Clinical associations of corneal neuromas with ocular surface diseases

Corneal neuromas,also termed microneuromas,refer to microscopic,irregula rly-shaped enlargements of terminal subbasal nerve endings at sites of nerve damage or injury.The formation of corneal neuromas results from damage to corneal nerves,such as following corneal pathology or corneal or intraocular surge ries.Initially,denervated areas of sensory nerve fibers become invaded by sprouts of intact sensory nerve fibers,and later injured axons regenerate and new sprouts called neuromas develop.In recent years,analysis of corneal nerve abnormalities including corneal neuromas which can be identified using in vivo confocal microscopy,a non-invasive imaging technique with microscopic resolution,has been used to evaluate corneal neuropathy and ocular surface dysfunction.Corneal neuromas have been shown to be associated with clinical symptoms of discomfort and dryness of eyes,and are a promising surrogate biomarker for ocular surface diseases,such as neuropathic corneal pain,dry eye disease,diabetic corneal neuropathy,neurotrophic keratopathy,Sjogren's syndrome,bullous keratopathy,post-refra ctive surgery,and others.In this review,we have summarized the current literature on the association between these ocular surface diseases and the presentation of corneal microneuromas,as well as elaborated on their pathogenesis,visualization via in vivo confocal microscopy,and utility in monitoring treatment efficacy.As current quantitative analysis on neuromas mainly relies on manual annotation and quantification,which is user-dependent and labor-intensive,future direction includes the development of artificial intelligence software to identify and quantify these potential imaging biomarkers in a more automated and sensitive manner,allowing it to be applied in clinical settings more efficiently.Combining imaging and molecular biomarkers may also help elucidate the associations between corneal neuromas and ocular surface diseases.

Fundus photography,fluorescein angiography,optical coherence tomography and electroretinography of preclinical animal models of ocular diseases

The eye is an immune-privileged and sensory organ in humans and animals.Anatomical,physiological,and pathobiological features share significant similarities across divergent species(1).Each compartment of the eye has a unique structure and function.The anterior and posterior compartments of the eye contain endothelium(cornea),epithelium(cornea,ciliary body,iris),muscle(ciliary body),vitreous and neuronal(retina)tissues,which make the eye suitable to evaluate efficacy and safety of tissue specific drugs(2).

Recent progress in N6-methyladenosine modification in ocular surface diseases

N6-methyladenosine(m6A)modification is a reversible process promoted by“writers”,inhibited by“erasers”,and processed by“readers”.During the last decade,increasing emphasis has been placed on the underlying roles of m6A modification owing to their great importance in biological significance.The abnormal regulation of m6A modification will lead to aberrant cellular behavior and various diseases.Recently,studies have demonstrated that m6A modification is closely associated with the genesis and progression of ocular surface diseases(OSDs).This review focus on the role of m6A modification and research progress in OSDs including fungal keratitis,herpes simplex keratitis,immunerelated keratoconjunctival diseases,pterygium,ocular chemical burns,and Graves’ophthalmopathy,which may provide new insights into and prospective applications for OSDs.

Spatial Correlation Module for Classification of Multi-Label Ocular Diseases Using Color Fundus Images

To prevent irreversible damage to one’s eyesight,ocular diseases(ODs)need to be recognized and treated immediately.Color fundus imaging(CFI)is a screening technology that is both effective and economical.According to CFIs,the early stages of the disease are characterized by a paucity of observable symptoms,which necessitates the prompt creation of automated and robust diagnostic algorithms.The traditional research focuses on image-level diagnostics that attend to the left and right eyes in isolation without making use of pertinent correlation data between the two sets of eyes.In addition,they usually only target one or a few different kinds of eye diseases at the same time.In this study,we design a patient-level multi-label OD(PLML_ODs)classification model that is based on a spatial correlation network(SCNet).This model takes into consideration the relevance of patient-level diagnosis combining bilateral eyes and multi-label ODs classification.PLML_ODs is made up of three parts:a backbone convolutional neural network(CNN)for feature extraction i.e.,DenseNet-169,a SCNet for feature correlation,and a classifier for the development of classification scores.The DenseNet-169 is responsible for retrieving two separate sets of attributes,one from each of the left and right CFI.After then,the SCNet will record the correlations between the two feature sets on a pixel-by-pixel basis.After the attributes have been analyzed,they are integrated to provide a representation at the patient level.Throughout the whole process of ODs categorization,the patient-level representation will be used.The efficacy of the PLML_ODs is examined using a soft margin loss on a dataset that is readily accessible to the public,and the results reveal that the classification performance is significantly improved when compared to several baseline approaches.

