Volume 12,Issue 5,2019 Table of Contents

1 Expression and role of calcitonin gene-related peptide in mouse Aspergillus fumigatus keratitis

Min Yin , Cui Li , Xu-Dong Peng , Gui-Qiu Zhao , Yuan Wu , Heng-Rui Zheng , Qian Wang , Qiang Xu , Nan Jiang

2019, 12(5):697-704. DOI: 10.18240/ijo.2019.05.01

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Abstract:
AIM: To investigate the expression and role of calcitonin gene-related peptide (CGRP) in the mouse models induced by Aspergillus fumigatus (A. fumigatus). METHODS: C57BL/6 mice were randomized into a control group and A. fumigatus keratitis group. The cornea photography was assessed under the slit lamp and the clinical score was recorded after infection. Western blot, real-time polymerase chain reaction (PCR) and immunohistofluorescence analysis were applied to detect CGRP expression in cornea of both groups. In vitro, tests were conducted with C57BL/6 mice macrophages to investigate CGRP expression after interaction with A. fumigatus. Cytokines expression induced by exogenous CGRP and the antagonist CGRP8-37 in A. fumigatus-exposed macrophages was evaluated by real-time PCR and ELISA. RESULTS: The cornea expression of CGRP was significantly elevated in C57BL/6 mice corneas and macrophages after A. fumigatus infection. After treatment with exogenous CGRP, the levels of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and IL-6 were reduced, and IL-10 level was increased in the A. fumigatus stimulated-macrophages. However, IL-1β, TNF-α and IL-6 levels were upregulated after pretreatment of CGRP8-37. But the mRNA levels of MIP-2, TGF-β and IL-10 were not changed. CONCLUSION: This study provides evidence that A. fumigatus increased CGRP expression. CGRP may play a protective role against inflammation in A. fumigatus keratitis.

2 Disparate expression of autophagy in corneas of C57BL/6 mice and BALB/c mice after Aspergillus fumigatus infection

Chen-Yu Li , Cui Li , Hui Li , Gui-Qiu Zhao , Jing Lin , Qian Wang , Xu-Dong Peng , Qiang Xu , Guo-Qiang Zhu , Jia-Qian Jiang

2019, 12(5):705-710. DOI: 10.18240/ijo.2019.05.02

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Abstract:
AIM: To determine the disparate expression of autophagy in the Aspergillus fumigatus (A. fumigatus) keratitis between susceptible C57BL/6 mice and resistant BALB/c mice. METHODS: C57BL/6 and BALB/c mice were used to establish fungal keratitis models. Disease severity and inflammatory response were observed by slit lamp microscopy in A. fumigatus-infected corneas of C57BL/6 and BALB/c mice at 1, 3 and 5d. Hematoxylin-eosin (H&E) staining was used to detect pathological changes of corneas. The expression of autophagy-related proteins Beclin-1, LC3, SQSTM1/p62, and LAMP-1 was assessed by Western blot in C57BL/6 and BALB/c mice at 1, 3 and 5d post infection (p.i.). Immunofluorescent staining was used to test the expression of LC3 in corneas after A. fumigatus infection. RESULTS: Keratitis severity was higher in C57BL/6 mice versus BALB/c mice at 1, 3 and 5d p.i. H&E staining showed that the number of inflammatory cells was larger and the severity of ulcer was higher in C57BL/6 mice than in BALB/c mice after stimulation with A. fumigatus. Higher expression of LAMP-1, Beclin-1, and LC3 was shown in C57BL/6 mice corneas than in BALB/c mice corneas at 1, 3 and 5d p.i., while the expression of p62 was lower in C57BL/6 mice. The fluorescence of LC3 was significantly increased in corneas of C57BL/6 mice compared with BALB/c mice after A. fumigatus infection. CONCLUSION: The expression of autophagy is higher in corneas of C57BL/6 mice than in BALB/c mice after A. fumigatus infection. Autophagy may be positively correlated with keratitis severity and pathological changes.

3 Expression of macrophage migration inhibitory factor in Aspergillus fumigatus keratitis

Qiang Xu , Li-Ting Hu , Qian Wang , Jing Lin , Nan Jiang , Cui Li , Gui-Qiu Zhao

2019, 12(5):711-716. DOI: 10.18240/ijo.2019.05.03

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Abstract:
AIM: To investigate the expression of macrophage migration inhibitory factor (MIF) and detect its role in the innate immune response of fungal keratitis (FK). METHODS: We collected the paraffin-embedded cornea tissues from 10 FK and 6 ocular trauma patients to explore the MIF expression by immunohistochemistry. Then we cultured telomease-immortalized human corneal epithelial cells (THCEs), stimulated by the hyphae suspension of Aspergillus fumigatus (A. fumigatus) to detect the change of MIF with or without the pretreatment of MIF inhibitor [4-Iodo-6-phenylpyrimidine (4-IPP)] by real-time polymerase chain reaction (PCR). The protein level of MIF was also tested by immunohistochemistry, and the level of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) mRNA were compared between normal, hyphae stimulated and 4-IPP pretreated groups by real-time PCR to study the influence of MIF on the expression of TNF-α and IL-6. Corneal severity of rats’ FK models was documented by clinical scores, and real-time PCR. Western blot and immunohistochemistry were used to test the expression of MIF, TNF-α and IL-6 in rats’ corneas. RESULTS: In the corneas of FK patients, there was much stronger expression of MIF than that in the normal group showed by immunohistochemistry. In cultured THCEs stimulated by A. fumigatus, the expression of MIF became stronger in both immunohistochemistry and PCR at 16, 24, 32 and 48h post infection (p.i.; P<0.01, P<0.01, P<0.01, P<0.05). After pretreated with 4-IPP, the expression of MIF reduced at 4, 8, 16h p.i. (P<0.05, P<0.05, P<0.05) and the downstream TNF-α and IL-6 decreased obviously (P<0.05, P<0.01). In rats with A. fumigatus keratitis, the relative mRNA and protein level of MIF increased than those in the normal group by PCR (at 1d: P<0.01, 3d: P<0.01, 5d: P<0.01), Western blot and immunohistochemistry. After blocked MIF with 4-IPP, the clinical outcomes of rat keratitis showed markedly reduced inflammatory response (P<0.01), with TNF-α and IL-6 decreased in accordance with those in THCEs by PCR (P<0.05, P<0.01). CONCLUSION: The expression of MIF increased significantly in FK patients, THCEs and rats stimulated by A. fumigatus. After blocked with 4-IPP, the expression of MIF reduced, and so did its downstream cytokines: TNF-α and IL-6. The inflammation reaction of the rats’ corneas lightened after pretreated with 4-IPP. MIF may play a role in the innate immune response of the corneal resistance against A. fumigatus.

