New approaches for diagnosis of dry eye disease

We reviewed the literature for different diagnostic approaches for dry eye disease(DED) including the most recent advances, contradictions and promising diagnostic tools and technique. We performed a broad literature search for articles discussing different methods for diagnosis of DED including assessment of tear osmolarity, tear film stability, ocular biomarkers and others. Articles indexed in PubMed and google scholar were included. With the growing cosmetic industry, environmental pollution, and booming of digital screens, DED is becoming more prevalent. Its multifactorial etiology renders the diagnosis challenging and invites the emergence of new diagnostic tools and tests. Diagnostic tools can be classified, based on the parameter they measure, into tear film osmolarity, functional visual acuity, tear volume, tear turnover, tear film stability, tear film composition, ocular biomarkers and others. Although numerous methods exist, the most accurate diagnosis can be reached through combining the results of more than one test. Many reported tests have shown potential as diagnostic/screening tools, however, require more research to prove their diagnostic power, alone or in combination. Future research should focus on identifying and measuring parameters that are the most specific to DED diagnosis.

Review of application of mass spectrometry for analyses of anterior eye proteome

Proteins have important functional roles in the body, which can be altered in disease states. The eye is a complex organ rich in proteins; in particular, the anterior eye is very sophisticated in function and is most commonly involved in ophthalmic diseases. Proteomics, the large scale study of proteins, has greatly impacted our knowledge and understanding of gene function in the post-genomic period. The most significant breakthrough in proteomics has been mass spectrometric identification of proteins, which extends analysis far beyond the mere display of proteins that classical techniques provide. Mass spectrometry functions as a "mass analyzer" which simplifies the identification and quantification of proteins extracted from biological tissue. Mass spectrometric analysis of the anterior eye proteome provides a differential display for protein comparison of normal and diseased tissue. In this article wepresent the key proteomic findings in the recent literature related to the cornea, aqueous humor, trabecular meshwork, iris, ciliary body and lens. Through this we identified unique proteins specific to diseases related to the anterior eye.

Investigation of changes in thickness and reflectivity from layered retinal structures of healthy and diabetic eyes with optical coherence tomography

OCT is usually employed for the measurement of retinal thickness. However, coherent reflected light carries more information characterizing the optical properties of tissue. Therefore, optical property changes may provide further information regarding cellular layers and early damage in ocular diseases. We investigated the possibility of OCT in detecting changes in the optical backscattered signal from layered retinal structures. OCT images were obtained from diabetic patients without retinopathy (DM, n = 38 eyes) or mild diabetic retinopathy (MDR, n = 43 eyes) and normal healthy subjects (n = 74 eyes). The thickness and reflectivity of various layered structures were assessed using a custom-built algorithm. In addition, we evaluated the usefulness of quantifying the reflectivity of layered structures in the detection of retinal damage. Generalized estimating equations considering within-subject inter-eye relations were used to test for differences between the groups. A modified p value of <0.001 was considered statistically significant. Receiver operating characteristic (ROC) curves were constructed to describe the ability of each parameter to discriminate between the eyes of DM, MDR and healthy eyes. Thickness values of the GCL + IPL and OPL showed a significant decrease in the MDR eyes compared to controls. Significant decreases of total reflectance average values were observed in all layers in the MDR eyes compared with controls. The highest AUROC values estimated for the total reflectance were observed for the GCL+IPL, OPL and OS when comparing MDR eyes with controls. Total reflectance showed a better discriminating power between the MDR eyes and healthy eyes compared to thickness values. Our results suggest that the optical properties of the intraretinal layers may provide useful information to differentiate pathological from healthy eyes. Further research is warranted to determine how this approach may be used to improve diagnosis of early retinal neurodegeneration.

EFFICACY OF PROSTAGLANDINS IN THE EYE

The prostaglandin derivatives have been approved for marketing for the last 6 years and have been shown to be more effective in lowering IOP than most previously available drugs. The distinguishing characteristics of the prostaglandin derivatives include a unique mechanism of action, once-daily dosing and the lack of systemic side effects. The prostaglandin derivatives that

Eye Rubbing as a Possible Cause of Clinical Progressive Keratoconus in a Forme Fruste Keratoconic Family

We report a case of a 21-year-old male patient who underwent corneal cross-linking (CXL) due to bilateral progressive keratoconus. Topographical screening of his family members was performed for the detection of possible familial keratoconus and showed abnormal topographical patterns resembling to Forme Fruste Keratoconus (FFK) in all the members of his family. The reported keratoconic patient that underwent CXL was the only individual of this family that referred eye rubbing in his personal ocular history;ocular and medical history of the other family members was clear. Eye rubbing could be a possible adjuvant risk factor that contributes to conversion of FFK to clinical progressive keratoconus.

