She politely declined, and stated that, instead, she was going to begin meditating and increasing her intake of green tea.
I was flabbergasted, and I’m now ashamed to admit that I dismissed her from my care—I decided that our approaches to her condition were too starkly different to work in her best interest. Remember, in the early 1990s, glaucoma diagnosis and management didn’t leave much room for “alternative” or “homeopathic” therapies. These days, this type of exchange between doctor and patient is a lot more common.
What is CAM? •
Complementary medicine is used together with conventional medicine. An
example of a complementary therapy is using aromatherapy to help lessen
a patient’s discomfort following surgery. •
Alternative medicine is used in place of conventional medicine. An
example of an alternative therapy is using a special diet to treat
cancer instead of undergoing surgery, radiation or chemotherapy that
has been recommended by a conventional doctor. Source: National Institutes of Health—National Center for Complementary and Alternative Medicine.
Whether or not we embrace all, some or none of the concepts of complementary and alternative medicine (CAM), we need to be aware of the research supporting—or refuting—their use so that we can provide our patients with the most accurate information possible.
Alternative Approaches
Glaucoma is a disease of multifactorial origin. Yet, increased intraocular pressure remains the only modifiable risk factor against the development of glaucomatous-associated optic nerve damage. Still, scientists continue to rapidly develop the body of knowledge about non-IOP-dependent mechanisms in the pathogenesis of glaucoma.
At the same time, many patients are seeking a more active role in their own care, and have access not only to traditional science as reported through popular media, but also to a wide variety of alternative theories.
At last count (10 years ago), at least one in 20 glaucoma patients reported using complementary or alternative medicine for their disease.1 Of these, more than half believed it was helpful. And, one-quarter of patients who used CAM for glaucoma did not discuss it with their eye doctor.
So, it’s not unusual for patients to seek answers by merging the traditional with the alternative: Does my sleeping position affect my glaucoma? Which foods, herbs or supplements might make my glaucoma eye drops work better? Is there anything to the theory of acupuncture augmenting glaucoma therapy?
At first blush, alternative approaches often seem a bit, well, “out there.” But sometimes there’s a scientific basis to explain what often begins as anecdotal evidence, and some of those “out there” ideas eventually become mainstream.
This article reviews a few of the best-understood mechanisms that are believed to contribute to ganglion cell damage in glaucoma—increased intraocular pressure, oxidative damage and vascular dysregulation at the optic nerve head—and discusses the associated alternative therapies for those processes.
Increased IOP
The current pharmaceutical approach to glaucoma management is aimed at reducing IOP. For decades, the body of evidence has pointed to elevated IOP as the primary risk factor in the advancement of optic nerve damage in glaucoma.2,3 In addition to mainstream medical therapy, several “alternative” approaches to reducing IOP have been investigated, with variable results.
Perhaps the most well known of these is THC, the active ingredient in marijuana.4 Although its action in lowering IOP is well established, the serious side effects and high abuse liability limit its widespread use.
Other alternative approaches likely hold more promise.
• Melatonin. The hormone melatonin is responsible for several functions, including regulation of seasonal and circadian rhythms.5 Melatonin is also involved in the dynamics of aqueous humor. Topical melatonin receptor agonists have demonstrated fairly impressive effects in reducing IOP in recent animal studies—reductions in IOP with these agents range from 19% to 28%.5,6 These effects are comparable to those achieved with currently available pharmaceutical agents.
To date, no significant adverse effects have been described with the topical application of melanin. However, bear in mind that this hormone is synthesized in many tissues in the body, not just the eye. The systemic absorption profile of topical melatonin drops has not yet been fully investigated, so the range of systemic effects with its potential topical use is not yet known.
Melatonin also serves as an antioxidant, potentially giving it a secondary mechanism by which to offer neuroprotection in glaucomatous eyes.7 Because of this dual action, melatonin receptor agonists may emerge as a useful adjunctive therapy in glaucoma.
• Acupuncture. Several recent animal studies have reported an IOP-lowering effect following acupuncture—a 15% reduction was seen in one study.8,9 At least one animal study has concluded that acupuncture preserves retinal function in induced glaucoma.10 But remember, animal studies sometimes involve first creating glaucoma by using destructive techniques, so the “glaucomatous” eyes likely have some structural and/or chemical differences as compared to human patients with glaucoma. So, results should be interpreted while keeping these potential differences in mind.
