Treatment Of Corneal Neovascularization Research Articles

Clinical Outcomes of Topical Bevacizumab for the Treatment of Corneal Neovascularization.

Background and objective In corneal neovascularization, the peri-corneal vascular structure grows into a normally avascular cornea. This is due to an imbalance between the angiogenic and anti-angiogenic factors that sustain corneal transparency. There are various etiologies of this condition, and they can be divided into infective or non-infective causes, such as inflammation, trauma, or surgical causes. Corneal neovascularization has been shown to improve with the current treatments using steroids and anti-vascular endothelial growth factors. This study aimed to evaluate the effectiveness of topical bevacizumab as an anti-angiogenic agent in patients with corneal neovascularization. Methods This retrospective study included patients who suffered corneal neovascularization of various etiologies and completed six months of topical bevacizumabtherapy between 2020 and 2022 at the Universiti Kebangsaan Malaysia Medical Centre. Results A total of 16 patients received treatment with topical bevacizumab over the three-yearstudy period. Based on specified inclusion and exclusion criteria, 12 patients were eligible for inclusion in this study. Eight patients (66%) showed improvement in terms of either 'clock hours' of improvement, morphology, or regression of corneal neovascularization. All infective causes of corneal neovascularization showed improvement on completion of bevacizumab compared to other causes. Conclusion Topical bevacizumab can be one of the treatment choices for corneal neovascularization. As the outcome varies depending on the severity and chronicity of the condition, the attending ophthalmologist should treat each case differently. Although topical bevacizumab is more effective in mild and moderate cases, the indications for its use in chronic cases remain debatable as the results are unfavorable in such cases.

Management of corneal neovascularization: Current and emerging therapeutic approaches.

Corneal neovascularization (CoNV) is a sight-threatening condition affecting an estimated 1.4 million people per year, and the incidence is expected to rise. It is a complication of corneal pathological diseases such as infective keratitis, chemical burn, corneal limbal stem cell deficiency, mechanical trauma, and immunological rejection after keratoplasties. CoNV occurs due to a disequilibrium in proangiogenic and antiangiogenic mediators, involving a complex system of molecular interactions. Treatment of CoNV is challenging, and no therapy thus far has been curative. Anti-inflammatory agents such as corticosteroids are the mainstay of treatment due to their accessibility and well-studied safety profile. However, they have limited effectiveness and are unable to regress more mature neovascularization. With the advent of advanced imaging modalities and an expanding understanding of its pathogenesis, contemporary treatments targeting a wide array of molecular mechanisms and surgical options are gaining traction. This review aims to summarize evidence regarding conventional and emerging therapeutic options for CoNV.

Harnessing silk fibroin microparticles for metformin delivery: A novel approach to treating corneal neovascularization

Corneal neovascularization (CV) poses significant challenges in ophthalmology, often leading to impaired vision and discomfort. Silk fibroin microparticles have emerged as promising candidates for drug delivery applications, owing to their biocompatibility, biodegradability, and controlled release characteristics. In the current research, metformin-loaded silk microparticles were developed, and their potential for treating corneal neovascularization was evaluated. Silk microparticles were prepared using silk fibroin and polyvinyl alcohol (PVA) at various weight ratios, facilitating phase separation to create a porous structure conducive to drug loading. Metformin (MT), a widely used antidiabetic agent with potential anti-angiogenic properties, was incorporated into the silk microparticles at different concentrations. The formulation termed TB (0.3 % MT loaded Microparticles) emerged as the most promising candidate was identified through comprehensive in vitro evaluations. In in vitro cytotoxicity studies, it was determined that all formulations provided cell viability above 80%, however, in permeability studies and encapsulation efficiency studies, TB was determined to be more effective than other formulations. TB demonstrated a particle size of approximately 8.9 ± 3.6 μm and an encapsulation efficiency of 96.3 ± 2.1%. In vitro release studies revealed that TB exhibited a burst release of 62% within the initial two days, followed by sustained release over a period of 14 days, consistent with Peppas-Sahlin kinetics. Mathematical modeling further corroborated the diffusion mechanism underlying drug release from TB microparticles. In vivo studies on rats and histochemical analyzes on corneas showed that TB exhibited efficacy comparable to dexamethasone, a standard treatment for CV, despite being administered once daily. Histological analyses of corneal tissues revealed reduced neovascularization and inflammation in the TB-treated group, underscoring its therapeutic potential. Overall, our findings highlight the promise of metformin-loaded silk fibroin microparticles as a novel therapeutic approach for managing CV, offering sustained drug release and enhanced efficacy in treating this challenging ocular condition.

