eye with green iris

Common Ocular Conditions in Clinical Practice

by Chris D. Meletis, ND, and Kimberly Wilkes

The eyes are often called the “window into one’s soul,” and with good reason. The eyes are the only part of the body where a doctor – using an ophthalmoscope and looking through the pupil – can non-invasively observe blood vessels and nerves. This is an amazing way to glean health status or trends, because the eyes are also windows into overall health. Damage that occurs in the eyes can indicate damage happening in the brain. Likewise, age-related macular degeneration can signal concurrent imbalances in thyroid hormones in some people.

This article will review many of the most common eye disorders, their risk factors, and the connection between ocular health and the health of other areas of the body. We will also discuss the research behind both well-known and lesser utilized but highly effective dietary supplements as well as lifestyle and dietary support for vision.

Age-Related Macular Degeneration

In individuals older than 50 years, age-related macular degeneration (AMD) is the most common reason for the occurrence of irreversible vision loss, particularly in developed countries.1 As the average age of the population rises, the number of individuals with AMD is expected to triple in the next three to four decades from 20 to 25 million to 60 to 75 million people globally.2

Macular degeneration occurs when the macula, the part of the eye involved in central vision and seeing fine details, is damaged. Most macular degeneration is age related. There are two types of age-related macular degeneration: nonexudative (dry) AMD and neovascular (wet) AMD. Dry AMD is the early stage of AMD. Eighty-five to 90% of all cases are the dry form.3

The presence of fatty deposits called drusen in the macula are a hallmark of dry AMD, which is associated with little to no vision loss, but increases the risk of developing advanced AMD. Wet AMD is the advanced form of the disease and accounts for only 10 to 15% of cases but is responsible for 90% of AMD-related blindness.

AMD progresses to the wet form when blood vessels begin to grow in an abnormal manner at the back of the eye (what’s known as angiogenesis). Blood or fluid from these vessels escapes into the macula. Scars develop that harm central vision and may lead to permanent blind spots.

Beyond aging itself, a number of risk factors exist for AMD, including cigarette smoking, genetics,1 and exposure to light, especially short wavelength light, including ultraviolet and blue light.4-6 Exposure to blue light is associated with abnormal synthesis of factors that trigger angiogenesis and cause the development or progression of AMD. The blue light spectrum in natural sunlight is believed to be the most important cause of ocular damage.

Due to the possibility that blue light exposure may play a role in the development of AMD, blue light-filtering intraocular lenses (IOLs) are being used as an alternative to traditional IOLs that only filter UV sunlight.7

Beyond sun exposure, modern humans encounter many other sources of blue light including fluorescent and LED lighting, flat-screen televisions, display screens of computers, electronic notebooks, smartphones, and other digital devices. Although these devices emit considerably less blue light than the sun, people spend a lot of time in front of these gadgets, often with their eyes close to the screens.

Another risk factor for AMD is high levels of homocysteine, an amino acid associated with an increased risk of cardiovascular disease.8,9 Studies have demonstrated a direct correlation between high homocysteine blood levels and an increased risk of AMD.8,9 In one study, homocysteine concentrations were 27.9% higher in individuals with wet AMD compared with the dry AMD group, and 21.9% higher compared with controls.10 Supplementation with folate, vitamins B6 and B12, and betaine are known to lower homocysteine concentrations, indicating homocysteine may be a modifiable risk factor for AMD.11,12 Furthermore, a randomized trial of women at increased risk of cardiovascular disease found that daily supplementation with folic acid, pyridoxine (vitamin B6), and vitamin B12 lowered the risk of AMD.13

Epigenetics are also involved in AMD. Epigenetics refer to modification of gene expression rather than changes in the genetic code itself. Epigenetics serve as a switch that turn genes on and off. Many environmental factors such as diet or exposure to toxins trigger these epigenetic changes in gene expression. One way in which gene expression is altered is through micro-RNAs (miRNAs). miRNAs are thought to be involved in the development of the retina and abnormal miRNA expression correlates with the development of AMD.14 Resveratrol inhibits neovascularization in the retina during rodent experiments and its beneficial ocular effects in animals and humans may be due to its ability to impact the expression of miRNAs.15 A study in rats indicated that resveratrol may be able to protect the retina against ischemia in part through a mechanism that involves its effects on miRNAs.16

Another factor related to an increased risk of AMD is eating a high-glycemic diet. Mice that consumed a high-glycemic diet developed many features of AMD, including retinal pigmented epithelial cell hypopigmentation and atrophy, lipofuscin accumulation, and photoreceptor degeneration.17 These abnormalities were not observed in mice that consumed a lower-glycemic diet. Interestingly, switching from the high-glycemic to the low-glycemic diet late in life halted or reversed these AMD features. Low-glycemic diets limited the accumulation of advanced glycation end products (AGEs), proteins or lipids that become glycated due to their exposure to sugars. Low-glycemic diets also were associated with reduced accumulation of long-chain polyunsaturated lipids and their peroxidation end-products and an increased amount of carnitine in the retina. The mechanism by which the diet affected the retina was thought to involve the microbiota. In mice consuming a low-glycemic diet, the microbiota produced a number of metabolites, especially serotonin, which inhibited the development of AMD features.17 Microbiota in the Clostridiales order were associated with AMD and the high-glycemic diet, whereas the low-glycemic diet correlated with a prevalence of Bacteroidales organisms, which were protective against AMD features. In a human study of 1,952 participants 49 years or older followed for 10 years, consumption of food with a higher mean dietary glycemic index correlated with an increased risk of early AMD.18 Conversely, individuals who ate low-glycemic breads and cereals such as oatmeal had a lower risk of incident early AMD.