One small series using human subjects found a mild, transient IOP-lowering effect for up to four weeks following an acupuncture treatment series, but the study lacked a control group.11 A comprehensive evaluation of the literature suggests that the existing evidence lacks sufficient quality and quantity to draw any conclusions about the efficacy of acupuncture in lowering IOP.12 At the same time, there is no evidence indicating that any ill effects will result from using acupuncture to augment conventional medical treatment. Some patients may wish to pursue this as complementary therapy, applying the “can’t hurt, might help” philosophy.
• Sleeping position. How patients sleep at night may pose another preventable risk factor in glaucoma. Several studies have recently reported an increase in IOP when patients are positioned in the supine position (lying down) as compared to an upright position.13,14 These differences may be even more pronounced in patients already diagnosed with normal-tension glaucoma.15
As a result, researchers have started looking at whether a simple modification in overnight sleeping position might lower the risk of glaucomatous nerve damage induced by overnight rises in IOP. A recent study found that an action as simple as having the patient sleep at a 30º incline may reduce nighttime IOP by up to 20% in some patients.16 Sleeping with two or three pillows may present a risk-free, non-invasive, no-cost, effective means to boost the effects of other glaucoma therapies, whether traditional or CAM.
Oxidative Stress and Vascular Dysregulation
We know that ocular blood flow disruptions play a direct and/or indirect role in glaucomatous optic neuropathy.7,16,17 Rather than being the result of a steady-state reduction in blood flow to the optic nerve (i.e., hypoperfusion), most experts agree that it is repeated mild reperfusion—resulting from fluctuations in systemic blood pressure and ocular perfusion pressure—that creates damage at the ganglion cell level.7
We also know that glaucoma patients, especially those with normal-tension glaucoma, have more variability in systemic blood pressure than do patients without glaucoma. This difference is most noticeable overnight and in the early morning, and it is more pronounced in older patients than younger patients.18-21 Several mechanisms are likely at play—perhaps the most important among them is oxidative stress caused by the low-level hypoperfusion and reperfusion.7
What is oxidative stress? Living cells use oxygen, and the metabolism of oxygen creates “reactive oxygen species,” or ROS. ROS are sometimes called “free radicals.” In an ideal state, the production of ROS would be counterbalanced exactly by the presence of antioxidants. An excess of ROS relative to antioxidants creates oxidative stress, which is believed to be at least partly responsible for cellular damage in many disease states, including glaucoma.22 In fact, the oxidative stress in glaucoma may actually be the underlying cause of increased intraocular pressure in glaucoma, rather than its result!23,24
Not all ROS are the same; likewise, the actions and behaviors of different antioxidants vary depending on several factors. Much of the current research in this area is aimed at differentiating the various ROS that are produced in eyes with glaucoma, and even further identifying which sub-structure of the ganglion cells (GC) are most affected. It appears that the GC mitochondria play an important role in regulating cell death, so targeting antioxidant therapy at these organelles is the target of much recent research activity.7,25-28 Incidentally, the same principles involving ROS and targeted antioxidant therapy apply in many other diseases, including age-related macular degeneration.
So, if fluctuations in blood flow to the nerve create oxidative stress, and oxidative stress causes ganglion cell damage, many would argue that it makes more sense to address these mechanisms—using traditional therapy or CAM—as opposed to just reducing IOP pharmacologically. The following dietary modifications and supplements deal with these mechanisms:
• Salt. Some researchers advocate combating vascular dysregulation, at least in part, by inducing an increase in systemic blood pressure. This can be done by deliberately supplementing the diet with the most commonly cited “culprit” in contributing to high blood pressure: ordinary table salt.29 Obviously, this approach is ill-advised for patients who have coexisting vascular conditions that would be exacerbated by an increase in systemic blood pressure. Nevertheless, in select patients, increasing blood pressure can be protective against those damaging fluctuations, especially the blood pressure “dips” that occur overnight.
• Omega-3 fatty acids. What other dietary modifications can help regulate the vascular system? There is little doubt that omega-3 fatty acids (FAs) are beneficial to virtually every system in our bodies, and the promotion of vascular health is certainly among the benefits. Some studies have found that omega-3 FAs may have a direct therapeutic benefit in glaucoma patients, despite the fact that one of the well-known effects of these substances is a mild reduction in systemic blood pressure—not an elevation, as with salt.
