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.

A surprising visual improvement following a prolonged 5-month retained subfoveal perfluorocarbon liquid

Dear Sir,I am Dr.Daniel Ting,from the Department of Ophthalmology,Singapore National Eye Centre,Singapore.I write to present a case of a surprising significant visual improvement following a prolonged 5-month retained subfoveal perfluorocarbon liquid.Retained perfluorocarbon liquid（PFCL）has been shown to cause decreased visual acuity,retinal pigment epithelial（RPE）toxicity,retinal degeneration and gravity deformation ,

Use of Perfluorocarbon Liquids in Complicated Retinal Detachments

We now have an additional tool to help in managing complicated retinal detachments. We look forward to the day when we can leave the liquid without having to remove it because of the possibility of ocular complications.

登革热病的眼部表现

Purpose To evaluate ocular manifestations associated with dengue fever. Design Retrospective case series and literature review. Methods Clinical records of pa tients with dengue fever who subsequently had ocular symptoms and signs develop were reviewed. The clinical presentation and ocular complication s were evaluated. Results Six patients, 5 females and 1 male, were seen with a s udden decrease in vision 6 to 7 days after the initial manifestations of dengue fever were identified. The diagnosis was confirmed by detection of dengue speci fic IgM antibodies (IgM enzyme linked immunoassay). The presenting best correc ted visual acuity ranged from 20/30 to counting fingers, and ocular involvement was bilateral but asymmetric in 5 cases and unilateral in 1 case. Fundus finding s included small, intraretinal, whitish lesions, with localized retinal and reti nal pigment epithelium (RPE) disturbance, small dot hemorrhages, and vascular sh eathing around the macula and the papillomacular bundle. Fluorescein angiography showed arteriolar focal knobby hyperfluorescence at the macula with mild staini ng of the vascular walls and leakage at the level of the RPE.All 5 cases that ha d indocyanine green angiography done showed early diffuse choroidal hyperfluores cence with late silhouetting of the larger choroidal vessels. Five patients rece ived steroid therapy: 1 topical, 2 periocular, and 2 oral. Over 2 to 4 months, R PE discoloration was observed over the affected areas. After the acute episode, 3 patients showed partial recovery of vision, and in the remaining patients, the visual acuity remained stable. Conclusions Ocular complications associated with dengue fever are rare but may result in permanent visual impairment.

Application of artifcial intelligence in cataract management:current and future directions

The rise of artifcial intelligence(AI)has brought breakthroughs in many areas of medicine.In ophthalmology,AI has delivered robust results in the screening and detection of diabetic retinopathy,age-related macular degeneration,glaucoma,and retinopathy of prematurity.Cataract management is another feld that can beneft from greater AI application.Cataract is the leading cause of reversible visual impairment with a rising global clinical burden.Improved diagnosis,monitoring,and surgical management are necessary to address this challenge.In addition,patients in large developing countries often sufer from limited access to tertiary care,a problem further exacerbated by the ongoing COVID-19 pandemic.AI on the other hand,can help transform cataract management by improving automation,efcacy and overcoming geographical barriers.First,AI can be applied as a telediagnostic platform to screen and diagnose patients with cataract using slit-lamp and fundus photographs.This utilizes a deep-learning,convolutional neural network(CNN)to detect and classify referable cataracts appropriately.Second,some of the latest intraocular lens formulas have used AI to enhance prediction accuracy,achieving superior postoperative refractive results compared to traditional formulas.Third,AI can be used to augment cataract surgical skill training by identifying diferent phases of cataract surgery on video and to optimize operating theater workfows by accurately predicting the duration of surgical procedures.Fourth,some AI CNN models are able to efectively predict the progression of posterior capsule opacifcation and eventual need for YAG laser capsulotomy.These advances in AI could transform cataract management and enable delivery of efcient ophthalmic services.The key challenges include ethical management of data,ensuring data security and privacy,demonstrating clinically acceptable performance,improving the generalizability of AI models across heterogeneous populations,and improving the trust of end-users.

