Current Eye Research最新文献

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.

Purpose: Oxidative stress, ultraviolet radiation, and calcium imbalance are key components in the onset and advancement of cataract, which continue to be the leading cause of blindness globally. An important newly discovered aging maker, Senescence marker protein 30 (SMP30) regulates calcium and participates in mitigating oxidative stress damage. Here, we examined the beneficial role of SMP30 in protecting against ultraviolet radiation type B (UVR-B)-induced cataract in rats.

Methods: Wistar rats (2 months) were arbitrarily assigned into 4 groups of 10 rats. These groups included the Control group, UVR-B group, adeno-associated virus 2 vectors negative control (AAV2-NC) group, and adeno-associated virus 2-mediated overexpression of SMP30 (AAV2-SMP30) group. The control group received Phosphate-buffered saline (PBS) via injection, while the AAV2-NC group and AAV-SMP30 group were separately injected with AAV2-NC and AAV2-SMP30 vectors. In addition to the control group, the remaining three experimental groups were subjected to ultraviolet light exposure 4 weeks post-injection. The lens opacity was examined by stereoscopic microscope, and the lenses were separated to measure oxidative damage parameters particularly superoxide dismutase (SOD), glutathione peroxidase (GPX), and Ca²⁺-ATPase activity. The localization and expression of SMP30 and Ca²⁺-ATPase in the lenses were determined using immunohistochemistry and RT-qPCR.

Results: After UVR-B irradiation, the AAV2-SMP30 group exhibited a substantial decrease in lens opacity compared to the UVR-B group. The results revealed a notable downregulation of SMP30 expression and the activities of SOD, GPX, and Ca²⁺-ATPase of rat lens following exposure to UVR-B radiation. However, SMP30 overexpression partially reversed these effects. In vivo experiments demonstrated SMP30 overexpression attenuated the UVR-B-induced decline in SOD, GPX, and Ca²⁺-ATPase activities.

Conclusion: This study demonstrates that SMP30 has the potential to reduce lens opacity caused by UVR-B by increasing antioxidant stress and regulating Ca²⁺-ATPase activity. SMP30 might be a cutting-edge target for the treatment of cataracts.

Purpose: Chronic inflammation plays an important role in the pathogenesis of choroidal neovascularization (CNV). This study aimed to investigate the effect of the CHF5074, a γ-secretase inhibitor, on angiogenesis in a laser-induced CNV model and elucidate its possible molecular mechanism.

Methods: Male C57/BL6J mice aged between 6 to 8 weeks were employed to set up a laser-induced model of CNV. Then, CHF5074 was injected intraperitoneally on the day after laser modeling, as well as on the second, third, and fourth days. Immunofluorescence staining was used to evaluate the retinal and choroidal complex. The markers used were CD31 for neovascularization and IBA1 for microglia staining in ocular tissue slices. Fundus fluorescein angiography on days 3d, 7d, and 14d analyzed neovascularization and leakage areas. Inflammatory indicators were examined by Western blot (WB) and enzyme-linked immunosorbent assay (ELISA). High-throughput whole-tissue sequencing of retinal choroids identified relevant cell pathways. Key regulatory factors modulated by CHF5074 were identified via WB. Co-culture of BV2 cells and human umbilical vein endothelial cells (HUVEC) were used to explore the function of CHF5074 on the inhibition of tube formation.

Results: CHF5074 significantly decreased CD31 expression in the choroid on 3d, 7d, and 14d post-laser modeling (p < 0.05) and decreased both neovascularization and leakage areas (p < 0.05). Additionally, CHF5074 significantly lowered TNF-α, IL-10, and IL-1β expression levels in the choroid (p < 0.05), as demonstrated by WB analysis and ELISA. High-throughput whole-tissue sequencing identified P38-MAPK, JNK, and Wnt signaling pathways associated with neovascularization. CHF5074 decreased P38 protein phosphorylation (p < 0.05) as confirmed by WB analysis. CHF5074 inhibited the tube formation of HUVECs co-cultured with LPS and ATP-treated BV2 cells.

Conclusion: CHF5074 significantly suppresses angiogenesis in laser-induced choroidal neovascularization models, suggesting its potential as a novel agent for preventing and treating CNV.

Purpose: Our aim was to examine the expression of PAX6 and keratocyte-specific markers in human limbal stromal cells (LSCs) in congenital aniridia (AN) and in healthy corneas, in vitro.

