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.

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).

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.

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.

Ocular diseases: immunological and molecular mechanisms

Many factors, such as environmental, microbial and endogenous stress, antigen localization, can trigger the immunological events that affect the ending of the diverse spectrum of ocular disorders. Significant advances in understanding of immunological and molecular mechanisms have been researched to improve the diagnosis and therapy for patients with ocular inflammatory diseases. Some kinds of ocular diseases are inadequately responsive to current medications;therefore, immunotherapy may be a potential choice as an alternative or adjunctive treatment, even in the prophylactic setting. This article first provides an overview of the immunological and molecular mechanisms concerning several typical and common ocular diseases; second, the functions of immunological roles in some of systemic autoimmunity will be discussed; third, we will provide a summary of the mechanisms that dictate immune cell trafficking to ocular local microenvironment in response to inflammation.

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.

Drug delivery in ocular diseases: Barriers and strategies

The eye is a complex organ made up of diversifed cells with specifed functions. Presence of anatomical, physi-ological and physiochemical barriers make it diffcult to deliver drugs in therapeutic amounts at intended sites. To overcome these, drug delivery scientists have fol-lowed two distinct yet complimentary approaches. The frst involves using alternate delivery routes to conven-tional ones allowing for more direct access to intended target sites. Second approach involves development of novel drug delivery systems providing better perme-ability, treatability and controlled release at target site. Combination of both these approaches are being uti-lized and optimized in order to achieve optimal therapy with minimal adverse effects.

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.

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.

Artificial intelligence in the anterior segment of eye diseases

Ophthalmology is a subject that highly depends on imaging examination.Artificial intelligence(AI)technology has great potential in medical imaging analysis,including image diagnosis,classification,grading,guiding treatment and evaluating prognosis.The combination of the two can realize mass screening of grass-roots eye health,making it possible to seek medical treatment in the mode of“first treatment at the grass-roots level,two-way referral,emergency and slow treatment,and linkage between the upper and lower levels”.On the basis of summarizing the AI technology carried out by scholars and their teams all over the world in the field of ophthalmology,quite a lot of studies have confirmed that machine learning can assist in diagnosis,grading,providing optimal treatment plans and evaluating prognosis in corneal and conjunctival diseases,ametropia,lens diseases,glaucoma,iris diseases,etc.This paper systematically shows the application and progress of AI technology in common anterior segment ocular diseases,the current limitations,and prospects for the future.

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.

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.

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.

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.

Nanotechnology-based strategies for treatment of ocular disease

Ocular diseases include various anterior and posterior segment diseases. Due to the unique anatomy and physiology of the eye, efficient ocular drug delivery is a great challenge to researchers and pharmacologists. Although there are conventional noninvasive and invasive treatments, such as eye drops,injections and implants, the current treatments either suffer from low bioavailability or severe adverse ocular effects. Alternatively, the emerging nanoscience and nanotechnology are playing an important role in the development of novel strategies for ocular disease therapy. Various active molecules have been designed to associate with nanocarriers to overcome ocular barriers and intimately interact with specific ocular tissues. In this review, we highlight the recent attempts of nanotechnology-based systems for imaging and treating ocular diseases, such as corneal d iseases, glaucoma, retina diseases, and choroid diseases. Although additional work remains, the progress described herein may pave the way to new,highly effective and important ocular nanomedicines.