Practical issues concerning tear protein assays in dry eye

Dry eye is a common clinical condition diagnosed by cumulative evidence of symptoms and signs.Many new treatments in dry eye are either expensive,invasive,have potential for side effects,or are not easily accessible.In severe dry eye,the ideal modality of treatment to begin with is often not clear as specific molecular disturbances are not evident from just examination of clinical manifestations.Assessing the effects of ongoing treatment is not straight forward since there is lack of agreement between clinical signs and symptoms.There is a need to have more objective methods of selecting treatment for dry eye and monitoring the effect of treatment.Recently,there are many new technologies applied to the discovery of tear biomarkers,for e.g.,mass spectrometry based proteomics techniques and multiplex assays such as the bead-based sandwich indirect immunofluorescent assays.Tear proteins assays have even been made available as point-of-care devices.This review focuses on the evidence for the involvements of tear proteins in dry eye,possible changes in tear concentrations with therapy and the strength of evidence regarding dry eye pathology.Much remains to be done in terms of developing office-based assays and ascertaining their reliability,but current evidence suggests that tear proteins have a role in the clinical practice of dry eye.

角膜屈光手术后人工晶状体植入度数的计算

目的分析应用 HolladayⅡ公式计算角膜屈光手术后人工晶状体(IOL)植入度数的准确性。方法角膜屈光手术后患者15例(15只眼),分成两组行超声乳化白内障吸除术联合 IOL 植入术。第一组(8只眼)应用 HolladayⅡ公式进行 IOL 度数计算,角膜屈光度根据手术医师经验计算获得,为 KS。第二组(7只眼)应用同一公式,但角膜屈光度应用患者的屈光度数计算获得,为 KR。比较超声乳化白内障吸除术后1个月的屈光度数与术前的预期屈光度数,并应用两者差的绝对值作为标准进行分析。结果两组超声乳化白内障吸除术后1个月的角膜屈光度数与术前预期屈光度数差的绝对值平均值依次为(0.90±0.22)D 和(0.99±0.22)D。结论应用 HolladayⅡ公式计算角膜屈光手术后行超声乳化白内障吸除术时植入 IOL 度数的准确性相对较高。KS 与 KR 在 HolladayⅡ公式中应用的差异无统计学意义。(中华眼科杂志,2006,42:888-891)

Optical coherence tomography angiography for the anterior segment

Optical coherence tomography angiography(OCTA)is a rapid and non-invasive technique for imaging vasculature in the eye.As OCTA can produce high-resolution cross-sectional images and allow depth-resolved analysis for accurate localization of pathology of interest,it has become a promising method for anterior segment imaging.Furthermore,OCTA offers a more patient-friendly alternative to the conventional invasive dye-based fluorescent angiography.However,conventional OCTA systems are typically designed and optimized for the posterior segment of the eye,and thus using OCTA for anterior segment imaging can present several difficulties and limitations.In this review,we summarized the recent developments and clinical applications in anterior segment OCTA(AS-OCTA)imaging,such as for the cornea,iris,sclera and conjunctiva.We also compared commercially available OCTA systems,discussed the limitations of adapting current OCTA technology for the anterior segment imaging,and proposed possible future directions for AS-OCTA systems.AS-OCTA provides potential for future clinical applications such as diagnosis of corneal and iris pathologies,pre-operative surgical planning,assessment of new antiangiogenic therapeutics or evaluation of limbal stem cell deficiency.With further development,OCTA for anterior segment imaging in the clinics may become common in the near future.

Pupil constriction can alter the accuracy of dark room provocative test

Background Primary angle-closure glaucoma （PACG） is a major cause of visual morbidity in East Asia. Dark-room provocative test （DRPT） has been used to determine which narrow angles have the risk to develop angle closure. However, the accuracy of DRPT might be altered because that after emerging from the dark room, the configuration of the angle is affected by the light of the slit-lamp and the appositionally closed angle reopens. The aim of this study was to examine the pupillary diameter in different light conditions and use it as a parameter to assess the accuracy of dark-room provocative test. Methods Patients with suspected primary angle-closure glaucoma undergoing DRPT were recruited. The anterior chamber angle was examined by anterior segment optical coherence tomography under the following conditions： （1） in standard room illumination; （2） after short-term dark-adaptation and （3） after DRPT. Mean values of pupil size and numbers of appositionally closed angle under different conditions were compared. Results A total of 47 eyes of 47 patients were analyzed. The pupil size after DRPT was smaller than that after short-term dark-adaptation （P 〈0.001） and smaller than that in standard room illumination （P=0.026）. The numbers of appositionally closed angles after short-term dark-adaptation were significantly larger than those after DRPT （P 〈0.001）. There was no significant difference between the numbers of appositionally closed angles in standard room illumination and after DRPT （P=-0.157）. Conclusions Constriction of pupil size immediately after prolonged dark room provocative test may lead to change in the angle configuration, which may lead to false negative results. We suggest a modified protocol of recording intraocular pressure immediately after DRPT and performing gonioscopy following short-term dark adaptation to improve the accuracy of angle closure assessment.

