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Year : 2023  |  Volume : 11  |  Issue : 2  |  Page : 81-86

Clinical and microbiological profile of pediatric infectious keratitis

1 Department of Cornea and Anterior Segment, CL Gupta Eye Institute, Moradabad, Uttar Pradesh, India
2 Department of Pediatric Ophthalmology, Strabismus and Neuro-Ophthalmology, CL Gupta Eye Institute, Moradabad, Uttar Pradesh, India
3 Department of Microbiology, CL Gupta Eye Institute, Moradabad, Uttar Pradesh, India
4 Department of Clinical Research, CL Gupta Eye Institute, Moradabad, Uttar Pradesh, India

Date of Submission26-Apr-2022
Date of Decision16-Nov-2022
Date of Acceptance08-Jan-2023
Date of Web Publication27-Apr-2023

Correspondence Address:
Ajit Kumar
Department of Cornea, Anterior Segment and Refractive Surgery, CL Gupta Eye Institute, Ram Ganga Vihar, Phase 2 (Ext), Moradabad - 244 001, Uttar Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcor.jcor_70_22

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Purpose: Corneal ulcers are more prevalent in tropical developing countries. The purpose of this study is to report the risk factors, microbiological profile, and treatment outcomes of infectious keratitis in children. Materials and Methods: Retrospective case series of 77 consecutive children aged 16 years or younger with a diagnosis of infectious keratitis treated at the cornea service of a tertiary eye care institute. Patient demographics, predisposing factors, microbial susceptibility, microbial smear and culture results, clinical course, and visual outcomes were analyzed. Results: The average age of patients was 9.1 years (range 8 days–16 years). The mean time from the onset of symptoms to the ophthalmological examination was 14.6 (18.9) days. The most common associated risk factor was ocular trauma (n = 32, 43%). A total of 32 (32/77, 42%) eyes were positive on the smear examination. Bacterial infection was reported in 30 (30/77, 39%) and fungal infection was reported in 9 (9/77, 12%) children. Staphylococcus was the most commonly isolated organism (13/39, 33%) followed by Streptococcus (9/39, 23%), Pseudomonas (6/39, 15%), and Fusarium spp. (6/39, 15%). Curvularia spp. was also identified in 3 (3/39, 8%) eyes. Nineteen (19/77, 25%) children require surgical intervention. Therapeutic penetrating keratoplasty was needed in two children. Conclusion: Contrary to previous reports, bacteria are more frequent etiological organisms than fungi causing pediatric infectious keratitis in this study population. Staphylococcus spp. was the most predominant causative organism. Curvularia was not identified in previously reported studies from India. Most of the patients were managed medically. Surgical intervention was less frequent.

Keywords: Clinical profile, infectious keratitis, North India, pediatric population

How to cite this article:
Khurana A, Kumar A, Agarwal P, Sharma M, Chauhan L. Clinical and microbiological profile of pediatric infectious keratitis. J Clin Ophthalmol Res 2023;11:81-6

How to cite this URL:
Khurana A, Kumar A, Agarwal P, Sharma M, Chauhan L. Clinical and microbiological profile of pediatric infectious keratitis. J Clin Ophthalmol Res [serial online] 2023 [cited 2023 Jun 8];11:81-6. Available from: https://www.jcor.in/text.asp?2023/11/2/81/374873

Corneal infections are known to be one of the most significant preventable causes of vision impairment after an unoperated cataract.[1] It is more prevalent in tropical developing countries.[2] During the past decade studies from India and abroad have reported the etiology of corneal infections in different climates and geographical locations.[3],[4],[5],[6],[7],[8] The study of geographical patterns of corneal infection and their antibiotic sensitivity is helpful in making treatment decisions.

