Interconnections between diabetic corneal neuropathy and diabetic retinopathy:diagnostic and therapeutic implications

Diabetic corneal neuropathy and diabetic retinopathy are ocular complications occurring in the context of diabetes mellitus.Diabetic corneal neuropathy refers to the progressive damage of corneal nerves.Diabetic retinopathy has traditionally been considered as damage to the retinal microvasculature.However,growing evidence suggests that diabetic retinopathy is a complex neurovascular disorder resulting from dysfunction of the neurovascular unit,which includes both the retinal vascular structures and neural tissues.Diabetic retinopathy is one of the leading causes of blindness and is frequently screened for as part of diabetic ocular screening.However,diabetic corneal neuropathy is commonly overlooked and underdiagnosed,leading to severe ocular surface impairment.Several studies have found that these two conditions tend to occur together,and they share similarities in their pathogenesis pathways,being triggered by a status of chronic hyperglycemia.This review aims to discuss the interconnection between diabetic corneal neuropathy and diabetic retinopathy,whether diabetic corneal neuropathy precedes diabetic retinopathy,as well as the relation between the stage of diabetic retinopathy and the severity of corneal neuropathy.We also endeavor to explore the relevance of a corneal screening in diabetic eyes and the possibility of using corneal nerve measurements to monitor the progression of diabetic retinopathy.

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.

Submacular hemorrhage:treatment update and remaining challenges

Submacular haemorrhage(SMH)is a sight threatening complication that can occur in exudative age related macular degeneration(AMD),but has been described to occur more frequently in eyes with polypoidal choroidal vasculopathy(PCV).Left untreated,SMH carries a grave visual prognosis.Thus,expedient diagnosis and effective management of this complication is of paramount importance.The treatment strategies for SMH include(I)displacement of blood from the fovea,usually by injection of an expansile gas;(II)pharmacologic clot lysis such as with recombinant tissue plasminogen activator(rtPA);and(III)treatment of the underlying choroidal neovascularization(CNV)or PCV,such as with anti-vascular endothelial growth factor(anti-VEGF)agents.These three strategies have been employed in isolation or in combination,some concurrently and others in stages.rtPA has demonstrable effect on the liquefaction of submacular clots but there are remaining uncertainties with regards to the dose,safety and the timing of initial and repeat treatments.Potential side effects of rtPA include retinal pigment epithelial toxicity,increased risk of breakthrough vitreous haemorrhage and systemic toxicity.In cases presenting early,pneumatic displacement alone with anti-VEGF may be sufficient.Anti-VEGF monotherapy is a viable treatment option particularly in patients with thinner SMH and those who are unable to posture post pneumatic displacement.

Corneal neuromediator profiles following laser refractive surgery

Laser refractive surgery is one of the most commonly performed procedures worldwide.In laser refractive surgery,Femtosecond Laser in Situ Keratomileusis and Refractive Lenticule Extraction have emerged as promising alternatives to microkeratome Laser in Situ Keratomileusis and Photorefractive Keratectomy.Following laser refractive surgery,the corneal nerves,epithelial and stromal cells release neuromediators,including neurotrophins,neuropeptides and neurotransmitters.Notably,nerve growth factor,substance P,calcitonin gene-related peptide and various cytokines are important mediators of neurogenic inflammation and corneal nerve regeneration.Alterations in neuromediator profiles and ocular surface parameters following laser refractive surgery are attributed to the surgical techniques and the severity of tissue insult induced.In this review,we will discuss the(1)Functions of neuromediators and their physiological and clinical significance;(2)Changes in the neuromediators following various laser refractive surgeries;(3)Correlation between neuromediators,ocular surface health and corneal nerve status;and(4)Future directions,including the use of neuromediators as potential biomarkers for ocular surface health following laser refractive surgery,and as adjuncts to aid in corneal regeneration after laser refractive surgery.

Diabetic corneal neuropathy as a surrogate marker for diabetic peripheral neuropathy

Diabetic neuropathy is a prevalent microvascular complication of diabetes mellitus,affecting nerves in all parts of the body including corneal nerves and peripheral nervous system,leading to diabetic corneal neuropathy and diabetic peripheral neuropathy,respectively.Diabetic peripheral neuropathy is diagnosed in clinical practice using electrophysiological nerve conduction studies,clinical scoring,and skin biopsies.However,these diagnostic methods have limited sensitivity in detecting small-fiber disease,hence they do not accurately reflect the status of diabetic neuropathy.More recently,analysis of alterations in the corneal nerves has emerged as a promising surrogate marker for diabetic peripheral neuropathy.In this review,we will discuss the relationship between diabetic corneal neuropathy and diabetic peripheral neuropathy,elaborating on the foundational aspects of each:pathogenesis,clinical presentation,evaluation,and management.We will further discuss the relevance of diabetic corneal neuropathy in detecting the presence of diabetic peripheral neuropathy,particularly early diabetic peripheral neuropathy;the correlation between the severity of diabetic corneal neuropathy and that of diabetic peripheral neuropathy;and the role of diabetic corneal neuropathy in the stratification of complications of diabetic peripheral neuropathy.

