The inducible nitric oxide synthaseinhibitor 1400W as a potential treatment for retinal diseases

The overproduction of reactive oxygen species is defined as oxidative stress.While deprived oxygen supply in tissues is known as hypoxia.These mechanisms contribute to the pathogenesis of several retinal diseases,like glaucoma,age-related macular degeneration(AMD),and retinal ischemia.Glaucoma is a neurodegenerative disease defined by a progressive loss of retinal ganglion cells(RGCs)and their axons causing visual field defects,which ultimately leads to blindness.While AMD pathogenesis is further characterized by soft drusen,it involves the retinal pigment epithelium and the Bruch’s membrane-choroid complex.

Non-Penetrating Femtosecond Laser Intrastromal Astigmatic Keratotomy Performed during Laser-Assisted Cataract Surgery: Results on Keratometric Astigmatism

Purpose: To investigate the efficacy of non-penetrating femtosecond laser intrastromal astigmatic keratotomy (ISAK) in terms of topographic and refractive changes. Methods: Retrospective study including 42 eyes (35 patients) with a corneal astigmatism between 0.5 and 1.5 D. All eyes underwent femtosecond laser-assisted cataract surgery with ISAK for astigmatism management using the Catalys laser system (Johnson & Johnson Vision). Visual acuity, refraction, as well as corneal topographic and corneal endothelial cell density (ECD) changes were evaluated during a 12-month follow-up. Astigmatic changes were analyzed using the Alpins vector method. Results: A significant reduction in manifest cylinder was observed at 1 month postoperatively (p = 0.03), with no significant changes afterwards (p = 0.90). A total of 38.1%, 52.4% and 59.2% of eyes had a manifest cylinder of 0.50 D or lower preoperatively and at 1 and 12 months after surgery, respectively. A significant reduction was found in topographic astigmatism at 1 month postoperatively (p < 0.01), with an additionally small but statistically significant reduction afterwards (p < 0.01). No significant changes in postoperative uncorrected (p = 0.97) and corrected visual acuities (p = 0.40) were observed during the follow-up. There was a trend to undercorrection of corneal astigmatism that decreased significantly over time. This led to some variability in changes of refractive astigmatism. A small but significant reduction in ECD was observed at 1 month postoperatively (p Conclusions: Femtosecond laser assisted ISAK is an effective and safe option to reduce corneal astigmatism during cataract surgery and consequently refractive astigmatism.

球结膜淋巴管与微血管的鉴别染色研究

目的探讨5′-核苷酸酶-碱性磷酸酶双染法在动物和人眼结膜淋巴管、微血管鉴别中的应用价值。方法使用5′-核苷酸酶-碱性磷酸酶双重染色法对中华猕猴、家猪及人离体眼结膜进行铺片染色,光镜拍照观察。结果猕猴、家猪离体眼及人离体眼结膜染色结果相似:淋巴管呈深棕色,微血管呈深蓝色。其中猕猴结膜管道显色最深。结论 5′-核苷酸酶-碱性磷酸酶双染法可以成功地将猕猴、家猪及人眼结膜中的淋巴管和微血管进行区分。猕猴是应用该双染法研究结膜淋巴管及血管网络分布的良好动物模型。(中国眼耳鼻喉科杂志,2007,7:17～19)

Comparison of visual acuity outcomes between ranibizumab and bevacizumab treatment in neovascular age-related macular degeneration

AIM: To compare visual acuity (VA) outcomes between intravitreal injection of bevacizumab and ranibizumab in the treatment of neovascular age-related macular degeneration (AMD). METHODS: We conducted a consecutive, retrospective case series study in patients with newly diagnosed all type choroidal neovascularization (CNV) secondary to AMD who received an intravitreal injection of bevacizumab (1.25mg) or ranibizumab (0.3mg) at Lions Eye Institute, Western Australia from Mar. 2006 to May 2008. All patients received injection at baseline with additional monthly injections given at the discretion of the treating physician. Main outcome measures were changes in VA. RESULTS: There were 371 consecutive patients received injection at least in one eye with at least 6 months of follow up (median of 12.0 months). Bevacizumab treatment prevented 221 out of 278 (79.5%) patient from losing < 15 letters in VA compared with 79 out of 93 (84.9%) of ranibizumab treated patients (P=0.25). While 68 (24.5%) of bevacizumab treated patients gained 15 letters of VA compared with 24 (25.8%) of ranibizumab treated patients (P=0.79). 75.3% and 66.2% patients benefited from ranibizumab and bevacizumab respectively with final VA better than 6/60 (P=0.10). Multivariate analysis showed that pre-treatment VA was negatively associated with benefit outcome. Assignment of injection was not associated with VA outcome of benefit after adjusting the covariate (P=0.857). CONCLUSION: There are no difference in treatment efficacy in terms of VA between bevacizumab and ranibizumab in routine clinical condition.

