Glaucoma and Systemic Health: Making the Connection

Glaucoma is well-established as a leading cause of blindness.¹ Management of this condition is mainly focused on lowering IOP by means of medications, laser procedures, and surgeries. Between discussing and choosing these treatment options, interpreting test data, and addressing other concerns, such as blur and dry eye, that frequently accompany glaucoma, visits with patients can be time-consuming and challenging. It may be easy to overlook effects that the systemic health of our patients may be having on their glaucoma, but these factors can be contributory to, if not outright causative of, glaucomatous damage. This article provides an overview of some of the more common reasons related to systemic factors worth monitoring in your patients with glaucoma.

MEDICATION-INDUCED COMPLICATIONS

Steroids are an important class of medications that help control inflammation throughout the body. However, their negative effect on IOP is well-known and poses an increased risk for patients with glaucoma.² Although we see this most commonly with topical use, periocular injection, or intraocular injection, any steroid introduced to the body can lead to an increase in IOP.³ For patients who are experiencing an unexplained spike in IOP, be sure to ask about any recent steroid use, including any injections they may have had elsewhere in the body. Likewise, it is prudent to advise patients who may be starting on a steroid to return to your office shortly after initiation to monitor for any steroid response.

It has recently been shown that calcium channel blockers—used mainly to lower blood pressure and to manage arrythmias, angina, and Raynaud disease, among other indications—are associated with a higher prevalence of glaucoma.⁴ Causes for this are unclear, but a leading hypothesis is the preferred nocturnal dosing, which may lead to hypotension and decreased ocular perfusion.⁴ Although there is no consensus on outright contraindication for the use of these medications in patients with glaucoma at this time, it may be wise to consider an alternative medication or to change to morning dosing in patients with progressing disease. These changes should be promptly communicated to the patient’s appropriate provider.

For patients with narrow-angle glaucoma, special consideration needs to be given to medications with anticholinergic properties that may induce mild pupillary mydriasis and propagate angle closure. Common medications in this category include first-generation antihistamines, such as diphenhydramine, brompheniramine, dimenhydrinate, and doxylamine. These drugs are readily available OTC to treat conditions such as allergy, cold relief, motion sickness, and insomnia. It is important that patients with anatomically narrow angles steer clear of these medications and any others that suggest caution with glaucoma, as angle closure is often what these warnings are attempting to help them avoid.

Among the more rare but potentially serious complications from medication use is topiramate-induced angle closure. Topiramate is an effective medication for treating migraines and epilepsy, and has also been shown to be an effective medication for weight loss.⁵ In some patients, choroidal effusions can form, leading to anterior rotation of the ciliary body and shallowing of the anterior chamber, ultimately resulting in bilateral angle closure (Figure 1).

To reverse this potentially devastating issue, patients need to be given cycloplegic agents, which shift the ciliary body posteriorly, ultimately alleviating the angle closure issue, along with hypotensive agents to aid in IOP lowering until the patient’s anatomy returns to normal. Patients with topiramate-induced choroidal effusions should also cease topiramate use and return to their provider to discuss alternative options.

EFFECTS Of CARDIOVASCULAR HEALTH

The effects of uncontrolled diabetes on ocular health are numerous, but one of the more vision-threatening complications in advanced disease is neovascular glaucoma. This form of glaucoma tends to be aggressive and difficult to treat, with many patients requiring surgical intervention for proper long-term IOP control. At a minimum, these patients are likely to receive intermittent to long-term intravitreal injections to keep neovascularization at bay. These injections have revolutionized retinal care in proliferative diabetic retinopathy, but continued injections may impede aqueous outflow and cause a chronic increase in IOP.⁶

Beyond neovascular glaucoma, diabetes is suggested to affect the development and progression of glaucoma via several pathways, including vascular dysregulation, decreased nerve factor expression via abnormal axonal transport, and neurodegenerative changes.⁷

Patients with systemic hypertension often ask about the correlation between systemic blood pressure and IOP. Although instantaneous effects on IOP are less likely, studies support that chronic elevation in systemic blood pressure correlates to a slight elevation in IOP.⁸ A further consideration for these patients is the possibility of hypotension with medication use. The biggest concern for this effect happens at nighttime, when IOP tends to elevate, which may lead to reduced ocular perfusion pressure and progressive glaucomatous damage. This should especially be considered in patients with normal-tension glaucoma (NTG) and those who are progressing despite normal in-office IOP readings.⁹

Patients with NTG particularly seem to have some level of damage, either directly or secondarily, associated with issues of cardiovascular health and vasoregulation (Figure 2). A retrospective study by Funk et al showed these patients are more likely to have problems with diabetes, hypertension, hypotension, migraine headache, and Raynaud syndrome.¹⁰ Among those who may be at highest risk are patients with Flammer syndrome, a condition most commonly seen in females characterized by cold hands and feet, red and white skin blotches during emotional stress, low body mass index, nocturnal hypotension, Raynaud syndrome, and migraines.¹¹

RESPIRATORY ISSUES

Obstructive sleep apnea (OSA) is present in upwards of 20% of patients who undergo community screenings and has been shown to be a risk factor for glaucoma development, especially in those with severe disease.¹² The effect from OSA is both vascular (hypoxia, increased resistance, oxidative stress) and mechanical (IOP fluctuation, increased intracranial pressure).¹³ Although continuous positive airway pressure is commonly used to keep the airway open and avoid some of these secondary factors, this may result in both increases and diurnal fluctuations in IOP, leading to progressive optic nerve damage.^14,15

The connections between chronic obstructive pulmonary disease and asthma to glaucoma remain mostly inconclusive.¹⁴ However, these patients are often treated with medications, such as corticosteroids and anticholinergics, including ipratropium, which may have negative effects on IOP, as stated earlier. For this reason, patients taking these medications should be monitored and educated accordingly.

THE NEUROLOGIC TIE-IN

Potential ties between glaucoma and neurodegenerative conditions, such as Alzheimer disease, Parkinson disease, and other dementias, remain of interest among researchers, given that commonalities exist in the chronic, progressive loss of neurons. However, studies remain mixed as to correlations between these conditions, with some reporting refuting information on correlation and risk of disease development.^16-20 Studies on possible common causative factors need to be performed before we can draw more definitive conclusions on correlation, but the intrigue for solutions that could alleviate several conditions remains. These patients can be somewhat challenging to follow, given that declines in mental or motor function may alter the reliability of visual field testing, potentially altering a key component of glaucoma monitoring.

BE FULLY INFORMED AND SHARE WHAT YOU KNOW

The associations between glaucoma and a patient’s systemic health are expansive. Although these factors may not be the first thing we pay mind to in a given optometric examination, it is important that we consider how medications and comorbidities may contribute to, or even outright cause, glaucomatous damage. Educating our patients on how these factors can affect their glaucoma and coordinating care with their appropriate providers can help us to preserve vision for the long run.