Lifestyle Habits and Glaucoma

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Summary:

Glaucoma is a major public health problem that is estimated to have affected over 111 million people worldwide in 2040. [1] Unfortunately, that number may be underestimated because a recent population study suggests that 10-50% of people with glaucoma are unaware that they have glaucoma. [2] This is because a large number of patients are typically asymptomatic until the later stages of the disease.  Glaucoma can be divided into two categories: open-angle glaucoma and angle-closure glaucoma.  In the United States, more than 80% of all glaucoma cases are open-angle cases. [2] However, worldwide the prevalence of primary open angle glaucoma (POAG) is highest in Africa affecting 4.2% of the population, and the prevalence of primary angle closure glaucoma (PACG) is highest in Asia affecting 1.09% of the population.[1]

Many genetic and environmental factors influence the development of glaucoma, and the complete pathophysiology is still unknown. Other risk factors such as: intraocular pressure (IOP), race, age, frailty, gender, myopia, systemic hypotension, systemic hypertension, vasospasm, and others have been linked with increased risk for glaucoma and developing glaucomatous injury – such as optic nerve thinning and atrophy and visual field deficits. While the pathophysiology of glaucoma is elusive, the pathology of glaucoma is generally thought to be associated with elevated IOP.[3] Normal IOP is thought to range between 10 and 21 mmHg, though glaucoma can still develop even within the normal IOP range. [4] As of now, the only causative risk factor that can be modified is IOP.  Since IOP is the only risk factor that can be modified, IOP management is extremely important in patient outcomes.  In recent years, there has been growing evidence of how lifestyle habits can influence IOP and ultimately the outcomes and progression of glaucoma. As medicine evolves to a more holistic approach, it is important to raise the awareness of how lifestyle habits can affect patients' management and treatment of glaucoma.  In this article we will explore what the literature tells us about common lifestyle habits and glaucoma.

Disease:

Glaucoma is a broad category of ocular disorders that all end in optic nerve damage and visual field defects. Its is defined as a group of neuropathies that characteristically lead to a degeneration of retinal ganglion cells and is one of the leading causes of irreversible blindness. The characteristic appearance of how glaucoma affects the optic nerve is what distinguishes glaucoma from other optic neuropathies. In glaucoma, there is progressive thinning of the neuroretinal rim of the optic nerve causing an enlargement of the optic-nerve cup. Enlargement of the optic-nerve cup is known as optic-nerve cupping. Increased optic-nerve cupping can result in optic nerve damage due to the loss of retinal ganglion cell axons and the supporting glia and vasculature.[4] Classification of glaucoma is based on the appearance of iridocorneal angle which is the angle between the iris and the cornea which determines whether the glaucoma is an open angle or closed angle glaucoma. Open-angle and closed-angle glaucoma can either be primary or secondary diseases. Secondary diseases can result from inflammation, tumor, medications such as corticosteroids, trauma or conditions such as pigment dispersion or pseudo-exfoliation. [2]

Risk Factors:

  • Age
  • Family History of glaucoma
  • Genetics
  • Frailty
  • Race
  • Type and degree of refractive error
  • Systemic hypertension
  • Systemic hypotension
  • Migraine
  • Pigmentary Dispersion Syndrome
  • Pseudoexfoliation Syndrome
  • Obstructive Sleep Apnea
  • Diabetes
  • Medication interaction and side effects (especially systemic or topical corticosteroids)
  • Degree of exposure to intraocular and intracranial pressure elevations and fluctuations
  • Smoking

[3]

Pathophysiology:

While the pathogenesis of glaucoma is not completely understood, there has been shown to be a link between IOP and retinal ganglion cell death. There are two independent pathways, trabecular meshwork and uveoscleral outflow pathway, that help regulate IOP by creating a balance between the aqueous humor secreted from the ciliary body and its drainage. [2] Patients that suffer from open-angle glaucoma have an increase in resistance to aqueous flow through the trabecular meshwork. In patients that suffer from closed-angle glaucoma there is obstruction of the drainage pathway which is typically caused by the iris. [2] Dysregulation of the drainage pathways can lead to increased IOP and can damage the posterior structures in the eye which include the optic nerve and its supporting vasculature. Despite the strong connection between increased IOP and retinal ganglion cell death, there are also cases of glaucoma in patients who have IOP within the normal range. Glaucoma in patients with normal IOP can be caused by impaired microcirculation, altered immunity, excito-toxicity, oxidative stress, and low cerebrospinal fluid creating a large pressure gradient across the lamina cribrosa. While there are cases of patients developing glaucoma with normal IOP, elevated IOP still remains the number one causative agent in developing glaucomatous changes. [5]

