Corneal Neovascularization Research Articles

Measurement of Aqueous Humor Viscosity in an Experimental Rabbit Model With Corneal Neovascularization.

This study investigated the relationship between aqueous humor (AH) viscosity and vascular endothelial growth factor-A (VEGF-A) in a corneal neovascularization (CNV) model. Ten female New Zealand rabbits were divided into two groups (n = 5 each). CNV was induced by alkaline burns on the right corneas of group B, whereas group A underwent a sham procedure. After 14days, at least 150µL of AH was extracted from both eyes. VEGF-A concentration was measured using ELISA, and AH viscosity was determined using a viscometer. Correlations between VEGF-A concentration, total protein concentration, and AH viscosity were assessed. VEGF-A concentration was significantly elevated in CNV-induced eyes than in noninduced eyes (6029.06 ± 7116.50 pg/mL vs. 115.63 ± 33.19 pg/mL, P < 0.01). Total protein concentration was also elevated in CNV-induced eyes (11.66 ± 9.86mg/mL) than in noninduced eyes (0.69 ± 0.06mg/mL, P < 0.01), and correlated positively with VEGF-A (r = 0.84, P < 0.01). AH viscosity was significantly increased in CNV-induced eyes (1.82 ± 1.28 mPa-s) compared to noninduced eyes (1.05 ± 0.01 mPa-s, P < 0.01) and correlated strongly with VEGF-A concentration in CNV-induced eyes (r = 1.00, p = 0.02). AH viscosity positively correlated with VEGF-A concentration, particularly in CNV-induced eyes with elevated VEGF-A levels. The correlation between VEGF-A levels and AH viscosity in an experimental model of corneal neovascularization suggests that AH viscosity could serve as a biomarker for predicting IOP or surgical outcomes in conditions like neovascular glaucoma.

Corneal Neovascularisation and Anti-VEGF Therapy

Cornea vascularisation is a significant cause of ocular morbidity. Disease or injury often triggers the development of new blood vessels in the cornea, compromising its clarity and impairing vision. Common causes of corneal neovascularisation include infections, chemical burns, and local and systemic inflammatory disorders. Topical corticosteroid eye drops remain the standard therapy; however, extended use of corticosteroids has been known to cause side-effects including cataracts and raised intraocular pressure. As such, an alternative therapy has been actively sought. Vascular endothelial growth factor (VEGF) is a major angiogenic factor implicated in neovascularisation. The success of anti-VEGF agents in managing leaking blood vessels in neovascular age-related macular degeneration provides an opportunity to explore its use in the treatment of corneal neovascularisation. The therapeutic potential of anti-VEGF agents has been evaluated in experimental models of corneal neovascularisation and clinical trials with variable results. Here, we review the study results and discuss the development of new strategies that may improve treatment outcomes for corneal neovascularisation.

Safety and efficacy of frequency-doubled Nd-YAG laser photocoagulation of different types of corneal neovascularisation (NLPC): a prospective study

PurposeFrequency doubling of neodymium-doped yttrium aluminum garnet (Nd-YAG) laser results in emission of photocoagulating 532 nm light compared with photolytic 1064 nm emission. The ergonomic benefits of solid-state lasers led...

Preserved bevacizumab (Avastin®) eye drops for application in multidose containers – an in-vitro characterisation

PurposeMonoclonal antibodies have made an immense contribution to the treatment of various human diseases. We aimed at investigating an affordable treatment option for veterinary patients with corneal neovascularization by adding the preservative benzalkonium chloride (BAC) to bevacizumab (Avastin®) for usage in multidose containers. A comprehensive analytical similarity assessment of preserved and unpreserved bevacizumab after dilution and storage was carried out.MethodsDiluted and preserved bevacizumab was analysed at different time points for a 4-week period and compared with unpreserved bevacizumab at the same concentrations at each time point. Native-PAGE, immunoblotting and HP-SEC were used to observe aggregation and degradation. DLS provided information about particle size and dispersity. Bevacizumab quantified by ELISA was conducted to determine its biological activity. Dose response curves and cell migration assays were performed to detect possible toxic effects and determine biological activity and efficacy of the drug using HUVECs.ResultsNative-PAGE, immunoblotting and HP-SEC analysis did not show any changes or degradation products in the presence of BAC and after storage compared to unpreserved bevacizumab. The overlapping intensity-based particle size distribution obtained from DLS showed similarity in all tested groups and homogeneity was maintained. ELISA accurately detected bevacizumab at different concentrations. HUVECs incubated with preserved or unpreserved bevacizumab showed a comparable effect on cell migration. No decrease in cell viability was detected.ConclusionEquivalence tests demonstrated that bevacizumab is stable after dilution, storage and preservation with BAC. Our study shows that preserved bevacizumab applied in mutidose containers can be considered as a cost-effective alternative to the otherwise single-dose treatments.

