Objective

To assess the trends in microbiological organisms identified from corneal scrapings from patients with infectious keratitis at a tertiary care medical centre in South India.

Methods

We reviewed the records of the microbiology laboratory at Aravind Eye Hospital in Madurai, India, from 2002 until 2012. We identified the microbiological causes of all corneal ulcers from the culture and smear results, and assessed for trends in bacterial and fungal keratitis over time.

Results

Of 23 897 corneal patients with ulcer with a corneal smear from 2002 to 2012 a fungal organism was identified in 34.3%, a bacterial organism in 24.7% and no organism in 38.3%. During this period, the annual number of keratitis cases due to bacteria decreased from 677 to 412, and the annual number due to fungus increased from 609 to 863. In analyses accounting for the total number of outpatients seen each year, the decline in number of smears positive for bacteria was statistically significant (p<0.001) but the increase in the number positive for fungus was not (p=0.73). The relative frequency of individual bacterial or fungal organisms remained relatively stable over this time.

Conclusions

At a tertiary eye care centre in South India, there has been a reduction in the numbers of smear-positive bacterial keratitis over the past 11 years. This decline likely reflects economic development in India and increased access to antibiotics.

Aims

To report trends in antibiotic resistance in cases of bacterial keratitis from a large eye hospital in South India.

Methods

In this retrospective cross-sectional study, the microbiology laboratory records of patients with infectious keratitis diagnosed at an eye hospital in South India from 2002 to 2013 were reviewed to determine the proportion with antibiotic non-susceptibility.

Results

3685 bacterial isolates had susceptibility testing performed over the 12-year period. The two most common organisms with resistance were Streptococcus pneumoniae (n=1204) and Pseudomonas aeruginosa (n=894). Antibiotic non-susceptibility was generally uncommon for these two organisms and no significant trends were detected over the course of the study. In contrast, Staphylococcus aureus (N=211) isolates demonstrated a significant increase in fluoroquinolone non-susceptibility over the 12-year study period. This coincided with a significant increase in methicillin-resistant S. aureus (MRSA) during the study period, though the increase in fluoroquinolone resistance was likewise seen in methicillin-sensitive S. aureus (MSSA). For example, ofloxacin resistance in MSSA increased from 11.1% in 2002 to 66.7% in 2013 (p=0.002). No trends were apparent for the aminoglycosides, cefazolin or vancomycin, for which in vitro non-susceptibility generally appeared to be low.

Conclusion

Resistance to antibiotics was generally stable for infectious keratitis isolates from a large eye hospital in South India, except for S. aureus, which experienced a significant increase in fluoroquinolone resistance from 2002 to 2013. Fluoroquinolone antibiotics currently have poor in vitro activity against both MRSA and MSSA in South India and are therefore not the ideal therapy for Staphylococcal corneal ulcers.

Purpose

To determine the intra-observer and inter-observer reliability of a novel ocular staining score among trained ophthalmologists.

Design

Reliability analysis within a prospective, observational, multicenter cohort study.

Methods

Those enrolled in the National Institutes of Health-funded Sjögren's International Collaborative Clinical Alliance (SICCA) who presented for follow-up at the University of California San Francisco, Aravind Eye Hospital, Johns Hopkins University, and the University of Pennsylvania were included. Study participants were graded using the ocular staining score by at least 2 masked SICCA-trained ophthalmologists. The primary outcome for this study was the intraclass correlation coefficient (ICC) for the total ocular staining score. ICCs were also calculated for tear break-up time (TBUT) and conjunctival and corneal staining.

Results

Total ocular staining score had an ICC of 0.91 for the right eye (95% confidence interval [CI] 0.85-0.96) and 0.90 for the left eye (95% CI 0.83-0.97). Corneal staining (right eye 0.86, 95% CI 0.76-0.93, left eye 0.90, 95% CI 0.81-0.95) and conjunctival staining (right eye 0.87, 95% CI 0.80-0.93, left eye 0.85, 95% CI 0.75-0.93) demonstrated excellent agreement. The ICC for TBUT was slightly lower (right eye 0.77, 95% CI 0.64-0.89; left eye 0.81, 95% CI 0.68-0.90).

Conclusions

Previous studies have shown that the ocular staining score is correlated with other diagnostic components of Sjögren syndrome. In this study, we demonstrate high reliability in grading among trained ophthalmologists, completing the validation of this test.

Purpose

We described the change in visual acuity experienced by eyes successfully treated for bacterial keratitis.

