Combined Corneal Cryotherapy and Conjunctival Flap for Adjuvant Treatment of Medically Resistant Acanthamoeba Keratitis: A Case Series

Technical Summary: Combined Corneal Cryotherapy and Conjunctival Flap for Medically Resistant Acanthamoeba Keratitis

Problem Statement
Refractory infectious keratitis caused by Acanthamoeba or fungal organisms presents a significant therapeutic challenge. Prolonged intensive topical and systemic antimicrobial regimens often result in severe pain, poor patient compliance, and failure to halt disease progression. When maximal medical therapy fails, the standard surgical intervention is therapeutic keratoplasty (penetrating or lamellar). However, performing keratoplasty on an actively infected cornea carries elevated risks, including recurrent infection, the need for additional grafts, and guarded visual prognosis due to inflammation and surface instability. There is a critical need for globe-sparing strategies that can eradicate infection and stabilize the ocular surface prior to optical reconstruction.

Methodology
This retrospective case series examined three patients (two with Acanthamoeba keratitis and one with mixed Acanthamoeba/Fusarium keratitis) treated at a tertiary referral center. All patients had demonstrated disease progression despite at least six weeks of intensive topical and systemic antimicrobial therapy.

The intervention involved a combined surgical approach:

1. Corneal Cryotherapy: Applied to the ulcer margins and bed using overlapping double freeze–thaw cycles targeting temperatures of −40°C or below. The goal was full-thickness treatment to disrupt microbial structures (specifically fungal hyphae and Acanthamoeba trophozoites).
2. Conjunctival Flap: A partial or complete flap was harvested from the superior bulbar conjunctiva, with care taken to preserve limbal stem cells. The flap was sutured to the cornea (8-0 Vicryl) and secured with fibrin tissue adhesive. Amniotic membrane was applied to the harvest site.
3. Adjunctive Measures: In one case, stromal injection of voriconazole was performed. Postoperative management included tailored continuation of topical and systemic antimicrobials (e.g., PHMB, chlorhexidine, voriconazole, miltefosine) based on clinical response.

Key Contributions
The paper describes a specific surgical protocol for "salvage" treatment in cases where medical management has failed. The primary contribution is the demonstration that combining targeted cryotherapy with a vascularized conjunctival flap can control infection and alleviate pain without immediate enucleation or therapeutic keratoplasty. The authors position this technique as a bridge to later optical keratoplasty, allowing the infection to be eradicated and the ocular surface to stabilize before vision-restoring surgery is attempted.

Results
All three cases demonstrated the following outcomes:

• Infection Control: The combined approach led to the resolution of infection in all eyes. Microbiologic confirmation (PCR and pathology) in the postoperative period showed no evidence of viable organisms.
• Symptom Relief: Substantial improvement in pain occurred within days of the procedure for all patients.
• Surgical Outcomes: No eyes required enucleation or exenteration. All patients subsequently underwent successful optical penetrating keratoplasty (PKP) within two months of the initial cryotherapy/flap procedure.
• Visual Acuity: All eyes recovered useful vision, with final best-corrected visual acuity ranging from 20/25 to 20/60.
  • Case 1: 20/25 (with scleral contact lens) at 4-year follow-up.
  • Case 2: 20/40 (with spectacles) at 1-year follow-up.
  • Case 3: 20/40 (with spectacles post-cataract surgery) at 6-month follow-up.

Significance and Claims
The authors claim that combined corneal cryotherapy and conjunctival flap placement represents a useful salvage option for refractory infectious keratitis. The technique offers a "globe-sparing" alternative that achieves infection control and ocular preservation, thereby permitting subsequent successful optical keratoplasty.

The paper notes that while cryotherapy alone may not eliminate resistant cystic forms of Acanthamoeba, the combination with continued anti-amoebic agents and the vascular support of the conjunctival flap appears effective. The authors emphasize that this approach reduces reliance on patient compliance with painful drop regimens and provides immediate pain relief. They explicitly state that this is an adjuvant treatment for medically resistant cases, not a replacement for conventional therapy, and acknowledge limitations including the small sample size, retrospective nature, and lack of standardized pain assessment. The study reinforces the viability of this combined strategy for preserving the globe in severe, drug-resistant infections.