Refined Anam-Net:Lightweight Deep Learning Model for Improved Segmentation Performance of Optic Cup and Disc for Glaucoma Diagnosis

In this work,we aim to introduce some modifications to the Anam-Net deep neural network(DNN)model for segmenting optic cup(OC)and optic disc(OD)in retinal fundus images to estimate the cup-to-disc ratio(CDR).The CDR is a reliable measure for the early diagnosis of Glaucoma.In this study,we developed a lightweight DNN model for OC and OD segmentation in retinal fundus images.Our DNN model is based on modifications to Anam-Net,incorporating an anamorphic depth embedding block.To reduce computational complexity,we employ a fixed filter size for all convolution layers in the encoder and decoder stages as the network deepens.This modification significantly reduces the number of trainable parameters,making the model lightweight and suitable for resource-constrained applications.We evaluate the performance of the developed model using two publicly available retinal image databases,namely RIM-ONE and Drishti-GS.The results demonstrate promising OC segmentation performance across most standard evaluation metrics while achieving analogous results for OD segmentation.We used two retinal fundus image databases named RIM-ONE and Drishti-GS that contained 159 images and 101 retinal images,respectively.For OD segmentation using the RIM-ONE we obtain an f1-score(F1),Jaccard coefficient(JC),and overlapping error(OE)of 0.950,0.9219,and 0.0781,respectively.Similarly,for OC segmentation using the same databases,we achieve scores of 0.8481(F1),0.7428(JC),and 0.2572(OE).Based on these experimental results and the significantly lower number of trainable parameters,we conclude that the developed model is highly suitable for the early diagnosis of glaucoma by accurately estimating the CDR.

Cost of Medical Treatment for Primary Open-Angle Glaucoma in Relation to Patients’ Income and Its Impact on the Prognosis of the Disease, in Bouaké University Hospital

Introduction: Medical treatment for POAG is continuous and lifelong treatment. The aim of this study was to evaluate the relationship between the cost of this treatment and patients’ income and the impact of this relationship on treatment compliance. Materials and Methods: Prospective cross-sectional study with a descriptive aim covering sociodemographic data, average incomes, and direct and indirect costs of treatment of 57 patients followed for POAG during the period from January 1, 2012, to December 31, 2016 (5 years). Results: The patients were aged 25 to 77 years (mean = 54.4 years) with a male predominance (sex ratio = 1.5). Retirees were the most represented (26.32%), followed by workers in the informal sector (14.04%) and housewives (12.28%). Patients who had an annual income less than or equal to 900,000 CFA francs (€1370.83) per year represented 56.14% and those who did not have health coverage represented 57.89%. The treatment was monotherapy (64.91%), dual therapy (31.58%) or triple therapy (3.05%) and the average ratio of “annual cost of treatment to annual income” was 0.56 with for maximum 2.23 and 0.02 as minimum. Patients who considered the cost of treatment unbearable for their income represented 78.95%. Conclusion: Prevention of blindness due to glaucoma requires early detection but also the establishment of health coverage mechanisms to improve compliance with medical treatment. In addition, consideration should be given to the development of glaucoma surgery in our country, the indication of which could be the first intention in certain patients, considering for those patients, the geographical and financial accessibility of medical treatment. .

Epidemiological, Clinical, Therapeutic and Evolutive Profile of Primary Open-Angle Glaucoma in a Cameroonian Population

