Pediatric Microbial Keratitis in Taiwanese Children: A Review of Hospital Cases

Objective  To study the clinical and microbiological characteristics of pediatric microbial keratitis in Taiwan.

Methods  The medical records of 81 eyes with microbial keratitis in 78 children aged 16 years or younger who were diagnosed and treated at Chang Gung Memorial Hospital, Taipei, Taiwan, from July 1, 1998, through December 31, 2002, were retrospectively reviewed. Predisposing factors, microbial culture results, clinical course, and visual outcomes were analyzed.

Results  Predisposing factors were contact lens wear (33 cases [40.7%]), trauma (17 cases [21.0%]), ocular disease (12 cases [14.8%]), and systemic disease (9 cases [11.1%]). Eight of the 33 contact lenses were rigid gas-permeable lenses that were worn overnight for orthokeratology. Forty-seven (58.0%) of the 81 eyes were culture positive. The most common isolates were Pseudomonas aeruginosa (21 eyes [44.7%]) and Staphylococcus aureus (9 eyes [19.1%]). Twelve (14.8%) of the 81 eyes required surgical intervention. Of the 68 eyes that had a best-corrected visual acuity available at the last follow-up, 33 eyes achieved best-corrected visual acuity of 20/25 or better.

Conclusions  Predisposing factors for pediatric infectious keratitis vary with age. In the teenage years, the most predominant risk factor is contact lens wear. Infectious keratitis resultant from overnight orthokeratology lenses should receive particular attention. Parents of children who consider overnight orthokeratology should evaluate the benefit of temporary myopia reduction and the risk of infection. Identification of predisposing factors and microorganisms may be helpful for early recognition and treatment of pediatric microbial keratitis.

Microbial keratitis is a serious, vision-threatening disease. Although the incidence of pediatric keratitis is low among cases of microbial keratitis,¹ it is of serious concern in children. In this patient population, amblyopia can result from severe corneal infection. The diagnosis and treatment of microbial keratitis in children are complicated by children's inability to provide complete information and to cooperate during examination and treatment.

Only a few studies^1-5 from the United States and India have been published on the clinical resolution of microbial keratitis in children. The purpose of this study was to review the characteristics of pediatric microbial keratitis including predisposing factors, clinical features, causative microbial pathogens, treatment modalities, and visual outcomes at our institution to provide background information and to facilitate future prevention and treatment of pediatric microbial keratitis.

A retrospective review of medical records of microbial keratitis cases that occurred in children (defined as being aged ≤16 years) who had an initial examination at Chang Gung Memorial Hospital, one of the largest tertiary medical centers in northern Taiwan, from July 1, 1998, through December 31, 2002, was conducted. The records were identified by a computer-based search of diagnosis codes. Inpatient and outpatient cases were included in this study. All of the collection of data for the study was in conformity with all country laws.

The criteria for inclusion in the study were a diagnosis of microbial (nonviral) keratitis based on microbiologic investigations and clinical findings including a corneal epithelial defect and stromal infiltrate. Those patients in whom topical antibiotics were administered before referral with negative culture results were included if the clinical findings were consistent with the diagnosis of an infectious ulcer.

The medical records were reviewed using a standardized protocol with particular emphasis on factors that predisposed a patient to corneal infection. Clinical evaluation included visual acuity (VA) assessment (when possible) and slitlamp biomicroscopy examination to determine the size and location of corneal infiltrates as well as the presence of hypopyon. Smears and cultures from corneal scrapings for bacteria, mycobacteria, and fungi were performed in all of the patients. Using standard techniques, the scrapings were inoculated in blood, chocolate, and modified Sabouraud agars, Lowenstein-Jensen agar slants, and thioglycolate broth. Culturing for Acanthamoeba was performed as indicated by clinical appearance or patient history.

