Corneal Ulcers
Corneal Ulcers
Corneal Ulcers
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2 0 1 2
Jason S. Calhoun, Mayo Clinic, Jacksonville, Fla.
Confronting
Corneal Ulcers
PINPOINTING ETIOLOGY IS CRUCIAL FOR TREATMENT DECISION MAKING
W
hen a large corneal ulcer is staring
you in the face, time is not on your
side. “Despite varying etiologies and
that raises high-stakes questions presentations, as well as dramatically
different treatment approaches at
about diagnosis and management. times, corneal ulcers have one thing
in common: the potential to cause devastating loss
of vision—often rapidly,” said Sonal S. Tuli, MD,
Four corneal experts provide a guide associate professor of ophthalmology, director
of the cornea and external diseases service, and
e y e n e t 45
in his eye or got poked in the eye, that foreign-
body sensation tells you there’s an epithelial defect,
which is a symptom more typical of a bacterial
Profiling the Ulcer ulcer,” said Dr. Tuli. “If it’s more of ‘a toothache
The number of ulcers seen in clinical practice in my eye’ or ‘when the light hits my eye, it really
depends largely on geography. “In the southern hurts,’ that’s more likely a nonbacterial or nonin-
United States, corneal ulcers are significantly more fectious keratitis.”
common than in northern states because it’s warm And how severe is the pain? If it’s Acanthamoeba
and humid, with lots of young people swimming keratitis, for example, patients typically complain
and sleeping in their contact lenses,” said Dr. Tuli. of far more pain than the physical findings would
Estimates of annual incidence in the United States suggest; if it’s herpetic keratitis, patients usually
range from 30,000 to 75,000.1,2 don’t have pain complaints, even though the ap-
Categories. Ulcers are primarily divided into in- pearance would suggest the presence of severe
fectious and noninfectious categories. Bacterial in- pain, said Dr. Mah.
fections (chiefly Pseudomonas and Staphylococcus) Consider the context. The clinician should seek
are by far the most common, but other microbes clues by asking the patient about environmental
include fungi (molds such as Fusarium and yeasts or social factors that could be related to the infec-
such as Candida), parasites (Acanthamoeba), and tion. For example, Were you wearing contact lenses
viruses (herpes simplex). Noninfectious ulcers in- when the problem started? Did you wear lenses
clude autoimmune, neurotrophic, toxic, and aller- while swimming or wash them in tap water? Have
gic keratitis, as well as chemical you been gardening, or have you encountered veg-
The first question is always whether burns and keratitis secondary to etation or dirt in another activity?
entropion, blepharitis, and a host It’s also important to talk about ocular history,
the keratitis is bacterial or not. of other conditions. in particular, such risk factors as previous herpetic
Talk to your patients. “As clini- keratitis, ocular surgery, current or recent use of
—Sonal S. Tuli, MD cians, we sometimes get sucked ocular medications, dry eye, or trauma. Systemic
into taking a quick look at the diseases, such as diabetes or rheumatoid arthritis,
eye to get the diagnostic process started without also predispose patients to corneal ulcers.3
really talking to the patient,” said Francis R. Mah, “If the patient wears contact lenses, that’s obvi-
MD, associate professor of ophthalmology and ously going to be a huge factor in swaying your
pathology and medical director of the Charles T. diagnosis toward infectious keratitis. However, the
Campbell Ophthalmic Microbiology Laboratory history and physical exam could reveal a sterile
at the University of Pittsburgh. “It’s imperative to contact lens–associated ulcer caused by the patient
take a detailed history to help identify the ulcer’s sleeping in contact lenses,” said Dr. Mah.
etiology.” Examine the eye. The physical exam should
Ask about pain. How does the patient describe include measurement of visual acuity, external ex-
the pain? “If a patient says it feels like he has a rock amination, and slit-lamp biomicroscopy. Bacterial
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ulcers are typically associated with a large amount can still get valuable information from a Gram
of necrotic material and an epithelial defect; other stain,” she said.
types are generally less necrotic and may have in- The site should be cultured even in patients al-
tact overlying epithelium.3 ready on antibiotics; it’s still possible to get positive
Culture the site. With the advent of fluoroquino- results, Dr. Tuli added. “If you don’t get a positive
lone antibiotics, which can treat both gram-nega- culture, you have to start considering nonbacterial
tive and gram-positive causes.”