Background: Sub-Saharan Africa has the highest prevalence of primary open-angle glaucoma (POAG), at 4.2%. The efficacy of medical treatment has been demonstrated and remains one of the treatments of choice for POAG. However, in sub-Saharan Africa, its effectiveness has many challenges, due to multiple factors, including cost and access to care. Thus, the present study aimed to determine the epidemiological, clinical, therapeutic and evolutive profile of primary open-angle glaucoma patients. Methodology: A descriptive cross-sectional study was carried out in two hospitals in western Cameroon. Epidemiological, clinical, therapeutic, and evolutionary data on intraocular pressure at one year after medical treatment were analyzed. SPSS version 23 software was used for statistical analysis, with a significant p-value set at 5%. Results: A total of 201 patients with POAG were included in the study. The population comprised 100 men and 101 women, with a mean age of 54 ± 12 years. At diagnosis, the mean intraocular pressure was 23.9 ± 8.70 mmHg for the right eye and 25.5 ± 9.57 mmHg for the left eye. The mean cup/disc ratio was 0.64 ± 0.2 [0.2-1] and 0.67 ± 0.19 [02-1] in the right and left eyes, respectively. Monotherapy was the most prescribed treatment [59.2%]. After one year of treatment, intraocular pressure was reduced by 15.5% with beta-blockers, 23.66% with prostaglandins, 19.11% with carbonic anhydrase inhibitors, 35, 92% with beta-blockers and carbonic anhydrase inhibitors, 25.92% with beta-blockers and prostaglandins, 48.03% with carbonic anhydrase inhibitors and prostaglandin agonists, and 38.77% with triple therapy. Taking glaucoma severity into account, a significant reduction in intraocular pressure at one year was observed in all participants [p 0.05]. However, the target pressure was obtained in 47%, 20% and 14% of eyes suffering of mild, moderate, and severe grade of POAG respectively. Conclusion: In the present study, there was a significant reduction in intraocular pressure after one year of medical treatment. However, the reduction in intraocular pressure does not allow the target pressure to be reached in severe forms. Thus, alternatives to the medical treatment of POAG should be discussed early in the present context. .

Selective laser trabeculoplasty as adjunctive treatment for open-angle glaucoma vs following incisional glaucoma surgery in Chinese eyes

BACKGROUND Selective laser trabeculoplasty(SLT)is a relatively safe and effective therapy in lowering intraocular pressures(IOP)for glaucoma.AIM To study the long-term effects of SLT on IOP and number of glaucoma medications used in Chinese eyes.METHODS This is a retrospective study in which 75 eyes of 70 patients with open-angle glaucoma(OAG,n=36)and eyes with prior glaucoma surgery(PGS,n=39)were included.Changes in mean IOP and number of glaucoma medications used evaluated at 1 d,1 wk,1 mo,3 mo,6 mo,12 mo,and 36 mo after laser treatment.RESULTS All patients(33 male,37 female)were Chinese.The mean age was 44.34±16.14years.Mean pre-SLT IOP was 22.75±2.08 mmHg in OAG and 22.52±2.62 mmHg in PGS.Mean IOP was significantly reduced 1 d,1 wk,1 mo and 3 mo after laser treatment(P<0.05,respectively).Whereas,there were no significant differences between baseline and SLT treated groups at the 6th month both in OAG(P=0.347,P>0.05)and in PGS(P=0.309,P>0.05).Six months after SLT treatment,some patients received retreatment of SLT or were given more topical IOP-lowering medication to control the IOP.By the end of our study,the average IOP decreased to 20.73±1.82 mmHg in OAG and 20.49±1.53 mmHg in PGS groups.The number of glaucoma medications used was significantly reduced until the end of 3 years compared to baseline.CONCLUSION SLT could reduce IOP as adjunctive treatment both in OAG and PGS groups.SLT significantly reduced the number of glaucoma medications used 3-years following treatment in glaucoma patients.

Abnormal Systemic and Ocular Responses to the Valsalva Manoeuvre in Primary Open-Angle Glaucoma:A Case for Autonomic Failure?

