Corneal Diseases in Children: Infectious Keratitis


Age

Treatment dose thrice daily

Prophylactic dose twice daily

Infants (up to 18 months)

100 mg (2.5 ml)

100 mg (2.5 ml)

Toddlers (18 months–3 years)

200 mg (5 ml)

200 mg (5 ml)

Young children (3–5 years)

300 mg (7.5 ml)

300 mg (7.5 ml)

Older children (6 years and older)

400 mg (10 ml)

400 mg (10 ml)



Topical steroids are contraindicated with active epithelial infection.

For stromal keratitis, the herpetic eye disease study (HEDS), which studied adult patients with herpetic infections, recommends using topical steroids (Barron et al. 1994); however, pediatric stromal keratitis, endotheliitis, and iridocyclitis are commonly treated with oral antivirals in combination with topical steroids (Hsiao et al. 2009; Liu et al. 2012). In children, adequate control of inflammation is crucial as persistent herpes-related inflammation can lead to corneal scarring and considerable visual impairment (Knickelbein et al. 2009). However, steroids, in addition to having numerous side effects, have been suggested to promote the development of resistant HSV strains (Revere and Davidson 2013). Newer targeted therapies have been studied in animal models to avoid the issues associated with steroids. Gene therapy utilizing plasmid and naked DNA encoding VEGF antagonists and inflammatory mediators, such as interleukin-18, have been studied in reducing HSV-associated neovascularization, for example (Stechschulte et al. 2001; Kim et al. 2005; Elbadawy et al. 2012). Anti-HSV IgG fab fragments have also been investigated and have been shown to be more effective than placebo in reducing viral titers and disease burden in mice (Berdugo et al. 2012). While these therapies are only in their most early stages of development, they may eventually come to play a large role in greatly reducing and, perhaps, curing herpetic eye disease.

For epithelial neurotrophic ulceration, topical antivirals are not indicated, and topical steroids and other anti-inflammatory medications should only be used with great caution in the presence of stromal inflammation. These patients are best managed with preservative-free lubrication. For refractory or severe cases, several nonmedical options can be tried including bandage contact lenses, amniotic membrane grafts, tarsorrhaphy, or conjunctival flaps.

For children with recurrent HSV prophylactic oral acyclovir may be recommended; kidney and liver function should be monitored with chronic use of systemic acyclovir (Liu et al. 2012; Revere and Davidson 2013). The recommended pediatric doses for prophylactic acyclovir are noted in Table 3.1.



EKC


Currently, treatment of adenoviral infections is mainly supportive as there are no therapies definitively proven to be effective in preventing or shortening the duration of the disease. Various drugs have been developed, however, that work primarily by interfering with human adenovirus replication; these drugs include zalcitabine, sanilbudine, cidofovir, ganciclovir, interferon beta, and anitosteopontine peptide, and N-chlorotaurine (Ghebremedhin 2014). While current literature suggests beneficial effects, randomized clinical trials are few.

When there are subepithelial infiltrates or pseudomembrane formation, topical corticosteroids can be employed to quiet the host response to infection with the understanding that steroids prolong viral replication and shedding. After infiltrates have cleared, steroids should be tapered very slowly as sudden withdrawal can cause subepithelial infiltrates to recur. In cases refractory to corticosteroids, topical cyclosporine A has been used.



Surgery and Other Nonmedical Interventions


When treated appropriately with antibiotics and/or steroids, less than one-fifth of children go on to require surgery (Al-Otaibi 2012). However, in rare cases of refractory or inadequately treated keratitis, surgical interventions may be necessary to help clear the infection, manage severe ulceration or perforation, or to remove corneal opacities that may obscure vision and cause secondary amblyopia. These interventions range from simple debridement—commonly used with fungal keratitis, HSK, and AK—to using cyanoacrylate tissue adhesive with bandage contact lenses for corneal thinning. Deep lamellar keratoplasty and therapeutic penetrating keratoplasty may be required for extensive ulceration or perforation. Surgery is best delayed until after medical treatment has cleared the infection and inflammation has quieted.

Most recently, several groups have demonstrated the efficacy of photo-activated chromophore for keratitis cross-linking, or PACK-CXL, in the treatment of microbial keratitis. PACK-CXL is thought to exert its therapeutic effects by multiple mechanisms that inhibit pathogen replication and prevent further destruction of host tissues (Hafezi and Randleman 2014). Despite its promise, PACK-CXL remains largely experimental while scientists work to optimize treatment parameters.


