is one of the common clinical entities that present to the optometric
practice. Patients usually present with some or all of the following:
acute pain, photophobia, lacrimation, bleph-arospasm, foreign-body
sensation, blurry vision and a history of contact lens wear or being
struck in the eye.111 Biomicroscopy of the injured
area often reveals diffuse corneal edema and epithelial disruption.
In severe cases, when edema is excessive, folds in Descemet's membrane
may be visible. Cobalt blue light inspection, following the instillation
of sodium fluorescein dye, will illuminate the denuded epithelium.
The newly created wound appears as a bright green area compared to
the rest of the cornea because the dye accumulates in the divot,
abrasion without fluorescein.
The cornea has
five distinct layers. Below the tears lies the corneal epithelium.
The corneal epithelium is actually composed of three tissues: the
stratified surface epithelium, the wing cell layer, containing the
corneal nerves and the mitotically active basement membrane. Below
the epithelium is the Bowman's membrane (a structure designed to
prevent penetrating injuries), 250 lamellar sheets of stroma, Descemet's
membrane, and finally the endothelium.
There are two
categories of corneal abrasion; superficial, not involving Bowman's
membrane and deep, penetrating Bowman's membrane, but not rupturing
Descemet's membrane. Abrasions may result from foreign bodies, contact
lenses, chemicals, fingernails, hair brushes, tree branches, dust
and the like.
The cornea has
remarkable healing properties. The epithelium adjacent to any insult
expands in size to fill in the defect, usually within 24 to 48 hours.5 Lesions
that are purely epithelial often heal quickly and completely without
scarring. Lesions that extend below Bowman's membrane possess an
increased risk for leaving a permanent opacity.5 Recent
data suggests that the integrity of the basement membrane following
the injury is a deciding factor in determining the regenerative character
of the corneal repair.7
For years contact
lenses have remained at the top of the list of consumer goods known
to perpetrate ocular injuries. Further, ulceration following contact
lens-induced corneal abrasion has been recognized and demonstrated
as a secondary phenomenon to suspect compliance, care and lens cleanliness.8 In
one study, ulcers were found only in corneas that were scratched
with contact lenses colonized by viable S. aureus.8 Bacteriologic
examination of lenses at the time of the event demonstrated the association.8
corneal abrasion begins with history. The time, place and activity
surrounding the injury should be recorded for both medical and legal
purposes. Visual acuity (VA) should be recorded before any procedures
or drops are given, if possible. If the blepharo-spasm is sufficiently
intense to preclude an acuity measurement, one drop of topical anesthetic
from a recently open bottle can be administered. The VA should be
measured immediately thereafter. The eye examination should proceed
in a logical fashion from external adenexa to funduscopic examination.
The eyelids should be everted and fornicies scrutinized to rule out
the presence of foreign material. Fluorescein dye (without anesthetic)
should be instilled to identify the corneal defects. The Seidel test
(painting of the wound with dye observing for aqueous leakage) is
used to uncover full-thickness injuries. The abrasion should be documented
for size, shape, location and depth. Any anterior chamber reaction
should be observed and noted as well. A dilated examination should
be completed to rule out posterior effects from the trauma.
abrasion with fluorescein staining.
is initiated by using adequate cycloplegia (the potency of which
should be determined on a case-by-case basis) and topical antibiotics
such as Polytrim (polymyxn B and trimethoprim, Allergan), gentamicin
or Tobrex (tobramicin, Alcon) or a fluoroquinolone (Vigamox, Zymar).
Bed rest, inactivity and over-the-counter analgesics can be used
to quiet acute pain. In cases where pain is severe, topical nonsteroidal
anti-inflammatory medications (Voltaren or Acular, qid) or a thin, low
water content bandage contact lens can be prescribed.16,
9, 10, 11
is no longer considered standard-of-care.1,2,46,10 Researchers
examined patients with corneal abrasion: 17 with an eye patch and
18 with no eye patch. There was no significant difference in percent
healing between the two groups, even when adjusted for age and initial
abrasion size. Consistent with the data of others, pressure patching
for corneal abrasions provides no benefit.10 Patching
must always be avoided in patients who wear contact lenses due to
the threat of microbial keratitis. Patients should be reevaluated
every 24 hours until the abrasion
- To prevent
recurrent erosion and reduce corneal edema, a hypertonic solution
or ointment may be prescribed along with the other medications
or after reepithelialization has occurred.5
- In cases where
excess epithelium impairs regrowth, a cotton-tipped applicator
saturated with anesthetic may be used to debride loose tissue.5
- When significant
secondary uveitis is present, topical steroids may be required.
subepithelial infiltration may be a sign of infection. Lesions
such as these should be considered vision threatening, warranting
treatment with fluoroquinolone antibiotic drops and consideration
OF NEW DRY EYE PRODUCTS
MANY YEARS, there were only two options for managing dry
eye syndrome: either put more moisture into the eye, or prevent
the moisture already present from evaporating too quickly.