Objective This study aimed to examine the association of primary open-angle glaucoma(POAG)with autonomic dysfunction by assessing the differences in systemic and ocular responses to an autonomic provocation test,the Valsalva manoeuvre(VM),between POAG patients and normal subjects.Methods Forty POAG and forty control subjects were subjected to the VM.Systemic and ocular parameters were measured at baseline,phase 2,and phase 4 of the VM(VM2 and VM4),where VM2 and VM4 are sympathetic and parasympathetic nervous activation states,respectively.Heart rate variability was used to assess the autonomic nervous activity,among which the high-frequency component(HF)and the low-frequency(LF)/HF ratio were used as indices of parasympathetic and sympathetic activation,respectively.Results POAG patients demonstrated higher sympathetic activation(LF/HF ratio median:2.17 vs.1.53,P=0.000)than controls at baseline and exhibited attenuated sympathetic and parasympathetic responses(a smaller change in LF/HF and HF values)during the VM than controls.During VM,the intraocular pressure(IOP),mean blood pressure(MAP),mean ocular perfusion pressure(MOPP),and the Schlemm’s canal area(SCAR)increased from baseline to VM2 and then decreased from VM2 to VM4 in both the POAG and control groups(all P<0.05).However,when we compared the changes above,the fluctuations in IOP,MAP,and MOPP were more pronounced in POAG than in controls(all P<0.05),while the changes in amplitudes of SCAR were smaller in POAG(P<0.05).Furthermore,from VM2 to VM4,the choroid thickness(ChT)in the POAG group was significantly decreased,while it was unchanged in normal subjects(P=0.258).A regression analysis showed a significant correlation of the baseline LF/HF with IOP change values(ΔIOP)from baseline to VM2 in POAG(R^(2)=0.147,P=0.014).Conclusion Patients with POAG showed more pronounced fluctuations in IOP,MAP,MOPP and ChT during the VM than controls.These reactions could be associated with autonomic dysfunction in POAG.

Etiology, pathogenesis, and diagnosis of neovascular glaucoma

Neovascular glaucoma is defined as iris and/or anterior chamber angle neovascularization associated with increased intraocular pressure. It is a secondary glaucoma that is most frequently caused by severe retinal ischemia. The most common diseases responsible for the development of neovascular glaucoma are diabetic retinopathy, ischemic central retinal vein occlusion,and ocular ischemic syndrome. Uncommon causes include ocular radiation, ocular tumors, uveitis and other miscellaneous conditions. Vascular endothelial growth factor is an important and likely predominant agent involved in the pathogenesis of intraocular neovascularization and neovascular glaucoma. The evolution of clinical and histopathological changes from predisposing conditions to the occurrence of rubeosis iridis and neovascular glaucoma is divided into four stages: prerubeosis, preglaucoma, open angle glaucoma, and angle-closure glaucoma.

Prevalence of Open-angle Glaucoma in Southwestern China: the Yongchuan Glaucoma Study

This study examined the prevalence of primary open-angle glaucoma（POAG） among residents aged ≥50 years living in Yongchuan district of Chongqing. Stratified cluster sampling was employed in random selection to estimate the prevalence of glaucoma from April to June, 2005. Twenty-nine villages or neighborhood communities were randomly selected in urban area（Zhongshan Road）, suburban area（Shanjiao Town） and exurban area（Zhutuo Town） of this district. All the respondents underwent detailed ophthalmic examinations. The examinations included questionnaire investigation, visual acuity test, naked-eye examination, measurement of peripheral anterior chamber depth（Van Herrick＇s technique）, detection of intraocluar pressure（IOP） with a Perkins hand-held applanation tonometer（HA-2） and examination of the optic disc by using a 78 diopters（D） lens（including the cup-disc ratio, cup/disc ratio asymmetries, horizontal and vertical diameter, notching and optic disc hemorrhages）. A total of 5938 residents were actually examined, and the response rate was 85.19%. The crude prevalence of POAG was 0.86%（n=51/5938, 95% CI 0.64%–1.11%）. There were 24 males and 27 females in the glaucoma group. The glaucoma prevalence was not significant different in case number between the male and female subjects（P=0.4900）. Furthermore, no association between age or schooling and POAG was noted（P=0.8030, 0.0734）. Out of 51 subjects with POAG, unilateral glaucoma-related blindness occurred in 38 subjects（74.5%） and bilateral glaucoma-related blindness was found in 7 subjects（13.7%）. This study exhibited that the prevalence of POAG was 0.86% among residents aged ≥50 years living in Yongchuan District of Chongqing. The vision loss caused by POAG in this population was obviously higher than that previously reported in other studies. Glaucoma management, detection of affected persons and handling of the burden of glaucoma should be the priorities of the agenda of local health authorities of Western China.

