Kyrieleis plaques are a rare retinal manifestation that has rarely been reported in Behcet's disease uveitis. We report the case of a 41-year-old man who presented with Behçet's disease uveitis combined with central serous chorioretinopathy. Laboratory studies showed positive for human leukocyte antigen B51. Polymerase chain reaction analysis of aqueous humor excluded infectious uveitis. Kyrieleis plaques were observed in the bilateral retinal arteries. These plaques persisted in both eyes after half a year of immunosuppressive treatments. Kyrieleis plaques are not limited to infectious uveitis; they can also be associated with Behçet's disease uveitis.

PURPOSE. Proliferative diabetic retinopathy (PDR) is a severe microvascular complication of diabetes mellitus. Although exosomes participate in various pathologic processes, their role in ocular pathologies is unclear. This study profiled exosomal microRNAs (exomiRNAs) in the vitreous humor (VH) of patients with PDR to elucidate their regulatory roles in PDR pathogenesis. METHODS. VH samples were obtained from 23 patients with PDR and 17 non-diabetic controls. Exosomes were isolated using ultracentrifugation and characterized via transmission electron microscopy, nanoparticle tracking analysis and Western blot. Highthroughput sequencing identified differentially expressed miRNAs (DEMs), followed by target gene prediction and bioinformatic analyses. The top DEMs were validated using quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS. Exosomes were isolated and characterized from VH samples. Sequencing analysis identified 843 unique miRNAs, with 60 showing significant differential expression between PDR and control groups (28 upregulated and 32 downregulated). The miR-451a and miR-486-5p were most upregulated; miR-204-5p and miR-211-5p were most downregulated. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses revealed DEM target genes enriched in endocrine, metabolic, signaling transduction, and intercellular adhesion pathways, notably cGMP-PKG, mTOR, and cAMP pathways. Network analysis identified miR-486-5p and miR-451a as key hubs. Validation by qRT-PCR confirmed the differential expression in the sequencing analysis. CONCLUSIONS. This study provides the comprehensive profile of vitreous exo-miRNAs in patients with PDR, identifying key DEMs and their potential regulatory networks. These findings indicate that vitreous exo-miRNAs, specifically miR-204-5p and miR486-5p, represent promising diagnostic biomarkers and potential therapeutic targets for PDR.

PurposeTo quantify the global impact of vision impairment in individuals aged 65 years and older between 1990 and 2019, segmented by disease, age, and sociodemographic index (SDI).MethodsUsing the Global Burden of Diseases 2019 (GBD 2019) dataset, a retrospective demographic evaluation was undertaken to ascertain the magnitude of vision loss over this period. Metrics evaluated included case numbers, prevalence rates per 100,000 individuals, and shifts in prevalence rates via average annual percentage changes (AAPCs) and years lived with disability (YLDs).ResultsFrom 1990 to 2019, vision impairment rates for individuals aged 65 years and older increased from 40,027.0 (95% UI: 32,232.9-49,945.1) to 40,965.8 (95% UI: 32,911-51,358.3, AAPC: 0.11). YLDs associated with vision loss saw a significant decrease, moving from 1713.5 (95% UI: 1216.2–2339.7) to 1579.1 (95% UI: 1108.3–2168.9, AAPC: −0.12). Gender-based evaluation showed males had lower global prevalence and YLD rates compared to females. Cataracts and near vision impairment were the major factors, raising prevalence by 6.95 and 2.11%, respectively. Cataract prevalence in high-middle SDI regions and near vision deficits in high SDI regions significantly influenced YLDs variation between 1990 and 2019.ConclusionOver the past three decades, there has been a significant decrease in the vision impairment burden in individuals aged 65 and older worldwide. However, disparities continue, based on disease type, regional SDI, and age brackets. Enhancing eye care services, both in scope and quality, is crucial for reducing the global vision impairment burden among the older adults.