Corneal endothelial neovascularization and glaucoma in X-linked Alport syndrome.

Variants in COL4A5 are responsible for X-linked Alport syndrome. It is characterized by kidney disease, sensorineural hearing loss and variable ocular abnormalities. In this case, a woman with corneal endothelial neovascularization, glaucoma, nuclear cataract, temporal retinal thinning, and renal defects was identified with a variant in COL4A5. We described a 64-year-old woman who was referred to our Eye Clinic due to a progressive decline in vision in both eyes over the course of two years. Corneal endothelial neovascularization, elevated intraocular pressure (31.2 mmHg and 27.8 mmHg in the right and left eyes, respectively), lens opacity, an increased cup-to-disc (C/D) ratio (0.8 in both eyes), and thinner retinal nerve fiber layer were detected upon examination. Concurrently, microscopic hematuria and proteinuria were observed. Following phacoemulsification and the administration of Latanoprost, intraocular pressure returned to within the normal range. Whole exome sequencing revealed a novel hemizygous missense pathogenic variant in COL4A5 (c.3980G > T (p.G1327V)). Importantly, this particular variant was not identified in the healthy daughter of the proband, underscoring its potential relevance to the observed clinical manifestations. Our study reports a novel phenotype observed in a 64-year-old woman, featuring corneal endothelial neovascularization and glaucoma, which has been linked to X-linked Alport syndrome caused by variants in COL4A5. This discovery contributes to the broadening of our understanding of the clinical heterogeneity associated with COL4A5 variants.

Navigating the path to corneal healing success and challenges: a comprehensive overview.

The cornea serves to protect the eye from external insults and refracts light to the retina. Maintaining ocular homeostasis requires constant epithelial renewal and an efficient healing process following injury. Corneal wound healing is a dynamic process involving several key cell populations and molecular pathways. Immediately after a large corneal epithelial injury involving limbal stem cells, conjunctival epithelial cells migrate toward the center of the wound guided by the newly formed electrical field (EF). Proliferation and transdifferentiation play a critical role in corneal epithelial regeneration. Corneal nerve endings migrate through the EF, connect with the migrating epithelial cells, and provide them with multiple growth factors. Finally, the migrated epithelial cells undergo differentiation, which is also regulated by corneal nerve endings. All these processes require energy and effective cellular cross-talk between different cell lines and extracellular matrix molecules. We provide an overview of the roles and interactions between corneal wound regeneration components that may help develop fascinating new targeted therapeutic strategies to enhance corneal wound healing with less injury-related corneal opacity and neovascularization.

Supercharged nanoadhesive through co-assembly of recombinant protein and tetrahedral DNA for corneal transplantation

Abstract Atraumatic tissue adhesive technology is highly desired for ophthalmic surgery, while numerous polymeric adhesives still face significant limitations in clinical ophthalmology, especially corneal transplantation. The biggest challenge is achieving rapid adhesion without creating polymer barrier or chemical toxicity from cross-linking. To develop a cornea-specific adhesive, we introduced a novel nanoadhesive constructed through protein-DNA co-assembly and applied it in corneal transplantation. Within this system, a rigid tetrahedral DNA framework was used to guide the spatial distribution of the polycationic recombinant proteins (K72) and act as the core of nanoadhesive for energy conversion during connecting tissues. The adhesive strength of this nanoadhesive achieved 2.3 kPa between corneal lenticules. After RGD peptide modification, this adhesive system significantly improved corneal epithelialization, reduced inflammation and neovascularization, and finally facilitated corneal repairing. This work is the first attempt of nanoadhesive in ophthalmic surgery, and provides a solution to develop novel ophthalmic-specific adhesives for clinical application.&amp;#xD;

A promising strategy for ocular noninvasive protein delivery: The case in treating corneal neovascularization.

A promising strategy for ocular noninvasive protein delivery: The case in treating corneal neovascularization.

AZD6738 Attenuates LPS-Induced Corneal Inflammation and Fibrosis by Modulating Macrophage Function and Polarization.

This study aimed to evaluate the therapeutic potential of AZD6738, an ATR inhibitor, in LPS-induced bacterial keratitis (BK) by targeting macrophage function and polarization. A murine model of LPS-induced BK was established, with AZD6738 (100µM) administered subconjunctivally and topically. Corneal opacity, edema, and inflammation were assessed using slit-lamp microscopy and histological analysis. Macrophage infiltration and fibrosis were evaluated via immunofluorescence, qPCR, and Western blotting. In vitro, RAW264.7 cells were treated with 2.5µM AZD6738 to examine its effects on cell viability, oxidative stress, and inflammation-related gene expression. AZD6738 significantly reduced corneal opacity, thickness, and neovascularization in LPS-treated mice. It suppressed macrophage infiltration, collagen deposition, and pro-inflammatory cytokine expression. In RAW264.7 cells, AZD6738 induced cell death, elevated ROS production, and downregulated inflammatory markers. ATR inhibition mitigated NF-κB activation and modulated macrophage polarization, attenuating M1 pro-inflammatory responses. AZD6738 effectively alleviates LPS-induced corneal inflammation and fibrosis by regulating macrophage function and polarization via the NF-κB signaling pathway. ATR inhibition represents a promising therapeutic strategy for the treatment of corneal inflammation.