Current applications of machine learning in the screening and diagnosis of glaucoma: a systematic review and Meta-analysis

AIM: To compare the effectiveness of two well described machine learning modalities, ocular coherence tomography(OCT) and fundal photography, in terms of diagnostic accuracy in the screening and diagnosis of glaucoma. METHODS: A systematic search of Embase and Pub Med databases was undertaken up to 1 st of February 2019. Articles were identified alongside their reference lists and relevant studies were aggregated. A Meta-analysis of diagnostic accuracy in terms of area under the receiver operating curve(AUROC) was performed. For the studies which did not report an AUROC, reported sensitivity and specificity values were combined to create a summary ROC curve which was included in the Meta-analysis.RESULTS: A total of 23 studies were deemed suitable for inclusion in the Meta-analysis. This included 10 papers from the OCT cohort and 13 from the fundal photos cohort. Random effects Meta-analysis gave a pooled AUROC of 0.957(95%CI=0.917 to 0.997) for fundal photos and 0.923(95%CI=0.889 to 0.957) for the OCT cohort. The slightly higher accuracy of fundal photos methods is likely attributable to the much larger database of images used to train the models(59 788 vs 1743). CONCLUSION: No demonstrable difference is shown between the diagnostic accuracy of the two modalities. The ease of access and lower cost associated with fundal photo acquisition make that the more appealing option in terms of screening on a global scale, however further studies need to be undertaken, owing largely to the poor study quality associated with the fundal photography cohort.

High interpretable machine learning classifier for early glaucoma diagnosis

AIM:To develop a classifier for differentiating between healthy and early stage glaucoma eyes based on peripapillary retinal nerve fiber layer(RNFL)thicknesses measured with optical coherence tomography(OCT),using machine learning algorithms with a high interpretability.METHODS:Ninety patients with early glaucoma and 85 healthy eyes were included.Early glaucoma eyes showed a visual field(VF)defect with mean deviation>-6.00 d B and characteristic glaucomatous morphology.RNFL thickness in every quadrant,clock-hour and average thickness were used to feed machine learning algorithms.Cluster analysis was conducted to detect and exclude outliers.Tree gradient boosting algorithms were used to calculate the importance of parameters on the classifier and to check the relation between their values and its impact on the classifier.Parameters with the lowest importance were excluded and a weighted decision tree analysis was applied to obtain an interpretable classifier.Area under the ROC curve(AUC),accuracy and generalization ability of the model were estimated using cross validation techniques.RESULTS:Average and 7 clock-hour RNFL thicknesses were the parameters with the highest impor tance.Correlation between parameter values and impact on classification displayed a stepped pattern for average thickness.Decision tree model revealed that average thickness lower than 82μm was a high predictor for early glaucoma.Model scores had AUC of 0.953(95%CI:0.903-0998),with an accuracy of 89%.CONCLUSION:Gradient boosting methods provide accurate and highly interpretable classifiers to discriminate between early glaucoma and healthy eyes.Average and 7-hour RNFL thicknesses have the best discriminant power.

Critical pathway for primary open angle glaucoma diagnosis

AIM： To develop a critical pathway for primary open angle glaucoma （POAG） diagnosis intended to be efficient, to unify criteria, reduce resource use and minimize costs to the health system. METHODS： We performed a systematic search on PubMed, Cochrane, Embase and ClinicalTrials.org databases and classified the quality of evidence from level I through III. RESULTS： A critical pathway was designed by setting a key-decision step by step model on the basis of the best current evidence. CONCLUSION： A critical pathway, evidence-based guideline, may be a useful tool intended to reduce costs while maintaining or even improving the quality of care for diagnosing a highly prevalent pathology such as open angle glaucoma.