4 Differentiation of human embryonic stem cells derived mesenchymal stem cells into corneal epithelial cells after being seeded on decellularized SMILE-derived lenticules

Yao Chen , Ye-Wei Yin , Yang Zhao , Xiao-Ying Wu , Kelly Young , Wei-Tao Song , Xiao-Bo Xia , Dan Wen

2019, 12(5):717-724. DOI: 10.18240/ijo.2019.05.04

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Abstract:
AIM: To evaluate the feasibility of mesenchymal stem cells (MSCs) to differentiate into corneal epithelial cells after being seeded on the decellularized small incision lenticule extraction (SMILE)-derived lenticules. METHODS: The fresh lenticules procured from patients undergoing SMILE for the correction of myopia were decellularized. The MSCs were subsequently cultivated on those denuded lenticules. The MSCs without lenticules were used as a control. The proliferation activity of the MSCs after seeding 24h was quantitatively determined with the Cell Counting Kit-8 (CCK-8) assay. Immunofluorescence staining and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were used to assess the marker expression in differentiated MSCs. RESULTS: The data showed that both fresh and decellularized lenticules could significantly promote the proliferation of MSCs, compared to that in control (P=0.02 for fresh lenticules, P=0.001 for decellularize ones, respectively). The MSCs seeded on both lenticules were positive for cytokeratin 3 (CK3) staining. The expression of CK3 increased 5-fold in MSCs seeded on fresh lenticules and 18-fold on decellularized ones, compared to that in control. There was a significant difference in the expression of CK3 in MSCs seeded on fresh and decellularized lenticules (P<0.001). The expression of CK8 and CK18 was similar in pure MSCs and MSCs seeded on fresh lenticules (P>0.05), while the expression of these markers was decreased in MSCs seeded on decellularized ones. CONCLUSION: These results suggest that the decellularized lenticules might be more suitable for MSCs to differentiate into corneal epithelial cells, which offers the prospect of a novel therapeutic modality of SMILE-derived lenticules in regenerative corneal engineering.

5 A novel mutation in FBN1 gene in autosomal dominant Marfan syndrome and macular degeneration in a Chinese consanguineous family

Ping-Bo Ouyang , Yuan Zhao , Ying-Qian Peng , Lu-Si Zhang , Jian Cao , Yun Li

2019, 12(5):725-730. DOI: 10.18240/ijo.2019.05.05

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Abstract:
AIM: To report a novel mutation in FBN1 gene in a Chinese consanguineous family with common Marfan syndrome (MFS) phenotype and an unusual bilateral macular degeneration. METHODS: Ophthalmic, cardiovascular and systemic examinations were performed, and genomic DNA extracted from all living family members. The 24-32 exon mutations of FBN1 gene were screened by Sanger Sequencing in all family members and 100 unrelated healthy Chinese individuals. RESULTS: In the four-generation family, classic MFS phenotypes were observed in all 5 patients, 2 of them had peculiar phenotype of bilateral macular degeneration. Mutation screening in FBN1 identified a heterozygous missense mutation (c.3932A>G, p.Y1311C) with co-segregation. This mutation was found with the MFS phenotypes in all 5 patients but not in unaffected members or unrelated controls. CONCLUSION: A Chinese consanguineous MFS family with uncommon bilateral macular degeneration and an unreported c.3932A>G mutation in FBN1 was identified. Our finding expands the FBN1 mutation spectrum and its possible role in the pathogenesis of Marfan syndrome.

6 Effect of etanercept on post-traumatic proliferative vitreoretinopathy

Xiao-Feng Chen , Mei Du , Xiao-Hong Wang , Hua Yan

2019, 12(5):731-738. DOI: 10.18240/ijo.2019.05.06

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Abstract:
AIM: To evaluate the safety and efficacy of intravitreal etanercept in the inhibiting of proliferative vitreoretinopathy (PVR) in a model of penetrating ocular injury. METHODS: Penetrating ocular injury on the retina of rabbit was induced, which was subsequently treated using 0.1 ?mL of sterile water or 0.1? mL of 12.5 mg/mL etanercept. The development of PVR was evaluated by fundus images, the B-scan, and the histopathology. The mRNA and protein expressions of tumor necrosis factor-α (TNF-α), transforming growth factor β (TGF-β) as well as connective tissue growth factor (CTGF) were examined at various time points after the etanercept injection with the reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blotting, respectively. The safety of etanercept was evaluated by injection of 12.5 mg/mL etanercept into a normal rabbit eye without penetrating trauma. RESULTS: Clinical assessment and grading clearly demonstrated that the PVR formation was prevented in etanercept-treated animals, which was confirmed via fundus images, B-scan and histopathology. The RT-PCR and Western blotting showed increased mRNA and protein expression of TNF-α, TGF-β as well as CTGF in the retina of rabbits following penetrating ocular injury, and these factors were dramatically mitigated by ocular etanercept treatment. In addition, there was no adverse effect of etanercept intravitreal injection in normal eyes without penetrating trauma, it showed normal structure and histology. CONCLUSION: The etanercept is a potential therapy for inhibiting PVR development. To assess the clinic application of the etanercept in preventing PVR, further clinical studies are required.