The duration of symptoms species, many clinicians
have dropped culturing When to Refer
can be helpful to the as part of their diag- Typically, when comprehensive ophthalmologists
nostic practice.4,5 Dr. see a patient with a corneal ulcer, they reflexively
differential diagnosis. Tuli said that it’s under- start fluoroquinolones. If the ulcer doesn’t notice-
Bacterial ulcers, for ex standable if you don’t
culture small peripheral
ably improve in a couple of days, they refer the case
to a cornea specialist or an academic institution.
ample, have a rapid onset ulcers. But, at the very But there are instances that require immedi-
least, you should always ate referral to a cornea specialist to make sure the
of symptoms compared culture central ulcers patient doesn’t go downhill quickly. For example,
and ulcers 2 mm or if an ulcer is larger than 2 mm, especially if it’s
with fungal ulcers, which larger prior to initiating located directly on the visual axis, or if there’s stro-
may take days to become therapy. “If you don’t
have access to all the
mal melting, anterior chamber inflammation, or
any scleral involvement at all, immediate referral is
problematic. culture media of a lab warranted, said Dr. Mah. Any suspicious or atypi-
(blood, chocolate, and cal presentation should also be strongly considered
—Natalie A. Afshari, MD Sabouraud agar), you for referral.
e y e n e t 47
rial ulcers is noncompliance, said Dr. Mah. “If the usually within the first 48 hours after initiating
ulcer is very serious or there was a delay in accurate antibiotic therapy.”
diagnosis and treatment, or if a patient has no sup- When to question the diagnosis. “Day 1, you do
port system to help with compliance, consider ad- a culture and start a fluoroquinolone. Day 2, you
mitting the patient to the hospital overnight.” expect the patient to feel at least no worse and,
Steroids: Use with care. Although using hopefully, a little better. Days 2, 3, and 4, the ulcer
The key to the differential strong antibiotics will sterilize the ulcer, should start consolidating and the appearance of
it won’t control the inflammatory reac- the eye should be noticeably improved,” said Dr.
diagnosis is to be very tion, which can be just as damaging to the Mah. “I have to reassure patients that vision is the
cornea as the infection itself, according to last thing to improve. But if you don’t have signs of
familiar with the presen Dr. Afshari. As soon as there is evidence at least some overall improvement in four to seven
that the antibiotic is working (e.g., the days, then start considering atypical causes of the
tation of a typical bacte epithelial defect is starting to close, or the keratitis. This is the time to refer the patient to a
rial ulcer so that when the culture shows sensitivity to antibiotics), cornea specialist.”
using corticosteroids will inhibit the in-
appearance and patient flammatory response and reduce corneal
cording to Dr. Mah. In addition, he suggested that Dosing regimen. Fungal keratitis requires medi-
clinicians maintain a high index of suspicion in the cation for six weeks on average. The dosing sched-
setting of contact lens wear and in humid weather ule doesn’t have to be as aggressive as for bacterial
conditions. ulcers because fungi don’t replicate as fast as bacte-
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ria. “Patients will need to be on medication for so doesn’t resolve, medical options are limited. Be-
long that you don’t want to exhaust them early on cause the topical medications do not penetrate
with an intensive schedule, raising the risk of non- deeply, Dr. Tu said that “trying different delivery
compliance,” said Dr. Tuli. methods, like injecting the antifungal directly into
Management of complicated cases. A particularly the stroma to achieve higher concentrations, is one
worrisome risk in infection with fungi, particu- well-documented option.” Corneal transplantation
larly molds, is deep penetration, not only into the should be considered urgently if there is risk of the
cornea but also into the eye itself. If the infection infection moving into the eye or adjacent sclera.
you should suspect HSV, especially if the patient not an infection but rather an inflammation caused
has a history of similar episodes. by the immune response to dead viral particles.
Types of HSV keratitis. Primary HSV infection A third type of keratitis associated with HSV
typically occurs in children, but the virus persists is what Dr. Tuli likes to call “a diabetic foot in
e y e n e t 49
the eye.” Each time the virus replicates, it bursts
out and kills off more nerves that supply the eye,
for epithelial
ulcers are con-
One trap some doctors fall into is
reducing sensation. The resultant hyposensitivity traindicated in treating for an extended period
can lead to unrecognized trauma, predisposing pa- stromal kera-
tients to neurotrophic keratitis (discussed below). titis because without results. We frequently see
they are inef-
Treatment fective (there
patients who come in having been
Antivirals. For epithelial ulcers, the mainstay of is no live vi- treated with topical antivirals for
treatment has been topical antivirals, specifically rus) and may
trifluridine drops (nine times a day) or ganciclovir cause toxicity. weeks on end. Not only is that toxic,
gel (five times a day). Topical Treat-
antivirals shouldn’t be used for ment is more but if a patient is not getting better
longer than 10 to 14 days be- complex in
4
cause they kill both normal and patients with
in seven to 10 days, the likelihood of
infected cells, leading to corneal
toxicity.8
herpetic nec-
rotizing kera-
its being a simple viral infection is
Gentle-wiping debridement titis, in which very low. —Elmer Y. Tu, MD
with a cotton-tipped applicator both live virus
may benefit epithelial ulcers, as and an immune response are present. “You have to
the infected cells come off easily, walk a tightrope trying to figure out which medi-
according to Dr. Tuli. In addi- cation to increase and which to decrease,” said Dr.