Coinheritance of OLFM2 and SIX6 variants in a Chinese family with juvenile-onset primary open-angle glaucoma: A case report

BACKGROUND Juvenile-onset primary open-angle glaucoma(JOAG),characterized by severe elevation of intraocular pressure and optic neuropathy prior to the age of 40,is a rare subtype of primary open-angle glaucoma.Several genetic mutations have been associated with JOAG.CASE SUMMARY The proband patient was a young male,diagnosed with primary open-angle glaucoma at the age of 27.The patient and his unaffected parents who have been excluded from classic genetic mutations for primary open-angle glaucoma were included to explore for other possible genetic variants through whole genome sequencing and bioinformatics analysis.In this trio,we found two heterozygous variants inherited from the parents in the proband:c.281G>A,p.Arg94His in OLFM2 and c.177C>G,p.Ile59Met in SIX6.Both genetic mutations are predicted through bioinformatics analysis to replace evolutionary conserved amino acids,therefore rendering a pathogenic effect on proteins.In contrast,very low frequencies for these genetic mutations were recorded in most common control databases.CONCLUSION This is the first report on coinherited mutations of OLFM2 and SIX6 in a JOAG family,which shows the complexity of JOAG inheritance.Large-scale clinical screening and molecular functional investigations on these coinherited mutations are imperative to improve our understanding of the development of JOAG.

A case of 9p deletion syndrome with congenital infantile glaucoma,effective method of diagnosis,and treatment

Dear Editor,I am Dr.Jia X from the Department of Ophthalmology,Second Xiangya Hospital,Central South University,Changsha,China.I write to present a rare case report of 9p deletion syndrome with congenital infantile glaucoma in an infant,accompanying with an effective method of both diagnosis and treatment.

A new strategy to interpret OCT posterior pole asymmetry analysis for glaucoma diagnosis

AIM：To detect early glaucoma by optical coherence tomography（OCT） posterior pole asymmetry analysis.METHODS：Totally 39 eyes from 39 healthy subjects,40 eyes from 40 mild glaucoma patients,33 eyes from 33 moderate glaucoma patients and 41 eyes from severe glaucoma patients were included in this study.All subjects underwent posterior pole asymmetry analysis（PPAA） of OCT and the posterior pole area was divided into three zones.Means,standard deviations and 95% confidence intervals of each zone asymmetry in control group were assessed.Retina thickness asymmetry（RTA） of different stage of glaucoma were compared for each zone,and receiver operating characteristic（ROC） curves were made to test the efficacy of strategies using different zones to discriminate glaucomatous eyes from the healthy ones.RESULTS：In a healthy population,RTA of the centre zone showed the minimal mean value（3.085 μm）,standard deviation（1.756）,and the narrowest 95% confidence interval（from 2.360 to 3.810 μm）.It was only in the center zone that RTA exhibited significant difference between control and moderate glaucoma group（P〈0.01）,as well as control and severe glaucoma group（P〈0.00001）.The strategy utilized in the center zone had the strongest diagnostic capability（zone 3 AUROC=0.816,P=0.0016） in comparison to that of the periphery area（zone 1 AUROC=0.675,P=0.0016;zone 2 AUROC=0.623,P=0.0197）,the whole posterior pole involved interpreting strategy showed inferior diagnostic power than the centre zone dependent strategy（z=2.851,P=0.0044）.CONCLUSION：Utilizing the posterior pole centre zone to interpret OCT PPAA results are more effective than making use of the whole posterior pole map.

