What is the treatment for corneal graft rejection vs failure?

Treatment of Corneal Graft Rejection vs Failure

Corneal graft rejection requires immediate aggressive corticosteroid therapy (topical, periocular, and systemic) to potentially reverse the process, while graft failure—whether primary or late—generally necessitates regrafting as the definitive management. 1

Corneal Graft Rejection: Aggressive Immunosuppression

The cornerstone of rejection treatment is early, aggressive corticosteroid therapy using multiple routes of administration. 1

Immediate Treatment Protocol

• Topical corticosteroids: Prednisolone acetate 1% hourly as first-line therapy 2, 3
• Periocular corticosteroids: Sub-Tenon or subconjunctival injections for severe cases 1
• Systemic corticosteroids:
  • Intravenous methylprednisolone 500 mg single pulse therapy shows superior outcomes compared to oral prednisone, particularly when treatment begins within 8 days (92.3% vs 54.5% graft survival) 3
  • Oral prednisone 60-80 mg daily is an alternative, though less effective 3

Critical Timing Considerations

Early presentation (≤8 days) dramatically improves outcomes with pulse IV corticosteroids, achieving >90% graft survival versus approximately 55% with oral therapy alone. 3 This emphasizes the importance of patient education regarding rejection warning signs: redness, photophobia, vision changes, and pain. 1

High-Risk Patient Modifications

For patients with recurrent inflammation history (herpes simplex keratitis, herpes zoster ophthalmicus, uveitis), standard protocols require augmentation with higher daily corticosteroid doses or oral antiviral agents. 1

Long-Term Prophylaxis

Maintaining patients on long-term low-dose topical corticosteroids (0.1% fluorometholone three times daily) significantly reduces rejection episodes after penetrating keratoplasty, with proven efficacy and minimal adverse effects. 4 However, monitor for steroid-induced IOP elevation and infectious crystalline keratitis. 1

Graft Failure: Regrafting as Definitive Management

Primary Graft Failure

Primary graft failure occurs when donor tissue fails to clear within the first 8 weeks postoperatively (4 weeks for endothelial keratoplasty) in the absence of other causative factors. 1

• Etiology: Inadequate endothelial cell function from damaged endothelium, insufficient cell numbers, or problems with corneal selection/processing/storage 1
• Management: Regrafting is generally required 1
• Important distinction: Excess surgical trauma causing persistent edema is not typically classified as primary graft failure; in EK, consider upside-down graft placement 1

Late Graft Failure

Late graft failure develops years after transplantation due to progressive endothelial cell loss, often accelerated by prior rejection episodes, infections, traumatic iritis, or elevated IOP. 1

• Contributing factors: Prior rejection reactions, infections, elevated IOP, surgical trauma, anterior chamber shallowing from wound dehiscence 1
• Management: Regrafting when visual function deteriorates significantly 1

Key Clinical Distinctions

Rejection is Potentially Reversible; Failure is Not

Rejection represents an active immunologic process that may respond to aggressive immunosuppression if caught early, whereas graft failure reflects irreversible endothelial dysfunction requiring tissue replacement. 1

Recognition of Rejection Signs

• Epithelial rejection: Rejection line/ridge with or without subepithelial infiltrates 1
• Stromal rejection: Stromal edema 1
• Endothelial rejection: Pigmented keratic precipitates, endothelial rejection line, anterior chamber reaction, corneal edema 1
• Note: Signs may be subtle or absent in endothelial keratoplasty cases 2

Common Pitfalls to Avoid

Never delay treatment while awaiting definitive diagnosis—early intervention within 8 days is critical for rejection reversal. 3 The difference between 92% and 55% graft survival hinges on this timing.

Do not prematurely discontinue topical corticosteroids in non-high-risk cases. Long-term low-dose maintenance (0.1% fluorometholone) prevents rejection without significant adverse effects. 4

Monitor all patients on chronic topical corticosteroids for IOP elevation through regular measurements, cup-to-disc ratio assessment, visual field testing, and OCT imaging of the retinal nerve fiber layer. 1

Rejection is the most frequent cause of corneal graft failure overall, making prevention through appropriate long-term immunosuppression and patient education paramount. 1