Corneal neovascularization (CNV) is the in-growth of new blood vessels from the pericorneal plexus into avascular corneal tissue as a result of oxygen deprivation. Maintaining avascularity of the corneal stroma is an important aspect of corneal pathophysiology as it is required for corneal transparency and optimal vision. A decrease in corneal transparency causes visual acuity deterioration. Corneal tissue is avascular in nature and the presence of vascularization, which can be deep or superficial, is always pathologically related.
Corneal neovascularization is a sight-threatening condition that can be caused by inflammation related to infection, chemical injury, autoimmune conditions, immune hypersensitivity, post-corneal transplantation, and traumatic conditions among other ocular pathologies. Common causes of CNV within the cornea include trachoma, corneal ulcers, phlyctenular keratoconjunctivitis, rosacea keratitis, interstitial keratitis, sclerosing keratitis, chemical burns, and wearing contact lenses for over-extended periods of time. Superficial presentations of CNV are usually associated with contact lens wear, while deep presentations may be caused by chronic inflammatory and anterior segment ocular diseases.
Corneal neovascularization has become more common worldwide with an estimated incidence rate of 1.4 million cases per year, according to a 1998 study by the Massachusetts Eye and Ear Infirmary. The same study found that the tissue from twenty percent of corneas examined during corneal transplantations had some degree of neovascularization, negatively impacting the prognosis for individuals undergoing keratoplasty procedures.
Presentation
Complications
In advanced stages, corneal neovascularization can threaten eyesight, which is why routine (annual) eye exams are recommended for contact lens patients.
Causes
CNV causes may be congenital in nature, such as with Aniridia, or acquired. Frequently, inflammatory, infectious, degenerative, traumatic or iatrogenic (e.g. contact lenses) conditions can be responsible for acquired CNV.
Some major acquired inflammatory conditions include graft rejection following keratoplasty, graft or host diseases of the new tissue, atopic conjunctivitis, rosacea, ocular pemphigoid, Lyell's syndrome, and Steven's Johnson syndrome.
Infections responsible for CNV range from bacterial (chlamydia, syphilis, pseudomonas), viral (herpes simplex & herpes zoster viruses), fungal (candida, aspergillus, fusarium), to parasitic (onchocerca volvolus) infection.
Degenerative diseases such as pterygiums and terrien's marginal degeneration may also be responsible.
Traumatic causes of CNV include ulceration, alkali burns, and stem cell deficiency.
One of the most common causes of corneal neovascularization is iatrogenic pathology from extended contact lens wear. This is especially likely with lenses made with older hydrogel materials such as HEMA (2-hydroxyethyl methacrylate) for both daily and extended wear. Such older hydrogel materials have a relatively low oxygen transmissibility so the cornea becomes starved of oxygen; this leads to the ingress of blood capillaries into the clear cornea, in an attempt to provide more oxygen to the affected area. Older estimates cite 128,000 to 470,000 cases of lens-induced CNV each year, but this may be decreasing due to the increasing popularity of daily disposable lenses.
The risk for CNV is elevated in certain instances for patients following penetrating keratoplasty without active inflammation or epithelial defects. For example, the condition is more likely to occur in those with active blepharitis, those who receive sutured knots in their host stromas, and those with a large recipient area.
Pathogenesis
The in-growth of new blood vessels is mediated by the upregulation of angiogenic cytokines. The enzyme metalloproteinase degrades the cornea's basement membrane and extracellular matrix, while proteolytic enzymes allow vascular epithelial cells to enter the stromal layer of the cornea.
When ocular inflammation occurs, corneal epithelial and endothelial cells, macrophages and certain inflammatory cells produce angiogenic growth factors, namely vascular endothelial growth factor (VEGF) and fibroblast growth factors. VEGF paves the way for new blood vessel formation by upregulating matrix metalloproteinases production by endothelial cells in the limbal vascular plexus.