Commentary on ten-year incidence of cataract surgery in urban southern China:the Liwan Eye Study

Background Among the global population,cataract blindness continues to account for a major proportion of visual impairment in adults aged 50 years and older(1,2).In developing nations,there are still significant barriers that lead to inequities in the reversal of cataracts,and these include lack of government funding,issues surrounding costs,and insufficient number of ophthalmologists(3).In China,cataract blindness continues to be a leading public-health issue due to its ageing population(4).It has been previously suggested that China has one of the lowest cataract surgery rates with Asia,with 1,067 cases performed per million population in 2014(5).

Sickle cell retinopathy and systemic disease

Sickle cell disease(SCD)is a widespread hemoglobinopathy that results in significant patient morbidity and mortality.Vascular occlusion can cause acute pain,acute chest syndrome,and avascular necrosis,while hemolysis and endothelial disruption can cause ischemic stroke,leg ulcers,pulmonary hypertension,and priapism.All ocular and orbital structures can be affected by SCD ischemic events,including orbital bone infarction,ischemic optic neuropathy,retinal artery occlusion,hyphema,secondary glaucoma,sickle cell maculopathy,and sickle cell retinopathy.Proliferative sickle cell retinopathy(PSR)is the most common cause of vision loss.Untreated PSR can lead to macular ischemia,vitreous hemorrhage,and tractional retinal detachment.Ophthalmic screening exams and multimodal imaging can lead to earlier detection of sickle cell retinopathy and improved patient outcomes.SCD patients undergoing vitreoretinal surgery may require coordination of care with hematologists to avoid ischemic complications.While hydroxyurea was the only United States Food and Drug Administration approved treatment for several decades,patients with SCD now have several more treatment options.Despite the United States screening all infants for SCD,there can be delays in diagnosis and treatment.This review article aims to provide an overview of sickle disease for the ophthalmologist,and to discuss emerging treatment options and current management of SCD ocular complications.

A growing field: the regulation of axonal regeneration by Wnt signaling

The canonical Wnt/β-catenin pathway is a highly conserved signaling cascade that plays critical roles during embryogenesis. Wnt ligands regulate axonal extension, growth cone guidance and synaptogenesis throughout the developing central nervous system （CNS）. Recently, studies in mammalian and fish model systems have demonstrated that Wnt/β-catenin signaling also promotes axonal regeneration in the adult optic nerve and spinal cord after injury, raising the possibility that Wnt could be developed as a therapeutic strategy. In this review, we summarize experimental evidence that reveals novel roles for Wnt signaling in the injured CNS, and discuss possible mechanisms by which Wnt ligands could overcome molecular barriers inhibiting axonal growth to promote regeneration. A central challenge in the neuroscience field is developing therapeutic strategies that induce robust axonal regeneration. Although adult axons have the capacity to respond to axonal guidance molecules after injury, there are several major obstacles for axonal growth, including extensive neuronal death, glial scars at the injury site, and lack of axonal guidance signals. Research in rodents demonstrated that activation of Wnt/β-catenin signaling in retinal neurons and radial glia induced neuronal survival and axonal growth, but that activation within reactive glia at the injury site promoted proliferation and glial scar formation. Studies in zebrafish spinal cord injury models confirm an axonal regenerative role for Wnt/β-catenin signaling and identified the cell types responsible. Additionally, in vitro and in vivo studies demonstrated that Wnt induces axonal and neurite growth through transcription-dependent effects of its central mediator β-catenin, potentially by inducing regeneration-promoting genes. Canonical Wnt signaling may also function through transcription-independent interactions of β-catenin with cytoskeletal elements, which could stabilize growing axons and control growth cone movement. Therefore, these studies suggest that Wnt-induced pathways responsible for regulating axonal growth during embryogenesis could be repurposed to promote axonal growth after injury.

Axial length development in children

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 10 mo of life. After 36 mo, 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.