Infectious keratitis in children is uncommon. It is one of the major causes of ocular morbidity due to permanent vision loss. In younger children, it may lead to amblyopia secondary to corneal scarring.[9] Infectious keratitis in children has different risk factors, levels of inflammation, and complications than in adults. These differences lead to poor visual prognosis.[10],[11] The diagnosis and treatment of infectious keratitis in children are difficult due to less cooperative children during examination and treatment.[2] Many studies of microbial keratitis in children have been published by different authors.[2],[3],[4],[5],[6],[7] In the majority of previous studies published during the 1990s, bacteria were more commonly isolated than fungi.[12],[13] Straphylococcus species was the most commonly isolated bacteria.[12],[13] However, in recent reports, fungi were the more common infectious agent isolated in culture followed by bacteria.[5] Most of these studies are from south India and were published a decade ago.[5],[12],[13]

Few studies on infectious keratitis in the pediatric population have been reported from India.[1],[3],[4],[12],[13] However, there is no published report from Uttar Pradesh. Uttar Pradesh has been one of the most highly populated states in India. It has the highest number of disabled persons (16% of the total disabled in India).[14] This study represents the recent trends of microorganisms causing infectious keratitis, its management, and treatment outcomes in the pediatric population from Uttar Pradesh (India). The objective of this study was to investigate the characteristics of infectious keratitis in children including predisposing factors, clinical features, causative microbial pathogens, treatment modalities, and visual outcomes in patients up to 16 years of age.

  Materials and Methods Top

This study has been approved by the institutional ethics committee. The research adhered to the principles of the Declaration of Helsinki. This is a retrospective review of clinical records of patients with diagnoses of infectious keratitis presented to us between January 2015 and December 2020. Diagnosis of infectious keratitis was made on the basis of clinical findings and microbiologic investigations such as corneal epithelial defect and stromal infiltrate. Records of all patients of ≤16 years of age with the presence of corneal stromal infiltrate on slit-lamp examination and a corneal scraping at the time of examination were included in the analysis.

Demographic data, medical history, history of ocular trauma, nature of trauma, use of contact lens, duration of the disease, previous steroid use, associated comorbidities, systemic disease, previous ocular surgery, clinical presentation, initial and final visual acuity, medication use before and after diagnosis, and need for surgical therapy for every patient were recorded. All patients had a detailed clinical evaluation followed by corneal scraping. Corneal scraping was taken from the edge and base of the ulcer in every patient using 15 no blood pressure blades under topical (or general anesthesia if needed). All aseptic precautions were taken during the procedure. The material obtained on scraping was subjected to standard microbiology evaluation. If at the presentation, the patient was on antibiotics and there are visible infiltrates then scraping was done for culture without stopping antibiotics. Moreover, if there is no infiltrate the previous medication was stopped and scraping was done after 48 h. Scrapping was done on the day of the presentation if the patient was not on antibiotics.

Every child underwent a comprehensive ophthalmic examination, including but not limited to, presenting uncorrected distance visual acuity (CDVA) and pinhole CDVA, best-corrected visual acuity (BCVA), slit-lamp biomicroscopy examination to determine the size and location of corneal infiltrate, and indirect ophthalmoscopy and intraocular pressure. Whenever the child was noncooperative, examination under anesthesia with a handheld slit-lamp ophthalmoscopy was done. Maximum height and width were taken as the size of the infiltrate and central height of hypopyon measured using the slit beam of the slit lamp. Ulcer with a midpoint within 3 mm of the geometric center of the cornea was categorized as central, midpoints between 3 and 6 mm of the geometric center as paracentral, and the rest was categorized as peripheral.

Corneal scrapings were obtained from the base and edge of the ulcer using a sterile surgical blade (# 15 on a Bard Parker Handle) under topical anesthesia (0.5% proparacaine hydrochloride) and slit-lamp magnification. Gram stain and 10% of potassium hydroxide (KOH) mount were included as a part of the standard protocol for microscopic evaluation of corneal smears. Gram-stained smears were examined at ×400 and ×1000 magnification, and the KOH preparations were examined at ×200 and ×400 under a light microscope. Scrapings for smears were collected before those for culture. Cultures were taken on fresh blood agar, chocolate agar, Sabouraud's dextrose agar, thioglycollate broth, and brain–heart infusion broth. These media were incubated at 25°C and 37°C. Cultures were examined daily during the 1st week, twice weekly for the next 3 weeks, and discarded after 3–4 weeks if there was no growth. Criteria for culture positivity were the growth of the organism at the site of inoculation on two or more solid media, growth at the site of inoculation on one solid media of an organism consistent with microscopy, or confluent growth of the same organism on one solid media and one liquid media. The growth on media was then identified and where appropriate was subjected to an antimicrobial susceptibility test. Cultured bacterial isolates were subjected to antimicrobial susceptibility testing to a range of antibiotics commonly used in the treatment of corneal ulcers. Antibiotic susceptibility was done by disc diffusion Kirby–Bauer method as per the Clinical and Laboratory Standards Institute guidelines, which classify organisms as susceptible, resistant, or immediately susceptible to antibiotics. All microbiology workup was conducted by two technicians under the supervision of a microbiologist.

