experimental studies [2]) revealed preexisting corneal blood vessels as strong(est) risk factor for subsequent immune rejections. In a recent meta-analysis of nearly 25,000 patients having undergone keratoplasty, we showed corneal neovascularization to be a significant risk factor for graft failure and rejection [18]. That risk increased with the number of corneal quadrants being affected by corneal neovascularization.

Summary for the Clinician

•Corneal (lymph)angiogenesis starts when the balance between proangiogenic and antiangiogenic factors in the cornea is shifted toward angiogenic growth factors.

•The most common clinical conditions associated with corneal angiogenesis are corneal inflammation (keratitis), hypoxia (contact lens), and limbal barrier defects (chemical burns).

•Corneal angiogenesis leads to reduced visual acuity by the physical presence of vessels itself, but also by leakage of water, lipids, and erythrocytes.

•Preexisting corneal blood and lymphatic vessels are a strong risk factor for subsequent immune rejections after keratoplasty.

The Importance of Corneal Hemand Lymphangiogenesis for Immune Reactions After Keratoplasty

Preexisting corneal blood vessels – as mentioned above – have long been identified as strong risk factors for immune rejection after keratoplasty [17]. But, until very recently, the role of the clinically invisible lymphangiogenesis as well as angiogenesis occurring only after keratoplasty was unclear [15, 19, 20].

Corneal Hemangiogenesis After Low-Risk Keratoplasty

More than 50 % of patients after low-risk keratoplasty (with preoperatively avascular corneas), postoperatively develop corneal angiogenesis within the first year [15]. New vessels are primarily located in the 6 °° and 12 °° position and tend to grow toward the outer suture turning points. In about 10 % of patients, these new vessels actually reach donor tissue. Experiments in the mouse model of low-risk keratoplasty recently have shown that these capillaries are always accompanied by biomicroscopically invisible lymph vessels [7, 9]. Indeed, experiments in the mouse model of low-risk keratoplasty recently identified postkeratoplasty neovascularization as a risk factor for subsequent immune rejections [7, 9]. An antihemand antilymphangiogenic therapy significantly improved graft survival after low-risk keratoplasty.