Volume 11,Issue 6,2018 Table of Contents

1 A preliminary study on the establishment of an animal model of conjunctivochalasis

Jing-Yun Gan , Qing-Song Li , Huan-Ming Zhou , Wei Zhang , Ling-Zhi Lian , Zhang Yu , Zhen-Yong Zhang

2018, 11(6):899-904. DOI: 10.18240/ijo.2018.06.01

[Abstract](1819) [HTML](256) [PDF 2.51 M](636)

Abstract:
AIM: To explore a feasible method on the establishment of an animal model of conjunctivochalasis (CCH). METHODS: Twelve clean-grade New Zealand white rabbits were divided into four groups (n=3/group): the control group (one received no interventions, and the others underwent subconjunctival injection of sterile water), the matrix metalloproteinases (MMPs) group (administered subconjunctival injection of MMP-3), the aging group (administered subcutaneous injection of D-galactose), the tumor necrosis factor-α (TNF-α) solution group (administered eye drops of TNF-α). Anterior segment photography, conjunctival tissue light microscopy and transmission electron microscopy (TEM) were performed after 12wk. RESULTS: Among all groups, the MMPs group had the following changes: the looser connection between the inferior bulbar conjunctiva and sclera; the more disordered collagen fibers (Trichrome staining) and the broken elastic fibers (Aldehyde-fuchsin staining); the focal necrosis of fibroblasts (TEM). CONCLUSION: Administration of MMPs may be a feasible method for the establishment of an animal model of CCH.

2 Regulation of lipoxygenase-1 and Dectin-1 on interleukin-10 in mouse Aspergillus fumigatus keratitis

Cheng-Ye Che , Ke-Lan Yuan , Gui-Qiu Zhao , Cui Li , Jing Lin , Guo-Qiang Zhu , Min Liu

2018, 11(6):905-909. DOI: 10.18240/ijo.2018.06.02

[Abstract](1027) [HTML](314) [PDF 630.46 K](624)

Abstract:
AIM: To investigate the regulation of lipoxygenase (LOX)-1 and Dectin-1 on interleukin-10 (IL-10) production in mice with Aspergillus fumigatus (A. fumigatus) keratitis. METHODS: The corneas of C57BL/6 mice were pretreated with LOX-1 inhibitor Poly(I) or Dectin-1 siRNA separately before the infection of A. fumigatus. Polymerase chain reaction (PCR) and Western blot were used to detect the expression of IL-10. RESULTS: The mRNA and protein expressions of IL-10 were significantly increased in mice with A. fumigatus keratitis. Compared with the group pretreated with sterile water before infection, Poly(I) pretreatment suppressed IL-10 expression significantly. Compared with the group pretreated with scrambled siRNA before infection, Dectin-1 siRNA pretreatment significantly reduced IL-10 expression in response to A. fumigatus infection. CONCLUSION: LOX-1 and Dectin-1 regulate IL-10 production in mouse A. fumigatus keratitis.

3 Bioinformatics analysis of microarray data to explore the key genes involved in HSF4 mutation-induced cataract

Rui Tian , Yang Xu , Wen-Wen Dou , Hui Zhang

2018, 11(6):910-917. DOI: 10.18240/ijo.2018.06.03

[Abstract](1887) [HTML](246) [PDF 2.69 M](611)

Abstract:
AIM: To reveal the mechanisms of heat-shock transcription factor 4 (HSF4) mutation-induced cataract. METHODS: GSE22362, including 3 HSF4-null lens and 3 wild-type lens, was obtained from Gene Expression Omnibus database. After data preprocessing, the differentially expressed genes (DEGs) were identified using the limma package. Based on Database for Annotation, Visualization and Integrated Discovery (DAVID) tool, functional and pathway enrichment analyses were performed for the DEGs. Followed by protein-protein interaction (PPI) network was constructed using STRING database and Cytoscape software. Furthermore, the validated microRNA (miRNA)-DEG pairs were obtained from miRWalk2.0 database, and then miRNA-DEG regulatory network was visualized by Cytoscape software. RESULTS: A total of 176 DEGs were identified in HSF4-null lens compared with wild-type lens. In the PPI network, FBJ osteosarcoma oncogene (FOS), early growth response 1 (EGR1) and heme oxygenase (decycling) 1 (HMOX1) had higher degrees and could interact with each other. Besides, mmu-miR-15a-5p and mmu-miR-26a-5p were among the top 10 miRNAs in the miRNA-DEG regulatory network. Additionally, mmu-miR-26a-5p could target EGR1 in the regulatory network. CONCLUSION: FOS, EGR1, HMOX1, mmu-miR-26a-5p and mmu-miR-15a-5p might function in the pathogenesis of HSF4 mutation-induced cataract.

4 Knobloch syndrome caused by homozygous frameshift mutation of the COL18A1 gene in a Chinese pedigree

Lu-Si Zhang , Hai-Bo Li , Jun Zeng , Yan Yang , Chun Ding

2018, 11(6):918-922. DOI: 10.18240/ijo.2018.06.04

[Abstract](2086) [HTML](254) [PDF 1.16 M](679)

Abstract:
AIM: To explore the clinical feature and genetic etiology of a Chinese Knobloch syndrome family. METHODS: Ocular examinations and magnetic resonance imagings (MRIs) were performed on the family. Whole exome sequencing was conducted on the two patients. Sanger sequencing was utilized to validate the presence of variation in the family as well as in 100 normal controls. Real-time quantitative polymerase chain reaction (PCR) was used to detect the expression level of COL18A1 in peripheral blood lymphocytes of the patients and normal carriers. RESULTS: The affected subjects presented with vision loss, exotropia, cataracts, retinal detachment, and other complications. A homozygous c.4759_4760delCT (p.Leu1587ValfsX72) mutation (rs398122391) in COL18A1 was identified in the two patients, cosegregating with the phenotypes, and did not be detected in 100 normal controls. This mutation caused significant decreased expression of COL18A1 mRNA in the patients. CONCLUSION: The findings strongly indicate that this mutation is the disease-causing mutation. Moreover, this is the first Knobloch syndrome pedigree reported in the Chinese population.

