The goal of this clinical trial is to learn if adjunctive topical Cyclosporine A eye drops combined with standard of care topical Natamycin treatment improves vision outcomes in patients with fungal keratitis.

This is a randomized, masked, clinical trial of patients with documented fungal infections of the cornea. In this trial participants are treated with (standard of care) topical natamycin for a minimum of 48 hours and then randomized in a 1:1:1 ratio to receive either topical Cyclosporine A (CsA) 0.1%, or CsA 2%, or placebo for 4 weeks. Natamycin will be continued until the corneal ulcer has resolved. The primary outcome of this pilot trial is best corrected visual acuity (BCVA) at 3 months. The specific aims of this trial are to:

• to determine if early use of topical cyclosporine A is a beneficial adjuvant to natamycin in the treatment of mild to moderate fungal keratitis.
• to determine if adjunctive 2% cyclosporine A demonstrates greater efficacy than 0.1% cyclosporine A in the treatment of fungal keratitis.
• to determine which ulcer characteristics, predict the most benefit from the addition of early topical cyclosporine.

In this study the investigators will partner with their cornea colleagues at the Aravind Eye Hospital. This is because the incidence of fungal corneal ulcers is among the highest in the world in this location.

Inclusion Criteria:

• Inclusion is based on presenting acuity, not ulcer size.
• Inclusion of 20/40 = 6/12 = 0.3 Log MAR and 20/400 = 3/60 = +1.3 Log MAR.
• Smear or culture positive for fungal keratitis, any length.
• Age 18 years.
• Willing to participate in study.

Exclusion Criteria:

• Co-infection with bacterial or viral keratitis.
• Corneal perforation.
• Requiring therapeutic keratoplasty for fungal keratitis.
• Unwilling or unable to follow up (e.g., living too far from hospital).
• Presenting acuity better than 20/40 = 6/12 = 0.3 Log MAR or worse than 20/400 = 3/60 = +1.3 Log MAR.
• Subjects taking cyclosporine at any concentration on presentation.
• Acuity worse than 20/200 = 6/60 = +1.0 Log MAR in unaffected eye.
• Pregnant women.
• Penetrating Keratoplasty.
• Presents with a 0-7 day history of topical steroid.

The treating and examining doctors and all participants will be masked to the identity of the medication in each group. The study drug will be labeled A, B ,C D, E, F with two letters to each treatment group. The only people who will not be masked is the pharmacist at Pondicherry who relabels the medications with the study drug code and maintains the master key of which drug belongs to which study label, the data analyst responsible for generating the randomization code, and a United States study coordinator who is responsible for relabeling protocol and training. The study coordinator at Aravind will not be informed of the master key but will be aware of the study drug allocation name as he/she will be dispensing study drug to the participant. The study coordinator at Aravind will review the drops with the patient each visit. The participants will be informed to not show the examining doctor any of the medications. The study doctors will not ask to see the study medications.