Current Eye Research最新文献

Purpose: Specific genetic factors might serve as markers for risk stratification of AMD progression, but their association with key features of AMD has not been fully elucidated. Thus, we investigated the association between overall and pathway-specific genetic risk scores (GRS) and lead loci (ARMS2, CFH) with AMD stages and features of high-risk nonlate AMD, including reticular pseudodrusen (RPD) and large drusen area (LDA).

Methods: We performed a cross-sectional analysis of data from the Rhineland Study, a population-based study in Bonn, Germany. We included 4016 individuals aged 50 years and older of European descent. GRS and pathway-specific subscores were constructed based on a large genome-wide association study of AMD. Subscores were generated based on gene-pathways associations (complement, extracellular matrix remodeling (ECM) and lipid metabolism). Associations were assessed using logistic and multinomial regression.

Results: The mean age of participants was 63.36 years and 1813 (45.1%) were men. The GRS was positive in 48.1% of individuals and increased, but did not fully overlap, across AMD stages. Pathway-specific subscores increased across AMD stages except for the ECM subscore, which only showed a trend for increasing in late AMD. Increasing overall GRS was associated with RPD and LDA (OR [95%CI] for RPD: 1.70 [1.33-2.15], for LDA: 1.64 [1.29-2.07]) among individuals with AMD. Similarly, higher complement and ECM subscores was associated with RPD, while for LDA, only an association with complement subscore was observed.

Conclusions: In a population-based setting, we confirmed higher genetic risk to be associated with more severe AMD and identified associations with high-risk features of intermediate AMD. Conjoint analyses suggested that high-risk features and late AMD might be differentially associated with genetic architecture in AMD, such as ECM remodeling. Incorporation of genetic information such as GRSs might improve AMD risk prediction strategies.

Purpose: The purpose of this study was to assess in-vitro efficacy of a suffusion of autologous serum withcyclosporine 0.05% (CsA) and sodium hyaluronate 0.1% (SH).

Methods: The expression of proinflammatory markers interleukin 6 (IL-6) and TNF-Alpha (TNF-α) in limbal epithelial cells was evaluated. Also, assessment of the stability of epithelial growth factor and transforming growth factor-beta (EGF, TGF-β) in the 50% combinations with autologous serum (AS) was done. The characteristics (pH, density, osmolality) of the two combinations were also evaluated. Additionally, cytotoxicity effect of given test compounds was evaluated on human limbal epithelial cells (LEpiC).

Results: The percentage of cells expressing IL-6 subjected to AS + SH and AS + CsA were 6.23% and 5.69% respectively. There was no significant difference in percentage of cells expressing TNF-α between the formulations (5.87%, 5.83% respectively). The growth factors; EGF and TGF-β remained stable forone month duration (on 2 and 4 weeks) at 4 °C without significant difference between the time intervals tested. The results of MTT assay suggested that limbal epithelial cells treated with AS + CsA and AS + SH combinations showed minimal toxicity however it was not significant statistically (p ≤ 0.05).

Conclusion: Two test combinations (AS + CsA, AS + SH) showed stable growth factors (EGF, TGF-β) and good anti-inflammatory property against pro-inflammatory markers. Also, the 2 combinations were found safe on cultured limbal epithelial cells. The novel combination of autologous serum in CsA may provide added benefit in dry eye disease (DED) through their combined anti-inflammatory and epitheliotropic effects.

Purpose: To comparatively evaluate the influence of different riboflavin formulations and soaking durations on the anterior segment optical coherence tomography (AS-OCT) findings following accelerated corneal crosslinking (ACXL) at 9 mW/cm² for in progressive keratoconus.

Methods: In this prospective study, consecutive patients with progressive keratoconus were randomized into 4 groups. Group 1: hydroxypropyl methylcellulose (HPMC)-based riboflavin for 10 min; Group 2: HPMC-based riboflavin for 20 min; Group 3: dextran-based riboflavin (0.1%) for 30 min. Riboflavin soaking was followed by ultraviolet-A irradiation at 9 mW/cm² for 10 min in all three groups. Group 4 underwent conventional CXL (CCXL) using Dresden protocol. The AS-OCT features of the crosslinked cornea were evaluated at postoperative month 1 and correlated to the clinical outcomes at postoperative month 12.

