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 of retinal thickness and blood flow in agerelated macular degeneration with reticular pseudodrusen

AIM:To investigate thickness characteristics and vascular plexuses in retinas with reticular pseudodrusen(RPD)as an early detection strategy for age-related macular degeneration(AMD).METHODS:This retrospective study included 24 subjects(33 eyes)with RPD and 25 heathy control subjects(34 eyes).The superficial capillary plexus(SCP)and the deep capillary plexus(DCP)of the retinal posterior poles were investigated with optical coherence tomography angiography(OCTA).Retinal thicknesses and vessel densities were analyzed statistically.RESULTS:The general retinal thicknesses of RPD eyes were significantly decreased(95%CI-14.080,-0.655;P=0.032).The vessel densities of DCP in RPD eyes were significantly increased in the global(95%CI 1.067,7.312;P=0.027),parafoveal(95%CI 0.417,5.241;P=0.022),and perifoveal(95%CI 0.181,6.842;P=0.039)quadrants.However,the vessel densities of the SCP were rarely increased in the eyes with RPD.CONCLUSION:The thinning of retinas in the RPD group suggests a reduction in the number of cells.Additionally,the increased vessel density of the DCP in retinas with RPD indicates a greater demand for blood supply,possibly due to the hypoxia induced RPD compensation caused by RPD in the outer retina.This study highlights the pathological risks associated with RPD and emphasizes the importance of early intervention to retard the progression of AMD.

Inhibition of VEGF-A expression in hypoxia-exposed fetal retinal microvascular endothelial cells by exosomes derived from human umbilical cord mesenchymal stem cells

Objective:This study aimed to investigate the potential of human umbilical cord mesenchymal stem cell(hucMSC)-derived exosomes(hucMSC-Exos)in inhibiting hypoxia-induced cell hyper proliferation and overexpression of vascular endothelial growth factor A(VEGF-A)in immature human fetal retinal microvascular endothelial cells(hfRMECs).Methods:Exosomes were isolated from hucMSCs using cryogenic ultracentrifugation and characterized through various techniques,including transmission electron microscopy,nanoparticle tracking analysis,bicinchoninic acid assays,and western blotting.The hfRMECs were identified using von Willebrand factor(vWF)co-staining and divided into four groups:a control group cultured under normoxic condition,a hypoxic model group,a hypoxic group treated with low-concentration hucMSC-Exos(75μg/mL)and a hypoxic group treated with high-concentration hucMSC-Exos(100μg/mL).Cell viability and proliferation were assessed using Cell Counting Kit-8(CCK-8)assay and EdU(5-ethynyl-2′-deoxyuridine)assay respectively.Expression levels of VEGF-A were evaluated using RT-PCR,western blotting and immunofluorescence.Results:Hypoxia significantly increased hfRMECs’viability and proliferation by upregulating VEGF-A levels.The administration of hucMSC-Exos effectively reversed this response,with the high-concentration group exhibiting greater efficacy compared to the lowconcentration group.Conclusion:In conclusion,hucMSC-Exos can dose-dependently inhibit hypoxia-induced hyperproliferation and VEGF-A overexpression in immature fetal retinal microvascular endothelial cells.

Comparation of effectiveness of silicone hydrogel contact lens and hydrogel contact lens in patients after LASEK

AIMTo conduct a comparative study of effectiveness of silicone hydrogel contact lens and hydrogel contact lens, which are used in patients after laser-assisted subepithelial keratomileusis (LASEK).METHODSSixty-three patients (121 eyes) with a spherical equivalent ≤-5.0 D were chosen after undergoing LASEK in 2012 at Guangdong General Hospital. They were randomly divided into 2 groups. The silicone hydrogel group included 32 cases (61 eyes) that wore silicone hydrogel contact lenses for 4-6d after the operation, while the hydrogel group included 31 cases (60 eyes) who wore hydrogel contact lenses for 4-6d after the operation. Patients' self-reported postoperative symptoms (including pain, photophobia, tears, and foreign body sensation) were evaluated. The healing time of the corneal epithelium, the visual acuity of patients without contact lens after epithelial healing, and the incidence of delayed corneal epithelial shedding were also assessed. The follow-up time was 1mo.RESULTSPostoperative symptoms were milder in the silicone hydrogel group than in the hydrogel group. There were significant differences in pain, foreign body sensation, and photophobia between the 2 groups (P<0.05), although there was no significant difference in postoperative tearing (P>0.05). The healing time of the corneal epithelium in the silicone hydrogel lens group was markedly shorter than that in the hydrogel group (4.07±0.25 vs 4.33±0.82d, t=2.43, P=0.02). Visual acuity without contact lenses after healing of the corneal epithelium was better in the silicone hydrogel group compared with the hydrogel group (χ2=7.76, P=0.02). There was no significant difference in the occurrence of delayed corneal epithelial shedding between the 2 groups (P>0.05).CONCLUSIONPatients with LASEK using silicon hydrogel contact lenses had less discomfort and shorter corneal epithelial healing time compared with those using hydrogel contact lenses, suggesting that silicon hydrogel contact lenses may be considered to be a better choice of bandage contact lens after LASEK.

