keratitis results from the interaction of a broad spectrum of pathogens
and a diverse range of host responses. Uncertainty about treatment endpoints
sometimes leads to toxic levels of antibiotic therapy and unnecessarily
frequent clinical review. This article draws on a comprehensive review
that can be referred to for further detail.1 It outlines a simplified
management strategy that is successful for the majority of cases and identifies
the point of failure when referral may be indicated.
keratitis is rare in the absence of predisposing factors which include
(1) contact lens wear, (2) ocular surface disease, eg (a) herpetic keratitis,
(b) corneal-anaesthesia, (c) exposure and (d) bullous keratopathy and (3)
trauma. Infection can present as an epithelial defect or corneal melt,
without inflammation, in the immunocompromised or in those using topical
steroids in whom corneal infiltration by leucocytes, the hallmark of microbial
keratitis, may be absent.
scraping is indicated whenever microbial keratitis is suspected. It provides
material for a microbiological diagnosis, debrides necrotic tissue and
enhances antibiotic penetration. Endophthalmitis does not follow bacterial
keratitis without corneal perforation (unlike fungal keratitis) so that
anterior chamber and vitreous taps are not indicated when perforation is
absent. Corneal culture materials should be available in the emergency
area and include, as a minimum, a slide for Gram staining and a blood agar
plate for aerobic incubation. Most corneal isolates in temperate areas,
including fungi, will grow on these media. Ocular specimens should be inoculated
directly onto the media avoiding the use of transport or storage media.
Some of the pathogens isolated from ocular infections may be considered
to be normal flora by non-ocular microbiologists, so it is important that
ophthalmologists liaise closely with the laboratory. A 21 gauge needle
may be used to take the specimens.
can be divided into a sterilisation phase and a healing phase with clearly
defined endpoints for clinical review and decision making. Clinical signs
may not indicate when corneal sterilisation has occurred, after starting
intensive therapy, because sterilisation often precedes both epithelial
healing and the resolution of inflammatory signs.
may also be delayed by preservative or agent related toxicity where intensive
topical treatment is prolonged. Intensive antibiotic therapy is given for
a limited period in the stetilisation phase and is followed by the healing
phase, in which reduced therapy is aimed at (1) limiting further inflammatory
damage, (2) preventing superinfection, and (3) promoting epithelial healing.
should consist of broad spectrum topical antibacterial treatment because
(1) a negative Gram stain does not exclude keratitis, (2) bacterial isolates
are far more common than fungi or amoebae and (3) polymicrobial infections
are common. This approach is continued unless the infecting agents are
identified, with their antimicrobial sensitivities, enabling specific therapy
choice of antibiotics now hes between the standard regimen of topical,
commercially unavailable, fortified aminoglycoside and fortified cephalosporin
drops (ie gentamicin 1.5% and cefuroxime 5%) or the new regime of fluoroquinolone
monotherapy with commercially available ciprofloxacin or ofloxacin 0.3%.
the standard and new regimens offer broad spectrum cover against the majority
of bacterial pathogens but fluoroquinolone monotherapy has advantages and
has been shown to have equal efficacy in recent clinical trials.2,3,4
However, fluoroquinolones may not adequately treat streptococcal keratitis
and comination therapy of a quinolone with a fortified cephalosporin may
be advisable in patients with ocular surface disease or in children in
whom streptococcal infection is more common. Currently both the standard
and fluoroquinolone regimen encounter bacteriola resistance in about 5%
of cases. Neither regimen treats fungal or acanthamoeba infection.
administration of topical antibiotic therapy for five days leaves a wide
rnargin of safety for most bacterial infections and compares well with
a gradual reduction of high dose antibiotic treatment.4
cases can be managed successfully as outpatients with initial review after
forty eight hours. Admission may be necessary where good compliance is
unlikely or for overnight treatment in severe infections (axial lesions,
lesions 6mm or more in diameter, or with 50%, or more stromal thinning).
Systemic antibiotics (ie ciprofloxacin 750mg bd) ire indicated where the
ulcer is close to the limbus. This may help protect from contiguous spread
of infection to the sclera and enhance antibiotic delivery to peripheral
lesions. Adjunctive treatment at this stige may include (1) dilating drops,
(2) analgesic medication or (3) hypotensive agents for secondary glaucoma.