To treat bacterial keratitis, a combination of topical cefazolin sodium (25 mg/mL) and amikacin (25 mg/mL) or ciprofloxacin (0.3%) alone was administered hourly. Subsequent modifications in antibiotic treatment were made according to the culture results, sensitivity testing results, and clinical response. For fungal keratitis, an hourly topical application of natamycin (5%) or amphotericin B (0.15%) was used to treat Fusarium or Candida infection, respectively. Topical polyhexamethylene biguanide and brolene were used for Acanthamoeba keratitis.

If data were available, visual outcome was recorded as VA using Snellen letter charts. For analysis, Snellen VA was converted to the logarithm of the minimum angle of resolution VA. A standard schedule was used to allocate the logarithm of the minimum angle of resolution VA for counting fingers, hand movements, light perception, and no light perception.⁶

Statistical analysis was performed by χ² and t tests to compare the mean differences between groups. Linear stepwise regression was used to determine factors associated with final visual outcome. Statistical significance was defined as P<.05. SPSS statistical software version 12 (SPSS, Inc, Chicago, Ill) was used for statistical analysis.

Seventy-eight patients (36 male and 42 female) were included in this retrospective study. The right eye was involved in 40 cases and the left in 41, with simultaneously bilateral infection in 3 patients. The median and mean ages of the patients were 10 and 10.3 years, respectively (range, 7 months to 16 years). The age distribution is shown in the Figure. For the purpose of comparison, all of the patients were divided into 2 age groups: 45 eyes in group 1 (ages ≤12 years) and 36 eyes in group 2 (ages >12 years). No significant difference was noted in sex between the 2 groups (P = .50).

Identifiable factors that contributed to the development of a microbial infection were detected in 76 of 81 eyes. The most prominent predisposing factor for pediatric microbial keratitis was contact lens wear, which was associated in 33 (40.7%) of the cases. Other predisposing factors included trauma (17 cases [21.0%]), ocular disease (12 cases [14.8%]), systemic illness (9 cases [11.1%]), and previous ocular surgery (5 cases [6.2%]) (Table 1).

There was significant difference between the 2 groups in the predisposing factors (P<.001). For the patients in group 1, ocular disease and trauma showed significantly (P = .04) and marginally (P = .05) greater chance to predispose to microbial keratitis, respectively. The most common and significant risk factor was contact lens wear for the patients in group 2 (P<.001). More specifically, in all cases except 1 (a 7-year-old boy wearing a therapeutic contact lens to treat corneal abrasion), soft contact lens–related corneal ulcers occurred in adolescence. The prevalence of trauma was distributed among all of the ages. Ocular and systemic diseases were important risk factors for microbial keratitis in very young and preschool-aged children.

The location of the corneal ulcers, as defined by the centration of the corneal infiltrate, was central in 37 (45.7%) of the 81 eyes, paracentral in 32 eyes (39.5%), and peripheral in 12 eyes (14.8%). The area of infiltrate was small (<2 mm) in 49 (60.5%) of 81 eyes, medium (2-6 mm) in 30 eyes (37.0%), and large (>6 mm) in 2 eyes (2.5%). Hypopyon was present in 10 eyes (12.3%). Two perforations were present in 2 eyes on admission to the hospital. There was no significant difference between the 2 groups in the pattern of clinical pictures (P = .65).

General anesthesia was required in 8 (9.8%) of 81 eyes to acquire corneal scrapings. Four patients underwent surgical intervention, such as removal of preexisting corneal sutures, at which time culture specimens were obtained. Four patients who were younger than 2 years required general anesthesia to obtain specimens for culture.

Forty-seven (58.0%) of the 81 eyes included in this study yielded positive cultures. Seven (14.9%) of the 47 culture-positive scrapings were polymicrobial. Fifteen (31.9%) of 47 culture-positive eyes and 24 (70.6%) of 34 culture-negative eyes were treated previously with antibiotics.