Cyclopamine inhibits corneal neovascularization and fibrosis by alleviating inflammatory macrophage recruitment and endothelial cell activation.

Cyclopamine inhibits corneal neovascularization and fibrosis by alleviating inflammatory macrophage recruitment and endothelial cell activation.

A small-molecule enhancer of STAT1 affects herpes simplex keratitis prognosis by mediating plasmacytoid dendritic cells migration through CXCR3/CXCL10.

A small-molecule enhancer of STAT1 affects herpes simplex keratitis prognosis by mediating plasmacytoid dendritic cells migration through CXCR3/CXCL10.

3D printed biomimetic bilayer limbal implants for regeneration of the corneal structure in limbal stem cell deficiency.

3D printed biomimetic bilayer limbal implants for regeneration of the corneal structure in limbal stem cell deficiency.

Nano-alkaline ion-excited NETs ablative eye drops promote ocular surface recovery.

Nano-alkaline ion-excited NETs ablative eye drops promote ocular surface recovery.

PROTAC based targeted degradation of LRG1 for mitigating corneal neovascularization

PROTAC based targeted degradation of LRG1 for mitigating corneal neovascularization

Mitsugumin 53 Inhibits Angiogenesis Through Regulating Focal Adhesion Turnover and Tip Cell Formation.

Our previous studies have identified mitsugumin 53 (MG53) as a novel regulator for angiogenesis by directly entering endothelial cells and modulating focal adhesion kinase (FAK) activation, but little is known about how rhMG53 is taken up by cells and how rhMG53 mediates cell movement. In the present study, we demonstrated that the knockdown of caveolin-1 and the clathrin inhibitor, pitstop-2, both significantly reduced the entry of rhMG53 into endothelial cells, indicating caveolae-dependent and clathrin-dependent endocytosis during this process. The internalised rhMG53 remarkably inhibited the phosphorylation of FAK and the downstream signalling molecule paxillin, consequently resulting in a significant decrease in focal adhesion turnover during endothelial cell spreading and migration. Using a 3D collagen culture model, we further found that rhMG53 significantly inhibited tip cell formation and tubulogenesis. Furthermore, rhMG53 also remarkably prevented alkaline injury-induced corneal neovascularization invivo. Taken together, these results indicate that rhMG53 inhibits angiogenesis through regulating focal adhesion turnover and tip cell formation. This may elucidate novel molecular mechanisms involved in rhMG53 uptake and rhMG53-modulated endothelial cell function and provide evidence for the potential utility of rhMG53 in treating diseases with excessive angiogenesis.

Engineered Neutrophil Nanovesicles for Inhibiting Corneal Neovascularization by Synergistic Anti-Inflammatory, Anti-VEGF, and Chemoexcited Photodynamic Therapy.

Corneal neovascularization (CorNV) develops under various pathological conditions and is one of the main causes of blindness. Due to that CorNV progression involves multiple steps, anti-vascular endothelial growth factor (VEGF) drugs alone could not sufficiently suppress this process, highlighting an urgent need for an efficient delivery system for the multi-step management of CorNV. In this study, a neutrophil nanovesicle-based eye drop (NCCR) is developed for CorNV therapy that simultaneously inhibits angiogenesis and inflammation, while eliminating pathological cells through chemoexcited photodynamic therapy (PDT). NCCR targets inflammatory lesions by leveraging the expression of chemokine receptors from the source cells. Then, NCCR exerts inhibitory effects on the sequential steps of neovascularization. First, it acts as a decoy and exerts an anti-inflammatory effect by neutralizing cytokines via its receptors on the surface of nanovesicles. Second, thioketals bond-linked ranibizumab is released in the high reactive oxygen species microenvironment of CorNV sites to bind VEGF, inhibiting vascular endothelial cell activation and proliferation. Finally, chemoexcited PDT eliminates preformed corneal blood vessels, disrupting tube formation and pericyte recruitment. The synergistic effects of NCCR on angiogenesis and inflammation, combined with the induction of apoptosis in neovessels via chemoexcited PDT, offer a novel and efficient strategy for CorNV treatment.