7 Identification of altered microRNAs in retinas of mice with oxygen-induced retinopathy

Lu-Si Zhang , Ye-Di Zhou , Ying-Qian Peng , Hui-Lan Zeng , Shigeo Yoshida , Tan-Tai Zhao

2019, 12(5):739-745. DOI: 10.18240/ijo.2019.05.07

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Abstract:
AIM: To identify disease-related miRNAs in retinas of mice with oxygen-induced retinopathy (OIR), and to explore their potential roles in retinal pathological neovascularization. METHODS: The retinal miRNA expression profile in mice with OIR and room air controls at postnatal day 17 (P17) were determined through miRNA microarray analysis. Several miRNAs were significantly up- and down-regulated in retinas of mice with OIR compared to controls by quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). Two databases including Targetscan7.1 and MirdbV5 were used to predict target genes that associated with those significantly altered miRNAs in retinas of mice with OIR. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were also conducted to identify possible biological functions of the target genes. RESULTS: In comparison with room air controls, 3 and 8 miRNAs were significantly up- and down-regulated, respectively, in retinas of mice with OIR. The qRT-PCR data confirmed that mmu-miR-350-3p and mmu-miR-202-3p were significantly up-regulated, while mmu-miR-711 and mmu-miR-30c-1-3p were significantly down-regulated in mice with OIR compared to controls. GO analysis demonstrated that the identified target genes were related to functions such as cellular macromolecule metabolic process. KEGG pathway analysis showed a group of pathways, such as Wnt signaling pathway, transcriptional misregulation in cancer, Mucin type O-glycan biosynthesis, and mitogen-activated protein kinase (MAPK) signaling pathway might be involved in pathological process of retinal neovascularization. CONCLUSION: Our findings suggest that the differentially expressed miRNAs in retinas of mice with OIR might provide potential therapeutic targets for treating retinal neovascularization.

8 Dose-dependent effects of NMDA on retinal and optic nerve morphology in rats

Lidawani Lambuk , Azliana Jusnida Ahmad Jafri , Igor Iezhitsa , Renu Agarwal , Nor Salmah Bakar , Puneet Agarwal , Aimy Abdullah , Nafeeza Mohd Ismail

2019, 12(5):746-753. DOI: 10.18240/ijo.2019.05.08

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Abstract:
AIM: To investigate dose-dependent effects of N-methyl-D-aspartate (NMDA) on retinal and optic nerve morphology in rats. METHODS: Sprague Dawley rats, 180-250 g in weight were divided into four groups. Groups 1, 2, 3 and 4 were intravitreally administered with vehicle and NMDA at the doses 80, 160 and 320 nmol respectively. Seven days after injection, rats were euthanized, and their eyes were taken for optic nerve toluidine blue and retinal hematoxylin and eosin stainings. The TUNEL assay was done for detecting apoptotic cells. RESULTS: All groups treated with NMDA showed significantly reduced ganglion cell layer (GCL) thickness within inner retina, as compared to control group. Group NMDA 160 nmol showed a significantly greater GCL thickness than the group NMDA 320 nmol. Administration of NMDA also resulted in a dose-dependent decrease in the number of nuclei both per 100 μm GCL length and per 100 μm2 of GCL. Intravitreal NMDA injection caused dose-dependent damage to the optic nerve. The degeneration of nerve fibres with increased clearing of cytoplasm was observed more prominently as the NMDA dose increased. In accordance with the results of retinal morphometry analysis and optic nerve grading, TUNEL staining demonstrated NMDA-induced excitotoxic retinal injury in a dose-dependent manner. CONCLUSION: Our results demonstrate dose-dependent effects of NMDA on retinal and optic nerve morphology in rats that may be attributed to differences in the severity of excitotoxicity and oxidative stress. Our results also suggest that care should be taken while making dose selections experimentally so that the choice might best uphold study objectives.

9 Hydrogen sulfide intervention in cystathionine-β-synthase mutant mouse helps restore ocular homeostasis

Akash K. George , Rubens P. Homme , Avisek Majumder , Anwesha Laha , Naira Metreveli , Harpal S. Sandhu , Suresh C. Tyagi , Mahavir Singh

2019, 12(5):754-764. DOI: 10.18240/ijo.2019.05.09

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Abstract:
AIM: To investigate the applications of hydrogen sulﬁde (H2S) in eye-specific ailments in mice. METHODS: Heterozygous cystathionine-β-synthase (CBS+/-) and wild-type C57BL/6J (WT) mice fed with or without high methionine diet (HMD) were administered either phosphate buffered saline (PBS) or the slow-release H2S donor: GYY4137. Several analyses were performed to study GYY4137 effects by examining retinal lysates for key protein expressions along with plasma glutamate and glutathione estimations. Intraocular pressure (IOP) was monitored during GYY4137 treatment; barium sulfate and bovine serum albumin conjugated fluorescein isothiocyanate (BSA-FITC) angiographies were performed for examining vasculature and its permeability post-treatment. Vision-guided behavior was also tested employing novel object recognition test (NORT) and light-dark box test (LDBT) recordings. RESULTS: CBS deficiency (CBS+/-) coupled with HMD led disruption of methionine/homocysteine (Hcy) metabolism leading to hyperhomocysteinemia (HHcy) in CBS+/− mice as reflected by increased Hcy, and s-adenosylhomocysteine hydrolase (SAHH) levels. Unlike CBS, cystathionine-γ lyase (CSE), methylenetetrahydrofolate reductase (MTHFR) levels which were reduced but compensated by GYY4137 intervention. Heightened oxidative and endoplasmic reticulum (ER) stress responses were mitigated by GYY4137 effects along with enhanced glutathione (GSH) levels. Increased glutamate levels in CBS+/− strain were prominent than WT mice and these mice also exhibited higher IOP that was lowered by GYY4137 treatment. CBS deficiency also resulted in vision-guided behavioral impairment as revealed by NORT and LDBT findings. Interestingly, GYY4137 was able to improve CBS+/− mice behavior together with lowering their glutamate levels. Blood-retinal barrier (BRB) appeared compromised in CBS+/− with vessels’ leakage that was mitigated in GYY4137 treated group. This corroborated the results for occludin (an integral plasma membrane protein of the cellular tight junctions) stabilization. CONCLUSION: Findings reveal that HHcy-induced glutamate excitotoxicity, oxidative damage, ER-stress and vascular permeability alone or together can compromise ocular health and that GYY4137 could serve as a potential therapeutic agent for treating HHcy induced ocular disorders.

