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Clinical science
Paediatric infectious keratitis: a case series of 107 children presenting to a tertiary referral centre
  1. Julia Dutra Rossetto1,2,
  2. Kara M Cavuoto1,
  3. Carla J Osigian1,
  4. Ta Chen (Peter) Chang1,
  5. Darlene Miller1,
  6. Hilda Capo1,
  7. Oriel Spierer1,3
  1. 1Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida, USA
  2. 2Department of Ophthalmology and Visual Sciences, Universidade Federal de São Paulo, Sao Paulo, Brazil
  3. 3Department of Ophthalmology, Tel Aviv Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
  1. Correspondence to Dr Oriel Spierer, Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, 900 NW 17th Street, Miami, Florida, 33136, USA; spierero{at}gmail.com

Abstract

Background/aims Corneal ulcers can result in severe visual impairment in children. The recent trends of paediatric microbial ulcerative keratitis in the USA are unknown. The purpose of this study is to report the risk factors, microbiological profile and treatment outcomes of paediatric microbial keratitis in South Florida.

Methods A university-based tertiary eye care centre retrospective case series between 1992 and 2015. Medical records of 107 paediatric patients (age <18 years) with the diagnosis of microbial ulcerative keratitis were analysed. Patient demographics, culture data, microbial susceptibility, management trends and patient outcomes were collected.

Results Mean age of patients was 13±4.6 years (range 0.2–17 years). The most common associated risk factor was contact lens wear (77.6%), followed by ocular trauma (8.4%). Systemic factors were present in 4.7% of cases. Cultures were taken from 89 patients. A total of 74 organisms were isolated from the 52 corneal scrapings with growth, yielding a 58.4% positivity rate. Seventeen microbial species were identified, with a predominance of Pseudomonas aeruginosa (46.2%), followed by Stenotrophomonas maltophilia (19.2%) and Fusarium (13.5%). Combined fortified antibiotics were the most common treatment (51.4%). Mean follow-up time was 40.6±91.6 weeks (range: 0.3–480 weeks). The mean visual acuity improved from 20/160 to 20/50 (p<0.0001). No therapeutic penetrating keratoplasty was needed.

Conclusions In this study, contact lens wear was the most frequent risk factor in infectious keratitis in children. P. aeruginosa was the most common microorganism present in our setting. The majority of the cases responded well to medical management.

  • Cornea
  • Infection
  • Microbiology
  • Contact lens
  • Child health (paediatrics)

https://doi.org/10.1136/bjophthalmol-2016-310119

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    Introduction

    Infectious keratitis is a serious cause of ocular morbidity in children as it can result in severe, permanent visual impairment. Microbial keratitis occurs less frequently in the paediatric population than in adults, with children accounting for approximately 13% of all cases.1 2 However, this disease has a greater impact on children, as they are at greater risk of irreversible ocular sequelae due to visual deprivation or anisometropia, with consequent amblyopia and lifelong visual impairment.2 3 Therefore, prompt diagnosis and treatment of microbial keratitis in children are of utmost importance. However, evaluation and management are often challenging in this age group due to poor cooperation for the ocular examination, culture collection and topical medication administration.

    Prior studies conducted in several countries have looked at the characteristics, risk factors and microbiological patterns of infectious keratitis. However, epidemiological patterns often vary according to the geographic location and population group, and may change over time.4 Currently, there is limited updated literature on the characteristics of paediatric microbial keratitis in the USA. The majority of previously published reports date back to the 1990s.1 5 6 In these reports, Pseudomonas aeruginosa was the most commonly isolated microorganism.1 5 The most frequent risk factors were trauma, prior ocular surgery, severe systemic illness and contact lens wear.1 5 6

    The present study analysed the patient characteristics, risk factors, microbiological profiles, management trends and treatment outcomes of microbial ulcerative keratitis in paediatric patients presenting to a university-based tertiary care centre in Florida.

    Materials and methods

    A retrospective review of medical and microbiological records was conducted at Bascom Palmer Eye Institute of all patients younger than 18 years with the diagnosis of microbial ulcerative keratitis between the years 1992 and 2015. This study was approved by the Institutional Review Board of the University of Miami Miller School of Medicine and complied with the principles outlined in the Declaration of Helsinki. The inclusion criteria included a clinical diagnosis of microbial keratitis, defined as the presence of a corneal stromal infiltrate with an overlying epithelial defect.7 Patients were excluded from the study if the diagnosis was viral or neurotrophic keratitis. The patients were identified using International Statistical Classification of Diseases 9 codes for keratitis (370 and subitems), and underlying condition such as Acanthamoeba (136.21) and Fusarium (118).