tion, oral antivirals like acyclo- Tuli. Many of these patients end up with long-term
(4) Herpes vir, valacyclovir, and famciclovir may shorten the problems, including glaucoma and corneal scar-
simplex virus course of the keratitis, said Dr. Tu. ring.
keratitis. Steroids: for stromal keratitis only. The treatment Other measures. Because eyes with viral keratitis
for stromal keratitis is topical steroids. In addi- are prone to superinfections, Dr. Tuli suggested
tion, patients are usually given oral antivirals as using a daily drop of antibiotic to protect against
prophylaxis to prevent spontaneous recurrence of bacterial infection. In addition, for patients who
epithelial disease while the patient is on steroids. are immunocompromised or have recurrent or
However, steroids are contraindicated in epithelial vision-threatening disease, chronic low-dose oral
keratitis because they would help the virus to rep- acyclovir or valacyclovir significantly reduces the
licate. Conversely, the topical antivirals prescribed risk of recurrence.
involvement or inflammation, it is most likely a ulcer supportively with some antibiotics and lubri-
sterile ulcer. “These are very responsive to ste- cating ointment,” said Dr. Tuli.
roids,” said Dr. Mah. “If you’re concerned about a Autoimmune-related keratitis (Fig. 5) is typically
secondary bacterial infection, I recommend giving associated with an underlying autoimmune disease
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such as rheumatoid arthritis or Sjögren syndrome. brication, collagenase inhibitors,
It’s essential to tag-team with the treating rheuma- and bandage contact lenses, as 6
tologist to manage the condition, according to Dr. well as treating the inflamma-
Tu. Moderate to severe ulcers can progress rapidly tion with topical steroids cau-
to melting and perforation. “If a patient has not tiously. However, some patients
yet received an underlying diagnosis, the biggest will go to great lengths to con-
hurdle initially is communicating to the rheuma- tinue using topical anesthetics
tologist just how serious the ocular condition is despite the damage. Psychother-
and getting him or her on board to treat the pa- apy may be indicated.
tient systemically with potentially life-threatening Allergic keratoconjunctivitis
medications.” comes in two types: vernal (seen
Although systemic immunomodulation is re- primarily in younger males, typically when the (6) Anesthetic
quired, some topical measures, such as lubricating weather is hot) and atopic (more typically seen in abuse ulcer.
the surface, may be helpful, said Dr. Tu. The clini- older women). These can lead to ulcers with sig-
cian may also consider using topical cyclosporine nificant vascularization and scarring.
to help heal the eye and immunosuppressant drops “If the ulcer is recognized early, before there’s
such as ascorbate to reduce the risk of stromal significant corneal involvement, a comprehensive
melting. ophthalmologist can treat it,” said Dr. Mah. Medi-
Neurotrophic ulcers are associated with many cal management typically includes antihistamines,
underlying conditions, including diabetes, HSV steroids, and bandage contact lenses. Some reports
infection, chemical burns, and overuse of topical say topical cyclosporine is helpful, added Dr. Mah,
anesthetics. The common finding is a decrease in who sometimes uses tacrolimus ointment (Pro-
corneal sensation. topic) applied to the lids in especially resistant
A neurotrophic ulcer generally has smooth, cases. “Carefully monitor Protopic use because the
thick, gray edges, with minimal inflammation; ointment can lead to some necrosis and skin color
and hypopyon may be present. Along with poor changes,” he cautioned.
corneal sensation, there is a decrease in the tearing A patient with significant allergic keratocon-
that is needed to protect the ocular surface; more- junctivitis usually has other allergic manifestations
over, the damaged corneal nerves endings can’t (such as allergic rhinitis or contact dermatitis) and
produce necessary growth factors to help heal the may already be under the care of an allergist/im-
eye. Thus, patients with neurotrophic ulcers have munologist. It’s important to work in tandem.
two problems, said Dr. Tuli: repeated minor trau- To fully treat such a patient, immunotherapy may
mas they can’t feel and impaired healing ability. be necessary; and an allergist/immunologist is
Minor neurotrophic ulcers can be managed far more experienced in administering immuno-
supportively with preservative-free artificial tears therapy shots than most ophthalmologists, said
and ointments. Prophylactic antibiotic drops are Dr. Mah.
generally added to the artificial tears. Adjunctive
medical and surgical approaches for more serious
ulcers are discussed below.
