Providing nutritional support for glaucoma management

Glaucoma is a deceptive and dangerous disease as most patients have few or no symptoms. Glaucomatous optic neuropathy is the leading cause of irreversible blindness worldwide and the second-leading cause of overall blindness (8%). Approximately 79 million persons worldwide have glaucoma, and approximately 2 million patients in the United States and more than 11 million worldwide are bilaterally blind from glaucoma.¹

The leading theory of the main cause of damage to the optic nerve is excessive fluid pressure within the eye, which can be caused by increased aqueous production, blockage of drainage ducts, and narrowing or closure of the iris angle. Because most cases of glaucoma report an increase in intraocular pressure, the goal of treatment is only to lower the eye pressure. Even in cases of normal-tension glaucoma (NTG), no other treatment modality exists but to lower eye pressure. Treatment that reduces intraocular pressure has been shown to improve outcomes in randomized clinical trials.^2-5 Yet even here, there is no cure but only slowing of the progression of the disease.

Traditional therapies

The traditional approach to diagnosing the disease is to measure intraocular pressure, evaluate the optic disc for signs of degeneration (cupping, pallor, etc.), and evaluate the peripheral visual field, where the primary vision loss occurs.

Control of intraocular pressure in glaucoma may require multiple drugs of different classes (Table). Use of glaucoma medications delays visual field loss by lowering intraocular pressure and reduces the absolute risk of progression by 17% in patients with early glaucoma.⁶ The United Kingdom Glaucoma Treatment Study, a multicenter, randomized, placebo-controlled trial, published results in 2015 showing longer visual field preservation in patients with primary open-angle glaucoma (POAG) taking latanoprost (Xalatan).⁷

Nutritional support

Although no studies prove a connection between specific foods or supplements and glaucoma, it’s safe to assume that diet and overall health can affect the disease. The eyes are part of the body so what supports overall health can support ocular structures as well. For people living with glaucoma and even those not at high risk for glaucoma, following nutritional advice on diet and lifestyle choices may help protect eyesight.

One theory on the incidence of glaucoma is related to stress. Prolonged stress leads to adrenal exhaustion, and exhausted adrenals are no longer able to produce aldosterone, which stabilizes the salt balance in the body. When too much salt is lost from the body, the tissue fluids build up and often will push into the eye, increasing the IOP and forcing the lens forward, as well as damage the optic nerve.

Foods rich in antioxidants and phytochemicals (natural compounds found in plants)—whole grains, berries, leafy greens, and nuts—may help protect against damage from free radicals, which have been linked to an increased risk of eye diseases like glaucoma. However, researchers say further studies are needed to determine whether these foods protect against retinal degeneration related to glaucoma.

Whole grains are rich in fiber, vitamins, and antioxidants. Fiber is essential for good health because it helps maintain a healthy digestive system, while vitamins and antioxidants help strengthen the immune system and protect the body from disease. All of these things can also help improve eye health.

Nuts are a good source of vitamin E, magnesium, and arginine, all of which are protective against glaucoma. Nuts are also rich in healthy fats, fiber, and antioxidants that fight oxidative stress, which can lead to cell damage. Increasing intake of these nutrients may reduce the risk of developing glaucoma.

Mirtogenol

Pycnogenol is a compound of natural chemicals that come from the bark of a European pine tree. It is thought to be an antioxidant that helps protect cells from damage. The active ingredients in pycnogenol can also be extracted from other sources, including peanut skin, grape seed, and witch hazel bark.

Mirtogenol is a combination tablet containing 40 mg of pycnogenol and 80 mg of Mirtoselect, standardized bilberry extract. A study in 2008 indicated that Mirtogenol may represent a safe preventive intervention for lowering the risk of developing symptomatic glaucoma by controlling IOP and improving ocular blood flow.⁸ A follow-up study using Mirtogenol with latanoprost showed improvements in retinal microcirculation that were statistically significant for all management groups.⁹

Capsanthin 50% (CapsiClear)

In a recent study, Wistar albino rats were treated with capsanthin 50% (CapsiClear) at low, mid, and high doses and IOP levels were compared to control and disease groups. In this study, IOP was induced by intravitreal injection of carbomer, which elevated levels. IOP was confirmed, the formula was administered for 28 days, and IOP was recorded weekly. The results showed that 28-day repeated administration of capsanthin 50% at dose levels of 20, 40 and 80 mg/kg reduced IOP from day 8 onward. The IOP returned to a level almost equal to that of the untreated groups.¹⁰

Capsanthin 50% did not result in clinical signs of toxicity, mortality, changes in body weight, or feed consumption. There were no treatment-related changes in hematology and clinical chemistry parameters. Based on the available results, it was concluded that daily oral administration of CapsiClear up to 80 mg/kg reduced the IOP in male Wistar rats.