    Patient characteristics including age, sex, predisposing factors, clinical presentation, treatment, outcomes, visual acuity (VA) at presentation and last follow-up, pathogens and susceptibility profiles were recorded. VA in young infants was evaluated by light response (considered as 2.6 in logarithm of minimal angle of resolution (LogMAR) scale), ability to fix and follow a target (considered as 2.3 in LogMAR scale) or by preferential looking with Teller Acuity Cards. In older children, VA was measured using Allen pictures or a Snellen chart.

    Corneal scrapings were placed on a slide for Gram stain, plated on chocolate, blood and Sabouraud agars and were also inoculated in thioglycolate broth. An experienced microbiology personnel identified isolates according to standard laboratory criteria. A culture was considered positive when there was growth of more than 50 colonies on one solid media, 10–50 colonies on two (or more) media or 1–10 colonies on one solid media and positivity on smear/thioglycolate broth. A fungal growth was considered positive when there was a growth of the same fungus on two or more solid media, 2+ colonies on one media or 1+ colony on one media and positive smear/thioglycolate broth. All growth had to be on ‘C’ streaks, and a growth not on ‘C’ streaks was considered a contaminant. In addition, the microbiology laboratory database was searched for susceptibility profiles. Susceptibility tests were performed using a combination of Vitek 2 (automated system), E-strips (bioMérieux, Durham, North Carolina, USA) and disk diffusion.

    Statistical analysis

    Statistical analysis was performed with SPSS software V.22. Continuous variables were analysed using independent t-test and categorical values were analysed with Pearson’s χ2 test. VA results were converted to LogMAR values for analysis. Factors influencing change in VA between first visit and last follow-up were evaluated using Spearman’s correlation and linear regression analysis. Analyses were two-tailed and significance was set at the 5% level.

    Results

    Demographics

    A total of 108 eyes (45.8% right eye) of 107 patients were included. More than half of the patients (54.2%) were male. The mean age at presentation was 13±4.6 years (range 0.2–17 years).

    Clinical examination

    The mean time from onset of symptoms to presentation was 7±13 days (range 1–100 days). Mean VA at presentation was 20/160±20/125 (range 20/20 to light perception). In nearly half of the patients (45.7%), VA was 20/60 or better. In 32 (29.9%) patients, VA was worse than 20/200. There was no difference in the presenting mean VA between the contact lens wearers and the patients with other risk factors (p=0.85). The corneal infiltrate was central or paracentral in 96 (89.7%) patients at presentation. Hypopyon was present in 20 (18.7%) patients.

    Risk factors

    All patients had a unilateral ulcer at presentation except for one patient with a recent history of contact lens wear who presented with bilateral corneal ulcers, secondary to Acanthamoeba. Among the predisposing ocular factors, 83 (77.6%) patients were contact lens wearers. Nine (8.4%) patients presented with ocular trauma, corneal abrasion or recent history of a corneal foreign body. None of the patients had a history of penetrating keratoplasty.

    Predisposing systemic factors were present in five (4.7%) patients. Two (1.9%) patients had type 1 diabetes mellitus, one (0.9%) patient had acute myeloid leukaemia with chemotherapy treatment, one (0.9%) patient had juvenile rheumatoid arthritis treated with oral prednisone and one (0.9%) patient had a tooth decay one day preceding the ocular symptoms.

    Microbiology and antimicrobial susceptibilities

    Cultures were taken from 89 (82.4%) eyes. For the remaining 19 eyes, a corneal culture was not obtained due to documented low-risk features such as a small ulcer diameter (<1 mm) and/or a peripheral location. Cultures were positive for microbial growth in 52 (58.4%) cases. Patients with hypopyon had a slightly higher rate of positive cultures (65.0%). Multibacterial infection, defined as two or more bacterial strains in the same sample, was identified in 10 eyes (19.2% of the positive cultures). Of the 37 negative cultures, 25 (67.6%) eyes received topical antibiotic treatment prior to culture. Neither prior treatment (p=0.41) nor age (p=0.38) correlated with culture positivity.

    A total of 74 organisms were isolated from corneal scrapings, and 17 microbial species were identified (table 1). Gram-negative bacilli were predominantly recovered, with P. aeruginosa being the most common, followed by Stenotrophomonas maltophilia. Fungi, mainly Fusarium sp and Acanthamoeba sp were the third and fourth most common isolates, respectively.

    View this table:
    Table 1

    Distribution of bacterial isolates among 52 positive cultures

    A high antimicrobial susceptibility rate (87.1% to 95.7%) to fluoroquinolones, aminoglycosides and third-generation cephalosporins was found (table 2). Two methicillin-resistant Staphylococcus aureus isolates were identified. Both isolates were also fluoroquinolone-resistant but susceptible to vancomycin.