5 Protective effects of ciliary neurotrophic factor on the retinal ganglion cells by injure of hydrogen peroxide

Wen-Jun Wang , Wei Jin , An-Huai Yang , Zhen Chen , Yi-Qiao Xing

2018, 11(6):923-928. DOI: 10.18240/ijo.2018.06.05

[Abstract](1299) [HTML](253) [PDF 859.56 K](629)

Abstract:
AIM: To explore the effect of ciliary neurotrophic factor (CNTF) on retinal ganglion cell (RGC)-5 induced by hydrogen peroxide (H2O2). METHODS: After cell adherence, RGC-5 culture medium was changed to contain different concentrations of H2O2 from 50 to 150 μmol/L at four time points (0.5, 1, 1.5 and 2h) to select the concentration and time point for H2O2 induced model. Two different ways of interventions for injured RGC-5 cells respectively were CNTF as an addition in the culture medium or recombinant lentiviral plasmid carrying CNTF gene transfecting bone mesenchymal stem cells (BMSCs) for co-culture with RGC-5. RESULTS: Compared to the control group, H2O2 led to RGC-5 death closely associated with concentrations and action time of H2O2 and we chose 125 μmol/L and 2h to establish the H2O2-induced model. While CNTF inhibited the loss of RGC-5 cells obviously with a dose-dependent survival rate. Nevertheless two administration routes had different survival rate yet higher rate in recombinant lentiviral plasmid group but there were no statistically significant differences. CONCLUSION: Both the two administration routes of CNTF have effects on RGC-5 cells induced by H2O2. If their own advantages were combined, there may be a better administration route.

6 Effect of Aβ protein on inhibiting proliferation and promoting apoptosis of retinal pigment epithelial cells

Zi Ye , Shou-Zhi He , Zhao-Hui Li

2018, 11(6):929-934. DOI: 10.18240/ijo.2018.06.06

[Abstract](1385) [HTML](285) [PDF 1.57 M](602)

Abstract:
AIM: To identify the effect and regulatory mechanism of amyloid β (Aβ) protein on retinal pigment epithelial (RPE) cells in cell proliferation and apoptosis, and clarify Aβ role in the pathogenesis of age-related macular degeneration (AMD). METHODS: The model of Aβ25-35 protein cytotoxicity in RPE cell was successfully established to investigate the effect of Aβ protein on RPE cells in vitro. Based on Aβ protein, the specific inhibitors (HY-50682 or BAY11-7082) or activating agent (lipopolysaccharide) was used to analyze the regulatory mechanism of Aβ protein to RPE cells on cell proliferation and apoptosis by flow cytometry, real-time polymerase chain reaction, Western blotting, enzyme-linked immunosorbent assay and dual-luciferase reporter gene assay. RESULTS: The number of RPE cells, treated with Aβ25-35 from 0.3 to 60 μmol/L, significantly reduce (P<0.01), and had the dose-dependent effect. Aβ protein 60 μmol/L inhibits the G1/S phase transition (P<0.01) and down-regulated cyclin E mRNA level (P<0.01). Similarly, Aβ25-35 induced a significant increase of cell apoptosis, accompanied by the significantly higher level of activated caspase 3 protein. Furthermore, nuclear factor-kappaB (NF-κB) activity and phosphorylated Iκ-Ba level would significantly lower in treated RPE cells. Using specific inhibitors or activating agent based on the Aβ, the cell numbers, NF-κB activity, phosphorylated Iκ-Ba level, receptor for advanced glycation endproducts (RAGE) gene expression levels, cyclin E mRNA level and activated caspase 3 level had accordingly changed by different methods, confirming that RAGE/NF-κB signaling pathway involved in the regulation of Aβ protein on RPE cell apoptosis and proliferation. CONCLUSION: Aβ protein inhibits cell proliferation and activates apoptosis via inactivation of the RAGE/NF-κB signaling pathway in RPE cell.

7 Protective effects of a novel drug RC28-E blocking both VEGF and FGF2 on early diabetic rat retina

Qian-Hui Yang , Yan Zhang , Jing Jiang , Mian-Mian Wu , Qian Han , Qi-Yu Bo , Guang-Wei Yu , Yu-Sha Ru , Xun Liu , Min Huang , Ling Wang , Xiao-Min Zhang , Jian-Min Fang , Xiao-Rong Li

2018, 11(6):935-944. DOI: 10.18240/ijo.2018.06.07

[Abstract](1850) [HTML](257) [PDF 3.43 M](862)

Abstract:
AIM: To investigate protective effects of a novel recombinant decoy receptor drug RC28-E on retinal damage in early diabetic rats. METHODS: The streptozotocin (STZ)-induced diabetic rats were randomly divided into 6 groups: diabetes mellitus (DM) group (saline, 3 μL/eye); RC28-E at low (0.33 μg/μL, 3 μL), medium (1 μg/μL, 3 μL), and high (3 μg/μL, 3 μL) dose groups; vascular endothelial growth factor (VEGF) Trap group (1 μg/μL, 3 μL); fibroblast growth factor (FGF) Trap group (1 μg/μL, 3 μL). Normal control group was included. At week 1 and 4 following diabetic induction, the rats were intravitreally injected with the corresponding solutions. At week 6 following the induction, apoptosis in retinal vessels was detected by TUNEL staining. Glial fibrillary acidic protein (GFAP) expression was examined by immunofluorescence. Blood-retinal barrier (BRB) breakdown was assessed by Evans blue assay. Ultrastructural changes in choroidal and retinal vessels were analyzed by transmission electron microscopy (TEM). Content of VEGF and FGF proteins in retina was measured by enzyme linked immunosorbent assay (ELISA). The retinal expression of intercellular cell adhesion molecule-1 (ICAM-1), tumor necrosis factor-α (TNF-α), VEGF and FGF genes was examined by quantitative polymerase chain reaction (qPCR). RESULTS: TUNEL staining showed that the aberrantly increased apoptotic cells death in diabetic retinal vascular network was significantly reduced by treatments of medium and high dose RC28-E, VEGF Trap, and FGF Trap (all P<0.05), the effects of medium and high dose RC28-E or FGF Trap were greater than VEGF Trap (P<0.01). GFAP staining suggested that reactive gliosis was substantially inhibited in all RC28-E and VEGF Trap groups, but the inhibition in FGF Trap group was not as prominent. Evans blue assay demonstrated that only high dose RC28-E could significantly reduce vascular leakage in early diabetic retina (P<0.01). TEM revealed that the ultrastructures in choroidal and retinal vessels were damaged in early diabetic retina, which was ameliorated to differential extents by each drug. The expression of VEGF and FGF2 proteins was significantly upregulated in early diabetic retina, and normalized by RC28-E at all dosages and by the corresponding Traps. The upregulation of ICAM-1 and TNF-α in diabetic retina was substantially suppressed by RC28-E and positive control drugs. CONCLUSION: Dual blockade of VEGF and FGF2 by RC28-E generates remarkable protective effects, including anti-apoptosis, anti-gliosis, anti-leakage, and improving ultrastructures and proinflammatory microenvironment, in early diabetic retina, thereby supporting further development of RC28-E into a novel and effective drug to diabetic retinopathy (DR).