Foveal thickness reduction after anti-vascular endothelial growth factor treatment in chronic diabetic macular edema

AIM：To report foveal thickness reduction in eyes with resolution of macular edema and recovery of a foveal depression after one-year of anti-vascular endothelial growth factor（anti-VEGF） therapy for center-involving diabetic macular edema（DME）.METHODS：Foveal thickness was assessed with optical coherence tomography to determine the central subfield foveal thickness（CSFT） and macular volume in 42 eyes with DME（CSFT〉275 μm）. Evaluations also included measurement of best-corrected visual acuity（BCVA）, and were performed at baseline, and upon foveal depression recovery achieved after 12 monthly intravitreal injections of either 1.5 mg/0.06 mL bevacizumab（n=21） or 0.5 mg/0.05 mL ranibizumab（n=21）. Data was compared to 42 eyes of normally sighted, non-diabetic, healthy individuals with similar age, gender and race distributions.RESULTS：Mean baseline BCVA was 0.59±0.04 and 0.32± 0.03 log MAR（P〈0.001） after treatment and resolution of DME, with all, but 3 eyes, showing BCVA improvement. Mean CSFT before treatment was 422.0±20.0 μm, and after treatment, decreased to 241.6±4.6 μm（P〈0.001）, which is significantly thinner than CSFT found in control subjects（272.0±3.4 μm; P〈0.001）. Moreover, in 33/42 DM eyes（79%）, CSTF was thinner than the matched control eye. Macular volume showed comparable results, but with lower differences between groups（control：8.5±0.4 mm^3; DME：8.2±1.0 mm^3; P=0.0267）.CONCLUSION：DME eyes show significantly lower foveal thickness than matched controls after DME resolution achieved with one-year anti-VEGF therapy. Further investigation into the reasonsfor this presumable retinal atrophy using fluorescein angiography and functional parameters as well as establishing possible predictors is warranted. This finding should be considered during the treatment of DME.

High-risk corneal allografts: A therapeutic challenge

Corneal transplantation is the most common surgical procedure amongst solid organ transplants with a high survival rate of 86% at 1-year post-grafting. This high success rate has been attributed to the immune privilege of the eye. However, mechanisms originally thought to promote immune privilege, such as the lack of antigen presenting cells and vessels in the cornea, are challenged by recent studies. Nevertheless, the immunological and physiological features of the cornea promoting a relatively weak alloimmune response is likely responsible for the high survival rate in "low-risk" settings. Furthermore, although corneal graft survival in "lowrisk" recipients is favourable, the prognosis in "high-risk" recipients for corneal graft is poor. In "high-risk" grafts, the process of indirect allorecognition is accelerated by the enhanced innate and adaptive immune responses due to pre-existing inflammation and neovascularization of the host bed. This leads to the irreversible rejection of the allograft and ultimately graft failure. Many therapeutic measures are being tested in pre-clinical and clinical studies to counter the immunological challenge of "high-risk" recipients. Despite the prevailing dogma, recent data suggest that tissue matching together with use of systemic immunosuppression may increase the likelihood of graft acceptance in "high-risk" recipients. However, immunosuppressive drugs are accompanied with intolerance/side effects and toxicity, and therefore, novel cell-based therapies are in development which target host immune cells and restore immune homeostasis without significant side effect of treatment. In addition, developments in regenerative medicinemay be able to solve both important short comings of allotransplantation:(1) graft rejection and ultimate graft failure; and(2) the lack of suitable donor corneas. The advances in technology and research indicate that wider therapeutic choices for patients may be available to address the worldwide problem of corneal blindness in both "low-risk" and "high-risk" hosts.