10 Conjunctival flora in anophthalmic patients: microbiological spectrum and antibiotic sensitivity

Alvaro Toribio , Teresa Marrodán , Isabel Fernández-Natal , Honorina Martínez-Blanco , Leandro Rodríguez-Aparicio , Miguel Á. Ferrero

2019, 12(5):765-773. DOI: 10.18240/ijo.2019.05.10

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Abstract:
AIM: To identify the spectrum and susceptibility pattern of isolated microorganisms from conjunctival flora of anophthalmic patients. METHODS: A cross-sectional clinical study including 60 patients with unilateral anophthalmia. Patients with use of antibiotic drops in their socket during the last month were also included. From each patient, three microbiological samples were taken from the lower conjunctival sac (healthy eye, pre-prosthesis, and retro-prosthesis space of socket). The 180 samples obtained were cultured. Isolates were identified and their antibiotic sensitivities were determined. RESULTS: A total of 251 isolates were recovered (62 isolates from healthy eye, 93 from pre-prosthesis, and 96 from retro-prosthesis space). The most common organism was Staphylococcus epidermidis, in both healthy eyes (64.5%) and sockets (45.5%). Altogether, coagulase-positive Staphylococci, Streptococci, and Gram-negative bacteria accounted for less than 15% of isolates in healthy eyes and more than 35% in sockets. Regarding the antibiotic sensitivities, there were no significant differences between isolates from sockets and healthy eyes. Nine patients recognized the use of self-prescribed antibiotic drops in their socket. In the healthy eyes of these subjects, Gram-positive microorganisms showed significantly greater resistance to aminoglycosides and tetracycline. CONCLUSION: Sockets of anophthalmic patients show a greater number of pathogens compared to healthy eyes. The use of antibiotic drops in the socket promotes a resistant flora not only in the socket but also in the healthy eye. Quinolones and macrolides may be better therapeutic options than aminoglycosides for treating conjunctivitis of anophthalmic sockets, since these antibiotics are less active against Staphylococcus epidermidis.

11 Safety & efficacy of single subconjunctival triamcinolone 5 mg depot vs topical loteprednol post cataract surgery: less drop cataract surgery

Jagadeesh Kumar Reddy , Vivek Chaitanya , Neeraj Shah , Venkata Prabhakar Guduru , Shadab Khan , Siddharthan Kuttupalayam

2019, 12(5):774-778. DOI: 10.18240/ijo.2019.05.11

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Abstract:
AIM: To do a randomized prospective interventional study for comparing the effects of a single subconjunctival triamcinolone acetonide (SCTA) injection to tapering topical loteprednol in patients undergoing phacoemulsification surgery under topical anesthesia. METHODS: A total of 400 patients were randomized into 2 groups; Group A (200 patients) received 5 mg SCTA at the end of surgery and topical ketorolac tromethamine (0.5%) with ofloxacin (0.3%) combination for 3wk. Group B (200 patients) received tapering topical loteprednol etabonate (0.5%) along with ofloxacin (0.3%) and ketorolac tromethamine (0.5%) for 3wk. Outcomes evaluated were intraocular pressure (IOP), anterior chamber cells/flare and macular oedema postoperatively at 1, 6 and 12wk. RESULTS: Baseline parameters were almost similar in both the groups. No statistical difference was seen between the preoperative and postoperative IOP values for Group A (P=0.82) and Group B (P=0.61) and postoperative IOP values in between both groups (P=0.14) at 1wk. Incidence of cells/flare postoperative was statistically not significant (P=0.82) in both groups at all follow up visits. Postoperative macular oedema was not observed at any follow up visit. CONCLUSION: SCTA appears to be an effective alternative to prolong postoperative topical steroid use.

12 Pediatric Nd:YAG laser capsulotomy in the operating room: review of 87 cases

Michael Kinori , Narasimhan Jagannathan , Anne M Langguth , Marjorie A Sasso , Marilyn B Mets , Bahram Rahmani , Hawke Yoon , Rebecca Mets-Halgrimson , Sudhi P Kurup , Janice L Zeid

2019, 12(5):779-783. DOI: 10.18240/ijo.2019.05.12

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Abstract:
AIM: To report a large series of children having Nd:YAG laser capsulotomy in the operating room using the lateral decubitus position. METHODS: Medical records of children who underwent Nd:YAG laser capsulotomy in the operating room at Ann & Robert H. Lurie Children’s Hospital of Chicago between September 2008 and April 2017 were reviewed. Induction of general anesthesia and intubation was performed in the supine position after which the patient was placed in lateral decubitus position. The Nd:YAG laser capsulotomy was performed using a standard protocol. At the completion of the procedure, the patient was turned back into the supine position and extubated. RESULTS: This study included 87 eyes of 60 patients. Patient’s age ranged from 1 to 18y (mean 6.4±4.1y). In most cases (84/87, 97%), the procedure was performed under general anesthesia. In all cases, good focus on the membrane was achieved, and the procedure was performed successfully. There were no intraoperative ocular or anesthesia-related complications. CONCLUSION: When performing Nd:YAG laser capsulotomy in the operating room, the lateral decubitus position allows an easy and safe approach without the risk of potentially devastating complications that have been associated with the previously described sitting and prone positions.