Additional Therapies and Follow-Up


To help relieve discomfort associated with infectious keratitis, patients should initially be instructed to apply refrigerated preservative-free tears, which can be liberally used with little worry for negative repercussions. However, patients should be reminded not to touch the applicator tip to the eyes, as they could transmit infection from one eye to the other. Patients whose discomfort cannot be adequately controlled with this simple measure can be prescribed cycloplegics and analgesics; for example, topical atropine, an anticholinergic that causes ciliary muscle paralysis, can be used for photophobia (Baig et al. 2014).

All pediatric patients who present with keratitis should be closely monitored for signs of improvement, as a failure to respond to appropriate therapy or further progression of disease could place patients at greater risk for significant visual impairment and secondary amblyopia. They should be carefully examined for full resolution of corneal infection, since even with apparent clinical improvement, pediatric patients may not be able to appropriately vocalize any residual symptoms which might be caused by astigmatism or corneal opacities.

Table 3.2 lists strategies for the management of infectious keratitis in children.


Table 3.2
Strategies for management of infectious keratitis is children





















1. A thorough history (timing/duration/previous treatment/risky behaviors with contact lens use/trauma) will aid in the differential diagnosis

2. Detection of any unusual features of the infiltrate (e.g., multi-focality, feathery edges, perineuritis) will aid in narrowing the diagnosis

3. Definitive diagnosis requires corneal cultures and smears. An exam under anesthesia may be needed, especially in very young children

4. Corneal imaging may be a useful diagnostic adjunct, depending upon the age and cooperation of the child

5. Initial therapy should include frequent administration of broad-spectrum antibiotics to cover both gram positive and gram negative organisms. Antibiotic coverage can be tailored once the causative agent is identified

6. Treatment with anti-fungal or anti-Acanthamoeba therapy is typically delayed until there is confirmation of the diagnosis by a positive smear or culture, or a suggestive imaging study

7. Close follow-up is essential to ensure that the ulcer is responding to therapy. Often the first sign that the infection is being successfully treated is a reduction in the density of the infiltrate (rather than the size). Medications should be tapered according to clinical response

8. Herpes simplex should always be kept in mind, especially when there is recurrent infection


Illustrative Cases


Case 1:

A healthy 16-year-old girl with a history of overnight use of contact lenses presented with the acute onset of pain, redness and reduced vision of the right eye. On exam, an ulcer with a small hypopyon was seen (Fig. 3.1). Corneal smear and cultures were performed. Fortified cefazolin and tobramycin drops were started hourly. The Gram stain showed Gram-negative rods and the corneal cultures grew abundant Pseudomonas aeruginosa. The cefazolin was discontinued and ciprofloxacin ointment was added at bedtime. The tobramycin was continued, at a gradually reduced dose as the ulcer improved. The ulcer healed over 2 weeks, leaving a minimal scar and mild corneal thinning. Spectacle best-corrected vision returned to 20/25.

A324108_1_En_3_Fig1_HTML.gif


Fig. 3.1
Pseudomonas aeruginosa keratitis (Case 1)

Case 2:

A healthy 10-year-old girl presented with a history of recurrent redness and reduced vision of her right eye. On exam, vision was reduced to 20/50. Mild conjunctival injection and a ring infiltrate were present (Fig. 3.2). Corneal sensation was reduced. A presumptive diagnosis of herpes simplex stromal keratitis was made. Oral acyclovir was begun at a dosage of 400 mg three times daily. Two days later, her symptoms had improved and the ring had resolved, although central corneal edema was present (disciform edema). Loteprednol 0.5% drops were added three times daily. Uncorrected vision returned to 20/20 over one month. The topical steroid was gradually tapered and eventually discontinued. Oral acyclovir was reduced to twice daily. She continued this prophylactic dose of acyclovir for one year, at which point it was discontinued. No further episodes occurred.

A324108_1_En_3_Fig2_HTML.jpg


Fig. 3.2
Herpes simplex stromal keratitis (Case 2)


Compliance with Ethical Requirements

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Conflict of Interest

Eubee B. Koo and Kathryn Colby declare that they have no conflict of interest.


Informed Consent

No human or animal studies were carried out by the authors for this article.


References



Akpek EK, Gottsch JD (2003) Immune defense at the ocular surface. Eye (Lond) 17:949–956


Al Otaibi AG, Allam K, Damri AJ et al (2012) Childhood microbial keratitis. Oman J Ophthalmol 5:28–31PubMedPubMedCentral


Al-Mujaini A, Al-Kharusi N, Thakral A, Wali UK (2009) Bacterial keratitis: perspective on epidemiology, clinico-pathogenesis, diagnosis and treatment. Sultan Qaboos Univ Med J 9:184–195PubMedPubMedCentral


Al-Otaibi AG (2012) Non-viral microbial keratitis in children. Saudi J Ophthalmol Off J Saudi Ophthalmol Soc 26:191–197


