What are the indications for penetrating keratoplasty (PK), corneal graft, and amniotic membrane transplantation in keratitis?

Surgical Management of Keratitis: Indications for Penetrating Keratoplasty, Corneal Grafts, and Amniotic Membrane Transplantation

Amniotic membrane transplantation should be used first-line for complicated keratitis with corneal thinning or small perforations to stabilize the ocular surface and avoid urgent keratoplasty, while penetrating keratoplasty is reserved for large perforations, medical treatment failure, or when infection cannot be controlled. 1, 2

Amniotic Membrane Transplantation (AMT) Indications

Primary Indications

• Corneal stromal thinning without frank perforation to decrease inflammation and stabilize the ocular surface 1
• Small corneal perforations where the goal is to seal the defect and restore globe integrity 1, 3, 4
• Impending perforation in eyes with progressive corneal melting 1
• Cases refractory to medical treatment where you want to avoid emergency keratoplasty and improve prognosis of subsequent elective keratoplasty 1, 5

Timing and Technique

• Apply AMT 2-5 days after initiating topical antibiotics while continuing antimicrobial therapy throughout 1
• Use double-layer AMT for perforations with anterior chamber collapse; single-layer for non-perforated ulcers 1, 6
• Continue antifungal or antibacterial treatment during and after AMT as there is risk of persistent infection 6, 5

Expected Outcomes

• Improved visual acuity at 6 months (demonstrated in RCT for bacterial keratitis) 1
• Decreased pain postoperatively and reduced corneal opacity density (shown in Pseudomonas keratitis) 1
• Does NOT improve corneal healing time, hypopyon size/duration, or depth of opacity 1
• 75-100% complete epithelialization rate depending on whether infection is active or controlled 6

Penetrating Keratoplasty (PK) Indications

Absolute Indications

• Large corneal perforations that cannot be sealed with AMT or tissue adhesive 1, 2
• Medical treatment failure where infection cannot be controlled with antimicrobial therapy alone 2
• Deep stromal involvement where the infection extends through all corneal layers 1, 2
• Therapeutic indication for unresponsive microbial infection requiring removal of infected tissue 2

Tectonic Indications

• Frank perforation or imminent perforation when corneal integrity is severely compromised 2
• Extremely thin cornea where structural support is needed 1
• Progressive disease despite maximal medical therapy 1

Special Scenarios

• Combined anterior segment pathology requiring iris reconstruction, cataract removal, IOL exchange, or vitrectomy 1, 2
• Peripheral involvement extending beyond 7.5-9.0 mm requiring oversized or tectonic grafts 1, 2
• All infectious keratitis with perforation requires central large penetrating keratoplasty for anatomical cure 3

Contraindications

• Multiple prior failed full-thickness transplants indicate poor prognosis 2
• Extensive anterior segment scarring compromises surgical outcomes 2
• Active infection with inappropriate corticosteroid use (especially Nocardia or fungal) leads to poor outcomes 2

Lamellar Keratoplasty (DALK) Indications

When to Choose DALK Over PK

• Stromal scarring that does NOT involve Descemet membrane or endothelium 1
• Desire to avoid endothelial rejection (though stromal rejection still occurs in 2-12% of cases) 1

When DALK is Contraindicated

• Deep stromal scarring where perforation is likely during Descemet membrane separation - use PK instead 1, 2
• History of Descemet membrane rupture (spontaneous or surgical) 1
• When baring of Descemet membrane cannot be achieved - visual outcomes are inferior to PK 1

Clinical Algorithm for Surgical Decision-Making

Step 1: Assess Corneal Integrity

• No perforation, progressive thinning: Consider AMT first to stabilize and avoid urgent surgery 1, 5
• Small perforation (<2mm): AMT with double-layer technique 1, 3, 4
• Large perforation (>2mm): Proceed directly to PK 3

Step 2: Assess Infection Control

• Infection responding to medical therapy: AMT can be performed during active phase (culture-positive) with continued antimicrobials 6, 5
• Infection NOT responding after 7-10 days: Consider therapeutic PK to remove infected tissue 2, 7

Step 3: Assess Depth of Involvement

• Anterior/mid-stroma only: AMT or DALK if no perforation risk 1, 6
• Full-thickness involvement or endothelial compromise: PK required 1, 2

Step 4: Consider Timing

• Emergency setting with active inflammation: AMT to stabilize, then elective PK 3-12 months later when inflammation resolved 5
• Controlled infection, stable eye: Elective PK or DALK as appropriate 5

Critical Pitfalls to Avoid

• Do NOT use corticosteroids during active infection, especially with fungal or Nocardia keratitis, as this worsens outcomes 2
• Do NOT perform emergency PK in highly inflamed eyes if AMT can stabilize the situation first - emergency keratoplasty has worse prognosis due to immunologic rejection 5
• Do NOT stop antimicrobial therapy after AMT - continue treatment as risk of persistent/recurrent infection exists 6, 5
• Do NOT attempt DALK when deep stromal scarring present - high risk of Descemet rupture requiring conversion to PK 1, 2
• Send all removed corneal tissue for pathologic and microbiologic analysis during therapeutic keratoplasty 1

Adjunctive Measures

• Tissue adhesive with Tenon's patch graft and cyanoacrylate glue can manage larger perforations as alternative to immediate PK 1
• Conjunctival flap may be used in cases refractory to medical treatment 1
• Descemet's stripping endothelial keratoplasty is emerging as tectonic alternative for perforation 1
• Oral tetracyclines (doxycycline/minocycline) or N-acetylcysteine to inhibit matrix metalloproteinases and counteract stromal thinning, though limited data exists 1