Toll-like receptor 2-mediated NF-kappa B pathway activation in ocular surface epithelial cells

Background:Gram-positive bacteria stimulate Toll-like receptor(TLR)2 and then activate the pro-inflammatory nuclear factor-kappa B(NF-κB)pathway.As the human ocular surface is heavily colonised by gram-positive cocci bacteria,a balance of activation/repression of NF-κB target genes is essential to avoid uncontrolled infection or autoimmune-related inflammation.It is advantageous to test NF-κB targeting molecules in an ocular surface culture system that allows assessment of temporal NF-κB activation in a longitudinal fashion without destruction of cells.Such initial testing under standardised conditions should reduce the number of molecules that progress to further evaluation in animal models.This study aims to establish an in-vitro cell culture system to assess NF-κB activation in the context of ocular surface cells.Methods:NF-κB activity was evaluated through a secretory alkaline phosphatase reporter assay(SEAP).Immunoblots and immunofluorescence were used to examine IκBαphosphorylation and p65/p50 nuclear localization.Monocyte chemoattractant protein-1(MCP-1)transcripts were evaluated by real time PCR and protein levels were measured by ELISA.Results:NF-κB activity in HCE-T cells treated with TLR2 activator Pam3CSK4 was higher than control cells at both 6 and 24 h.Pam3CSK4-stimulated NF-κB activation was inhibited by IκK inhibitors,Wedelolactone and BMS-345541.In Pam3CSK4 treated cells,active NF-κB subunits p50 and p65 increased in cell nuclear fractions as early as 1.5 h.Although the level of total IκB-αremained constant,phospho-IκB-αincreased with treatment over time.In the culture media of Pam3CSK4-stimulated cells,MCP-1 protein level was increased,which was suppressed in the presence of IκK inhibitors.Conclusion:NF-κB pathway can be activated by the TLR2 ligand and inhibited by IκK inhibitors in the ocular surface cell culture system.This cell culture system may be used to evaluate TLR-related innate defences in ocular surface diseases.

Different fundus imaging modalities and technical factors in AI screening for diabetic retinopathy:a review

Background:Effective screening is a desirable method for the early detection and successful treatment for diabetic retinopathy,and fundus photography is currently the dominant medium for retinal imaging due to its convenience and accessibility.Manual screening using fundus photographs has however involved considerable costs for patients,clinicians and national health systems,which has limited its application particularly in less-developed countries.The advent of artificial intelligence,and in particular deep learning techniques,has however raised the possibility of widespread automated screening.Main text:In this review,we first briefly survey major published advances in retinal analysis using artificial intelligence.We take care to separately describe standard multiple-field fundus photography,and the newer modalities of ultrawide field photography and smartphone-based photography.Finally,we consider several machine learning concepts that have been particularly relevant to the domain and illustrate their usage with extant works.Conclusions:In the ophthalmology field,it was demonstrated that deep learning tools for diabetic retinopathy show clinically acceptable diagnostic performance when using colour retinal fundus images.Artificial intelligence models are among the most promising solutions to tackle the burden of diabetic retinopathy management in a comprehensive manner.However,future research is crucial to assess the potential clinical deployment,evaluate the cost-effectiveness of different DL systems in clinical practice and improve clinical acceptance.