Ischemic penumbra in retina endures： vascular neuropathology is reconciled

A physiological state of＂normoxia＂obtains when tissue oxygen tension（pO_2）is sufficient to drive mitochondrial respiration throughout a volume of cells.Between 30-40%of the available oxygen is normally extracted from hemoglobin as it passes through neural tissue.

The 100 most influential papers about cataract surgery:a bibliometric analysis

AIM：To identify the 100 most cited papers in cataract surgery,we performed a comprehensive bibliometric analysis basing on the literature search on the Thomson Reuters Web of Knowledge.METHODS：The number of citations,including the total citations,latest 5y citations and average citation number per year（ACY）,authorship,year of publication,major topics,journal of publication,country and institution of origin of each paper were recorded and then analyzed.Pearson’s correlation analysis was conducted to evaluate the correlation between the published year and the number of citations.The correlation between journal’s impact factor（IF）and number of citations was assessed as well.RESULTS：The most cited paper was the classic paper done by the European Society of Cataract＆Refractive Surgeons（ESCRS）group.This paper focused on the topic of endophthalmitis.Not only the most cited papers originated from the USA,but also some American institutions like Johns Hopkins University,Harvard Medical School,etc.had the most citations.Pearson’s correlation analysis indicated that the latest 5y citations and ACY were significantly related with the published year（5y citations：r=0.615,P〈0.001;ACY：r=0.657,P〈0.001）,whereas no association between the total number of citations and published year was found（r=0.045）.Moreover,the IFs of journals were found to have no significant effect on the number of total citations.CONCLUSION：To our knowledge,this is the first study on the most influential papers in cataract surgery aftera comprehensive research of relevant literatures.The present work may provide us concise information concerning the development history of cataract surgery over the past 66y.

Distribution pattern of axonal cytoskeleton proteins in the human optic nerve head

Glaucoma is one of the leading causes of blindness in the developed world.It is a progressive optic neuropathy where structural loss of retinal ganglion cell（RGC）axons corresponds with functional visual field defect.Glaucoma is distinguished from other optic neuropathies by its selective loss of RGC axons.Superior and inferior peripheral nerve sectors are found to be most vulnerable to pressure induced injury whereas the inner temporal sector is most resilient（Quigley et al.,1988）.

The interplay between inflammation,immunity and commensal microflora in glaucomatous neurodegeneration

The immensely diverse and rich human gut microbiome has a huge potential to impact health and disease(1).Gut microbiome dysbiosis has been associated with gastro-intestinal inflammatory conditions and extra-intestinal disorders;such as stroke,depression,neurodegenerative,cardiovascular and metabolic disorders(2-6).In the September 2018 issue of nature communications,Chen and colleagues report the findings from a study that found commensal microflora-induced T cell responses mediate progressive neurodegeneration in glaucoma,in mouse glaucoma models(7).

Time spent outdoors and myopia:establishing an evidence base

Myopia is a highly prevalent refractive error in Asia(1).Although mild myopia does not have serious ocular ramifications,pathological myopia is associated with the development of various ocular pathologies that can lead to irreversible visual loss or blindness(2).The prevalence of visual impairment attributable to pathologic myopia is 0.2-1.4% in Asian populations(3).Over the past few generations,the prevalence of myopia has increased significantly(4).In urbanized areas of East

A key role for PTP1B in dendritic cell maturation, migration, and T cell activation

Dendritic cells(DC)are the major antigen-presenting cells bridging innate and adaptive immunity,a function they perform by converting quiescent DC to active,mature DC with the capacity to activate naı¨ve T cells.They do this by migrating from the tissues to the T cell area of the secondary lymphoid tissues.Here,wedemonstrate thatmyeloid cell-specific genetic deletion of PTP1B(LysM PTP1B)leads to defects in lipopolysaccharide-driven bone marrow-derivedDC(BMDC)activation associated with increased levels of phosphorylated Stat3.We showthatmyeloid cell-specific PTP1Bdeletion also causes decreased migratory capacity of epidermal DC,aswell as reduced CCR7 expression and chemotaxis to CCL19 by BMDC.PTP1B deficiency in BMDC also impairs their migration in vivo.Further,immature LysM PTP1B BMDC display fewer podosomes,increased levels of phosphorylated Src at tyrosine 527,and loss of Src localization to podosome puncta.In co-culture with T cells,LysM PTP1B BMDC establish fewer and shorter contacts than control BMDC.Finally,LysMPTP1BBMDCfail to present antigen to T cells as efficiently as controlBMDC.These data provide first evidence for a key regulatory role for PTP1B in mediating a central DC function of initiating adaptive immune responses in response to innate immune cell activation.