13 Efficacy and safety of micropulse laser trabeculoplasty for primary open angle glaucoma

Ying Hong , Si-Jia Song , Bo Liu , Kiana Hassanpour , Chun Zhang , Nils Loewen

2019, 12(5):784-788. DOI: 10.18240/ijo.2019.05.13

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Abstract:
AIM: To evaluate the efficiency and safety of micropulse laser trabeculoplasty (MLT) for primary open angle glaucoma (POAG) patients. METHODS: Retrospective study. POAG patients undergoing MLT in Peking University Third Hospital from June 2016 to November 2017. Seventy-two eyes of 72 POAG patients were enrolled. Only one eye of each patient was treated by MLT. The intraocular pressure (IOP) before MLT and at 1d, 1, 4, 12 and 24wk and glaucoma medication before and after treatment were compared. RESULTS: The IOP was 20.6±5.9 mm Hg before MLT and 20.8±6.8 mm Hg at 2h after MTL. The IOP at 1d, 1, 4, 12 and 24wk was 17.9±4.4, 18.0±4.3, 17.5±3.4, 17.0±2.7, and 16.5±2.9 mm Hg, respectively. The IOP before and after MLT demonstrated a statistically significant difference by ANOVA analyses (F=5.797, P<0.001). Least significant difference t-tests showed there was no statistically significant difference between pre-MLT IOP within 2h after MLT (P=0.207). The statistically significant difference was confirmed between the pre-MLT IOP at 1d, 1, 4, 12 and 24wk after MLT (P=0.006, 0.009, 0.001, <0.001, <0.001, respectively). The number of glaucoma medications before MLT was 1.7±1.4 and 1.5±1.4 24wk after MLT with a significantly statistical difference (t=2.219, P=0.031) CONCLUSION: MLT is effective and safe for POAG patients. No patient experienced IOP spikes after MLT. The IOP 6mo after treatment decreased significantly with less glaucoma medication.

14 Retinal nerve fiber layer changes based on historic CD4 nadir among HIV positive patients undergoing glaucoma evaluation

Sarah H. Van Tassel , Paul Petrakos , Elizabeth Marlow , Elizabeth Mauer , Harjot K. Singh , Anna M. Demetriades

2019, 12(5):789-794. DOI: 10.18240/ijo.2019.05.14

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Abstract:
AIM: To determine relationships between retinal nerve fiber layer (RNFL) thickness and nadir CD4 cell count in human immunodeficiency virus (HIV) positive patients evaluated for glaucoma suspicion. METHODS: Data were reviewed for 329 HIV positive patients evaluated for glaucoma suspicion. High-definition optical coherence tomography (OCT) RNFL measurements were obtained at least 6mo apart. Analyses were performed to identify relationships between nadir CD4 count and RNFL thickness. RESULTS: Totally 110 eyes of 55 patients met inclusion criteria, of which 46 eyes were from subjects with nadir CD4<200 cells/mm3 and 64 had nadir CD4≥200 cells/mm3. Patients with nadir CD4<200 cells/mm3 had significantly thicker superior (119.7±18.6 µm) and temporal (63.8±11.7 µm) quadrants at time of initial OCT compared to the superior (112.8±16.8 µm, P=0.048) and temporal (57.1±11.9 µm, P=0.004) quadrants of patients with higher nadir CD4. This trend toward thicker RNFL among subjects with lower nadir CD4 cell counts persisted at the time of follow up OCT where participants with nadir CD4<200 cells/mm3 showed average RNFL thickness in the superior and temporal quadrants of 117.9±18.3 µm and 63.8±12.8 µm, respectively, compared to a superior thickness of 110.5±16.9 µm (P=0.034) and temporal thickness of 57.3±11.6 µm (P=0.007) among those with higher nadir CD4. CONCLUSION: Patients with lower nadir CD4 cell counts have thicker RNFL in the superior and temporal quadrants compared to those with higher nadir CD4 counts. RNFL thickness in HIV positive patients may be affected by historic HIV disease control and should be considered when evaluating HIV positive patients for glaucoma.

15 Inflammatory model in patients with primary open angle glaucoma and diabetes

Anca Pantalon , Otilia Obadă , Daniela Constantinescu , Crenguța Feraru , Dorin Chiseliță

2019, 12(5):795-801. DOI: 10.18240/ijo.2019.05.15

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Abstract:
AIM: To assess the inflammatory cytokines expression in aqueous humor in diabetic primary open angle glaucoma (POAG) patients. METHODS: A cross-sectional study on 87 eyes, distributed as following: 26 eyes from diabetic patients, 16 eyes with POAG and 21 eyes from diabetic POAG patients; healthy controls (24 eyes) were recruited from patients undergoing conventional cataract surgery. A volume of 100 μL of aqueous humor (AH) was collected during phacoemulsification and 21 inflammatory markers were quantified using a Luminex® cytometric bead assay: IL-1Ra, IL-1α, IL-1β, IL-5, IL-6, IL-10, IL-17, GM-CSF, IFNγ, CCL2, CCL3, CCL4, CXCL5, CXCL8, bFGF, VEGF, TNFα. Main changes in cytokine profile were analyzed and compared between groups. Data on demographics, duration of glaucoma, intraocular pressure (IOP), number of anti-glaucoma substances were recorded for correlation analysis and prediction models. RESULTS: Significant differences in cytokine expression between groups were detected for CXCL5 (P<0.001), CXCL8 (P=0.004), IL-1α (P<0.001), IL-2 (P<0.001), CCL4 (P=0.003), CCL5 (P<0.001) and TNFα (P=0.05). Post-hoc analysis identified IL-2 (P=0.009) and CXCL5 (P<0.001) as “separation markers” between POAG and diabetic POAG eyes. In POAG patients, the “separation markers” could highly predict the TNFα levels F(1, 16)=14.639, P<0.001, whereas in diabetic patients F(1, 24)=4.844, P=0.006 and diabetic POAG patients F(1, 19)=2.358, P=0.05 the level of prediction was inferior. CONCLUSION: Our results reveal an inflammatory model based on increased TNFα levels in POAG eyes. Simultaneous co-stimulatory molecules and additional inflammatory pathways need to be further explored in diabetic POAG cases, since the prediction model could only partially explain the increased TNFα level in this category of patients.

