Fine-needle Diathermy Combined With Subconjunctival Bevacizumab for Corneal Neovascularization

Evaluation of Combined Fine-needle Diathermy and Subconjunctival Bevacizumab Injection in the Treatment of Corneal Neovascularization

The goal of this clinical trial is to evaluate the efficacy and safety of combined fine-needle diathermy and subconjunctival Bevacizumab injection in patients with corneal neovascularization.

The main questions it aims to answer are:

Does combined fine-needle diathermy and subconjunctival Bevacizumab injection promote regression of corneal neovascularization? Is the treatment safe and well tolerated by patients?

Participants will:

Undergo a baseline evaluation, including assessment of disease duration, ocular history, systemic medical history, and presenting symptoms.

Undergo a detailed ophthalmic evaluation, including best-corrected visual acuity, intraocular pressure measurement, slit-lamp examination, corneal photography, and anterior segment optical coherence tomography (AS-OCT). Provide informed consent after explanation of potential risks and benefits of the procedure.

1. Background and Rationale Corneal neovascularization (CNV) is a pathological condition characterized by the ingrowth of blood vessels from the limbal vascular plexus into the normally avascular cornea. CNV has various etiologies, including infectious keratitis, inflammatory ocular surface diseases, trauma, chemical injury, contact lens-related complications, limbal stem cell deficiency, and other corneal disorders. The presence of corneal neovascularization can affect corneal transparency, induce lipid deposition and scarring, reduce visual acuity, and increase the risk of corneal graft rejection.

   Many treatment modalities have been used to manage CNV, including topical corticosteroids, laser photocoagulation, anti-vascular endothelial growth factor (anti-VEGF) therapy, and fine-needle diathermy (FND). Fine-needle diathermy directly occludes established corneal blood vessels and has demonstrated effectiveness in reducing mature corneal neovascularization. Bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF), inhibits angiogenesis and may reduce the formation and recurrence of corneal neovessels. The combination of FND and subconjunctival bevacizumab injection may provide a synergistic therapeutic effect by targeting both existing vessels and VEGF-mediated angiogenesis.

   Although both fine-needle diathermy and bevacizumab have been used individually in the treatment of corneal neovascularization, there is currently limited evidence regarding the long-term efficacy and safety of combining these two treatment modalities. Most published studies have involved small sample sizes, short follow-up periods, or have focused primarily on the outcomes of either fine-needle diathermy or anti-VEGF therapy alone.

2. Objectives Primary objective: to evaluate corneal neovascularization regression at 12 months after combined fine-needle diathermy and subconjunctival Bevacizumab injection.

   Secondary Objective: to assess the visual acuity, corneal clarity, recurrence of neovascularization, and treatment-related adverse events.

3. Study design:

   This is a prospective, single-arm, interventional clinical trial conducted at the Cornea Department of HoChiMinh City Eye Hospital. This study will enroll a total of 51 eyes.

   The study period spans from April 2026 to April 2028, including a 12-month follow-up for each participant.

4. Participants Eligible Participants are adults aged > 18 years with a diagnosis of corneal neovascularization involving at least one quadrant of the cornea, confirmed by slit-lamp examination Corneal neovascularization is stable with no evidence of progression for at least 4 weeks.

5. Surgical technique:

   The corneal neovascularization is identified under an operating microscope. A curved 10-0 nylon needle is inserted into the corneal stroma, with the needle oriented either parallel or perpendicular to the neovessel, depending on the vessel location and surgical accessibility.

   The target blood vessels are cauterized through a 10-0 nylon needle using low-power monopolar diathermy (1-2 mA). Diathermy is applied for approximately 1-2 seconds and discontinued once mild focal corneal stromal whitening or edema is observed, and the neovessels demonstrate visible contraction. After that, the needle is removed from the corneal stroma, and a subconjunctival injection of Bevacizumab (2.5mg/0.1ml) is injected into the subconjunctival space adjacent to the limbus.

6. Follow-up Protocol:

   Participants will be followed at 1 week, 1 month, 3 months, 6 months, and 12 months after treatment. At each visit, the following will be assessed: Best-corrected visual acuity, intraocular pressure, ocular surface examination, corneal photography, and recording of treatment-related adverse events.

7. Outcome Measures Primary outcome: Percentage reduction in corneal neovascularization area at 12 months. Corneal photographs will be obtained at baseline and follow-up visits. The neovascularized corneal area will be measured using ImageJ software. The primary outcome is the percentage reduction in corneal neovascularization area at 12 months compared with baseline.

   Secondary outcomes: Change in best-corrected visual acuity, corneal clarity, and recurrence of corneal neovascularization after treatment. Rates of postoperative complications: pain, subconjunctival hemorrhage, corneal epithelial defects, corneal edema, and other ocular complications.

8. Data Collection and Management All data will be recorded in standardized case report forms and entered into a secure electronic database. Data quality will be reviewed regularly by the study monitoring committee.

9. Statistical Analysis

   Descriptive statistics will be used to summarize demographics and baseline characteristics. Differences between groups will be assessed using:

   Student's t-test for continuous variables, Chi-square or Fisher's exact test for categorical outcomes, Kaplan-Meier survival analysis for surgical success, P-values <0.05 considered statistically significant.

10. Safety considerations Experienced cornea surgeons will perform all surgical procedures. Standard aseptic and surgical safety protocols will be followed. Any serious adverse event (SAE) will be reported to the Institutional Review Board (IRB) and the study monitoring committee.

11. Significance of the study This is the first prospective clinical study in Vietnam to evaluate the long-term outcomes of combined fine-needle diathermy and subconjunctival bevacizumab injection for corneal neovascularization. The findings may provide evidence to support the effectiveness and safety of this combined approach, contribute to the development of treatment recommendations, and improve clinical management of patients with corneal neovascularization.

Inclusion Criteria:

• Age over 18 years.
• Diagnosis of corneal neovascularization involving at least one quadrant of the cornea, confirmed by slit-lamp examination.
• Corneal neovascularization is stable with no evidence of progression for at least 4 weeks.
• Agreement to participate in the study and ability to comply with outpatient follow-up requirements

Exclusion Criteria:

• Pregnant or breastfeeding women.
• History of hypersensitivity or allergy to bevacizumab or any component of the study medication.
• Presence of severe systemic disease that would preclude study participation or surgical intervention, including coagulation disorders or uncontrolled cardiovascular disease.
• Active ocular infection or acute conjunctivitis at the time of enrollment.
• Persistent corneal epithelial defect or delayed corneal epithelial healing.
• History of ocular surgery within 3 months before study enrollment.
• Corneal neovascularization associated with uncontrolled secondary glaucoma.
• Inability or unwillingness to comply with study treatment or follow-up visits.