Methods: Primary human LSCs were extracted from individuals with aniridia (AN-LSCs) (n = 8) and from healthy corneas (LSCs) (n = 8). The cells were cultured in either normal-glucose serum-containing cell culture medium (NGSC-medium) or low-glucose serum-free cell culture medium (LGSF-medium). Analysis of PAX6 and keratocyte-specific markers was conducted using qPCR and Western blotting. The keratocyte-specific markers included Collagen I (COL1A1), Collagen III (COL3A1), Collagen V (COL5A1), α-smooth muscle actin (ACTA2), Aldehyde Dehydrogenase 3 Family, Member A1 (ALDH3A1), Keratocan (KER), Lumican (LUM), and CD34.

Results: PAX6 mRNA expression exhibited a significant decrease in AN-LSCs compared to LSCs in both NGSC- and LGSF-medium (p = 0.04; p = 0.014). There was a marked reduction in COL5A1 mRNA expression (p = 0.011), accompanied by notably higher ALDH3A1 and KER mRNA levels (p = 0.007; p = 0.013) in AN-LSCs compared to LSCs when using NGSC-medium. In LGSF-medium, AN-LSCs showed a significant increase in COL1A1 and COL5A1 mRNA expression compared to LSCs (p = 0.048; p = 0.002). Moreover, COL1A1 and α-SMA protein expression were significantly elevated in AN-LSCs compared to LSCs in LGSF-medium (p = 0.048, p = 0.008).

Conclusions: Our investigation affirms the altered expression of PAX6 and keratocyte-specific markers in AN-LSCs relative to healthy controls. Both NGSC- and LGSF-medium exerted distinct effects on both LSCs and AN-LSCs. The observed variations in PAX6 and keratocyte-specific marker expression in AN-LSCs may play a pivotal role in the development and progression of aniridia-associated keratopathy.

Purpose: Glaucoma filtration surgery (GFS) stands as a paramount clinical intervention for glaucoma. Nonetheless, the prevalent cause of GFS failure is filtration bleb scarring, and the role of inflammation and immune response in contributing to fibrosis remains elusive.

Methods: The study employed 30 female Sprague-Dawley rats (8 weeks old, 200-250 g) to assess the anti-scarring impact of the Chemokine (C-C motif) receptor 5 (CCR5)-Chemokine (C-C motif) ligand 5 (CCL5) antibody after GFS. Additionally, anti-fibrotic effects on HConFs were examined, creating an intra-operative inflammatory response using damaged-HConFs supernatant medium (DHSM). In vitro and in vivo validation aimed to elucidate the potential anti-fibrotic molecular mechanism of the CCR5-CCL5 antibody.

Results: The CCR5-CCL5 antibody effectively prolonged filtration bleb duration and enhanced the functionality of the filtered bleb. Improved postoperative intraocular pressure values (IOP) and morphological images were observed in the CCR5-CCL5 antibody-treated group. Histochemical staining and cellular experiments confirmed the antifibrotic function of the CCR5-CCL5 antibody. Notably, M2-type macrophage polarization was reduced in the CCR5-CCL5 antibody-treated model. CCL5-induced fibrosis in HConFs was mediated through the PI3K/Akt signaling pathway. Consistently, inhibition of PI3K/Akt significantly attenuated the profibrotic effects of CCR5-CCL5. Mechanistically, the CCL5 antibody exerts its antifibrotic effect by targeting CCR5 on HConFs, leading to the inhibition of the PI3K/Akt mechanism.

Conclusions: This study unveils that CCR5-CCL5 promotes fibrosis in GFS through inflammatory stimulation of HConFs and enhanced activation of the PI3K/Akt signaling pathway. The findings suggest that intraoperative CCR5-CCL5 antibody treatment could serve as a cost-effective therapeutic agent or a useful adjuvant in preventing ocular bleb scar formation.

Purpose: To evaluate the role of computed tomography-dacryocystography (CT-DCG) in the management of traumatic secondary acquired lacrimal duct obstruction (SALDO) and study its correlation with the intra-operative findings.

Methods: Retrospective interventional case series. Eighty-five lacrimal drainage systems (LDS) of 79 patients diagnosed with traumatic SALDO, who underwent pre-operative CT-DCG, between January 2019 and June 2023, were analyzed. The lacrimal intervention included endoscopic dacryocystorhinostomy (En-DCR), external DCR(Ex-DCR), or dacryocystectomy (DCT) based on the clinical presentation, CT-DCG findings, local and systemic factors. Anatomical and functional outcomes were assessed.

Results: Eighty-five LDS of 79 patients with a mean age of 32 years and male predominance (n = 70, 89%) were studied. The median time of trauma to clinical presentation was 12 months and the duration of epiphora was 8 months. Naso-orbito-ethmoid fractures were seen in 56 (66%) cases and cribriform plate fracture in 5 (6%) patients. CT-DCG revealed a dilated sac in 60 (71%) LDS, shrunken in 13 (15%), while the sac could not be visualized in 3 (4%) LDS. Relative lacrimal sac displacement was seen in 51 (64%) LDS of which 21 (41%) were displaced posteriorly, 18 (35%) superiorly, 5 (10%) inferiorly, and 8 (16%) into the anterior orbit. Sac - duct junction was the most common location of obstruction (n = 78, 92%). At a mean follow up period of 3.5 months, 62 of the 63 LDS surgeries performed (98%) demonstrated anatomical and functional success. Of the 63 operated LDS, CT-DCG findings corroborated with intra-operative findings in 60 (95%) LDS.