Cell transplantation to replace retinal ganglion cells faces challenges-the Switchboard Dilemma

The mammalian retina displays incomplete intrinsic regenerative capacities;therefore,retina degeneration is a major cause of irreversible blindness such as glaucoma,agerelated macular degeneration and diabetic retinopathy.These diseases lead to the loss of retinal cells and serious vision loss in the late stage.Stem cell transplantation is a great promising novel treatment for these incurable retinal degenerative diseases and represents an exciting area of regenerative neurotherapy.Several suitable stem cell sources for transplantation including human embryonic stem cells,induced pluripotent stem cells and adult stem cells have been identified as promising target populations.However,the retina is an elegant neuronal complex composed of various types of cells with different functions.The replacement of these different types of cells by transplantation should be addressed separately.So far,retinal pigment epithelium transplantation has achieved the most advanced stage of clinical trials,while transplantation of retinal neurons such as retinal ganglion cells and photoreceptors has been mostly studied in pre-clinical animal models.In this review,we opine on the key problems that need to be addressed before stem cells transplantation,especially for replacing injured retinal ganglion cells,may be used practically for treatment.A key problem we have called the Switchboard Dilemma is a major block to have functional retinal ganglion cell replacement.We use the public switchboard telephone network as an example to illustrate different difficulties for replacing damaged components in the retina that allow for visual signaling.Retinal ganglion cell transplantation is confronted by significant hurdles,because retinal ganglion cells receive signals from different interneurons,integrate and send signals to the correct targets of the visual system,which functions similar to the switchboard in a telephone network-therefore the Switchboard Dilemma.

Surgical management of uveitis-glaucoma-hyphema syndrome

AIM:To report outcomes of patients after intraocular lens(IOL)repositioning or exchange for the version of the uveitisglaucoma-hyphema(UGH)syndrome that does not include closed loop anterior chamber IOL(nUGH).METHODS:Chart review of patients with nUGH who underwent IOL repositioning or exchange by one surgeon were reviewed.The main outcome measures were best corrected visual acuity(BCVA)as a decimal fraction preoperatively and postoperatively after IOL repositioning or exchange.Clinical findings evaluated included the presence of uveitis,hyphema,elevated intraocular pressure(IOP),and other complications such as pigment dispersion or vitreous hemorrhage.The number of anti-inflammatory and glaucoma medications were assessed before and after IOL repositioning or exchange.RESULTS:The study included 14 pseudophakic eyes.The median time at the onset of contemporary UGH after cataract extraction and IOL implantation(CE/IOL)was7.5 y.IOL repositioning or exchange was performed at a mean duration of 8.1±4.7 mo(median:4 mo)after onset of UGH.The mean BCVA was improved from 0.45±0.26 preoperatively after onset of UGH syndrome to 0.76±0.22(P=0.016)after IOL repositioning or exchange.Among the14 eyes,uveitis,elevated IOP,and hyphema were present preoperatively in 13,13,and 6 eyes,respectively.Uveitis and hyphema resolved in all cases after IOL surgery.The mean IOP was reduced from 26.4±4.5 mm Hg preoperatively to 14.7±4.9 postoperatively(P=0.01).The mean number of glaucoma medications used was reduced from 1.7±1.1 medications preoperatively to 0.8±1.08(P=0.04)postoperatively.CONCLUSION:IOL repositioning or exchange is an effective treatment in many cases for medically resistant contemporary UGH syndrome.

Comparative Ligandomic Analysis of Human Lung Epithelial Cells Exposed to PM2.5

Objective To investigate whether exposure to particulate matter of diameter equal to or less than 2.5μm(PM2.5)alters the response of lung epithelial cells to extrinsic regulation by globally profiling cell surface ligands and quantifying their binding activity.Methods Human A549 lung epithelial cells(LECs)were treated with or without PM2.5.Ligandomic profiling was applied to these cells for the global identification of LEC-binding ligands with simultaneous quantification of binding activity.Quantitative comparisons of the entire ligandome profiles systematically identified ligands with increased or decreased binding to PM2.5-treated LECs.Results We found 143 ligands with increased binding to PM2.5-treated LECs and 404 ligands with decreased binding.Many other ligands showed no change in binding activity.For example,apolipoprotein E(ApoE),Notch2,and growth arrest-specific 6(Gas6)represent ligands with increased,decreased,or unchanged binding activity,respectively.Both ApoE and Gas6 are phagocytosis ligands,suggesting that phagocytic receptors on LECs after stimulation with PM2.5 were differentially upregulated by PM2.5.Conclusion These results suggest that the newly-developed ligandomics is a valuable approach to globally profile the response of LECs to PM2.5 in terms of regulating the expression of cell surface receptors,as quantified by ligand binding activity.This quantitative ligandome profiling will provide indepth understanding of the LEC molecular response on the cell surface to particulate matter air pollution.