    View this table:
    Table 2

    Antimicrobial susceptibility for positive cultures

    Treatment

    Initial empirical treatment consisted of combined fortified antibiotics in the majority of cases (51.4%), with the most frequent combination being tobramycin with vancomycin (38.3% of all cases). Treatment with single agent such as a fluoroquinolone (30.8% of cases) was also a common approach. Fungal keratitis was present in 12 eyes and topical natamycin was the most common initial treatment. For Acanthamoeba keratitis, treatment included a combination of polyhexamethylene biguanide 0.02% and propamidine isethionate 0.1% eye drops.

    Change in empirical treatment was necessary in 34.6% of cases after microbiological results. Topical corticosteroids were added in 56 (52.3%) patients. The mean antibiotic treatment duration was 38±48 days (range 1–240 days).

    Clinical outcome

    The mean follow-up time was 40.6±91.6 weeks (range 0.3–480 weeks). VA on last follow-up visit was recorded for 99 (92.5%) patients. Of these, (81.8%) had a final VA of ≥20/60 and 10 (10.1%) had ≤20/200. Mean VA improved significantly from 20/160±20/125 on first visit to 20/50±20/80 (range 20/20 to light perception) on last follow-up (p<0.0001). Final VA correlated with presenting VA (Spearman’s ρ=0.541, p<0.001) and with age (Spearman’s ρ=−0.470, p<0.001), that is, older children had better VA at final visit than younger children. The correlations existed also after multiple linear stepwise regression analysis including risk factors and culture result (positive or negative) (p<0.001 for both presenting VA and age). Although there was no change in the presenting VA between patients with contact lens and other risk factors (ocular trauma, corneal abrasion and corneal foreign body) (p=0.85), patients with contact lens had a better final VA than patients with other risk factors (p=0.006; figure 1).

    Figure 1
    Figure 1

    Visual acuity at presentation and at final exam among children with infectious keratitis, with contact lens and with other risk factors. Other risk factors include ocular trauma, corneal abrasion and a recent history of corneal foreign body.

    None of the patients underwent therapeutic corneal transplantation (urgent corneal transplantation to save the globe). Two (1.9%) patients required later an optical penetrating keratoplasty for visual rehabilitation due to residual corneal scar. One patient, with a history of contact lens use, presented with a large central corneal ulcer, positive for P. aeruginosa. The keratitis resolved when treated with tobramycin, but resulted in a large central scar. The second patient had a history of left facial paralysis and lagophthalmos following brain tumour resection. He had a large central corneal ulcer, positive for coagulase-negative staphylococci and was treated with moxifloxacin and tarsorrhaphy.

    Nineteen (17.8%) patients were lost to follow-up or continued treatment with their referring ophthalmologist before full resolution of the infection.

    Discussion

    The current study looked at 107 children with microbial keratitis in South Florida. The main predisposing factor was contact lens use and the predominant pathogen was P. aeruginosa. We found that combined fortified antibiotics were the most frequent initial treatment and overall patients had good clinical outcomes with significant improvement in VA.

    In our study, contact lens use was the predominant risk factor (77.6% of patients), in accordance with recent reports from Asia.2 4 8 9 A National Electronic Injury Surveillance System research for medical device-associated adverse events among children reported that contact lens wear was the most frequent cause of keratitis, accounting for more than one-fifth of the cases.10 Severe keratitis secondary to contact lens wear has been increasing over time, with direct and indirect medical care costs estimated to be approximately US$1496 per case and an annual cost of US$58 million.11 The second most frequent risk factor, ocular trauma, was the inciting event in 8.4% of our patients, a much lower rate than previous North American reports (34%–44%).1 5 6 In these studies, ocular trauma as a risk factor for infectious keratitis was more prevalent in patients aged ≤3 years. As the majority of our patients were older, this may explain the lower rate of ocular trauma. Systemic risk factors accounted for approximately 5% of cases. This rate is lower than the 14%–27% rates, which were reported in previous studies.1 5 6 We speculate that the small number of microbial keratitis cases associated with systemic diseases stems from the nature of our institute being an outpatient referral centre as compared with an inpatient paediatric hospital.

    The mean time from onset of symptoms to presentation was 7 days. Nevertheless, our study had two patients who presented long after the onset of symptoms with one who presented after 60 days and the other after 100 days. Both were contact lens wearers who had smouldering symptoms and were treated by their local ophthalmologist. Only later in their clinical course they were referred to our institute and corneal cultures were obtained, revealing Acanthamoeba keratitis.

    The present report found a positive culture rate of 58.4%, comparable to Asian studies, which varied from 49% to 58%.2–4 12 13 Other studies looking at childhood microbial corneal ulcers in the USA reported a higher positive culture rate, ranging from 76% to 87%.1 5 6 A possible explanation is that a high percentage of patients (67.6%) received topical antibiotic treatment prior to obtaining cultures, which could inhibit microbial growth. In addition, limited cooperation may have reduced the bacterial load as cultures were obtained while the child was awake and unsedated.