16 Microvascular changes after conbercept therapy in central retinal vein occlusion analyzed by optical coherence tomography angiography

Yang Deng , Qi-Wen Zhong , Ai-Qi Zhang , Xiao-Juan Cai , Ming-Zhi Lu , Shao-Chong Zhang , Li-Shi Su , Hui Chen , Ying Lin , Li-Mei Sun , Guan-Di Chen , Li-Ting Zhong , Chen-Jin Jin , Wei Chi

2019, 12(5):802-808. DOI: 10.18240/ijo.2019.05.16

[Abstract](1889) [HTML](259) [PDF 1.27 M](697)

Abstract:
AIM: To investigate microvascular changes in eyes with central retinal vein occlusion (CRVO) complicated by macular edema before and after intravitreal conbercept injection and evaluate correlations between these changes and best-corrected visual acuity (BCVA) and retinal thickness. METHODS: Twenty-eight eyes of 28 patients with macular edema caused by CRVO were included in this retrospective study. All patients received a single intravitreal conbercept injection to treat macular edema. BCVA and the results of optical coherence tomography angiography (OCTA) automatic measurements of the vessel density in the superficial (SCP) and deep retinal capillary plexus (DCP), the foveal avascular zone (FAZ) area, the FAZ perimeter (PERIM), the vessel density within a 300-μm wide ring surrounding the FAZ (FD-300), the acircularity index (AI), the choriocapillaris flow area, and retinal thickness were recorded before and at one month after treatment and compared with the results observed in age- and sex- matched healthy subjects. RESULTS: The vessel density in the SCP and DCP, the FD-300, and the flow area of the choriocapillaris were all significantly lower in CRVO eyes than in healthy eyes, while the AI and retinal thickness were significantly higher (all P<0.05). After treatment, retinal thickness was significantly decreased, and the mean BCVA had markedly improved from 20/167 to 20/65 (P=0.0092). The flow area of the choriocapillaris was also significantly improved, which may result from the reduction of shadowing effect caused by the attenuation of macular edema. However, there were no significant changes in SCP and DCP vessel density after treatment. The flow area of the choriocapillaris at baseline was negatively correlated with retinal thickness. CONCLUSION: OCTA enables the non-invasive, layer-specific and quantitative assessment of microvascular changes both before and after treatment, and can therefore be used as a valuable imaging tool for the evaluation of the follow-up in CRVO patients.

17 Task sharing: situation analysis about capacity and resources for management of diabetic retinopathy in Pakistan

Mufarriq Shah , Ayesha Noor , C Alex Harper , Jill Elizabeth Keeffe

2019, 12(5):809-814. DOI: 10.18240/ijo.2019.05.17

[Abstract](1168) [HTML](242) [PDF 320.89 K](555)

Abstract:
AIM: To assess the capacity and resources of eye care facilities, using the WHO Health Systems Framework, to manage diabetic retinopathy (DR) through task sharing. METHODS: Using purposive sampling, four participants (administrators) from four selected hospitals in two provinces in Pakistan were recruited for this cross-sectional study. A survey, to assess the capacity and resources of the selected eye care facilities for the feasibility to adopt task sharing in management of DR to prevent vision loss, was emailed to participants who were asked to complete. Responses to open-ended questions were entered into a Microsoft Excel spread sheet and inductive approach was applied for analysis. RESULTS: All the surveyed eye care facilities offer eye care services for people with diabetes and DR. All surveyed eye care facilities have a shortage in the number of human resources across all cadres. Optometrists and mid-level eye care workers did not have active roles in DR screening and management in all four hospitals. All the hospitals surveyed did not have a computerized record management system for patients who visit ophthalmologists for eye examinations. Equipment for detection and management of DR were short in number and main users were ophthalmologists. There was no policy for population-based screening program for detection of DR in any of the surveyed hospitals. CONCLUSION: A system-based approach to manage DR is needed. The capacity of eye care facilities and the potential to improve access of people with diabetes to eye care services can be enhanced through implementation of task sharing.

18 Axial length development in children

Austin Bach , Victor M. Villegas , Aaron S. Gold , Wei Shi , Timothy G. Murray

2019, 12(5):815-819. DOI: 10.18240/ijo.2019.05.18

[Abstract](2540) [HTML](256) [PDF 426.04 K](900)

Abstract:
AIM: To study ocular axial lengths in pediatric subjects without intraocular pathology. METHODS: An Institutional Review Board-approved consecutive retrospective chart review of axial lengths measured in pediatric subjects who underwent examination under anesthesia due to positive family history of retinoblastoma or other inherited ocular disease. Only subjects without any intraocular pathology in either eye were included. Subjects were stratified into age groups. An axial length model using a logarithmic regression algorithm was calculated. RESULTS: Data from 330 eyes of 165 subjects were included in the study. The mean age at the time of examination was 30.62 (SD 18.04)mo. The steepest increase in axial length was present during the first 10mo of life. After 36mo, there was no statistically significant axial length growth. CONCLUSION: This study presents the biggest series of pediatric axial lengths in healthy eyes. The axial length model developed with these data may assist in the diagnosis and management of a wide variety of pediatric ophthalmic diseases.

19 Prevalence of amblyopia among preschool children in central south China

Yun-Ping Li , Meng-Wen Zhou , Susan H Forster , Si-Ying Chen , Xin Qi , Hui-Ming Zhang , Jing Luo

2019, 12(5):820-825. DOI: 10.18240/ijo.2019.05.19

[Abstract](1559) [HTML](254) [PDF 388.92 K](597)