Consideration of corneal biomechanics in the diagnosis and management of keratoconus: is it important?

Keratoconus is a bilateral,non-inflammatory,degenerative corneal disease.The occurrence and development of keratoconus is associated with corneal thinning and conical protrusion,which causes irregular astigmatism.With the disruption of the collagen organization,the cornea loses its shape and function resulting in progressive visual degradation.Currently,corneal topography is the most important tool for the diagnosis of keratoconus,which may lead to false negatives among the patient population in the subclinical phase.However,it is now hypothesised that biomechanical destabilisation of the cornea may take place ahead of the topographic evidence of keratoconus,hence possibly assisting with disease diagnosis and management.This article provides a review of the definition,diagnosis,and management strategies for keratoconus based on corneal biomechanics.

Unintended changes in ocular biometric parameters during a 6-month follow-up period after FS-LASIK and SMILE

Background:Corneal refractive surgery has become reliable for correcting refractive errors,but it can induce unintended ocular changes that alter refractive outcomes.This study is to evaluate the unintended changes in ocular biometric parameters over a 6-month follow-up period after femtosecond laser-assisted laser in situ keratomileusis(FS-LASIK)and small incision lenticule extraction(SMILE).Methods:156 consecutive myopic patients scheduled for FS-LASIK and SMILE were included in this study.Central corneal thickness(CCT),mean curvature of the corneal posterior surface(K_(pm)),internal anterior chamber depth(IACD)and the length from corneal endothelium to retina(ER)were evaluated before and after surgery over a 6-month period.Results:Both the FS-LASIK and SMILE groups(closely matched at the pre-surgery stage)experienced flatter Kpm,shallower IACD and decreased ER 1 week post-surgery(P<0.01),and these changes were larger in FS-LASIK than in SMILE group.During the 1 week to 6 months follow up period,K_(pm),IACD and ER remained stable unlike CCT which increased significantly(P<0.05),more in the FS-LASIK group.Conclusions:During the follow up,the posterior corneal surface became flatter and shifted posteriorly,the anterior chamber depth and the length from the corneal endothelium to retina decreased significantly compared with the pre-surgery stage.These unintended changes in ocular biometric parameters were greater in patients undergoing FS-LASIK than SMILE.The changes present clear challenges for IOL power calculations and should be considered to avoid affecting the outcome of cataract surgery.

Towards standardizing retinal optical coherence tomography angiography:a review

The visualization and assessment of retinal microvasculature are important in the study,diagnosis,monitoring,and guidance of treatment of ocular and systemic diseases.With the introduction of optical coherence tomography angiography(OCTA),it has become possible to visualize the retinal microvasculature volumetrically and without a contrast agent.Many lab-based and commercial clinical instruments,imaging protocols and data analysis methods and metrics,have been applied,often inconsistently,resulting in a confusing picture that represents a major barrier to progress in applying OCTA to reduce the burden of disease.Open data and software sharing,and cross-comparison and pooling of data from different studies are rare.These inabilities have impeded building the large databases of annotated OCTA images of healthy and diseased retinas that are necessary to study and define characteristics of specific conditions.This paper addresses the steps needed to standardize OCTA imaging of the human retina to address these limitations.Through review of the OCTA literature,we identify issues and inconsistencies and propose minimum standards for imaging protocols,data analysis methods,metrics,reporting of findings,and clinical practice and,where this is not possible,we identify areas that require further investigation.We hope that this paper will encourage the unification of imaging protocols in OCTA,promote transparency in the process of data collection,analysis,and reporting,and facilitate increasing the impact of OCTA on retinal healthcare delivery and life science investigations.

