Which organisms most often cause nontuberculous mycobacterial keratitis?

Mycobacterium tuberculosis and Mycobacterium bovis

Nocardia asteroides and Actinomyces species

Mycobacterium leprae and Mycobacterium marinum

Where does the infiltrate lie in post-LASIK nontuberculous mycobacterial keratitis?

At the flap interface In LASIK cases the infiltrate lies at the flap interface and can spread laterally beneath the flap, so lifting the flap is sometimes needed to obtain a sample.

Which culture media should be requested when mycobacterial keratitis is suspected?

Lowenstein-Jensen or Middlebrook Cultures on Lowenstein-Jensen or Middlebrook media should be requested, and because growth takes days to weeks, treatment is often started before the result returns.

Non-nutrient agar with E coli overlay

What is the traditional first-line topical agent for nontuberculous mycobacterial keratitis?

Fortified amikacin Amikacin as a topical fortified preparation is the traditional first-line agent, with the final choice guided by susceptibility testing.

Which drug class is commonly combined with amikacin for mycobacterial keratitis?

A macrolide such as clarithromycin Fortified amikacin is often given together with a macrolide such as clarithromycin or azithromycin, and treatment is prolonged, often for months.

An aminoglycoside such as tobramycin

A biguanide such as chlorhexidine

Which post-LASIK interface condition is sterile, appears early, and responds to steroids?

Diffuse lamellar keratitis Diffuse lamellar keratitis is sterile, occurs early after LASIK and responds to steroids, whereas a late interface infiltrate misread as DLK and treated with steroids gets worse.

Why can early fluoroquinolone treatment mislead the clinician in mycobacterial keratitis?

Partial activity gives brief improvement before worsening Some fluoroquinolones have partial activity against the organism, so the ulcer improves briefly and then worsens, which can be read as a culture-negative infection.

It sterilises the cornea within 48 hours

It produces a drug-induced epithelial defect

It raises intraocular pressure and masks the infiltrate

How long should follow-up continue after the infiltrate of mycobacterial keratitis has cleared?

One week, because recurrence is not seen

Only until the epithelium has closed

Twenty-four hours after stopping the drops

Nontuberculous Mycobacterial Keratitis: Signs, Care

Nontuberculous mycobacterial keratitis (NTM keratitis) is a slowly progressive corneal infection caused by environmental mycobacteria, most often Mycobacterium chelonae and Mycobacterium abscessus.

It follows refractive surgery, trauma with soil or water contamination, and contact lens wear, and it is frequently misdiagnosed as a fungal or herpetic infection.

The delay in diagnosis is the main problem, and the key step is to think of the organism.

What Is Nontuberculous Mycobacterial Keratitis?

These organisms live in water, soil, and dust, and they are resistant to many disinfectants and antibiotics.

Infection usually occurs through a break in the epithelium or through a surgical wound, and the course is measured in weeks and not in days.

Post-LASIK infections have been reported in clusters, which points to a contaminated source such as water or instruments.

The infection is uncommon in the general population, but it has a clear tendency to follow procedures in which the stromal interface is exposed.

Clinical Features

The patient has pain and redness that are often out of proportion to the early findings, or sometimes less than expected.

The infiltrate is gray-white, often with a ground-glass appearance and irregular, feathery or wreath-like margins.

Satellite lesions may be present, which can resemble fungal keratitis.

In LASIK cases the infiltrate lies at the flap interface, and it can spread laterally beneath the flap.

Anterior chamber reaction is usually mild, and hypopyon is uncommon until late in the disease.

Corneal melting occurs if the infection is not controlled.

Test your knowledge 10 questions from this article

Diagnosis

A scraping for smear and culture is needed, and the laboratory should be told that mycobacteria are suspected.

Acid-fast stains, such as Ziehl-Neelsen or auramine-rhodamine, can show the organisms, and cultures on Lowenstein-Jensen or Middlebrook media should be requested.

Growth takes days to weeks, so treatment is often started before the result is available.

Confocal microscopy can help to show organisms in the stroma, and PCR is useful when it is available.

When the interface is involved, lifting the flap to obtain a sample is sometimes needed.

Differential Diagnosis

Fungal keratitis: feathery edges and satellites, usually with a history of plant trauma (see fungal versus bacterial keratitis)
Herpetic stromal keratitis: reduced sensation, dendritic history, and a response to antivirals
Acanthamoeba keratitis: severe pain and a ring infiltrate (see Acanthamoeba keratitis)
Diffuse lamellar keratitis: sterile, early after LASIK, and responsive to steroids

Nontuberculous Mycobacterial Keratitis: The Slow Ulcer That Fails Standard Therapy

Treatment

Amikacin is the traditional first-line agent, used as a topical fortified preparation, often together with a macrolide such as clarithromycin or azithromycin.