Genome Editing VEGFA Prevents Corneal Neovascularization In Vivo.

Corneal neovascularization (CNV) is a common clinical finding seen in a range of eye diseases. Current therapeutic approaches to treat corneal angiogenesis, in which vascular endothelial growth factor (VEGF) A plays a central role, can cause a variety of adverse side effects. The technology of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 can edit VEGFA gene to suppress its expression. CRISPR offers a novel opportunity to treat CNV. This study shows that depletion of VEGFA with a novel CRISPR/Cas9 system inhibits proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs) in vitro. Importantly, subconjunctival injection of this dual AAV-SpCas9/sgRNA-VEGFA system is demonstrated which blocks suture-induced expression of VEGFA, CD31, and α-smooth muscle actin as well as corneal neovascularization in mice. This study has established a strong foundation for the treatment of corneal neovascularization via a gene editing approach for the first time.

Intermittent Topical Bevacizumab for Treatment of Pediatric Corneal Neovascularization after Keratitis

Introduction : Corneal neovascularization imposes pediatric patients to risk of amblyopia. Current treatment of corneal neovascularization consists of topical steroids, nonsteroidal anti-inflammatory medications, immunomodulatory agents, anti-Vascular Endothelial Growth Factor (anti-VEGF) and few surgical procedures. Anti-VEGF shows promising results in treating corneal neovascularization but is difficultto obtain in developing countries such as Indonesia. We report intermittent topical use of Bevacizumab as antiVEGF in a child experiencing corneal neovascularization in the settings of limited antiVEGF availability.
 Case Illustration : A 5-year-old girl presented with corneal neovascularization after keratitis. Topical fluorometholone 4 times a day for 3 weeks was given with no clinical improvement. An intermittent topical Bevacizumab was started, each episode of treatment lasted 4 days. Corneal neovascularization regressed after 1 episode of treatment and thus continued until a total of 2 treatment episodes. She improved clinically on treatment, with some residual corneal scarring. Visual acuity improved from logMar 0.5 to logMar 0.2 following treatment.
 Discussion : Bevacizumab regresses corneal neovascularization by inhibiting proangiogenic factor VEGF which is upregulated in neovascularization. Topical Bevacizumab ability to penetrate cornea was contributed by defective corneal epithelial overlying neovascularization. Long-term use of antiVEGF may hinder VEGF beneficial role on wound recovery and trigger unwanted side effects.
 Conclusion : Intermittent short-term use of topical bevacizumab may be effective to treat corneal neovascularization during acute period in pediatric patient and is safely tolera

Exploring Corneal Neovascularization: An Integrated Approach Using Transcriptomics and Proteomics in an Alkali Burn Mouse Model.

Corneal neovascularization (CNV) impairs corneal transparency and visual acuity. The study aims to deepen our understanding of the molecules involved in CNV induced by alkali burns, facilitate a better grasp of CNV mechanisms, and uncover potential therapeutic targets. Eighty-four mice were selected for establishing CNV models via alkali burns. On days 3, 7, and 14 after the burns, corneal observations and histological investigations were conducted. An integrated analysis of RNA sequencing (RNA-seq)-based transcriptomics and label-free quantitative proteomics was performed in both normal and burned corneas. Bioinformatics approaches, encompassing Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, were applied to discern differentially expressed genes (DEGs) and crucial signaling pathways. Four potentially CNV-related genes were validated using quantitative real-time PCR (qRT-PCR) and Western blot. Significant CNV was observed on the seventh day. Forty-one genes were differentially expressed in neovascularized corneas, with 15 upregulated and 26 downregulated at both mRNA and protein levels. Bioinformatics analysis revealed that these DEGs participated in diverse biological processes, encompassing retinol and retinoic acid metabolism, neutrophil chemotaxis, and actin filament assembly, along with significant enrichment pathways like cytochrome P450, tyrosine, and phenylalanine metabolism. The upregulation of lymphocyte cytosolic protein 1 (LCP1) and cysteine and glycine-rich protein 2 (CSRP2) genes and the downregulation of transglutaminase 2 (TGM2) and transforming growth factor-beta-induced (TGFBI) genes were confirmed. We analyzed gene expression differences in mouse corneas 7 days after alkali burns, finding 41 genes with altered expression. The exact role of these genes in CNV is not fully understood, but exploring angiogenesis-related molecules offers potential for CNV treatment or prevention.

