Ocular Immunology & Inflammation, 2015; 23(2): 180–183

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ISSN: 0927-3948 print / 1744-5078 online
DOI: 10.3109/09273948.2013.870214

LETTER TO THE EDITOR

Staphylococcus aureus Blepharitis Associated with

Multiple Corneal Stromal Microabscess, Stromal
Edema, and Uveitis
Ana Boto-de-los-Bueis1, Almudena del Hierro Zarzuelo1, Adela Garcı́a Perea2,
Manuela de Pablos2, Natalia Pastora1, and Susana Noval1

1
Opthalmology Department, La Paz Universitiy Hospital, idiPaz. Paseo de la Castellana 261,
Madrid, 28046, Spain and 2Microbiology Department, La Paz Universitiy Hospital, idiPaz

ABSTRACT
We report a case of an immunocompetent woman with atypical marginal keratitis. She presented with recurrent
episodes of multiples microabscess distributed in a triangular pattern associated with stromal oedema and
anterior chamber uveitis, affecting both eyes, but not simultaneously. The episodes responded to steroid drops,
corneal inflammation was coincidental with a worsening of her blepharitis in the affected eye and S. aureus was
isolated from the lids.
Keywords: Blepharitis, catharral, keratitis, marginal, microabscess, multiple, Staphyloccocus aureus

Recurrent multiple corneal lesions can be associated
with immune-mediated ocular disorders, such as
Epstein-Barr virus (EBV) multifocal keratitis,1 archi-
pelago keratitis due to herpes simplex virus (HSV),2
or Thygeson keratitis.3 The differential diagnosis of
multiple corneal infiltrates also includes catarrhal
staphylococcal marginal keratitis.4 Catarrhal ulcers as
well as phlyctenular keratoconjunctivitis are derived
from an immune reaction in patients sensitized to
staphylococcal antigens. Catarrhal ulcers can be
multiple and are typically characterized by a circum-
ferential progression of marginal infiltrates, while
corneal phlyctenules typically are one nodule that
appears first at the limbus and may latter migrate
to clear cornea, with strands of superficial corneal
blood vessels following the course of the phyctenule.5
Both are usually a complication of longstanding
staphylococcal blepharitis, but it has been suggested
that other factors may be necessary for the initiation
of the catarrhal ulcers in addition to the existence
of S. aureus on the lid margin as an immune
abnormality of the ocular surface of the affected eye,
or the condition of contact between the cornea and the
lid margin.6
A healthy, nonatopic, 47-year-old woman com-
plained of pain and blurred vision in her left eye. Her
personal medical history was irrelevant, except for
a previous episode of lumbar pain that had been
studied by the internal medicine department years
ago without etiology. Her right eye (OD) was
amblyopic. Data concerning ophthalmological history
revealed multiple acute episodes of both eyes over the
past 18 years, which had been previously described as
acute anterior uveitis, keratouveitis, subepithelial–
intrastromal infiltrates, dendriform keratitis, and
marginal keratitis. These episodes had been mostly
clinically diagnosed and treated as herpetic. She also
reported an episode of infectious keratitis in 2006, in
which Staphylococcus aureus was isolated from the
corneal scrap and a polymerase chain reaction (PCR)
showed negative results for HSV, varicella zoster
virus (VZV), and cytomegalovirus (CMV) and a left
eye episode diagnosed and treated as archipelago
keratitis in 2007 (Figure 1A).

Received 31 July 2013; revised 13 November 2013; accepted 21 November 2013; published online 7 January 2014
Correspondence: Ana Boto-de-los-Bueis, Opthalmology Department, La Paz Universitiy Hospital, idiPaz, Paseo de la Castellana 261, Madrid,
28046 Spain, Email: mail@anaboto.es

180
 S. aureus stromal microabscess 181

In December 2009, she complained of blurred
vision, pain, and photophobia in her left eye. An
ophthalmic examination disclosed a visual acuity of
20/60 in the right amblyopic eye and 20/160 in her
left eye. The right eye was normal in appearance
except for mild meibomitis and a paracentral corneal
scar without blood vessels. The left eye showed
blepharoconjunctivitis with erythematous popular
lesions on the superior nasal skin; multiple anterior
stromal microabscesses situated on the periphery of
the superior nasal cornea; stromal diffuse infiltration
and edema; a paracentral scar; and 2+ grade anterior