8 Two-year outcomes of ab interno trabeculectomy with the Trabectome for Chinese primary open angle glaucoma: a retrospective multicenter study

Ya-Long Dang , Xiao Wang , Wan-Wei Dai , Ping Huang , Nils A Loewen , Chun Zhang , China Trabectome Study Group , International Trabectome Study Group

2018, 11(6):945-950. DOI: 10.18240/ijo.2018.06.08

[Abstract](1845) [HTML](251) [PDF 341.20 K](567)

Abstract:
AIM: To evaluate the 2-year efficacy and safety of ab interno trabeculectomy with the Trabectome in Chinese primary open angle glaucoma (POAG) patients. METHODS: This was a multicenter, retrospective, observational study and included POAG patients with or without visually-significant cataracts. The Chinese patients were enrolled from three glaucoma centers and a group of comparable Japanese POAG patients was analyzed from our international Trabectome database. The patients received Trabectome or a combined surgery with phacoemulsification and intraocular lens implantation. The primary outcome was intraocular pressure (IOP) reduction. Secondary outcomes included reduction of glaucoma medications, surgical complications, and success at 2y. Success was defined as: 1) IOP≤21 mm Hg and at least 20% IOP reduction from baseline after 3mo at any two consecutive visits; 2) no additional glaucoma surgery required. RESULTS: A total of 42 Chinese POAG patients from three glaucoma centers were enrolled. Twelve patients underwent Trabectome surgery combined with phacoemulsification and intraocular lens implantation while the remainder underwent Trabectome surgery alone. Thirteen patients had a history of failed glaucoma surgery and were considered as complicated cases. In China data, the mean preoperative IOP was 21.4±1.23 mm Hg. The Trabectome lowered IOP to 17.9±1.8 mm Hg at 2y (P=0.05). The number of glaucoma medications also decreased significantly from a baseline of 2.0±0.9 to 1.1±0.8 at 2y post-surgery (P=0.04). The overall 2-year success rate was 78%, with patients undergoing combined surgery having a higher success rate compared with those undergoing Trabectome surgery alone (100% vs 76%). In Japan data, the mean preoperative IOP was 20.8±7.7 mm Hg. The Trabectome lowered IOP to 12.20±2.0 mm Hg at 2y. The number of glaucoma medications also decreased significantly from a baseline of 2.1±0.9 to 3.4±0.6 at 2y post-surgery. In all patients, no major complications were seen. CONCLUSION: Surgery with the Trabectome appears to be an efficient and safe procedure in Chinese POAG patients in the long-term.

9 A new diagnostic model of primary open angle glaucoma based on FD-OCT parameters

Ya-Jie Zheng , Ying-Zi Pan , Xue-Ying Li , Yuan Fang , Mei Li , Rong-Hua Qiao , Yu Cai

2018, 11(6):951-957. DOI: 10.18240/ijo.2018.06.09

[Abstract](1446) [HTML](237) [PDF 630.29 K](591)

Abstract:
AIM: To build a clinical diagnostic model of primary open angle glaucoma (POAG) using the normal probability chart of frequency-domain optical coherence tomography (FD-OCT). METHODS: This is a cross-sectional study. Total 133 eyes from 133 healthy subjects and 99 eyes from 99 early POAG patients were included in the study. The retinal nerve fibre layer (RNFL) thickness parameters of optic nerve head (ONH) and RNFL3.45 scan were measured in one randomly selected eye of each subject using RTVue-100 FD-OCT. Then, we used these parameters to establish the diagnostic models. Four different diagnostic models based on two different area partition strategies on ONH and RNFL3.45 parameters, including ONH traditional area partition model (ONH-T), ONH new area partition model (ONH-N), RNFL3.45 traditional area partition model (RNFL3.45-T) and RNFL3.45 new area partition model (RNFL3.45-N), were built and tested by cross-validation. RESULTS: The new area partition models had higher area under the receiver operating characteristic (AROC; ONH-N: 0.990; RNFL3.45-N: 0.939) than corresponding traditional area partition models (ONH-T: 0.979; RNFL3.45-T: 0.881). There was no statistical difference among AROC of ONH-T, ONH-N, and RNFL3.45-N. Nevertheless, ONH-N was the simplest model. CONCLUSION: The new area partition models had higher diagnostic accuracy than corresponding traditional area partition models, which can improve the diagnostic ability of early POAG. In particular, the simplest ONH-N diagnostic model may be convenient for clinical application.