Bone morphogenetic protein 4 thermosensitive hydrogel inhibits corneal neovascularization by repairing corneal epithelial apical junctional complexes

Corneal neovascularization (CNV) is a heavy attribute of blinding disease changes. Existing medications need numerous infusions and have a limited absorption. Investigating novel drugs with safety, efficacy, and convenience is crucial. In this study, we developed a bone morphogenetic protein 4 (BMP4)-loaded poloxamer-oxidized sodium alginate (F127-OSA) thermosensitive hydrogel. The 14 % F127-OSA hydrogel transformed from sol to gel at 31–32 °C, which might extend the application period on the ocular surface. The hydrogel's porous structure and uniform dispersion made it possible for drugs to release gradually. We used a suture-induced rat CNV model to investigate the mechanism of CNV inhibition by hydrogel. We discovered that F127-OSA hydrogel loaded with BMP4 could significantly reduce the length and area of CNV, relieve corneal edema, and stop aberrant epithelial cell proliferation. The hydrogel's efficacy was superior to that of the common solvent group. Additionally, BMP4 thermosensitive hydrogel repaired ultrastructure, including microvilli, intercellular junctions, and damaged apical junctional complexes (AJCs), suggesting a potential mechanism by which the hydrogel prevented CNV formation. In conclusion, our investigation demonstrates that F127-OSA thermosensitive hydrogel loaded with BMP4 can repair corneal epithelial AJCs and is a promising novel medication for the treatment of CNV.

A Synergistic Therapy With Antioxidant and Anti-VEGF: Toward its Safe and Effective Elimination for Corneal Neovascularization.

Corneal neovascularization (CNV) is one of the leading causes of blindness in the world. In clinical practice; however, it remains a challenge to achieve a noninvasive and safe treatment. Herein, a biocompatible shell with excellent antioxidant and antivascularity is prepared by co-assembly of epigallocatechin gallate/gallic acid and Cu (II). After loading glucose oxidase (GOx) inside, the shell is modified with dimeric DPA-Zn for codelivering vascular endothelial growth factor (VEGF) small interfering RNA (VEGF-siRNA). Meanwhile, the Arg-Gly-Asp peptide (RGD) peptide-engineered cell membranes coating improves angiogenesis-targeting and is biocompatible for the multifunctional nanomedicine (CEGs/RGD). After eye drops administration, CEGs/RGD targets enrichment in neovascularization and CEGs NPs enter cells. Then, the inner GOx consumes glucose with a decrease in local pH, which in turn leads to the release of EGCE and VEGF-siRNA. As a result, the nanomedicines significantly reduce angiogenesis and inhibit CNV formation through synergistic effect of antioxidant and antivascular via down-regulation of cluster of differentiation 31 and VEGF. The nanomedicine represents a safe and efficient CNV treatment through the combined effect of antioxidant/gene, which provides important theoretical and clinical significance.

Development of injectable hyaluronic acid-based hydrogels with antioxidant activity for the treatment of corneal neovascularization

Corneal neovascularization (CNV) is a condition that can severely adversely affect corneal transparency, culminating in visual disturbances and potential blindness. The need to manage this condition by frequently administering glucocorticoid eye drops can increase the risk of adverse side effects while reducing the odds that patients will comply with treatment regimens. Given that CNV often coincides with elevated levels of reactive oxygen species (ROS) production, in this study a sunitinib-loaded injectable antioxidant hydrogel was developed using hyaluronic acid and tannic acid. This hydrogel was effectively able to eliminate free radicals including ABTS and DPPH, normalizing intracellular ROS levels while protecting against H2O2-induced apoptosis. This sunitinib-loaded hydrogel also effectively inhibited the proliferation and tube formation activity of endothelial cells, while also inhibiting oxidative stress, inflammatory activity, and CD31 expression, thereby effectively preserving corneal transparency, promoting more rapid epithelialization, and inhibiting alkali burn-induced CNV in vivo. This sunitinib-loaded hydrogel may thus hold great promise as a novel tool for treating CNV and corneal alkali burns.

