Association For Research In Vision And Ophthalmology Research Articles

Utilizing a composite citation index for evaluating clinical ophthalmology research: insights into gender, nationality, and self-citation among top ophthalmology researchers.

To compare the performance of a composite citation score (c-score) and its six constituent citation indices, including H-index, in predicting winners of the Weisenfeld Award in ophthalmologic research. Secondary objectives were to explore career and demographic characteristics of the most highly cited researchers in ophthalmology. A publicly available database was accessed to compile a set of top researchers in the field of clinical ophthalmology and optometry based on Scopus data from 1996 to 2021. Each citation index was used to construct a multivariable model adjusted for author demographic characteristics. Using area under the receiver operating curve (AUC) analysis, each index's model was evaluated for its ability to predict winners of the Weisenfeld Award in Ophthalmology, a research distinction presented by the Association for Research in Vision and Ophthalmology (ARVO). Secondary analyses investigated authors' self-citation rates, career length, gender, and country affiliation over time. Approximately one thousand unique authors publishing primarily in clinical ophthalmology/optometry were analyzed. The c-score outperformed all other citation indices at predicting Weisenfeld Awardees, with an AUC of 0.99 (95% CI: 0.97-1.0). The H-index had an AUC of 0.89 (95% CI: 0.83-0.96). Authors with higher c-scores tended to have longer career lengths and similar self-citation rates compared to other authors. Sixteen percent of authors in the database were identified as female, and 64% were affiliated with the United States of America. The c-score is an effective metric for assessing research impact in ophthalmology, as seen through its ability to predict Weisenfeld Awardees.

Japan to Global Eye Genetics Consortium: Extending Research Collaboration for Inherited Eye Diseases.

Japan Eye Genetics Consortium (JEGC) was established in 2011 to migrate research system to all-Japan structure for collecting phenotype-genotype information for inherited retinal diseases and other retinal diseases including hereditary optic neuropathy and hereditary glaucoma. Diagnostic team was assembled to maintain quality of diagnostic and to collect phenotype information to database in Tokyo Medical Center (TMC). Over the past 10 years, 1538 pedigree [2788 deoxyribonucleic acid (DNA) samples] was collected from 38 ophthalmology departments and eye hospitals. Whole exome analysis has improved diagnostic rate from ~17% in 2011 to 53% in 2021, with 27% of known variants, 18% of novel variants in known gene, 8% of potential novel disease-causing genes, and 47% of pedigree with unknown cause. Approximately 70% of Japanese patients were affected by novel mutation or by unknown cause. In 2014, Asian Eye Genetics Consortium (AEGC) was established by researchers from Hong Kong, India, Japan, and the US, later renamed to Global Eye Genetics Consortium (GEGC) to expand the idea of collaborative research on rare genetic eye diseases in Asia, Middle East, Africa, and South America. GEGC phenotype-genotype database, GenEye, was constructed to collect and catalog genetic eye diseases at global scale. Over 200 members from 30 countries, GEGC now has 200 members from 30 continents, performing scientific programs, young investigator visiting program, and GEGC organized session at the meetings of the Asia-Pacific Academy of Ophthalmology (APAO), The Association for Research in Vision and Ophthalmology (ARVO), All India Ophthalmological Society (AIOS), World Ophthalmology Congress (WOC), and International Society for Eye Research (ISER).

Association for Research in Vision and Ophthalmology (ARVO) - 2022 Annual Meeting. Denver/Virtual - May 1-4 and 11-12, 2022

Association for Research in Vision and Ophthalmology (ARVO) - 2022 Annual Meeting. Denver/Virtual - May 1-4 and 11-12, 2022

Tribology and the Ocular Surface.