Lifestyle Modifications:

Currently, medication and laser trabeculoplasty are considered first line therapy in the management of glaucoma. If glaucomatous changes continue to progress, surgical approaches are considered. As the pathophysiology is not linear and several components individualize a person’s “type of glaucoma,” treatment is also individualized. As people are becoming increasingly knowledgeable about the detrimental side effects of medications and procedures, there has been more interest in learning about lifestyle modifications as a non-pharmacological approach to managing glaucoma. As patients continue to grow an interest in having control of their health, it is the physician's responsibility to be able to inform and communicate effectively to patients how lifestyle modifications can help manage their disease, and additionally improve overall compliance to therapy.

Diet and Glaucoma

Dietary Nitrates and Dark leafy greens

Nitrates, a dietary source found in dark leafy greens (represents 80% of nitrate intake), are converted to nitric oxide once ingested. Nitric oxide has been shown to be protective against glaucoma through vasodilation and increased aqueous humor outflow and decreased episcleral venous pressure.[6] One study showed that Schlemm canal cells produced a markedly reduced amount of nitric oxide in glaucomatous eyes compared to non-glaucomatous eyes.[7] Using data from the Nurses' Health Study and Health Professionals Follow-up Study, Kang and colleagues[8] demonstrated that patients with higher dietary nitrate intake had lower risk of developing POAG (20-30% reduced risk).

Omega-3 fatty acids

Omega-3 fatty acids have recently been connected to improved ocular health, particularly in retinal health. The benefit with glaucoma is controversial at this time. Eicosapentaenoic acid and docosahexaenoic acid (DHA), which are found in omega-3 fatty acids, have been shown to modulate systemic microcirculation and ocular blood flow. A recent population-based study was able to demonstrate how omega-3’s influence on the vascular system can lower the likelihood of glaucomatous optic neuropathy, increase ocular blood flow and decrease IOP. [5] A prospective study evaluated the effect of oral DHA supplementation on the IOP in patients with pseudoexfoliative (PEX) glaucoma. They showed that 6 months oral DHA supplementation resulted in a statistically significant reduction in IOP.[9] However, in another study, it was found that having a high ratio of omega-3 to omega-6 fatty acids can increase the risk of glaucoma.[10]

Dietary supplements

Vitamins

There exists a wide body of research on the role of dietary supplements and glaucoma, however many of the results are conflicting and inconclusive. Beyond including vitamins as part of a healthy diet, there is no evidence to support specific vitamin supplementation in reducing the risk of or treating glaucoma.[11] Promising studies continue to emerge. A study in mice found that Vitamin B3 reduced vulnerability to glaucoma by preventing IOP-induced mitochondrial dysfunction[12], and a clinical trial with 57 participants found that Vitamin B3 supplementation improved inner retinal function (measured by ERG) in glaucoma patients.[13] A meta-analysis by Li and colleagues demonstrated no association between serum levels of different vitamins (B6, B12, and D) and different types of glaucoma, including POAG, normal tension glaucoma, and PEX glaucoma.

The potential role of oral nicotinamide (the amide form of Vitamin B3) has been recently investigated in glaucoma, due to its potential neuroprotective effects. De Moraes and colleagues[14] evaluated the effect of a combination of oral nicotinamide and pyruvate on the visual field parameters compared to placebo in glaucoma patients. They showed a significant improvement in the rate of change of pattern standard deviation and a higher number of improving testing locations in the nicoinamide+pyruvate group, suggesting its potential role in improving visual function in glaucoma patients. However, there were no significant differences in the mean deviation and visual field index between both groups.