Incidence of Primary Open-Angle Glaucoma at the Flamboyants Communal Medical Center of Conakry, Guinea

Background: Primary Open-Angle Glaucoma (POAG) is a chronic, progressive optic neuropathy of multifactorial origin defined by alterations in the visual field, progressive loss of optic nerve fibers and ganglion cells, and an open iridocorneal angle in gonioscopy. It is the world’s leading cause of irreversible blindness. There is no epidemiological study in Guinea that allows us to locate the real level of the problem. The objective of this study is to determine the hospital incidence of POAG at the Centre Médical Communal (CMC) in the Flamboyants. Patients and Method: This was a descriptive cross-sectional study with a prospective collection for one year, from April 1, 2020 to March 31, 2021, in patients aged at least 40 years, received in consultation at the CMC in the Flamboyants. The diagnostic criterion for a new case of glaucoma was the presence in a patient of the following two signs: (excavation of the optical disc C/D ≥ 0.5 and alteration of the visual field) with an open angle at least stage 4 of the Shaffer and Etienne classification associated or not with ocular hypertonia and having never received anti glaucoma treatment. We described variables related to sociodemographic characteristics, visual acuity, intraocular pressures, papillary excavations, and visual field surveys. Informed consent from patients was sought and obtained. The confidentiality of the files was guaranteed. Results: 68 new cases of POAG were diagnosed out of 3220 consultations, an incidence rate of 2.11%. The average age was 58.2 years (10.64 with a male predominance of 63.23%. A family history of glaucoma was present in 11.36% of cases. Visual acuity was poor Conclusion: This study has shown us that POAG in our environment is relatively common, early onset, and rapidly evolving. The implementation of a rapid and reliable screening strategy by the Eye Health Program will make it possible to manage glaucoma from the earliest stages.

Supraciliary microstenting with phacoemulsification in patients with open-angle glaucoma and cataracts

Elevated intraocular pressure(IOP)is a major risk factor for the development or progression of glaucoma.Lowering IOP is the only proven therapeutic approach to the management of glaucoma.IOP can be lowered by medication,laser treatment or surgery(1).Generally,instillation of IOP-

SEQUENTIAL INTRAOCULAR PRESSURE MEASUREMENTS IN SUSPECTED OPEN-ANGLE GLAUCOMA

Objective To evaluate the variations of intraocular pressure （lOP） in suspected open-angle glaucoma （OAG） patients. Methods The variations of lOP were measured in 216 eyes of suspected OAG patients at 4-hour intervals for 48 h. Based on the results of the serial lOP measurements, optic disc changed and visual field defected, the patients were diagnosed as primary OAG （ POAG ）, normal tension glaucoma （NTG）, ocular hypertension （ OHT） , or physiologic cup （PC）. Results After the serial lOP measurements, 16. 7% of the suspected OAG patients were diagnosed as POAG, 32. 4% as NTG, 24. 5% as OHT, and 26. 4% as PC. The highest percentages of the POAG group had peak lOP at 8 AM （19. 4% ） and their trough lOP at 10 PM （27. 8% ） ; the NTG group had peak lOP at 12 AM （18. 6% ） and their trough lOP at 12 PM （22. 9% ） ; the OHT group had peak lOP at 4 AM （22. 6% ） and their trough lOP at 10 PM （26. 4% ） ; and the PC group had peak lOP at 4 AM （ 21. 1% ） and their trough lOP at 12 PM （ 21. 1% ）. The percentages of peak lOP outside clinic （ 8 AM - 4 PM） in the POAG, NTG, OHT and PC groups were 55. 6%, 50. 0%, 58. 4% and 45. 7%, respectively. The mean magnitude of variance was 5. 1 - 6. 7 mmHg in those suspected OAG patients. There was a strong positive correlation in lOP between both eyes at each time point of measurement and the variation curves of the right and left eyes had parallel profiles in those suspected OAG patients. Conclusion Serial measurement of lOP is still needed, in order not to miss the peak and the trough lOP readings in suspected OAG patients, which helps in better management of glaucoma.

