Glaucoma 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 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).

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 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 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?

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

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

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.

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; jweizer@umich.edu.

  1. Lagrange F. Du Glaucome et de L'hypotonie; Leur Traitement Chirurgical. Paris: Librairie Octave Doin; 1922.
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