New Screening Approach for Ocular Diseases

Objective: Present a new screening approach for ocular diseases. Method: Transversal, retrospective, single center study that analyzed medical records of patients from a social project on the prevention of blindness and amblyopia, which aimed at: 1) Detect the main ocular disorders such as amblyopia, primary angle-closure suspect (PACS);glaucoma suspect (GS);predisposing retinal detachment lesions (PRDL);age-related macular degeneration (AMD), and diabetic retinopathy (DR);2) Perform cataract diagnosis;3) Provide guidance and treatment for allergic conjunctivitis. 4) Prescribe glasses for children until 14 years of age. Participants were examined by a single specialist, holder of a post-doctoral degree in ophthalmology, with 36 years of experience and a sub-specialization in retina and vitreous. All data were analyzed in 2022. Results: The examiner diagnosed 42 cases of PACS, 21 of GS, 8 of PRDL, 14 of AMD, 3 of DR, 40 of cataract and 31 cases of allergic conjunctivitis. Thirty-three participants younger than 14 were prescribed glasses. Other pathologies included retinal detachment, papilledema, corneal ulcer, suspected conjunctival squamous cell carcinoma, retinal vasculitis, strabismus, uveitis, bilateral papilla paleness and lacrimal duct obstruction. Out of the 297 cases examined, 168 participants presented some type of alteration that could compromise their vision. Conclusion: The examiner’s experience and knowledge were decisive factors for the quick diagnosis, advice, screening and/or treatment of several ocular diseases. The social project results reveal that the primary care and/or the screening performed by a specialist are likely to reduce blindness cases.

Annexin A1 in the nervous and ocular systems

The therapeutic potential of Annexin A1,an important member of the Annexin superfamily,has become evident in results of experiments with multiple human systems and animal models.The anti-inflammatory and pro-resolving effects of Annexin A1 are characteristic of pathologies involving the nervous system.In this review,we initially describe the expression sites of Annexin A1,then outline the mechanisms by which Annexin A1 maintains the neurological homeostasis through either formyl peptide receptor 2 or other molecular approaches;and,finally,we discuss the neuroregenerative potential qualities of Annexin A1.The eye and the nervous system are anatomically and functionally connected,but the association between visual system pathogenesis,especially in the retina,and Annexin A1 alterations has not been well summarized.Therefore,we explain the beneficial effects of Annexin A1 for ocular diseases,especially for retinal diseases and glaucoma on the basis of published findings,and we explore present and future delivery strategies for Annexin A1 to the retina.

Medical and surgical approach to ocular surface reconstruction

Ocular surface disease(OSD)can have a severe impact on patients as it can lead to visual impairment and persistent discomfort.Ocular surface reconstruction(OSR)is an approach to the management of ocular diseases that cause structural damage to the ocular surface.OSR encompasses both medical and surgical treatment options.In this review,we discuss the medical and surgical strategies used in OSR.Medical management often aims to treat tear insufficiency,inflammation,and keratinization.Surgical treatments may be employed for a variety of reasons,including failure of medical management.This may include improving the oculo-palpebral structures in order to improve lid positioning and tear film.Additional therapies focus on improving tear production,such as through salivary gland transplantation.In situations where the ocular surface is so severely damaged that there is loss of limbal stem cells,limbal stem cell transplant(LSCT)may be indicated.Other surgeries such as amniotic membrane transplant(AMT)and conjunctival flaps(CFs)can help promote corneal healing.Finally,in severe situations where the cornea is beyond salvage,corneal transplantation,such as a penetrating keratoplasty(PKP),can be considered.OSR often requires a combination of medical and surgical approaches targeted to each specific patient’s presentation in order to achieve optimal outcomes.

Prognosis value of Chinese Ocular Fundus Diseases Society classification for proliferative diabetic retinopathy on postoperative visual acuity after pars plana vitrectomy in type 2 diabetes