Effects of Dexpanthenol on Corneal Neovascularization and Inflammation on Rat Model.

To evaluate the effect of subconjunctival injection of dexpanthenol on corneal neovascularization and inflammation in rats with induced chemical burns. This experimental study included 40 female albino Wistar rats. Chemical burns were induced in the right eye of all rats on the first day, and the left eye was used as a control. Rats were randomly divided into 5 groups. The no-treatment group (group 1) received no injections. Balanced salt solution injection in the sham group (group 2), dexpanthenol injection in the dexpanthenol group (group 3), bevacizumab injection in the bevacizumab group (group 4), and combined dexpanthenol and bevacizumab injection in the combined group (group 5) were administered subconjunctivally on day 7. The right corneas of all rats were photographed on days 7 and 14 to evaluate corneal neovascularization. The 2 corneal images were compared, and the differences were analyzed. All rats were euthanized, and the corneas were isolated. The levels of tumor necrosis factor-alpha (TNF-α), vascular endothelial growth factor-A, malondialdehyde (MDA), apoptosis, reduced glutathione (GSH), and total oxidant status were measured in rat corneas. Dexpanthenol reduced corneal neovascularization, and the difference was significant compared with the no-treatment and sham groups (P < 0.05). No significant difference in corneal neovascularization was observed between the dexpanthenol and bevacizumab groups. Dexpanthenol had a significant positive effect on vascular endothelial growth factor-A, TNF-α, total oxidant status, MDA, and GSH levels compared with the sham group (P < 0.05). Dexpanthenol may help control corneal neovascularization and inflammation after chemical burns.

Analysis of the relevant factors for corneal graft rejection in the southern Liaoning region from 2019 to 2023.

The study aimed to review the etiology of corneal blindness and investigate the relative risk of corneal graft rejection (CGR) in the southern Liaoning region. The clinical records of 359 patients (394 eyes) who underwent corneal transplantation at the Department of Keratoconus of the Third People's Hospital of Dalian from January 2019 to December 2023 were retrospectively analyzed. The data included patients' age, gender, occupation, diagnosis, surgical procedure, postoperative immune rejection, and neovascularization. The data were collected and descriptively analyzed to characterize the etiology of corneal blindness and to analyze the risk factors for postoperative immune rejection after corneal transplantation using logistic regression. The mean age of the patients who underwent corneal transplantation was 55.90 ± 0.80 years, and there were more male patients than female patients with corneal blindness. Infectious keratitis (41.1%) was reported as the leading cause of corneal blindness, and penetrating corneal transplantation was the main surgical procedure for the recovery of sight. Preoperative corneal vascularization and penetrating corneal graft rejection were identified as risk factors for immune rejection of corneal grafts. The preoperative corneal vascularization was performed (p = 0.044, OR = 2.607). Penetrating keratoplasty (PKP) was performed (p = 0.024, OR = 1.953), and deep anterior lamellar keratoplasty was also performed (p = 0.801, OR = 1.088). Viral infections (p < 0.001, OR = 16.871) were the major risk factor for preoperative corneal neovascularization (CNV) compared to other etiologies, such as fungal infections (p < 0.001, OR = 0.018), mechanical ocular trauma (p < 0.001, OR = 0.034), immune keratitis (p = 0.023, OR = 0.152), and endothelial dysfunction (p < 0.001, OR = 0.054). Infectious keratitis was identified as the major cause of corneal blindness in the southern Liaoning region over the past 5 years. Penetrating keratoplasty and preoperative corneal vascularization were the risk factors for corneal graft rejection. In addition, virus-derived keratitis was considered to be the main risk factor for corneal neovascularization, and deep anterior lamellar keratoplasty was not found to have an effect on corneal graft rejection in this study.

Corneal cross-linking.

Corneal cross-linking.

Cosmetic Therapeutic Keratopigmentation.

To analyze indications safety and potential complications of cosmetic therapeutic corneal keratopigmentation to treat disfiguring aspect of opaque corneas. Eight eyes of 8 consecutive patients were enrolled in therapeutic corneal keratopigmentation. Surgery was performed using manual technique, and a two-plane corneal dissection was performed. In the deeper pocket, brown pigment was injected to mimic iris color. In the more superficial and smaller pocket, black pigment was used to simulate pupillary opening. Seven out of 8 eyes had significant improvements in cosmesis after surgery. One patient did not have a major improvement due to significant superficial corneal neovascularization. In two eyes, there was pigment fading in the postoperative period, but no additional surgeries were performed. No complications were noted in any of the patients. Therapeutic corneal keratopigmentation can lead to a significant change in ocular appearance and may improve self-esteem and overall life quality. Pigment fading and corneal neovascularization can be a potential problem. Careful patient selection and counseling are important to avoid patients seeking unachievable results.