Pseudomonas aeruginosa Keratitis: Pathogen Genotype Impacts Clinical Presentation and Outcomes

Abstract

Purpose: : To assess how cytotoxicity and invasiveness, two P. aeruginosa virulence factors, affect corneal ulcer baseline characteristics and clinical outcomes.

Methods: : Clinical data and corneal isolates from the NEI-funded Steroids for Corneal Ulcers Trial (SCUT) investigating the effect of adjunctive topical corticosteroids for bacterial keratitis were used. P. aeruginosa isolates from the trial were genotyped using PCR for exotoxins U and S, which have been shown to confer the properties of cytotoxicity and invasiveness, respectively. Baseline characteristics including visual acuity, infiltrate/scar size, and location of ulcer were compared using a t-test or Fisher’s exact test. The main outcome measure compared was change in visual acuity at 3 months using Huber robust regression, with and without controlling for steroid treatment.

Results: : Fifty-six P. aeruginosa isolates with a classically invasive genotype and eighteen isolates with a classically cytotoxic genotype were analyzed. Mean baseline infiltrate/scar size was 4.66 and 3.61 mm for invasive and cytotoxic ulcers, respectively (p=0.049). When controlling for the effect of location, invasive ulcers presented with an approximately three and a half line better visual acuity (p=0.008). Invasive ulcers had approximately three and a half lines less improvement in visual acuity at 3 months compared to cytotoxic ulcers (p=0.03). Steroids were associated with approximately five and a half lines less improvement in the cytotoxic subgroup (p=0.07) but were associated with two and a half lines greater improvement in the invasive subgroup (p=0.04) compared to placebo.

Conclusions: : Ulcers caused by P. aeruginosa strains with the invasive genotype presented with better visual acuity; however, these ulcers were associated with significantly less improvement at 3 months compared to cytotoxic ulcers . Furthermore, steroids were associated with better outcomes for invasive P. aeruginosa corneal ulcers but worse outcomes for cytotoxic ulcers. These results suggest that a tailored treatment approach by subtype may be advisable for P. aeruginosa keratitis.

Keywords: pseudomonas • keratitis • microbial pathogenesis: clinical studies