IntroductionTribology is known as the science of friction, lubrication and the determination of what occurs when two surfaces slide against one another. The required partners in this science are a minimum of two surfaces and relative motion. Tribology could be a key factor in dissecting the issues that surround and confound dry eye in patients as well as contact lens discomfort and intolerance. Specifically, it is this issue that is a potential causative underlying factor that could lead to conditions like lid wiper epitheliopathy (LWE).MethodsPeer-reviewed literature was reviewed as It pertains to ocular tribology and the application to the ocular anatomy. A PubMed review was performed using the keywords: tribology, friction, lid wiper epitheliopathy, contact lens, and dry eye. All manuscripts were reviewed for mentions of tribology and friction. The exact same process was performed with The Association for Research in Vision and Ophthalmology (ARVO) abstracts.ResultsIn relation to the ocular surface, tribology describes the mechanical interactions between the upper and lower lid wipers and the globe. The Stribeck curve can be applied, as the sliding partners are separated by a complex, lubricating tear film. The surface brush anatomy at the eye to eyelid juncture reduces friction and alters the Stribeck curve in favor of the hydrodynamic regime, allowing for high velocity movement with minimal wear. Changes to the tear film or the introduction of a contact lens can displace the Stribeck curve, increase friction, and induce wear thus leading to patient symptomology.ConclusionFurther studies may provide new insight into contact lens discomfort and ocular surface disease, including LWE; however, adaptation of tribology work performed in vitro to in vivo patient care is challenging.

CD23 mediated the induction of pro-inflammatory cytokines Interleukin-1 beta and tumor necrosis factors-alpha in Aspergillus fumigatus keratitis.

CD23 mediated the induction of pro-inflammatory cytokines Interleukin-1 beta and tumor necrosis factors-alpha in Aspergillus fumigatus keratitis.

MAP4K4 is Involved in the Neuronal Development of Retinal Photoreceptors

Differentiated from multipotent neural progenitors, the development of retinal photoreceptors is under sophisticated programming of multiple genes. Mitogen-activated protein kinase kinase kinase kinase-4 (MAP4K4) is one of the upstream regulators in the mitogen-activated protein kinase (MAPK) signaling pathway, associated to neurodegeneration. However the role of MAP4K4 in retina—an extension of neural system—remains unknown. In the present study, we generated knockout models of C57BL/6j mice in vivo and 661W cells in vitro to unfold the mechanism of MAP4K4 during neuronal development of retinal photoreceptors. We identified the linkage between the Map4k4 ablation induced murine homozygous lethality and neural tube malformation during the embryonic phase from EM9.5 to EM10.5, providing a collateral evidence for the involvement of MAP4K4 in early stage embryonic neural formation. To further clarify the participation of MAP4K4 in neurogenesis of photoreceptors, we subjected 661W cells of both Map4k4 +/+ and Map4k4 -/- to staurosporine. Later, spatiotemporal development and remodeling of photoreceptor cells were detected. Ablation of Map4k4 leaded to vulnerability of photoreceptor nerites during induced neuronal development. By monitoring transcriptional and protein variation of MAPK signaling pathway targeted factors, we discovered the imbalanced neurogenesis factors occurring in Map4k4 -/- cells. MAP4K4 promoted jun proto-oncogene (c-JUN) phosphorylation and recruited other factors related to nerve growth, convoying the photoreceptors to robust formation of neurites. Together, MAP4K4 showed decisiveness in the programming fate of retinal photoreceptors through molecular modulations, which may be providing a new insight into the blueprint of visual formation. Funding Statement: This study was supported by the National Natural Science Foundation of China (81670874 and 81670885), the Natural Science Foundation of Gurangdong Province of China (2020A1515010144), the Fundamental Research Funds and the Open Research Funds of the State Key Laboratory of Ophthalmology. Declaration of Interests: The authors declare no conflicts of interest. Ethics Approval Statement: All animal experiments in this study were approved by and in compliance with the guides of the Animal Experimentation Ethics Committee of State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China (Approval Number: 2017-083). All animal experiments were performed in accordance with the Association for Research in Vision and Ophthalmology (ARVO) Statement for the Use and Care of Animals in Ophthalmic and Vision Research.

Visual cycle modulators versus placebo or observation for the prevention and treatment of geographic atrophy due to age-related macular degeneration.

Visual cycle modulators versus placebo or observation for the prevention and treatment of geographic atrophy due to age-related macular degeneration.

The transition of ARVO journals to open access

Key points In January 2016, the three journals of the Association for Research in Vision and Ophthalmology (ARVO) transitioned to gold open access. Increased author charges were introduced to partially offset the loss of subscription revenue. Submissions to the two established journals initially dropped by almost 15% but have now stabilized. The transition has not impacted acceptance rates and impact factors, and article pageviews and downloads may have increased as a result of open access.