Nitric oxide

Nitric oxide (NO) is involved in the vasodilation of smooth muscle in the cardiovascular, urogenital, respiratory, gastrointestinal, and immune systems. It also has a role in angiogenesis, platelet aggregation, and the musculoskeletal system with regulating bone formation. The mechanism of action is through direct and/or indirect means. NO has a dual role in the inflammatory process, with both excessively low or high concentrations leading to pathology. At high concentrations, NO can be proinflammatory and pathologic while also having desired antimicrobial effects.

Foods that can increase production of NO include beets, root vegetables, garlic, dark chocolate (in moderation), leafy greens,
nuts and seeds, citrus fruits, pomegranates, and watermelon.

Nicotinamide adenine dinucleotide

Nicotinamide adenine dinucleotide (NAD) is a coenzyme that is essential to life and is found in every cell of all living things. NAD is required to catalyze reactions for more than 400 enzymes, more than any other vitamin-derived coenzyme. It is one of the top essential molecules for life because it is involved in many physiological and pathological functions including adenosine triphosphate (ATP) production in the mitochondria and oxidation of fatty acids and amino acids, DNA damage repair, oxidative stress, inflammation, cellular senescence, and others.

Several studies have shown that mitochondrial function may underlie both susceptibility and resistance to developing glaucoma. Mitochondria meet high energy demand, in the form of ATP, which is required for the maintenance of optimum retinal ganglion cell (RGC) function. Reduced NAD levels have been closely correlated to mitochondrial dysfunction and have been implicated in several neurodegenerative diseases including glaucoma. NAD provides neuroprotective effects by increasing oxidative phosphorylation, buffering and preventing metabolic stress, and increasing mitochondrial size and motility.¹¹ Supplements that decrease inflammation like glutathione, berberine, or curcumin can help increase NAD levels. Likewise, a supplement to decrease senescent cells such as quercetin may also help increase systemic NAD levels.

Antioxidants

IOP-independent mechanisms contributing to the development of glaucomatous neurodegeneration include oxidative stress, excitotoxicity, mitochondrial dysfunction (as described above), and impaired ocular blood flow. In the concept of oxidative stress in POAG, the leading role is given to ischemia-reperfusion processes as the main reasons for the formation of reactive oxygen species (ROS). An increase in IOP levels provokes a spasm of the retinal blood vessels, leading to a reduction of the blood circulation of the retina. Subsequent natural reperfusion also contributes to the development of oxidative species. The resumption of oxygen supply to tissues is accompanied by a higher concentration of ROS, which causes the formation of free radicals and massive damage to cellular structures.¹²

Berries are rich in antioxidants, which can help prevent oxidative stress that contributes to glaucoma. A study published in JAMA Ophthalmology found that eating plenty of berries could lower the risk of developing the disease by as much as a quarter. Berries such as raspberries, blackberries, and strawberries contain resveratrol, a compound found in red wine that has been linked to lower rates of glaucoma. In addition, blueberries are packed with anthocyanins—pigments responsible for their deep color and antioxidant properties.

Astaxanthin (AST) is another powerful antioxidant that has been studied for its effect on IOP. One study investigated the cytoprotective effect of AST on RGC degeneration using an NTG mouse model. The results revealed that the antioxidative stress effects of AST inhibit RGC degeneration in the retina and may be useful in the treatment of NTG.¹³

A recent meta-analysis was conducted to clarify the relationship between vitamin intake and glaucoma risk.¹⁴ The study performed 5 meta-analyses of existing studies to summarize the evidence on the association between vitamin intake and glaucoma risk. The initial search identified 689 studies, 8 of which (262,189 patients) met the eligibility criteria for the meta-analysis. The results of this study demonstrated that high-dose intake of vitamins A and B, but not vitamins C, D, or E, was associated with a low prevalence of glaucoma.