Analysis of corneal nerve plexus in corneal confocal microscopy images

Small Aδand C nerve fibers of the sensory and autonomic nervous systems constitute 70–90%of peripheral nerve fibers including corneal nerves(Muller et al.,2003).Corneal nerves originate from the ophthalmic branch of the trigeminal nerve and enter the cornea at the limbus radially from all directions toward the central cornea at the level of anterior and middle stroma.The subepithelial nerve plexus lies at the interface between the Bowman layer and anterior stroma.They then divide into smaller branches and turn 90°toward Bowman’s layer(Muller et al.,2003),travelling between Bowman’s layer and the basal epithelial layer and forming the sub-basal nerve plexus(Muller et al.,2003).

AB014. Metabolomics in retinal angiogenic diseases

Retinal angiogenic diseases,such as diabetic retinopathy(DR)and age-related macular degeneration(AMD)represent the leading causes of vision impairment in developed countries.There is strong evidence that dysregulated metabolic pathways contribute to DR as known risk factors do not explain all cases and the phenomenon of metabolic memory persists for decades or longer.Some early studies also showed that changes of plasma metabolic profiles are associated with AMD.Metabolic abnormalities can be explored using the techniques of the new science of metabolomics.In this presentation,several metabolomics workflows as well as the application of data independent acquisition mass spectrometry(DIA-MS)in metabolomics will be discussed.Our recent findings from metabolomics studies on DR and AMD will be presented.

Review Integration of smartphone technology and artificial intelligence for advanced ophthalmic care:A systematic review

Background:The convergence of smartphone technology and artificial intelligence(AI)has revolutionized the landscape of ophthalmic care,offering unprecedented opportunities for diagnosis,monitoring,and management of ocular conditions.Nevertheless,there is a lack of systematic studies on discussing the integration of smart-phone and AI in this field.Main text:This review includes 52 studies,and explores the integration of smartphones and AI in ophthalmology,delineating its collective impact on screening methodologies,disease detection,telemedicine initiatives,and patient management.The collective findings from the curated studies indicate promising performance of the smartphone-based AI screening for various ocular diseases which encompass major retinal diseases,glaucoma,cataract,visual impairment in children and ocular surface diseases.Moreover,the utilization of smartphone-based imaging modalities,coupled with AI algorithms,is able to provide timely,efficient and cost-effective screening for ocular pathologies.This modality can also facilitate patient self-monitoring,remote patient monitoring and enhancing accessibility to eye care services,particularly in underserved regions.Challenges involving data pri-vacy,algorithm validation,regulatory frameworks and issues of trust are still need to be addressed.Furthermore,evaluation on real-world implementation is imperative as well,and real-world prospective studies are currently lacking.Conclusions:Smartphone ocular imaging merged with AI enables earlier,precise diagnoses,personalized treat-ments,and enhanced service accessibility in eye care.Collaboration is crucial to navigate ethical and data security challenges while responsibly leveraging these innovations,promising a potential revolution in care access and global eye health equity.

Epidemiology of diabetic retinopathy,diabetic macular edema and related vision loss

Diabetic retinopathy(DR)is a leading cause of vision-loss globally.Of an estimated 285 million people with diabetes mellitus worldwide,approximately one third have signs of DR and of these,a further one third of DR is vision-threatening DR,including diabetic macular edema(DME).The identification of established modifiable risk factors for DR such as hyperglycemia and hypertension has provided the basis for risk factor control in preventing onset and progression of DR.Additional research investigating novel risk factors has improved our understanding of multiple biological pathways involved in the pathogenesis of DR and DME,especially those involved in inflammation and oxidative stress.Variations in DR prevalence between populations have also sparked interest in genetic studies to identify loci associated with disease susceptibility.In this review,major trends in the prevalence,incidence,progression and regression of DR and DME are explored,and gaps in literature identified.Established and novel risk factors are also extensively reviewed with a focus on landmark studies and updates from the recent literature.

Electrospun Aligned PCL/Gelatin Scaffolds Mimicking the Skin ECM for Effective Antimicrobial Wound Dressings

Bacterial infections and multidrug-resistant bacteria are major health burdens in wound care.Biocompatible antimicrobial agents,e.g.,ε-polylysine(ε-PL),provide a broad spectrum of antibacterial properties and support dermal cell growth.Here,ε-PL was incorporated into polycaprolactone(PCL)/gelatin electrospun scaffolds collected at varying rotation speeds.Then,the samples were crosslinked using dopamine hydrochloride to provide highly proliferative dressings with broad antimicrobial activity.The morphological study showed that the electrospun wound dressings were smooth,continuous,and bead-free,with a mean diameter ranging from 267±7 to 331±8 nm for all random and aligned nanofibers.The fiber alignment of the electrospun PCL/gelatin scaffolds improved their tensile strength and modulus.Moreover,nanofiber mats are highly hydro-philic,which is crucial for an efficient wound dressing.The samples also demonstrated high antimicrobial properties against common wound bacterial strains,including methicillin-resistant Staphylococcus aureus(MRSA),Staphylococcus aureus(SA),Escherichia coli(EC),Acinetobacter baumannii(AB),and Pseudomonas aeruginosa(PA).Mammalian cell prolifera-tion and morphology assays involving primary human dermal fibroblasts(hDFs)and immortalized keratinocytes(HaCaT)showed excellent biocompatibility of the electrospun mats and remarkably aligned mats.Furthermore,aligned mats showed more cell migration than randomly oriented mats,which is desirable for more efficient wound healing.Therefore,it can be concluded that aligned PCL/gelatin mats containingε-PL are promising for potential use in wound dressings.