Trifocal intraocular lenses versus bifocal intraocular lenses after cataract extraction among participants with presbyopia.

Presbyopia occurs when the lens of the eyes loses its elasticity leading to loss of accommodation. The lens may also progress to develop cataract, affecting visual acuity and contrast sensitivity. One option of care for individuals with presbyopia and cataract is the use of multifocal or extended depth of focus intraocular lens (IOL) after cataract surgery. Although trifocal and bifocal IOLs are designed to restore three and two focal points respectively, trifocal lens may be preferable because it restores near, intermediate, and far vision, and may also provide a greater range of useful vision and allow for greater spectacle independence in individuals with presbyopia. To assess the effectiveness and safety of implantation with trifocal versus bifocal IOLs during cataract surgery among participants with presbyopia. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2019, Issue 9); Ovid MEDLINE; Embase.com; PubMed; ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We did not use any date or language restrictions in the electronic search for trials. We last searched the electronic databases on 26 September 2019. We searched the reference lists of the retrieved articles and the abstracts from the Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO) for the years 2005 to 2015. We included randomized controlled trials that compared trifocal and bifocal IOLs among participants 30 years or older with presbyopia undergoing cataract surgery. We used standard Cochrane methodology. We identified five studies conducted in Europe with a total of 175 participants. All five studies assessed uncorrected distance visual acuity (primary outcome of the review), while some also examined our secondary outcomes including uncorrected near, intermediate, and best-corrected distance visual acuity, as well as contrast sensitivity. Study characteristics All participants had bilateral cataracts with no pre-existing ocular pathologies or ocular surgery. Participants' mean age ranged from 58 to 64 years. Only one study reported on gender of participants, and they were mostly women. We assessed all the included studies as being at unclear risk of bias for most domains. Two studies received financial support from manufacturers of lenses evaluated in this review, and at least one author of another study reported receiving payments for delivering lectures with lens manufacturers. Findings All studies compared trifocal versus bifocal IOL implantation on visual acuity outcomes measured on a LogMAR scale. At one year, trifocal IOL showed no evidence of effect on uncorrected distance visual acuity (mean difference (MD) 0.00, 95% confidence interval (CI) -0.04 to 0.04; I2 = 0%; 2 studies, 107 participants; low-certainty evidence) and uncorrected near visual acuity (MD 0.01, 95% CI -0.04 to 0.06; I2 = 0%; 2 studies, 107 participants; low-certainty evidence). Trifocal IOL implantation may improve uncorrected intermediate visual acuity at one year (MD -0.16, 95% CI -0.22 to -0.10; I2= 0%; 2 studies, 107 participants; low-certainty evidence), but showed no evidence of effect on best-corrected distance visual acuity at one year (MD 0.00, 95% CI -0.03 to 0.04; I2= 0%; 2 studies, 107 participants; low-certainty evidence). No study reported on contrast sensitivity or quality of life at one-year follow-up. Data from one study at three months suggest that contrast sensitivity did not differ between groups under photopic conditions, but may be worse in the trifocal group in one of the four frequencies under mesopic conditions (MD -0.19, 95% CI -0.33 to -0.05; 1 study; I2 = 0%, 25 participants; low-certainty evidence). In two studies, the investigators observed that participants' satisfaction or spectacle independence may be higher in the trifocal group at six months, although another study found no evidence of a difference in participant satisfaction or spectacle independence between groups. Adverse events Adverse events reporting varied among studies. Two studies reported information on adverse events at one year. One study reported that participants showed no intraoperative or postoperative complications, while the other study reported that four eyes (11.4%) in the bifocal and three eyes (7.5%) in the trifocal group developed significant posterior capsular opacification requiring YAG capsulotomy. The certainty of the evidence was low. There is low-certainty of evidence that compared to bifocal IOL, implantation of trifocal IOL may improve uncorrected intermediate visual acuity at one year. However, there is no evidence of a difference between trifocal and bifocal IOL for uncorrected distance visual acuity, uncorrected near visual acuity, and best-corrected visual acuity at one year. Future research should include the comparison of both trifocal IOL and specific bifocal IOLs that correct intermediate visual acuity to evaluate important outcomes such as contrast sensitivity and quality of life.