Aldave AJ, King JA, Cunningham ET (2001) Ocular syphilis. Curr Opin Ophthalmol 12:433–441PubMed


Alizadeh H, Neelam S, Hurt M, Niederkorn JY (2005) Role of contact lens wear, bacterial flora, and mannose-induced pathogenic protease in the pathogenesis of amoebic keratitis. Infect Immun 73:1061–1068PubMedPubMedCentral


AlonsoDeVelasco E, Verheul AF, Verhoef J, Snippe H (1995) Streptococcus pneumoniae: virulence factors, pathogenesis, and vaccines. Microbiol Rev 59:591–603PubMedPubMedCentral


Aly R, Levit S (1987) Adherence of Staphylococcus aureus to squamous epithelium: role of fibronectin and teichoic acid. Rev Infect Dis 9 (Suppl 4):S341–50


Bacon AS, Frazer DG, Dart JK et al (1993) A review of 72 consecutive cases of Acanthamoeba keratitis, 1984-1992. Eye (Lond) 7(Pt 6):719–725


Baig AM, Zuberi H, Khan NA (2014) Recommendations for the management of Acanthamoeba keratitis. J Med Microbiol 63:770–771PubMed


Bang S, Edell E, Eghrari AO, Gottsch JD (2010) Treatment with voriconazole in 3 eyes with resistant Acanthamoeba keratitis. Am J Ophthalmol 149:66–69PubMed


Bannerman TL, Rhoden DL, McAllister SK et al (1997) The source of coagulase-negative staphylococci in the Endophthalmitis Vitrectomy Study. A comparison of eyelid and intraocular isolates using pulsed-field gel electrophoresis. Arch Ophthalmol 115:357–361PubMed


Barron BA, Gee L, Hauck WW et al (1994) Herpetic eye disease study. A controlled trial of oral acyclovir for herpes simplex stromal keratitis. Ophthalmology 101:1871–1882PubMed


Basak SK, Deolekar SS, Mohanta A et al (2012) Bacillus cereus infection after Descemet stripping endothelial keratoplasty. Cornea 31:1068–1070PubMed


Baum J, Barza M (1983) Topical vs subconjunctival treatment of bacterial corneal ulcers. Ophthalmology 90:162–168PubMed


Beattie TK, Tomlinson A, McFadyen AK et al (2003) Enhanced attachment of acanthamoeba to extended-wear silicone hydrogel contact lenses: a new risk factor for infection? Ophthalmology 110:765–771PubMed


Behlau I, Gilmore MS (2008) Microbial biofilms in ophthalmology and infectious disease. Arch Ophthalmol 126:1572–1581PubMed


Beigi B, Algawi K, Foley-Nolan A, O’Keefe M (1994) Herpes simplex keratitis in children. Br J Ophthalmol 78:458–460PubMedPubMedCentral


Beneish RG, Williams FR, Polomeno RC, Flanders ME (1987) Herpes simplex keratitis and amblyopia. J Pediatr Ophthalmol Strabismus 24:94–6


Berdugo M, Larsen IV, Abadie C et al (2012) Ocular distribution, spectrum of activity, and in vivo viral neutralization of a fully humanized anti-herpes simplex virus IgG Fab fragment following topical application. Antimicrob Agents Chemother 56:1390–1402PubMedPubMedCentral


Boggild AK, Martin DS, Lee TY et al (2009) Laboratory diagnosis of amoebic keratitis: comparison of four diagnostic methods for different types of clinical specimens. J Clin Microbiol 47:1314–1318PubMedPubMedCentral


Bottone EJ, Qureshi MN, Asbell PA (1992) A simplified method for demonstration and isolation of Acanthamoeba organisms from corneal scrapings and lens care systems. Am J Ophthalmol 113:214–215PubMed


Brook I, Barrett CT, Brinkman CR et al (1979) Aerobic and anaerobic bacterial flora of the maternal cervix and newborn gastric fluid and conjunctiva: a prospective study. Pediatrics 63:451–455PubMed


Butt AL, Chodosh J (2006) Adenoviral keratoconjunctivitis in a tertiary care eye clinic. Cornea 25:199–202PubMed


Callegan MC, Engel LS, Hill JM, O’Callaghan RJ (1994) Corneal virulence of Staphylococcus aureus: roles of alpha-toxin and protein A in pathogenesis. Infect Immun 62:2478–2482PubMedPubMedCentral


Chaurasia S, Ramappa M, Ashar J, Sharma S (2014) Neonatal infectious keratitis. Cornea 33:673–676PubMed


Chirinos-Saldaña P, Bautista de Lucio VM, Hernandez-Camarena JC et al (2013) Clinical and microbiological profile of infectious keratitis in children. BMC Ophthalmol 13:54PubMedPubMedCentral