Peripapillary and macular vascular densities in healthy,ocular hypertensive,and different stages of glaucomatous eyes

AIM:To investigate vascular changes in different stages of glaucoma and to evaluate the role of optical coherence tomography angiography(OCTA)in the early diagnosis of glaucoma.METHODS:Glaucoma patients and healthy controls(n=29 eyes)were investigated in this cross-sectional comparative study.Glaucoma patients were grouped as ocular hypertension(n=44 eyes),preperimetric glaucoma(PPG;n=32 eyes),early glaucoma(EG;n=35 eyes),moderate stage glaucoma(MG;n=36 eyes),and advanced glaucoma(AG;n=35 eyes).Peripapillary and macular vascular densities(VDs)of all participants were compared and correlations of VDs and retinal nerve fiber layer thickness(RNFLT),ganglion cell analysis(GCA),and visual field(VF)tests were evaluated.Area under the receiver operation characteristic curves(AUC)of the peripapillary and macular VD parameters were obtained.RESULTS:VD values decreased with the progression of glaucoma.Most peripapillary and macular VD parameters of PPG and EG groups were lower than healthy controls(P<0.001).There was no significant difference in RNFLT between the PPG and EG groups,but most peripapillary and macular VDs were found to be lower in EG group than in PPG group(P<0.05).In most disease group,VDs were significantly correlated with OCT parameters(P<0.001)and VF index(P<0.05).There were no significant correlations between VF and RNFLT indices in the AG group,but significant correlations were found between VF and VD values(P<0.05).AUC for discriminating between healthy and glaucomatous eyes were highest in whole image peripapillary VD(AUC:0.865,0.929,and 0.986,respectively in EG,MG,and AG groups).CONCLUSION:OCTA can be used in the early diagnosis of glaucoma and can be useful in follow-up of the advanced disease.In cases where limitations or suspicions in structural and functional tests are present,OCTA can be used as a supportive diagnostic test,both in EG and AG.

Association of age at diagnosis of diabetes with subsequent risk of age-related ocular diseases and vision acuity

BACKGROUND The importance of age on the development of ocular conditions has been reported by numerous studies.Diabetes may have different associations with different stages of ocular conditions,and the duration of diabetes may affect the development of diabetic eye disease.While there is a dose-response relationship between the age at diagnosis of diabetes and the risk of cardiovascular disease and mortality,whether the age at diagnosis of diabetes is associated with incident ocular conditions remains to be explored.It is unclear which types of diabetes are more predictive of ocular conditions.AIM To examine associations between the age of diabetes diagnosis and the incidence of cataract,glaucoma,age-related macular degeneration(AMD),and vision acuity.METHODS Our analysis was using the UK Biobank.The cohort included 8709 diabetic participants and 17418 controls for ocular condition analysis,and 6689 diabetic participants and 13378 controls for vision analysis.Ocular diseases were identified using inpatient records until January 2021.Vision acuity was assessed using a chart.RESULTS During a median follow-up of 11.0 years,3874,665,and 616 new cases of cataract,glaucoma,and AMD,respectively,were identified.A stronger association between diabetes and incident ocular conditions was observed where diabetes was diagnosed at a younger age.Individuals with type 2 diabetes(T2D)diagnosed at<45 years[HR(95%CI):2.71(1.49-4.93)],45-49 years[2.57(1.17-5.65)],50-54 years[1.85(1.13-3.04)],or 50-59 years of age[1.53(1.00-2.34)]had a higher risk of AMD independent of glycated haemoglobin.T2D diagnosed<45 years[HR(95%CI):2.18(1.71-2.79)],45-49 years[1.54(1.19-2.01)],50-54 years[1.60(1.31-1.96)],or 55-59 years of age[1.21(1.02-1.43)]was associated with an increased cataract risk.T2D diagnosed<45 years of age only was associated with an increased risk of glaucoma[HR(95%CI):1.76(1.00-3.12)].HRs(95%CIs)for AMD,cataract,and glaucoma associated with type 1 diabetes(T1D)were 4.12(1.99-8.53),2.95(2.17-4.02),and 2.40(1.09-5.31),respectively.In multivariable-adjusted analysis,individuals with T2D diagnosed<45 years of age[β95%CI:0.025(0.009,0.040)]had a larger increase in LogMAR.Theβ(95%CI)for LogMAR associated with T1D was 0.044(0.014,0.073).CONCLUSION The younger age at the diagnosis of diabetes is associated with a larger relative risk of incident ocular diseases and greater vision loss.

