Aetiology

Microbial keratitis is a sight-threatening infection of the cornea

The commonest bacterial corneal pathogens are:

• Pseudomonas sp. (Gram -ve)
• Staphylococcus sp. (Gram +ve)
• Streptococcus sp. (Gram +ve)
• other Gram -ve organisms

Note: severe contact lens-related infections tend to be Gram -ve, particularly Pseudomonas species

Fungal infection causes a small proportion of infectious keratitis cases in temperate regions; however, in tropical climates it can cause up to 50% of cases. The most common fungal corneal pathogens are:

• Candida sp. (yeast-like)
• Fusarium sp. (filamentous)
• Aspergillus sp (filamentous)

Predisposing factors

Bacterial keratitis is usually associated with one or more of the following:

• contact lens wear (incidence 4–5 times higher in CL wearers than non-wearers). The risk of MK with overnight corneal reshaping contact lenses (ortho-K) is similar to rates associated with use of daily wear soft contact lenses. The main risk factors for CL-related MK are:
  • increased days of wear
  • poor hand, lens and storage case hygiene
  • youth
  • male gender
  • smoking
  • internet purchase of lenses, particularly cosmetic lenses
• ocular surface disease, including:
  • corneal exposure
  • corneal decompensation
  • chronic epithelial defect
  • neurotrophic keratopathy, e.g. secondary to HSK or diabetes
• ocular trauma or surgery, including loose or broken sutures
• immune compromise
• topical steroid use
• lid margin infection (usually Staphyloccocal)

Fungal keratitis (filamentous) is usually secondary to trauma involving organic material; it can also be contact lens or solution related
Fungal keratitis (yeast-like) most usually complicates ocular surface disease or in immunocompromised patients

Symptoms of microbial keratitis (bacterial, fungal)

Pain, moderate to severe (usually acute onset, rapid progression)
Redness, photophobia (may be severe), discharge, blurred vision (especially if lesion on visual axis)
Awareness of white or yellow spot on cornea
Usually unilateral

Signs of microbial keratitis (bacterial, fungal)

Lid oedema
Epiphora
Discharge (mucopurulent or purulent)
Conjunctival hyperaemia and infiltration
Corneal lesion usually single (central or mid-peripheral)

• excavation of epithelium, Bowman’s layer, stroma (tissue necrosis)
• stromal infiltration beneath lesion
• stromal oedema with folds in Descemet’s membrane
• endothelial fibrin plaque beneath lesion
• optical coherence tomography (OCT) may be helpful in determining depth of involvement

Anterior chamber activity (flare, cells, hypopyon or coagulum if severe)

Fungal keratitis produces similar signs to bacterial keratitis; however, it has been claimed that deep lesions, those having a feathery edge, raised profile, presence of satellite lesions and the presence of endothelial plaque are all features suggestive of a fungal as opposed to a bacterial infection. Fungal keratitis may develop more slowly (however Fusarium infection can progress rapidly and invasively)

Differential diagnosis

Corneal infiltrative lesions (contact lens related or marginal keratitis; see separate Clinical Management Guidelines)

• peripheral, small (0.5-1.5 mm) with less anterior chamber response
• not a marker for increased risk of bacterial infection

Acanthamoeba keratitis (see Clinical Management Guideline). Suspect AK if multiple epithelial or subepithelial infiltrates, perineural infiltrates or dendritiform epithelial lesions)

Management by optometrist

Practitioners should recognise their limitations and where necessary seek further advice or refer the patient elsewhere

GRADE* Level of evidence and strength of recommendation always relates to the statement(s) immediately above

Cease contact lens wear. Warn contact lens wearers not to discard their lenses or lens cases, but to retain them if needed for culture
(GRADE*: Level of evidence=low, Strength of recommendation=strong)

Emergency (same day) referral is indicted if any of the following signs are present:

• infiltrate >1mm
• 2 or more adjacent lesions
• location 3mm or less from corneal centre
• AC reaction (≥10 cells in a 1mm beam (≥ 1+ on the SUN scale)
• signs suggestive or fungal or acanthamoeba keratitis
• high likelihood of poor patient compliance to treatment

These sight-threatening characteristics are indications for microbiological culture, which should be performed prior to initiating antimicrobial therapy.
(GRADE*: Level of evidence=low, Strength of recommendation=strong

Empirical treatment for lesions (<1mm) in the absence of the above clinical characteristics is based fluoroquinolone monotherapy e.g. gutt levofloxacin/moxifloxacin hourly day and night for 48 hours, then every 2 hours daily for 72 hours, then every 4 hours for 7 days. Monitor closely during this period and refer same day if not healing or if symptoms worsen
(GRADE*: Level of evidence=low, Strength of recommendation=strong)

Management category

A1: emergency (same day) referral to ophthalmologist without intervention if fungal keratitis is suspected or any of the sight threatening characteristics of bacterial keratitis described above are present. Emphasise to the patient the urgency of the condition and instruct them to attend the local hospital eye department or hospital A&E the same day, explaining that you will leave a message so that they are expected. Telephone the department to explain what you have done, preferably leaving your message with a doctor or other health care professional. Advise patient to take lenses and lens case for possible culture.