In vivo investigation of the effectiveness of reactive oxygen species-responsive nanomedicine in suppressing corneal neovascularization

Objective To evaluate the effectiveness of reactive oxygen species (ROS)-responsive nanomedicine in suppressing corneal neovascularization (CNV) in vivo. Methods ROS-responsive nanomedicine (ROS-TK-5/siVEGF), which consists of vascular endothelial growth factor (VEGF) small interfering RNA (siRNA) and thioketal linkage was synthesized by the Michael addition.The cumulative release of siVEGF from nanomedicine under oxidant conditions was assessed by agarose gel electrophoresis.Thirty-nine VEGFR2-luc-KI transgenic mice were used in this study, of which 30 mice were randomly divided into a normal control group, a PBS control group, an ROS-TK-5/NC group, an ROS-TK-5/siVEGF group, and a ranibizumab group, with 6 mice in each group.The ROS levels in the corneal tissue after alkali burning were tested by dihydroethidium (DHE) staining in the other 9 mice.In each group, alkali-burned mice were subconjunctivally injected with 10 μl of a different formula every two days.The effectiveness of nanomedicine in attenuating CNV was evaluated by slit-lamp microscopy and an in vivo imaging system (IVIS) at 7, 14, and 21 days after alkali burning. The use and care of the animals complied with the Statement of the Association for Research in Vision and Ophthalmology (ARVO) and the Guidelines of the Animal Experimental Committee of Liberation Army General Hospital.The study protocol was approved by the Ethics Committee of Liberation Army General Hospital (No.2018-X14-82). Results After treathrent with an aqueous solution without ROS, only 5%-10% of the siVEGF was released from the nanoparticles within 10 hours.In contrast, about 70% of the siVEGF was released from the nanoparticles after treatment with 10 mmol/L H2O2 within 10 hours.The relative fluorescent intensities in the corneal stromal layer at 7 days and 14 days after alkali burning were 5.403±0.306 and 2.930±0.255, respectively, which was significantly greater than those in the normal control group (1.003±0.015) (both at P<0.05). The CNV areas were statistically different among the four groups at various time points (Fgroup=49.855, P<0.01; Ftime=65.556, P<0.01). The CNV area was significantly reduced in the ROS-TK-5/siVEGF and ranibizumab groups compared with the PBS control and ROS-TK-5/NC groups at 7 days and 14 days after modeling, and the CNV area was more effectively reduced in the ROS-TK-5/siVEGF group than the ranibizumab group at 7 days and 14 days after modeling (all at P<0.05). At day 21 after modeling, the CNV area was significantly reduced in the ROS-TK-5/siVEGF and ranibizumab groups compared to the PBS control and ROS-TK-5/NC groups (all at P<0.05). IVIS showed that the corneal fluorescent intensity was statistically different among the four groups at various times (Fgroup=27.193, P=0.003; Ftime=51.062, P<0.01). The corneal fluorescent intensities were significantly reduced in the ROS-TK-5/siVEGF and ranibizumab groups compared to the PBS control and ROS-TK-5/NC groups at 7 days and 14 days after modeling; in addition, the corneal fluorescent intensity was more effectively reduced in the ROS-TK-5/siVEGF group in comparison with the ranibizumab group at 7 days and 14 days after modeling (all at P<0.05). At 21 days after modeling, the corneal fluorescent intensity was significantly reduced in the ROS-TK-5/siVEGF and ranibizumab groups compared to the PBS control and ROS-TK-5/NC groups (all at P<0.05). Conclusions ROS-TK-5/siVEGF nanomedicine effectively attenuates alkali burn-induced CNV formation and appears to have a better effect in comparison with ranibizumab at an early stage. Key words: In vivo imaging system; Alkali burn; Corneal neovascularization; Reactive oxygen species; Nanomedicine

Association for Research in Vision and Ophthalmology (ARVO) に参加して

Association for Research in Vision and Ophthalmology (ARVO) に参加して

Effects of enriched environment on the subunits N-mehyl-D-aspartate receptors at the 17th area of the visual cortex in adult amblyopia rats

