Volume 12,Issue 1,2019 Table of Contents

1 5-aza-2’-deoxycytidine in the regulation of antioxidant enzymes in retinal endothelial cells and rat diabetic retina

Man-Yun Xie , Yan Yang , Ping Liu , Yan Luo , Shi-Bo Tang

2019, 12(1):1-7. DOI: 10.18240/ijo.2019.01.01

[Abstract](2157) [HTML](249) [PDF 816.20 K](810)

Abstract:
AIM: To investigate the roles of a DNA methyltransferase (DNMT) inhibitor 5-aza-2’-deoxycytidine (5-aza-dC) in the regulation of antioxidant enzymes in diabetic retinopathy (DR) models. METHODS: DNMTs expressions and activity, and changes of two key antioxidant enzymes in DR, MnSOD (encoded by SOD2 gene) and glutathione S-transferase theta 1 (GSTT1), were quantified in the isolated human retinal endothelial cells (HRECs) exposed to high glucose (HG) with or without 5-aza-dC treatment. The downstream exacerbating factors including vascular endothelial growth factor (VEGF), intercellular adhesion molecule 1 (ICAM-1) and matrix metalloproteinase 2 (MMP2), which are implicated in the pathogenesis of DR and closely related to oxidative stress were also analyzed. The key parameters were confirmed in the retina from streptozotocin (STZ) diabetic rats. RESULTS: DNMTs expression and DNMT activity was induced in HRECs exposed to HG. Hyperglycemia decreased MnSOD and GSTT1 expression. 5-aza-dC administration effectively suppressed DNMTs expression and activity and reversed the MnSOD and GSTT1 expression under HG condition. VEGF, ICAM-1 and MMP2 induced by HG were also suppressed by 5-aza-dC treatment. Similar results were observed in the retina from STZ diabetic rats. CONCLUSION: Our findings suggest that DNA methylation may serves as one of the mechanisms of antioxidant defense system disruption in DR progression. Modulation of DNA methylation using pharmaceutic means such as DNMT inhibitors could help maintain redox homeostasis and prevent further progression of DR.

2 Two novel variants in CYP1B1 gene: a major contributor of autosomal recessive primary congenital glaucoma with allelic heterogeneity in Pakistani patients

Yar Muhammad Waryah , Muhammad Iqbal , Shakeel Ahmed Sheikh , Muhammad Azhar Baig , Ashok Kumar Narsani , Muhammad Atif , Munir Ahmad Bhinder , Attiq Ur Rahman , Azam Iqbal Memon , Muhammad Suleman Pirzado , Ali Muhammad Waryah

2019, 12(1):8-15. DOI: 10.18240/ijo.2019.01.02

[Abstract](1443) [HTML](251) [PDF 835.71 K](773)

Abstract:
AIM: To find the CYP1B1 mutations associated with primary congenital glaucoma (PCG) in Pakistani consanguineous pedigrees. METHODS: After getting informed consent, 11 consanguineous pedigrees belonging to different ethnic groups were enrolled. Detailed medical history was recorded and pedigrees were drawn. The standard ophthalmological examination was done to characterize the phenotype. Genomic DNA was extracted from 10 mL whole blood and coding exons and exon intron boundaries of CYP1B1 gene were directly sequenced. Bioinformatics tools were used to model the mutant protein and predict the effect of novel variants on protein structure and function. RESULTS: Sequencing analysis revealed 5 different CYP1B1 variants in 7 families (7/11; 64%), including two novel variants. A common mutation, p.R390H was found in four families, whereas p.P437L was found once in a family. Two novel variants, a homozygous non sense variant p.L13* and a compound heterozygous variant, p.P350T along with p.V364M were segregating with PCG in two families. All the patients had the variable onset and severity of the disease. The success rate of early clinical interventions was observed dependent on mutation types and position. Two different haplotypes were associated with frequently found mutation, p.R390H. CONCLUSION: Identification of novel CYP1B1 variants reassert the genetic heterogeneity of Pakistani PCG patients. The patients with missense mutations show severe phenotypic presentations and poor vision after surgical interventions as compare to patients with null variants. This may help to better understand the role of CYP1B1 mutations in the development of PCG and its course of pathogenicity.

3 Metabolic profile analysis of free amino acids in experimental autoimmune uveoretinitis rat plasma

Jun-Guo Guo , Xin-Miao Guo , Xing-Rong Wang , Jing-Zhen Tian , Hong-Sheng Bi

2019, 12(1):16-24. DOI: 10.18240/ijo.2019.01.03

[Abstract](1815) [HTML](257) [PDF 1.62 M](729)

Abstract:
AIM: To determine the differences of amino acid (AA) levels in experimental autoimmune uveoretinitis (EAU). METHODS: AA analysis of the plasma samples in EAU rats induced by interphotoreceptor retinoid-binding protein emulsion were performed with high performance liquid chromatography (HPLC) and phenylisothiocyanate (PITC) pre-column derivation methods were performed. Using partial least squares discriminant analysis (PLS-DA), the potential biomarkers were identified in EAU rat plasma, and the metabolic pathways related to EAU were further analyzed. RESULTS: The method results showed that linear (r≥0.9957), intra-day reproducible [relative standard deviation (RSD)=0.04%-1.33%], inter-day reproducible (RSD=0.06%-2.07%), repeatability (RSD=0.03%-0.89%), stability (RSD=0.05%-2.48%) and recovery (RSD=1.98%-4.39%), with detection limits of 0.853-11.4 ng/mL. The metabolic profile in EAU rats was different from that in the control groups five AAs concentrations were increased and nine AAs were reduced. Moreover, five metabolic pathways were related to the development of EAU. CONCLUSION: The developed method is a simple, rapid and convenient for determination of AAs in EAU rat plasma, and these findings will provide a comprehensive insight on the metabolic profiling of the pathological changes in EAU.