10 Effect of the posterior corneal surface on total corneal astigmatism in patients with age-related cataract

Ying-Ying Jin , Zhen Zhou , Xiao-Yong Yuan , Hui Song , Xin Tang

2018, 11(6):958-965. DOI: 10.18240/ijo.2018.06.10

[Abstract](1634) [HTML](264) [PDF 1.24 M](631)

Abstract:
AIM: To explore the effect of the posterior astigmatism on total corneal astigmatism and evaluate the error caused by substituting the corneal astigmatism of the simulated keratometriy (simulated K) for the total corneal astigmatism in age-related cataract patients. METHODS: A total of 211 eyes with age-related cataract from 164 patients (mean age: 66.8±9.0y, range: 45-83y) were examined using a multi-colored spot reflection topographer, and the total corneal astigmatism was measured. The power vector components J0 and J45 were analyzed. Correlations between the magnitude difference of the simulated K and total cornea astigmatism (magnitude differenceSimK-Tca), anterior J0, and absolute meridian difference (AMD) between the anterior and posterior astigmatisms were calculated. To compare the astigmatism of the simulated K and total cornea both in magnitude and axial orientation, we drew double-angle plots and calculated the vector difference between the two measures using vector analysis. A corrective regression formula was used to adjust the magnitude of the simulated K astigmatism to approach that of the total cornea. RESULTS: The magnitude differenceSimK-Tca was positively correlated with the anterior corneal J0 (Spearman’s rho= 0.539; P<0.001) and negatively correlated with the AMDR (Spearman’s rho=-0.875, P<0.001). When the anterior J0 value was larger than 1.3 D or smaller than -0.8 D, the errors caused by determining the total corneal astigmatism with the karatometric calculation tended to be greater than 0.25 D. An underestimation by 16% was observed for against the rule (ATR) astigmatism and an overestimation by 9% was observed for with the rule (WTR) astigmatism when ignoring the posterior measurements. CONCLUSION: Posterior corneal astigmatism should be valued for more precise corneal astigmatism management, especially for higher ATR astigmatism of the anterior corneal surface. We suggest a 9% reduction in the magnitude of the simulated K in eyes with WTR astigmatism, and a 16% addition of the magnitude of the simulated K in eyes with ATR astigmatism.

11 Comparison of immersion ultrasound and low coherence reflectometry for ocular biometry in cataract patients

Yan Li , Hong-Xun Li , Yang-Chen Liu , Ya-Tu Guo , Jian-Min Gao , Bin Wu , Nan Zhang , Dong Liu , Xiao-Yong Yuan

2018, 11(6):966-969. DOI: 10.18240/ijo.2018.06.11

[Abstract](1215) [HTML](261) [PDF 810.65 K](624)

Abstract:
AIM: To compare the results of axial length (AL) biometry in cataract eyes by three methods: immersion B-ultrasound (IB) biometry, immersion A-ultrasound (IA) biometry and optical low coherence reflectometry. METHODS: In this prospective observational study of eyes with cataract AL measurements were performed using immersion ultrasound and optical low coherence reflectometry device. The results were evaluated using Bland-Altman analyses. The differences between both methods were assessed using the paired t-test, and its correlation was evaluated by Pearson coefficient. RESULTS: Eighty eyes of 80 patients (39 men and 41 women) for cataract surgery were included in the study. The values of AL could be got from all 80 eyes by IB and IA, the difference of AL measurements between IA and IB was of no statistical significance (P=0.97); the mean difference in AL measurements was -0.031 mm (P=0.26; 95%CI, -0.09 to 0.02); linear regression showed an excellent correlation (r=0.98, P<0.0001). Forty-five of eighty eyes with results of AL measurements, which can be obtained by three methods; the difference of AL measurements was of no statistical significance (IA vs IB, P=0.18; IA vs Lenstar, P=0.51; IB vs Lenstar, P=0.07); linear regression showed an excellent correlation (IA vs IB, r=0.99; IA vs Lenstar, r=0.96; IB vs Lenstar, r=0.96); Bland-Altman analysis also showed good agreement between the two methods [IA vs IB, 95% limits of agreement (LoA), -0.36 to 0.28 mm; IA vs Lenstar, 95% LoA, -0.65 to 0.69 mm; IB vs Lenstar, 95% LoA, -0.55 to 0.68 mm]. CONCLUSION: Measurements with the optical low coherence reflectometry correlated well with IB and IA. In the eyes with serious refractive medium opacity, the measurements of AL could not be achieved or existed deviations when using optical low coherence reflectometry device. Under such circumstances, we should choose IA or IB as the optimization method to obtain measurements, in order to get much more accurate results.

12 Macular pigment and serum zeaxanthin levels with Goji berry supplement in early age-related macular degeneration

Shang Li , Na Liu , Li Lin , Er-Dan Sun , Jian-Da Li , Peng-Kun Li

2018, 11(6):970-975. DOI: 10.18240/ijo.2018.06.12

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Abstract:
AIM: To evaluate the efficacy of Goji berry supplementation on improving macular pigment, serum zeaxanthin levels and visual acuity in patients with early age-related macular degeneration (AMD). METHODS: A total of 114 patients (aged from 51 to 92y, mean age 69.53±8.41y) with early AMD were enrolled in our prospective, randomized controlled study. The included patients were assigned randomly to the Goji group (n=57) with 25 g of Goji berries supplementation per day for 90d and the control group (n=57) with their normal diet for 90d. Macular pigment optical density (MPOD) was measured using heterochromatic flicker photometry (HFP). The levels of serum lutein (L)/zeaxanthin (Z) were analyzed using high-performance liquid chromatography (HPLC). MPOD, serum L/Z levels and best corrected visual acuity (BCVA) were recorded at baseline and 90d. RESULTS: In the Goji group, there were no statistically significant differences in the serum L levels between the baseline (0.199±0.149 μmol/mL) and 90d (0.203±0.181 μmol/mL) (t=-0.186, P=0.850); however the serum Z levels were increased at 90d (0.101±0.087 μmol/mL) compared with those at the baseline (0.029±0.032 μmol/mL) (t=6.412, P<0.001). Patients treated with Goji berry for 90d showed an elevated MPOD (0.877±0.202 DU) from the baseline (0.731±0.205 DU) (t=-4.741, P=0.000). In contrast to the control group, the serum Z levels and MPOD were higher in the Goji group at 90d (both P<0.05). At 90d, patients with Goji berry supplementation had a relative decrease in BCVA (0.21±0.18 logMAR) compared with the baseline (0.27±0.20) (t=2.397, P=0.020). CONCLUSION: Overall, daily supplementation with Goji berry for 90d improves MPOD by increasing serum Z levels rather than serum L levels in early AMD patients. Goji berry may be an effective therapeutic intervention for preventing the progression of early AMD.

