESULTS: The mean preoperative IOP was 30.6±7.35 mm Hg. Of the 42 eyes, 2 eyes were required conversion to trabeculectomy for the absence of Schlemm’s canal. Of remained 40 eyes, 38 eyes (95%) achieved successful IOP control. The average postoperative IOP was 11.69±4.18 mm Hg at 12mo. The mean reduction was 18.91 mm Hg (P<0.0001). Eighteen (75%) eyes presented a reduction in corneal diameter, and 25 (62.5%) eyes presented a C/D ratio reversal after the surgery. There was no serious complication in any patients over the follow-up period. CONCLUSION: Viscocanalostomy combined with trabeculotomy and mitomycin C is useful in the management of primary congenital glaucoma.

Abstract:AIM: To analyze cytokines as biomarkers for evaluation of severity of glaucoma. METHODS: This was a prospective case-control study including 29 eyes with glaucoma. Besides, 28 eyes with senile cataract were used as control. Patients were classified into four groups: acute angle closure glaucoma (AACG), chronic angle closure glaucoma (CACG), primary open angle glaucoma (POAG) and senile cataract. Undiluted vitreous samples were collected, then vitreous concentrations of 9 types of cytokines were determined by cytometric bead assay system: γ-interferon (IFNg), interleukin (IL)-10, IL-2, IL-4, IL-5, interferon-γ-inducible protein (IP)-10, monocyte chemoattractant protein (MCP)-1, tumor necrosis factor (TNF) -α, and vascular endothelial growth factor (VEGF). We also recorded the intraocular pressure (IOP) of patients in each group and Pearson correlated analysis was performed to analysis the correlation between each type of cytokine with IOP. RESULTS: Vitreous levels of IL-2, IL-5, MCP-1, TNF-α and IP-10 were significantly higher (P<0.05) in AACG group. Patients with AACG, CACG and POAG have higher IOP than senile cataract, but we didn’t find any significant correlation between IOP with any type of the cytokines. CONCLUSION: Inflammation and immune reaction have a strong link with the pathology of glaucoma especially AACG. Some cytokines may act as biomarkers to evaluate the severity of glaucoma. Anti-inflammatory treatments and controlling of IOP are necessary for the therapy of glaucoma.

Abstract:AIM: To evaluate ocular surface changes and its correlation with the central corneal subbasal nerve fibre layer in chronic glaucoma patients. METHODS: A prospective comparative study of ocular surface evaluation was performed in 50 eyes of 25 patients using two or more antiglaucoma medications for at least 6mo and 50 eyes of 25 normal subjects without any ocular problems as controls. The study parameters evaluated included visual acuity, intraocular pressure, ocular surface evaluation parameters [fluorescein break-up time (FTBUT), Schirmer’s I test, ocular surface staining scores and ocular surface disease index score (OSDI)], central corneal sensation (Cochet Bonnett aesthesiometer), central subbasal nerve fiber layer density (SBNFLD) by confocal microscopy. RESULTS: The mean values in the glaucoma cases and control groups respectively were as follows: OSDI score (35.89±16.07/6.02±3.84; P=0.001), Schirmer’s I test score (7.63±2.64 mm/12.86±1.93 mm; P=0.001), FTBUT (9.44±2.76s/11.8±1.88s; P=0.001), corneal (5.7±2.33/ 1.1±0.58; P=0.001) and conjunctival staining score (5.06±1.94/0.84±0.46; P=0.001), corneal sensitivity (4.68±0.44/5.07±0.37; P=0.076), mean subbasal nerve fiber number (3.58±0.99/5.40±1.70; P=0.001), SBNFL length (1101.44±287.56 μm/1963.70±562.56 μm; P=0.001) and density (6883.94±1798.03 μm/mm2/12 273.15±3516.04 μm/mm2; P=0.001). Dry eye severity of level 2 and 3 was seen in 66% of glaucoma group. Corneal (R2=0.86) and conjunctival staining (R2=0.71) and OSDI score (R2=0.67) showed statistically significant negative correlation with central corneal SBNFLD while FTBUT (R2=0.84), corneal sensitivity (R2=0.52) showed positive correlation to central corneal SBNFLD in the long term topical antiglaucoma medication group. CONCLUSION: Ocular surface changes and antiglaucoma therapy induced dry eye is found to be associated with decreased SBNFLD in eyes on long term topical antiglaucoma medications.