Subconjunctival injections should be avoided.
and fungal kerititis are rarely rapidly progressive and may be exacerbated
by bacterial superinfection. Specific investigations and treatment regimens,
involving a much more prolonged sterilisation phase, are required for both
and lie outside the scope of this review. However, unless there is clear
clinical evidence (or a Gram stain) suggesting non-bacteriid infection,
it is appropriate to commence treatment with intensive broad spectrum antiibiotics
for a defined initial period.
review at two days is to detect rapidly progressive cases and assess the
culture results. Daily review can be confusing as the inflammatory reaction
may be enhanced by endotoxin release within the first 48 hours.
definite progression at this stage (increased stromal thinning or a clear
expansion of the ulcer) is unusual, and implies that patients are either
insensitive to, or not complying with, antimicrobial therapy.
rapid early progression can be treated by admitting patients to ensure
compliance and reviewing the microbiology results. Unless these indicate
resistance to the primary therapy, with a change to a more appropriate
antibiotic, then continue initial broad spectrum antibiotic therapy until
two days of hourly treatment day and night have been followed by a further
three days of hourly treatment during the day. Further progression after
this point is then an indication for specialist referral.
or actual perforation indicate urgent referral as emergency penetrating
keritoplasties in these circumstances carry a poor prognosis for vision,
are difficult to perform well, and can often be avoided even after a perforation.
cultures should be incubated for a minimum of 14 days before being reported
as culture negative, growth of most pathogens can be expected ifter 48
progress is satisfactory, there is no indication for altering antibiotic
therapy. But sensitivity testing can be invaluable in guiding the choice
of a more appropriate antibiotic where bacterial keratitis is progressive.
at one week is necessary to determine whether the disease is progressive
or resolving. Clear evidence of poor compliance or, in culture positive
cases, resistance to the initial antibiotic choice are indications for
re-entering the sterilization phase using appropriate specific therapy.
Deteriorating or static cases should be referred, whereas cases in which
resolution is partial but incomplete may safely enter a second phase of
treatment directed at encouraging healing.
is commonly retarded by persisting inflammation, treatment toxicity or
untreated underlying ocular surface disease. Antibiotic treatment should
be reduced to prophylactic levels at this stage to avoid toxicity and unpreserved
medication used where possible.
surface disorders (ie dry eyes, exposure, entropion and blepharitis) must
be treated. Complete resolution of anterior chamber and comeal inflammatory
signs is normal in microbial keratitis without steroid treatment. However,
topical steroids may speed re-epithelisation and resolution of the inflammatory
response although their use will enhance fungal or herpetic infection and
may increase the risk of perforation by inhibiting wound healing. In corneal
graft recipients, without evidence of fungal infection, steroid therapy
should be introduced at the outset to protect against a rejection episode.
review after one week of the healing phase (ie week 3 after presentation),
referral may be indicated as indolent ulceration may be due to unusual
organisms, usually of low virulence, with continued disease progression,
slow healing is occurring patients can continue with the healing phase
regimen until resolution is complete.
DS, Kart JKG (1995). Strategies for the management of microbial keratitis.
Br J Ophthalmol 1995; 79; 777-86.
O'Brien TP. Maguire MG, Fink NE, Alfonso E, McDonnell P (1995). Efficacy
of ofloxacin vs cefazolin and tobramycin in the therapy for bacterial keratitis.
Report from the Bacterial Keratitis Study research Group. Arch-Ophthalmol
1995; 113; 1257-65.
Hyndiuk RA, Eiferman RA, Caldwell DR, Rosenwasser GO, Santos CI, Katz HR,
Badrinath SS, Reddy MK, Adenis JP, Klauss V. Comparison of ciprofloxacin
ophthalmic solution 0.3% to fortified tobramycin-cefazolin in treating
bacterial corneal ulcers. Ciprofloxacin Bacterial keratitis Study Group.
Ophthalmology 1996; 103; 1854-62.
The Ofloxacin Study Group (1997). Ofloxacin monotherapy for the primary
treatment of microbial keratitis: a double-masked randomised controlled
trial with conventional dual therapy. Ophthalmology 1997; in press.