13 The role of intravitreal ranubizumab in the treatment of familial exudative vitreoretinopathy of stage 2 or greater

Yue-Zhu Lu , Guang-Da Deng , Jing-Hua Liu , Hong Yan

2018, 11(6):976-980. DOI: 10.18240/ijo.2018.06.13

[Abstract](1574) [HTML](248) [PDF 638.58 K](723)

Abstract:
AIM: To evaluate the role of intravitreal ranubizumab (IVR) in the treatment of familial exudative vitreoretinopathy (FEVR) of stage 2 or greater either as primary or an ajunct to conventional treatments. METHODS: Retrospective, non-controlled clinical study. Thirty patients (37 eyes) diagnosed with FEVR were enrolled. Twenty patients (66.67%) were male and 10 patients (33.33%) were female. Age ranged from 0.4 to 35 years old (median 3y). IVR was used either as primary or as a combined therapy according to the retinal neovasuclar activities. The follow up ranged from 1 to 57mo with mean 16.73±15.73 (median 11)mo. The treatment effect of retinal neovasuclar activites were recorded as well as the ocular and systemic side effects. RESULTS: Among 30 patients (37 eyes), 10 eyes received single IVR, 1 eye received 2 injections. Three eyes were treated with IVR and simutanous laser photocoagulation. Laser indirect ophthalmoscopy (LIO) was applied in 5 eyes 1mo after the primary IVR. Seven eyes were treated surgically following the primary IVR due to persistent retinal neovasuclar activities and retinal traction. IVR was used as combined treatment with vitrectomy in 11 eyes. Retinal neovascular regression was notified 1mo following the primary IVR in all eyes. Neither systemic nor ocular complications were recorded. CONCLUSION: IVR may be an effective modality in the treatment of FEVR either as primary or as an ajunct to the conventional therapies. The long term effect and safty of IVR still need further research.

14 Short-term outcomes after the loading phase of intravitreal bevacizumab and subthreshold macular laser in non-center involved diabetic macular edema

Edgar Cuervo-Lozano , Jesús Hernán González-Cortés , Abraham Olvera-Barrios , Ezequiel Treviño-Cavazos , Josué Rodríguez-Pedraza , Karim Mohamed-Noriega , Jesús Mohamed-Hamsho

2018, 11(6):981-985. DOI: 10.18240/ijo.2018.06.14

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Abstract:
AIM: To compare the effectiveness of intravitreal bevacizumab and subthreshold macular photocoagulation (SMP), for the treatment of non-center involved diabetic macular edema (non-CI DME). METHODS: Prospective, randomized, controlled clinical study included patients with type 2 diabetes, non-CI DME and best-corrected visual acuity (BCVA) of 0.30 logMAR or better. Each eye was randomized into three groups: group 1, monthly intravitreal bevacizumab; group 2, single SMP; group 3, single SMP and monthly bevacizumab. Main outcome measures were BCVA, and macular thickness measured with optical coherence tomography as macular central subfield thickness (CST), macular area of greater thickness (MAGT) and total macular volume (TMV). Results were analyzed after 3mo. RESULTS: A total of 32 eyes were included. Group 3 improved in BCVA (0.19±0.16 to 0.12±0.14 logMAR; P=0.041) and in TMV (7.90±0.57 to 7.65±0.73 mm3; P=0.025). Group 1 improved in MAGT (325±26.26 to 298.20±44.85 μm; P=0.022) and TMV (7.79±0.57 to 7.50±0.56 mm3, P=0.047). Group 2 didn’t show significant improvement of any variable. CONCLUSION: The loading phase of bevacizumab as monotherapy or combined with SMP is superior to SMP as monotherapy in providing short-term visual and anatomical improvement in non-CI DME.

15 Clinical observations of vitreoretinal surgery for four different phenotypes of X-linked congenital retinoschisis

Chen Zhao , Qi Zhang , Hai-Ying Jin , Pei-Quan Zhao

2018, 11(6):986-990. DOI: 10.18240/ijo.2018.06.15

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Abstract:
AIM: To evaluate the outcomes of vitreoretinal surgery for four different phenotypes of X-linked retinoschisis (XLRS). METHODS: This study included thirty-one eyes of 25 patients who developed XLRS with severe complications. Among the 31 eyes, there were 7 eyes with vitreous hemorrhage, 8 eyes with retinal detachment and vitreous hemorrhage, and 16 eyes with rhegmatogenous retinal detachment. All of the patients underwent standard three-port pars plana vitrectomy. All of the eyes were divided into 4 groups before surgery according to a modified classification scheme, with the first three groups as follows: group A, with foveal cystic schisis; group B with macular lamellar schisis; and group C with foveolamellar changes. Peripheral schisis was not present in these 3 groups; however, group D was a complex group with both macular and peripheral changes. One year after surgery, we analyzed the best corrected visual acuity and postoperative anatomical and functional outcomes of these 4 groups. RESULTS: There were 7 eyes in group A (22.6%), 1 eye in group B (3.2%), 15 eyes in group C (48.4%) and 8 eyes in group D (25.8%). Postoperative anatomical and functional outcomes were satisfactory at the last visit, while the mean visual acuity was increased to 0.27±0.11, with a significant difference (t=-1.049, P=0.000) compared with the results before surgery (0.1±0.08). Visual acuity was improved in 23 eyes (74.2%). Complications were found in three eyes: two eyes with proliferative vitreoretinopathy and traction retinal detachment 10 and 12mo after surgery, respectively; and one eye with vitreous hemorrhage 15mo after surgery. These eyes were in groups C and D. The retinas remained attached in these 3 eyes after reoperation. CONCLUSION: We should pay greater attention to XLRS with foveolamellar changes because it is the most changeable phenotype. Once complications occur, vitreoretinal surgery can significantly improve visual acuity and restore the anatomic structure of the retina.