Abstract:AIM: To find new biomarkers for uveal melanoma (UM) by analyzing the serum peptidome profile. METHODS: Proteomic spectra in patients with UM before and after operation were analyzed and compared with those of healthy controls. Magnetic affinity beads were used to capture serum peptides and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometer were used to compile serum peptide profiles. RESULTS: A panel of 49 peptides were differentially expressed between UM patients and controls, of which 33 peptides were of higher intensities in patient group and 16 peptides were of higher intensities in control group. Based on combined use of these potential markers, peptides with mean molecular masses of 1467 and 9289.0 Da provide high sensitivity (83.3%), specificity (100%) and accuracy rate (93.0%) together to differentiate melanoma patients from healthy controls. At the time point of 6mo postoperatively, the levels of many peptides differentially expressed before surgery showed no more statistical difference between the patients and the control group. Fibrinogen α-chain precursors were identified as potential UM markers. CONCLUSION: We have shown that a convenient and fast proteomic technique, affinity bead separation and MALDI-TOF analysis combined with bioinformatic software, facilitates the identification of novel biomarkers for UM.

Abstract:AIM: To assess the frequency and associated risk factors of diabetic retinopathy among Sudanese individuals with diabetes attending Makka Eye complex in Khartoum, Sudan. METHODS: The cross sectional hospital based study recruited 316 individuals with diabetes from Makkah Eye Complex Retina Clinic. Standard questionnaire was used to collect demographic data, medical history and life style characteristics. Blood samples were taken to measure HbA1c and lipid profile. Fundus and slit lamp examination were performed for screening of diabetic retinopathy. RESULTS: Among 316 participants, 187 (59.2%) were males and 129 (40.8%) were females. The mean age of participants was 58.7±10.5y. The overall frequency of retinopathy was 261 (82.6%). The percentages of the total participants with proliferative diabetic retinopathy (PDR) were 126 (39.9%) and non-proliferative diabetic retinopathy (NPDR) were 135 (42.7%). Importantly, duration of diabetes mellitus (DM) (72.2% of more than 10y), being on oral hypoglycaemic drugs (versus insulin), and hypertension were all significant risk factors for diabetic retinopathy (P=0.00, 0.01 and 0.00 respectively). Complications of diabetes like diabetic foot (17.7%), history of amputation (6.7%) and clinically significant macular edema (CSME) (47.4%) of the eyes were all significant risk factors (P<0.05). Logistic regression analysis showed that duration of diabetes, hypertension and CSME were found to be absolute risk factors (P=0.007, 0.003 and 0.000 respectively). Duration of DM of more than 10y have more than double risk (OR=2.8), while having hypertension triples the risk of retinopathy (OR=3.1). CONCLUSION: High rates of diabetic retinopathy are noted among individuals with diabetes attending Makkah Eye hospital in capital Khartoum. Urgent strategies are needed to monitor and treat hypertension and optimize diabetes control in individuals with diabetes. More investment in diabetes services is urgently needed.

Abstract:AIM: To investigate the potential effect that odd and even-order monochromatic aberrations may have on the accommodation response of the human eye. METHODS: Eight healthy subjects with astigmatism below 1 D, best corrected visual acuity 20/20 or better and normal findings in an ophthalmic examination were enrolled. An adaptive optics system was used in order to measure the accommodation response of the subjects’ eyes under different conditions: with the natural aberrations being present, and with the odd and even-order aberrations being corrected. Three measurements of accommodation response were monocularly acquired at accommodation demands ranging from 0 to 4 D (0.5 D step). RESULTS: The accommodative lag was greater for the accommodative demands of 1.5, 3, 3.5 and 4 D for the condition in which the even-order aberrations were corrected, in comparison to that obtained for the natural aberrations and corrected odd-order aberrations for the same accommodation demands. No statistically significant differences were found between the accommodation responses under the three conditions. CONCLUSION: The odd and even-order aberrations are not helping the visual system to accommodate, because their partial correction do not affect the accommodation performance.

Abstract:AIM: To determine which IIRC scheme was used by retinoblastoma centers worldwide and the percentage of D eyes treated primarily with enucleation versus globe salvaging therapies as well as to correlate trends in treatment choice to IIRC version used and geographic region. METHODS: An anonymized electronic survey was offered to 115 physicians at 39 retinoblastoma centers worldwide asking about IIRC classification schemes and treatment patterns used between 2008 and 2012. Participants were asked to record which version of the IIRC was used for classification, how many group D eyes were diagnosed, and how many eyes were treated with enucleation versus globe salvaging therapies. Averages of eyes per treatment modality were calculated and stratified by both IIRC version and geographic region. Statistical significance was determined by Chi-square, ANOVA and Kruskal-Wallis tests using Prism. RESULTS: The survey was completed by 29% of physicians invited to participate. Totally 1807 D eyes were diagnosed. Regarding IIRC system, 27% of centers used the Children’s Hospital of Los Angeles (CHLA) version, 33% used the Children’s Oncology Group (COG) version, 23% used the Philadelphia version, and 17% were unsure. The rate for primary enucleation varied between 0 and 100% and the mean was 29%. By IIRC version, primary enucleation rates were: Philadelphia, 8%; COG, 34%; and CHLA, 37%. By geographic region, primary enucleation rates were: Latin America, 57%; Asia, 40%; Europe, 36%; Africa, 10%, US, 8%; and Middle East, 8%. However, systemic chemoreduction was used more often than enucleation in all regions except Latin America with a mean of 57% per center (P<0.0001). CONCLUSION: Worldwide there is no consensus on which IIRC version is used, systemic chemoreduction was the most frequently used initial treatment during the study period followed by enucleation and primary treatment modality, especially enucleation, varied greatly with regards to IIRC version used and geographic region.