Fluoroquinolones such as moxifloxacin have activity against some species, and the choice should be guided by susceptibility testing.

Treatment is prolonged, often for months, and a flap lift with irrigation or flap amputation may be needed for interface disease.

Topical steroids are avoided until the infection is controlled.

Deep infections that do not respond may need therapeutic keratoplasty.

Patients must be told that the course is long and that follow-up should be close.

Why the Diagnosis Is Often Late

The infiltrate evolves slowly, and in the first weeks it may look like a mild, culture-negative infection that improves briefly on a fluoroquinolone and then worsens.

The early response to a broad-spectrum antibiotic can mislead the clinician, because some fluoroquinolones have partial activity against the organism.

Several clinicians have noted that the interface infiltrate after LASIK may be misread as diffuse lamellar keratitis or as a sterile reaction, and that the use of steroids in that setting makes the infection worse.

A high index of suspicion is therefore needed in any post-LASIK patient who has a late infiltrate, particularly when other cases have been seen from the same surgical center.

Risk Factors and Prevention

Exposure to contaminated water, instruments, or solutions is the main link in postoperative clusters.

Contact lens wearers who shower or swim in lenses are at risk, and so are patients with a history of trauma in a contaminated environment.

Surgical centers should follow strict sterilization routines and should report clusters of delayed postoperative infections to the public health authority.

Patients should be advised to avoid water exposure in the early postoperative period and to report increasing pain or redness promptly.

Prognosis

With early diagnosis and a prolonged course of appropriate antibiotics, many eyes heal with a scar and acceptable vision.

Delayed treatment leads to stromal necrosis, and some eyes need keratoplasty.

Follow-up should continue for several months after the infiltrate has cleared, because relapse after stopping treatment has been described.

References

Chandra NS, Torres MF, Winthrop KL, et al. Cluster of Mycobacterium chelonae keratitis cases following laser in-situ keratomileusis. Am J Ophthalmol. 2001;132:819-830.
Girgis DO, Karp CL, Miller D. Ocular infections caused by non-tuberculous mycobacteria: update on epidemiology and management. Clin Exp Ophthalmol. 2012;40:467-475.
Mannis MJ, Holland EJ, eds. Cornea. 4th ed. Elsevier; 2017.
American Academy of Ophthalmology. Basic and Clinical Science Course, Section 8: External Disease and Cornea. AAO; current edition.

Test yourself

A few questions straight from this article.

1 / 10 0 correct

Which organisms most often cause nontuberculous mycobacterial keratitis?
NTM keratitis is caused by environmental mycobacteria, most often Mycobacterium chelonae and Mycobacterium abscessus, which live in water, soil and dust.
Over what time course does nontuberculous mycobacterial keratitis typically progress?
Infection follows a break in the epithelium or a surgical wound, and the course is measured in weeks rather than days, which is why diagnosis is often delayed.
Where does the infiltrate lie in post-LASIK nontuberculous mycobacterial keratitis?
In LASIK cases the infiltrate lies at the flap interface and can spread laterally beneath the flap, so lifting the flap is sometimes needed to obtain a sample.
Which stains demonstrate mycobacteria on a corneal scraping?
Acid-fast stains such as Ziehl-Neelsen or auramine-rhodamine can show the organisms, and the laboratory should be told that mycobacteria are suspected.
Which culture media should be requested when mycobacterial keratitis is suspected?
Cultures on Lowenstein-Jensen or Middlebrook media should be requested, and because growth takes days to weeks, treatment is often started before the result returns.
What is the traditional first-line topical agent for nontuberculous mycobacterial keratitis?
Amikacin as a topical fortified preparation is the traditional first-line agent, with the final choice guided by susceptibility testing.
Which drug class is commonly combined with amikacin for mycobacterial keratitis?
Fortified amikacin is often given together with a macrolide such as clarithromycin or azithromycin, and treatment is prolonged, often for months.
Which post-LASIK interface condition is sterile, appears early, and responds to steroids?
Diffuse lamellar keratitis is sterile, occurs early after LASIK and responds to steroids, whereas a late interface infiltrate misread as DLK and treated with steroids gets worse.
Why can early fluoroquinolone treatment mislead the clinician in mycobacterial keratitis?
Some fluoroquinolones have partial activity against the organism, so the ulcer improves briefly and then worsens, which can be read as a culture-negative infection.
How long should follow-up continue after the infiltrate of mycobacterial keratitis has cleared?
Follow-up should continue for several months after the infiltrate clears, because relapse after stopping treatment has been described.