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Corneal Graft Rejection

URGENT — Cornea

Symptoms

Decreased vision (often the first sign).

Mild pain, redness, and photophobia.

History of corneal transplantation (months to years prior).

May be asymptomatic; detected during routine follow-up.

Clinical Findings

Endothelial rejection

  • Khodadoust line (pathognomonic): A line of keratic precipitates (KPs) sweeping across the donor endothelium.
  • Keratic precipitates localized specifically to the donor endothelium.
  • Stromal and/or epithelial edema.

Stromal rejection

  • Krachmer spots: Subepithelial infiltrates.
  • Localized stromal neovascularization.

Epithelial rejection

  • Irregularly elevated epithelial rejection line.

Other clinical signs

  • Circumcorneal conjunctival injection.
  • Anterior chamber (AC) inflammation (cell and flare).
  • Neovascularization extending to or onto the graft.
  • Broken or loose graft sutures.

Etiology

Immune mechanism

  • Host immune response against donor corneal antigens; endothelial rejection is the most visually threatening form.

Risk factors

  • Prior graft failure, corneal neovascularization, or large/eccentric grafts.
  • Active inflammation at time of surgery or pediatric recipient.

Triggers

  • Loose/broken sutures or suture-related neovascularization.
  • Intercurrent illness, trauma, recent surgery, or non-compliance with steroid regimen.

Red Flags

Khodadoust line → active endothelial rejection; requires aggressive therapy within 24 hours.

New stromal edema, subepithelial infiltrates, or AC reaction in a grafted eye.

Sudden decreased vision or redness in a transplant patient → rejection until proven otherwise.

Treatment delay >1–2 weeks significantly reduces the chance of graft survival.

Investigations

Clinical history

  • Time since transplant and original surgical indication (e.g., HSV).
  • Current medication compliance and recent changes in steroid frequency.

Slit-lamp exam

  • Search for the Khodadoust line and localized KPs.
  • Document Krachmer spots, edema, and neovascularization.
  • Evaluate suture integrity and check for signs of infection.

Microbiology

  • If suture infection is suspected: Remove suture and send for smears/cultures.

Treatment

Endothelial rejection (intensive)

  • Topical: Prednisolone acetate 1% q1h or Difluprednate 0.05% q2h while awake.
  • Ointment: Dexamethasone 0.1% at bedtime.
  • Systemic: Oral Prednisone 40–80 mg daily (tapered based on response).
  • Hospitalization: For high-risk/severe cases, consider IV Methylprednisolone 500 mg (1–3 doses).

Epithelial & stromal rejection

  • Topical steroids: Required, though typically less frequent than for endothelial forms.

Adjunctive care

  • Cycloplegia: Cyclopentolate 1% tid for comfort and AC inflammation.
  • IOP Control: Manage elevated intraocular pressure as needed.
  • Immunosuppression: Topical Cyclosporine (0.05–2%) as an adjunct for treatment or prevention.

Special considerations

  • Suture Infection: Remove suture, culture, and start intensive antibiotics; reduce steroid frequency.
  • HSV History: Start or increase suppressive oral antiviral therapy.

Clinical Pearl

Corneal graft rejection is an ophthalmic emergency. The Khodadoust line (endothelial KPs) is pathognomonic. Intensive steroids started within 24 hours can often reverse the process and salvage the graft.

Differential Diagnosis

  • Suture abscess or microbial keratitis
  • Epithelial downgrowth (scalloped border, non-responsive to steroids)
  • Elevated IOP with secondary epithelial edema
  • Late endothelial decompensation
  • Recurrent disease (e.g., HSV or dystrophy)

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