4 TNF-α gene polymorphisms: association with age-related macular degeneration in Russian population

Valeriy Chernykh , Alla Shevchenko , Vladimir Konenkov , Viktor Prokofiev , Alena Eremina , Alexander Trunov

2019, 12(1):25-29. DOI: 10.18240/ijo.2019.01.04

[Abstract](2053) [HTML](252) [PDF 369.67 K](679)

Abstract:
AIM: To study polymorphisms in promotor regions of tumor necrosis factor (TNF)-α TNF-863A/C (rs1800630), TNF-308A/G (rs1800629), and TNF-238A/G (rs361525) in patients with age-related macular degeneration (AMD) and associations of complex TNF-α genotypes with AMD. METHODS: One hundred and two patients (82 women, 20 men; mean age 64.2±1.2y) with AMD and 100 healthy age- and sex-matched controls (82 women, 18 men; 60±1.4y) were included in the study. All subjects were Caucasian, all subjects and their parents were inhabitants of Russia. Genomic DNA was obtained from EDTA-preserved blood using the standard phenol-chloroform method. Polymorphisms were detected by polymerase chain reaction followed by the restriction fragment length polymorphism method. The following TNF-α genotypes were studied: TNF-α-238 AA, GA, GG, TNF-α-308 AA, GA, GG, TNF-α-863 AA, CA, CC. RESULTS: Differences in TNF-α-863 and TNF-α-238 genotypes frequencies in patients with AMD and healthy controls were not found. The distribution of TNF-α-308 AA and TNF-α-308 GA genotypes was significantly different between the studied group and the controls [odds ratios (OR) =0.22, P=0.0287 and OR=2.91, P=0.0063, respectively]. TNF-863CC/TNF-308GA and TNF-308GA/TNF-238GG genotypes were associated with the increased risk of AMD (OR=2.48, P=0.0332 and OR=2.51, P=0.0187, respectively). Five genotypes combinations appeared to be protective. CONCLUSION: In the present study, single nucleotide polymorphisms and complex polymorphisms of one of the key inflammatory cytokines TNF-α, and a number of significant associations of these polymorphisms with AMD in Russian population have been shown. Complex analysis of genotypes could be important in AMD risk factors detection and studying pathogenesis.

5 Genome-wide DNA hypermethylation and homocysteine increase a risk for myopia

Edward Hsi , Yung-Song Wang , Chia-Wei Huang , Ming-Lung Yu , Suh-Hang Hank Juo , Chung-Ling Liang

2019, 12(1):38-45. DOI: 10.18240/ijo.2019.01.06

[Abstract](1731) [HTML](251) [PDF 955.01 K](724)

Abstract:
AIM: To test for the association between genome-wide methylation and myopia in human and mice. METHODS: Long interspersed nucleotide element 1 (LINE-1) methylation levels were used to surrogate genome-wide methylation level. We first tested for the association between high myopia (<-6 D) and LINE-1 methylation in leukocytes in 220 cases and 220 control subjects. Secondly, we validated the results of LINE-1 methylation in eyes from the form deprivation myopia (FDM) mice. Furthermore, we calculated the correlation of LINE-1 methylation levels between leukocyte DNA and ocular DNA in the mice. We also tested whether dopamine can alter LINE-1 methylation levels. RESULTS: The LINE-1 methylation level was significantly higher in the myopic human subjects than controls. The upper and middle tertiles of the methylation levels increased an approximately 2-fold (P≤0.002) risk for myopia than the lower tertile. Similarly, FDM mice had high LINE-1 methylation levels in the leukocyte, retina and sclera, and furthermore the methylation levels detected from these three tissues were significantly correlated. Immunohistochemical staining revealed higher levels of homocysteine and methionine in the rodent myopic eyes than normal eyes. Dopamine treatment to the cells reduced both LINE-1 methylation and DNA methyltransferase levels. CONCLUSION: LINE-1 hypermethylation may be associated with high myopia in human and mice. Homocysteine and methionine are accumulated in myopic eyes, which may provide excess methyl group for genome-wide methylation.

6 Riboflavin/ultraviolet A-induced collagen cross-linking in rabbit corneal scar

You-Huan Cai , Tai-Xiang Liu , Hai-Xiang Li

2019, 12(1):46-50. DOI: 10.18240/ijo.2019.01.07

[Abstract](1016) [HTML](241) [PDF 831.46 K](722)