Objective To explore the effect of enriched environment on the level of NR2A and NR2B subunits of N-mehyl-D-aspartate (NMDA) receptors which belong to glutamate receptors with excitability at the 17th area of the visual cortex in amblyopia rats after the critical period, and to understand the possible mechanism of synaptic plasticity of the visual cortex in adult amblyopia rats. Methods Eighty Wistar rats were divided into normal group and experimental group by random number table.Right eyelids of all rats were sutured through the whole critical period in order to establish monocular deprivation (MD) amblyopia model.The rats in experimental group were divided into the amblyopia group, standard environment (SE) group and environmental enrichment (EE) group on P45 in random.The sutured right eyelids were opened on P46 in the SE group and EE group.All rats were sacrificed to get the 17th area of the left visual cortex on P60, P75 and P105.Three rats were used at different time points from each group.The Ⅰ-Ⅵ layers of the visual cortex area 17 were observed by using hematoxylin-eosin staining.The expression of NMDA-NR2A and NMDA-NR2B was detected by immunohistochemistry.Integrated optical density of NMDA-NR2A and NMDA-NR2B was detected by using special image analysis software (Image-Pro Plus 6.0). The use of animals complied with Regulation on the Managenment Experimental Ainimals from Shandong Eye Institute and Association for Research in Vision and Ophthalmology (ARVO). Results The positive expression of NMDA-NR2A and NMDA-NR2B were observed in the visual cortex.The positive cells were mostly round or elliptical and mainly expressed in cell membrane.The expression of NMDA-NR2A in P60, P75 and P105 from four groups had statistical differences (all at P 0.05). Conclusions The plasticity of visual cortex exists not only in the critical period but also after the critical period of visual development.EE, as a non-invasion method, can improve and recover the synaptic plasticity in visual cortex of adult rats by the expression of NMDA-NR2A and NMDA-NR2B. Key words: Amblyopia; Visual cortex; Synapse; Enriched environment; N-mehyl-D-aspartate receptors

Cell-Based Gene Therapy Using the Sleeping Beauty Transposon System Reduces Neovascularisation in Rats

Background: Age-related macular degeneration (AMD) is a progressive retinal disorder, characterised by imbalanced pro- and anti-angiogenic signals, leading vision loss. The aim of this study was to evaluate the effect of ex vivo cell-based gene therapy on primary cells with stable expression of human pigment epithelium derived factor (PEDF) release using the non-viral Sleeping Beauty (SB100X) transposon system delivered by miniplasmids free of antibiotic resistance markers (pFAR4). Methods: Rat retinal pigment epithelial cells (RPEs) and iris pigment epithelial cells (IPEs) were co-transfected with pFAR4-ITRs CMV PEDF BGH and pFAR4-CMV-SB100X-SV40 plasmids. Laser-induced choroidal neovascularization (CNV) was performed in rats and transfected primary cells (tRPE and tIPE) were injected into the subretinal space. The leakage and CNV areas, vascular endothelial growth factor (VEGF), PEDF protein expression, metalloproteinase 2 and 9 (MMP-2/9) and microglial/macrophage markers were measured and evaluated. Findings: The animals injected with tRPE/IPE cells significantly showed a reduction in the leakage area at 14 days while at 7 days only tIPE cells showed a significant reduction. The CNV area at 7 days was reduced with tRPE/IPE cells. There was a significant increase in PEDF and PEDF/VEGF ratio with tRPE cells along with a reduction in the MMP-2 activity. Activated microglial fluorescence intensity increased in all groups analyzed. Interpretation: Our data demonstrate that a single administration of SB100X-engineered RPE/IPE cells release enough hPEDF to favour an anti-angiogenic environment that ultimately reduces CNV suggest that ex vivo non-viral gene therapy could be an effective and safe therapeutic option for angiogenic retinal diseases. Funding: This work was supported by the European Union’s Seventh Framework Programme for research, technological development and demonstration, grant agreement no. 305134 and Fundacion Jesus Gangoiti Barrera. LGG received a predoctoral grant from the Asociacion de Amigos de la Universidad de Navarra. Declaration of Interest: A. Garcia-Layana is consultant in Thea, Allergan, Bayer, Novartis and Roche Laboratories. Z. Izsvak and Z. Ivics are co-inventors on several patents on Sleeping Beauty transposon technology. Ethical Approval: The study was performed according to the Association for Research in Vision and Ophthalmology (ARVO) Resolution on the Use of Animals in Ophthalmic and Vision Research and approved by the Ethics Committee for Animal Research of the University of Navarra (protocol approval number 023-13).