Topical anesthetic
abuse (Fig. 6) is part of
When and the differential diagnosis
When Not to when the ulcer appears
Supporting the surface. Most adjunctive medical
Use Steroids as a disciform, nonheal-
ing epithelial defect. “It and surgical interventions for corneal ulcers focus
Inflammation but no shoots up the list if the on providing surface support—with lubrication,
infection —> Use patient is a health care collagenase inhibitors, and growth factors—and
No inflammation —> worker or has been treat- shielding the cornea. Approaches include bandage
Do not use ed for everything but is contact lenses, punctal occlusion, autologous se-
Infection —> Use still not improving,” said rum eyedrops, amniotic membrane, and tarsorrha-
cautiously with anti Dr. Mah. “It’s a diagnosis phy, among others.
of exclusion.” The first In cases of stromal melting, topical collagenase
son a l s. t ul i, md
microbials (after
you’re sure the anti step is to eliminate the inhibitors such as N-acetylcysteine, doxycycline,
microbial is working) anesthetics. Dr. Tuli also or medroxyprogesterone as well as oral vitamin C
recommends providing 1,000 mg per day may be prescribed. Cyanoacrylate
—Sonal S. Tuli, MD
surface support with lu- glue, a Gunderson (conjunctival) flap, or penetrat-
e y e n e t 51
ing keratoplasty may be indicated. “Time is on our side, unlike during the diagnostic
Ultimately, the treatment approach has to be phase,” said Dr. Afshari. “After the infection has
individualized to each condition. Take bandage resolved and the ulcer has scarred over, we wait to
contact lenses, for example. With an active infec- see if the scarring will improve over time. Then we
tion, they’re contraindicated. try to improve vision without surgery, with either
“You don’t want to hide dirt rigid gas-permeable or scleral contact lenses that
Fungal infections may benefit from under the rug, so to speak” said encompass the scar and give a new curvature. In
earlier surgical intervention. If the Dr. Afshari. “But, in contrast, selected cases, we do phototherapeutic keratectomy
we do use bandage contact lenses to erase some of the superficial scar, smoothing out
fungal ulcer is in the center of the for neurotrophic ulcers, because the surface.” If these don’t work, lamellar or pen-
those we want to cover to pro- etrating keratoplasty is the final step.
cornea and is not responding to mote healing.”
Managing perforation. When 1 Pepose JS, Wilhelmus KR. Am J Ophthalmol. 1992;
antifungals, corneal transplantation an ulcer perforates the cornea, 114(5):630-632.
with clear margins may be consid tissue glue is applied if the defect 2 Jeng BH et al. Arch Ophthalmol. 2010;128(8):1022-1028.
is less than 2 mm. Otherwise, 3 American Academy of Ophthalmology. Preferred Practice
ered, before the infection spreads a partial or penetrating kera- Pattern Guidelines: Bacterial Keratitis – Limited Revision;
toplasty is needed. That said, 2011. Available at www.aao.org/ppp.
further. —Natalie A. Afshari, MD corneal transplants are not the 4 McDonnel PJ et al. Am J Ophthalmol. 1992;114(5):531-
best option for neurotrophic 538.
ulcers. “If the patient can’t heal her own cornea, 5 Rodman RC et al. Ophthalmology. 1997;104(11):1897-
she’ll have the same problem with a transplanted 1901.
cornea,” said Dr. Tuli. 6 http://eyewiki.aao.org/Fungal_Keratitis.
Corneal scars can wait. For repairing the scarring 7 Dart JKG et al. Am J Ophthalmol. 2009;148(4):487-499.
caused by a bacterial infection that has resolved, 8 http://eyewiki.aao.org/Herpes_Simplex _Virus_Keratitis.
Don’t miss the sympo- • Herpes Simplex Keratitis: When Herpes Isn’t a Den-
sium on Non-bacterial drite, and Vice Versa (Sunday, Nov. 11, 10:15 a.m. to
Infectious Keratitis, a 12:15 p.m.)
combined meeting with • Diagnosis and Treatment Modalities in Cases of
the Cornea Society. It Moderate and Recalcitrant Fungal Keratitis (Sunday,
includes eight sessions covering many of the topics in Nov. 11, 2 to 3 p.m.)
this feature, as well as the 2012 Castroviejo Lecture. • Atypical Keratitis (Monday, Nov. 12, 10:15 a.m. to
(Monday, Nov. 12, 2 to 4 p.m.) 12:15 p.m.)
Several relevant instruction courses are also sched- • Help! A Corneal Ulcer Just Walked In! What Do I Do
uled throughout the Joint Meeting, including: Next? (Tuesday, Nov. 13, 2 to 3 p.m.)
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