is a nodular inflammation of the perilimbal tissues that occurs secondary
to an allergic hypersensitivity response of the cornea.16 The
disease has a worldwide distribution and is most often seen in the first
and second decades in women (60%) living in crowded or impoverished quarters.
disease has been associated with systemic disorders such as Behçet's disease,
tuberculosis, HIV and rosacea among others.46 Patients typically
present with symptoms of tearing, ocular irritation, mild to severe photophobia
and a history of similar episodes.13,6 If the underlying cause
is staphylococcus, a rope-like, mucopurulent discharge may be present.2
There are two
distinct types of phlyctenular lesions: corneal and conjunctival.
Biomicroscopic evaluation of a conjunctival (vascularized) phlyctenule
reveals a 1mm to 3mm, hard, slightly elevated, yellowish-white nodule,
surrounded by a hyperemic response, in the vicinity of the inferior
limbus. The lesions tend to be bilateral. Corneal phlyctenules produce
more severe symptoms. They usually begin adjacent to the limbus as
a white mound, with a radial pattern of vascularized conjunctival
vessels on the conjunctival side.2 The lesion may then
migrate toward the center of the cornea, progressing as a gray-white,
superficial ulcer surrounded by infiltrate in the areas where the
lesion has been.16
The exact mechanism
by which phlyctenules are produced is unclear.
Histologically, they are composed of lymphocytes, histocytes and
plasma cells. Polymorphonuclear leukocytes are found in necrotic
lesions.2 Their formation seems to be the result of a
delayed hypersensitivity reaction to tuberculin protein, Staphyloccocus
aureus, Coccidioides immitis, Chlamydia, ocular rosacea, some varieties
of interstitial parasites, or Candida albicans.13 Rarely
are cases idiopathic; such a diagnosis should be made by exclusion.
of phlyctenular keratoconjuntivitis begins with patient education
to improve eyelid hygiene. Lid scrubs two to three times a day, along
with artificial tears and ointments, may soothe and reverse mild
cases. Moderate to severe cases require topical steroidal or steroidal/antibiotic
combination medicines. Cycloplegia is only necessary if significant
inflammation is present. In mild cases, lid scrubs and copious lubrication
may suffice. In most cases, prednisolone acetate (Pred Forte, Allergan),
one drop, q2h-qid is sufficient. A combination agent such as Tobradex
is an excellent option. If the suspected etiology is staph or rosacea,
250mg of oral tetracycline qid or 250mg erythromycin qid, along with
topical antibiotic ointments such as bacitracin or erythromycin hs,
should be added.6 Additionally, topical metronidazole
(Metrogel, Galderma) applied to the skin tid is also effective. Because
tetracycline can damage and discolor the teeth of children, it is
contraindicated in persons under the age of 10. Here, doxycycline,
100mg tid, or erythromycin 250mg qid po, may be substituted.13,6 Treatment
should continue for two to four weeks. In suspicious cases, a chest
X-ray, PPD, HIV titre and HLA typing (BehcetHLAB51) should
doses of oral and topical steroids and antibiotics may continue to
relieve patients' signs and symptoms. This practice is acceptable,
provided that the patient tolerates the regimen. Weekly follow-up
is recommended. Once significant improvement is noted, the steroid
should be tapered. The antibiotic coverage should continue, prophylactically,
until the steroid is removed. Eyelid hygiene should be maintained
- Other potential
differential diagnoses include infiltrates secondary to chronic
blepharitis, inflamed pingueculum, herpes simplex and infectious
or marginal corneal
FLUOROQUINOLONES: COMBATING OR PROMOTING BACTERIAL RESISTANCE?
ARGUE that the fluoroquinolones represent the most potent and
beneficial antibiotic agents currently available. Whether for
peri-operative prophylaxis or management of bacterial ocular
infection, fluoroquinolone antibiotics are clearly the market
leader at this time. These drugs work by inhibiting the function
of crucial bacterial enzymes involved in cellular replication.