Dietary Supplement Crocetin Has a Suppressive Effect Against Myopia Progression: A Randomized Clinical Trial

Background: The natural carotenoid crocetin has been reported to suppress experimental myopia in mice. The purpose of this study is to investigate the minimum effective dosage and the preventive efficacy of crocetin with a murine model and human subjects, respectively. Methods: Three-week-old male mice (C57B6/J) were equipped with a -30 diopter (D) lens. Changes of refractive errors and axial lengths (AL) were evaluated to determine the minimum effective dosage. A multicenter randomized double-blind placebo-controlled clinical trial was performed with 69 participants aged 6 to 12 years, whose cycloplegic spherical equivalent refractions (SER) were between -1.5 and -4.5 D. We evaluated AL elongation and change of SER for 24 weeks. A mixed effect model was used for analysis using both eyes. Findings: As the minimum dose, 0.001% of crocetin containing extract chow showed a significant (P<0.001) suppressive effect against both refractive and AL changes in the murine model. 7.5 mg/day of crocetin, which is the equivalent dosage to the animal experiment, was administered in the clinical trial. Two participants dropped out and 67 children completed this trial. The change of SER (D) in the placebo group, -0.41±0.05 (mean±standard deviation), was significantly greater than that in the crocetin group, -0.33±0.05 (P=0.049). The AL elongation (mm) in the placebo group, 0.21±0.02, was significantly greater than that in the placebo group, 0.18±0.02 (P=0.046). Interpretation: Dietary crocetin showed a suppressive effect of myopia progression in children. Trial Registration Number: This trial was also registered by Japic Clinical Trials Information with the registration number JapicCTI-173777. Funding: This study was supported by ROHTO Pharmaceutical Co., Tsubota Laboratory Inc., and Specified contribution from Keio University. Declaration of Interest: The current study was financially supported from ROHTO Pharmaceutical Co.,Ltd., Tsubota Laboratory, Inc., and the specified contribution from Keio University. Patents have been registered for the therapeutic effects of crocetin (patent application no. 2017-210596 by Tsubota Laboratory, Inc. and Rohto Pharmaceutical Co., Ltd.) and applied for the design of the mouse eyeglass by Tsubota Laboratory, Inc. (patent application no. 2017-41349). Ethical Approval: This trial was approved by the institutional review board of Keio University School of Medicine (approval no. 20180079) and Medical Corporation Heishinkai OPHAC Hospital Ethical Review Committee (approval no. 1011PC). All procedures were performed in accordance with the National Institutes of Health (NIH) guidelines for work with laboratory animals and the Association for Research in Vision and Ophthalmology (ARVO) statement for the Use of Animals in Ophthalmic and Vision Research, and were approved by the Institutional Animal Care and Use Committee at Keio University (registration no.3930).

Inhibitory effect of bromfenac sodium hydrate ophthalmic solution on alkali burn induced-corneal neovascularization in rats