The eyes were treated initially based on clinical evaluation and microbiological smear examinations. The eyes with positive fungal smears were treated with 5% natamycin suspension on an hourly basis during waking hours. Topical voriconazole 1% was supplemented for larger and deeper fungal ulcers. The eyes with smears showing Gram-positive organisms were treated with a topical preparation of 5% fortified cefazolin eye drops on an hourly basis. If Gram-negative organisms were identified by smear examinations, 0.3% gatifloxacin on an hourly basis was used during waking hours. In cases where smear and culture were negative, cefuroxime 0.5% and ciprofloxacin 0.3% were started on an hourly basis.

Treatment in the bacterial cases was based on the antibiotic susceptibility test and fungal keratitis was started with natamycin (5%) suspension with or without voriconazole (1%) eye drops administered half-hourly. In culture-negative cases, empirical therapy using broad-spectrum antibiotics (fortified cefuroxime 5% hourly and ciprofloxacin 0.3% hourly) that have a broad spectrum of activity against Gram-negative and Gram-positive organisms was started. Cycloplegic agents such as atropine sulfate 1%, homatropine 1%, or cyclopentolate 1% instilled three times a day reduce ciliary spasm and produce mydriasis, thereby relieving pain and preventing synechiae formation. If required, an oral analgesic for pain was used. Tissue adhesive (TA) using N-butyl cyanoacrylate with a bandage contact lens (BCL) application was performed in cases with marked thinning or corneal perforation <2 mm. Therapeutic penetrating keratoplasty was performed in cases with advanced disease at presentation, where there was no response to medical therapy or when a large perforation was present.

Statistical evaluation

The Kolmogorov–Smirnov test and Q–Q plot assessed the normal distribution of data. Mean, standard deviation, and range were presented for continuous data. t-test, Chi-square test, and Fisher's exact test were used to compare variables. All statistical analyses were performed using SPSS software version 22 (IBM Corp, Armonk, NY, USA). P < 0.05 were considered statistically significant. All P values are two-sided.

  Results Top

Medical records of 77 children with a diagnosis of infectious keratitis aged between 0 and 16 years were reviewed. Fifty-seven patients were male (74%) and 20 (26%) female children. In 44 (57%) children, the left eye was affected. A total of 59 (77%) children belonged to rural locations. The average age of all patients was 9.1 ± 4.9 years (range 8 days–16 years). There were 2 (2/77, 3%) newborns (0–28 Days), 10 (10/77, 13%) infants (29 days–2 years), 14 (14/77, 18%) preschool age (3–6 years), 25 (25/77, 32%) school age (7–12 years), and 26 (26/77, 34%) adolescents (12–16 years). The median time from the onset of symptoms to the ophthalmological examination was 8 ± 18.9 days (range 1 day–90 days). Predisposing factors were identified in 41 (41/77, 54%) children with two or more factors occurring in 10%. Ocular trauma was associated with 33 (33/77, 43%) children. Other predisposing factors included concomitant ocular diseases (five children, [6%]), prolonged steroid treatment (nine children, [12%]), and systemic illness (two children, [3%]). A total of 48 (48/77, 62%) children were using topical antibiotics at the time of presentation. The causes of ocular trauma were injury from sugarcane leaves, wood particles, insects, dust, and sticks.

Perforation was present in five eyes at the time of presentation, corneal melt in one eye, and corneal laceration was present in one eye. Hypopyon was present in 22 (22/77, 29%) eyes. The location of the corneal ulcer was central in 35 (35/77, 46%), paracentral in 26 (26/77, 34%), peripheral in 8 (8/77, 10%), and total in 8 (8/77, 10%) children. Mean infiltrate size 11.5 ± 7.1 mm2 (range: 1–24 mm2).

