What is the treatment for corneal neovascularization?

Treatment of Corneal Neovascularization

Anti-VEGF therapy (bevacizumab, ranibizumab, or aflibercept) combined with topical corticosteroids represents the primary medical treatment for corneal neovascularization, with surgical options reserved for refractory cases or specific etiologies requiring ocular surface reconstruction. 1, 2

First-Line Medical Management

Anti-VEGF Therapy

• Initiate anti-VEGF agents as the cornerstone of treatment since VEGF is the most important mediator of corneal angiogenesis and these agents have demonstrated efficacy in blocking vessel formation 1, 2
• Bevacizumab (off-label), ranibizumab, or aflibercept can be administered via:
  • Topical application (most common initial approach) 2
  • Subconjunctival injection for deeper penetration 1
  • Intrastromal injection for established vessels 3
• Anti-VEGF therapy prevents progression of neovascularization and may induce regression of existing vessels 1, 2

Corticosteroids

• Add topical corticosteroids immediately since inflammation is a key pathophysiologic driver of corneal neovascularization 2, 4
• Corticosteroids remain the mainstay of treatment by addressing the underlying inflammatory cascade 2
• Angiostatic steroids have proven effective in animal models for inhibiting corneal neovascularization 4

NSAIDs

• Consider topical nonsteroidal anti-inflammatory agents as adjunctive therapy to reduce inflammation without steroid-related side effects 4, 3

Address Underlying Etiology

Critical pitfall: Failing to identify and treat the causative factor will result in treatment failure regardless of anti-angiogenic therapy used. 5, 2

• Contact lens-related: Discontinue lens wear immediately and switch to daily disposable lenses or glasses 5
• Infectious keratitis: Treat with appropriate antimicrobial therapy before addressing neovascularization 5, 2
• Ocular surface disease: Manage underlying dry eye, blepharitis, or limbal stem cell deficiency 5, 2
• Chemical injury: Initiate aggressive ocular surface reconstruction protocols 2
• Herpes stromal keratitis: Add antiviral prophylaxis to prevent recurrence 5

Second-Line and Surgical Options

Laser Photocoagulation

• Argon laser photocoagulation can be used to directly occlude established vessels, though this may cause corneal scarring 4, 3
• Reserve for vessels that fail to regress with medical therapy 3

Photodynamic Therapy

• Photodynamic therapy has shown effectiveness in animal models for transiently restoring corneal "angiogenic privilege" 4
• Consider for refractory cases unresponsive to anti-VEGF and corticosteroids 3

Fine Needle Diathermy and Cautery

• Direct vessel occlusion techniques can be employed for isolated, superficial vessels 3
• Risk of scarring limits widespread use 3

Surgical Reconstruction

• Ocular surface reconstruction (including limbal stem cell transplantation or amniotic membrane grafting) is indicated when limbal stem cell deficiency drives the neovascularization 2
• Corneal transplantation may be necessary when scarring and lipid deposition have already compromised visual acuity beyond medical salvage 5, 3

Emerging Therapies

• Local gene therapy targeting angiogenic pathways represents a promising future direction 5
• siRNA and tyrosine kinase inhibitors are under investigation as more targeted anti-VEGF approaches 1
• These therapies aim to disrupt specific steps in proangiogenic factor synthesis and action 3

Treatment Algorithm

1. Immediately discontinue or treat the causative factor (contact lenses, infection, inflammation) 5, 2
2. Start combination therapy: Topical anti-VEGF + topical corticosteroid 1, 2
3. Reassess at 4-8 weeks: If inadequate response, escalate to subconjunctival or intrastromal anti-VEGF injections 1, 3
4. Consider laser photocoagulation for persistent vessels after 12-16 weeks of medical therapy 4, 3
5. Refer for surgical intervention if medical and laser therapies fail, or if limbal stem cell deficiency requires reconstruction 2, 3

Critical Pitfalls to Avoid

• Do not delay treatment: Established neovascularization leads to irreversible corneal scarring, lipid deposition, and edema that significantly compromise visual prognosis 5
• Do not use anti-VEGF monotherapy: The inflammatory component requires concurrent corticosteroid treatment 2, 4
• Do not ignore the underlying cause: Treating vessels without addressing etiology results in recurrence 5, 2
• Monitor for corticosteroid complications: Prolonged use can cause elevated intraocular pressure and cataract formation 2