Objective To investigate the inhibitory effect of bromfenac sodium hydrate ophthalmic solution on corneal neovascularization (CNV) induced by alkali burn. Methods A total of 192 specific pathogen free (SPF) degree adult male Sprague-Dawley (SD) rats were used in this study.One hundred and seventy-two rats were chosen to establish CNV model with alkali burn in the right eyes.Following alkali burn, rats were randomly divided into CNV group, model control group, bromfenac sodium group and fluorometholone group, with 43 rats (43 eyes) in each group.Another 20 rats (40 eyes) served as normal control group.One day after modeling, the model control group, bromfenac sodium group and fluorometholone group received phosphate buffer saline (PBS), bromfenac sodium hydrate ophthalmic solution and 0.1% fluorometholone eye drops, respectively.The state of cornea and anterior chamber and the growth of CNV of rats in each group were observed by slit-lamp microscope every day after modeling.At 1, 3, 7, 14, 21 and 28 days after modeling, the anterior segment photos of the experimental eyes were captured, and the percent of cornea areas covered by CNV was calculated.At 7, 14 and 28 days after modeling, the eye tissue sections were stained with hematoxylin and eosin staining and immunohistochemistry staining to evaluate the expressions of CD45 and VEGF-A.Real-time quantitative PCR and enzyme-linked immunosorbent assay (ELISA) were used to detect the expression of COX-2 and VEGF mRNA and protein level.The use and care of the animals complied with the Statement of the Association for Research in Vision and Ophthalmology(ARVO). Results Each model group showed corneal edema and opacification 1 day after modeling.The corneal edema was aggravated 7 days after modeling.On the 14th day after modeling, the degree of corneal opacity and edema decreased gradually.On the 28th day after modeling, leucoma was observed in CNV group and model control group, and nebula was observed in bromfenac sodium group and fluorometholone group.At 7, 14, 21 and 28 days after modeling, the percentages of CNV areas in bromfenac sodium group and fluorometholone group were significantly lower than those in CNV group and model control group (all at P 0.05). On the 7th day after modeling, the thinning of corneal epithelial layer, edema and arrangement disorder of stroma layer were observed, and the expression of VEGF-A was positive in all model groups; a small amount of CD45 positive inflammatory cell infiltrations were observed in CNV group and model control group.On the 14th and 28th day after modeling, CNV was seen in the center of cornea in CNV group and model control group; the epithelial keratosis and reduction of corneal edema were seen in each group, and no inflammatory cell infiltration was observed in each group.On the 7th day after modeling, the expressions of COX-2 and VEGF mRNA in CNV group and model control group were significantly higher than those in normal control group, bromfenac sodium group and fluorometholone group (all at P<0.05), the expressions of COX-2 and VEGF protein in bromfenac sodium group were significantly lower than those in CNV group (all at P<0.05). The corneal perforation rate in model control group and bromfenac sodium group was 10% (1 case in 10 rats). The corneal perforation rate in fluorometholone group was 30% (3 cases in 10 rats). In each model group, 10% to 30% rats had hyphema. Conclusions Bromfenac sodium hydrate ophthalmic solution can inhibit the formation and growth of CNV after alkali burn in rats.This effect may be mediated by regulating COX-2 expression, reducing inflammation and inhibiting VEGF production. Key words: Corneal neovascularization; Alkali burn; Bromfenac sodium; Cyclooxygenase-2

Proceedings of the Association for Research in Vision and Ophthalmology and Champalimaud Foundation Ocular Oncogenesis and Oncology Conference.

The 2018 Ocular Oncogenesis and Oncology Conference was held through a partnership of the Association for Research in Vision and Ophthalmology (ARVO) and the Champalimaud Foundation. Twenty-one experts from international ocular oncology centers, from the Champalimaud Clinical Centre and the Champalimaud Foundation Cancer Research Program, and from patient advocacy organizations, delivered lectures on subjects that ranged from global ocular oncology, to basic research in mechanisms of ocular malignancy, to clinical research in ocular cancers, and to anticipated future developments in the area. The scientific program of the conference covered a broad range of ocular tumors—including uveal melanoma, retinoblastoma, ocular surface tumors, and adnexal and intraocular lymphomas—and pathogenesis and management were deliberated in the context of the broader systemic cancer discipline. In considering the latest basic and clinical research developments in ocular oncogenesis and oncology, and providing the opportunity for cross-talk between ocular cancer biologists, systemic cancer biologists, ocular oncologists, systemic oncologists, patients, and patient advocates, the forum generated new knowledge and novel insights for the field. This report summarizes the content of the invited talks at the 2018 ARVO-Champalimaud Foundation Ocular Oncogenesis and Oncology Conference.

Professor Philip J. Rosenfeld: OCT angiography and its application in macular diseases

Dr. Philip J. Rosenfeld ( Figure 1 ) received both his MD and PhD degrees from the Johns Hopkins School of Medicine, and he completed a research fellowship and residency in Ophthalmology at the Massachusetts Eye and Ear Infirmary, Harvard Medical School. Following his residency, Dr. Rosenfeld completed a Vitreoretinal fellowship at the Bascom Palmer Eye Institute, University of Miami Miller School of Medicine. In 1996, he joined the faculty of the Bascom Palmer Eye Institute where he is now an associate professor of Ophthalmology. Dr. Rosenfeld is a member of the American Academy of Ophthalmology (AAO), the American Society of Retinal Specialists (ASRS), the Retina Society, the Macula Society, and the Association for Research in Vision and Ophthalmology (ARVO).