But remember: It’s not the absolute systolic or diastolic pressure that is suspected of causing optic nerve damage in glaucoma, but rather the repeated fluctuations in ocular perfusion pressure. Stabilization is the key concept, which may be why omega-3 FAs are linked to positive outcomes in some glaucoma studies.30,31
• Magnesium. Magnesium is also believed to improve vascular regulation.29,32
• Antioxidants. A host of known antioxidants have been suggested to combat the ROS that seem to be more prevalent in glaucoma patients. The most studied include polyphenolic compounds, notably the widely publicized resveratrol contained in red wine.29 Other sources of antioxidants: dark chocolate, ubiquinone (coenzyme Q10), anthocyanosides (found in bilberries) and turmeric.29
Ginkgo biloba extract (GBE) is unique in this antioxidant class, because it specifically acts upon the mitochondria.28 Additionally, GBE probably acts in other ways, and it may even have a positive effect in vascular regulation.33
And, yes, my former patient’s green tea (in fact, all tea) also contains antioxidants that may be protective against glaucoma.34 No single antioxidant has yet emerged as the “best” antioxidant to potentially reduce the risk of cellular damage in glaucoma—but this is an area of intense interest.
Complementary and alternative medicine is playing an increasingly important role in our available management strategies for our glaucoma patients. Perhaps even more importantly, patients have access to information sources about these therapies, and may choose to experiment with them on their own. So, we need to stay abreast of scientific developments in this area so that we can knowledgeably and open-mindedly discuss all available management options with our patients.
Dr. Reed is an associate professor at Nova Southeastern University, where she teaches ocular disease and primary clinical care.
1. Rhee DJ, Spaeth GL, Myers JS, et al. Prevalence of the use of complementary and alternative medicine for glaucoma. Ophthalmology. 2002 Mar;109(3):438-43.
2. Morrison JC. Elevated intraocular pressure and optic nerve injury models in the rat. J Glaucoma. 2005 Aug;14(4):315-7.
3. Niesel P, Flammer J. Correlations between intraocular pressure, visual field and visual acuity, based on 11 years of observations of treated chronic glaucomas. Int Ophthalmol. 1980 Dec;3(1):31-5.
4. Gerra G, Zaimovic A, Gerra ML, et al. Pharmacology and toxicology of Cannibis derivatives and endocannabinoid agonists. Recent Pat CNS Drug Discov. 2010 Jan;5(1):46-52.
5. Andres-Guerrero V, Alarma-Estrany P, Molina-Martinez IT, et al. Ophthalmic formulations of the intraocular hypotensive melatonin agent 5-MCA-NAT. Exp Eye Res. 2009 Mar;88(3):504-11.
6. Serle JB, Wang RF, Peterson WM, et al. Effect of 5-MCA-NAT, a putative melatonin MT3 receptor agonist, on intraocular pressure in glaucomatous monkey eyes. J Glaucoma. 2004 Oct;13(5):385-8.
7. Mozaffarieh M, Grieshaber MC, Orgul S, et al. The potential value of natural antioxidative treatment in glaucoma. Surv Ophthalmol. 2008 Sep-Oct;53(5):479-505.
8. Kim MS, Yoo JH, Seo KM, et al. effects of electroacupuncture on intraocular pressure and hemodynamic parameters in isoflurane anesthetized dogs. J Vet Med Sci. 2007 Nov;69(11):1163-5.
9. Kim MS, Seo KM, Nam TC. Effect of acupuncture on intraocular pressure in normal dogs. J Vet Med Sci 2005 Dec;67(12):1281-2.
10. Chan HH, Leung MC, So KF. Electroacupuncture provides a new approach to neuroprotection in rats with induced glaucoma. J Altern Complement Med. 2005 Apr;11(2):315-22.
11. Kurusu M, Watanabe K, Nakazawa T, et al. Acupuncture for patients with glaucoma. Explore (NY). 2005 Sep;1(5):372-6.
12. Law SK, Li T. Acupuncture for glaucoma. Cochrane Database Syst Rev. 2007 Oct 17;(4):CD006030.
13. Jorge J, Ramoa-Marques R, Lourenço A, et al. IOP variations in the sitting and supine positions. J Glaucoma. 2010 Feb 15 [Epub ahead of print].