Vessel density and En-face segmentation of optical coherence tomography angiography to analyse corneal vascularisation in an animal model

Background:Optical coherence tomography angiography(OCTA)is a novel non-invasive angiography technology that has recently been extensively studied for its utility in anterior segment imaging.In this study,we compared a split-spectrum amplitude decorrelation angiography(SSADA)OCTA and an optical micro-angiography(OMAG SD)OCTA system to current angiographic technique,indocyanine green angiography(ICGA),to assess corneal vascularisation in an animal model.Methods:We imaged 16 rabbits,(one eye per animal)with corneal vascularisation using SSADA OCTA(AngioVue;Optovue Inc.,USA),OMAG OCTA(Angioscan;RS-3000 Nidek Co.Ltd.,Japan)and ICGA in the same region of interest of the cornea at successive time-points.We then analysed all scanned images for vessel density measurements and used paired t-tests and Bland-Altman plots to examine for significant differences.The en-face segmentation images from each of the OCTA scans were also extracted and were matched at every 50μm segmentation to be compared for vessel density at the respective depths.Results:Bland-Altman plots revealed a good agreement between all three imaging techniques(P>0.05)for all vessel density measurements computed,and the ranges of 95%limit of agreement were acceptable from a clinical perspective.No significant difference was reported,with ICGA(μ=16.52±8.94%)being more comparable to the OMAG OCTA(μ=16.23±9.51%;p=0.50)than the SSADA OCTA(μ=17.09±7.34%;p=0.33)system.Also,a good correlation value(r>0.9)was obtained when comparing the vessel density measurements of the en-face segmentations between the OCTA systems.Conclusions:Comparable vessel density quantification between the two OCTA systems,and with ICGA was obtained.Segmentation analysis of the vasculature at different depths showed varied performance in the two OCTA systems relative to each other.The implications of the study may help to aid in the development of better OCTA algorithms for the anterior segment and its use in clinical translational research.

Correction to: Vessel density and En-face segmentation of optical coherence tomography angiography to analyse corneal vascularisation in an animal model

In the original publication of this article[1]the algorithm of the OCTA(Nidek RS-3000)was described incorrectly as OMAG(Optical micro angiography).However,the system uses CODAA(Complex OCT signal difference angiography).Thus,‘OMAG’in the article should be replaced with‘CODAA’,and‘Optical micro angiography’should be replaced with‘Complex OCT signal difference angiography’!

Additive effect of cerebral atrophy on cognition in dementia-free elderly with cerebrovascular disease

Objective To explore the additive effect of neurodegenerative diseases,measured by atrophy,on neurocognitive function in Asian dementia-free elderly with cerebrovascular disease(CeVD).Methods The present study employed a cross-sectional design and was conducted between 2010 and 2015 among community-dwelling elderly participants recruited into the study.Eligible participants were evaluated with an extensive neuropsychological battery and neuroimaging.The weighted CeVD burden scale comprising markers of both small-and large-vessel diseases was applied,with a score of≥2,indicating significant CeVD burden.Cortical atrophy(CA)and medial temporal atrophy(MTA)were graded using the global cortical atrophy scale and Schelten's scale,respectively.Global and domain-specific(attention,executive function,language,visuomotor speed,visuoconstruction,visual memory,and verbal memory)neurocognitive performance was measured using a locally validated neuropsychological battery(Vascular Dementia Battery,VDB).Results A total of 819 dementia-free participants were included in the analysis.Among none-mild CeVD subjects,there was no significant difference in the global cognitive performance across atrophy groups(no atrophy,CA,and CA+MTA).However,in moderate-severe CeVD subjects,CA+MTA showed significantly worse global cognitive performance compared with those with CA alone(mean difference=?0.35,95%CI?0.60 to?0.11,p=0.002)and those without atrophy(mean difference=?0.46,95%CI?0.74 to?0.19,p<0.001,p<0.001).In domain-specific cognitive performance,subjects with CA+MTA performed worse than other groups in visual memory(p=0.005),executive function(p=0.001)and visuomotor speed(p<0.001)in moderate-severe CeVD but not in none-mild CeVD.Conclusions and relevance Atrophy and moderate-severe CeVD burden showed an additive effect on global and domain-specific cognitive performance.This study highlights the importance of investigating the mechanisms of clinico-pathological interactions between neurodegenerative processes and vascular damage,particularly in the pre-dementia stage.