Association for Research in Vision and Ophthalmology (ARVO) - 2018 Annual Meeting. Honolulu, Hawaii, USA - April 29-May 3, 2018

Association for Research in Vision and Ophthalmology (ARVO) - 2018 Annual Meeting. Honolulu, Hawaii, USA - April 29-May 3, 2018

The 0.19 mg Fluocinolone Acetonide Intravitreal Implant – A Review on its Use in Diabetic Macular Oedema from the Association for Research in Vision and Ophthalmology Annual Meeting 2018

Diabetic macular oedema (DMO) is a complication of diabetic retinopathy and a leading cause of visual impairment in patients with diabetes. ILUVIEN® (Alimera Sciences Inc., Alpharetta, GA, USA) is an intravitreal implant of fluocinolone acetonide (FAc), which is indicated in Europe for the treatment of vision impairment associated with chronic DMO that is considered insufficiently responsive to available therapies. This article reviews the clinical effectiveness and safety of the FAc implant from real-world studies presented at the Association for Research in Vision and Ophthalmology (ARVO) 2018 Annual Meeting. Review findings: Evidence from real-world studies, with the FAc implant in persistent or recurrent DMO, show consistent outcomes at a similar time point with those reported in the pivotal randomised controlled trials (RCTs). Real-world studies have also shown that the FAc implant led to improvements in visual acuity and central retinal thickness, as well as reductions in treatment burden. Increases in intraocular pressure (IOP) observed in these studies were consistent with those reported at a similar time point in the RCTs and with the effect of other corticosteroid treatments. Expert opinion and conclusions: The results suggest that FAc offers a clinical and cost-effective alternative in the treatment of persistent or recurrent DMO. There are low risks of raised IOP and cataract formation, both of which are amenable to treatment.

Feasibility of constructing keratectasia animal model using collagenase type II

Background Keratoconus is a chronic and progressive non-inflammatory ectatic disorder characterized by corneal thinning and irregular corneal topography, and its pathgenesis is a hot topic.A suitable animal model of keratoconus is still lacking, which limits the progress of relevant research.Corneal ectasia is a main anatomical basis of keratoconus, so we assume that keratoconus model could be constructed by simulating corneal ectasia. Objective This study was to investigate the influence of collagenase type Ⅱ on biomechanical responses detected by corneal visualization Scheimpflug technology (Corvis ST) and the feasibility of construction of rabbit model of corneal ectasia using collagenase type Ⅱ. Methods This study protocol was approved by Ethic Committee of Peking University First Hospital and followed the Statement about experimental animal use and care from Association for Research in Vision and Ophthalmology (ARVO). Keratectasia models were established in 10 right eyes of 10 New Zealand white rabbits by soaking 8 mm-diameter central cornea using collagenase type Ⅱ solution prepared by PBS solution containing 15% dextran (200 μl of 5 mg/ml) for 30 minutes after epithelial debridement, and only 200 μl PBS solution containing 15% dextran was used in the same way in the left eyes as controls.The average corneal curvature (Km) and central corneal thickness (CCT) were measured with hand-held electronic corneal curvature meter and corneal ultra-sonic pachymetry respectively before modeling and 14 days after modeling.Corneal biomechanical parameters and intraocular pressure were measured in vivo by using Corvis ST at day 14 after modeling.The rabbits were sacrificed at day 14 after modeling, and corneal sections were prepared for hematoxylin-eosin staining and transmission electron microscopic examination. Results There were no significant differences in Km and CCT between model group and control group before modeling (Km: [48.28±2.29]D vs.[48.82±1.63]D; CCT: [356.50±19.13]μm vs.[356.20±21.66]μm; both at P>0.05). The Km increased to (48.87±2.27)D and CCT decreased to (340.40±19.84)μm at day 14 after modeling, which were significantly different from (46.86±1.47)D and (367.80±23.38)μm ( both at P 0.05). The morphology and ultrastructure examinations revealed that the arrangement of collagen fibers was loose and disorder and the interfiber space was enlarged in comparison with control group. Conclusions Collagenase type Ⅱ can lower corneal biomechanical properties.Soaking of cornea with collagenase type Ⅱ may be a potential way to establish a keratectasia animal model. Key words: Biomechanical properties; Cornea/pathology; Collagenase type Ⅱ; Deformation amplitudes; Keratoconus; Keratectasia/chemical induced; Rabbits; Corneal visualization Scheimpflug technology