14. Kiuchi T, Motoyama Y, Oshika T. Postural response of intraocular pressure and visual field damage in patients with untreated normal-tension glaucoma. J Glaucoma. 2009 Jun 12 [Epub ahead of print].
15. Buys YM, Alasbali T, Jin YP, et al. Effect of sleeping in a head-up position on intraocular pressure in patients with glaucoma. Ophthalmology. 2010 Feb 24. [Epub ahead of print].
16. Sung KR, Lee S, Park SB, et al. Twenty-four hour ocular perfusion pressure fluctuation and risk of normal-tension glaucoma progression. Invest Ophthalmol Vis Sci. 2009 Nov;50(11):5266-74.
17. Moore D, Harris A, Wudumm D, et al. Dysfunctional regulation of ocular blood flow: A risk factor for glaucoma? Clin Ophthalmol. 2008 Dec;2(4):849-61.
18. Kim YK, Oh WH, Park KH, et al. Circadian blood pressure and intraocular pressure patterns in normal tension glaucoma patients with undisturbed sleep. Korean J Ophthalmol. 2010 Feb;24(1):23-8.
19. Graham SL, Drance SM. Nocturnal hypotension: role in glaucoma progression. Surv Ophthalmol. 1999 Jun;43 Suppl 1:S10-6.
20. Galambos P, Vifiadis J, Vilchez SE, et al. Compromised autoregulatory control of ocular hemodynamics in glaucoma patients after postural change. Ophthalmology. 2006 Oct;113(10):1832-6.
21. Kida T, Liu JH, Weinreb RN. Effect of aging on noctural blood flow in the optic nerve head and macula in healthy human eyes. J Glaucoma. 2008 Aug;17(5):366-71.
22. Mozaffarieh M, Flammer J. A novel perspective on natural therapeutic approaches in glaucoma therapy. Expert Opin Emerg Drugs. 2007 May;12(2)195-8.
23. Kahn MG, Giblin FJ, Epstein DL. Glutathione in calf trabecular meshwork and its relation to aqueous humor outflow facility. Invest Ophthalmol Vis Sci. 1983 Sep;24(9):1283-7.
24. Saccà SC, Pascotto A, Camicione P, et al. Oxidative DNA damage in the human trabecular meshwork: clinical correlation in patients with primary open-angle glaucoma. Arch Ophthalmol. 2005 Apr;123(4):458-63.
25. Reddy PH. Mitochondrial medicine for aging and neurodegenerative diseases. Neuromolecular Med. 2008;10(4):291-315.
26. Reddy PH. Role of mitochondria in neurodegenerative diseases: mitochondria as a therapeutic target in Alzheimer’s disease. CNS Spectr. 2009 Aug;1(8 Suppl7):8-13.
27. Sas K, Robotka H, Toldi J, et al. Mitochondria, metabolic disturbances, oxidative stress and the kynurenine system, with focus on neurodegenerative disorders. J Neurol Sci. 2007 Jun 15;257(1-2):221-39.
28. Abu-Ameri KK, Morales J, Bosley TM. Mitochondrial abnormalities in patients with primary open-angle glaucoma. Invest Ophthalmol Vis Sci. 2006 Jun;47(6):2533-41.
29. Mozaffarieh M, Flammer J. Is there more to glaucoma than lowering IOP? Surv Ophthalmol. 2007 Nov;52 Suppl 2:2174-9.
30. Nguyen CT, Bui BV, Sinclair AJ, et al. Dietary omega 3 fatty acids decrease intraocular pressure with age by increasing aqueous outflow. Invest Ophthalmol Vis Sci. 2007;48(2):756-762.
31. Nguyen CT, Vingrys AJ, Bui BV. Dietary omega-3 fatty acids and ganglion cell function. Invest Ophthalol Vis Sci. 2008 Aug;49(8):3586-94.
32. Aydin B, ONol M, Hondur A, et al. The effect of oral magnesium therapy on visual field and ocular blood flow in normotensive glaucoma. Eur J Ophthalmol. 2010 Jan-Feb;20(1):131-5.
33. Chung HS, Harris A, Kristinsson JK, et al. Ginkgo biloba extract increases ocular blood flow velocity. J Ocul Pharmacol Ther. 1999 Jun;15(3):233-40.
34. Chu KO, Chan KP, Wang CC, et al. Green tea catechins and their oxidative protection in the rat eye. J Agric Food Chem. 2010 Feb 10;58(3):1523-34.
