Femtosecond Laser-assisted Corneal Debridement for Herpes Simplex Keratitis

Study Overview
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Brief Summary
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The purpose of the study is to learn if adding femtosecond laser-assisted corneal debridement to a standard therapy of oral ganciclovir can help shorten the healing time of herpes simplex epithelial keratitis (HSK).

Official Title
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A Randomized Controlled Clinical Trial of Corneal Debridement for the Treatment of Herpes Simplex Epithelial Keratitis

Conditions
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Herpes Simplex Keratitis

Intervention / Treatment
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* Procedure: FLDEB
* Drug: Ganciclovir (GCV)
* Device: Femtosecond laser


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged between 18 and 80 years old; Epithelial ulceration in a dendritic or geographic pattern, characteristic of infection with herpes simplex virus, and within 7 days of onset; Ulcer's stromal involvement < 120 micron, as indicated by anterior segment optical coherence tomography; Informed consent signed by patient or legal guardian. Having the ability to comply with study assessments for the full duration of the study. Exclusion Criteria: Clinical signs of a cause other than herpes simplex virus for the epithelial keratitis; Antivirus or corticosteroid treatment within 6 months; Active stromal keratitis or iritis; History of allergy or adverse reaction to ganciclovir; High myopia with a spherical equivalent of -15.0 D or less; Corneal or ocular surface infection within 30 days prior to study entry; Ocular surface malignancy; Uncontrolled diabetes with most recent Hemoglobin A1c greater than 8.5%; Renal failure with creatinine clearance< 25ml/min; Alanine aminotransferase > 40IU/L, or aspartate aminotransferase > 40IU/L; Platelet levels < 150,000 or > 450,000 per microliter; Hemoglobin < 12.0 g/dL (male) or < 11.0 g/dL (female); Prothrombin time > 16s and activated partial thrombin time > 35s in patients not accepting anticoagulant therapy; An international normalized ratio greater than 3 in patients accepting anticoagulant therapy; Pregnancy (positive test) or lactation; Participation in another simultaneous medical investigation or clinical trial; Severe cicatricial eye disease; Conjunctival scarring with fornix shortening; Severe dry eye disease as determined by Schirmer's test < 2mm at least in one eye; Any medical or social condition that in the judgement of the investigator would interfere with or serve as a contraindication to adherence to the study protocol or ability to give informed consent; Active immunological diseases; History of allo-limbal transplantation, penetrating keratoplasty or anti-glaucoma filtering surgeries.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FLDEB combined with GCV orally<br>Femtosecond laser-assisted cornea debridement (FLDEB) combined with ganciclovir (GCV) orally. | Procedure: FLDEB<br>* The eye will be anesthetized, and femtosecond laser technology will be used to remove epithelial tissue (diameter: 8mm; depth: 100micron) that includes the loosened diseased corneal epithelial cells. Antibiotic ointments and drops will be instilled postoperatively.<br>* Other names: Femtosecond laser-assisted corneal debridement;Drug: Ganciclovir (GCV)<br>* Patient will be treated with GCV orally (200mg, 3 times a day, for 14 days).<br>Device: Femtosecond laser<br>* A commercial femtosecond laser to create a particular shaped graft for transplantation.<br>|
| Active Comparator: GCV orally<br>Ganciclovir (GCV) orally only | Drug: Ganciclovir (GCV)<br>* Patient will be treated with GCV orally (200mg, 3 times a day, for 14 days).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Healing time | Time to complete corneal epithelial healing | 14 ± 1 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Corneal re-epithelization | Assessing complete corneal re-epithelization at day 14±1 using slit-lamp microcopy | 14 ± 1 days | 
| Corneal opacity and vascularization | Assessing corneal opacity and vascularization using slit-lamp microcopy | Baseline, 14 ± 1 days, 3 months | 
| Best-corrected visual acuity | Assessing best-corrected visual acuity using ETDRS chart | Baseline, 14 ± 1 days, 3 months | 
| Corneal power and astigmatism | Assessing changes of corneal power and astigmatism using autorefractor keratometer | Baseline, 14 ± 1 days, 3 months | 
| Corneal sensation | Assessing corneal sensation using Cochet-Bonnet esthesiometer | Baseline, 14 ± 1 days, 3 months | 
| Recurrence | Assessing recurrent HSK using slit-lamp microcopy | 3 months |