16 Short term effect of choroid thickness in the horizontal meridian detected by spectral domain optical coherence tomography in myopic children after orthokeratology

Wan-Qing Jin , Sheng-Hai Huang , Jun Jiang , Xin-Jie Mao , Mei-Xiao Shen , Yan Lian

2018, 11(6):991-996. DOI: 10.18240/ijo.2018.06.16

[Abstract](2400) [HTML](255) [PDF 864.52 K](673)

Abstract:
AIM: To investigate choroidal thickness changes in the horizontal meridian after orthokeratology. METHODS: This is a prospective cross-sectional observed study. Subjects (n=30; 11.3±1.7y) with low-to-moderate myopia (-1.0 to -6.0 diopters), wore orthokeratology (Ortho-K) lenses for 3mo. Before and after Ortho-K, OCT scans were made through the fovea in the horizontal meridian. Choroid thickness around the fovea was acquired by custom software. The analyzed regions along the horizontal meridian were divided into 7 equal zones. Ocular parameters were measured by Lenstar LS 900 non-contact biometry. RESULTS: Only the right eye ocular parameters were analyzed in this study. Before Ortho-K, choroidal thickness along the horizontal meridian was 273.7±31.8 μm in the temporal zone, 253.1±38.6 μm in the macula zone, and 194.8±52.2 μm in the nasal zone. After Ortho-K, the choroid was thicker in each horizontal zone (P<0.05). The increased thickness was greatest in the temporal zone (13.5±22.5 μm) and least in the nasal zone (8.4±14.2 μm). The axial length (AL) increased 0.02 mm (P>0.05). The choroid thickness change in each horizontal zone was negatively correlated with AL (r, -0.3 to -0.4; P<0.05) except one of the nasal zones. CONCLUSION: In myopic children, the thickness of the choroid is greatest in the temporal zone and thinnest in the nasal zone. After nightly Ortho-K for 3mo, the thickness increase along the horizontal meridian. The choroid thickness changes are negatively correlated with the change of AL.

17 Correlations between the optic nerve head morphology and ocular biometrics in highly myopic eyes

Xiu-Juan Zhao , Huai-Yan Jiang , Yong-Hao Li , Bing-Qian Liu , Hong-Xia Xu , Jie Zhou , Xiao-Hong Chen , Can-Can Lyu , Wei Ma , Jin Ma , Xiao-Ling Liang , Chen-Jin Jin , Xiao-Yan Ding , Lin Lu

2018, 11(6):997-1001. DOI: 10.18240/ijo.2018.06.17

[Abstract](1915) [HTML](248) [PDF 502.31 K](735)

Abstract:
AIM: To analyze peripapillary atrophy β/γ zone (PPA-β/γ) and the optic disc ovality index, and to assess their associations with the axial length (AL), refractive error, best corrected visual acuity (BCVA), choroidal thickness (CT), and age in highly myopic eyes. METHODS: This was a retrospective observational case series. The study included 667 patients consecutively examined for highly myopic eyes [spherical equivalent ≤-6.0 diopters (D) and AL≥26 mm] with or without myopic retinopathy. Each patient went through a comprehensive ophthalmological examination that included spectral domain optical coherence tomography (SD-OCT) of the macula, A-mode ultrasonography, and a cycloplegic refraction test. The ovality index and PPA-β/γ area were measured from optic disc photographs. RESULTS: A significant association was seen between PPA-β/γ area and the ovality index (P=0.000, r=-0.232). The PPA-β/γ area increased significantly with a longer AL, older age, worse BCVA, higher refractive error, and thinner choroid (P<0.01). The oval disc was significantly correlated with a longer AL, older age, worse BCVA, higher refractive error, larger PPA-β/γ area, and thinner choroid (P<0.01). CONCLUSION: The PPA-β/γ zone and ovality index in highly myopic eyes show distinct associations with the AL, refractive error, BCVA, age, and CT.

18 Aflibercept for diabetic macular oedema: a Meta-analysis of randomized controlled trials

Chu Luan Nguyen , Andrew Lindsay , Eugene Wong , Michael Chilov

2018, 11(6):1002-1008. DOI: 10.18240/ijo.2018.06.18

[Abstract](1168) [HTML](261) [PDF 1.62 M](622)

Abstract:
AIM: To evaluate the relative efficacy and safety of aflibercept for treatment of diabetic macular oedema (DMO). METHODS: A comprehensive search in MEDLINE, CENTRAL and EMBASE was undertaken for randomized controlled trials (RCTs) comparing intravitreal anti-vascular endothelial growth factor (anti-VEGF) versus another treatment. Primary outcome measures were proportion of patients with at least 15 letters of gain or loss on a logMAR visual acuity chart, and change in best corrected visual acuity (BCVA) and central macular thickness (CMT) from baseline. Safety outcomes were rates of death, thromboembolic events and any systemic or ocular serious adverse events. The final search was performed on November 2017. RESULTS: Four RCTs were included. Only one trial compared efficacy and safety of aflibercept with bevacizumab and ranibizumab over 1 or 2y. Three trials were included for Meta-analysis comprising 661 patients (331 in the aflibercept, and 330 in the photocoagulation group). Aflibercept was more efficacious compared to photocoagulation in the proportion of patients with at least 15 letters of improvement and worsening, and in improvement of BCVA and reduction in CMT at 1 or 2y. The safety estimates at 1 or 2y did not differ statistically. CONCLUSION: Aflibercept offers superior benefits over photocoagulation in improving and preserving vision, with no differences in safety. Further comparative effectiveness trials between aflibercept and other anti-VEGF agents will aid ophthalmologists in treatment decisions.

19 The J-shape association of serum total IgE levels with age-related cataract

Sangshin Park , Nam-Kyong Choi

2018, 11(6):1009-1012. DOI: 10.18240/ijo.2018.06.19

[Abstract](1616) [HTML](249) [PDF 361.78 K](595)

Abstract:
AIM: To address the association between serum total IgE levels and age-related cataract in adults. METHODS: The study participants consisted of 1052 adults aged 40y or older in the Korean National Health and Nutrition Examination Survey 2010. We performed multivariable logistic regression analyses using the quartile cut-points of total IgE levels. RESULTS: The odds ratios (ORs) for nuclear and any cataract with ≥267 kU/L of serum IgE levels were 1.75 [95% confidence intervals (CI), 1.04-2.96] and 2.00 (95%CI, 1.22-3.27), respectively, comparing to 35-87 kU/L. Interestingly, participants with ≤35 kU/L of IgE levels (OR, 1.67; 95%CI, 1.02-2.72) also had higher risk for any cataract than those with 35-87 kU/L. The risk for any cataract (OR, 1.48; 95%CI, 1.03-2.13) was higher in participants with high total IgE levels (>150 kU/L), comparing to normal participants. CONCLUSION: Our findings indicate a J-shaped relationship between serum IgE levels and age-related cataract.