Chong E-M, Wilhelmus KR, Matoba AY et al (2004) Herpes simplex virus keratitis in children. Am J Ophthalmol 138:474–475PubMed


Choo JD, Holden BA, Papas EB, Willcox MDP (2009) Adhesion of Pseudomonas aeruginosa to orthokeratology and alignment lenses. Optom Vis Sci 86:93–97PubMed


Choudhuri KK, Sharma S, Garg P, Rao GN (2000) Clinical and microbiological profile of Bacillus keratitis. Cornea 19:301–306PubMed


Clarke B, Sinha A, Parmar DN, Sykakis E (2012) Advances in the diagnosis and treatment of acanthamoeba keratitis. J Ophthalmol 2012:484892PubMedPubMedCentral


Clarke DW, Niederkorn JY (2006) The immunobiology of Acanthamoeba keratitis. Microbes Infect 8:1400–1405PubMed


Colin J, Le Grignou M, Le Grignou A et al (1982) Ocular herpes simplex in children (author’s transl). Ophthalmologica 184:1–5PubMed


Costerton JW, Lam J, Lam K, Chan R (1983) The role of the microcolony mode of growth in the pathogenesis of Pseudomonas aeruginosa infections. Rev Infect Dis 5(Suppl 5):S867–S873PubMed


Cruz OA, Sabir SM, Capo H, Alfonso EC (1993) Microbial keratitis in childhood. Ophthalmology 100:192–196PubMed


Dajcs JJ, Austin MS, Sloop GD et al (2002) Corneal pathogenesis of Staphylococcus aureus Strain Newman. Invest Ophthalmol Vis Sci 43:1109–1115PubMed


Dart JK (1988) Predisposing factors in microbial keratitis: the significance of contact lens wear. Br J Ophthalmol 72:926–930PubMedPubMedCentral


Dart JK, Seal DV (1988) Pathogenesis and therapy of Pseudomonas aeruginosa keratitis. Eye (Lond) 2(Suppl):S46–S55


Dart JKG, Radford CF, Minassian D et al (2008) Risk factors for microbial keratitis with contemporary contact lenses: a case-control study. Ophthalmology 115:1647–54, 1654.e1–3


Dart JKG, Saw VPJ, Kilvington S (2009) Acanthamoeba keratitis: diagnosis and treatment update 2009. Am J Ophthalmol 148:487.e2–499.e2


Davis SD, Sarff LD, Hyndiuk RA (1979) Comparison of therapeutic routes in experimental Pseudomonas keratitis. Am J Ophthalmol 87:710–716PubMed


de Freitas D, Sato EH, Kelly LD, Pavan-Langston D (1992) Delayed onset of varicella keratitis. Cornea 11:471–474PubMed


Dix RD (2006) Pathogenesis of herpes simplex ocular disease. In: Tasman W, Jaeger EA (eds) Duane’s ophthalmology, 2006th edn. Lippincott Williams & Wilkins, Philadelphia


Durnian JM, Naylor G, Saeed AM (2004) Ocular syphilis: the return of an old acquaintance. Eye (Lond) 18:440–442


Elbadawy HM, Gailledrat M, Desseaux C et al (2012) Targeting herpetic keratitis by gene therapy. J Ophthalmol 2012:594869PubMedPubMedCentral


Emery PW, Sanderson P (1995) Effect of dietary restriction on protein synthesis and wound healing after surgery in the rat. Clin Sci (Lond) 89:383–388


Epstein RJ, Wilson LA, Visvesvara GS, Plourde EG (1986) Rapid diagnosis of Acanthamoeba keratitis from corneal scrapings using indirect fluorescent antibody staining. Arch Ophthalmol 104:1318–1321PubMed


Erdem E, Evcil Y, Yagmur M et al (2014) Non-contact lens use-related Acanthamoeba keratitis in southern Turkey: evaluation of risk factors and clinical features. Eur J Ophthalmol 24:164–172PubMed


Erie JC, Nevitt MP, Hodge DO, Ballard DJ (1993) Incidence of ulcerative keratitis in a defined population from 1950 through 1988. Arch Ophthalmol 111:1665–1671PubMed


Evans DJ, Fleiszig SMJ (2013) Microbial keratitis: could contact lens material affect disease pathogenesis? Eye Contact Lens 39:73–78PubMedPubMedCentral


Farooq AV, Shukla D (2012) Herpes simplex epithelial and stromal keratitis: an epidemiologic update. Surv Ophthalmol 57:448–462PubMedPubMedCentral


Fernández de Castro LE, Al Sarraf O, Hawthorne KM et al (2006) Ocular manifestations after primary varicella infection. Cornea 25:866–867PubMed

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