Summary

The eyes are extensions of the brain and are nourished as much as any other part of the body. Nerve tissue is some of the most highly metabolically active tissue and needs an abundance of proper nutrients to function properly. Given the state of dietary options that are offered by the standard American diet, it is increasingly critical that we pay more attention to our diets as we age. Unfortunately, this is not a priority for the general public and many are overwhelmed with conflicting information about proper nutrition. Thus, it behooves the eye care practitioner to study the role of food and nutrients for proper healthy functioning, not just to resolve chronic disease but also to prevent these diseases from occurring at all.

References

1. Quigley HA, Broman AT. The number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol. 2006;90(3):262-267. doi:10.1136/bjo.2005.081224

2. Kass MA, Heuer DK, Higginbotham EJ, et al. The Ocular Hypertension Treatment Study: a randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma. Arch Ophthalmol. 2002;120(6): 701-830. doi:10.1001/archopht.120.6.701

3. Heijl A, Leske MC, Bengtsson B, et al; Early Manifest Glaucoma Trial Group. Reduction of intraocular pressure and glaucoma progression: results from the Early Manifest Glaucoma Trial. Arch Ophthalmol. 2002;120(10):1268-1279. doi:10.1001/archopht.120.10.1268

4. The AGIS Investigators. The Advanced Glaucoma Intervention Study (AGIS): 7. The relationship between control of intraocular pressure and visual field deterioration. Am J Ophthalmol. 2000;130(4):429-440. doi:10.1016/s0002-9394(00)00538-9

5. Vass C, Hirn C, Sycha T, Findl O, Bauer P, Schmetterer L. Medical interventions for primary open angle glaucoma and ocular hypertension. Cochrane Database Syst Rev. 2007;2007(4):CD003167. doi:10.1002/14651858.CD003167.pub3

6. Heijl A, Leske MC, Bengtsson B, et al; Early Manifest Glaucoma Trial Group. Reduction of intraocular pressure and glaucoma progression: results from the Early Manifest Glaucoma Trial. Arch Ophthalmol. 2002;120(10):1268-1279. doi:10.1001/archopht.120.10.1268

7. Garway-Heath DF, Crabb DP, Bunce C, et al. Latanoprost for open-angle glaucoma (UKGTS): a randomised, multicentre, placebo-controlled trial. Lancet. 2015;385(9975):1295-1304. doi:10.1016/S0140-6736(14)62111-5

8. Steigerwalt RD, Gianni B, Paolo M, Bombardelli E, Burki C, Schönlau F. Effects of Mirtogenol on ocular blood flow and intraocular hypertension in asymptomatic subjects. Mol Vis. 2008;14:1288-1292.

9. Gizzi C, Torino-Rodriguez P, Belcaro G, Hu S, Hosoi M, Feragalli B. Mirtogenol supplementation in association with dorzolamide-timolol or latanoprost improves the retinal microcirculation in asymptomatic patients with increased ocular pressure. Eur Rev Med Pharmacol Sci. 2017;21(20):4720-4725.

10. Shanmugham, V, Subban R. Capsanthin from capsicum annum fruits exerts anti-glaucoma, antioxidant, anti-inflammatory activity, and corneal pro-inflammatory cytokine gene expression in a benzalkonium chloride-induced rat dry eye model. J Food Biochem. 2022;46(10):e14352. doi:10.1111/jfbc.14352

11. Tribble JR, Otmani A, Sun S, et al. Nicotinamide provides neuroprotection in glaucoma by protecting against mitochondrial and metabolic dysfunction. Redox Biol. 2021;43:101988. doi:10.1016/j.redox.2021.101988

12. Karpilova M.A., Poluyanova A.D. [Antioxidant nutraceuticals for glaucoma.] Vestn Oftalmol. 2020;136(4. Vyp. 2):317-323. doi:10.17116/oftalma2020136042317

13. Kikuchi K, Dong Z, Shinmei Y, et al. Cytoprotective effect of astaxanthin in a model of normal intraocular pressure glaucoma. J Ophthalmol. 2020;2020:9539681. doi:10.1155/2020/9539681

14. Han FF, Fu XX. Vitamin intake and glaucoma risk: a systematic review and meta-analysis. J Fr Ophtalmol. 2022;45(5):519-528. doi:10.1016/j.jfo.2021.10.010.