Abstract:
AIM: To evaluate the biomechanical stability of the corneal scar treating with riboflavin and ultraviolet A (UVA). METHODS: Totally 86 New Zeal rabbits were divided into control group (group A, n=8) and trauma groups [group B (n=27), group C (n=24) and group D (n=27)]. Then groups B, C and D were divided into three sub-groups according to the time points of sacrifice, i.e. groups Ba, Ca and Da (4wk, n=8); Bb, Cb and Db (6wk, n=8); Bc (n=11), Cc (n=8) and Dc (8wk, n=11). The right corneas of these 78 rabbits in the trauma groups were penetrated. Group B were only sutured. Group C were treated with corneal cross-linking (CXL) immediately after suturing. Group D were treated with CXL seven days after suturing. The corneal scar strips of 4.0×10.0 mm2 were cut and the stress and Young’s modulus at 10% strain were evaluated. Samples from the three rabbits of group Bc and three of group Dc were used to measure the expression of alpha smooth muscle action (α-SMA). RESULTS: The mechanical strength of the corneal scar increased with time, and was strongest at 8wk after the injury. The ultimate stress of corneal scar (group D) were 2.17±0.52 MPa, 2.92±0.63 MPa, and 4.21±0.68 Mpa at 4wk, 6wk and 8wk, respectively; Young’s modulus were 10.94±1.57 MPa, 11.16±2.50 MPa, and 13.36±2.10 Mpa, which were higher than that of other groups except for normal control. The expression of α-SMA in group B and group D were 0.28±0.11 and 0.65±0.20, respectively, and the difference was statistically significant (P=0.048). CONCLUSION: CXL with riboflavin/UVA at seven days after suturing improved the biomechanical properties of corneal scars most effectively in the present study.

7 One-year outcomes of intravitreal conbercept combined rescue therapy for polypoidal choroidal vasculopathy in a Chinese population: a real-life clinical data

Hui-Jun Qi , En-Zhong Jin , Ming-Wei Zhao

2019, 12(1):51-57. DOI: 10.18240/ijo.2019.01.08

[Abstract](1304) [HTML](249) [PDF 996.28 K](672)

Abstract:
AIM: To evaluate the real-life clinical outcomes of intravitreal injection of conbercept combined rescue therapy for polypoidal choroidal vasculopathy (PCV). METHODS: This was an open label, single center, and interventional study. All enrolled patients were treated initially with three consecutive monthly intravitreal conbercept injections (0.5 mg). Additional conbercept injections were administered upon substantial polyp regression with improved visual acuity (VA). Eyes with partial or no polyp regression and poor VA were rescue treated with photodynamic therapy (PDT) for subfoveal polyps or thermal laser photocoagulation for extrafoveal polyps. Best-corrected visual acuity (BCVA), central foveal thickness (CFT) and polyp regression were observed as primary outcomes. Side effects were also collected during the follow-up period. RESULTS: A total of 56 eyes (56 patients) with PCV were included. BCVA increased significantly from the baseline of 43.52±24.21 letters to 55.88±21.94 letters (P<0.001) at 12mo, while CFT decreased significantly from 457.41±207.86 μm to 247.98±127.08 μm (P<0.001). All patients showed polyp regression. Twenty-three eyes achieved complete polyp regression after the three initial injections, which increased to 44 eyes at 12mo. Seventeen eyes underwent rescue therapy, among which 2 eyes treated with PDT and 15 eyes treated with laser photocoagulation. A mean of 4.30±1.43 injections were given per eye. No intraocular inflammation, retinal or vitreous hemorrhage, or systemic complication occurred. CONCLUSION: Conbercept is an effective and safe option for the treatment of PCV in Chinese population. The treatment regimen of three initial conbercept injections followed by additional injections or rescue therapies is efficacious for treating PCV.

8 Evaluation of spectral domain optical coherence tomography parameters in discriminating preperimetric glaucoma from high myopia

Xiao-Yu Xu , Hui Xiao , Jing-Yi Luo , Xing Liu

2019, 12(1):58-65. DOI: 10.18240/ijo.2019.01.09

[Abstract](1903) [HTML](247) [PDF 1.26 M](701)

Abstract:
AIM: To evaluate the diagnostic ability of macular ganglion cell-inner plexiform layer (GCIPL) thickness obtained by spectral-domain optical coherence tomography (SD-OCT) in discriminating non-highly myopic eyes with preperimetric glaucoma (PPG) from highly myopic healthy eyes. METHODS: A total of 254 eyes, including 76 normal controls (NC), 116 eyes with high myopia (HM) and 62 non-highly myopic eyes with PPG were enrolled. The diagnostic ability of OCT parameters was accessed by the areas under the receiver operating characteristic (AUROC) curve in two distinguishing groups: PPG eyes with non-glaucomatous eyes including NC and HM (Group 1), and PPG eyes with HM eyes (Group 2). Differences in diagnostic performance between GCIPL and RNFL parameters were evaluated. RESULTS: The minimum (AUROC curve of 0.782), inferotemporal (0.758) and inferior (0.705) GCIPL thickness were the top three GCIPL parameters in discriminating PPG from non-glaucomatous eyes, all of which had statistically significant lower diagnostic ability than average RNFL thickness (0.847). In discriminating PPG from HM, the best GCIPL parameter was minimum (0.689), statistically significant lower in diagnostic ability than average RNFL thickness (0.789) and three other RNFL thickness parameters of temporal and inferotemporal clock-hour sectors. CONCLUSION: The minimum GCIPL thickness is the best GCIPL parameter to detect non-highly myopic PPG from highly myopic eyes, whose diagnostic ability is inferior to that of average RNFL thickness and RNFL thickness of several temporal and inferotemporal clock-hour sectors. The average RNFL thickness is recommended for discriminating PPG from highly myopic healthy eyes in current clinical practice in a Chinese population.