FIGURE 1. (A) Left eye episode diagnosed and treated as archipelago keratitis in 2007, with multiple microabscesses in the supero
temporal cornea. (B) December 2009, left eye showing ulcerative blepharitis with superior lid oedema, erythema and erythematous
macular lesions on the superior nasal lid skin; conjunctival hyperemia; multiple anterior stromal microabscesses situated on the
superior nasal cornea and one infiltrate positioned in the inferior corneal; stromal diffuse infiltration and oedema. (C) November 2012,
right eye showed mild conjunctival hyperemia, and 3 anterior stromal infiltrates associated with mild anterior diffuse stromal
infiltration. (D) November 2012, her left eye showed superior lid oedema and an erythematous superior nasal lid lesion, meibomitis,
and conjunctival injection. The left cornea presented with multiple stromal infiltrates positioned in the supero nasal cornea moving
away from the limbus with a convexity border. (E–F) June 2013, right and left eyes showing eyelid margin without inflammation and
cornea without scarring or corneal neovascularization (barely perceptible paracentral scarring, on both eyes, detected in 2009, are not
seen in the pictures).

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182 A. Boto-de-los-Bueis et al.
chamber inflammation (Figure 1B). IOP was bilater-
ally within normal limits. We performed a multiple
PCR from the aqueous humor, which was negative
for HSV, VZV, CMV, EBV, and HHV 6. With the
suspected diagnosis of herpetic archipelago keratitis,
she received treatment with oral famciclovir and 1%
prednisolone acetate, which was tapered, and lid
hygiene for the blepharitis. The episode resolved after
4 months of treatment without vascular pannus or
corneal scarring. The results of a serology test for the
herpes simplex virus were negative for IgG and IgM
and the results of an enzyme immunoassay (EIA) for
syphilis was negative for IgG.
In February 2012, she again complained of pain
and photophobia in her OS and an examination
showed blepharitis and multiple corneal micro-
abscesses affecting the supero nasal cornea. Culture
and sensitivity from a left superior lid culture
showed Staphylococcus aureus, sensitive to methicillin
and ciprofloxacin. The corneal scrap was negative for
bacteria, fungus, and Acanthamoeba, and the corneal
multiple PCR was negative for the herpes family
virus. We treated the episode with 1% prednisolone
acetate for 1 month and 100 mg doxycycline for
5 months and we consulted with the dermatology
department, which ruled out acne rosacea.
In November 2012, she presented with pain but this
time in her right eye, which showed an acute
meibomitis and 3 anterior stromal infiltrates in the
inferior cornea (Figure 1C). Two weeks later she
also complained of pain in her left eye, which
presented with a new episode of multiple stromal
infiltrates positioned in the supero nasal cornea
and fitted with the eyelid inflammation location
(Figure 1D), associated with stromal diffuse infiltra-
tion and edema, and also with keratic precipitates
and a 2+ grade anterior chamber inflammation.
The left corneal scrape was processed for
bacterial, fungal, and Acanthamoeba cultures and for
the herpes family virus PCR; the aqueous humor
was processed for the herpes family virus PCR; all of
the results were negative. We treated both eyes with
fusidic acid ophthalmic gel for 3 weeks and 1%
prednisolone eyedrops with resolution at 5 weeks
without sequelae.
The last examination was performed in June 2013
and her visual acuity was 20/60 OD and 20/20 OS,
with no new scars from the episodes described above
(Figure 1E, F). The cultures of both superior lids were
negative and the Demodex examination on the lashes
was negative.
Staphylococcal marginal keratitis has been des-
cribed as localized peripheral stromal infiltrates that
spread paralleling the contour of the limbus. The
infiltrates are separated from the limbus and the
anterior chamber is typically quiet.7 Often, there are
signs of chronic staphylococcal blepharoconjunctivitis.
We believe that our case shares some characteristics
with this entity: first, the corneal scrapes were
negative and the episodes responded to steroid
drops; second, corneal inflammation was coincidental
with a worsening of her blepharitis in the affected
eye and the location of the keratitis fitted with the
location of the lid inflammation; and third, S. aureus
was isolated from the lids. Because the keratitis of our
patient consisted of multiple stromal inflammatory
infiltrates and was associated with stromal edema and
anterior chamber reaction, we can perhaps consider
our case as an atypical and severe staphylococcal
‘‘marginal’’ keratitis.
Staphylococcal marginal keratitis and phlyctenular
keratoconjunctivitis are noninfectious inflammatory
processes of the ocular surface that share some
similarities and both may be related to blepharitis,
but we excluded phlyctenulosis as a possibility
because our patient did not presented the typical
features of this entity, as nodules, limbus affectation,
or vascularizaded scars. On the contrary, archipelago
keratitis may be an atypical presentation of herpetic
keratitis, which is described as a multiple unilateral
keratitis consisting of multiple foci of peripheral
ulcers with intense underlying inflammatory infil-
trates, positioned in a linear radial pattern, and
extending centrally from a limbal lesion.2 This was
our first suspicion, but we observed that some of the
keratitis episodes, usually the most severe, were
coincidental with an acute blepharitis, and this
association pointed to staphylococcal marginal kera-
titis as the cause.
Marginal keratitis affects immunocompetent
humans and is the result of enhanced cell-mediated
immunity at the limbus to cell wall antigens of the
S. aureus located in the eyelids.8 However, there is
no clear information regarding which factors con-
tribute to the development of corneal involvement
associated with eyelid margin disease. Several studies
have tried to identify whether the features of the
S. aureus isolated in corneal or lid inflammation
differs from the S. aureus isolated in the healthy eye.
The staphylococcal enterotoxins, also known as
superantigens (SAg), can activate T cells without
processing by antigen presenting cells at picomolar
concentrations, and have been associated with an
increased severity of other immune disorders, such
as atopic dermatitis, but SAg are unlikely to play
a central role in the development of marginal
keratitis.9 S. aureus clones6 or toxins (alpha-, beta-,
delta-lysine) produced by S. aureus10 are also not
necessarily important for the initiation of the catarrhal
ulcer.
Probably we should focus our attention not only on
the microbial antigens that stimulate this delayed-
type hypersensitivity reaction, but also on the
characteristics of the patient who suffers from the
Ocular Immunology & Inflammation