Purpose To compare short-term anatomical outcomes observed in optical coherence tomography (OCT) between intravitreal injection (IVI) with anti-vascular endothelial growth factor (VEGF) agent aflibercept (IVA) and subthreshold micropulse laser (SML) therapy in chronic central serous chorioretinopathy (cCSC).Methods Thirty-nine eyes of 36 patients with symptomatic cCSC in this retrospective study received either IVA or SML between December 2020 and August 2022. Spectral-domain-OCT (SD-OCT) findings were compared between the two treatment groups in terms of central macular thickness (CMT), serous subretinal fluid (SRF) height, the presence of pigment epithelial detachment (PED) and subretinal hyperreflective foci (HF) at baseline and one-month follow-up visits.Results Both groups showed significant reductions in CMT and SRF at one-month follow-up visit. However, there were no statistically significant differences between the IVA and SML groups. Complete SRF resolution was observed in 10 out of 21 and 7 out of 18 eyes in the IVA and SML groups, respectively; however, retinal pigment epithelial (RPE) damage remained persistent in patients with PEDs at baseline.Conclusions Both IVA and SML were effective in treating cCSC. IVA and SML treatments had comparable effects in reducing CMT and SRF in eyes with cCSC. Further prospective studies with larger sample sizes and long-term follow-up visits are warranted to identify the long-term efficacy.

Age-related macular degeneration (AMD) causes irreversible vision-loss among the elderly in industrial countries. Neovascular AMD (nAMD), which refers to late-stage AMD, is characterized by severe vision-threatening choroidal neovascularization (CNV). Herein, we constructed a global metabolic network of nAMD, based on untargeted metabolomic and lipidomic analysis of plasma samples collected from sixty subjects (30 nAMD patients and 30 age-matched controls). Among the nAMD and control groups, 62 and 44 significantly different metabolites were detected in the positive and negative ion modes, respectively. Grouping analysis further showed that lipid and lipid-like molecule-based superclasses contained the highest number of significantly different metabolites. Lipidomic analysis revealed that 53 lipids among the nAMD and control groups differed significantly; these belonged to four major lipid categories (glycerophospholipids, sphingolipids, glycerolipids, and fatty acids). A discriminative biomarker panel comprising 16 metabolites and lipids, which was constructed using multivariate statistical machine learning methods, could effectively identify nAMD cases. Among these 16 compounds, eight were lipids that belonged to three lipid categories (glycerophospholipids, sphingolipids, and prenol lipids). The top three biomarkers with the highest importance scores were all lipids (a glycerophospholipid and two sphingolipids), highlighting the crucial role played by glycerophospholipid and sphingolipid pathways in nAMD. These differences between the metabolic and lipid profiles of nAMD patients and elderly individuals without AMD provide a readout of the overall metabolic status of nAMD. Further insights into the identified discriminative biomarkers may pave the way for future diagnostic and therapeutic interventions for nAMD.

Proliferative diabetic retinopathy (PDR) is an advanced stage of diabetic retinopathy (DR), characterized by retinal neovascularization. It is a progressive fundus disease and a severe complication of diabetes that causes vision impairment. Hyperglycemia-induced persistent low-grade inflammation is a crucial factor underlying the pathogenesis of DR-associated damage and contributing to the progression of PDR. Highly enriched polyunsaturated fatty acids (PUFAs) in the retina are precursors to oxidized metabolites, namely, oxylipins, which exert pro-inflammatory or anti-inflammatory (resolving) effects under different pathological conditions and have been implicated in diabetes. To evaluate differences in oxylipin levels in the vitreous obtained from PDR and non-diabetic subjects, we performed a targeted assessment of oxylipins. A total of 41 patients with PDR and 22 non-diabetic control subjects were enrolled in this study. Vitreous humor obtained during routinely scheduled vitrectomy underwent a targeted but unbiased screening for oxylipins using mass spectrometry-based lipidomics. We found 21 oxylipins showing statistically significant differences in their levels between PDR and non-diabetic subjects (p < 0.05). Lipoxygenase (LOX)- and cytochrome P450 (CYP)- derived oxylipins were the most affected, while cyclooxygenase (COX) oxylipins were affected to a lesser extent. When categorized by their precursor PUFAs, ±19,20-EpDPE, a CYP product of docosahexaenoic acid (DHA) and 12S-HETE, a LOX product of arachidonic acid (ARA), were increased by the largest magnitude. Moreover, of these 21 oxylipins, 7 were considered as potential biomarkers for discriminating PDR patients from the non-diabetic controls. Our results indicate that altered oxylipin levels in the vitreous implicate an underlying imbalanced inflammation-resolution homeostasis in PDR.