9 The prognosis of trabeculectomy in primary angle- closure glaucoma patients

Jun-Dong Zhu , Li-Lian Xie , Zhi-Yuan Li , Xiao-He Lu

2019, 12(1):66-72. DOI: 10.18240/ijo.2019.01.10

[Abstract](1545) [HTML](232) [PDF 1.01 M](648)

Abstract:
AIM: To evaluate whether the level of thrombospondin-1 (TSP-1) in aqueous humor can predict the prognosis of trabeculectomy in patients with primary angle-closure glaucoma (PACG). METHODS: This case-control study involved 26 patients with PACG who experienced a failed trabeculectomy (case group) and 78 age- and sex-matched patients with PACG who underwent successful trabeculectomy (control group). Aqueous humor was collected at the time of trabeculectomy and tested for TSP-1 and TGF-β2 levels with an enzyme-linked immunosorbent assay method. Logistic regression modeling was used to assess the risk factors for failed trabeculectomy. RESULTS: The mean TSP-1 aqueous concentrations were significantly higher in the case group (20.67±9.79 ng/mL) than the control group (5.17±2.29 ng/mL) (P<0.001). The transforming growth factor-β2 (TGF-β2) aqueous concentrations were significantly different between the case and control group, at 3633.25 and 1090.24 pg/mL, respectively (P<0.001). Logistic regression analysis revealed TSP-1 level as an independent risk factor for a failed trabeculectomy (OR=3.540; 95%CI=1.092-11.482). CONCLUSION: The aqueous humor TSP-1 and TGF-β2 levels are higher in PACG eyes with failed trabeculectomy than with successful trabeculectomy at one year. The aqueous humor TSP-1 level is an independent risk factor associated with failed trabeculectomy.

10 Comparison of ring 1 parameters in 37-segment multifocal electroretinography between onset and offset conditions of ring 2 to 4 in normal subjects

Jun Ho Yoo , Cheolmin Yun , Jaeryung Oh , Seong-Woo Kim

2019, 12(1):73-78. DOI: 10.18240/ijo.2019.01.11

[Abstract](1217) [HTML](262) [PDF 785.33 K](610)

Abstract:
AIM: To investigate whether the response of a central hexagonal element corresponding to the macular area in conventional multifocal electroretinography (mfERG) tests was the same as that of experimental mfERG using single central hexagonal element stimulation. METHODS: Prospective, observational study. Thirty healthy subjects were included in this study. mfERG recordings were performed according to two protocols: stimulus with 37 hexagonal elements (protocol 1), and stimulus with a single central element created by deactivating the other 36 hexagonal elements (protocol 2). We compared differences between ring 1 parameters in each protocol. RESULTS: In protocol 1, the first positive component (P1) implicit time and P1 amplitude were 37.8±1.8ms and 6.3±2.7 μV. After single element stimulation (protocol 2), double positive waves appeared. The implicit time and amplitude of P1 were 40.7±2.4ms (P<0.001) and 9.1±3.3 μV (P=0.001), respectively. The implicit time and amplitude of the second positive component (P2) were 68.0±4.5ms (P<0.001, compared with P1 in protocol 1) and 12.3±4.7 μV (P<0.001, compared with P1 in protocol 1), respectively. The amplitude of P2 in protocol 2 was about two times higher than that of P1 in protocol 1. CONCLUSION: mfERG responses of a central hexagonal element in a single element stimulation protocol are different from those of multiple element stimulation. The positive wave is more enhanced compared to that of the conventional protocol and it elongated into two wavelets.

11 Fluorescein angiography of retinal vascular involution after intravitreal injection of ranibizumab for retinopathy of prematurity

Yong Cheng , Tie-Gang Liu , Wei-Yi Li , Ming-Wei Zhao , Jian-Hong Liang

2019, 12(1):79-82. DOI: 10.18240/ijo.2019.01.12

[Abstract](1888) [HTML](250) [PDF 426.95 K](664)

Abstract:
AIM: To describe the involution patterns of vessel growth of retina through fluorescein angiography (FA) of children, who had been under treatment up to 1y previously intravitreal ranibizumab (IVR) as monotherapy for retinopathy of prematurity (ROP). METHODS: This is a retrospective study. The medical information and FA of 17 children (34 eyes) whose area of avascular retina from the ora serrata was more than two disc diameters (DD) were analyzed. RESULTS: Among 34 eyes, all were the presence of finger-shaped vessels and arteriolar-venular shunts (100%, 34/34 eyes). Popcorn abnormalities were found in most of the eyes (94.1%, 32/34 eyes). Furthermore, in many cases (23.5%, 8/34 eyes), there were leakage persisting in the region of the junction between avascular and vascular retina. In contrast, just 2 eyes (5.9%) showed damage of retinal capillary bed and 3 eyes (8.8%) showed large area of retinal pigment epithelium (RPE) atrophy. CONCLUSION: Although IVR can be very effective in ROP, we should remain cautious as infants may remain avascular peripheral retinas and abnormal vessel. FA allows accurate visualization of vessel abnormalities in eyes with ROP, which will be helpful to affect assessment of disease activity and therapeutic effect.