Exploring the role of interleukin-27 as a regulator of neuronal survival in central nervous system diseases

Interleukin-27 is a pleiotropic cytokine that is involved in tissue responses to infection,cell stress,neuronal disease,and tumors.Recent studies in various tissues indicate that interleukin-27 has complex activating and inhibitory properties in innate and acquired immunity.The availability of recombinant interleukin-27 protein and mice with genetic deletions of interleukin-27,its receptors and signaling mediators have helped define the role of interleukin-27 in neurodegenerative diseases.Interleukin-27 has been well-characterized as an important regulator of T cell activation and differentiation that enhances or suppresses T cell responses in autoimmune conditions in the central nervous system.Evidence is also accumulating that interleukin-27 has neuroprotective activities in the retina and brain.Interleukin-27 is secreted from and binds to infiltrating microglia,macrophage,astrocytes,and even neurons and it promotes neuronal survival by regulating pro-and anti-inflammatory cytokines,neuroinflammatory pathways,oxidative stress,apoptosis,autophagy,and epigenetic modifications.However,interleukin-27 can have the opposite effect and induce inflammation and cell death in certain situations.In this review,we describe the current understanding of regulatory activities of interleukin-27 on cell survival and inflammation and discuss its mechanisms of action in the brain,spinal cord,and retina.We also review evidence for and against the therapeutic potential of interleukin-27 for dampening harmful neuroinflammatory responses in central nervous system diseases.

The role of monocytes in optic nerve injury

Monocytes,including monocyte-derived macrophages and resident microglia,mediate many phases of optic nerve injury pathogenesis.Resident microglia respond first,followed by infiltrating macrophages which regulate neuronal inflammation,cell proliferation and differentiation,scar formation and tissue remodeling following optic nerve injury.However,microglia and macrophages have distinct functions which can be either beneficial or detrimental to the optic nerve depending on the spatial context and temporal sequence of their activity.These divergent effects are attributed to pro-and anti-inflammatory cytokines expressed by monocytes,crosstalk between monocyte and glial cells and even microglia-macrophage communication.In this review,we describe the dynamics and functions of microglia and macrophages in neuronal inflammation and regeneration following optic nerve injury,and their possible role as therapeutic targets for axonal regeneration.

Combined pars plana vitrectomy and Baerveldt glaucoma implant placement for refractory glaucoma

AIMTo evaluate outcomes of combined pars plana vitrectomy and Baerveldt glaucoma implant (PPV-BGI) placement for refractory glaucoma.METHODSThe medical records of 92 eyes (89 patients) that underwent PPV-BGI were retrospectively reviewed, including 43 eyes with neovascular glaucoma (NVG) and 49 eyes with other types of glaucoma (non-NVG).RESULTSOutcome measures were visual acuity (VA), intraocular pressure (IOP), glaucoma medical therapy, complications, and success [VA&#x0003e;hand motions (HM), IOP&#x02265;6 mm Hg and &#x02264;21 mm Hg, no subsequent glaucoma surgery]. Cumulative success rates for the non-NVG group and NVG group were 79% and 40% at 1y, respectively (P=0.038). No difference in the rates of surgical success were found between pars plana and anterior chamber tube placement. Preoperative IOP (mean&#x000b1;SD) was 30.3&#x000b1;11.7 mm Hg in the Non-NVG group and 40.0&#x000b1;10.6 mm Hg in the NVG group, and IOP was reduced to 15&#x000b1;9.5 mm Hg in the non-NVG group and 15&#x000b1;10.5 mm Hg in the NVG at 1y. Number of glaucoma medications (mean&#x000b1;SD) decreased from 2.7&#x000b1;1.3 in the non-NVG group and 2.8&#x000b1;1.3 in the NVG group preoperatively to 0.76&#x000b1;1.18 in the non-NVG group and 0.51&#x000b1;1.00 in the NVG group at 1y. Improvement in VA of &#x02265;2 Snellen lines was observed in 25 (27%) eyes, although only 33% of non-NVG eyes and 2.3% of NVG eyes maintained VA better than 20/200 at 1y. Nonclearing vitreous hemorrhage was the most common postoperative complication occurring in 16 (17%) eyes, and postoperative suprachoroidal hemorrhages developed in 5 (5.4%) eyes.CONCLUSIONPPV-BGI is a viable surgical option for eyes with refractory glaucoma, but visual outcomes are frequently poor because of ocular comorbidities, especially in eyes with NVG. The location of tube placement does not influence surgical outcome and should be left to the discretion of the surgeon.