Ophthalmic lubricating solutions, more commonly known as
artificial tears, have remained the mainstay of dry eye therapy
since their introduction in the 1940s.1 Freeman
introduced the first silicone punctal plug in 1975,2 and
other devices to prevent surface evaporation (e.g. Moist
Eye moisture panels from EagleVision) have joined the ranks
over the years, but these modalities have never been able
to supplant artificial tear therapy from its #1 position.
review of an online health product service (www.drugstore.com)
reveals over 50 distinct items when the term "artificial
tears" is entered in the search engine! With so many products
to choose from, it can be frustrating and intimidating for
both patients and practitioners to know which option to select.
The following is a review of some of the more recent products
introduced for therapy of dry eye syndrome.
in Artificial Tears
their popularity and success, two significant difficulties
still exist with artificial tears. The biggest issue is duration
of action; patients frequently report only fleeting relief
(on the order of five to 10 minutes) after instillation of
many tear supplements. Also of concern is the addition of
preservatives in many artificial tears, which can be a significant
source of toxicity, particularly when these preparations
are used frequently. Therefore, manufacturers have begun
producing thicker, more viscous agents that increase corneal
contact time without blurring vision. Examples of such products
include Refresh Liquigel (Allergan), GenTeal Gel (Novartis),
TheraTears Liquid Gel (Advanced Vision Research), and Systane
(Alcon). Also, manufacturers have introduced several preservative-free
solutions and "disappearing preservatives" to address the
issue of toxicity. Virtually every line of dry eye products
includes a preservative-free version (e.g., Tears Naturale
PF, Hypotears PF, etc.), but only three product lines contain
preservatives that break down soon after instillation. These
include: GenTeal (Novartis, preserved with GenAqua, or sodium
perborate), Tears Again (Cynacon/Ocusoft, preserved with
Dissipate), and Refresh Tears (Allergan, preserved with Purite).
a small company based in Oregon launched a unique product
that has captured the interest of many exhibit hall attendees.
Nature's Tears (Bio-Logic Aqua Technologies) is described
by the manufacturer as an all natural moisturizing mist for
the eyes consisting simply of tissue culture grade water
with no preservatives or propellants. Rather than being instilled
as a drop, Nature's Tears is sprayed toward the eyes from
a distance of 12 to 18 inches. The premise? Artificial tears
flood the ocular surface, washing away the lipid and mucin
layers and depleting normal enzymes, claims the manufacturer.
However, Nature's Tears mist allows for replenishing of the
aqueous component without disturbing the other tear layers.
This is an intriguing theory, and the product possesses a
significant novelty factor. However, there is a lack of significant
prospective studies demonstrating that this product is any
more effective than other artificial tear supplements.
summer of 1999, the FDA Ophthalmic Drugs Subcommittee advisory
panel unanimously recommended not to approve Allergan's formulation
of topical cyclosporine for the treatment of keratoconjunctivitis
sicca. One of the reasons cited was that the solution vehicle
showed very similar efficacy to the drug itself, and hence
there was no significant difference between the controls
and the study group. Undaunted, Allergan decided to manufacture
this unique vehicle, an emulsion of castor oil and lubricants
in an aqueous solution, and market it directly to the public
as an over-the-counter product. In the fall of 2002, Refresh
Endura was launched.
to Allergan, Endura is the first lubricant eye drop for dry
eye that treats all three layers of the tear film. It is
preservative-free and packaged in single-use, disposable
vials. Controlled clinical trials with Endura showed enhanced
fluorescein tear break-up time, as well as diminished symptoms
of dryness and irritation in patients using the solution
two to four times daily over 90 days. Clinical practice has
shown it to be an excellent and well-tolerated solution,
particularly suited for patients with lipid deficiencies
secondary to meibomian gland dysfunction.
2003, Alcon introduced a unique artificial tear product.
Systane, which utilizes the demulcent technology of hydroxypropyl
(HP) guar, increases in viscosity after contacting the ocular
surface. This change is based on pH value. Systane is a liquid
in the bottle at a pH of 7.0, but when placed in the eye
(which has a pH of ~7.4), a chemical reaction occurs. HP
guar binds to the ocular surface and simultaneously crosslinks
with borate ions in the solution, forming a network with
a gel-like consistency. The result is a more viscous ocular
lubricant that, according to Alcon, provides extended relief
of dry eye symptoms and generates a protective coating on
the ocular surface. In theory, this coating serves as a temporary
corneal bandage, allowing the epithelial cells to heal and
reestablish healthy microvilli and a normal glycocalyx.
randomized, controlled clinical trial, dry eye patients receiving
Systane four times daily for six weeks showed a statistically
significant reduction in surface staining, dryness and foreign-body
sensation, as well as increased tear break up time.3,4 Mild
blurring for 30 seconds after instillation was the most significant
adverse effect. Personal experience with Systane has shown
it to be an outstanding choice for patients with moderate
to severe dry eye who are not ameliorated with normal viscosity
tear solutions. It is also excellent for managing minor corneal
trauma or exposure keratopathy.