Results: The study enrolled 26 eyes of 26 patients in each group. In groups 1 and 2, the AS-OCT findings were similar (p > .05) and the demarcation lines depth (DLD) were deep as obtained following CCXL. The DLD was significantly shallower in group 3 compared to the other groups (p < .01). There were no between-group differences in regards to the visual, refractive, keratometric, and tomographic outcomes at postoperative month 12. No significant endothelial cell loss or any other clinically significant adverse event was encountered in any patient's eye at 12 months follow-up.

Conclusion: Although structural variations were noted in the crosslinked cornea, DLDs observed following ACXL (9 mW/cm²) using HPMC-based solution for 10 or 20 min were similar to those observed following CCXL. Whereas, ACXL (9 mW/cm²) using dextran-based solution for 30 min resulted in the shallowest DLD. Despite these remodeling differences, the visual, refractive and tomographic outcomes of all groups were comparable at postoperative 1-year follow-up. Studies with a greater number of patients and longer follow-ups are required to establish any relation between AS-OCT characteristics of crosslinked cornea and ACXL efficacy.

Purpose: To analyze the role of Slit2 in lens epithelial cell oxidative damage and its underlying mechanism.

Methods: Human lens epithelial cells (SRA01/04 cells) and rat transparent lens were cultured with H₂O₂ to establish cell oxidative stress models and rat cataract models. Immunohistochemistry, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blot assays were employed to detect Slit2 levels within age-related cataracts(ARC) lens anterior capsule samples, rat cataract models, and cell oxidative stress models. In this study, qRT-PCR and Western blot assays were performed to derermine E-cadherin, N-cadherin, occludens1(ZO-1), α-SMA(α‑smooth muscle actin), Bcl-2, Bax, p-AKT, and AKT levels. In addition, Flow cytometry were performed to examine reactive oxygen species (ROS) and cell apoptosis. Cell viability, invasion, and migration were detected by CCK8, Transwell, and Wound healing.

Results: Increased expression of Slit2 was found in ARC lens anterior capsule samples, H₂O₂-induced rat cataract models, and Human lens epithelial cells (HLECs) oxidative stress models. H₂O₂ significantly increased cell apoptosis and ROS generation, also accelerating cell migration, invasion, and epithelial-mesenchymal transition (EMT). In addition, H₂O₂ treatment repressed AKT phosphorylation and cell viability. Knock-down of Slit2 promoted cell viability and AKT phosphorylation levels, as well as repressed cell invasion, migration, apoptosis, ROS production and EMT.

Conclusion: Slit2 promoted lens epithelial cells oxidative stress damage via the AKT signalling pathways, providing a novel insight in ARC treatment.

Purpose: Autophagy dysregulation triggers extracellular matrix remodeling via changes in cellular collagen levels and protease secretion. However, the effect of autophagy on scleral extracellular matrix remodeling in the context of myopia is not fully understood. In this study, we measured the level of autophagy in sclera of form deprivation myopic guinea pigs; we also sought a correlation between the level of autophagy in human scleral fibroblasts and the extent of COL1A1 synthesis.

Methods: We measured the level of COL1A1 expression and the levels of autophagic protein markers in scleral tissues in vivo using a form deprivation myopic guinea pig model. Rapamycin and chloroquine were respectively used to activate and inhibit autophagy in cultured human scleral fibroblasts. COL1A1 gene and protein expression levels were analyzed via quantitative real-time polymerase chain reaction, Western blotting, and immunofluorescence. Levels of autophagy-related proteins were assessed via Western blotting.

Results: The sclera of form deprivation myopic guinea pig eyes exhibited decreased expression of COL1A1 and increased expression level of autophagy. After chloroquine exposure, human scleral fibroblasts exhibited decreased autophagy and increased COL1A1 expression.

Conclusion: Inhibition of scleral fibroblast autophagy increased COL1A1 expression at the gene and protein levels, thus explaining the effect of autophagy on collagen synthesis by scleral fibroblasts.