Fruits

Diets high in fruits such as have been shown to lower the risk of glaucoma development. The most discussed benefit is through antioxidants. As oxidative stress is associated with optic nerve injury, fruits high in antioxidants, such as pomegranate, acai berries, cranberries offer the most neuroprotection. [15] Giaconi and colleagues[16] demonstrated that higher consumption of fruits and vegetables rich in Vitaimin C, E, and carotenoids were associated with lower risk of glaucoma in African-American women.

Alcohol

Although alcohol intake may be associated with transient IOP reduction[17][18], chronic alcohol intake may increase the risk of open-angle glaucoma on the long-term.[19] A recent systematic review, including ten studies showed that chronic alcohol intake was associated with higher IOP and higher prevalence of ocular hypertension. Moreover, any use of alcohol was associated with increased odds of open-angle glaucoma by 1.18. However, it should be noted that the current evidence certainty was very low.[19]

Caffeine

1,3,7-trimethylxanthine, recognized as caffeine, is a common ingredient of popular beverages such as tea, coffee and soda pops. Li and colleagues conducted a meta-analysis to evaluate the effect of caffeine consumption on IOP in both healthy individuals and glaucoma patients. They showed that caffeine intake was not associated with IOP increase in healthy individuals; however, it was associated with transient increase in IOP (ranging from 0.34 mmHg at 30 minutes to approximately 2.4 mmHg one hour post-intake) in patients with a history of glaucoma or ocular hypertension.[20] Several studies have shown no significant association with caffeine intake and prevalence of glaucoma except in patients with a positive family history of glaucoma[21] or those who are genetically predisposed.[22] Additionally, a recent study by Yuan and colleagues[23] showed that increased caffeine consumption (especially individuals who drank 2-3 cups of coffee per day or more than cups of tea per day) has been associated with increased macular retinal nerve fiber layer thickness.

Herbal supplements

The role of several herbal supplements in glaucoma management have been studied as well. For example, gingko balboa extract has showed some promising findings because of its antioxidant and anti-inflammatory properties. Some studies demonstrated the role of gingko balboa extract in increasing peripapillary blood flow, stabilizing mitochondrial function, and improving visual field indices; however, human studies have shown contradicting studies.[11] One study showed no visual field improvements in normal tension glaucoma patients using gingko balboa extract.[24] In contrast, Sari and colleagues demonstrated a significant visual field improvement in POAG patients on gingko balboa extract.[25] Another herbal supplement is Erigeron breviscapus hand-mazz (EBHM), which has been suggested to improve the axoplasmic flow in ganglion cells. One study reported a potential role in protecting VF in POAG patients; however, the literature is limited to draw a solid conclusion.[26][27]

Flavonoids are plant-based polyphenolic compounds found abundantly in red wine, dark chocolate, berries, citrus fruits and teas. A meta-analysis evaluated the effect of flavonoids on visual function of glaucoma patients and demonstrated that flavonoid intake was associated with significant improvements in the mean deviation of the visual field.[28]

Takeaway:

It should be recommended to patients that a well-balanced diet can provide benefits in managing glaucoma. While there is conflicting evidence, omega-3 intake should be consumed in moderation until further research is concluded. Increased intake of dietary leafy vegetables is recommended. Oral supplementation of a combination of nicotinamide and pyruvate may have a potential role in the future; however, further research is needed. Heavy caffeine intake should be advised against due to its transient elevations in IOP, especially in genetically predisposed patients or those with a positive family history of glaucoma. Chronic alcohol consumption can lead to many systemic complications and increased risk of glaucoma.

Exercise and Glaucoma

Aerobic Exercise

Several studies have evaluated the association between aerobic exercises and IOP.[29] Gillmann and colleagues showed that walking and cycling resulted in mild increase in IOP during the activity, followed by an IOP reduction.[30] Another study showed that running resulted in an IOP reduction of about 2 mmHg; however, the IOP returned back to the baseline within 30 minutes after the exercise.[31] A recent systemic review including 16 studies showed evidence that moderate aerobic exercise can lead to transient IOP reduction.[29] It has been widely studied that cardiac and vascular dysfunction can lead to elevated intraocular pressures which aerobic exercises optimize. [32] A 2015 study by Hetch et. al., compared the IOP outcomes between medication versus 30 minutes of daily exercise in a group of newly diagnosed glaucoma patients The study concluded that the exercise group had a significant drop in IOP as compared to its medically treated counterparts. [33] This study gives us further evidence that exercise done in moderation is protective in managing glaucoma.