20 Refractive surgery: the most cost-saving technique in refractive errors correction

Seyed-Farzad Mohammadi , Cyrus Alinia , Maryam Tavakkoli , Alireza Lashay , Hormoz Chams

2018, 11(6):1013-1019. DOI: 10.18240/ijo.2018.06.20

[Abstract](1707) [HTML](254) [PDF 303.01 K](619)

Abstract:
AIM: To compare the lifetime and annual economic burden of spectacles, contact lenses, and refractive surgery in correction of refractive errors. METHODS: This is a cross-sectional study with convenience sampling which 120 patients were interviewed in a tertiary referral hospital in the Iranian health care system. The bottom-up based cost of illness approach was estimated using a face-to-face interview to assess the direct and indirect cost of different refractive errors correction of any correction technologies. RESULTS: Correction with spectacle imposes a total direct cost of US dollar (US$) 342.5 (±8.41) per year and US$9373.5 (±230.1) per lifetime to each patient. These figures for the contact lenses were obtained US$198.3 (±0.12) and US$5203.1 (±256.3) and for refractive surgery were obtained US$19.1 (±1.2) and US$568.1 (±64.6), respectively. Overall, based on age-adjusted prevalence rates, astigmatism had the highest share of refractive errors economic burden with a lifetime direct cost of slightly less than US$5.49 billion, while hyperopia and myopia imposed less than US$5.24 and 4.2 billion on patients, respectively. The annually imposed cost on each individual Iranian patient with refractive errors is US$308.5. CONCLUSION: Based on 18mo post refractive surgery course observation, which is generalized to whole life, refractive surgery significantly imposed much less cost compared with spectacles and contact lenses. Refractive errors among Iranians result in considerable economic burden. Using the refractive surgery instead of other two correction methods has the ability to reduce this economic loss in the future.

21 Fruit and vegetable consumption and its relation to risk of asthenopia among Chinese college students

Fang Guo , Qiang Zhang , Meng-Nan Fan , Le Ma , Chu Chen , Xiao-Hong Liu , Hong Jiang , Yan Liu

2018, 11(6):1020-1027. DOI: 10.18240/ijo.2018.06.21

[Abstract](2519) [HTML](268) [PDF 391.38 K](622)

Abstract:
AIM: To investigate the associations between fruit and vegetable consumption and risk of asthenopia among Chinese college students. METHODS: A total of 1022 students were selected from five universities by a multi-stage stratified cluster sampling method. They were surveyed via a self-administered questionnaire including socio-demographic features, dietary and lifestyle habits, eye-related symptoms, eye care habits and history of diseases. Ascertainment of asthenopia was based on participants' subjectively reported symptoms. The associations between fruit and vegetable intake with asthenopia risk were assessed using multivariate logistic regression analysis. RESULTS: There were no significant associations between total fruit and vegetable, total vegetable, or fruit and the risk of asthenopia. Higher intake of dark-green leafy vegetable was likely to be inversely associated with asthenopia risk [odd ratio (OR): 0.60; 95%CI: 0.37-0.97; Ptrend=0.21] after controlling for nondietary and dietary risk factors. Stratified analysis showed that the inverse association between dark-green leafy vegetable intake and asthenopia risk was limited to participants with suboptimal eyesight (OR: 0.45; 95%CI: 0.25-0.82; Ptrend=0.05), wearing glasses (OR: 0.35; 95%CI: 0.17-0.72; Ptrend=0.03) or using computer ≥3h/d (OR: 0.48; 95%CI: 0.25-0.93; Ptrend=0.08). CONCLUSION: A higher consumption of dark-green leafy vegetable is associated with a lower asthenopia risk among college students with suboptimal eyesight and poor eye care habits.

22 Clinical application of accommodating intraocular lens

You-Ling Liang , Song-Bai Jia

2018, 11(6):1028-1037. DOI: 10.18240/ijo.2018.06.22

[Abstract](4381) [HTML](292) [PDF 608.68 K](814)

Abstract:
The present review describes recent advances in application of accommodating intraocular lenses (AIOLs). Standard monofocal intraocular lenses (MIOLs) only correct distance vision, while AIOLs are designed to allow both good distance vision and near vision, which is achieved through the contraction and relaxation of ciliary muscles by providing transformation of the axial movement or curvature of the lens. Thus, AIOLs may be a better choice for those patients who demand a higher level of visual performance. Since techniques to analyze the performance of AIOLs have not been standardized, and there is a variety of both subjective and objective methods, it is hard to measure the performance of these intraocular lenses. By evaluating advantages and disadvantages of various AIOLs, and introducing techniques for measurement the performance postoperative, this paper can provide some relative information on choosing the type of AIOLs in the clinic.

23 Nanotechnology in retinal drug delivery

Sibo Jiang , Yesenia L Franco , Yan Zhou , Jianjun Chen

2018, 11(6):1038-1044. DOI: 10.18240/ijo.2018.06.23

[Abstract](2487) [HTML](253) [PDF 691.93 K](786)

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Retinal diseases, including age-related macular degeneration (AMD) and diabetic retinopathy (DR) are the leading causes of blindness in adults over the age of 50 years in the US. While most of those conditions do not have a cure, currently available treatment options attempt to prevent further vision loss. For many ophthalmic drugs, an efficient delivery system to provide maximum therapeutic efficacy and promote patient compliance remains an unmet medical need. An exploration of literature via PubMed spanning from 2007 to 2017 was conducted to identify studies that have evaluated nanotechnology as platforms for delivering therapeutic agents to the posterior segment of the eye where the retina is located. Until now, four routes that have been utilized for retinal drug delivery are the intravitreal, periocular, subretinal, and systemic routes. Intravitreal injections are now widely used in clinical practice due to their ability to directly target the back of the eye but are highly invasive procedures that may cause several complications, particularly with repeated uses over a short timespan. Nanotechnology shows great promise to revolutionize retinal drug delivery, offering many advantages such as a targeted delivery system towards the specific site of the retina as well as sustained delivery of therapeutic agents. In this review, specific eye anatomy and constraints on ocular drug administration are illustrated. Further, we list and highlight several examples of nanosystems, such as hydrogels, liposomes, dendrimers, and micelles, used via different drug delivery routes to treat various retinal diseases.

