spp have historically been a relatively rare cause of bacterial keratitis, the incidence of Nocardia
spp keratitis may be increasing, especially in India.15
Previous case series from South India have shown that Nocardia
spp were responsible for a small proportion of bacterial ulcers, however in SCUT, Nocardia
was the third most commonly-isolated organism.5,16
Prior reports have evaluated outcomes in Nocardia
keratitis in a retrospective manner, and no information is available on the utility of corticosteroids for this type of keratitis. In this prospective subanalysis of a clinical trial, we found that Nocardia
keratitis generally had good outcomes, but the use of corticosteroids resulted in larger infiltrate/scar sizes, suggesting they may not be appropriate for treating this disease. Additionally, treatment with fluoroquinolones as monotherapy in two-thirds of cases resulted in good median visual acuity (approximately 20/25), despite having variable in vitro
Overall, patients did not have a high degree of vision loss at enrollment (approximate Snellen equivalent 20/40), and outcome visual acuity was good (approximate Snellen equivalent 20/25). Nocardia
keratitis cases had significantly less improvement at 3 months in visual outcomes and infiltrate/scar size than ulcers due to all other bacteria. This indicates that there may not have been room for dramatic improvement, as seen in ulcers of other etiologies.11
We did not find any difference in baseline characteristics or clinical outcomes across species of Nocardia
. Patients with Nocardia
spp ulcers had a significantly delayed presentation compared to ulcers with non-Nocardia
ulcers. Despite this, infiltrate/scar size was almost identical in ulcers due to Nocardia
vs. other bacterial organisms, and visual acuity was significantly better at enrollment in Nocardia
ulcers. It is possible that the scars of Nocardia
spp ulcers may be less opaque or dense than non-Nocardia ulcers, but this was not assessed in this study.
The use of topical corticosteroids in bacterial corneal ulcers is controversial. Corticosteroids may reduce inflammation that can lead to ocular damage, however there is a risk that they may exacerbate the infection and cause corneal melting.17–20
The primary SCUT analysis found no overall difference in safety and efficacy between adjunctive corticosteroid therapy and placebo.16
The effect of topical corticosteroids on Nocardia
spp ulcers has not been previously well characterized. Case reports have suggested that topical corticosteroids may result in recurrence of the infection and prolonged healing time.21
In this study, we found that the use of adjunctive corticosteroids was associated with significantly larger infiltrate/scar sizes at 3 months in Nocardia
keratitis cases. There was no difference in visual acuity, time to re-epithelialization, or perforation between the corticosteroid and placebo arms. Epithelial healing may not be an appropriate indicator for improvement in Nocardia
keratitis, because the disease can progress despite epithelial defect healing. However, these findings suggest that caution should be taken when treating patients with presumed Nocardia
keratitis with corticosteroids.
There have been few reports in the literature about the response of Nocardia
keratitis to fluoroquinolones. In vitro
studies have shown that Nocardia
isolated from keratitis has variable susceptibilities to fluoroquinolones4,5
, and in this study, gatifloxacin had the best activity, followed by moxifloxacin. Nearly all isolates were susceptible to amikacin. It is not clear how Nocardia
keratitis responds clinically to treatment with fluoroquinolones. To date, studies of Nocardia
keratitis in vivo
have focused primarily on treatment with amikacin. In this study, all patients were started on moxifloxacin as the initial treatment per study protocol. Treating physicians were allowed to change or add antibiotics if they felt it was medically necessary. Approximately one third of patients had amikacin added to their moxifloxacin regimen, generally within the first week of treatment. Patients who had amikacin added to their treatment regimen had more severe ulcers at presentation, with worse visual acuity and larger infiltrate/scar sizes. They also had worse visual acuity outcomes, suggesting these are cases that were more difficult to treat. The cases that received only moxifloxacin steadily improved, but were less severe at presentation. These results suggest that for less severe Nocardia ulcers, moxifloxacin monotherapy may be a viable treatment option. However, no definitive conclusions about the efficacy of moxifloxacin for the treatment of Nocardia
keratitis can be drawn from this study, as this study was not designed to compare the efficacies of amikacin and moxifloxacin.
This study must consider several limitations. While Nocardia spp was the third most commonly-isolated organism during the course of the trial, only 55 samples were isolated, resulting in a small study sample size. There was a relatively small number of each Nocardia species, making comparisons between species difficult. Due to the small sample size, we are unlikely to have detected even a moderate effect on visual acuity. However, we did find a difference in infiltrate/scar size, showing that we did have sufficient power to detect this difference. As a subanalysis of a larger clinical trial, this study may suffer a selection bias resulting from the clinical trial's exclusion criteria, such as the exclusion of ulcers with a descemetocoele. Some excluded patients may have been Nocardia spp cases; no information was collected on patients who were excluded. However, because this study was part of a prospective, randomized, controlled trial, all patients followed a standardized treatment protocol and had standardized study measurements of visual acuity, infiltrate/scar and epithelial defect size at pre-specified time points. This methodology improves our ability to make a direct comparison in this subgroup to ulcers from other organisms, and allows us to assess the utility of corticosteroids in a rigorous manner. Although the use of corticosteroids resulted in worse infiltrate scar, this did not appear to affect visual acuity. However, it is possible that high contrast acuity may not disclose an adverse effect on visual function that might be revealed by other measures such as contrast sensitivity.
In this study, Nocardia spp ulcers improved less over the course of treatment compared to ulcers of other etiologies, but Nocardia ulcers may have had less room for improvement given that they presented with better visual acuity. The use of corticosteroids was associated with a worse infiltrate/scar size at 3 months. The susceptibility of isolates to fluoroquinolones was variable; however, cases that were treated only with moxifloxacin, which were in general less severe at presentation than those where amikacin was added, had good clinical outcomes, suggesting that moxifloxacin may be an acceptable treatment for such cases. Clinical outcomes in Nocardia keratitis generally are good, but there is no evidence that corticosteroids are of benefit in ulcers due to this organism, and in fact may result in worse outcomes.