Pseudomonas aeruginosa was the most commonly isolated organism (21 cases [44.7%]), followed by Staphylococcus aureus (9 cases [19.1%]). Overall, gram-negative bacilli composed 69.0% (32 cases) of all bacterial isolates, and gram-positive cocci accounted for 36.2% (17 cases) of the isolates. Less common findings were fungi (3 cases [6.4%]), gram-positive bacilli (1 case [2.1%]), and Acanthamoeba (1 case [2.1%]). The rate of isolation of gram-positive bacteria was significantly higher in group 1 patients (P = .01). Group 2 patients (aged >12 years) had a marginally greater chance to acquire a gram-negative bacilli infection when compared with group 1 patients (aged ≤12 years) (P = .05). The variety of bacteria isolated and identified in the positive scrapings is summarized in Table 2.

The spectrum of organisms varied depending on the risk factors (P<.001). Rates of isolation of gram-positive and gram-negative bacteria were similar for some risk factors such as trauma and ocular and systemic diseases. However, gram-negative bacteria rather than gram-positive bacteria were isolated more frequently in contact lens wearers (Table 3).

All of the study patients were treated with fortified or empirical antimicrobials. Twelve (14.8%) of the 81 patients required surgical intervention. Of these 12 patients, the following procedures were performed: trichiasis correction (3 patients), suture removal owing to abscess (2 patients), tarsorrhaphy (2 patients), traumatic flap wound irrigation with antibiotic wash (1 patient), amniotic membrane transplantation (2 patients), therapeutic penetrating keratoplasty (1 patient), and a patch graft (1 patient).

Best-corrected VA (BCVA) of the study patients was recorded in 68 eyes at the time of the last follow-up examination, which ranged from 3 to 44 months following initial examination. Four patients (6 eyes) were lost to follow-up examination because of severe systemic diseases, and 7 other children were unable to cooperate with VA evaluations. Thirty-three eyes had BCVA of 20/25 or better, 16 eyes had BCVA between 20/30 and 20/40, 11 eyes had BCVA between 20/40 and 20/200, and 8 eyes had BCVA worse than 20/200. Of the 22 children who were not older than 8 years and had recordable vision, 11 were at risk for amblyopia. There was no significant difference in final VA (logarithm of the minimum angle of resolution) between the 2 groups (independent sample t test, P = .98). Features seen in patients with a poor vision outcome included polymicrobial infection, fungal infection, systemic disease, and ocular disease.

Microbial keratitis occurs infrequently in childhood. In one article¹ about all cases of microbial keratitis in southern California, pediatric keratitis composed 11% of the cases. In our study, pediatric keratitis composed 13.1% of all cases of infectious keratitis (data not shown). In those patients with keratitis, children differ from adults in many ways, including difficulty in patient examination, level of inflammation, difficulty in administering topical medications, and risk of amblyopia. The results of published studies on pediatric microbial keratitis are summarized in Table 4. The average age of patients in our study seems to be higher than that of other studies except the study by Cruz et al.²

Trauma has been implicated as the leading cause of childhood microbial keratitis.^1-5 However, contact lens wear rather than trauma was the leading predisposing factor in our study.

The higher proportion of contact lens–related infection in our series may be explained by the relatively high prevalence of myopia and the popularity of contact lens use by adolescents in Taiwan. Although we tried to obtain information about the lens material (brand and type) and the cleaning regimen and solutions, the data were unfortunately not available. Most of the 33 contact lens wearers claimed they did not use correct disinfectant with their lenses or wore the lenses overnight. Most Taiwanese children who start to wear soft contact lenses are junior high school students aged approximately 13 years. Thus, it is paramount to instill in children the importance and habit of proper contact lens hygiene.