Methods

This was a prospective cohort study of a subset of study participants who had previously enrolled in the Steroids for Corneal Ulcers Trial (SCUT). All study participants had been diagnosed with culture-proven bacterial keratitis before enrollment in SCUT and subsequently were randomized to adjunctive topical corticosteroids or placebo. During SCUT, we monitored study participants at enrollment, 3 weeks, 3 months, and 12 months. We invited a subset to complete a comprehensive eye examination approximately 4 years after enrollment in SCUT. Certified refractionists assessed best spectacle-corrected visual acuity (BSCVA) using the same protocol at each study visit.

Results

We examined 50 SCUT participants at 4 years after enrollment. Among those in this cohort, mean logMAR BSCVA at enrollment was 0.85 (Snellen equivalent, 20/160; 95% confidence interval [CI], 0.71-0.99). On average, visual acuity improved by 2.9 logMAR lines from enrollment to 3 weeks (P < 0.001), 1.2 lines from 3 weeks to 3 months (P = 0.002), and 0.8 lines from 3 to 12 months (P = 0.01). The BSCVA did not change significantly between 12 months and 4 years (0.04-line improvement, P = 0.88). After controlling for visual acuity at enrollment, BSCVA was not significantly different between the corticosteroid and placebo groups at 4 years (P = 0.53).

Conclusions

Cases of bacterial keratitis may continue to demonstrate improvements in visual acuity up to 12 months following diagnosis, but further improvements are unlikely. These findings may guide the appropriate timing of surgical intervention in these patients. (ClinicalTrials.gov number, NCT00324168.).

Importance

Scarring from bacterial keratitis remains a leading cause of visual loss.

Objective

To determine whether topical corticosteroids are beneficial as an adjunctive therapy for bacterial keratitis if given early in the course of infection.

Design, setting, and participants

The Steroids for Corneal Ulcers Trial (SCUT) was a randomized, double-masked, placebo-controlled trial that overall found no effect of adding topical corticosteroids to topical moxifloxacin hydrochloride in bacterial keratitis. Here, we assess the timing of administration of corticosteroids in a subgroup analysis of the SCUT. We define earlier administration of corticosteroids (vs placebo) as addition after 2 to 3 days of topical antibiotics and later as addition after 4 or more days of topical antibiotics.

Main outcomes and measures

We assess the effect of topical corticosteroids (vs placebo) on 3-month best spectacle-corrected visual acuity in patients who received corticosteroids or placebo earlier vs later. Further analyses were performed for subgroups of patients with non-Nocardia keratitis and those with no topical antibiotic use before enrollment.

Results

Patients treated with topical corticosteroids as adjunctive therapy within 2 to 3 days of antibiotic therapy had approximately 1-line better visual acuity at 3 months than did those given placebo (-0.11 logMAR; 95% CI, -0.20 to -0.02 logMAR; P = .01). In patients who had 4 or more days of antibiotic therapy before corticosteroid treatment, the effect was not significant; patients given corticosteroids had 1-line worse visual acuity at 3 months compared with those in the placebo group (0.10 logMAR; 95% CI, -0.02 to 0.23 logMAR; P = .14). Patients with non-Nocardia keratitis and those having no topical antibiotic use before the SCUT enrollment showed significant improvement in best spectacle-corrected visual acuity at 3 months if corticosteroids were administered earlier rather than later.

Conclusions and relevance

There may be a benefit with adjunctive topical corticosteroids if application occurs earlier in the course of bacterial corneal ulcers.

Purpose

To perform a Bayesian analysis of the Mycotic Ulcer Treatment Trial I (MUTT I) using expert opinion as a prior belief.

Methods

MUTT I was a randomized clinical trial comparing topical natamycin or voriconazole for treating filamentous fungal keratitis. A questionnaire elicited expert opinion on the best treatment of fungal keratitis before MUTT I results were available. A Bayesian analysis was performed using the questionnaire data as a prior belief and the MUTT I primary outcome (3-month visual acuity) by frequentist analysis as a likelihood.

Results

Corneal experts had a 41.1% prior belief that natamycin improved 3-month visual acuity compared with voriconazole. The Bayesian analysis found a 98.4% belief for natamycin treatment compared with voriconazole treatment for filamentous cases as a group (mean improvement 1.1 Snellen lines, 95% credible interval 0.1-2.1). The Bayesian analysis estimated a smaller treatment effect than the MUTT I frequentist analysis result of 1.8-line improvement with natamycin versus voriconazole (95% confidence interval 0.5-3.0, P = 0.006). For Fusarium cases, the posterior demonstrated a 99.7% belief for natamycin treatment, whereas non-Fusarium cases had a 57.3% belief.

Conclusions

The Bayesian analysis suggests that natamycin is superior to voriconazole when filamentous cases are analyzed as a group. Subgroup analysis of Fusarium cases found improvement with natamycin compared with voriconazole, whereas there was almost no difference between treatments for non-Fusarium cases. These results were consistent with, though smaller in effect size than, the MUTT I primary outcome by frequentist analysis. The accordance between analyses further validates the trial results. (ClinicalTrials.gov number, NCT00996736.).