12 Evaluation of dynamic stereopsis in intermittent exotropia patients

Jing Zhong , Da-Ming Deng , Zi-Dong Chen , Jin-Rong Li , Jun-Peng Yuan , Lei Feng , Ai-Hou Wang , Min-Bin Yu

2019, 12(1):83-88. DOI: 10.18240/ijo.2019.01.13

[Abstract](1419) [HTML](250) [PDF 505.52 K](647)

Abstract:
AIM: To delineate the characteristics of the dynamic stereopsis test and analyze related parameters in intermittent exotropia [X(T)] patients. METHODS: Fifty-seven X(T) patients and 55 normal subjects were enrolled in this study. The normal and X(T) groups were used to test the reproducibility and reliability of the dynamic stereopsis test, and Bangerter filters with densities of 0.2 were then used to simulate suppression to test for traditional and dynamic stereopsis. In the X(T) group, the measurements included 1) dynamic stereopsis test comprising three parts: motion+disparity, motion only and disparity only; 2) ocular deviation angle; 3) Bagolini striated lens test; 4) disease course; and 5) Titmus stereopsis test. RESULTS: The test-retest reliability of the dynamic stereopsis method was 0.901 in the normal and X(T) groups, and none of the X(T) patients were able to pass the static and dynamic stereopsis tests after using the 0.2 Bangerter filter. The accuracy rate was greater than 80% in the normal group and 31.81%, 36.36%, and 45.45% for the motion+disparity, motion-only and disparity-only components of the traditional test for X(T) patients diagnosed with stereoblindness via traditional tests, respectively. Patients with a long disease course (>1y) had worse dynamic stereopsis than those with a short disease course (<1y; P<0.05, Chi-square test). The deviation angle was not correlated with the motion+disparity, disparity-only, or the motion-only test components (all P>0.05, Chi-square test). CONCLUSION: Dynamic stereopsis is preserved in certain X(T) patients diagnosed with stereoblindness via traditional tests. A long disease course was shown to be a negative factor for dynamic stereopsis in X(T) patients which might be associated with worse progression, and provide good references clinically.

13 Management of tear trough deformity with and without tear trough-orbicularis retaining ligament complex release in transconjunctival blepharoplasty: a comparative study

Tamer Ismail Gawdat , Engy Abd Eltawab Elsherif , Yomna Amr Alahmadawy , Yehia Salah Eldin Mostafa

2019, 12(1):89-93. DOI: 10.18240/ijo.2019.01.14

[Abstract](1739) [HTML](239) [PDF 634.62 K](614)

Abstract:
AIM: To evaluate the effect of releasing the orbicularis retaining ligament (ORL) complex of the tear trough combined with the transconjunctival blepharoplasty in the surgical management of tear trough deformity compared with the effect of blepharoplasty alone. METHODS: A prospective, randomized (by closed envelope technique), controlled surgical trial which included 50 patients (100 eyes) with bilateral visible tear trough deformity and lower eyelid fat bulging, was divided into two groups where 25 patients (50 eyes) had tear trough-ORL release with blepharoplasty and 25 patients (50 eyes) didn’t. Qualitative and quantitative assessments of tear trough deformity were done at 6mo postoperatively, achieving grade 0 or 1 of Barton’s classification was considered a success. Standardized photographic documentation of each patient was done pre and postoperatively, also assessment of the patients’ satisfaction postoperatively was done and ranked as excellent, very good, good or fair. RESULTS: There was statistically significant difference between the two groups in the overall aesthetic results postoperatively regarding the qualitative and quantitative analysis of the tear trough deformity, where patients who had tear trough-ORL complex release had more successful outcomes than those of the second group. CONCLUSION: ORL release should be done in patients with tear trough deformity in order to release the tethering effect of this ligament which causes the prominence of the naso jugal groove.

14 Deep-learning classifier with ultrawide-field fundus ophthalmoscopy for detecting branch retinal vein occlusion

Daisuke Nagasato , Hitoshi Tabuchi , Hideharu Ohsugi , Hiroki Masumoto , Hiroki Enno , Naofumi Ishitobi , Tomoaki Sonobe , Masahiro Kameoka , Masanori Niki , Yoshinori Mitamura

2019, 12(1):94-99. DOI: 10.18240/ijo.2019.01.15

[Abstract](2568) [HTML](245) [PDF 811.64 K](719)

Abstract:
AIM: To investigate and compare the efficacy of two machine-learning technologies with deep-learning (DL) and support vector machine (SVM) for the detection of branch retinal vein occlusion (BRVO) using ultrawide-field fundus images. METHODS: This study included 237 images from 236 patients with BRVO with a mean±standard deviation of age 66.3±10.6y and 229 images from 176 non-BRVO healthy subjects with a mean age of 64.9±9.4y. Training was conducted using a deep convolutional neural network using ultrawide-field fundus images to construct the DL model. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and area under the curve (AUC) were calculated to compare the diagnostic abilities of the DL and SVM models. RESULTS: For the DL model, the sensitivity, specificity, PPV, NPV and AUC for diagnosing BRVO was 94.0% (95%CI: 93.8%-98.8%), 97.0% (95%CI: 89.7%-96.4%), 96.5% (95%CI: 94.3%-98.7%), 93.2% (95%CI: 90.5%-96.0%) and 0.976 (95%CI: 0.960-0.993), respectively. In contrast, for the SVM model, these values were 80.5% (95%CI: 77.8%-87.9%), 84.3% (95%CI: 75.8%-86.1%), 83.5% (95%CI: 78.4%-88.6%), 75.2% (95%CI: 72.1%-78.3%) and 0.857 (95%CI: 0.811-0.903), respectively. The DL model outperformed the SVM model in all the aforementioned parameters (P<0.001). CONCLUSION: These results indicate that the combination of the DL model and ultrawide-field fundus ophthalmoscopy may distinguish between healthy and BRVO eyes with a high level of accuracy. The proposed combination may be used for automatically diagnosing BRVO in patients residing in remote areas lacking access to an ophthalmic medical center.