Development of Osthole-Loaded Microemulsions as a Prospective Ocular Delivery System for the Treatment of Corneal Neovascularization: In Vitro and In Vivo Assessments.

Osthole (OST), a natural coumarin compound, has shown a significant inhibitory effect on corneal neovascularization (CNV). But, its effect on treating CNV is restricted by its water insolubility. To overcome this limitation, an OST-loaded microemulsion (OST-ME) was created to improve the drug's therapeutic effect on CNV after topical administration. The OST-ME formulation comprised Capryol-90 (CP-90), Cremophor® EL (EL-35), Transcutol-P (TSP) and water, and sodium hyaluronate (SH) was also included to increase viscosity. The OST-ME had a droplet size of 16.18 ± 0.02 nm and a low polydispersity index (0.09 ± 0.00). In vitro drug release from OST-ME fitted well to the Higuchi release kinetics model. Cytotoxicity assays demonstrated that OST-ME was not notably toxic to human corneal epithelial cells (HCECs), and the formulation had no irritation to rabbit eyes. Ocular pharmacokinetics studies showed that the areas under the concentration-time curves (AUC0-t) in the cornea and conjunctiva were 19.74 and 63.96 μg/g*min after the administration of OST-ME, both of which were 28.2- and 102.34-fold higher than those after the administration of OST suspension (OST-Susp). Moreover, OST-ME (0.1%) presented a similar therapeutic effect to commercially available dexamethasone eye drops (0.025%) on CNV in mouse models. In conclusion, the optimized OST-ME exhibited good tolerance and enhanced 28.2- and 102.34-fold bioavailability in the cornea and conjunctiva tissues compared with suspensions in rabbit eyes. The OST-ME is a potential ocular drug delivery for anti-CNV.

Aflibercept Loaded Eye-Drop Hydrogel Mediated with Cell-Penetrating Peptide for Corneal Neovascularization Treatment.

Corneal neovascularization (CoNV) is a major cause of visual impairment worldwide. Currently, available treatment options have limited efficacy and are associated with adverse effects due to biological barriers and clearance mechanisms. To address this challenge, a novel topical delivery system is developed-Gel 2_1&Eylea-an aflibercept-loaded eye-drop hydrogel mediated with cell-penetrating peptide 1. Gel 2_1&Eylea demonstrates superior membrane permeability, increased stability, and prolonged drug retention time on the ocular surface, and thus may improve drug efficacy. In a rabbit CoNV model, Gel 2_1&Eylea significantly reduces the density of neovascularization with no adverse effects on normal corneoscleral limbal vessels, demonstrating high efficacy and biocompatibility. This work identifies a promising treatment for CoNV which has the potential to benefit other ocular neovascular diseases.

Preliminary Study on the Effect of Intrastromal Anti-Vascular Endothelial Growth Factor Injections on Corneal Neovascularization Using Anterior Segment Optical Coherence Tomography Angiography

