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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 or the condition of contact between the cornea and the
with immune-mediated ocular disorders, such as lid margin.6
Epstein-Barr virus (EBV) multifocal keratitis,1 archi- A healthy, nonatopic, 47-year-old woman com-
pelago keratitis due to herpes simplex virus (HSV),2 plained of pain and blurred vision in her left eye. Her
or Thygeson keratitis.3 The differential diagnosis of personal medical history was irrelevant, except for
multiple corneal infiltrates also includes catarrhal a previous episode of lumbar pain that had been
staphylococcal marginal keratitis.4 Catarrhal ulcers as studied by the internal medicine department years
well as phlyctenular keratoconjunctivitis are derived ago without etiology. Her right eye (OD) was
from an immune reaction in patients sensitized to amblyopic. Data concerning ophthalmological history
staphylococcal antigens. Catarrhal ulcers can be revealed multiple acute episodes of both eyes over the
multiple and are typically characterized by a circum- past 18 years, which had been previously described as
ferential progression of marginal infiltrates, while acute anterior uveitis, keratouveitis, subepithelial–
corneal phlyctenules typically are one nodule that intrastromal infiltrates, dendriform keratitis, and
appears first at the limbus and may latter migrate marginal keratitis. These episodes had been mostly
to clear cornea, with strands of superficial corneal clinically diagnosed and treated as herpetic. She also
blood vessels following the course of the phyctenule.5 reported an episode of infectious keratitis in 2006, in
Both are usually a complication of longstanding which Staphylococcus aureus was isolated from the
staphylococcal blepharitis, but it has been suggested corneal scrap and a polymerase chain reaction (PCR)
that other factors may be necessary for the initiation showed negative results for HSV, varicella zoster
of the catarrhal ulcers in addition to the existence virus (VZV), and cytomegalovirus (CMV) and a left
of S. aureus on the lid margin as an immune eye episode diagnosed and treated as archipelago
abnormality of the ocular surface of the affected eye, 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 scar without blood vessels. The left eye showed
vision, pain, and photophobia in her left eye. An blepharoconjunctivitis with erythematous popular
ophthalmic examination disclosed a visual acuity of lesions on the superior nasal skin; multiple anterior
20/60 in the right amblyopic eye and 20/160 in her stromal microabscesses situated on the periphery of
left eye. The right eye was normal in appearance the superior nasal cornea; stromal diffuse infiltration
except for mild meibomitis and a paracentral corneal 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).
chamber inflammation (Figure 1B). IOP was bilater- We believe that our case shares some characteristics
ally within normal limits. We performed a multiple with this entity: first, the corneal scrapes were
PCR from the aqueous humor, which was negative negative and the episodes responded to steroid
for HSV, VZV, CMV, EBV, and HHV 6. With the drops; second, corneal inflammation was coincidental
suspected diagnosis of herpetic archipelago keratitis, with a worsening of her blepharitis in the affected
she received treatment with oral famciclovir and 1% eye and the location of the keratitis fitted with the
prednisolone acetate, which was tapered, and lid location of the lid inflammation; and third, S. aureus
hygiene for the blepharitis. The episode resolved after was isolated from the lids. Because the keratitis of our
4 months of treatment without vascular pannus or patient consisted of multiple stromal inflammatory
corneal scarring. The results of a serology test for the infiltrates and was associated with stromal edema and
herpes simplex virus were negative for IgG and IgM anterior chamber reaction, we can perhaps consider
and the results of an enzyme immunoassay (EIA) for our case as an atypical and severe staphylococcal
syphilis was negative for IgG. ‘‘marginal’’ keratitis.
In February 2012, she again complained of pain Staphylococcal marginal keratitis and phlyctenular
and photophobia in her OS and an examination keratoconjunctivitis are noninfectious inflammatory
showed blepharitis and multiple corneal micro- processes of the ocular surface that share some
abscesses affecting the supero nasal cornea. Culture similarities and both may be related to blepharitis,
and sensitivity from a left superior lid culture but we excluded phlyctenulosis as a possibility
showed Staphylococcus aureus, sensitive to methicillin because our patient did not presented the typical
and ciprofloxacin. The corneal scrap was negative for features of this entity, as nodules, limbus affectation,
bacteria, fungus, and Acanthamoeba, and the corneal or vascularizaded scars. On the contrary, archipelago
multiple PCR was negative for the herpes family keratitis may be an atypical presentation of herpetic
virus. We treated the episode with 1% prednisolone keratitis, which is described as a multiple unilateral
acetate for 1 month and 100 mg doxycycline for keratitis consisting of multiple foci of peripheral
5 months and we consulted with the dermatology ulcers with intense underlying inflammatory infil-
department, which ruled out acne rosacea. trates, positioned in a linear radial pattern, and
In November 2012, she presented with pain but this extending centrally from a limbal lesion.2 This was
time in her right eye, which showed an acute our first suspicion, but we observed that some of the
meibomitis and 3 anterior stromal infiltrates in the keratitis episodes, usually the most severe, were
inferior cornea (Figure 1C). Two weeks later she coincidental with an acute blepharitis, and this
also complained of pain in her left eye, which association pointed to staphylococcal marginal kera-
presented with a new episode of multiple stromal titis as the cause.
infiltrates positioned in the supero nasal cornea Marginal keratitis affects immunocompetent
and fitted with the eyelid inflammation location humans and is the result of enhanced cell-mediated
(Figure 1D), associated with stromal diffuse infiltra- immunity at the limbus to cell wall antigens of the
tion and edema, and also with keratic precipitates S. aureus located in the eyelids.8 However, there is
and a 2+ grade anterior chamber inflammation. no clear information regarding which factors con-
The left corneal scrape was processed for tribute to the development of corneal involvement
bacterial, fungal, and Acanthamoeba cultures and for associated with eyelid margin disease. Several studies
the herpes family virus PCR; the aqueous humor have tried to identify whether the features of the
was processed for the herpes family virus PCR; all of S. aureus isolated in corneal or lid inflammation
the results were negative. We treated both eyes with differs from the S. aureus isolated in the healthy eye.
fusidic acid ophthalmic gel for 3 weeks and 1% The staphylococcal enterotoxins, also known as
prednisolone eyedrops with resolution at 5 weeks superantigens (SAg), can activate T cells without
without sequelae. processing by antigen presenting cells at picomolar
The last examination was performed in June 2013 concentrations, and have been associated with an
and her visual acuity was 20/60 OD and 20/20 OS, increased severity of other immune disorders, such
with no new scars from the episodes described above as atopic dermatitis, but SAg are unlikely to play
(Figure 1E, F). The cultures of both superior lids were a central role in the development of marginal
negative and the Demodex examination on the lashes keratitis.9 S. aureus clones6 or toxins (alpha-, beta-,
was negative. delta-lysine) produced by S. aureus10 are also not
Staphylococcal marginal keratitis has been des- necessarily important for the initiation of the catarrhal
cribed as localized peripheral stromal infiltrates that ulcer.
spread paralleling the contour of the limbus. The Probably we should focus our attention not only on
infiltrates are separated from the limbus and the the microbial antigens that stimulate this delayed-
anterior chamber is typically quiet.7 Often, there are type hypersensitivity reaction, but also on the
signs of chronic staphylococcal blepharoconjunctivitis. characteristics of the patient who suffers from the