24 The measurement of time spent outdoors in child myopia research: a systematic review

Jing Wang , Xian-Gui He , Xun Xu

2018, 11(6):1045-1052. DOI: 10.18240/ijo.2018.06.24

[Abstract](1988) [HTML](248) [PDF 434.71 K](674)

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The purpose of this article is to summarize the methods most commonly used to measure time spent outdoors and provide a comprehensive review of time and activity recording methods with the aim of encouraging the development of new methods. PubMed, Embase and the Cochrane Library were searched from Jan. 1st, 1990 to Aug. 31th, 2017. Studies including the following specific terms: “outdoor”, “outside”, “outdoor activity”, “outside activity”, “outdoor time”, “outside time”, and “outdoor AND measurement of time spent outdoors” were considered for this review. In total, three kinds of outdoor time measurements were discussed. Questionnaires have the longest history and are the most thoroughly revised instruments for assessing time spent outdoors, but recall bias is their most substantial drawback. Global positioning system (GPS) tracking can distinguish between indoor and outdoor locations, but its utility is limited due to several factors such as subject compatibility. Light exposure measurement devices are newly emerging, but all of these devices require good subject cooperation. Further efforts and exploration are needed to develop better methods and new tools to record exposure to the outdoors in real time. Moreover, inventing a new device by combining two or more types of devices mentioned above and using the latest technology of en ergy supplementation and autoswitching may make the best use of the advantages and bypass the disadvantages of each tool.

25 Lateral rectus muscle recession and the vertical palpebral fissure height: to do or not to do inter-muscular septum dissection?

Mohammad Ali Abtahi , Alireza Zandi , Eslam Mandegarfard , Hamidreza Jahanbani-Ardakani , Behzad Mahaki , Seyed-Hossein Abtahi

2018, 11(6):1053-1055. DOI: 10.18240/ijo.2018.06.25

[Abstract](1540) [HTML](268) [PDF 307.66 K](620)

Abstract:
In this study, we aimed to evaluate changes of vertical palpebral fissure height (VPFH) after unilateral lateral rectus muscle recession. Twenty-five and twenty-six patients who were candidates for lateral rectus muscle recession were assigned into “with” and “without” intermuscular septum dissection study arms. The VPFH was measured at one-day before surgery and in two weeks and three months, postoperatively. Three months after surgery, significant increase of VPFH was observed in both groups (Paired t-test; P=0.005). Also, less widening of VPFH was observed in “with intermuscular septum dissection” group (Change in VPFH in “with intermuscular septum dissection” vs “without intermuscular septum dissection” groups: 0.48 mm vs 1.34 mm; ANCOVA test; P<0.001). However, such results were not observed two weeks post-operatively (Change in VPFH in “with intermuscular septum dissection” vs “without intermuscular septum dissection” groups: -0.28 mm vs 0.28 mm; ANCOVA test; P=0.302). Intermuscular septum dissection is recommended in lateral rectus muscle recession to partially prevent the undesirable increment of VPFH.

26 Reduction in interhemispheric functional connectivity in the dorsal visual pathway in unilateral acute open globe injury patients: a resting-state fMRI study

Lei Ye , Ran Wei , Xin Huang , Wen-Qing Shi , Qi-Chen Yang , Qing Yuan , Pei-Wen Zhu , Nan Jiang , Biao Li , Qiong Zhou , Fu-Qing Zhou , Yi Shao

2018, 11(6):1056-1060. DOI: 10.18240/ijo.2018.06.26

[Abstract](1982) [HTML](248) [PDF 1013.16 K](634)

Abstract:
This study investigated the changes in interhemispheric functional connectivity (FC) of the whole brain in open globe injury (OGI) patients, using voxel-mirrored homotopic connectivity (VMHC), and their relationships with clinical features. Totally, 16 male and 2 female acute OGI patients and 18 sex, age, and education-matched healthy volunteers were enrolled in the study. All subjects were scanned through functional magnetic resonance imaging (fMRI). Receiver operating characteristic (ROC) curves analyses had been used to identify the VMHC in these brain areas could be used as biomarkers to distinguish OGI and from healthy control (HC). The mean VMHC values in multiple brain areas and clinical OGI manifestations were evaluated with a Pearson correlation analysis. OGI patients had significantly decreased VMHC in the bilateral calcarine/lingual/cuneus (BA18, 19, 30) and middle occipital gyrus (BA18, 19). The OGI patients had abnormal interhemispheric FC in the dorsal visual pathway, which may represent the pathophysiological mechanism that underlies acute vision loss after OGI.

27 Fungal corneal endotheliitis: a series of case reports

Shuang-Yong Wang , Hai-Feng Zhu , Yan Cheng , Jie Wu , Ying Tian

2018, 11(6):1061-1065. DOI: 10.18240/ijo.2018.06.27

[Abstract](1547) [HTML](257) [PDF 1.99 M](611)

Abstract:

28 Challenging treatment of bilateral multiple infection panuveitis in HIV/AIDS patients

Widya Artini , Soedarman Sjamsoe , Made Susiyanti

2018, 11(6):1066-1070. DOI: 10.18240/ijo.2018.06.28

[Abstract](1765) [HTML](256) [PDF 1.88 M](641)

Abstract:

29 Multispectral imaging in detecting early retinal pigment epithelial atrophy

Jie Zhang , Ying-Bai Chen , Zi-Kui Yu , Lin Liu

2018, 11(6):1071-1074. DOI: 10.18240/ijo.2018.06.29

[Abstract](1529) [HTML](240) [PDF 1.67 M](607)

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30 Comment on “Anterior lamellar recession for management of upper eyelid cicatricial entropion and associated eyelid abnormalities”

Naser Owji

2018, 11(6):1075-1076. DOI: 10.18240/ijo.2018.06.30

[Abstract](970) [HTML](261) [PDF 435.13 K](582)

Abstract:

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Volume 11,Issue 6,2018 Table of Contents