15 Measuring nasolacrimal duct volume using computed tomography images in nasolacrimal duct obstruction patients in Korean

Jin-Hwan Park , Jung-Ah Huh , Jun-Feng Piao , Hwa Lee , Se-Hyun Baek

2019, 12(1):100-105. DOI: 10.18240/ijo.2019.01.16

[Abstract](1398) [HTML](231) [PDF 967.76 K](619)

Abstract:
AIM: To investigate nasolacrimal duct (NLD) volume in Korean patients and to examine the correlation between NLD volume and obstruction. METHODS: Of patients who underwent orbital computed tomography from March 2013 to January 2016, patients diagnosed with NLD obstruction were classified into the patient group and patients without obstruction were classified into the control group. The NLD volume was measured using the Image J program, which showed the NLD in axial, coronal, and sagittal images on computed tomography. RESULTS: The average value of men’s NLD volume, 265.33±90.57 mm3, was significantly larger than women’s, 211.87±68.61 mm3 (P=0.009). In the patient group, the NLD volume of the obstructed eyes, 242.49±82.93 mm3, and the non-obstructed eyes, 225.20±73.20 mm3, were significantly higher than the control group, 217.61±82.04 mm3 (P<0.001, P<0.001). CONCLUSION: The NLD volume is larger in men than in women in Korean adults. If there is NLD obstruction in women, the NLD volume is larger and it is judged that inflammatory reaction caused a chronic change in the bone around the NLD and affect the measurement of NLD volume.

16 The association between socioeconomic status and visual disability among older adults in China

Wan-Wei Dai , Jia-Min Gao , Ping He , Zheng Ma , Xiao-Xiao Tian , Xiao-Ying Zheng

2019, 12(1):106-113. DOI: 10.18240/ijo.2019.01.17

[Abstract](1589) [HTML](236) [PDF 347.69 K](606)

Abstract:
AIM: To investigate the association between socioeconomic status (SES) and visual disability (VD) among older Chinese adults. METHODS: We obtained data from the Second National Sample Survey on Disability, conducted in China in 2006. A total number of 192 375 older adults (aged≥65y) were screened for suspected VD via interviews with trained examiners. Those who screened positively for VD were referred to ophthalmologists to obtain a final diagnosis. RESULTS: VD was prevalent among 7.29% of Chinese adults aged 65 and older, and was higher in rural areas (8.71%) than in urban areas (4.82%). After adjusting for SES indicators and covariates, we found that less-educated older adults were more likely to suffer from VD, with an odds ratio (OR) of 2.50 (95%CI: 2.26-2.82) for illiterates, compared with those who graduated from senior high school or above. Older adults who were in the lowest income quintile were more at risk of VD, with an OR of 1.81 (95%CI: 1.68-2.95), compared with adults in the highest income quintile. In urban areas, when compared with adults who graduated from senior high school or above, those who did not continue their education after junior high school, primary school, or those who were illiterate, were more likely to suffer from VD, with an OR of 1.35 (95%CI: 1.51-1.59), 1.84 (95%CI: 1.60-2.12), and 2.63 (95%CI: 2.27-3.04), respectively. Lower levels of income were statistically significant when associated with VD. In rural areas, adults who were illiterate had an OR of 2.21 (95%CI: 1.75-2.79) when compared to adults with senior high school or above education level. Per capita, household income remained significantly associated with VD. Older adults who were ≥85, female, single, and residing in rural areas were associated with higher risks of VD. CONCLUSION: Individual-level SES among the elderly, in the form of education and income, is associated with VD among elderly Chinese adults in both urban and rural areas; however, the association is stronger in rural areas. Further studies are still required to explore the mechanism behind the relationships.

17 How to improve Iranians’ vision health: on the national policy of preventing Iranians’ blindness

Behzad Damari , Alireza Mahdavi , Maryam Hajian

2019, 12(1):114-122. DOI: 10.18240/ijo.2019.01.18

[Abstract](1527) [HTML](262) [PDF 322.24 K](612)

Abstract:
AIM: To review vision health situation of Iranian community, analyze its determinants, and discuss the adopted improvement strategies by the Iran Ministry of Health and Medical Education (MOHME). METHODS: This was a rapid situation analysis with a qualitative approach in three parts of recognition, orientation and implementation. The data were gathered via review of upstream documents, national and international experiences, and experts and stakeholders’ opinions. RESULTS: Eradicating trachoma, increasing human resources, increasing educational and research centers and promotion of ophthalmic technologies were important achievements in the field of vision health in Iran. Through these achievements, it seemed that the pattern of causes of blindness and low vision was similar to that of the developed countries. However, the review of Iranians’ vision health indicators showed that a considerable percent of the blindness and low vision was avoidable through a national program demanding 3 types of interventions in social determinants of health (SDH), community education, and increasing the access to health care services by integrating the necessary services in primary health care system. CONCLUSION: Managing the issue requires attentions from a national committee for preventing blindness with participation of all stakeholders, implementing a national survey on vision health, preparation of the primary level health centers including employment and education of community health workers (Behvarzes), optometrists and general practitioners, fair distribution of specialized human resources and establishing at least one specialized center in each province for referring patients from the primary levels.

