AbstractPurposeTo compare topical cyclosporine‐A 2% eye drop (Cs‐A) with prednisolone acetate 1% eye drop for treatment of herpetic stromal keratitis (HSK).MethodsIn this randomized clinical trial, 38 eyes of 33 patients with HSK were randomly assigned to receive either 2% Cs‐A or 1% prednisolone acetate eye drops. All subjects received oral acyclovir 400 mg twice a day. Slit‐lamp examination, Scheimpflug tomography corneal optical densitometry (Pentacam®, Oculus Inc., Wetzlar, Germany), best‐corrected visual acuity (BCVA), and intra‐ocular pressure (IOP) were evaluated at the first visit, and 14 and 30 days after the treatment.ResultsWithin‐group analysis revealed significant improvement of total cornea optical density after 30 days of treatment in both groups (30.3 ± 10.5 to 28.3 ± 9.8, p < 0.001 for prednisolone group, and 30.5 ± 8.8 to 28.8 ± 8.3 p < 0.001 for Cs‐A group, mean ± SD). We were not able to disclose any significant difference between the two groups regarding the improvement of cornea optical density (p = 0.66). Best‐corrected visual acuity (BCVA) logMAR significantly improved in both groups after 30 days of treatment (0.20 ± 0.52, p = 0.002 in prednisolone group, and 0.24 ± 0.31, p < 0.001 in Cs‐A group, mean ± SD). Analysis between groups did not show a significant difference of BCVA improvement (p = 0.45). We did not observe any severe side effect attributable to drugs.ConclusionsCs‐A 2% and prednisolone acetate 1% topical eye drops are effective for treatment of HSK.