Clinical patterns and characteristics of uveitis in a secondary hospital in southern China

AIM: To investigate the characteristics of uveitis in a secondary hospital in southern China.METHODS: We reviewed all records of patients with uveitis at Hengli Hospital from January 2008 to December2011. Demographic data, past history, ophthalmic examinations and other laboratory tests were analyzed.RESULTS: One hundred and ninety-nine uveitis patients were enrolled in this study, including 134(67.3%) males and 65 females(32.7%) with an average age of 41.0 ±15.1y. The anatomical distribution included103(51.8%) cases of anterior uveitis, followed by panuveitis(65, 32.7%), posterior uveitis(29, 14.6%) and intermediate uveitis(2, 1.0%). Of the 98(49.2%) non-idiopathic cases, there were 10.1% Behcet’s disease,9.5% Vogt-Koyanagi-Harada(VKH) syndrome, 7.5%infectious uveitis, 7.5% traumatic uveitis and 3.5%postoperative uveitis.CONCLUSION: Idiopathic anterior and posterior uveitis,Behcet’s disease, VKH syndrome, infectious uveitis and traumatic uveitis are the most common uveitis entities in a secondary hospital in southern China. Additional measures should be taken to prevent infectious and traumatic uveitis.

Methotrexate for chronic non-necrotizing anterior scleritis in Chinese patients

AIM:To evaluate the effectiveness and corticosteroidsparing capabilities of methotrexate(MTX)in the treatment of chronic non-necrotizing anterior scleritis in Chinese patients.METHODS:A retrospective chart review of all patients with active anterior scleritis between January 2015 and June 2019 was conducted.All patients received 10 to 15 mg/wk MTX orally,and corticosteroids(10 to 40 mg/d prednisolone or equivalent methylprednisolone)with slow tapering.Topical corticosteroid eye drops(1%prednisolone actate,0.1%dexmathosone or 0.1%fluoromethalone)were applied to control comorbid anterior uveitis at presentation or during follow up.The main outcomes were inflammation control and corticosteroid-sparing success,and secondary outcomes were reduction of immunosuppression load and best-corrected visual acuity(BCVA).RESULTS:Thirty-two eyes(22 patients)were included.The proportion of patients who achieved corticosteroidsparing success was 50.0%at 3mo and 77.3%at 12mo[8(36.4%)patients discontinued corticosteroid].The proportion of eyes that achieved inflammation control was 59.4%at 3mo and 78.1%at 12mo.The immunosuppression load was 5.14±0.87 at presentation and 2.76±2.34 at 12mo(P<0.01).BCVA maintained unchanged or improved in 29(90.6%)of all affected eyes.One patient discontinued MTX treatment because of an abnormal liver function test,and no other serious adverse effects were observed.CONCLUSION:According to this pilot study,low dose MTX appear to be a well-tolerated and effective treatment for chronic non-necrotizing anterior scleritis patients in the Chinese population.

Absence of ephrin-A2/A3 increases retinal regenerative potential for Müller cells in Rhodopsin knockout mice

