Twelfth Edition - Review of Optometry

interleukin-1b, tumor necrosis factor
alpha) and matrix metalloproteinases,
which in turn activate inflammatory
cells at the ocular surface. 14,18,19 These
inflammatory events lead to apoptotic
death of surface epithelial cells and
goblet cells. 20 Other factors, such as
autoimmune targeting of the ocular
surface and noxious environmental
stimuli, can amplify these initiating
inflammatory events.
Tear film instability may also
initiate a dry eye state in the
absence of or preceding tear
hyperosmolarity. Tear instability
results from local deficiencies
which causes the tear film
to break up too rapidly, thereby
minimizing the protective effect
to the ocular surface; usually this
is described as a TFBUT that is
less than the blink interval. 21 This
phenomenon induces local drying
of the exposed surface, which
can result in surface epithelial damage
and disturbance of the glycocalyx and
goblet cell mucins. 10 Like osmolarity,
tear instability can be spurred by a
host of factors, including allergic eye
disease, chronic use of preserved topical
medications (particularly those with
benzalkonium chloride) and contact
lens wear. 22-24
Management
Historically, management of dry eye
syndrome has been aimed at replenishing
the eyes’ moisture and/or delaying
evaporation of the patient’s natural
tears. The first line of defense typically
involves the use of ophthalmic
lubricants or “artificial tears.” The
purpose of these agents is to alleviate
symptoms and, in some cases, to
promote healing of the ocular surface
and corneal epithelium. A great deal
of diversity exists within this market,
and practitioners should familiarize
themselves with the various options as
24A REVIEW OF OPTOMETRY APRIL 15, 2010
well as their respective active and inactive
ingredients.
In theory, artificial tears may be
used as often as necessary. When
beginning therapy however, lubricants
should be dosed more frequently and
regularly; later, this therapy can be
tapered based upon patient response
Sodium fluorescein in dry eye: note areas of negative staining,
mucus filaments and diffuse epitheliopathy.
and compliance. Highly symptomatic
patients may benefit from products
that demonstrate enhanced ocular surface
residence time, such as Systane
Ultra (Alcon Laboratories), which
provide relief with less frequent instillation.
Solutions have a distinct advantage
over ointments, as they tend to
induce less visual impairment. In addition,
experts recommend that patients
with more advanced diseases employ
non-preserved artificial tear products,
to avoid any potential for toxicity. 16,25
Patients who do not respond to tear
rehabilitative/lubrication therapy alone
may require treatment with topical
immunomodulatory agents, such as
Restasis (0.05% cyclosporine A ophthalmic
emulsion, Allergan) or topical
steroids. Cyclosporine works by
suppressing T-cells and inhibiting
their activation, while downregulating
T-cell mediated cytokine production.
26 In clinical trials, 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 therapy. 27
The use of topical corticosteroids (e.g.,
0.5% loteprednol etabonate q.i.d. for
two to four weeks) in conjunction with
Restasis therapy may hasten recovery
and further diminish symptoms
associated with dry eye. 16,25,28
Long-term use of topical steroids
is not recommended however,
due to the potential for cataractogenesis
and ocular hypertension.
Oral medications and nutritional
supplements are another
potential therapy for patients
with dry eye syndrome secondary
to meibomian gland disease. The
use of oral tetracycline therapy
(e.g., doxycycline 50mg -100mg
daily for six to 12 weeks) may be
beneficial in patients who fail to
improve with lubricating drops
and lid hygiene. Tetracyclines demonstrate
a host of anti-inflammatory
effects, which have proven beneficial
in those with various forms of blepharitis.
29,30 Omega-3 fatty acid supplements
may provide similar benefits in
restoring meibomian gland function
and tear stability, though the body
of evidence for such therapy is still
emerging. 31
Oral secretagogues are sometimes
used to manage advanced cases of
aqueous deficient dry eye, such as those
encountered in Sjögren’s syndrome.
Salagen (pilocarpine HCl 5mg, MGI
Pharma) and Evoxac (cevimeline HCl
30mg, SnowBrand Pharmaceuticals)
are muscarinic agonists, which stimulate
non-selective secretion from exocrine
glands via autonomic pathways,
resulting in enhanced tear production.
32,33 It should be noted that these
agents are specifically indicated for
xerostomia (dry mouth) associated
with Sjögren’s syndrome or certain