Background Corneal neovascularization, is a serious condition affecting large percentage of the population. Not only does corneal neovascularization decrease vision and cause corneal edema, but also, it is highly associated with graft rejections. Anti-VEGF has been used in many studies to treat corneal neovascularization with promising results. Recently, evaluation of corneal neovascularization using Optical Coherence Tomography Angiography (OCTA) has been explored and has shown to be promising. Objective To evaluate the effect of intrastromal injection of Anti-VEGF using the swept source anterior segment OCTA on corneal neovascularization. Patients and Methods This pilot study was done in a cohort, prospective manner. The study was done on 10 eyes of 10 patients with corneal neovascularization who were planned for keratoplasty or after keratoplasty. Intrastromal injection of Anti-VEGF using a 30 Gauge needle at a concentration of 5 mg/0.2 mL [2.5%] was done for patients involved in this study. OCTA was done 48 hours before injection, 1 week and 1 month after injection. OCTA images were compared to evaluate the effect of Anti-VEGF on corneal neovascularization. Results Compared with the pre-operative period, at 1 week postoperatively, 9 cases have shown decreased corneal neovascularization, with only 1 case that showed no regression and seemed to be unresponsive to the single injection of Anti-VEGF. At 1 month period, 8 cases had increased vascularization (re-vascularized), 1 case had decreased vascularization again (completely disappeared) and 1 case stayed the same with no change. Cases that have revascularized, have not returned back to the original vascularization level. Using OCTA colored, black and white images, we were able to picture blood vessels in 3-D image and detect subtle changes in corneal neovascularization. Using the OCTA cross-sectional images, we were able to estimate the vessels depths. In 6 cases, vessels were located in the posterior 25% of the cornea (Deep), in 2 cases they were located in the anterior 25 % (Superficial) and in 2 cases they were between the anterior 25 % and the posterior 25% (Mid-stromal). Vessel density was not possible to calculate in this study. Conclusion Bevacizumab intrastromal injections seem to be a very effective temporary method in decreasing corneal neovascularization despite the level of neovascularization. Repeated Bevacizumab injections might be needed to eliminate corneal neovascularization completely. Bevacizumab seems to have a peak action at 1 week period and then its effect seems to ware off gradually. OCTA was able to visualize vessels in 3-D image, even under vascularized corneal scars. OCTA was able to recognize subtle changes in corneal neovascularization, that were not visible by slit lamp.

Inflammation-responsive molecular-gated contact lens for the treatment of corneal neovascularization

Corneal neovascularization (CNV) badly damages the corneal transparency, resulting in visual disturbance and blindness. The frequent administration of glucocorticoid eye drops in clinical increases the possibility of side effects and reduces patient compliance. Considering CNV is often accompanied by an increase in ROS production, a ROS-responsive monomer 2-(methylthio)ethyl methacrylate was introduced into the matrix as a “gating switch”. The prepared dexamethasone contact lenses (MCLs@Dex) showed a significant H2O2-responsive release for 168 h. To avoid corneal hypoxia and neovascularization caused by long-term wearing, high‑oxygen-permeability fluorosiloxane materials were incorporated. The oxygen permeability of MCLs@Dex was 4 times that of commercially available hydrogel contact lenses and had ultra-low protein adsorption, which meets the requirements of long-term wearing. In vivo pharmacokinetic studies showed that MCLs@Dex increased the mean residence time by 19.7 times and bioavailability by 2.29 times compared with eye drops, validating the ROS response and sustained release properties. More importantly, MCLs@Dex had satisfactory effects on reducing inflammation and decreasing the related cytokines and oxidative stress levels, and demonstrated significant inhibition of neovascularization, with a suppression rate of 76.53% on the 14th day. This responsive drug delivery system provides a promising new method for the safe and effective treatment of ocular surface diseases.

Preparation of a Sunitinib loaded microemulsion for ocular delivery and evaluation for the treatment of corneal neovascularization in vitro and in vivo.

Background: Corneal neovascularization (CNV) is a pathological condition that can disrupt corneal transparency, thus harming visual acuity. However, there is no effective drug to treat CNV. Sunitinib (STB), a small-molecule multiple receptor tyrosine kinase inhibitor, was shown to have an effect on CNV. The purpose of this study was to develop an STB microemulsion (STB-ME) eye drop to inhibit CNV by topical application. Methods: We successfully prepared an STB-ME by the phase inversion emulsification method, and the physicochemical properties of STB-MEs were investigated. The short-term storage stability, cytotoxicity to human corneal epithelial cells, drug release, ocular irritation, ocular pharmacokinetics and the inhibitory effect on CNV were evaluated in vitro and in vivo. Results: The optimal formulation of STB-ME is composed of oleic acid, CRH 40, Transcutol P, water and sodium hyaluronate (SH). It is a uniform spherical particle with a mean droplet size of 18.74 ± 0.09nm and a polydispersity index of 0.196 ± 0.004. In the in vitro drug release results, STB-ME showed sustained release and was best fitted by a Korsmeyer-Peppas model (R 2 = 0.9960). The results of the ocular pharmacokinetics in rabbits showed that the formulation containing SH increased the bioavailability in the cornea (2.47-fold) and conjunctiva (2.14-fold). STB-ME (0.05% and 0.1%), administered topically, suppressed alkali burn-induced CNV in mice more effectively than saline, and high-dose (0.1%) STB-ME had similar efficacy to dexamethasone (0.025%). Conclusion: This study provides a promising formulation of STB-ME for the inhibition of CNV by topical administration, which has the excellent characteristics of effectiveness, sustained release and high ocular bioavailability.