Müller cells(MC) are considered dormant retinal progenitor cells in mammals.Previous studies demonstrated ephrin-As act as negative regulators of neural progenitor cells in the retina and brain.It remains unclear whether the lack of ephrin-A2/A3 is sufficient to promote the neurogenic potential of MC.Here we investigated whether the MC is the primary retinal cell type expressing ephrin-A2/A3 and their role on the neurogenic potential of Müller cells.In this study, we showed that ephrin-A2/A3 and their receptor EphA4 were expressed in retina and especially enriched in MC.The level of ephrin As/EphA4 expression increased as the retina matured that is correlated with the reduced proliferative and progenitor cell potential of MC.Next, we investigated the proliferation in primary MC cultures isolated from wild-type and A2~(–/–) A3~(–/–) mice by 5-ethynyl-2′-deoxyuridine(EdU) incorporation.We detected a significant increase of EdU~+ cells in MC derived from A2~(–/–) A3~(–/–) mice.Next, we investigated the role of ephrin-A2/A3 in mice undergoing photoreceptor degeneration such as Rhodopsin knockout(Rho~(–/–)) mice.To further evaluate the role of ephrin-A2/A3 in MC proliferation in vivo, EdU was injected intraperitoneally to adult wild-type, A2~(–/–) A3~(–/–), Rho~(–/–) and Rho~(–/–) A2~(–/–) A3~(–/–) mice and the numbers of EdU~+ cells distributed among different layers of the retina.Ephrin As/EphA4 expression was upregulated in the retina of Rho~(–/–) mice compared to the wild-type mice.In addition, cultured MC derived from ephrin-A2~(–/–) A3~(–/–) mice also expressed higher levels of progenitor cell markers and exhibited higher proliferation potential than those from wild-type mice.Interestingly, we detected a significant increase of EdU~+ cells in the retinas of adult ephrin-A2~(–/–) A3~(–/–) mice mainly in the inner nuclear layer;and these EdU~+ cells were co-localized with MC marker, cellular retinaldehyde-binding protein, suggesting some proliferating cells are from MC.In Rhodopsin knockout mice(Rho~(–/–) A2~(–/–) A3~(–/–) mice), a significantly greater amount of EdU~+ cells were located in the ciliary body, retina and RPE than that of Rho~(–/–) mice.Comparing between 6 and 12 weeks old Rho~(–/–) A2~(–/–) A3~(–/–) mice, we recorded more EdU~+ cells in the outer nuclear layer in the 12-week-old mice undergoing severe retinal degeneration.Taken together, Ephrin-A2/A3 are negative regulators of the proliferative and neurogenic potentials of MC.Absence of ephrin-A2/A3 promotes the migration of proliferating cells into the outer nuclear layer and may lead to retinal cell regeneration.All experimental procedures were approved by the Animal Care and Use Committee at Schepens Eye Research Institute, USA(approval No.S-353-0715) on October 24, 2012.

Comparison of Ex‑PRESS implantation versus trabeculectomy combined with phacoemulsification in primary open‑angle glaucoma:a retrospective in vivo confocal microscopy study

Background:To compare the efficacy of Ex-PRESS implantation versus trabeculectomy combined with phacoemulsification.Methods:A retrospective 12-month study on patients with coincident primary open-angle glaucoma(POAG)and cataract.The patients underwent combined phacoemulsification and Ex-PRESS implant(Phaco-ExPRESS,n=35)or phacotrabeculectomy(Phaco-Trab,n=35).The morphological structures of the filtering bleb were examined by slitlamp,anterior segment optical coherence tomography(AS-OCT)and in vivo confocal microscopy(IVCM).Complete success was defined as postoperative intraocular pressure(IOP)<18 mmHg without the use of anti-glaucoma medication.Qualified success was defined as postoperative IOP<18 mmHg with or without anti-glaucoma medications.The data were collected preoperatively and postoperatively at 2 weeks,1 month,3 months,6 months,and 12 months.Results:No significant difference in the variables such as age,IOP and perimetry was found between the groups of Phaco-ExPRESS and Phaco-Trab.At the one-year postoperative visit for filtering blebs,Phaco-ExPRESS increased the mean area of epithelial microcysts significantly from 0.10±0.05 to 0.20±0.09μm^(2)perμm^(2),while Phaco-Trab decreased the mean area significantly from 0.08±0.04 to 0.04±0.06μm^(2)perμm^(2).Notably,the hyperreflective dots detected by IVCM decreased by 84.9%in Phaco-ExPRESS but increased by 36.3%in Phaco-Trab.The hyperreflective dots were further identified as neutrophil-and monocyte-like cells.The number of these cells were negatively correlated with the microcysts area(r=−0.7,P<0.01)but positively associated with the grade of connective tissue(r=0.5,P<0.01).By creating different microstructural changes in the filtering blebs,Phaco-ExPRESS produced a higher complete success rate(84.9%vs.41.2%,P<0.01)and significant decrease in the number of anti-glaucoma medications(P<0.01)when compared with those in Phaco-Trab.However,the qualified success showed no significant difference between the two groups(100.0%vs.91.2%,P=0.24).Conclusions:At the one-year follow-up,Phaco-ExPRESS generated better filtering bleb with larger area of microcysts,looser connective tissues,and less inflammation than that of Phaco-Trab,providing adequate IOP control and less IOP-lowering medications.These findings indicate that Phaco-ExPRESS could be more preferred than Phaco-Trab for the treatment of patients with coincident POAG and cataract.

Global burden of vision loss attributable to household air pollution from 1990 to 2019:A trend analysis and 10-year prediction

To the Editor:Blindness and vision loss(BVL)constitute a growing concern affecting an ever-expanding global population.[1]Globally,approximately 40%of the population relies on burning solid fuels for both cooking and heating.Household air pollution(HAP)predominantly arises from the incomplete combustion of solid fuels used for cooking.Nowadays,the adverse effects of HAP on eye health in human have ascended as a salient concern for environmental,ophthalmic,and public health.[2]Gaining a comprehensive understanding of the burden and temporal trends of BVL due to HAP is the essential basis for health program planning.