Conversely, it is noteworthy that 8 of 33 contact lens wearers were enrolled in a program of overnight orthokeratology. There was no significant difference in the culture results and final visual outcomes between the patients with soft contact lenses and orthokeratology, but the patients with overnight orthokeratology were younger than those with soft contact lenses (Table 5). Overnight orthokeratology is gaining popularity for the treatment of myopia in children because good vision can result without the aid of glasses or contact lenses in the daytime. Another reason for its popular use among children is that some parents often have the false belief that orthokeratology itself can halt or even reverse the progression of myopia, which is especially appealing given the high prevalence of myopia in children in Taiwan. Infectious keratitis associated with overnight orthokeratology may be related to a disrupted epithelial surface secondary to the compressive forces of the reverse geometry lenses and may be aggravated by a relatively compromised ocular surface from overnight lens wear.⁷ To our knowledge, there are no data so far about whether infectious keratitis occurs with greater frequency in patients with orthokeratology than in other contact lens wearers or the general population, but we believe that the potential for the vision-threatening complication of infectious keratitis should not be overlooked.^8-12

Ocular and systemic diseases, which may affect ocular surface integrity, were significant predisposing factors in pediatric corneal ulceration in this and other series.^1-5 Pediatricians and physicians should be alerted to this problem and need to closely monitor these patients.

The prevalence of different organisms responsible for microbial keratitis varies in different regions of the world.^13-15 In general, there is an increased prevalence of pseudomonal and fungal infections in southern latitudes (Taiwan is located in the subtropical zone). Staphylococcal and streptococcal infections tend to occur in cooler northern climates. The organisms isolated in the pediatric population have a distribution similar to that seen in the adult population.^1-5

In our study, P aeruginosa was the most common isolate (21 culture-positive cases [44.7%]). Similar results have been reported in studies from southern California and Florida.^1,2 Other studies conducted in New Orleans, La, Philadelphia, Pa, and India have reported a markedly lower prevalence of P aeruginosa.^3-5 The reason for the dominance of P aeruginosa infection in our study may not reflect its geographical prevalence but rather that contact lens wearers accounted for 33 (40.7%) of the cases. P aeruginosa is the most predominant pathogen of contact lens–related corneal ulcers,^16-18 as we found in our study (Table 3).

Differences in the spectrum of causative organisms were found between age and risk factor groups (Table 2 and Table 3). Gram-positive and gram-negative bacteria seemed to be equally responsible for microbial keratitis associated with trauma and ocular and systemic diseases. Adequate culture acquisition and broad-spectrum antibiotic coverage are necessary while handling such an infection. Gram-negative bacteria (particularly Pseudomonas and Serratia species) were associated with contact lens wear, which was the most predominant risk factor for microbial keratitis in teenagers.

Our 58.4% recovery rate in bacterial cases seen in corneal cultures is almost the same as the recovery rate found in a study from India⁴ but is lower than the recovery rates found in other studies of pediatric corneal ulceration.^1-3,5 We believe that the main cause of our low positive-culture rate is the frequent use of antibiotics before referral. With the introduction of empirical topical antibiotics such as fluoroquinolones, more patients are apt to receive antibiotic therapy before specimens are collected for culture. In addition, we scraped the cornea to take a specimen for smear first, which might reduce the bacterial load remaining in the corneal lesion. Thus, the small amount of culture material available in corneal ulcer samples may not produce enough organism growth, especially in the small corneal ulcers.

In our study, 49 eyes (60.5%) had small ulcers. This observation contrasts with other studies that commonly document centrally located, moderately sized ulcers.^1-5 Because we included both inpatients and outpatients, there might have been more mild cases. It is important to distinguish noninfectious corneal infiltrates from microbial keratitis, especially in patients with small ulcers. In our series, a moderate amount of pain, an overlying epithelial defect, surrounding corneal edema, or anterior chamber reaction in the patients with small corneal ulcers suggested the diagnosis of infectious keratitis.¹⁹ However, it is difficult to assess the degree of pain and the reliability of slitlamp examination results in young children. Thus, it is important to obtain corneal scrapings for cultures in young children with corneal ulcerations before antimicrobial therapy is initiated. Many physicians assume that it is difficult to obtain corneal specimens from children. However, chloral hydrate sedation (50-100 mg/kg of body weight) or mild restraint can allow for specimen retrieval.³ If necessary, examination under general anesthesia should be done to examine children adequately and obtain cultures.