Subconjunctival conbercept for the treatment of corneal neovascularization.

To investigate the effectiveness and safety of subconjunctival injection of conbercept in the treatment of corneal neovascularization (CNV). The data on 10 consecutively recruited patients with CNV who received a subconjunctival conbercept (1 mg) once, and measured the area, length, and diameter of neovascularization before and after (1d, 1, 2wk, and 1mo) treatment as well as the occurrence of systemic and ocular complications after treatment were analyzed. There was a statistically significant reduction in the area of CNV one day after treatment (mean±SD: 38.46±11.36 mm2), compared with before treatment (42.46±12.80 mm2, P<0.01). There was also a statistically significant reduction in the length (3.86±1.80 mm vs 4.64±1.77 mm, P<0.01) and diameter (0.044±0.022 vs 0.060±0.026, P<0.05) of CNV, one week after treatment comparing to before treatment. The reduction in all three parameters was maximized at two weeks after treatment (area: 29.49±8.83 mm2, P<0.001; length: 3.50±1.88 mm, P<0.001; and diameter: 0.038±0.017 mm, P<0.01). No severe systemic or ocular complication was observed during the study. During the observation period of one-month, subconjunctival injection of conbercept is an effective and safe method for the reduction of CNV. It may be effective as a preoperative drug for neovascular corneal transplantation.

Efficient ocular delivery of siRNA via pH-sensitive vehicles for corneal neovascularization inhibition

Corneal neovascularization (CoNV)-induced blindness is an enduring and challenging condition with limited management options. Small interfering RNA (siRNA) is a promising strategy for preventing CoNV. This study reported a new strategy using siVEGFA to silence vascular endothelial growth factor A (VEGFA) for CoNV treatment. To improve the efficacy of siVEGFA delivery, a pH-sensitive polycationic mPEG2k-PAMA30-P(DEA29-D5A29) (TPPA) was fabricated. TPPA/siVEGFA polyplexes enter cells via clathrin-mediated endocytosis, resulting in higher cellular uptake efficiency and comparable silencing efficiency than that of Lipofectamine 2000 in vitro. Hemolytic assays verified that TPPA safe in normal physiological environments (pH 7.4) but can easily destroy membranes in acidic mature endosomes (pH 4.0). Studies on the distribution of TPPA in vivo showed that it could prolong the retention time of siVEGFA and promote its penetration in the cornea. In a mouse model induced by alkali burn, TPPA efficiently delivered siVEGFA to the lesion site and achieved VEGFA silencing efficiency. Importantly, the inhibitory effect of TPPA/siVEGFA on CoNV was comparable to that of the anti-VEGF drug ranibizumab. Delivering siRNA using pH-sensitive polycations to the ocular environment provides a new strategy to efficiently inhibit CoNV.

Effect of Conbercept on Corneal Neovascularization in a Rabbit Model

ABSTRACT Objective To study the efficacy of Conbercept for the treatment of corneal neovascularization (NV) in a rabbit model. Methods NV was induced by placing sutures. Eight rabbits were used as a control. The other 136 rabbits were randomly divided into two equal groups, and 68 rabbits in each group were divided into four subgroups and given different treatments. Time-course photographs, histological examination, and enzyme-linked immunoassay ELISA analysis for vascular endothelial growth factor were performed at weeks 1, 2, and 3 after injection placement. Results At weeks 1, 2, and 3 after injection placement, there was less expression of corneal NV and VEGF in the conbercept-treated groups than in the saline-treated control groups and less corneal NV and VEGF were expressed in the early treatment group than in the late treatment group. At weeks 2 and 3 after injection, there were fewer corneal NV (length and area) in the early intrastromal injection group with conbercept than in the early subconjunctival injection group with conbercept and a smaller diameter of corneal NV than in the late intrastromal injection group treated with conbercept. Histological examination showed a smaller diameter of corneal NV in all eyes in conbercept-treated groups 1 w after injection than before injection. Treatment with subconjunctival injection with conbercept led to a larger diameter at weeks 2 and 3 than at week 1. Conclusions Subconjunctival and intrastromal administrations of conbercept effectively inhibit corneal NV in rabbits, and the latter has the better effect. The effect is the best in the group with cornea intrastromal injection of conbercept 1 w after suture. Early administration of conbercept may successfully inhibit corneal NV in an animal model.

