Femtosecond Laser-assisted Corneal Debridement for Herpes Simplex Keratitis

• FLDEB (Procedure), also known as Femtosecond laser-assisted corneal debridement: 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.
• Ganciclovir (GCV) (Drug): Patient will be treated with GCV orally (200mg, 3 times a day, for 14 days).
• Femtosecond laser (Device): A commercial femtosecond laser to create a particular shaped graft for transplantation.

Primary outcomes

• Healing time [14 ± 1 days]: Time to complete corneal epithelial healing

Secondary outcomes

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

Sex: All, ages: 18 Years to 80 Years

Inclusion Criteria:

1. Aged between 18 and 80 years old;
2. Epithelial ulceration in a dendritic or geographic pattern, characteristic of infection with herpes simplex virus, and within 7 days of onset;
3. Ulcer's stromal involvement < 120 micron, as indicated by anterior segment optical coherence tomography;
4. 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:

1. Clinical signs of a cause other than herpes simplex virus for the epithelial keratitis;
2. Antivirus or corticosteroid treatment within 6 months;
3. Active stromal keratitis or iritis;
4. History of allergy or adverse reaction to ganciclovir;
5. High myopia with a spherical equivalent of -15.0 D or less;
6. Corneal or ocular surface infection within 30 days prior to study entry;
7. Ocular surface malignancy;
8. Uncontrolled diabetes with most recent Hemoglobin A1c greater than 8.5%;
9. Renal failure with creatinine clearance< 25ml/min;
10. Alanine aminotransferase > 40IU/L, or aspartate aminotransferase > 40IU/L;
11. Platelet levels < 150,000 or > 450,000 per microliter;
12. Hemoglobin < 12.0 g/dL (male) or < 11.0 g/dL (female);
13. 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;
14. Pregnancy (positive test) or lactation;
15. Participation in another simultaneous medical investigation or clinical trial;
16. Severe cicatricial eye disease; Conjunctival scarring with fornix shortening;
17. Severe dry eye disease as determined by Schirmer's test < 2mm at least in one eye;
18. 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;
19. Active immunological diseases;
20. History of allo-limbal transplantation, penetrating keratoplasty or anti-glaucoma filtering surgeries.

• Yizhi Liu, M.D.Ph.D., Principal investigator, Zhongshan Ophthalmic Center, Sun Yat-sen University
• Ting Huang, M.D.Ph.D., Principal investigator, Zhongshan Ophthalmic Center, Sun Yat-sen University