AIM: To compare the postoperative visual acuity among eyes with proliferative diabetic retinopathy(PDR) of different stages after pars plana vitrectomy(PPV) in type 2 diabetic patients. METHODS: A retrospective study was conducted for PDR eyes undergoing PPV in type 2 diabetic patients. All patients were divided into three groups based on Chinese Ocular Fundus Diseases Society(COFDS) classification for PDR: Group A(primary vitreous hemorrhage), Group B(primary fibrovascular proliferation) and Group C(primary vitreous hemorrhage and/or fibrovascular proliferative combined with retinal detachment). The postoperative visual acuity and the change between postoperative and preoperative visual acuity were compared among three groups. The associated risk factors for postoperative visual acuity were analyzed in the univariate and multiple linear aggression. RESULTS: In total, 195 eyes of 195 patients were collected in this study, including 71 eyes of 71 patients in Group A, 75 eyes of 75 patients in Group B and 49 eyes of 49 patients in Group C. The eyes in Group A got better postoperative best-corrected visual acuity(BCVA) compared to the eyes in Group B and C(0.48±0.48 vs 0.89±0.63, P<0.001;0.48±0.48 vs 1.04±0.67, P<0.001;respectively). The eyes in Group A got more improvement of BCVA compared to the eyes in Group B and C(1.07±0.70 vs 0.73±0.68, P=0.004;1.07±0.70 vs 0.77±0.78, P=0.024;respectively). In the multiple linear regression analysis, primary fibro-proliferative type(β=0.194, 95%CI=0.060-0.447, P=0.01), retinal detachment type(β=0.244, 95%CI=0.132-0.579, P=0.02), baseline log MAR BCVA(β=0.192, 95%CI=0.068-0.345, P=0.004), silicone oil tamponade(β=0.272, 95%CI=0.173-0.528, P<0.001) was positively correlated with postoperative log MAR BCVA. Eyes undergoing phacovitrectomy had better postoperative BCVA(β=-0.144, 95%CI=-0.389 to-0.027, P=0.025). CONCLUSION: PDR eyes of primary vitreous hemorrhage type usually have better visual acuity prognosis compared to primary fibrovascular proliferation type and retinal detachment type. COFDS classification for PDR may have a high prognostic value for postoperative visual outcome and surgical management indications.

Potential applications of artemisinins in ocular diseases

Artemisinin, also named qinghaosu, is a family of sesquiterpene trioxane lactone originally derived from the sweet wormwood plant(Artemisia annua), which is a traditional Chinese herb that has been universally used as anti-malarial agents for many years. Evidence has accumulated during the past few years which demonstrated the protective effects of artemisinin and its derivatives(artemisinins) in several other diseases beyond malaria, including cancers, autoimmune disorders, inflammatory diseases, viral and other parasiterelated infections. Recently, this long-considered antimalarial agent has been proved to possess anti-oxidant, anti-inflammatory, anti-apoptotic and anti-excitotoxic properties, which make it a potential treatment option for the ocular environment. In this review, we first described the overview of artemisinins, highlighting the activity of artemisinins to other diseases beyond malaria and the mechanisms of these actions. We then emphasized the main points of published results of using artemisinins in targeting ocular disorders, including uveitis, retinoblastoma, retinal neurodegenerative diseases and ocular neovascularization. To conclude, we believe that artemisinins could also be used as a promising therapeutic drug for ocular diseases, especially retinal vascular diseases in the near future.

Neutrophil-to-lymphocyte ratio in ocular diseases: a systematic review

AIM: To summarize the results of studies investigating neutrophil-to-lymphocyte ratio(NLR) and to identify the role of NLR in ocular diseases. METHODS: With the aim of identifying the studies related to NLR, a search was conducted on http://www.ncbi.nlm.nih.gov/pubmed by utilizing the key words "neutrophil lymphocyte ratio, ocular diseases, and eye diseases" up to February 2018. All of the original articles were assessed according to date of publications, countries, clinics and topics. Studies about ocular inflammatory diseases were evaluated according to their qualifications, review methods and results. RESULTS: A total of 4473 publications, including original research articles and reviews were screened. The number of publications was shown a regular logarithmic increase over the years. The majority of studies were performed by clinics in Turkey and many of these publications were performed by oncology and cardiology clinics. A total of 75 publications were identified to be about ocular diseases. CONCLUSION: Elevated NLR as a cheap, reproducible, and readily available marker could be used as a diagnostic and/or prognostic marker in ocular diseases.

