Comparison Of Adjuvant 0.02% Chlorhexidine Gluconate With 1% Povidone-Iodine In The Management Of Fungal Keratitis: A Randomized Controlled Trial

Considering the scarcity of options for drugs in the management of fungal keratitis, there has always been a search for better alternative drugs are readily available, inexpensive and easy to formulate. We aimed to compare the efficacy of 1% povidone-iodine with 0.02% chlorhexidine gluconate as adjunctive treatment for fungal keratitis and to determine whether adjuvant therapy with these drugs is non-inferior to standard antifungal therapy.

This study was a randomized, controlled, single-blinded, non-inferiority, three-arm trial, conducted in the Cornea and Refractive surgery services of the Advanced Eye Center of the Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India

Participants with evidence of fungal infection on smear microscopy or in vivo confocal microscopy were randomized to receive either adjuvant 1% povidone-iodine (group 1), adjuvant 0.02% chlorhexidine (group 2) or standard antifungal therapy (group 3). The primary outcome measure was time to ulcer healing. Patients were assessed at baseline, day 3, 7, 14, 21, 60 and 90 for final best spectacle-corrected visual acuity (BSCVA) at 3 months, scar/infiltrate size, infiltrate depth, time to re-epithelization, microbiological cure rate, need for therapeutic penetrating keratoplasty and change in fungal hyphal density on in vivo confocal microscopy. 

Fifty-six cases of fungal keratitis were randomized to three groups and 48 patients with 16 patients in each group were included in the primary analysis. We found that there was no difference in time to ulcer healing in the groups after controlling for baseline epithelial size defect through Cox proportional hazards regression (hazard ratio: group 1-1.38, p=0.47, group 2- 2.07, p=0.08). There was no difference between the three groups for BSCVA at day 90 (p=0.56), change in ulcer size (p=0.94), time to re-epithelization (p=0.88), need for TPK (p= 0.25) and change in fungal hyphae density on IVCM (p=0.85). Only Group 2 showed statistically significant improvement in per cent epithelial defect size from baseline at follow-up (p<0.001). 

We found no significant difference in the time to ulcer healing, final BSCVA, time to re-epithelization, microbiological cure rate, or need for TPK in the groups. There was no benefit of adding 1% povidone-iodine to the standard antifungal therapy. It was observed that cases that received adjuvant 0.02% chlorhexidine gluconate showed significantly better improvement in ulcer dimensions from baseline, especially in the first week of therapy, likely suggesting that it appears to be effective in the initial “sterilization phase”. This could also indicate a possible synergistic effect of chlorhexidine with standard anti-fungal drugs by possibly increasing drug penetration into the infected cornea.