Purpose: Neodymium yttrium aluminum garnet (Nd:YAG) laser capsulotomy is considered gold standard in the treatment of posterior capsule opacification (PCO). In this laboratory study, we measured spectral transmission to evaluate the image contrast and analyze the impact of Nd:YAG associated defects in presbyopia-correcting intraocular lenses (IOLs).

Methods: Two hydrophobic, acrylic IOLs as classic multifocal lenses with diffractive ring segments and different amount of near addition (A, B), one hydrophilic, trifocal IOL (C), one sector-shaped, plate haptic IOL (D) and one hydrophobic, enhanced depth of focus (EDOF) IOL (E) were studied. Measurements included surface topography characterization, United States Air Force resolution test chart (USAF) analysis, spectral transmittance measurements and through focus contrast measurement. Measurements were done with unaltered samples, damages (n = 7) were intentionally created in the central 3.5 mm zone using a photodisruption laser (2.0 mJ) and measurements were repeated.

Results: Significant differences were shown between unmodified samples and samples with YAG pits. The YAG-pits decreased the image contrast and spectral transmission and changed results of USAF test images. The imaging contrast decreased to 66%, 64%, 60%, 52% and 59% with the YAG shots in samples (A-E). The light transmission decreased to 88%, 87%, 92%, 79% and 91% (A-E) on average between 400 nm to 800 nm. In all IOLs a reduction of the relative intensity of transmitted light was observed.

Conclusion: The image performance of all tested presbyopia-correcting IOLs is significantly influenced and disturbed by YAG-pits. The intensity of transmitted light is reduced in the wavelength between 450-800 nm. USAF test targets show worse results compared to unmodified samples and contrast is significantly deteriorated. No ranking/rating among tested IOLs should be made as many other factors play a role in real world scenario. High care should be taken when performing Nd:YAG capsulotomy on premium IOLs to avoid any damages.

Purpose: Affecting one-third of the population worldwide and increasing, the sight-threatening condition myopia is causing a significant socio-economic burden. To better understand its etiology, recent studies investigated the role of ocular and systemic rhythms, yet results are conflicting. Here we profiled 24-h variations of axial length of the eye and salivary melatonin concentration in young adults with and without myopia and explored the potential impacts of bedtime on these rhythms.

Methods: A total of 25 healthy young adults (age 25.0 ± 4.8 years, 13 females) completed this study, including 13 myopes (mean spherical equivalent refractive error -2.93 ± 1.46 diopters) and 12 non-myopes (0.14 ± 0.42 diopters). Saliva sample collection and axial length measurements were repeated for seven times over 24 h starting from 8 am. Information on sleep and chronotype was collected at first visit with the Pittsburgh Sleep Quality Index and the Morningness-Eveningness Questionnaire.

Results: Significant diurnal rhythms of axial length and salivary melatonin concentration were identified in both refractive groups (both p < 0.001), with no myopia-related rhythm difference (interaction of measurement time-point × myopia, p = 0.9). Late bedtime was associated with altered rhythms (p = 0.009) and smaller diurnal change (p = 0.01) in axial length. Elevated melatonin levels were observed in myopes (p = 0.006) and in late sleepers (p = 0.017).

Conclusions: These findings suggest that sleep/wake cycles may be involved in the regulation of axial length rhythms. Further research is needed to determine if there exists a causal relationship between the two.

Purpose: To explore the contribution and impact of fibrous scleral remodeling in the early recovery from lens induced myopia of chicks.

Method: Refractive error, axial length and histopathological studies were performed on chicks subject to myopic influence with -10 D goggles unilaterally on the day of hatching for a period of 14 days, after which the eyes were enucleated and immediately fixed for histopathological assessment. Three groups, myopia (measurements taken directly after 14 days), early recovery from induced myopia (chicks allowed a three-hour recovery period by removing goggles before analysis) and control (no goggles) were evaluated. The histological slides were assessed with bright field microscopy using Leica image analysis software.

Results: Early recovery from induced myopia resulted in a significant increase in the thickness of fibrous sclera to levels twice as high as the ones observed in the control or myopia groups. Histochemical staining revealed three times increase in fibroblast cell count of the early recovery from induced myopia group along with a statistically significant increase in levels of elastin contents relative to the control. However, fibroblast morphometry revealed no difference in maximum cell diameter, perimeter, and area between all experimental groups.