Iron is an essential component in many biological processes in the human body. It is critical for the visual phototransduction cascade in the retina. However, excess iron can be toxic. Iron accumulation and reduced efficiency of intracellular antioxidative defense systems predispose the aging retina to oxidative stress-induced cell death. Age-related macular degeneration (AMD) is characterized by retinal iron accumulation and lipid peroxidation. The mechanisms underlying AMD include oxidative stress-mediated death of retinal pigment epithelium (RPE) cells and subsequent death of retinal photoreceptors. Understanding the mechanism of the disruption of iron and redox homeostasis in the aging retina and AMD is crucial to decipher these mechanisms of cell death and AMD pathogenesis. The mechanisms of retinal cell death in AMD are an area of active investigation; previous studies have proposed several types of cell death as major mechanisms. Ferroptosis, a newly discovered programmed cell death pathway, has been associated with the pathogenesis of several neurodegenerative diseases. Ferroptosis is initiated by lipid peroxidation and is characterized by iron-dependent accumulation. In this review, we provide an overview of the mechanisms of iron accumulation and lipid peroxidation in the aging retina and AMD, with an emphasis on ferroptosis.

Dear Editor,I am Dr.Fang Fang, from the Department of Ophthalmologyof the Second Xiangya Hospital of Central South University in Changsha, Hunan Province, China. I write to present a case report of retinal detachment with Gaucher disease（GD）.GD is a chronic, progressive, autosomal recessive lipidstorage disease caused by mutations in the lysosomal enzyme β-glucosidase（glucocerebrosidase）, normally present in

Li, Huiling MD, PhD; Guo, Xiaojian MD, PhD; Tang, Luosheng MD, PhDEditor(s): Toth, Cynthia A.; Schneider, Eric W.; Folgar, Francisco A. Author Information

Purpose Transdifferentiation of human Tenon fibroblasts to myofibroblasts and subsequent deposition of extracellular matrix is a key step in the scarring after glaucoma filtration surgery. The p38 signaling pathway plays an important role in cell proliferation and differentiation, and its upstream regulators and downstream molecules are widely distributed in the eye. We aimed to investigate the role of p38 in the activation of Tenon fibroblasts and that of the anti-fibrotic mechanism of rosiglitazone in the modulation of the p38 signaling pathway. Methods Cultured Tenon fibroblasts were stimulated with transforming growth factor (TGF)-β1. Activation of p38 was examined by western blot analysis. Rosiglitazone and blocking of the p38 signaling pathway by SB203580 were used to antagonize stimulation by TGF-β1. Fibroblast motility was examined by wound closure assay; alpha-smooth muscle actin, connective tissue growth factor, and collagen type I were determined by qPCR and western blot. Expression and localization of alpha-smooth muscle actin were determined by immunofluorescence staining. Results Phosphorylated p38 was upregulated in fibroblasts stimulated with TGF-β1, and this effect was substantially inhibited by rosiglitazone. Proliferation and migration of fibroblasts were suppressed by rosiglitazone and SB203580. Expression of alpha-smooth muscle actin, connective tissue growth factor, and collagen type I were decreased at the mRNA and protein levels by rosiglitazone and SB203580. However, the inhibitory effect of SB203580 on transcription and protein expression was weaker than that of rosiglitazone. Similar phenomena were found on immunofluorescence microscopy of alpha-smooth muscle actin. Conclusions The p38 signaling pathway mediates the TGF-β1-induced transdifferentiation of human Tenon fibroblasts to myofibroblasts. Rosiglitazone can exert anti-fibrotic activity by interfering with the TGF-β/p38 signaling pathway and might be useful for modulating scar formation after glaucoma filtration surgery.