Neuro-rejuvenation for neuronal function

Neurodegenerative eye diseases, such as glaucoma, cause irreversible vision loss in millions of patients worldwide, creating serious medical, economic and social issues. Like other mammalian central nervous system tracts, optic nerve intrinsically lacks the capacity for axonal growth and its surrounding environment is also non-permissive to regeneration. Any axonal damage also triggers a vicious cycle of retinal ganglion cell （RGC） death. Exploring methods that can enhance RGCs survival and promote axonal regeneration will not only enable vision restoration for millions of patients, but also shed light on the treatment of other neurodegenerative diseases. In this review article, we will go through three current approaches to cure neu- rodegenerative eye diseases, including cell based therapy, neuro-regeneration and neuro-rejuvenation.

Long-term chorioretinal changes following strabismus surgery——possible occult needle penetration

Dear Editor,cleral penetration during strabismus surgery was k3 first reported over 50 years ago[1].Early manuscripts reported the incidence of this complication around 10%[1].However,more recent studies suggest that this rate may have decreased[2-3].

Widefield optical coherence tomography of foveal dragging in retinopathy of prematurity

Dear Editor,Despite substantial advances in neonatal medicine, retinopathy of prematurity (ROP) continues to be a serious therapeutic challenge⑴.Visual acuity loss in patients with ROP has been associated with structural retinal abnormalities (including retinal detachment, retinal folds, and pigmentary retinopathy), cataract, glaucoma, and amblyopia due to refractive error or strabismus[2].

Cost analysis of childhood glaucoma surgeries using the US Medicaire allowable costs

AIM: To analyze and calculate the relative cost of various childhood glaucoma surgical interventions per mm Hg intraocular pressure(IOP) reduction($/mm Hg).METHODS: Representative index studies were reviewed to quantitate the reduction of mean IOP and glaucoma medications for each surgical intervention in childhood glaucoma. A US perspective was adopted, using Medicare allowable costs to calculate cost/mm Hg IOP reduction($/mm Hg) at 1y postoperatively.RESULTS: At 1y postoperatively, the cost/mm Hg IOP reduction was $226/mm Hg for microcatheter-assisted circumferential trabeculotomy, $284/mm Hg for cyclophotocoagulation, $288/mm Hg for conventional ab-externo trabeculotomy, $338/mm Hg for Ahmed glaucoma valve, $350/mm Hg for Baerveldt glaucoma implant, $351/mm Hg for goniotomy, and $400/mm Hg for trabeculectomy.CONCLUSION: Microcatheter-assisted circumferential trabeculotomy is the most cost-efficient surgical method to lower IOP in childhood glaucoma, while trabeculectomy is the least cost-efficient surgical method.

Atrophy and Fibrosis of Extra-Ocular Muscles in Anti-Acetylcholine Receptor Antibody Myasthenia Gravis

Myasthenia gravis (MG) is an autoimmune disorder involving the neuromuscular junction that frequently affects the extra-ocular muscles (EOMs). It has been described as a very rare cause of bilateral EOM atrophy, but histological analysis of such cases is lacking. A 66-year-old man presented with two months of right eyelid drooping and vertical diplopia. Examination showed bilateral ophthalmoparesis and complete right ptosis. The remainder of his exam was normal, and an MRI showed small EOMs. Acetylcholine receptor antibodies were elevated, establishing the diagnosis of MG. Oral corticosteroids and pyridostigmine followed by azathioprine improved his ptosis, but not his ophthalmoparesis. One year later he had surgical correction of his diplopia, and the resected superior rectus muscle showed complete replacement of EOM by connective tissue. MG can rarely cause bilateral EOM atrophy, which is characterized histologically by fibrosis in the muscle itself. Atrophy in the EOMs of a myasthenic patient may indicate a poor response to medical management alone.