2002, the FDA approved Restasis (0.05% cyclosporine ophthalmic
emulsion) for the treatment of keratoconjunctivitis sicca,
making it the first commercially available pharmaceutical
therapeutic agent for the treatment of dry eye. This topical
solution is classified as an immunomodulatory agent by the
manufacturer (Allergan), and is approved "for patients with
keratoconjunctivitis sicca...whose tear production is presumed
to be suppressed due to ocular inflammation."
studies, Restasis was shown to ameliorate symptoms in up
to 44% of patients and improve basal tear production (as
demonstrated by Schirmer testing) in up to 59% of patients
after six months of treatment.5 Additionally,
a reduction in conjunctival T-lymphocyte infiltration was
noted after six months of cyclosporine therapy.6
heralds Restasis as the first drug proven to effectively
treat a cause of dry eye disease, rather than only temporarily
alleviate symptoms. But although this product has yielded
good results in clinical trials, practitioners have been
somewhat reluctant to actively prescribe Restasis for several
reasons. First, many are confused as to precisely which dry
eye patients will benefit from this therapy. Second, ocular
burning has been reported as an adverse event in up to 17%
of individuals utilizing the drug.5 Third, the
time frame of six months may seem irrationally long for some
practitioners and patients to observe improvement in the
disease course (even though many patients experience improvement
after only a few weeks). Finally, the retail cost of Restasis
is somewhat expensive as compared to conventional therapy,
on the order of $80 to $100 per month. While these issues
cannot be ignored, the fact remains that Restasis may offer
great potential benefit to many of our patients. Practitioners
need to remain open minded and personally evaluate this product
on at least a few patients before reaching the conclusion
that it is too slow, too uncomfortable or too expensive.
Restasis is prescribed on a bid basis.
on the Horizon
products remain under investigation for the treatment of
dry eye syndrome. Diquafosol tetrasodium, a topical agent
referred to as INS365 Ophthalmic by Inspire Pharmaceuticals,
has been shown to activate P2Y2 receptors in the mucosal
cells of the palpebral conjunctiva.7,8 These receptors
are believed to regulate a variety of cellular responses.
used topically on the ocular surface, INS365 has been shown
to pull salt, water and mucin from conjunctival cells, effectively
creating an artificial tear comprised of purely endogenous
components.7 Inspire Pharmaceuticals filed a new
drug application for INS365 in June 2003, and received an
approvable letter from the FDA on December 22, 2003. A launch
of this product is anticipated sometime in 2004.
in clinical trials is 15(S)-HETE (15-hydroxyeicosatetraenoic
acid) from Alcon Laboratories. Like INS365, this product
is best described as a secretagogue, in that it induces secretions
from bodily tissues. Specifically, when instilled in the
eye, 15(S)-HETE stimulates production of the glycoprotein
Muc1.9 Muc1 is an important component of the tear
mucin layer; enhancement of this element may help to alleviate
corneal injury and restore corneal integrity in dry eye patients.
KC. Use of methylcellulose in ophthalmology. Arch Ophthalmol
JM. The punctum plug: evaluation of a new treatment for the
dry eye. Trans Am Acad Ophthalmol Otolaryngol 1975; 79(6):OP874-9.
MT, Hearn CJ, Meadows DL, Stein JM. Results of a clinical
evaluation with a new artificial tear solution containing
HP-Guar. Invest Ophthalmol Vis Sci 2003; 44: E-Abstract 2483.
S, Stone RP, Christensen MT, et al. Extensions in tear film
break-up time after instillation of hp-guar artificial tear
substitute. Invest Ophthalmol Vis Sci 2003; 44: E-Abstract
K, Stevenson OD, Mundorf TK, Reis BL. Two multicenter, randomized
studies of the efficacy and safety of cyclosporine ophthalmic
emulsion in moderate to severe dry eye disease. CsA Phase
3 Study Group. Ophthalmology 2000;107(4):631-9.
KS, Tisdale AS, Stern ME, et al. Analysis of topical cyclosporine
treatment of patients with dry eye syndrome: Effect on conjunctival
lymphocytes. Arch Ophthalmol 2000; 118(11):1489-96.
JE, Jumblatt MM. Regulation of ocular mucin secretion by
P2Y2 nucleotide receptors in rabbit and human conjunctiva.
Exp Eye Res 1998; 67(3):341-6.
T, Murakami T, Nagano T, et al. INS365 suppresses loss of
corneal epithelial integrity by secretion of mucin-like glycoprotein
in a rabbit short-term dry eye model. J Ocul Pharmacol Ther
DA, McDonough TJ, Roberts L, et al. The mucin secretagogue
15(S)-HETE protects the cornea and improves tear film integrity
in a rabbit model of lacrimal gland inflammation induced
dry eye. Invest Ophthalmol Vis Sci 2003; 44: E-Abstract 2498.
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the fibrotic repair phenotype in cornea: implications
for surgical outcomes. Invest Ophthalmol Vis Sci
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the pain associated with simple corneal abrasion
without delaying healing? Ann Emerg Med 2003; 41(1):134-40.
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reports in this section