The Impact on Glaucoma from the OUTSIDE IN - New York Eye and ...

Typically with ocular antihypertensive toxicity, most of
the redness occurs in the lower third of the eye, on
the inferior bulbar conjunctiva and the inferior tarsus,
particularly medially, where the tears are swept
toward the lacrimal drainage system. When I observe
redness on the inferior tarsus and the patient is using
1 or more ocular antihypertensives, I suspect toxicity.
—Stephen C. Pflugfelder, MD
degeneration. Consequently, they develop relative corneal
anesthesia, and stop complaining of symptoms. Conversely,
some patients with early stages of OSD and minimal
epitheliopathy complain bitterly. In early-stage OSD, there may
be an inflammatory-mediated hyperesthesia of the nerve,
similar to that which occurs in a chronic pain syndrome.
CAUSES OF OCULAR SURFACE DISEASE
AND PATIENTS AT RISK
Dr Parrish: What are some of the extrinsic and intrinsic causes
of OSD?
Dr Lewis: In terms of extrinsic causes, geography can play a
part. In Sacramento, California, where I practice, the humidity
is low compared with many other regions of the United States.
Consequently, we note a dry eye problem, particularly in the
spring and summer. In addition, my practice is in a farming
valley, where there is exposure to many allergens. When
these environmental causes of OSD are combined with
blepharoconjunctivitis, contact lens wear, or the toxic effects
of preservatives in ocular medical therapy, patients experience
significant discomfort.
Dr Parrish: Meibomian gland dysfunction is an important
intrinsic cause of OSD, particularly subclinical evaporative dry
eye in older adults.
Dr Herndon: With older age, I certainly see eyelid issues as a
contributor. Thus, I pay close attention to the impact of
ectropion or entropion on the ocular surface.
Dr Lewis: Although Sjögren syndrome is cited as an associated
systemic finding with OSD, 8 I do not observe the syndrome as a
common concomitant condition. I do, however, see connective
tissue diseases as a common comorbidity. Interestingly, I find
that female patients complain more about red eye and irritation,
even though I see the problem more often in male patients.
Dr Pflugfelder: I agree with Dr Lewis: in my experience, male
patients complain less often than female patients, which is
counterintuitive, because women typically have a higher pain
threshold than men.
Dr Parrish: In my experience, male patients are more likely than
female patients to develop severe rosacea and concomitant
keratitis or lid margin disease.
Dr Pflugfelder: In addition to the autoimmune conditions, I often
see 2 diseases in the elderly that affect the ocular surface:
diabetes and Parkinson disease. When patients with diabetes
develop neuropathy that affects the corneal nerves, the result is
a decrease in blink rate, which diminishes the spread of tears.
Likewise, patients with moderate-to-severe Parkinson disease
do not blink often, which results in tear stagnation along the
lower lid and the development of blepharitis. Also, certain
antidepressants, urinary antispasmodics, and antihistamines
should be considered potential extrinsic causes of OSD.
<strong>The</strong> anticholinergic effects of these commonly prescribed
medications can reduce tear production. 9
THE EFFECTS OF PRESERVATIVES
ON OCULAR STRUCTURES
<strong>The</strong> Effects of Preservatives on
the Ocular Surface
Dr Parrish: Most commercially available ocular
antihypertensives contain preservatives, and the most
commonly employed preservative is benzalkonium chloride
(BAK). <strong>The</strong> deleterious effects of BAK on the ocular surface
have received a great deal of attention. Dr Pflugfelder, can you
provide an evidence-based summary of the safety of BAK as a
preservative in ocular preparations?
Dr Pflugfelder: <strong>The</strong> literature is replete with various toxic
effects of BAK in in vitro conjunctival and corneal epithelial cell
models, 10,11,12 in vivo animal models, 13,14,15 and clinical trials. 16
BAK is a detergent, and as such, the chemical compound can
have direct effects on the lipid layer in the cell membrane. BAK
has been found to disrupt the corneal epithelial tight junction
proteins, particularly occludin, which results in loss of the
barrier function in the apical epithelium and in rapid loss of
cells. This may account for the observed epitheliopathy with
BAK. 11 And, in the concentrations present in commercially
available ocular preparations, BAK can also cause programmed
cell death, apoptosis, and necrosis in epithelial cells. 10-12,15,17
BAK also has been found to incite various inflammatory
mediators, including cytokines, chemotactic factors, and
metalloproteinases that further cause loss of cells. 18-20
Dr Parrish: Additionally, a recent study by Sarkar and
colleagues showed that the application of BAK elicited corneal
neurotoxicity and reduced aqueous tear production in vivo and
in vitro in mouse eyes. 21 Although mouse eyes may not be
analogous to human eyes, the findings show the depth and
breadth of BAK’s deleterious effects. Clinical evidence has
demonstrated BAK’s dose-dependent relationship with OSD and
its negative effect on patient QOL. 1-3,22
Dr Moster: Patients using multiple topical agents are being
overexposed to BAK. <strong>The</strong> negative effect BAK has on the ocular
surface may be in part responsible for the symptomatology we
so often observe in clinical practice. 1-3
Dr Herndon: BAK’s detergent-like properties became clear to
me at, of all places, a local rib restaurant. Following my meal, I
proceeded to open a wet nap package. I noticed the active
ingredient of the cleanser was BAK. (Figure 3)
<strong>The</strong> Effects of Preservatives
on the Trabecular Meshwork
Figure 3. Example of a wet nap
product, with BAK as the cleanser,
commonly provided in restaurant
settings.
Photo Courtesy of
Leon W. Herndon, MD
Dr Parrish: It is difficult to accept the notion that as clinicians,
we may be harming the eye’s internal structures (ie, trabecular
meshwork) with the medicine that we prescribe. However, the
5