Lee and colleagues showed that walking was associated with lower rates of visual field progression in patients with glaucoma. They reported that for each 5000 steps daily or two and half hours of non-sedentary life , the visual field progression significantly reduced by 10%.[34] Pan and colleagues[35] showed that for every additional 10 minutes of evening activity per day, the odds of visual field progression in POAG patient was reduced by 15%. Additionally, a recent study showed a slower rate of ganglion cell-inner plexiform layer thinning with increased activity.[36]

Weightlifting

The evidence for how weightlifting influences glaucoma is mixed. Exercises that required isometric holds, such as weightlifting, result in a transient increase in IOP followed by IOP reduction to near baseline levels within the first minute. While this transient increase in IOP is normally harmless and natural, there is risk of optic nerve damage in vulnerable populations (normal tension glaucoma, etc). [15] In the Avunduk et. al study, the effects of isometric and isokinetic weightlifting exercises both lowered IOP, but isokinetic exercises providing a more significant decrease in IOP. [37] Another study showed that IOP spikes during leg compresses may reach up to ~41 mmHg during the exercise. These IOP spikes may carry a risk of further damage in susceptible patients.[38]

Yoga

Yoga is a common practice for individuals wanting to participate in a healthier lifestyle. Unfortunately, certain yoga exercises (head down positions, activities that require sudden head movement, or using wind instruments) can be harmful for patients suffering from glaucoma, in particular those at-risk for disease progression. When performing yoga, popular positions such as “downward dog” and the “forward bend" have been shown to significantly increase IOP by placing the head/eyes lower than the heart.[39] Other yoga poses such as handstands have been shown to elevate IOP approximately two-fold. [40]

Swimming

An association between glaucoma progression and wearing swimming goggles, which can lead to a transient, significant IOP increase in healthy individuals. [11] While the strength of this association is not well defined and most evidence come from case reports; it may be prudent to advise at-risk patients of this association.[41]

High Intensity workouts

A good general rule of thumb is that everything should be done in moderation which includes high intensity workouts. It was shown that vigorous exercise performed daily was associated with higher prevalence of glaucoma compared to participants that performed vigorous exercise three days a week. [42] The same publication suggests that vigorous exercise may increase the concentration of free radicals in the body, while oxidative stress have been linked to structural optic nerve damage, inflammatory reactions, and may play a role in the progression of glaucoma. [43]

Body Mass Index

There is conflicting findings regarding the relationship between body mass index (BMI), IOP, and glaucoma. Body mass index has been shown to be positively correlated with IOP, while inversely associated with prevalence of glaucoma.[11] Studies have shown that patients experiencing sudden weight loss (i.e. post bariatric surgery) have lower post-operative IOP values. A recent study showed that bariatric surgery was associated with reduced risk of ocular hypertension, glaucoma, and use of glaucoma medications.[44] Further investigation needs to be done on the pathophysiology of this association and the effect of concurrent changes in body composition and metabolism.[11]

Takeaway:

In summary, walking and moderate intensity exercise that optimizes cardiac and vascular function can decrease the IOP and risk of glaucomatous changes. It is general consensus to avoid valsalva poses such as downward dog in yoga or heavy weightlifting in at risk populations. It may be advisable not to use swimming goggles with caution in susceptible individuals.

Sleep and Glaucoma

Sleeping Position

Intraocular pressure has been shown to be influenced by the position of which patients slept in. It was previously shown that changing from sitting to supine position increases IOP by about 1-2 mmHg in healthy individuals and by 4 mmHg in patients with glaucoma.[45] Few studies showed that changing from supine to lateral decubitus position may increase the IOP by about 1.5-2 mmHg for the eye in dependent position and by 0.5-1 mmHg for eye in non-dependent position.[45]

Another study explored the possibility of whether IOP was influenced by the mechanical forces of the pillow when someone sleeps face down. It was shown that patients that slept with their face in the pillow had an increase in IOP of 2.5 +/- 1.1 mmHg as compared to the control subjects. [33]