Ocular manifestations of children with atopic dermatitis in Saudi Arabia

AIM:To examine the incidence of ocular abnormalities in children with atopic dermatitis(AD)in Saudi Arabia and its association with the severity of AD.METHODS:This is a cross-sectional study on 50 children with AD who were between 5 and 16 years of age.The severity of AD was evaluated using the SCORing Atopic Dermatitis(SCORAD)index.All the children underwent slit lamp exams,visual acuity assessment,intraocular pressure measurement,and corneal topography.The children were considered to have an ophthalmic abnormality if one or more of the following signs were present:glaucoma,keratoconus suspicion,in addition to lid,conjunctival,corneal,lenticular,or retinal abnormalities.RESULTS:Based on the SCORAD severity index,14%of children had mild AD(7/50),38%had moderate AD(19/50),and nearly half had severe AD.More than half the children exhibited facial involvement,and half had peri-orbital signs.The mean SCORAD index was 35.75.The mean age was 10.48±3.6y,and the cohort showed a slight male predominance(54%males).Both eyes of the 50 children in the cohort were studied.Based on the ocular examinations,92%of the patients showed ocular abnormalities:lid abnormalities(27/50)followed by keratitis(22/50).Four patients had moderate risk for keratoconus in one eye and eight patients were suspected to have keratoconus.However,SCORAD severity index was not associated with age,sex,or the number or presence of ophthalmic abnormalities.CONCLUSION:This is the first study in Saudi Arabia to evaluate the prevalence of ocular manifestations in children with AD.The results indicate that the majority of children with AD have ocular abnormalities that mainly include lid abnormalities.Based on these findings,larger scale studies are needed to affirm whether regular screening for ophthalmic abnormalities would be beneficial for children with AD in terms of early intervention and prevention of sight-threatening complications.

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.

Comparison of the meibomian gland dysfunction in patients with chronic ocular graft-versus-host disease and Sjogren's syndrome

AIM: To investigate the abnormalities in the meibomian gland in patients with dry eye disease(DED) associated with chronic ocular graft-versus-host disease(coGVHD) in comparison with Sj?gren's syndrome(SS), a major form of aqueous deficient DED and meibomian gland dysfunction(MGD), a common cause of evaporative DED.METHODS: A total 135 eyes of 135 subjects included in this study: patients with DED associated with coGVHD(n=30), patients with SS(n=35), patients with MGD(n=35), and normal controls(n=35). All participants completed the Ocular Surface Disease Index(OSDI) questionnaire, ocular surface examination [Schirmer test, tear film breakup time(TFBUT), and ocular surface staining], and meibomian gland assessment [meiboscore(gland dropout detected on meibography using infrared camera of the Keratograph 5 M), meibum expressibility score(MES), meibum quality score(MQS), lid margin abnormality]. In addition, correlations of meibomian gland characteristics with ocular surface parameters as well as disease severity score were investigated in coGVHD group.RESULTS: The coGVHD group showed significantly higher meiboscore, MES, and MQS than the other 3 groups(all P<0.05). In the coGVHD group, parameters of meibomian gland showed a significant correlation each other and those of ocular surface. The correlation between meibomian gland parameters and severity score of co GVHD was also established(meiboscore, r=0.62; MES, r=0.47; MQS, r=0.47; lid margin abnormality score, r=0.55; all P<0.05).CONCLUSION: Patients with DED associated with co GVHD show poorer gland morphology and worse glandfunction than other types of DED. In addition, meibomian gland damage is not only associated with ocular surface damage but also disease severity of coGVHD.

Reliability of Chinese web-based ocular surface disease index questionnaire in dry eye patients:a randomized,crossover study

AIM:To assess the reliability of web-based version of ocular surface disease index in Chinese(C-OSDI)on clinically diagnosed dry eye disease(DE)patients.METHODS:A total of 254 Chinese participants(51%male,129/254;mean age:27.90±9.06 y)with DED completed paper-and web-based versions of C-OSDI questionnaires in a randomized crossover design.Ophthalmology examination and DED diagnosis were performed prior to the participants being invited to join the study.Participants were randomly designated to either group A(paper-based first and webbased second)or group B(web-based first and paper-based second).Final data analysis included participants that had successfully completed both versions of the C-OSDI.Demographic characteristics,test-retest reliability,and agreement of individual items,subscales,and total score were evaluated with intraclass correlation coefficients(ICC),Spearman rank correlation,Wilcoxon test and Rasch analysis.RESULTS:Reliability indexes were adequate,Pearson correlation was greater than 0.8 and ICCs range was 0.827 to 0.982;total C-OSDI score was not statistically different between the two versions.The values of mean-squares fit statistics were very low compared to 1,indicating that the responses to the items by the model had a high degree of predictability.While comparing the favorability 72%(182/254)of the participants preferred web-based assessment.CONCLUSION:Web-based C-OSDI is reliable in assessing DED and correlation with the paper-based version is significant in all subscales and overall total score.Webbased C-OSDI can be administered to assess individuals with DED as participants predominantly favored online assessment.