18 Intraocular pressure fluctuation and the risk of glaucomatous damage deterioration: a Meta-analysis

Zhen-Zhen Guo , Karen Chang , Xin Wei

2019, 12(1):123-128. DOI: 10.18240/ijo.2019.01.19

[Abstract](1816) [HTML](247) [PDF 701.29 K](728)

Abstract:
AIM: To systematically review whether the increased fluctuation of intraocular pressure (IOP) is a risk factor for open angle glaucoma (OAG) progression. METHODS: Scientific studies relevant to IOP fluctuation and glaucoma progression were retrieved from MEDLINE, EMBASE and CENTRAL databases, and were listed as references in this paper. The hazard ratio (HR) was calculated by using fixed or random-effects models according to the heterogeneity of included studies. RESULTS: Individual data for 2211 eyes of 2637 OAG patients in fourteen prospective studies were included in this Meta-analysis. All studies were longitudinal clinical studies with follow-up period ranging from 3 to 8.5y. The combined HR was 1.23 (95%CI 1.04-1.46, P=0.02) for the association between IOP fluctuation and glaucoma onset or progression with the evidence of heterogeneity (P<0.1). Subgroup analyses with different types of IOP fluctuation were also evaluated. Results indicated that the summary HR was 0.98 (95%CI 0.78-1.24) in short-term IOP fluctuation group, which showed no statistical significance with heterogeneity, whereas, the combined HR was 1.43 (95%CI 1.13-1.82, P=0.003) in long-term IOP fluctuation group without homogeneity. Sensitivity analysis further showed that the pooled HR was 1.10 (95%CI 1.03-1.18, P=0.004) for long-term IOP fluctuation and visual function progression with homogeneity among studies (P=0.3). CONCLUSION: Long-term IOP fluctuation can be a risk factor for glaucoma progression based on the presented evidence. Thus, controlling the swing of IOP is crucial for glaucoma or glaucoma suspecting patients.

19 Valproic acid’s effects on visual acuity in retinitis pigmentosa: a systemic review and Meta-analysis

Wen-Jun Chen , Li Ma , Ming-Shu Li , Xiang Ma

2019, 12(1):129-134. DOI: 10.18240/ijo.2019.01.20

[Abstract](1425) [HTML](259) [PDF 2.20 M](655)

Abstract:
AIM: To gain a better understanding of the overall efficacy of valproic acid (VPA) treatment for retinitis pigmentosa (RP). METHODS: Publications in PubMed, EMBASE, Cochrane Library, Web of Science and Clinicaltrials.gov were searched for clinical trials of patients with RP assigned to treatment with VPA. Patients’ pre- and post-treatment visual field (VF) and best-corrected visual acuity (BCVA) scores were extracted and compared to assess changes. RESULTS: A total of 78 reports were retrieved and 6 studies involving 116 patients were included in the Meta-analysis. The combined results showed a significant decrease in logarithm of minimal angle of resolution (logMAR) scores, calculated using baseline and post-treatment BCVA (P<0.00001, mean difference=-0.05, 95%CI: -0.05, -0.04, I2=36%) scores, which means there was considerable improvement in visual acuity. Meanwhile, more BCVA changes were observed in short-term (≤6mo) treatment studies (P<0.00001, mean difference=-0.05, 95%CI: -0.05, -0.04, I2=38%), studies conducted in Asia (P<0.00001, mean difference=-0.05, 95%CI: -0.05, -0.04, I2=4%), studies with a sample size of 30 or fewer patients (P<0.00001, mean difference=-0.05, 95%CI: -0.05, -0.04, I2=38%) and prospective studies (P<0.00001, mean difference=-0.05, 95%CI: -0.05, -0.04, I2=0%). However, VPA’s effect on VF was inconsistent across studies (P=0.75, mean difference=-22.76, 95%CI: -160.56, 115.05, I2=68%). CONCLUSION: This Meta-analysis reveals that most RP patients who were treated with VPA showed improvement in BCVA. However, its effect on VF remains inconsistent. VPA may be a promising treatment for RP.

20 Image-guided lens extraction surgery: a systematic review

Eirini-Kanella Panagiotopoulou , Panagiota Ntonti , Maria Gkika , Aristeidis Konstantinidis , Irfan Perente , Doukas Dardabounis , Konstantinos Ioannakis , Georgios Labiris

2019, 12(1):135-151. DOI: 10.18240/ijo.2019.01.21

[Abstract](1669) [HTML](249) [PDF 380.12 K](641)

Abstract:
A systematic review of the recent literature regarding the current image-guided systems used for cataract surgery or refractive lens exchange was performed based on the PubMed and Google Scholar databases in March 2018. Literature review returned 21 eligible studies. These studies compared image-guided systems with other keratometric devices regarding their accuracy, repeatability and reproducibility in measurement of keratometric values, astigmatism magnitude and axis, as well as in IOL power calculation. Additionally, the image-guided systems were compared with conventional manual ink-marking techniques for the alignment of toric IOLs. In conclusion, image-guided systems seem to be an accurate and reliable technology with measurements of high repeatability and reproducibility regarding the keratometry and IOL power calculation, but not yet interchangeable with the current established and validated keratometric devices. However, they are superior over the conventional manual ink-marking techniques for toric IOL alignment.

21 Differentiation of retinal ganglion cells from induced pluripotent stem cells: a review

Shang-Li Ji , Shi-Bo Tang

2019, 12(1):152-160. DOI: 10.18240/ijo.2019.01.22

[Abstract](2635) [HTML](253) [PDF 439.52 K](729)

Abstract:
Glaucoma is a common optic neuropathy that is characterized by the progressive degeneration of axons and the loss of retinal ganglion cells (RGCs). Glaucoma is one of the leading causes of irreversible blindness worldwide. Current glaucoma treatments only slow the progression of RGCs loss. Induced pluripotent stem cells (iPSCs) are capable of differentiating into all three germ layer cell lineages. iPSCs can be patient-specific, making iPSC-derived RGCs a promising candidate for cell replacement. In this review, we focus on discussing the detailed approaches used to differentiate iPSCs into RGCs.