General anesthesia was required in 12 (12/77, 16%) patients to acquire corneal scraping. A total of 32 (32/77, 42%) eyes were positive for microbial organisms on microbiological smear examination. Of them, the organism was identified in 23 (23/32, 72%) eyes. Of smear-negative eyes, the fungus was identified in three eyes and bacteria in 11 eyes. Ten eyes were positive on KOH and 29 on Gram's stain. Seven eyes were positive on both KOH and Gram's stains. Of KOH-positive eyes, fungal organisms were identified in six eyes. Similarly, in Gram's positive eyes, bacteria were identified in 21 eyes.

The culture report was positive in 39 (39/77, 51%) children. A total of 48 (62%) children were previously treated with antibiotics. Of them, 26 (26/48, 54%) children were culture negative and 22 (22/48, 46%) were culture-positive. Bacterial infection was reported in 30 (30/77, 39%) patients and fungal infection was reported in 9 (9/77, 12%) patients. Staphylococcus was the most commonly isolated organism (13/39 33%) followed by Streptococcus pneumoniae (9/39, 23%) and Fusarium spp.(6/39, 15%). Other isolated organisms were Pseudomonas aeruginosa (6/39, 15%), Curvularia spp. (2/39, 5%), and Aspergillus flavus (1/39, 3%) [Table 1].
Table 1: Microorganisms isolated from corneal ulcer in children

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The antibiogram of the isolated organisms is presented in [Table 2]. The reported studies have had significant heterogeneity (I2 = 95.3%, 95% confidence interval [CI]: 91.8%–97.4%; Cochrane's Q = 86.6; P ≤ 0.0001). There was a significant difference between bacterial organisms versus fungal organisms isolated [odds ratio 6.5, 95% CI 1.1–36.0, P = 0.03, [Figure 1]]. The odds ratio suggests that the odds of bacterial organism identification was 6.5 times higher than a fungal organism in pediatric infective keratitis.
Figure 1: Forrest plot of identified studies suggests that the bacteria more likely to be a causal organism than a fungal organism in Pediatric infectious keratitis (PIK) patients

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Table 2: Antibiogram of bacterial isolates

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A total of 19 (25%) children required surgical intervention. Therapeutic penetrating keratoplasty was performed in two, TA with BCL in nine, tarsorrhaphy in one child, pars plana vitrectomy with pars plana lensectomy with intraocular antibiotic injection in five, and scleral patch graft was performed in one child. The evisceration of the eye was done in one child. BCVA was recorded in 55 (78%) children at the time of presentation. Presenting BCVA of 20/25 or better was recorded in 13 (24%), 20/30–20/60 in 9 (16%), 20/60–20/200 in 9 (16%), and worse than 20/200 in 24 (44%) children. At the past follow-up, BCVA of 20/25 or better was recorded in 17 (31%), 20/30–20/60 in 11 (20%), 20/60–20/200 in 10 (18%), and worse than 20/200 in 18 (33%) children. This improvement in BCVA was found to be statistically significant (P = 0.001; Fisher's exact test) [Figure 2]. In the rest three children, BCVA could not be assessed due to preverbal or noncooperative patients. Out of four smear positives for fungal element and culture-negative cases, two cases achieved final VA of 20/20 and 20/30, respectively, TA + BCL was done in one case and one case was lost to follow-up.
Figure 2: Distribution of visual acuity at presentation and at final follow-up

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  Discussion Top

Our study's culture positivity rate (49%) was consistent with the previous reports on microbial keratitis in children.[2],[4],[8],[12],[13] Sixty-six percent of children with negative corneal cultures were treated with antibiotics before presenting to our institute. This may account for the low positivity rate. The reported culture-positive rate ranged from 34% to 89.3% in different studies.[3],[13],[15],[16],[17],[18] Spectrum of causative organisms of microbial keratitis varies with different geographical locations.[2] Previous studies reported that bacteria were children's most common cause of infectious keratitis.[2],[3],[5],[10] Aruljyothi et al. reported that fungi were more prevalent etiological organisms causing infectious keratitis in children.[4] Gram-positive microorganism are the most prevalent etiological agent causing microbial keratitis in children.[2],[3],[5],[11] Pseudomonas and  Staphylococcus epidermidis Scientific Name Search  also isolated in children with infective keratitis.[6],[13] The presence of Gram-positive bacteria in our study was also the most prevalent. Singh et al. and Kunimoto et al. found that Staphylococcus species were more prevalent than Streptococcus pneumonia.[3],[4] P. aeruginosa was the major Gram-negative organism reported from 10% to 44% of culture-positive children.[2],[3],[6],[13],[16],[18] The lower proportion of P. aeruginosa identification in our study may be explained by the rarity of contact lens wearers in this series. P. aeruginosa is the most predominant pathogen of contact lens-related corneal ulcers.[19],[20],[21]