Abstract:AIM: To develop a critical pathway for primary open angle glaucoma (POAG) diagnosis intended to be efficient, to unify criteria, reduce resource use and minimize costs to the health system. METHODS: We performed a systematic search on PubMed, Cochrane, Embase and ClinicalTrials.org databases and classified the quality of evidence from level I through III. RESULTS: A critical pathway was designed by setting a key-decision step by step model on the basis of the best current evidence. CONCLUSION: A critical pathway, evidence-based guideline, may be a useful tool intended to reduce costs while maintaining or even improving the quality of care for diagnosing a highly prevalent pathology such as open angle glaucoma.

Abstract:Pterygium is a common ocular surface disease induced by a variety of factors. The exact pathogenesis of pterygium remains unclear. Numbers of genes and proteins are discovered in pterygium and they function differently in the occurrence and development of this disease. We searched the Web of Science and PubMed throughout history for literatures about the subject. The keywords we used contain pterygium, gene, protein, angiogenesis, fibrosis, proliferation, inflammation, pathogenesis and therapy. In this review, we summarize the aberrant expression of a range of genes and proteins in pterygium compared with normal conjunctiva or cornea, including growth factors, matrix metalloproteinases and tissue inhibitors of metalloproteinases, interleukins, tumor suppressor genes, proliferation related proteins, apoptosis related proteins, cell adhesion molecules, extracellular matrix proteins, heat shock proteins and tight junction proteins. We illustrate their possible mechanisms in the pathogenesis of pterygium as well as the related intervention based on them for pterygium therapy.

Abstract:In this review, we summarize the progression of several parameters assessed by spectral-domain optical coherence tomography (SD-OCT) in recent years for the detection of glaucoma. Monitoring the progression of defects in the retinal nerve fiber layer (RNFL) thickness is essential. Imaging and analysis of retinal ganglion cells (RGCs) and inner plexiform layer (IPL), respectively, have been of great importance. Optic nerve head (ONH) topography obtained from 3D SD-OCT images is another crucial step. Other important assessments involve locating the Bruch’s membrane opening (BMO), estimating the optic disc size and rim area, and measuring the lamina cribrosa displacement. Still other parameters found in the past three years for glaucoma diagnosis comprise central retinal artery resistive index, optic disc perfusion in optical coherence tomography angiography (OCTA) study, peripapillary choroidal thickness, and choroidal area in SD-OCT. Recently, several more ocular fundus parameters have been found, and compared with the earlier parameters to judge the accuracy of diagnosis. While a few of these parameters have been widely used in clinical practice, a fair number are still in the experimental stage.

Abstract:A systematic review of the recent literature regarding pseudophakic monovision as a reliable methods for presbyopia correction was performed based on the PubMed, MEDLINE, Nature and the American Academy of Ophthalmology databases in July 2015 and data from 18 descriptive and 12 comparative studies were included in this narrative review. Pseudophakic monosvision seems to be an effective method for presbyopia with high rates of spectacles independence and minimal dysphotopsia side-effects, that should be considered by the modern cataract surgeons.

Abstract:In the majority of countries, there is a shortage of donor corneas for corneal transplantations. This study investigated the impact of organ transplantation scandals on corneal donation rate at the University Hospital Tübingen. Each deceased patient was considered as a potential corneal donor. An ophthalmic resident handled with stable methods of procedures the corneal donor procurement from 2009 to 2015. The rates of corneal donation were examined and analyzed. Among the 5712 hospital deaths, consent for corneal donation was obtained in 711 cases. The mean annual corneal donation rate was 12.4%. Since 2009, the donation rate per year could be increased with exception of 2013 and 2015. In the end of 2012 and 2014 two huge organ donation scandals were known in Germany. In the following years 2013 and 2015 corneal donation rate decreased significantly (P=0.0181 and P=0.0006). We concluded that transplantation scandals have a significant impact on corneal donation rate. Improving professional's performance through full transparency and honesty is very important to earn trust of potential donors and their families.

Abstract:To compare surgically induced astigmatism (SIA) of different surgeons, who perform the same main incision. Two hundred and seventy eyes underwent cataract surgery with phacoemulsification by four different surgeons (A, B, C, and D). A 3-step, 3.0 mm, superotemporal for the right eye and superonasal for the left eye clear corneal incision was performed. A comparison in SIA among A, B, C and D surgeon was made. No significant difference was found in SIA at both first and sixth postoperative month between different surgeons (P>0.05). SIA is more dependent on incisional characteristics and preoperative astigmatism and less on the surgeon.

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