Download Managing Systemic Disease in the Glaucoma Patient

COVER STORY
Managing Systemic
Disease in the
Glaucoma Patient
Many systemic diseases may be correlated with glaucoma. Conversely, glaucoma treatments
can affect a patient’s other systemic diseases.
BY JENNIFER SOMERS WEIZER, MD
G
laucoma has been described as a “sick eye in a
sick body,”1 and there has been much research
on systemic diseases that may cause or correlate with the development of glaucoma.
Likewise, the medical treatments often prescribed for
glaucoma can affect a patient’s systemic health and
underlying medical comorbidities. This article concentrates on the relationship of primary open-angle glaucoma with systemic illnesses.
WHICH SYSTEMIC DISEASES CORRELATE
WITH GLAUCOMA’S DEVELOPMENT?
Systemic Hypotension
There is reasonable evidence to support the concept
that systemic hypotension, whether caused primarily
or by the overtreatment of systemic hypertension, can
cause glaucoma to develop and worsen its progression.2,3 This is particularly true for normal-tension glaucoma (NTG), and the effects of hypotension seem to be
even worse if the patient’s blood pressure dips too low
nocturnally.3,4
Systemic Hypertension
Although there seems to be a relationship between
systemic blood pressure, as it relates to ocular perfusion
pressure, and glaucoma, the evidence is contradictory
about systemic hypertension and glaucoma.3 It has been
suggested that the extremes of blood pressure, both
too low and too high, may be deleterious for glaucoma.5
Blood pressure measurements, however, do not correlate
38 GLAUCOMA TODAY NOVEMBER/DECEMBER 2014
Figure 1. Raynaud phenomenon. Reprinted with permission from Lebwohl MG, Heymann WR, Berth-Jons J, Coulson
I. Treatment of Skin Disease: Comprehensive Therapeutic
Strategies. Philadelphia: WB Saunders; 2014.
well with IOP measurements. Many large-scale studies have addressed the hypertension question, but the
results are not conclusive. More research is needed to
obtain better answers.
Migraine and Vasospasm
Migraine and vasospasm appear to be related to the
development of NTG in particular.3 At this point, however, there is no good evidence to show that treating
migraine or vasospasm offers benefits in terms of glaucoma (Figure 1).
COVER STORY
THE RELATIONSHIP BETWEEN SJÖGREN AND DRY EYE
By Paul Singh, MD
For many patients, dry eye disease (DED) is a persistent
problem that leads to a level of discomfort highly detrimental to their quality of life. During counseling, these patients
often tell me that they have visited three or four doctors in
an attempt to get relief from the burning, itching, fluctuating
vision, and redness. Although we eye care professionals aggressively treat conditions such as uveitis and corneal abrasion, we
often have a more relaxed approach to treating DED. Not only
should we be more diligent in relieving the uncomfortable—
even painful—symptoms of this syndrome, we should also
consider every manifestation of DED as a hallmark of a potential systemic disease. Diagnosing Sjögren syndrome in patients
with DED, for example, can help provide a clearer, targeted
treatment path.
DIAGNOSIS
As many as 4 million people in the United States suffer from
Sjögren syndrome, but only 1 million have been diagnosed.1-3
This discrepancy is largely due to the fact that biomarkers
associated with traditional Sjögren syndrome testing—Sjögrenspecific antibody A, Sjögren-specific antibody B, rheumatoid
factor, and antinuclear antibody—are not specific or sensitive enough to accurately identify the disease at an early
stage. A new serology test for Sjögren syndrome (Sjö; Nicox)
includes the identification of three novel biomarkers—salivary
gland protein-1, carbonic anhydrase-6, and parotid secretory protein—in addition to the aforementioned traditional
biomarkers. This comprehensive diagnostic panel helps to
detect Sjögren syndrome earlier and with a high specificity and
sensitivity.4 The test also displays markers indicative of other
autoimmune diseases such as rheumatoid arthritis.