B2: For lesions (<1mm) in the absence of the above defined sight threatening characteristics. Alleviation and palliation: normally no referral to ophthalmologist

Possible management by ophthalmologist

Corneal scrape (for culture and determination of antibiotic sensitivities) followed by initiation of intensive (round the clock) treatment with one or more antibiotics. Corneal isolate studies show changing patterns of bacterial pathogenesis and the development of resistant strains

Polymerase chain reaction [PCR] technique may be used to identify causative organisms

Possible admission to hospital when good compliance is unlikely, or for overnight treatment of severe infections (axial lesions, lesions 6mm or more in diameter, or with 50% or more stromal thinning)

Cycloplegia

Hypotensive agents for secondary glaucoma

Topical steroids (only when infection controlled) – not well supported by evidence base

Amphotericin B (as 0.15% eye drops) is the drug of choice in fungal keratitis caused by yeasts (e.g. Candida)

Fungal infections usually require combined topical (e.g. natamycin 5%, econazole 1% or voriconazole 1%) and oral (e.g. voriconazole) therapy. Clinical strategies continue to evolve

Evidence base

*GRADE: Grading of Recommendations Assessment, Development and Evaluation (www.gradeworkinggroup.org)

Sources of evidence

Bullimore MA, Mirsayafov DS, Khurai AR, Kononov LB, Asatrian SP, Shmakov AN, Richdale K, Gorev VV. Pediatric Microbial Keratitis With Overnight Orthokeratology in Russia. Eye Contact Lens. 2021;47(7):420-425.

Carnt N, Samarawickrama C, White A, Stapleton F. The diagnosis and management of contact lens-related microbial keratitis. Clin Exp Optom 2017;100:482-493

Cheung N, Nagra P, Hammersmith K. Emerging trends in contact lens-related infections. Curr Opin Ophthalmol. 2016;27:327-332

Dahlgren MA, Lingappen A, Wilhelmus KR. The Clinical Diagnosis of Microbial Keratitis. Am J Ophthalmol. 2007;143(6):940–4

FlorCruz NV, Evans JR. Medical interventions for fungal keratitis. Cochrane Database Syst Rev. 2015;4:CD004241

Herretes S, Wang X, Reyes JM. Topical corticosteroids as adjunctive therapy for bacterial keratitis. Cochrane Database Syst Rev. 2014;10:CD005430

Jabs DA, Nussenblatt RB, Rosenbaum JT; Standardization of Uveitis Nomenclature (SUN) Working Group. Standardization of uveitis nomenclature for reporting clinical data. Results of the First International Workshop. Am J Ophthalmol. 2005 Sep;140(3):509-16.

Jongkhajornpong P, Nimworaphan J, Lekhanont K, Chuckpaiwong V, Rattanasiri S. Predicting factors and prediction model for discriminating between fungal infection and bacterial infection in severe microbial keratitis. PLoS One. 2019;14(3):e0214076.

Lin A, Rhee MK, Akpek EK, Amescua G, Farid M, Garcia-Ferrer FJ, Varu DM, Musch DC, Dunn SP, Mah FS; American Academy of Ophthalmology Preferred Practice Pattern Cornea and External Disease Panel. Bacterial Keratitis Preferred Practice Pattern®. Ophthalmology. 2019;126(1):P1-P55

McDonald EM, Ram FS, Patel DV, McGhee CN. Topical antibiotics for the management of bacterial keratitis: an evidence-based review of high quality randomised controlled trials. Br J Ophthalmol. 2014;98(11):1470- 7

Shalchi Z, Gurbaxani A, Baker M, Nash J. Antibiotic resistance in microbial keratitis: ten-year experience of corneal scrapes in the United Kingdom. Ophthalmology. 2011;118(11):2161-5

Stapleton F, Shrestha GS, Vijay AK, Carnt N. Epidemiology, Microbiology, and Genetics of Contact Lens-Related and Non-Contact Lens-Related Infectious Keratitis. Eye Contact Lens. 2022;48(3):127-133.

Ung L, Wang Y, Vangel M, Davies EC, Gardiner M, Bispo PJM, Gilmore MS, Chodosh J. Validation of a Comprehensive Clinical Algorithm for the Assessment and Treatment of Microbial Keratitis. Am J Ophthalmol. 2020;214:97-109.

Microbial keratitis (bacterial, fungal)
Version 13
Date of search 06.05.22
Date of revision 26.05.22
Date of publication 20.12.22
Date for review 05.05.24
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