Scleral resection in chronic central serous chorioretinopathy complicated by exudative retinal detachment

Background:Effective therapeutic options are limited for the management of chronic central serous chorioretinopathy(CSCR)complicated by exudative retinal detachments(RD).The authors describe the resolution of one such case following partial thickness scleral resection with mitomycin C.Case presentation:This 39-year-old male presented with a unilateral inferior exudative RD in the right eye.There was no history of steroid use either locally or systemically.The fundus fluorescein angiogram showed window defects and leaks typical of chronic CSCR.The axial length was 21.06 mm in the right eye and 21 mm in the left eye.Thickening of the ocular coats was evident on ocular ultrasound.Considering an axial length in the borderline-low range inferotemporal and inferonasal partial thickness scleral resection with mitomycin C was performed.The exudative RD resolved at 4 months.Conclusion:Partial thickness scleral resection may be considered as an option for treating chronic CSCR patients with borderline-low axial length complicated by exudative RD.

Biomechanical diagnostics of the cornea

Corneal biomechanics has been a hot topic for research in contemporary ophthalmology due to its prospective applications in diagnosis,management,and treatment of several clinical conditions,including glaucoma,elective keratorefractive surgery,and different corneal diseases.The clinical biomechanical investigation has become of great importance in the setting of refractive surgery to identify patients at higher risk of developing iatrogenic ectasia after laser vision correction.This review discusses the latest developments in the detection of corneal ectatic diseases.These developments should be considered in conjunction with multimodal corneal and refractive imaging,including Placido-disk based corneal topography,Scheimpflug corneal tomography,anterior segment tomography,spectral-domain optical coherence tomography(SD-OCT),very-high-frequency ultrasound(VHF-US),ocular biometry,and ocular wavefront measurements.The ocular response analyzer(ORA)and the Corvis ST are non-contact tonometry systems that provide a clinical corneal biomechanical assessment.More recently,Brillouin optical microscopy has been demonstrated to provide in vivo biomechanical measurements.The integration of tomographic and biomechanical data into artificial intelligence techniques has demonstrated the ability to increase the accuracy to detect ectatic disease and characterize the inherent susceptibility for biomechanical failure and ectasia progression,which is a severe complication after laser vision correction.

Automated Behavioral Phenotyping Reveals Presymptomatic Alterations in a SCA3 Genetrap Mouse Model

Characterization of disease models of neurodegenerative disorders requires a systematic and comprehensive phenotyping in a highly standardized manner. Therefore, automated high-resolution behavior test systems such as the homecage based LabMaster system are of particular interest. We demonstrate the power of the automated LabMaster system by discovering previously unrecognized features of a recently characterized atxn3 mutant mouse model. This model provided neurological symptoms including gait ataxia, tremor, weight loss and premature death at the age of 12 months usually detectable just 2 weeks before the mice died. Moreover, using the LabMaster system we were able to detect hypoactivity in presymptomatic mutant mice in the dark as well as light phase. Additionally, we analyzed inflammation, immunological and hematological parameters, which indicated a reduced immune defense in phenotypic mice. Here we demonstrate that a detailed characterization even of organ systems that are usually not affected in SCA3 is important for further studies of pathogenesis and required for the preclinical therapeutic studies.

Review of in-vivo characterisation of corneal biomechanics

The study of corneal biomechanics in vivo has been evolving fast in recent years.While an organised corneal structure is necessary for its transparency,resistance to occasional external insults and bearing the intraocular pressure(IOP),which several clinically relevant events can disturb.This review focuses on three techniques that are available for clinical use,namely the Ocular Response Analyzer(Reichert Ophthalmic Instruments,Buffalo,NY,USA),the Corvis ST(Oculus Optikgerate GmbH,Wetzlar,Germany)and the Brillouin Optical Scattering System(Intelon Optics Inc.,Lexington,MA,USA).The principles and the main parameters of each device are discussed along with their strategies to improve accuracy in the IOP measurement,corneal ectasia diagnosis,evaluation of corneal cross-linking procedures,and planning of corneal refractive surgeries.

初级医疗中关于非炎症性眼疼痛的评估

眼部疼痛很普遍，大约2％～5％的综合门诊患者主诉涉及眼部及眼周边疼痛的情况（眼部、眼周边、眼眶周边的疼痛在文中统称为眼部疼痛）。在新西兰眼科急诊的患者中，大于50％的患者由综合门诊转诊而来。，绝大部分主诉都包含眼部疼痛。笔者建议，这些人中，如果在初诊时可以得到较好的诊断，那么转诊人数将会下降。