This leads to disruption of the DNA, which prevents bacteria
from replicating, resulting in rapid death of the invading organisms.
fluoroquinolones include Vigamox (0.5% moxifloxacin, Alcon) and
Zymar (0.3% gatifloxacin, Allergan). They differ chemically and
pharmacologically from previous generations with respect to side
chains located at the C-7 and C-8 positions. These side chains
impart enhanced bactericidal activity and prevent bacterial defenses
from rendering the drugs inert. Subsequently, these new drugs
display excellent intrinsic activity against both common and
atypical bacterial pathogens. And, while many common bacterial
strains are known to have developed resistance to older fluoroquinolones
such as ciprofloxacin and ofloxacin,1 these organisms
appear to be fully susceptible to the new fourth-generation fluoroquinolones.
has demonstrated that these new drugs are significantly more
potent against a wide range of bacterial pathogens.2,3 In
addition, at least one of the new fourth-generation fluoroquinolones,
Vigamox, boasts improved dosing (tid vs. qid), higher concentration
(0.5% vs. 0.3%), more neutral pH (6.8 vs. 4.5 to 6.0), and absence
of added preservatives such as benzalkonium chloride. Clearly,
with all these advantages, what could possibly deter the eye
care community from immediately adopting this medication as the
new drug of choice?
many have expressed hesitation to begin utilizing the new fourth-generation
fluoroquinolones like Vigamox and Zymar for fear of creating
new, resistant strains of bacteria.
After all, it has been less than 15 years since Ciloxan and Ocuflox were introduced,
and we are already seeing significant resistance to these drugs. Hence, some
argue that if we use our new "big guns" on routine ocular infections, rather
than reserve them for severe infections, we will promote and accelerate the
process of resistance.
all antibiotics are subject to resistance over time, the new
fourth-generation fluoroquinolones stand the best chance of overcoming
this trend. By their very design, they have been engineered to
defy bacterial resistance. Older fluoroquinolones are known to
target the enzyme DNA gyrase (topoisomerase II) in Gram-negative
bacteria, and topoisomerase IV in Gram-positive bacteria. By
contrast, the new fourth-generation drugs have the capacity to
block both of these enzymes simultaneously in both Gram-positive
and Gram-negative bacteria; this means that, for resistance to
occur, mutations would have to occur simultaneously at two sites
rather than just one. Another characteristic of the new drugs
helps to combat bacterial efflux, a process by which the pathogens
actively pump the drugs out of the cytoplasm. The surest way
to prevent resistance is to not use doses below that recommended
in the product insert. Antibiotics should not be tapered. They
should be used to their desired effect and then abruptly discontinued.
Using sublethal dosing will lead to resistance. For example,
Vigamox is dosed tid. Dosing should not be below tid.
No one can
predict the future, but one observation can be made with relative
confidence--the continued use of older, second- and third-generation
fluoroquinolones will certainly not help to overcome the current
trends in bacterial resistance. The fourth-generation fluoroquinolones,
on the other hand, offer our current patients the best possibility
for a positive outcome. Whether for surgical prophylaxis or the
treatment of bacterial ocular infection, drugs such as Vigamox
and Zymar deserve serious consideration.
Goldstein MH, Kowalski RP, Gordon YJ. Emerging fluoroquinolone
resistance in bacterial keratitis: A 5-year review. Ophthalmology
- Mather R, Karenchak LM, Romanovski
EG, et al. Fourth-generation fluoroquinolones: New weapons
in the arsenal of ophthalmic
antibiotics. Am J Ophthalmol 2002; 133(4):163-6.
RP, Dhaliwal DK, Karenchak LM, et al. Gatifloxacin and moxifloxacin:
An in vitro susceptibility comparison to
levofloxacin, ciprofloxacin, and ofloxacin using bacterial
keratitis isolates. Am J Ophthalmol 2003; 136(3):500-5.
- Cullom RD, Chang B. Cornea : Phylectenulosis. In : Cullom RD,
Chang B. The Wills Eye Manual: Office and Emergency Room Diagnosis
of Eye Disease. Philadelphia, PA: J.B. Lippincott Co. 1994;64-65.
- Wagoner MD, Bajart AM, Allansmith MR. Phlyctenulosis. In: Fraunfelder
FT, Roy FH Current Ocular Thearapy 3. Philadelphia,
PA ; W.B. Saunders Co. 1990 :454-456.
- Schimmel DJ. Infiltrative
Keratitis. In: Onofrey, B.E. Clinical Optometric Pharmacology
and Therapeutics. Philadelphia, PA: J.B.
Lippincott Co. 1994; 1-13.
- Hochedez P, Zeller V, Truffo,
C, et al. Lymph-node tuberculosis in patients infected or not with
HIV: general characteristics,
clinical presentation, microbiological diagnosis and treatment.
Pathol Biol 2003; 51(89):496-502.
- Hashida N, Ohguro
N, Yamamoto S, et al. Unusual neutrophil infiltration under
the soft contact lens in a patient with Behcet's
disease. Jpn J Ophthalmol 2003; 47(5):469-72.
BH, Gurwood AS. Recurrent phlyctenular keratoconjunctivitis:
a forme fruste manifestation of rosacea. Optometry 2001; 72(3):179-84.
reports in this section