Abstract:
AIM: To determine the prevalence and factors associated with amblyopia among children aged 30-83mo in central south of China. METHODS: A population-based, cross-sectional study was conducted in children aged 30-83mo in Changsha (an urban city) and Zhangjiajie (a rural area) in central south of China. Clinical examinations including ocular alignment, ocular motility, visual acuity (VA), prism cover test, cycloplegic refraction, slit lamp examination and fundus examination were performed by trained study ophthalmologists and optometrists. Unilateral amblyopia was defined as a 2-line difference between eyes with VA<20/32 in the worse eye and with coexisting anisometropia [≥1.00 D spherical eutivalent (SE) for hyperopia, ≥3.00 D SE for myopia, and ≥1.50 D for astigmatism], strabismus, or past or present visual axis obstruction. Bilateral amblyopia was defined as VA in both eyes <20/40 (≥ 48-month-old) and <20/50 (< 48-month-old), with coexisting hyperopia ≥4.00 D SE, myopia ≤-6.00 D SE, and astigmatism ≥2.50 D, or past or present visual axis obstruction. RESULTS: There were 8042 children enrolled and 7713 children were screened. The amblyopia prevalence in children aged 30-83mo was 1.09% (95% confidence interval, 0.86%-1.35%) with no age (P=0.81), gender (P=0.46) or area distribution (P=0.93) differences. Of these, 0.68% were unilateral cases and 0.41% were bilateral cases. Underlying causes included anisometropia (40%), binocular refractive error (36%), strabismus (14%) and deprivation (10%). Hyperopia combined with astigmatism was the frequent refractive error for ametropic and anisometropic amblyopia. CONCLUSION: In this rural and urban Chinese population, 1.09% of children with 30-83mo of age had amblyopia, a prevalence rate similar to that of many other studies. Anisometropia and refractive error are the most common causes of unilateral and bilateral amblyopia respectively.

20 Phacoemulsification with or without goniosynechialysis for angle-closure glaucoma: a global Meta-analysis based on randomized controlled trials

Nuo Wang , Song-Bai Jia

2019, 12(5):826-833. DOI: 10.18240/ijo.2019.05.20

[Abstract](1566) [HTML](247) [PDF 1.16 M](608)

Abstract:
AIM: To compare the benefits and potential harms of routine phacoemulsification (phaco) alone and combined surgery with goniosynechialysis (GSL) for angle-closure glaucoma (ACG) and coexisting lens opacity, as shown in different randomized controlled trials (RCTs). METHODS: A systematic review was conducted searching several databases including PubMed, Cochrane Library, EMBASE, ClinicalTrials.gov from the inception to September 2018 for RCTs with data published on the effects and safety of phaco and intraocular lens implantation combined with GSL or routine cataract surgery alone. Several studies were recruited which reported data at baselines and postoperative follow-up, including the mean values of postoperative intraocular pressure (IOP) and mean numbers of anti-glaucoma medications using postoperatively. The numbers of complications happening were also included. Fixed-effect and random-effect models were applied, and the quality of evidence was evaluated. RESULTS: Analysis of the seven included RCTs, with a total number of 321 participants (358 eyes) diagnosed with ACG and cataract, received a solo procedure (phaco group) or a combined surgery (phaco-GSL group) randomly, and follow-up periods ranging from 2 to 12mo postoperatively. The involved studies showed that the mean value of IOP between the two groups at 3 (four studies, one study follow-up at 2mo postoperative was included), 6, 12mo postoperative were not significantly different. Only two studies reported the change in IOP value at 12mo compared with baseline but showed no significant differences between the two interventions. Although three studies did not have the significant difference in the number of medications using to reduce IOP at 3mo postoperatively, two studies reported that the participants using fewer anti-glaucoma medications at 12mo postoperative in the phaco group than in the phaco-GSL surgery group. CONCLUSION: The analysis provides a low to moderate-quality evidence that phaco-GSL surgery lead to an equivalent IOP-lowering effect. The phaco-GSL surgery may not help patients to reduce the consumption of anti-glaucoma eyedrops in the long period. The results of this analysis suggested that additional GSL may not be necessary for primary angle closure glaucoma (PACG) patients. Further studies, especially RCTs with more participants and longer follow-up time were needed to provide more sufficient data.

21 Ocular manifestations of internal carotid artery dissection

Jin-Xin Song , Xue-Mei Lin , Zhao-Qin Hao , Song-Di Wu , Yong-Xin Xing

2019, 12(5):834-839. DOI: 10.18240/ijo.2019.05.21

[Abstract](1638) [HTML](245) [PDF 310.19 K](624)

Abstract:
Internal carotid artery dissection (ICAD) results from disruption of the intima of the arterial wall, and can lead to intrusion of blood into the arterial wall and form an intramural hematoma. The hematoma can compress the true lumen of the vessel, causing functional stenosis or occlusion. The classic triad signs of ICAD include pain in the ipsilateral neck, head and orbital regions; a (partial) Horner syndrome; and cerebral or retinal ischemia. However, not all ICAD patients present with this classic signs. In some cases, ocular manifestations are the initial (and sometimes the only) findings. We summarize the ocular manifestations associated with ICAD in 3 categories: visual symptoms, oculosympathetic palsy, and ocular motor nerve palsy.

22 Visual and refractive outcomes of posterior chamber phakic IOL in stable keratoconus

Sherif H Emerah , Moataz M Sabry , Hisham A Saad , Waleed A Ghobashy

2019, 12(5):840-843. DOI: 10.18240/ijo.2019.05.22

[Abstract](1447) [HTML](258) [PDF 347.15 K](691)

Abstract:
We evaluated the visual and refractive outcomes after phakic visian toric implantable collamer lens (ICL) insertion in stable keratoconus (KC). This retrospective study investigated toric ICL implantation in 14 eyes of 8 patients with stable KC. After 6mo, the mean uncorrected distance visual acuity improved significantly from 0.77 to 0.15 logMAR. The mean best corrected distance visual acuity (BCDVA) improved from 0.18±0.1 to 0.15±0.1 logMAR. Fifty percent of eyes maintained their preoperative BCDVA; 42.8% gained one line. There was no statistical difference in high order or coma aberration. The mean refractive manifest spherical equivalent (MSE), mean refractive manifest spherical error, mean manifest astigmatism decreased significantly postoperatively. At 6mo postoperatively, our achieved mean spherical equivalent was approximately 74%. No intraoperative or postoperative complications occurred. Toric ICL implantation was effective, predictable and safe to correct refractive error and improve visual acuity in patients with stable KC.