All of the eyes in this study were treated with topical fortified or empirical antimicrobials. In pediatric patients with microbial keratitis who resist treatment or in children who have inadequate antibiotic levels owing to crying, some researchers have suggested repeated subconjunctival injections under sedation instead of topical antimicrobial application.^1,20 However, in our experience as well as reports by others researchers, most ulcers (including those in children aged <3 years) could be treated successfully with topical antibiotics alone.^2-4 The rate of surgery (12 cases [14.8%]) in our patients was similar to the rates reported in other comparable studies.^1-5

In our study, poor visual outcome was associated with systemic disease, ocular disease, polymicrobial infection, and fungal infection. As previously described, ocular and systemic diseases had more predominant associations with microbial keratitis in young children (aged ≤7 years) in this study. In addition, microbial keratitis related to ocular disease had a greater chance of being a polymicrobial infection (Table 3). The sequelae of corneal ulceration in early childhood would put the children at risk for anisometropia or stimulus-deprivation amblyopia, which may lead to permanent visual impairment. The visual prognosis for fungal keratitis has usually been reported as poor.^13-15,21,22

Fong et al²¹ conducted a 10-year study of microbial keratitis mainly affecting the adult population in Taiwan. They found that contact lens-related pseudomonal keratitis was the most common form of microbial keratitis in Taiwan, which is similar to our results in pediatric patients. Parmar et al²² from India divided the patients with microbial keratitis into 3 groups: a pediatric group, an elderly group, and a control group between 17 and 64 years of age. They found that microbial keratitis in pediatric patients was more likely to have a bacterial cause, nonsevere ulcers, and a better chance of resolution with medical therapy alone when compared with that in the general adult population. Our results seem to have a similar trend, although we did not have a control group.

This study is limited by its retrospective design because of variations in the protocol with different physician preferences, and there are the inherent flaws of VA at the last follow-up as an outcome measure. This study is also limited by the inclusion criteria because only 47 (58.0%) of the keratitis cases were culture-proven keratitis. Microorganisms can be isolated in approximately 40% to 80% of cases even under ideal conditions^1-8; this recovery rate plummets with antibiotic pretreatment. Both culture-positive and culture-negative cases were included in our series so as not to bias the epidemiologic data. There are other acknowledged limitations. Our cases may have been more difficult because our hospital is a referral center, a factor that might bias the analysis of clinical characteristics and risk factors. Finally, this study included both inpatients and outpatients, which is different from other studies of childhood microbial keratitis.^1,2,4,5 However, this patient inclusion criterion is similar to the patient selection of another study.³ Nevertheless, this patient selection criterion might influence data interpretation.

To our knowledge, this study represents the first case series review of microbial keratitis in children to be published in 5 years and is the second largest study in this field. Our findings indicate that the predisposing factors for childhood infectious keratitis change with age. The most predominant risk factor was contact lens wear. About one fourth of contact lens–related corneal ulcerations were associated with overnight orthokeratology, a result worthy of special attention given the increased popularity of overnight orthokeratology. Eye care practitioners who perform overnight orthokeratology have an obligation to warn their patients of this potential vision-threatening complication. Part of this obligation entails educating patients about the importance of strict adherence to proper contact lens hygiene.

The findings concerning the nature of and risk factors for pediatric microbial keratitis in Taiwan, particularly with respect to the prevalence of the various causative organisms in this study, may provide important background information to aid in the prevention of vision-threatening complications. Although a thorough eye examination, adequate culture acquisition, and initiation of therapy are difficult in younger children, these measures should not be compromised. With early diagnosis and proper management and treatment, a good visual outcome is possible in children with microbial keratitis.

Correspondence: Samuel C. M. Huang, MD, Department of Ophthalmology, Chang Gung Memorial Hospital, No. 199, Tung-Hwa North Road, Taipei, Taiwan (huangsam@ms9.hinet.net).

Submitted for Publication: July 23, 2006; final revision received September 28, 2006; accepted October 8, 2006.

Financial Disclosure: None reported.