    Our series showed a high incidence of P. aeruginosa (46.2%), fungal (23.1%) and Acanthamoeba (11.5%) isolates, all favoured both by the high index of contact lens use and Florida tropical climate, as previously seen in Taiwan and Hong Kong.2 4 9 P. aeruginosa and fungal keratitis are also associated with ocular trauma.1 3 5 12 14 An earlier study from Florida between the years 1980 and 1991 showed that the incidence of P. aeruginosa was 34% among children with infectious keratitis and that only 12% of corneal ulcers were related to contact lens wear.5 In the current report, contact lens wear was associated with 78.3% of infections. We hypothesise that this difference might be related to the increase in myopia prevalence.15 16 In contrast to our results in children, infectious keratitis in adults in South Florida has shown a trend of increased incidence of Staphylococcus aureus and a decreased incidence of P. aeruginosa.17

    Empirical monotherapy with fluoroquinolones in non-severe infectious keratitis is a reasonable option and may serve as first treatment of choice for many ophthalmologists.18 19 Non-fortified monotherapy treatment has less toxicity, high tolerability and promotes faster re-epithelialisation in comparison with fortified combined treatment.20–22 When the infiltrate is close to the visual axis or larger than 1–2 mm, a combination of fortified antibiotics against Gram-positive and Gram-negative bacteria is the recommended approach.8 23 In our centre, there is no official treatment protocol and each individual ophthalmologist defined the initial treatment. Combined fortified antibiotics followed by fluoroquinolones alone were the main treatment previous to microbiological profile release. The treatment was adequate for bacterial susceptibilities of our isolates, as shown by the high susceptibility rates (87% and higher) for fluoroquinolones, aminoglycosides and third-generation cephalosporins and by the favourable outcomes.

    Studies published in the 1990s reported that between 14% and 28% of paediatric infectious keratitis cases would eventually need surgical intervention for eye salvage or visual rehabilitation.1 5 6 Most recent reports showed this percentage to be much lower ranging from 0% to 6%,8 9 13 23 although one recent study reported 3 out of 16 paediatric patients who required surgical management.24 In the current study, none of the children needed urgent surgical treatment such as therapeutic penetrating keratoplasty or amniotic membrane application. Only 1.9% of patients required late optical corneal transplantation for visual rehabilitation. These encouraging outcomes are in agreement with most of recent studies.

    Few studies in children report initial VA and analyse visual improvement.8 13 Wong et al8 showed mean VA to improve from 20/36 to 20/27 in 26 patients with microbial ulcerative keratitis. Al Otaibi et al13 in a study of 45 children with keratitis reported that the number of patients with VA of ≥20/40 increased from 18 on initial examination to 28 on last follow-up exam. The current study, comprising >100 participants, found a significant VA improvement during follow-up period. VA of ≥20/60 was documented in 81 (81.8%) patients at the time of last follow-up as compared with 48 (46.2%) patients on presentation. In addition, older children had better VA at final visit than younger children. This might be explained, at least partially, by the assignment of light response and ability to fix and follow a target to LogMAR scale in the younger children.

    There are several limitations to the current study, including its retrospective nature. While the clinical characteristics of the corneal ulcer guided the management for each patient, different physicians may have implemented non-standardised treatment regimens and follow-up protocols. As our institute is a tertiary referral centre, patients may have followed-up with their referring physician, thus their full clinical course was not available for review. Despite these limitations, this report provides a relevant updated data regarding the risk factors, clinical characteristics and microbiology in paediatric infectious keratitis.

    Although a rare event, corneal ulcers in children can lead to permanent visual impairment. To our knowledge, this is the largest series describing paediatric corneal ulcer cases in the USA. Our series shows that with prompt evaluation, appropriate treatment and close monitoring, children may have an optimal response to medical treatment.

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    View Abstract

    Footnotes

    • Contributors Design and conduct of the study: JDR, KMC, CJO, TCC, DM, HC, OS; collection: JDR, KMC, CJO, OS, management: KMC, TCC, DM, HC, analysis and interpretation of the data: JDR, KMC, CJO, TCC, DM, HC, OS; preparation: JDR, KMC, CJO, OS, review: TCC, DM, HC and approval: JDR, KMC, CJO, TCC, DM, HC, OS of the manuscript.

    • Funding JDR: funded by CAPES Foundation, Ministry of Education of Brazil, Brasília, Brazil. KMC, TCC, DM and HC: supported by NIH Center Core Grant P30EY014801, Research to Prevent Blindness Unrestricted Grant.

    • Competing interests None declared.

    • Ethics approval Institutional Review Board of the University of Miami Miller School of Medicine.

    • Provenance and peer review Not commissioned; externally peer reviewed.

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