Conclusion: Recovery from induced experimental myopia results in fibrous scleral remodeling. Significant increase in the scleral thickness is related to heightened cell proliferation and elastic fiber contents. These results indicate that the fibrous sclera is not a passive component in the emmetropization process, but rather plays a significant and active role in the adaptation changes of the eye during early recovery from induced myopia.

Purpose: Diabetic retinopathy (DR) is the most common complication of diabetes mellitus. Stimulator of interferon genes (STING) plays an important regulatory role in the transcription of several genes. This study aimed to mine and identify hub genes relevant to STING in DR.

Methods: The STING-related genes (STING-RGs) were extracted from MSigDB database. Differentially expressed STING-RGs (DE-STING-RGs) were filtered by overlapping differentially expressed genes (DEGs) between DR and NC specimens and STING-RGs. A PPI network was established to mine hub genes. The ability of the hub genes to differentiate between DR and NC specimens was evaluated. Additionally, a ceRNA network was established to investigate the regulatory mechanisms of hub genes. Subsequently, the discrepancies in immune infiltration between DR and NC specimens were further explored. Additionally, we performed drug predictions. Finally, RT-qPCR of peripheral blood samples was used to validate the bioinformatics results.

Results: A grand total of four genes (IKBKG, STAT6, NFKBIA, and FCGR2A) related to STING were identified for DR. The AUC values of all four hub genes were greater than 0.7, which indicated that the diagnostic value was acceptable. The ceRNA network contained four hub genes, 170 miRNAs, and 135 lncRNAs. In addition, immunoinfiltration analysis demonstrated that the abundance of activated B cells was notably different between the DR and NC specimens. Moreover, 32 drugs were included in the drug-gene network, with twelve drugs targeting STAT6, nine drugs targeting NFKBIA, four drugs targeted IKBKG, and seven drugs targeted FCGR2A. The expression of the four hub genes in blood samples determined by RT-qPCR was consistent with our analysis.

Conclusion: In conclusion, four hub genes (IKBKG, STAT6, NFKBIA, and FCGR2A) related to STING with a diagnostic value for DR were identified by bioinformatics analysis, which might provide new insights into the evaluation and treatment of DR.

Purpose: The potential risks and benefits of cataract surgery, in context of congenital aniridia (CA), are not widely understood, yet. Our purpose was to investigate the effect of lens properties on visual acuity (VA), aniridia-associated keratopathy (AAK) stage and presence of glaucoma at the Homburg Aniridia Center.

Methods: CA subjects, examined at the Department of Ophthalmology of Saarland University between June 2003 and January 2022, were included. VA, slit-lamp examination, AAK grade, and glaucoma evaluation data were extracted from the medical records, from the first visit to the center. Eyes were categorized as clear lens, cataract, pseudophakic, aphakic, or subluxated lens. Patients were grouped by age (0-10, 10-20, 20-40, 40+ years).

Results: In 553 eyes of 286 CA subjects (age 19.9 ± 19.9 (0-83) years, 46.1% males), analysis revealed significant differences in VA and mean IOP (ANOVA p < 0.0001; p = 0.001, respectively) with lens status. Lens status was strongly associated with AAK Grade and glaucoma presence (p < 0.0001 for both). In age subgroups, AAK Stage was strongly associated with lens status in the 0-10 years (p < 0.001), 10-20 years (p < 0.001), and 40+ years (p = 0.02) groups and lens status was strongly associated with glaucoma presence in the 0-10 years (p = 0.003) and 20-40 years (p = 0.002) groups. AAK Stage was the most advanced in pseudophakic and aphakic eyes and presence of glaucoma was more pronounced in pseudophakic, aphakic and subluxated lens eyes.

Conclusions: In a large population of CA, previous cataract surgery was associated with higher AAK Grade and presence of secondary glaucoma both in postoperatively pseudophakic and aphakic eyes. Our data indicate that caution is warranted with cataract surgery in congenital aniridia.