22 Trans-scleral cyclophotocoagulation: a tale of two probes

Cara E. Capitena Young , Malik Y. Kahook , David A. Ammar , Leonard K. Seibold

2019, 12(1):161-164. DOI: 10.18240/ijo.2019.01.23

[Abstract](1507) [HTML](232) [PDF 595.45 K](739)

Abstract:
To compare the histological effects of trans-scleral cyclophotocoagulation (TCP) performed with two different probes, the G-probe (IRIDEX Medical Instruments, Mountain View, CA, USA) and the Ciliprobe (Katalyst Surgical, Chesterfield, MO, USA). TCP was performed on two human cadaver eyes from the same corpse. The vertical meridian was marked and opposite sides were treated using either the G-probe or Ciliprobe. The first eye was treated with each probe at 2000ms/2000 mW and the second eye at 3000ms/1500 mW. Histological examination revealed separation and loss of the non-pigmented ciliary epithelium as well as vacuolization in all sections for both probes and settings. Changes to the non-pigmented ciliary epithelium treated at 3000ms/1500 mW were similar between the two probes. A slightly more complete separation of the non-pigmented epithelium was noted on the Ciliprobe treated sections as compared to the G-probe treated sections in the eye treated at 2000ms/2000 mW. Therefore, in human cadaver eyes, both the G-probe and Ciliprobe produced separation, vacuolization, and loss of the non-pigmented ciliary epithelium at two different, clinically utilized settings.

23 Comparison of encirclage and cryotherapy with argon laser in the management of traumatic cyclodialysis cleft

Gitanjli Sood , Vinata Rajendran , Ronnie George , Tarun Sharma , Rajiv Raman

2019, 12(1):165-168. DOI: 10.18240/ijo.2019.01.24

[Abstract](2490) [HTML](244) [PDF 455.86 K](554)

Abstract:
The study compared anatomical and functional outcome of a novel technique of encirclage and cryotherapy with the conventional argon laser in the management of traumatic cyclodialysis cleft in 19 patients (10: encirclage and 9: argon laser). The postoperative anatomical success was taken as rise in intraocular pressure (IOP) more than 6 mm Hg or the closure of cleft on gonioscopy or ultrasound biomicroscopy (UBM). Visual outcome was measured as change in logMAR visual acuity. Traumatic cataract and hypotony were present in majority. IOP>6 mm Hg was noted in 90% of encirclage group and in 77.70% of argon laser group. Two cases had non-closure of cleft. Encirclage is comparable to argon laser in terms of anatomical and functional success with possible advantage of single procedure and use in cases with failed laser.

24 Effect of glaucoma on identification of bottle cap color in ophthalmic medications

Jonathan Paul , Jon David Hammer , Roozbeh Akhtari , Brede Skillings , Daniel B. Moore

2019, 12(1):169-171. DOI: 10.18240/ijo.2019.01.25

[Abstract](1411) [HTML](242) [PDF 281.07 K](616)

Abstract:
A prospective, nonrandomized, observational trial of 60 glaucoma patients to correlate visual acuity and visual field with ability to distinguish bottle cap color of commonly used ophthalmic medications was conducted. A total of 103 eyes from 60 patients (30 women) were evaluated. The mean logMAR acuity was 0.34±0.54 (approximately 20/45 Snellen acuity), average Humphrey Visual Field (HVF) mean deviation was -8.58±8.69 dB, mean Ishihara plates (out of 14) were 11.78±4.15, and bottle cap color score (out of 10) was 8.56±2.51. Multiple linear regression analysis revealed an independent correlation of visual acuity (P=0.0137) and Ishihara score (P<0.001) with cap color score, but no significant effect with visual field mean deviation (P>0.05). Glaucoma patients with poor visual acuity, but not necessarily advanced visual field loss, are likely to have difficultly identifying the color of their bottle caps. Physicians should be cognizant of this potential issue when reviewing medications with patients.

25 Differences in intraocular lens power calculation in patients with sub-foveal choroidal neovascularization

Xing-Chao Shentu , Ya-Lan Cheng , Zhi-Qing Chen , Zhao-An Su , Li Zhang

2019, 12(1):172-174. DOI: 10.18240/ijo.2019.01.26

[Abstract](1603) [HTML](0) [PDF 1.75 M](595)

Abstract:

26 Toxic anterior segment syndrome after implantation of phakic implantable collamer lens

Erick Hernandez-Bogantes , Arturo Ramirez-Miranda , Andrew Olivo-Payne , Alexandra Abdala-Figuerola , Alejandro Navas , Enrique O. Graue-Hernandez

2019, 12(1):175-177. DOI: 10.18240/ijo.2019.01.27

[Abstract](1318) [HTML](0) [PDF 1.21 M](621)

Abstract:

27 Comment on “A case of hypermature cataract formation following implantation of an implantable collamer lens with an Aquaport”

Mark Packer

2019, 12(1):178-178. DOI: DOI:10.18240/ijo.2019.01.28

[Abstract](1378) [HTML](0) [PDF 184.98 K](599)

Abstract:

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Volume 12,Issue 1,2019 Table of Contents