Mesenchymal stem cell-derived extracellular vesicles as a new therapeutic strategy for ocular diseases

Mesenchymal stem cells(MSCs) have attracted considerable attention for their activity in the treatment of refractory visual disorders. Since MSCs were found to possess the beneficial effects by secreting paracrine factors rather than direct differentiation, MSC-derived extracellular vesicles(EVs) were widely studied in various disease models. MSCs generate abundant EVs, which act as important mediators by exchanging protein and genetic information between MSCs and target cells. It has been confirmed that MSC-derived EVs possess unique antiinflammatory, anti-apoptotic, tissue repairing, neuroprotective, and immunomodulatory properties, similar to their parent cells. Upon intravitreal injection, MSC-derived EVs rapidly diffuse through the retina to alleviate retinal injury or inflammation. Due to possible risks associated with MSC transplantation, such as vitreous opacity and pathological proliferation, EVs appear to be a better choice for intravitreal injection. Small size EVs can pass through biological barriers easily and their contents can be modified genetically for optimal therapeutic effect. Hence, currently, they are also explored for the possibility of serving as drug delivery vehicles. In the current review, we describe the characteristics of MSC-derived EVs briefly, comprehensively summarize their biological functions in ocular diseases, and discuss their potential applications in clinical settings.

Beneficial effects of saffron(Crocus sativus L.) in ocular pathologies, particularly neurodegenerative retinal diseases

Saffron(Crocus sativus L.)has been traditionally used in food preparation and as a medicinal plant.It currently has numerous therapeutic properties attributed to it,such as protection against ischemia,as well as anticonvulsant,antidepressant,anxiolytic,hypolipidemic,anti-atherogenic,anti-hypertensive,antidiabetic,and anti-cancer properties.In addition,saffron has remarkable beneficial properties,such as anti-apoptotic,anti-inflammatory and antioxidant activities,due to its main metabolites,among which crocin and crocetin stand out.Furthermore,increasing evidence underwrites the possible neuroprotective role of the main bioactive saffron constituents in neurodegenerative diseases,such as Parkinson’s and Alzheimer’s diseases,both in experimental models and in clinical studies in patients.Currently,saffron supplementation is being tested for ocular neurodegenerative pathologies,such as diabetic retinopathy,retinitis pigmentosa,age-related macular degeneration and glaucoma,among others,and shows beneficial effects.The present article provides a comprehensive and up to date report of the investigations on the beneficial effects of saffron extracts on the main neurodegenerative ocular pathologies and other ocular diseases.This review showed that saffron extracts could be considered promising therapeutic agents to help in the treatment of ocular neurodegenerative diseases.

A review on vasohibin and ocular neovascularization

Ischemic and neovascular disease is one of the most difficult ocular diseases to deal with nowadays.Redundancy,poor visual acuity and decreased life quality are bothering patients and ophthalmologists for decades.After vascular endothelial growth factor(VEGF)was found to be a primary factor in promoting retinal angiogenesis,intravitreal injection of anti-VEGF drugs has been the firstline treatment.Whereas,some patients are refractory to this therapy and problems of economic burden,local complications and adverse effects promote researches into other possible targets.The vasohibin(VASH)family is a newly-investigated factor in modulating ocular angiogenesis.The family includes VASH1 and VASH2,which show opposite effects of inhibiting and accelerating angiogenesis respectively.Positive results have been reported in cellular and animal experiments.With further researches,it can be a promising future target of treating ocular neovascular diseases.

Progress in exosomes and their potential use in ocular diseases

Exosomes contain a variety of biological active substances such as proteins,miRNAs,lncRNAs and lipids,and exosomes from different cells play different biological functions.Exosomes,as a carrier,are involved in many pathological processes such as nerve injury and repair,vascular regeneration,immune response,and fibrosis formation.It plays an important role in the treatment of eye diseases such as glaucoma,diabetic retinopathy,and keratitis.This paper reviews the research progress of exosomes in various diseases in vivo,which provides a new way for the treatment of eye diseases.

Metabolomics and biomarkers in ocular matrix: beyond ocular diseases

According to the recent report,there are 870 million people suffer from ocular diseases worldwide.The present approaches for diagnosis are morphological examination,imaging examination and immunological examination,regrettably,they lack of sensitivity and difficult to make a definite diagnosis in the early stage.Systemic biology as an effective method has been used in clinical diagnosis and treatment for diseases,especially metabolomics which is more attractive with high sensitivity and accuracy.Although previous researches had been confirmed that endogenous metabolites in the ocular matrix play a crucial role in the progress of diseases related diseases,the standard protocols and systematic summary about the biomarker researches based on ocular matrix has not been established.This review article highlights the pretreatment for ocular matrix and the new biomarkers expressed by the eye diseases,expected to promote the application of biomarkers in the diagnosis and treatment of eye diseases.

Effect of flavone on the ocular blood flow and formation of choroidal neovascularization

AIMTo investigate the effect of flavone on ocular blood flow in rabbit eyes and the formation of choroidal neovascularization (CNV) in rat model of age-related macular degeneration (AMD).