23 Comparison of OA-2000 and IOL Master 500 using in cataract patients with high myopia

Ya-Li Du , Geng Wang , Hui-Chun Huang , Li-Yu Lin , Chuang Jin , Li-Fang Liu , Xiu-Ru Liu , Ming-Zhi Zhang

2019, 12(5):844-847. DOI: 10.18240/ijo.2019.05.23

[Abstract](1777) [HTML](256) [PDF 929.68 K](796)

Abstract:
This study was designed to compare optical biometry measurements and predicted refraction in cataract patients with high myopia [axial length (AL) ≥26 mm] using OA-2000 and IOL Master 500. Ocular biometry measurements were performed using both biometers before surgery. Uneventful cataract surgery was performed in all patients. Postoperative manifest refraction was obtained 3wk after surgery or later. A total of 67 eyes were examined. The AL, keratometry (K), and anterior chamber depth (ACD) of the two biometers showed excellent agreement. Predicted errors were similar and a strong positive correlation was observed (r=0.909). Out of 21 eyes (31.34%) with unsuccessful AL readings using the IOL Master 500, 20 eyes of them could be measured using OA-2000. Therefore, the biometric parameters measured by the two biometers showed good agreement. However, OA-2000 had a lower AL measurement failure rate.

24 Free autologous internal limiting membrane transplantation in the treatment of large macular hole

Fei-Yan Ma , Rui-Jie Xi , Peng-Fei Chen , Yu-Hua Hao

2019, 12(5):848-851. DOI: 10.18240/ijo.2019.05.24

[Abstract](1109) [HTML](247) [PDF 693.94 K](572)

Abstract:
We evaluated the clinical efficacy of free internal limiting membrane (ILM) flap transplantation for the treatment of large macular hole over 500 μm in 42 consecutive patients. Quantified evaluation of the post-operative macular anatomy restoration was performed by spectral-domain optical coherence tomography in the 12mo follow-up. The results showed 41 eyes achieved successful closure (97.6%). Postoperative best corrected visual acuity, ellipsoid layer, and external limiting membrane disruption were significantly improved at all follow-up time points. The central foveal thickness was significantly higher at 1mo. We concluded that free ILM flap transplantation proves to be effective to achieve anatomical and functional improvement for the treatment of large macular hole.

25 The macular microstructure repair and predictive factors of surgical outcomes after vitrectomy for idiopathic macular hole

Jing-Ling Zou , Jun Zeng

2019, 12(5):852-857. DOI: 10.18240/ijo.2019.05.25

[Abstract](966) [HTML](254) [PDF 791.48 K](610)

Abstract:
To evaluate the macular microstructure repair and explore the factors related to those changes and visual improvement after vitrectomy for idiopathic macular hole (IMH). Totally 19 eyes of 18 IMH patients who underwent macular hole (MH) surgery were evaluated with best-corrected visual acuity (BCVA) and spectral-domain optical coherence tomography (SD-OCT) images. All 19 eyes closed at 6mo postoperatively. BCVA was observed gradually improved (P<0.001), with subretinal fluid (SRF) gradually absorbed (P=0.021) and the rate of external limiting membrane (ELM) defects gradually decreased (P=0.011) with follow-up time. Poorer postoperative logMAR BCVA correlated with larger MH minimum diameter (P<0.001), larger MH basal diameter (P=0.008), longer symptom duration (P=0.002) and poorer preoperative logMAR BCVA (P=0.010). More improvement in BCVA correlated only with poorer preoperative in logMAR BCVA (P=0.002). The earlier reconstruction of ELM was associated with smaller MH basal diameter (P=0.022) and shorter symptom duration (P=0.008). In conclusion, smaller basal diameter of MH and shorter symptom duration were key factors in earlier reconstruction of ELM.

26 Correlation analysis and multiple regression formulas of refractive errors and ocular components

Chao-Kai Chang , Jui-Teng Lin , Yong Zhang

2019, 12(5):858-861. DOI: 10.18240/ijo.2019.05.26

[Abstract](1197) [HTML](236) [PDF 565.72 K](561)

Abstract:
The multiple regression formulas and correlation of ocular components with refractive errors are presented by Gaussian optics. The refractive error changing rate for the cornea and lens power, the axial length, anterior chamber depth (ACD) and vitreous chamber depth (VCD) are calculated, including nonlinear terms for more accurate rate functions than the linear theory. Our theory, consistent with the empirical data, shows that the Pearson correlation coefficients for spherical equivalent (SE) and ocular components are highest for SE with axial length, ACD and VCD and weakest for corneal power, lens power and lens thickness. Moreover, our regression formulas show the asymmetric feature of the correlation that the axial length, ACD and VCD are more strongly correlated (with higher negative regression constants) with refractive errors in eyes with hyperopia than in eyes with myopia, particularly for severe hyperopia.

27 Late traumatic flap dislocation seven years after femtosecond laser-assisted in situ keratomileusis

María T. Alvarez , Andrea Montesel , Laurent Bataille

2019, 12(5):862-865. DOI: 10.18240/ijo.2019.05.27

[Abstract](832) [HTML](242) [PDF 1.38 M](594)

Abstract:

28 Combined Descemet stripping automated endothelial keratoplasty and intravitreal dexamethasone implant for concomitant pseudophakic bullous keratopathy and cystoid macular edema

Gabriella Cirigliano , Marco R Pastore , Alberto A Perrotta , Chiara De Giacinto , Daniele Tognetto

2019, 12(5):866-869. DOI: 10.18240/ijo.2019.05.28

[Abstract](927) [HTML](248) [PDF 975.39 K](545)

Abstract:

29 A presumed iridocyclitis developed to panophthalmitis caused by a non-metallic intraocular foreign body

Yan Weng , Jian Ma , Li Zhang , Hong-Ying Jin , Xiao-Yun Fang

2019, 12(5):870-872. DOI: 10.18240/ijo.2019.05.29

[Abstract](959) [HTML](248) [PDF 820.54 K](595)

Abstract:

30 Peripheral ulcerative keratitis and otitis media as initial symptoms of Wegener’s granulomatosis: a case report

Jing Liang , Wei Fan , Rong-Di Yuan

2019, 12(5):873-876. DOI: 10.18240/ijo.2019.05.30

[Abstract](911) [HTML](231) [PDF 1.26 M](593)

Abstract:

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Volume 12,Issue 5,2019 Table of Contents