What are the causes of corneal transplant (keratoplasty) rejection?

From the Guidelines

Corneal transplant rejection requires immediate treatment with intensive topical corticosteroids to prevent graft failure, as highlighted in the 2024 study on corneal edema and opacification preferred practice pattern 1. The first-line treatment typically involves prednisolone acetate 1% administered every 1-2 hours while awake for the first few days, then gradually tapered based on clinical response. For severe cases, oral prednisone (1 mg/kg/day) may be added for 3-5 days, as part of a comprehensive approach to manage rejection reactions, which are the most frequent cause of corneal graft failure 1. In cases resistant to steroids, topical cyclosporine 0.05% or tacrolimus 0.03% can be used as adjunctive therapy. Patients should immediately contact their ophthalmologist if they experience symptoms of rejection: redness, decreased vision, pain, or light sensitivity. Prevention is crucial, involving strict adherence to prescribed post-transplant medications, typically including topical steroids and antibiotics, and maintaining the patient on long-term topical steroid may reduce the risk of rejection, but the patient should be monitored for steroid-related pressure increase and infectious keratitis 1. Regular follow-up appointments are essential for early detection of rejection signs, especially in high-risk cases or those with a history of recurrent inflammation. The risk of rejection is highest in the first year after surgery but can occur at any time, which is why vigilance and prompt treatment are vital for preserving corneal clarity and vision. Key factors to consider in managing corneal transplant rejection include:

• Early aggressive treatment with topical, periocular, and systemic corticosteroids
• Identification of high-risk cases or those with a history of recurrent inflammation
• Maintaining the patient on long-term topical steroid to reduce the risk of rejection
• Monitoring for steroid-related complications such as pressure increase and infectious keratitis
• Regular follow-up appointments for early detection of rejection signs.

From the Research

Corneal Transplant Rejection

• Corneal transplant rejection is a significant concern in ophthalmology, with rejection being the leading cause of corneal graft failure 2.
• The use of immunosuppressive therapy is necessary to prevent graft rejection, with topical corticosteroids being the gold standard 2.
• Systemic immunosuppression with two or more agents may be helpful in preventing corneal graft rejection in high-risk patients 3.

Immunosuppressive Agents

• Corticosteroids are the most commonly used immunosuppressive agents, but they can induce glaucoma, cataract, infections, and epithelial defects 2.
• Cyclosporin has a specific effect on inhibiting interleukin-2 transcription and can effectively prevent graft rejection in high-risk recipients, but it may induce severe side effects 2.
• Mycophenolate mofetil and FK 506 are promising drugs, but their use is not routine in preventing corneal graft rejection 2.
• Systemic mycophenolate mofetil may reduce the risk of graft rejection, but its effect on clear graft survival is unclear 4.

Treatment Regimens

• The management of high-risk corneal transplantation is challenging and involves numerous measures, including the use of systemic immunosuppressive agents 5.
• In high-risk cases, corticosteroids alone may provide insufficient immunosuppression, and systemic cyclosporine may be needed in exceptional cases 6.
• Topical cyclosporin can effectively replace steroids in case of dexamethasone-induced glaucoma and graft infection, but it can also induce serious corneal epithelial defects 2.

Outcomes

• Clear graft survival and graft rejection are the primary outcomes in assessing the effectiveness of immunosuppressants in preventing corneal graft rejection 4.
• Visual acuity and quality of life are also important outcomes, but they are not always reported in studies 4.
• The current evidence on the effect of immunosuppressants in preventing graft failure and rejection after high- and normal-risk keratoplasty is largely low quality due to the limited number of trials and risk of bias 4.