Obstructive Sleep Apnea

Obstructive sleep apnea has also been linked with increased risk of developing or worsening glaucoma. Obstructive sleep apnea has been shown to both increase the risk for cardiovascular dysfunction and hypertension, both of which can cause hyperplasia of vascular endothelium, increase episcleral venous pressure and diminish aqueous outflow. The end product is elevated IOP and higher risk of glaucomatous changes. [46] A recent meta-analysis conducted by Cheong and colleagues, including a total of 4,566,984 patients from 46 studies, demonstrated that obstructive sleep apnea increase the odds of glaucoma by almost 4 fold. After adjusting for other confounding factors, such as diabetes mellitus and hypertension, obstructive sleep apnea increase the risk of glaucoma by 40%.[47]

Takeaway:

In summary, sleeping with the head of bed elevated and avoiding mechanical forces on the eye while sleeping are two modifications that can decrease IOP. Additionally, it is also recommended to have appropriate treatment of obstructive sleep apnea with both nightly CPAP use and weight-loss to mitigate vascular endothelial dysfunction.

Smoking and Glaucoma

Tobacco Smoke

Compounds in tobacco damage the eye through mechanisms such as alterations in ocular perfusion, increased concentration of free radicals and a decrease in antioxidant levels in ocular tissue and aqueous humor – ultimately increasing optic nerve damage in of itself and through elevated IOP.[48] Apoptotic and inflammatory markers in the aqueous humor and in the plasma were also found to be increased in glaucoma patients that smoke indicating there is increased cell inflammation and death. Despite this understanding, the relationship between glaucoma and smoking remains elusive. There have been studies that have attempted to find associations between smoking and glaucoma but have failed to provide strong linear evidence. It has been hypothesized that this failure is due to the complexity of the relationship and several confounding factors. [43] One study showed that smokers had significantly higher IOP compared to non-smokers.[49] In contrast, another study demonstrated no significant relationship between smoking and IOP.[50]

Although the association between smoking and IOP is controversial, recent evidence showed that in POAG patients heavy smoking was associated with faster rates of visual field progression and retinal nerve fiber layer thinning.[51][52] Mahmoudinezhad and colleagues showed that a smoking intensity of more than 20 pack/year was associated with increased odds of visual field progression by more than 2-fold compared to non-smokers.[51] Another study showed that using more than 8 pack-year was associated with a significantly faster retinal nerve fiber layer thinning.[52]

Marijuana

When used for treatment of glaucoma, marijuana has been shown to transiently lower IOP for up to 3-4 hours. With such a short half-life, marijuana would have to be dosed 5-6 times a day to maintain a therapeutic effect. Such frequent dosing expose the patient to other side effects of marijuana. Moreover, chronic marijuana use has been associated with tolerance with reduced effect over time, requiring increased dosing.[53] The American Glaucoma Society recommended against the use of marijuana for management of glaucoma citing the lack of scientific evidence and the short duration of action. [43][54]

Takeaway:

While smoking tobacco and its relationship to glaucoma may be complex, there is consensus that smoking tobacco is detrimental systemically. Even though the studies are mixed, it can be presumed that the toxic compounds found in tobacco smoke either provide no health benefits or are damaging to ocular health. Marijuana use in glaucoma has yet to find any substantial evidence to support its therapeutic use. Despite transiently lowering IOP, it is still not recommended for managing glaucoma.

Conclusion:

The difficulty in a diagnosis of glaucoma is the unknown visual and functional impact it can have on a person. The pathophysiology, risk factors and outcomes are individualized and variable making it a difficult disease process to feel in control of and understand. As a physician it is imperative to help simplify the steps of glaucoma, the repercussions of progression, and what can be done to preserve their vision.

The discussion of lifestyle modification enables patients to make impactful improvements in their life and vision. While studies are on-going, currently literature supports a healthy, moderate lifestyle incorporating a diet high in antioxidants and nitric oxide, 30 minutes of moderate intensity and aerobic exercises, improving sleep practices and avoiding using tobacco and marijuana. A key point from current literature is maintaining balance in life choices. Lifestyle modifications along with medication, laser procedures and surgical management offer several graded steps in managing a patient’s glaucoma and preserving their vision and functionality.

Additional Resources

References

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