AIM:To observe the optical coherence tomography ( OCT ) images of idiopathic macular hole ( IMH ) on patients before and after vitrectomy and internal limiting membrane peeling ( ILMP) surgery, and to analyze the relationship between the macular hole configuration and the postoperative best corrected visual acuity so as to offer a potential index to effectively predict visual outcome in eyes with idiopathic macular holes. METHODS:A total of 32 consecutive patients of IMH (7 males, 25 females) receiving the operation of PPV and ILMP were performed with routine ophthalmologic and OCT examination before and after the operation.The best-corrected visual acuity ( BCVA ) in the follow-up period was recorded.The minimum diameter, the base diameter, the hole height before the operation, and the macular retinal thickness before and after the operation were measured respectively by the analytical model of OCT.The correlation between macular hole index ( MHI) and BCVA post operation was analyzed using SPSS 13.0. RESULTS: The negative correlation was observed between the post operative BCVA and the minimum diameter and the base diameter before the operation ( r=-0.524, -0.610, P<0.01 ); There were no significant correlation between the post operative BCVA and the hole height and the macular retinal thickness (r=-0.064, 0.003, P>0.05).The positive correlation was observed between the postoperative BCVA and the MHI before operation (r=0.457, P<0.01); The cut-off value of MHI was defined as 0.5 by clinical observation.Postoperative BCVA in the MHI≥0.5 group was much better than that in the MHI<0.5 group (Mann-Whitney Test, U=30.0, W=135, P<0.01).The postoperative BCVA of patients with IMH was much better than that before the operation. CONCLUSION:The smaller the minimum diameter and the base diameter is, the better the post operative BCVA. The MHI is easy to calculate, and patients of MHI ≥0.5 have a better postoperative BCVA, MHI can be used as clinical evaluation-index for operation selection. The PPV combined with IMLP can effectively treat the IMH based on the OCT result.

Acute retinal necrosis syndrome is a serious syndrome caused by virus infection (mainly are varicella zoster virus and Herpes simplex virus, few are Epstein-Barr virus and cytomegalovirus), characterized by severe panuveitis accompanied with retinal arteritis, much exudation in peripheral retina, necrotizing retinitis, highly vitreous opacity, post-retinal detachment, which damage the visual function badly. In spite of the low incidence, the disease is difficult to be diagnosed correctly and it develops very quickly. If the patients would not be cured timely, it is likely leading to blindness. So early correct diagnosis and treatment is of great significance, and this article reviews the treatment of ARNS.

With the development of vitreous surgery technology, patient's expectation of postoperative visual function has been raised. Therefore, the accurate measurement of intraocular lens degree in silicone oil-filled eyes has become an increasingly important factor influencing the prognosis of patients. This article offers a review of the present situation and prospect in this study field.

Objective To investigate the VEGF-C expression and lymph vessel counts in retinoblastoma(RB) and normal retina tissue,to study their interrelationship and clinicopathological significance.Method Envision immunohistochemistry stainings of VEGF-C and D2-40 were performed in 30 retinoblastoma and 15 normal retina tissues,which was routinely paraffin imbedded.Results The positive rate of VEGF-C expression and lymph vessel counts were higher in RB tissue than normal control(P<0.01);Samples from the clinical stage Ⅰ,differentiated type,uninvolved optic nerve and life span ≥2 year cases had higher expression of VEGF-C and higher lymph vessel counts than those from clinical stage Ⅲ,undifferentiated type,involved optic nerve and life span <2 year cases(P<0.05 or P<0.01).Lymph vessel counts in VEGF-C positive samples were much higher than negative ones.Conclusion VEGF-C expression and lymph vessel counts maybe useful markers of RB progression,biological behavior and prognosis;VEGF-C might have promotive effect on lymphangiogenesis in RB tissue.