The positivity of fungal infections reported by previous authors from other countries ranges from 4% to 54.2%.[2],[6],[12] In our study, positive fungal infection was reported in 23.1%. Singh et al. also reported a similar prevalence of fungal infection. However, this prevalence of fungal infection is higher than the reported prevalence by Kunimoto et al.[12] (17.2%) and Vajpayee et al.[13] (10%) from India. Fusarium solani was the predominant fungal pathogen similar to the reported studies.[2],[3],[17],[20] In our study, Curvularia was also identified in two eyes. Curvularia was not identified in previous reports on pediatric infectious keratitis from India.[3],[4],[11],[12] We did not identify any protozoan as a causative organism of infectious keratitis in this series as reported in other similar series.[2],[4],[14] The lack of identifying any protozoan in the study is one of the limitations of this study. This may be because recent diagnostic methods, such as confocal scanning were not used in this study.

We found that Staphylococcus species were resistant to sulfamethoxazole. All of them were sensitive to oxacillin. All these antibiotics act against Gram-positive bacteria. Chirinos-Saldaña et al.[18] reported high resistance of Staphylococcus species to these antibiotics. However, in this study, most of them were susceptible to cefazolin and oxacillin. All cases were sensitive to aminoglycosides (amikacin and gentamicin) and vancomycin similar to the previous study by Chirinos-Saldaña et al.[18] In this series, Streptococcus spp. were susceptible to cefazolin and vancomycin. They showed high resistance to amikacin. However, previous studies reported that Streptococcus spp. were susceptible to the majority of antibiotics.[16],[18] Fluoroquinolones (ciprofloxacin, gatifloxacin, moxifloxacin, and ofloxacin) demonstrate poor potency against Staphylococcus spp. and Streptococcus spp. Spierer et al. reported high microbial susceptibility to fluoroquinolones.[13] High variability in sensitivity patterns of these microorganisms against different antibiotics was found in all published reports. Therefore, an antibiogram is recommended before treating infections caused by these microorganisms. The retrospective design of the study has its own limitations. PCR and specific culture for Acanthamoeba was not done in this study for every patient. Doing culture to identify Acanthamoeba is not a routine microbiological practice in the study area. Specific culture will be done only on the basis of clinical suspicion.

Since there were inconsistencies in the prevalence of bacterial and fungal organisms isolated in cases of infectious keratitis among children reported in studies from India. The meta-analysis of identified studies suggests that the bacteria are 6.5 times more likely to be a causal organism than a fungal organism in Pediatric infectious keratitis (PIK) patients. Since performing meta-analysis is not the primary objective of this study. The list of studies considered in this analysis may not be exhaustive. The selection of studies was done during the comparison of our results with previously reported studies from India.

The average age of children in this series is similar to other reported studies on pediatric infectious keratitis.[2],[3],[4] In this study, male preponderance was reported, similar to other studies.[3],[8],[16] The mean time from the onset of symptom to diagnosis was almost 2 weeks. In this series, the majority (76%) of the patient population belonged to rural areas. Awareness of parents and the unavailability of cornea specialists in nearby areas may be the reasons behind this delay in diagnosis and treatment. This highlights the poor eye care-seeking behavior of the population in the study area.

  Conclusion Top

Staphylococcus was the most commonly isolated organism. Ocular trauma due to sugarcane leaves is a major risk factor for pediatric microbial keratitis in the study area. There is a need to create parent awareness regarding the possibility of ocular trauma with sugarcane leaves in children.

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Conflicts of interest

There are no conflicts of interest.

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  [Table 1], [Table 2]


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