Identification and validation of key biomarkers and potential therapeutic targets for primary open-angle glaucoma

Primary open-angle glaucoma(POAG)is a prevalent cause of blindness worldwide,resulting in degeneration of retinal ganglion cells and permanent damage to the optic nerve.However,the underlying pathogenetic mechanisms of POAG are currently indistinct,and there has been no effective nonsurgical treatment regimen.The objective of this study is to identify novel biomarkers and potential therapeutic targets for POAG.The mRNA expression microarray datasets GSE27276 and GSE138125,as well as the single-cell high-throughput RNA sequencing(sc RNA-seq)dataset GSE148371 were utilized to screen POAGrelated differentially expressed genes(DEGs).Functional enrichment analyses,protein-protein interaction(PPI)analysis,and weighted gene co-expression network analysis(WGCNA)of the DEGs were performed.Subsequently,the hub genes were validated at a single-cell level,where trabecular cells were annotated,and the mRNA expression levels of target genes in different cell clusters were analyzed.Immunofluorescence and quantitative real-time PCR(q PCR)were performed for further validation.DEGs analysis identified 43 downregulated and 32 upregulated genes in POAG,which were mainly enriched in immune-related pathways,oxidative stress,and endoplasmic reticulum(ER)stress.PPI networks showed that FN1 and DUSP1 were the central hub nodes,while GPX3 and VAV3 were screened out as hub genes through WGCNA and subsequently validated by q PCR.Finally,FN1,GPX3,and VAV3 were determined to be pivotal core genes via single-cell validation.The relevant biomarkers involved in the pathogenesis of POAG,may serve as potential therapeutic targets.Further studies are necessary to unveil the mechanisms underlying the expression variations of these genes in POAG.

Clinical relevance of the glucocorticoid receptor gene polymorphisms in glucocorticoid-induced ocular hypertension and primary open angle glaucoma

AIM: To avoid the side effects of ocular hypertension of glucocorticoid(GC) usage in eye, we must identify susceptible individuals, which exists in about one-third of all population. Further, the majority of all primary open angle glaucoma(POAG) patients show this phenotype.Glucocorticoid receptor(GR) regulates C responsiveness in trabecular meshwork(TM) cells. In this study, single nucleotide polymorphism(SNP) genotyping was used to determine whether there are differences in the Bcl I(rs41423247) and N363S(rs6195) polymorphisms of the GR gene in healthy and POAG patients, and glucocorticoid-induced ocular hypertension(GIOH)populations.METHODS: Three hundred and twenty-seven unrelated Chinese adults, including 111 normal controls, 117 GIOH subjects and 99 POAG patients, were recruited. DNA samples were prepared and the Bcl I and N363 S polymorphisms were screened using real-time polymerase chain reaction(RT-PCR)-restriction fragment length polymorphism(RFLP) analysis. Frequencies of the Bcl I and N363 S polymorphisms were determined and compared using Fisher’s exact test and the Chi-squared test.RESULTS: Only the Bcl I polymorphism was identified in the Chinese Han population. The frequency of the G allele was 21.6 % in normal controls, 18.3% in GIOH patients, and 13.64% in the POAG patients. There was no significant difference in polymorphism or allele frequency in the 3 groups. Furthermore, no N363 S polymorphism was found in the study subjects.CONCLUSION: The Bcl I polymorphisms in GR gene had no association with GIOH and POAG patients, and N363 S polymorphism might not exist in the Chinese Han population. Therefore, the Bcl I polymorphism might not be responsible for the development of GC-induced ocular hypertension or POAG.