AIM: To evaluate anatomical and visual outcomes of episcleral macular buckling (EMB) for posterior retinal detachment in silicone oil filled eyes associated with myopic macular hole.METHODS: Five cases of EMB for initial failure of retinal reattachment after internal limiting membrane (ILM) peeling and silicone oil tamponade caused by myopic macular hole were retrospectively reviewed. A silicone sponge sutured directly across the macular region was performed on the silicone oil filled eyes. Silicone oil was removed no sooner than 1 month post-EMB. The duration of follow -up time after removal of silicone oil was more than 3 months.RESULTS: Retinas of five eyes were all reattached at the last follow up. The postoperative vision ranged from counting fingers to 0.08.CONCLUSION: Anatomical results improved after EBM for posterior retinal detachment in silicone oil filled eyes associated with myopic macular hole, which was not evident for visual outcome.

AIM: To compare the efficacy of prophylactic vitrectomy for acute retinal necrosis syndrome(ARN) with routine treatment in Chinese patients, thereby investigate the necessity of prophylactic vitrectomy for ARN.METHODS: Thirty patients (37 eyes) were retrospectively included in this study. The eyes were divided into 2 groups by treatment, including routine treatment, which consisted of antiviral medication and vitrectomy after retinal detachment (RD) (n=21), and prophylactic vitrectomy, which consisted of antiviral medication and vitrectomy for the prevention of RD performed during the active inflammatory phase (n=16). The extent of necrosis was determined by fundus photographs at the time of presentation (for eyes with mild vitreous opacity) or the drawings in the operation records. Necrosis of the 37 eyes was divided into 3 grades, including peripheral, middle-peripheral and extensive. The follow-up period ranged from 8 to 57 months. Differences in visual acuity and necrosis between groups were identified using independent samples t-test.RESULTS: Necrosis was more extensive in the routine treatment group than in the prophylactic vitrectomy group (P<0.05). In the routine treatment group, conservative treatment improved necrosis and prevented RD in 6 eyes (29%). Seven eyes (33%) obtained anatomical success, but retinal redetachment occurred in 8 eyes (57%). There were also 5 eyes (24%) developed ocular hypotony or atrophy. Ten eyes (48%) achieved equal or increased visual acuity. In the prophylactic vitrectomy group, RD occurred in 2 eyes (13%). Twelve eyes (75%) were completely anatomically successful, and 10 eyes underwent silicone oil removal. Only one eye (6%) became ocular hypotony. Fourteen eyes (88%) achieved equal or increased visual acuity. The prophylactic vitrectomy group achieved better vision trends than the routine treatment group (P<0.05). Eyes with peripheral necrosis had better visual outcomes than those with mid-peripheral (P<0.05) or extensive (P<0.05) necrosis. However, there was no significant difference between eyes with mid-peripheral and extensive necrosis (P=0.3008)CONCLUSION: Prophylactic vitrectomy can prevent RD and improve the prognosis of ARN, making it an option for cases with rapidly progressing necrosis despite antiviral treatment and cases with moderate to extensive necrosis and severe vitreous opacity.

AIM:To evaluate the repeatability of central corneal thickness (CCT) measurement by entacam, and agreement of CCT measured by Pentacam and ultrasound pachymetry (USP) in Chinese myopia. Thereby investigate the possibility of Pentacam as a substitute for USP in CCT measurement before refractive surgery. The effects of corneal curvature measured by Pentacam on CCT were also evaluated. METHODS:One hundred and forty-eight right eyes of 148 individual with myopia were included in this study. Three successive Pentacam CCT measurements followed by 10 successive ultrasound pachymetry were carried out in the 148 eyes. Mean of CCT taken by each device was calculated for comparison. According to the CCT measured by USP, all the 148 eyes were divided into 3 groups: <520µm, 520-560µm, >560µm. For all eyes and each group the CCT obtained by Pentacam and USP were compared. Anterior corneal curvature of the 148 eyes was also adopted for correlation analysis with CCT obtained by ultrasound pachymetry. In addition, CCT measurement using 60 random selected Scheimpflug images was performed by 3 skilled investigators at different time, and this was repeated for 3 times by a forth investigator to assess repeatability of Pentacam CCT measurement using Scheimpflug images. RESULTS:Intraclass correlation coefficient (ICC) analysis revealed high intraobserver repeatability (ICC=0.994, F=158.60, P<0.001) for CCT measurement by Pentacam. The interobserver (ICC=0.998, F=494.73, P<0.001) and intraobserver (ICC=0.997, F=383.98, P<0.001) repeatability for Pentacam CCT measurements using Scheimpflug images were also excellent. There was high positive correlation between the CCT values measured by Pentacam and ultrasound pachymetry (r=0.963, P<0.001). Bland-altman plots showed that the Pentacam underestimate the CCT by 8.02µm compared with ultrasouond pachymetry. The differences between Pentacam and USP increased as the CCT readings by USP increased (Pentacam vs USP: slope=-0.04, P<0.05). The 95% upper and lower limits of agreement between CCT values obtained from the two devices were +9.33µm and -25.37µm. No significant association could be found between CCT and anterior corneal curvature. CONCLUSION:Inter- and intraobserver variability for CCT measurements by Pentacam was considerably below clinically significant levels. CCT of myopia obtained by Scheimpflug camera, Pentacam, were highly correlated to that by ultrasound pachymetry. However, the values obtained are not directly interchangeable between Pentacam and ultrasound pachymetry as the 95% limits of agreement are relatively wide. Pentacam can be a useful instrument for measuring CCT in candidates to refractive surgery in clinic.

