Blood Vessels in the Cornea

The cornea, the transparent front portion of the eye, plays a crucial role in focusing light onto the retina. It is unique among body tissues due to its transparency, which is essential for clear vision. For this reason, the cornea is typically avascular, meaning it does not contain blood vessels under normal conditions. Instead, it receives nourishment and oxygen from alternative sources. However, under certain pathological conditions, new blood vessels may invade the corneal tissue, leading to a condition known as corneal neovascularisation. Understanding the presence and role of blood vessels in the cornea is vital for comprehending corneal physiology, pathology, and clinical management of ocular diseases.

Structure and Function of the Cornea

The cornea is a dome-shaped, avascular tissue composed of five principal layers: the epithelium, Bowman’s layer, stroma, Descemet’s membrane, and endothelium. It acts as the eye’s primary refractive surface, contributing approximately two-thirds of the eye’s total focusing power. The absence of blood vessels in the cornea allows light to pass through unobstructed, ensuring optical clarity.
To maintain its avascularity and transparency, the cornea relies on a delicate balance of metabolic processes and structural integrity. Oxygen is supplied mainly from the tear film on its surface and from the aqueous humour within the anterior chamber. Nutrients, including glucose and amino acids, diffuse into the cornea from the aqueous humour and, to a lesser extent, from the limbal blood vessels surrounding the corneal margin.

Mechanisms Maintaining Corneal Avascularity

The maintenance of corneal avascularity depends on both anatomical and biochemical mechanisms. The epithelial and endothelial barriers restrict fluid and protein leakage into the corneal stroma, preventing opacification. Biochemically, anti-angiogenic factors such as endostatin, angiostatin, and soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) inhibit the growth of new blood vessels.
Furthermore, the limbus — a narrow transition zone between the cornea and sclera — serves as a physical and functional boundary preventing vascular encroachment. The balance between pro-angiogenic and anti-angiogenic signals within this region is critical to maintaining corneal clarity. Any disruption in this equilibrium may predispose the cornea to neovascularisation.

Corneal Neovascularisation

Corneal neovascularisation refers to the growth of new blood vessels into the cornea, usually from the limbus. This process is an abnormal response to hypoxia, inflammation, infection, or trauma. The newly formed vessels compromise corneal transparency, leading to reduced visual acuity and, in severe cases, blindness.
Common causes include:

• Contact lens overuse: Extended wear limits oxygen availability, promoting hypoxia and subsequent vessel formation.
• Infectious keratitis: Bacterial, viral, or fungal infections can trigger inflammatory responses leading to neovascularisation.
• Chemical injuries: Alkali burns and other chemical exposures destroy the corneal epithelium, allowing vascular ingrowth.
• Immune-mediated disorders: Conditions such as Stevens–Johnson syndrome and ocular cicatricial pemphigoid are also associated with vascular invasion.

The process of neovascularisation is driven primarily by the upregulation of vascular endothelial growth factor (VEGF) and other pro-angiogenic cytokines. Inflammatory cells such as macrophages and neutrophils play an active role in releasing these mediators, thereby facilitating vascular proliferation and migration.

Clinical Implications and Management

The presence of blood vessels within the cornea can have significant clinical implications. Beyond impairing vision, corneal vascularisation may complicate corneal transplantation, as the immune privilege of the graft is reduced in vascularised corneas, increasing the risk of graft rejection.
Management strategies aim to control underlying causes and inhibit further vessel growth. Approaches include:

• Pharmacological therapy: Topical corticosteroids and non-steroidal anti-inflammatory drugs (NSAIDs) help suppress inflammation. Anti-VEGF agents such as bevacizumab and ranibizumab are increasingly used to block vascular proliferation.
• Surgical interventions: Procedures such as photodynamic therapy, laser coagulation, or fine-needle diathermy can occlude established vessels.
• Contact lens modification: Switching to high-oxygen-permeable or daily disposable lenses can alleviate hypoxia-induced vascularisation.
• Treatment of underlying conditions: Management of infections or autoimmune diseases is essential to prevent recurrence.

Research and Therapeutic Developments

Ongoing research focuses on developing novel anti-angiogenic therapies and regenerative approaches to restore corneal transparency. Gene therapy targeting VEGF signalling pathways, bioengineered corneal substitutes, and stem cell transplantation are promising fields of study. Advances in imaging techniques, such as optical coherence tomography angiography (OCTA), now allow clinicians to visualise and quantify corneal vessels with high precision, improving both diagnosis and treatment monitoring.

Significance in Ophthalmology

The study of blood vessels in the cornea offers critical insights into ocular immunology, wound healing, and angiogenesis. Understanding the mechanisms underlying corneal avascularity not only aids in managing eye diseases but also contributes to broader biomedical knowledge about vascular regulation. The cornea’s natural transparency and immune privilege make it an exceptional model for investigating vascular biology and the effects of anti-angiogenic therapies.