THE TEST IN PRACTICE
I use Sjö in my practice to identify a potential systemic
etiology in DED patients whom I suspect of having deeper
problems. I have found that close to 40% of my DED patients
also experience dry mouth and dry skin, yet some do not
Hyperthyroidism
Graves disease is associated with glaucoma, most likely
due to the orbital congestion that can raise IOP (Figure 2).
No clear relationship between hypothyroidism and glaucoma, however, has been established in the literature.2,3
Diabetes Mellitus
Some large studies have implicated diabetes mellitus
as a risk factor for glaucoma, but other studies have not
notice those symptoms until I question them. This is valuable
information, as it relates to the possibility of systemic disease,
particularly Sjögren, which attacks the lacrimal and salivary
glands and, if left untreated and unmonitored, increases
patients’ risk of developing lymphoma.5 Knowing if an autoimmune cause underlies a patient’s DED enables me to tailor
my treatment plan accordingly and ultimately improve his or
her outcomes.
Once my colleagues and I decided to start screening for
Sjögren syndrome in our practice, we leveraged our established
relationships with rheumatologists, who are able to manage
affected patients from a systemic standpoint. When an autoimmune disease has been diagnosed, many promising medications can be prescribed, including hydroxychloroquine and
other immunosuppressors. Just as with numerous other diseases, beginning treatment early in the disease state increases
the chances of controlling symptoms and progression.
CONCLUSION
As eye care practitioners, it is important for us to take
advantage of improvements in the diagnosis and treatment
of diseases such as Sjögren syndrome that were previously
misunderstood and underdiagnosed. By taking this front-line
approach, we gain relevance and, more importantly, become
better physicians.
Paul Singh, MD, is an ophthalmologist at The Eye
Centers of Racine & Kanosha in Racine, Wisconsin.
He acknowledged no financial interest in the product
or company mentioned herein. Dr. Singh may be
reached at [email protected].
1. Sjögren’s Syndrome Foundation. Sjögren’s Syndrome Foundation. 2001. http://www.sjogrens.org. Accessed
September 5, 2013.
2. Kassan SS, Moutsopoulos HM. Clinical manifestations and early diagnosis of Sjögren syndrome. Arch Intern Med.
2004;164:1275-1284.
3. Liew M, Zhang M, Kim E, et al. Prevalence and predictors of Sjögren’s syndrome in a prospective cohort of patients
with aqueous-deficient dry eye. Br J Ophthalmol. 2012;96:1498-1503.
4. Shen L, Suresh L, Lindemann M, et al. Novel autoantibodies in Sjögren’s syndrome. Clin Immunol. 2012;145:251255.
5. Pillemer SR. Lymphoma and other malignancies in primary Sjögren’s syndrome. Ann Rheum Dis. 2006;65(6):704706.
found such an association.3 At this point, there is no net
conclusive evidence supporting the relationship between
the two diseases, so screening glaucoma patients for diabetes is not recommended.2
Sleep Apnea
Although recent studies have suggested a relationship
between sleep apnea and glaucoma, the evidence is
conflicting overall. IOP has been shown to rise during
NOVEMBER/DECEMBER 2014 GLAUCOMA TODAY 39
COVER STORY
a-2 Blockers
This category of eye drops includes brimonidine and
apraclonidine. These agents can cause decreases in blood
pressure and pulse, drowsiness, dizziness, and dry mouth.7
Figure 2. Graves disease.
continuous positive airway pressure treatment of
obstructive sleep apnea.6 More research is needed to
determine if a link between these diseases truly exists.
Miscellaneous
Several small studies have implicated increased blood
viscosity, particularly dysregulated platelet aggregation, as
a risk factor for glaucoma.3 Other studies suggest a relationship between autonomic nervous system dysfunction
and glaucoma, particularly in the case of NTG.3 There is
also weak evidence supporting autoimmune diseases as
contributing to glaucoma’s development.3 Although a
possible link between the pathophysiology of Alzheimer
dementia and glaucoma is tantalizing, evidence does not
yet exist to support this correlation.3 Further work must
be done to clarify these relationships.