Purpose

To compare the clinical course of Nocardia species keratitis with keratitis resulting from other bacterial organisms and to assess the effect of corticosteroids as adjunctive therapy using data collected from the Steroids for Corneal Ulcers Trial.

Design

Subgroup analysis of a randomized controlled trial.

Methods

setting: Multicenter randomized controlled trial. study population: Five hundred patients with bacterial keratitis randomized 1:1 to topical corticosteroid or placebo who had received at least 48 hours of topical moxifloxacin. intervention/observation procedure: Topical prednisolone phosphate 1% or placebo and clinical course of Nocardia keratitis. main outcome measures: Best spectacle-corrected visual acuity and infiltrate or scar size at 3 months from enrollment.

Results

Of 500 patients enrolled in the trial, 55 (11%) had a Nocardia corneal ulcer. Patients with Nocardia ulcers had better presentation visual acuity compared with non-Nocardia ulcers (median Snellen visual acuity, 20/45, compared with 20/145; P < .001) and comparable 3-month visual acuity (median, 20/25, vs 20/40; P = .25). Nocardia ulcers had approximately 2 lines less of improvement in visual acuity compared with non-Nocardia ulcers (0.21 logarithm of the minimal angle of resolution; 95% confidence interval, 0.09 to 0.33 logarithm of the minimal angle of resolution; P = .001). This difference may reflect the better starting visual acuity in patients with Nocardia ulcers. In Nocardia ulcers, corticosteroids were associated with an average 0.4-mm increase in 3-month infiltrate or scar size (95% confidence interval, 0.03 to 0.77 mm; P = .03).

Conclusions

Nocardia ulcers responded well to treatment. They showed less overall improvement in visual acuity than non-Nocardia ulcers, but had better presentation acuity. Corticosteroids may be associated with worse outcomes.

Bacterial keratitis is a leading cause of visual impairment worldwide. However, the natural history of treated bacterial keratitis has not been well characterized. We performed a secondary analysis of the Steroids for Corneal Ulcers Trial (SCUT; clinicaltrials.gov #NCT00324168) to better characterize the rate of visual acuity improvement after successful antimicrobial treatment.

Purpose

To describe temporal trends in Pseudomonas aeruginosa resistance to moxifloxacin in keratitis isolates from South India.

Methods

The Steroids for Corneal Ulcers Trial (SCUT) was a randomized, double-masked, placebo-controlled trial assessing outcomes in patients with culture positive bacterial corneal ulcers randomized to receive prednisolone phosphate or placebo. All patients received moxifloxacin, and susceptibility to moxifloxacin was measured at baseline using Etest. We investigated trends in moxifloxacin susceptibility of P. aeruginosa during 2007, 2008, and 2009 isolated in SCUT in South India.

Results

There were 89 P. aeruginosa isolates during 2007, 2008, and 2009 in SCUT that were eligible for this study. There was an increase in the proportion of resistant isolates from 19% in 2007 to 52% in 2009 (p = 0.02, χ(2) test for trend). Logistic regression showed that there was a 2-fold increase in odds of resistance per 1 year increase during the study period (odds ratio 2.16, 95% confidence interval 1.09-4.26, p = 0.027).

Conclusions

We found a sharp increase in the proportion of isolates that were resistant to moxifloxacin from 2007 to 2009. Further work needs to be done to characterize the nature of this increase.

Purpose

To determine risk factors and clinical signs that may differentiate between bacterial, fungal, and acanthamoeba keratitis among patients presenting with presumed infectious keratitis.

Design

Hospital-based cross-sectional study.

Methods

We examined the medical records of 115 patients with laboratory-proven bacterial keratitis, 115 patients with laboratory-proven fungal keratitis, and 115 patients with laboratory-proven acanthamoeba keratitis seen at Aravind Eye Hospital, Madurai, India, from 2006-2011. Risk factors and clinical features of the 3 organisms were compared using multinomial logistic regression.

Results

Of 95 patients with bacterial keratitis, 103 patients with fungal keratitis, and 93 patients with acanthamoeba keratitis who had medical records available for review, 287 (99%) did not wear contact lenses. Differentiating features were more common for acanthamoeba keratitis than for bacterial or fungal keratitis. Compared to patients with bacterial or fungal keratitis, patients with acanthamoeba keratitis were more likely to be younger and to have a longer duration of symptoms, and to have a ring infiltrate or disease confined to the epithelium.

Conclusions

Risk factors and clinical examination findings can be useful for differentiating acanthamoeba keratitis from bacterial and fungal keratitis.