condition. In 2005, Tomo Suzuki found that HLA-A26,
HLA-B35, and HLA-DRB1*08 were significantly
increased in phlyctenular keratitis related to meibo-
mitis, so some genetic predisposition may underly
the different types of ocular surface inflammatory
diseases associated with meibomian inflammation.11
In that paper, the therapeutic management of the
phlyctenular keratitis was also relevant because by
focusing on the treatment of meibomitis with the
specific antimicrobial agents for the bacteria isolated
and using treatment intravenously in severe cases,
the ocular surface inflammation was eradicated.
Topical corticosteroids are the mainstay in the treat-
ment of Staphylococcus marginal keratitis and may be
use in combination with a broad-spectrum topical
antibiotic in cases with epithelial breakdown, with lid
hygiene and topical antibiotic for lids to decrease
recurrences. Tetracycline causes a significant decrease
in the production of lipase and inhibition of growth
in S. aureus strains and can be effective in the long-
term management of patients with meibomian
keratoconjunctivitis.12
This case describes the presentation and course
of recurrent multiple stromal keratitis associated with
S. aureus blepharitis, with some clinical particularities
10. Seal D, Ficker L, Ramakrishnan M, et al. Role of staphylo-
that have not previously been described.
11. Suzuki T, Mitsuishi Y, Sano Y, et al. Phlyctenular keratitis
DECLARATION OF INTEREST
12. Dougherty JM, McCulley JP, Silvany RE, Meyer DR. The
The authors report no conflicts of interest. The authors
alone are responsible for the content and writing of
the paper.
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S. aureus stromal microabscess 183
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