WHICH GLAUCOMA TREATMENTS CAN
AFFECT SYSTEMIC DISEASES?
ß-blockers
ß-blocker eye drops such as timolol act upon ß-1 and
ß-2 receptors. The ß-1 blockade can decrease cardiac
contractility and heart rate, lower systemic blood pressure, and cause an irregular pulse. The ß-2 blockade
can increase bronchospasm in patients with underlying
asthma or chronic obstructive pulmonary disease. For
these reasons, ß-blocker eye drops are generally contraindicated in patients with asthma, bronchospasm,
chronic obstructive pulmonary disease, heart failure,
sinus bradycardia, atrioventricular block, and cardiogenic shock.4,7 Betaxolol, a selective ß-1 blocker, may
not have the bronchospastic effects of nonselective
ß-blockers.
ß-blockers can also affect the central nervous system,
leading to headaches, depression, anxiety, confusion,
dysarthria, hallucinations, a tendency to somnolence, and
lethargy.7
40 GLAUCOMA TODAY NOVEMBER/DECEMBER 2014
Carbonic Anhydrase Inhibitors
Particularly when taken orally as acetazolamide or
methazolamide, carbonic anhydrase inhibitors (CAIs)
can cause dysesthesia of the fingers and around the lips,
frequent urination, a lack of energy, anorexia, weight
reduction, urolithiasis (kidney stones), metabolic acidosis,
and hematopoietic cell restraint anemia. CAIs can potentiate the metabolic effects of other diuretics when taken
concurrently, necessitating the monitoring of patients
for hypokalemia and hyperuricemia.4 These systemic side
effects, while theoretically possible, do not generally occur
when the eye drop forms of CAIs (ie, dorzolamide and
brinzolamide) are used.7
Parasympathomimetic Drugs
This category of eye drops, including pilocarpine, can
activate secretory glands and smooth muscles. Systemic
side effects can therefore include drooling, sweating, diarrhea, nausea/vomiting, stomachache, asthma, bradycardia, hallucinations, and depression.7
CONCLUSION
Research has clarified some of the complex relationships between glaucoma and systemic diseases, but
others remain unclear and deserve further investigation. In general, patients can reduce the systemic side
effects of eye drops by closing their eyes or performing
5 minutes of punctal occlusion immediately after instillation.7 If the eye provider is not certain whether or not
a glaucoma treatment may negatively affect a patient’s
systemic issues, his or her primary care provider should
be consulted. n
Jennifer Somers Weizer, MD, is an associate
professor of ophthalmology and visual sciences at the Kellogg Eye Center, University of
Michigan, in Ann Arbor. Dr. Weizer may be
reached at (734) 763-8122; [email protected].
1. Lagrange F. Du Glaucome et de L’hypotonie; Leur Traitement Chirurgical. Paris: Librairie Octave Doin; 1922.
2. Lama P. Systemic diseases and glaucoma. In: Schacknow PN, Sample JR, eds. The Glaucoma Book: a Practical,
Evidence-Based Approach to Patient Care. New York, NY: Springer; 2010:689-709.
3. Pache M, Flammer J. A sick eye in a sick body? Systemic findings in patients with primary open-angle glaucoma.
Surv Ophthalmol. 2006;51:179-212.
4. Salim S, Shields MB. Glaucoma and systemic diseases. Surv Ophthalmol. 2010;55(1):64-77.
5. He Z, Vingrys AJ, Armitage JA, Bui BV. The role of blood pressure in glaucoma. Clin Exp Optom. 2011;94(2):133149.
6. Kiekens S, de Groot V, Coeckelbergh T, et al. Continuous positive airway pressure therapy is associated with an
increase in intraocular pressure in obstructive sleep apnea. Invest Ophthalmol Vis Sci. 2008;49(3):934-940.
7. Inoue K. Managing adverse effects of glaucoma medications. Clin Ophthalmol. 2014;8:903-913.