Corneal Neovascularization: Causes
Corneal neovascularization develops when chronic hypoxia, inflammation, infection, trauma, or limbal stem cell deficiency disrupts the normal balance between angiogenic and antiangiogenic factors that maintain corneal avascularity. 1, 2
Primary Etiologic Categories
Contact Lens-Related Causes
- Chronic hypoxia from contact lens wear is one of the most common causes, resulting from mechanical irritation, prolonged wearing time, poor lens hygiene, or use of low oxygen-transmissible materials 3
- Risk factors include soft contact lenses, infrequent lens replacement, prolonged daily wear duration, and preservative exposure in lens care solutions 3
- Contact lens-related keratoconjunctivitis can progress from focal to diffuse or circumferential corneal neovascularization if left untreated 3
Inflammatory and Allergic Conditions
- Vernal keratoconjunctivitis causes corneal neovascularization through chronic inflammation, particularly in hot, dry climates, with giant papillary hypertrophy and limbal involvement 3
- Rosacea conjunctivitis leads to corneal neovascularization via chronic blepharitis, meibomian gland dysfunction, and evaporative dry eye, typically with inferior corneal involvement 3
- Atopic keratoconjunctivitis produces neovascularization through persistent ocular surface inflammation and limbal stem cell compromise 3
Mechanical and Structural Causes
- Floppy eyelid syndrome causes neovascularization through chronic nocturnal eyelid ectropion and mechanical trauma to the superior cornea, associated with obesity and sleep apnea 3
- Giant papillary conjunctivitis from exposed sutures, ocular prostheses, or contact lenses creates localized mechanical irritation leading to vascular ingrowth 3
Medication and Preservative Toxicity
- Topical medications and preservatives (glaucoma drops, NSAIDs, antibiotics, antivirals) cause chronic keratoconjunctivitis that can progress to pannus formation and neovascularization 3
- Multiple concurrent eye medications or frequent dosing increases risk through cumulative toxic effects 3
Infectious and Immune-Mediated Causes
- Herpes stromal keratitis triggers neovascularization through persistent inflammation and stromal damage 1
- Ocular mucous membrane pemphigoid causes progressive conjunctival cicatrization and limbal stem cell deficiency leading to corneal vascularization 3
Pathophysiologic Mechanism
The cornea normally maintains avascularity through a balance between angiogenic factors (VEGF, FGF, PDGF, IL-6, IL-7, IL-8) and antiangiogenic molecules (angiostatin, endostatin, pigment epithelium-derived factor) 1, 4. When ocular insults tip this balance toward angiogenesis, new blood vessels invade from the limbus into normally avascular corneal tissue 2, 5.
Key Triggering Factors
- Hypoxia from contact lens wear or limbal stem cell deficiency upregulates VEGF expression 1, 2
- Inflammation from any cause releases pro-angiogenic cytokines and growth factors 2, 4
- Trauma (chemical, thermal, surgical) disrupts the limbal barrier and angiogenic balance 1, 5
- Limbal stem cell deficiency removes the anatomic and biochemical barrier to vascular ingrowth 3
Clinical Pitfalls
Do not overlook giant fornix syndrome in elderly women with chronic mucopurulent conjunctivitis, as this can progress to corneal neovascularization and perforation if the superior fornix coagulum is not addressed 3. The condition presents with enlarged superior fornix and ptosis, requiring more than standard antibiotic therapy 3.
Recognize that dupilumab-associated ocular surface disease can present with conjunctival and limbal injection in patients with severe atopic dermatitis, though corneal neovascularization is not explicitly listed as a sequela in current guidelines 3.
In vernal keratoconjunctivitis, corneal neovascularization represents advanced disease requiring aggressive management before considering procedures like corneal cross-linking, as active inflammation increases risk of sterile keratitis 3.