Pre-clinical safety of topically administered sunitinib-loaded lipid and polymeric nanocarriers targeting corneal neovascularization

Three different types of sunitinib-loaded (SUN-loaded) nanocarriers were compared, aiming at the topical treatment of corneal neovascularization (CNV): polymeric nanospheres (NS), liposomes (LIP), and solid lipid nanoparticles (SLN). Three out of eleven formulations prepared for an optimization study – the best SUN-loaded nanocarrier of each assessed type (NS, LIP, and SLN) – were selected, based on their size, polydispersity index (PdI), drug load (DL), and encapsulation efficiency (EE). These three optimal formulations were further characterized by nanoparticle tracking analysis (NTA), electron paramagnetic resonance (EPR) spectroscopy, and zeta potential. In vitro SUN release profiles were obtained for the optimal formulations, along with ex vivo corneal permeability/retention studies, and ocular tolerance assays, namely: the bovine corneal opacity and permeability (BCOP) assay, the HET-CAM test (hen’s egg test – chorioallantoic membrane), and hemolytic potential (HP) assay. None of the optimal formulations exhibited toxicity or potential for ocular irritation. SLN showed higher surface fluidity, drug release more suitable for topical ocular applications, besides greater SUN corneal retention. Our results suggest that SLN are the best CNV-targeting SUN-loaded nanocarriers for clinical translation when compared to their NS and LIP analogues.

Effect of Intra-Stromal Bevacizumab on Corneal Vascularization

Purpose: To study the effect of Intra-stromal Bevacizumab on corneal vascularization. Study Design: Quasi experimental study. Place and Duration of Study: Outpatient department of the Combined Military Hospital, Multan from April 2022 to August 2022. Methods: Thirty patients were recruited through non-probability, convenience sampling technique. Ethical approval was taken from Institutional Review Board. Complete ocular examination was performed by a consultant ophthalmologist and patients with corneal neovascularization were included in the study. Area of corneal vascularization was measured on slit lamp. After taking all the aseptic measures and administering anesthetic eye drops, patients were administered 0.2 ml of (2.5 mg/0.1 mL) Bevacizumab (Avastin, Roche) using an ophthalmic microscope. The patient was then called for a follow up after 4 weeks and then the grade of corneal vascularization was checked by a consultant ophthalmologist on slit lamp examination. Data analysis was doneusing SPSS version 25. Results: Mean age of the patients was 43.4 ± 13.7 years (range 25 to 72 years). Male to female ratio was 2:3. There was significant decrease in the area of corneal neovascularization from 2.78mm ± 0.30 to 2.50mm ± 0.27 (p = 0.0003). The mean change in the area of corneal neovascularization was 10.07%. Two patients had sub-conjunctival hemorrhage which settled over due course of time. Conclusion: Intra-stromal Bevacizumab resulted in significant reduction in vascularized area of cornea with minimal side effects indicating that intra-stromal Bevacizumab is an effective and safe modality in the treatment of corneal neovascularization.

Insights into corneal re‐vascularization and vascular remodelling in the eye

AbstractWhile corneal neovascularization is a well‐known, sight‐threatening condition presenting a risk for corneal transplant rejection and failure, corneal revascularization has received much less attention. Although ocular revascularization is well studied in the context of regrowth of choroidal vessels following regular anti‐angiogenic injections for age‐related macular degeneration, the corneal context is less well documented. Here, the differences between initial and subsequent episodes of corneal neovascularization are explored, as well as the underlying changes at the mechanistic, structural and biochemical levels, through basic studies in the murine cornea. Repeat neovascularization is found to be more aggressive than the vessel ingrowth in an initial phase, pointing towards a memory effect in the corneal tissue. Furthermore, these regrown vessels are more resistant to treatment than initial vessels, which can have implications for the long‐term treatment and rebound of corneal vessels and prognosis for graft survival. We also highlight several factors that may be driving this aggressive revascularization response, with an eye towards future interventions aimed at preventing revascularization following initial treatments for corneal neovascularization.