AIM: To investigate the effect of Bak Foong Pills (BFP) on the expression of beta -amyloid (A beta) in rats retina with optic nerve transaction, and its roles and possible mechanisms in protecting optic nerve damage.METHODS: Seventy-two healthy, Sprague-Dawley, adult rats were randomly assigned to three groups: negative control group (control group), optic nerve transection group (model group) and BFP treatment group (BFP group, 100 mu g/mL) followed by establishing optic nerve transection model. The expression of A beta was measured at 48 hours by Western-blotting. Moreover, the expressions of Bcl-2, Bax and Caspase-3 mRNA were evaluated at 48 hours by reverse transcriptase polymerase chain reaction (RT-PCR).RESULTS: There were significant differences among the control, model and BFP groups in the expression of A beta (all P <0.01). A beta expression was significantly higher in the model and BFP groups than that in the control group (P< 0.01), with a more significant reduction in the BFP group than that in the model group (P <0.01). Moreover, there were also significant differences among the three groups in the expressions of Bcl-2/Bax (Bcl-2: anti-apoptotic; Bax: proapoptotic) and Caspase-3 mRNA (proapoptotic) (all P< 0.01). Bcl-2/Bax ratio was significantly lower and Caspase-3 mRNA expression was significantly higher in the model and BFP groups than those in the control group (P<0.01), with a significant growing of Bcl-2/Bax and reduction of Caspase-3 in the BFP group than those in the model group (P<0.01).CONCLUSION: BFP can down-regulate A beta expression in retina and may inhibit apoptosis and protect optic nerve by enhancing Bcl-2/Bax ratio and inhibiting Caspase-3 pathway.

Objective To explore the clinical effect of transpupillary thermotherapy(TTT)for the treatment of chronic central serous chorioretinopathy(CSC).Methods Twenty-four eyes of twenty-two patients with long-standing CSC who opted for TTT and observation were enrolled in this study,TTT was performed using 810nm infrared diode laser. The primary average visual acuity is 0.4±0.25,all patients underwent international standard vision acuity measurement,fundus fundus examination,fundus fluorescein angiography(FFA) and optical coherence tomography(OCT).Follow-up was scheduled at 1,2 and 6 months. Success was defined as resolution of neurosensory on OCT and disappearance of leakage on FFA at 3 months,and failure as persistence of the same.Results Following treatment of TTT,complete resolution of neurosensory detachment on OCT and disappearance of leakage on FFA was seen in seventeen eyes(70.83%)at month 1,twenty-one eyes (87.50%) at month 2 and twenty-three eyes(95.83%)at month 6,one eye had persistent subretinal fluid at month 6.Fourteen eyes(58.33%)had≥3 lines of improvement at final following visit.Conclusion Transpupillary thermotherapy could be a safely therapeutic option in patients with chronic CSC and subfoveal leaks,and it may affect the vision prognosis by shortening the persistent serous elevation of macula.