REGRESSION OF ANTERIOR SEGMENT NEOVASCULARISATION FOLLOWING CAROTID ENDARTERECTOMY IN A PA-TIENT SUFFERING FROM OCULAR IS-CHAEMIC SYNDROME

Purpose: To report a case of bilateral regression of anterior segment neovascularisation after carotid endarterectomy in a patient with bilateral ocular ischaemic syndrome (OIS). Patient and Methods: Case report. A 61 year-old man suffering from bilateral ocular ischaemic syndrome causing iris neovascularisation (NVI) and neovascular glaucoma (NVG), was planned for bilateral panretinal photocoagulation (PRP) and endarterectomy. PRP was technically only possible in his right eye, while endarterectomy was performed in both carotids. Results: Bilateral complete NVI regression was observed a month after surgery. Conclusion: In some OIS uveal ischaemia could be the major responsible for NVI. Carotid endarterectomy benefits patients who have more than 70% stenosis and improves ocular blood flow, so it should be considered in patients suffering OIS with NVI unre- spective of other cerebral ischaemic symptoms.

Drug delivery in ocular diseases: Barriers and strategies

The eye is a complex organ made up of diversified cells with specified functions. Presence of anatomical, physiological and physiochemical barriers make it difficult to deliver drugs in therapeutic amounts at intended sites. To overcome these, drug delivery scientists have followed two distinct yet complimentary approaches. The first involves using alternate delivery routes to conventional ones allowing for more direct access to intended target sites. Second approach involves development of novel drug delivery systems providing better permeability, treatability and controlled release at target site. Combination of both these approaches are being utilized and optimized in order to achieve optimal therapy with minimal adverse effects.

Myelinosome organelles in pathological retinas: ubiquitous presence and dual role in ocular proteostasis maintenance

The timely and efficient elimination of aberrant proteins and damaged organelles, formed in response to various genetic and environmental stressors, is a vital need for all cells of the body. Recent lines of evidence point out several non-classical strategies employed by ocular tissues to cope with aberrant constituents generated in the retina and in the retinal pigmented epithelium cells exposed to various stressors. Along with conventional strategies relying upon the intracellular degradation of aberrant constituents through ubiquitin-proteasome and/or lysosome-dependent autophagy proteolysis, two non-conventional mechanisms also contribute to proteostasis maintenance in ocular tissues. An exosome-mediated clearing and a myelinosome-driven secretion mechanism do not require intracellular degradation but provide the export of aberrant constituents and “waste proteins” outside of the cells. The current review is centered on the non-degradative myelinosome-driven secretion mechanism, which operates in the retina of transgenic Huntington’s disease R6/1 model mice. Myelinosome-driven secretion is supported by rare organelles myelinosomes that are detected not only in degenerative Huntington’s disease R6/1 retina but also in various pathological states of the retina and of the retinal pigmented epithelium. The intra-retinal traffic and inter-cellular exchange of myelinosomes was discussed in the context of a dual role of the myelinosome-driven secretion mechanism for proteostasis maintenance in different ocular compartments. Special focus was made on the interplay between degradative and non-degradative strategies in ocular pathophysiology, to delineate potential therapeutic approaches to counteract several vision diseases.

A narrative review of ocular surface disease considerations in the management of glaucoma

s from those searches were screened for relevance to our review topics.Publications were included if the subjects included glaucoma patients,and if ocular surface outcomes were described.Non-English papers were excluded.Key Content and Findings:Topical glaucoma medications frequently cause adverse effects on the ocular surface,both through direct action of the medications themselves as well as through toxicity from their associated preservatives.Optimization of the ocular surface may improve medication compliance rates.Traditional surgical treatments for glaucoma,such as trabeculectomy,can exacerbate OSD by disrupting the ocular surface but can also reduce the need for chronic medications.Optimization of ocular surface health is imperative in reducing trabeculectomy complication rates,while also potentially reducing the need for trabeculectomy in patients that are able to achieve intraocular pressure control through improved drop tolerability.The introduction of MIGS represents a promising alternative to existing therapies and has been shown to alleviate the overall medication burden.It would be reasonable to assume that decreasing the medication burden could reduce OSD prevalence and severity.However,more research is needed to directly assess the extent of improvement seen after MIGS.Conclusions:A comprehensive understanding of the importance of OSD in medical and surgical management of glaucoma is essential in optimizing patient care and improving outcomes.