Conclusion: CT-DCG helps decide the surgical approach, possible complications, intra-operative course and hence has the potential to influence the outcomes. A thorough understanding of CT-DCG, therefore, should be a part of a Dacryologist's armamentarium for managing complex SALDO.

Purpose: To assess the retinal and choroidal microvascular changes in patients with benign essential blepharospasm (BEB) and to investigate the factors that may be effective on microvascularity.

Methods: This study included patients with BEB and healthy controls. All participants underwent a comprehensive examination followed by optical coherence tomography angiography (OCTA). Macular vascular perfusion density (VPD), foveal avascular zone (FAZ), and subfoveal choroidal thickness (CT) were measured. The clinical findings of the BEB group and the administration of botulinum toxin A (BTx-A) prior to OCTA imaging were recorded retrospectively from the medical records.

Results: A total of 16 patients with BEB and 20 healthy controls were included in this study. VPD values in all quadrants of the superficial and deep macular capillary plexus were significantly different in the BEB group compared to the control group (each p-value <0.05). In the choriocapillaris layer, VPD was significantly higher in the superior, nasal, and temporal quadrants compared to the control group (each p-value <0.05). The BEB group exhibited significantly smaller superficial and deep FAZ values compared to the control group, consistent with the observed increase in vascular density (each p-value <0.05). CT was thinner in the BEB group, although not statistically significant (p = 0.138). No correlation was found between the total dose of BTx-A administered to the BEB group and OCTA parameters (each p-value >0.05).

Conclusion: Benign essential blepharospasm may be associated with increased retinal vascular density in the superficial and deep capillary plexus and decreased FAZ area.

Purpose: to evaluate changes in retinal microvasculature and sensitivity (RS) preceding the appearance of diabetic retinopathy (DR) among patients with type 1 diabetes (T1D).

Methods: in this observational cross-sectional cohort study, vascular parameters measured by OCTA and RS evaluated by microperimetry were assessed in patients with T1D without DR (no-DR), T1D with mild DR (m-DR), and healthy controls.

Results: Sixty-two eyes of 31 patients with T1D and 40 eyes of 20 healthy patients were included. OCTA examinations did not yield any significant differences in terms of perfusion density (PD), vascular density (VD), foveal avascular zone (FAZ) area, FAZ perimeter or FAZ circularity between patients with diabetes (no-DR vs. m-DR). However, comparisons between healthy controls and patients with diabetes (both no-DR and m-DR groups) revealed statistically significant differences in PD, VD, and FAZ area. Similarly, no significant differences were observed between no-DR and m-DR groups regarding RS, gaze fixation stability (GFS), or macular integrity (MI). Nevertheless, mean RS and MI were significantly impaired in patients with T1D, both in no-DR and m-DR groups, compared to healthy controls. A statistically significant positive correlation was observed between RS and PD and between FAZ area and RS.

Conclusion: although no differences were found between patients with diabetes without DR and those with mild DR, these patients already demonstrated some degree of retinal impairment, both structural and functional, when compared to healthy controls. Our data support the hypothesis that neurodegeneration occurs together with microvascular damage at early stages of diabetes.

Purpose: Silicone oil (SO) has been used as a vitreous tamponade for decades. Surgical complications such as glaucoma, cataract, or emulsification are well known. Despite that, increasing case reports of unexplained visual loss after SO removal is concerning because there is no treatment available. This article describes practical complications related to SO use and advantages/disadvantages for consideration regarding the choice of a vitreous substitute in practice.

Methods: A literature review was conducted for publications related to silicone oil, heavy silicone oil, and vitreous substitutes.

Results: This article summarizes the SO chemical and physical properties including both SO and heavy SO and postoperative complications such as corneal decompensation, glaucoma, hypotony, cataract, optic neuropathy. Surgical complications such as over/underfilling, SO migration/emulsification, sticky SO and proliferative vitreoretinopathy (PVR) simulating epiretinal membranes formation, recurrent retinal detachments, SO unexplained visual loss, and permanent SO, are described. A brief overview on potential vitreous substitutes is presented.

Conclusion: The decision to use SO as vitreous substitute in daily practice is based on the severity of retinal diseases and surgeon experience. SO potential complications must not be underestimated. The pursuit of novel safer vitreous substitutes is imperative.