Another connection exists between AMD and thyroid hormones. Human retinal pigment epithelial cells express thyroid hormone receptors, an effect which may lead to thyroid hormones triggering damaging effects including depletion of hyaluronic acid.19 In a study of 5,573 people 55 years old or older, even among subjects whose free thyroxine (FT4) levels were normal, individuals who had the highest FT4 levels had a 1.34-fold greater risk of developing AMD, compared to those whose FT4 concentrations hovered in the middle range.20 Furthermore, higher FT4 concentrations were associated with an increased risk of retinal pigment alterations. This led the researchers to conclude that thyroid hormone is involved in more than just promoting the progression of AMD and may actually be involved in its development.

In addition to addressing all of the aforementioned risk factors for AMD, supplementation with the carotenoids lutein and zeaxanthin provide effective support. In some studies, lutein has improved macular pigment optical density and visual sensitivities in patients with early AMD.21 A combination of nutrients used in the Age-Related Eye Disease Study 2 (vitamin C, vitamin E, zinc, copper, and lutein) along with 10 mg meso-zeaxanthin given to patients with non-advanced AMD led to significant increases in macular pigment and improvements in measures of visual function.22 Lutein and zeaxanthin have been shown to reduce the progression from early AMD to the late form of the disease.21 Dietary intake of lutein and zeaxanthin may result in a 26% reduced risk for late AMD.23

Cataracts

A cataract causes the normally clear lens of the eye to become cloudy or opaque. In the United States, over half of those aged 65 and over have cataracts.24 There are three types of age-related cataracts: nuclear cataracts that affect the center of the eye lens, cortical cataracts that impact the edges of the lens, and posterior subcapsular cataracts, which affect the rear of the lens.

Risk factors vary depending on the type of cataract. Aging, higher hemoglobin A(1c) – a marker of blood sugar control over time – and history of diabetes mellitus are independent risk factors for cortical-only lens opacities.24 Aging, smoking cigarettes, and myopia (nearsightedness) independently increase the risk of nuclear-only cataracts.24 Higher systolic blood pressure and history of diabetes are both independent risk factors for posterior subcapsular cataracts.24 Aging, myopia, diabetes, higher systolic blood pressure, female gender, and large drusen independently raise the risk for mixed cataracts.24

Diabetes is an important risk factor for all types of age-related cataracts. High blood sugar is thought to increase the risk of cataracts through direct glycation of lens proteins.24 Furthermore, sugar alcohols synthesized through the aldose reductase pathway are directly toxic to the lens of the eye.24 Individuals with diabetes mellitus may also have high levels of calcium, impacting the lens crystallins and leading to opacification of the lens.25 Better diabetes control may therefore inhibit the formation of cataracts.

Myopia is another common risk factor. The role that myopia may play in nuclear cataracts may involve a longer vitreous cavity in this group of subjects resulting in reduced delivery of nutrients to the posterior lens and consequently impaired oxidative defense mechanisms leading to free radical damage.25,26

N-acetylcarnosine lubricant eye drops may play a role in improving visual function in people with cataracts. In older subjects with cataracts treated with 1% N-acetylcarnosine lubricant eye drops, visual acuity and glare sensitivity markedly improved compared with controls, who did not experience any improvement in visual function.27 There is indication that the mechanism of action of N-acetylcarnosine may involve reducing the rate of telomere shortening in lens cells exposed to oxidative stress in the absence of sufficient antioxidant protection.27 Telomeres are protective caps at the end of chromosomes. As telomeres are worn down with aging and other factors, this leaves the chromosomes vulnerable to damage.
As with macular degeneration, dietary intake of lutein and zeaxanthin correlated with a lower risk of nuclear or posterior subcapsular cataracts in a dose-response manner.28

Glaucoma

Glaucoma is a neurodegenerative disorder that damages the optic nerve and leads to impaired vision and blindness. Globally, 64.3 million people suffer from the disease and that number is expected to rise to 111.8 million in 2040.29 Open-angle glaucoma is characterized by increased intraocular pressure. Glaucoma-related degeneration occurs due to direct damage to the retinal ganglion cells caused by high intraocular pressure, ischemia, and aging. Recent evidence also suggests that glaucoma may be a disease that originates in the central nervous system (CNS) and moves downstream to the optic nerve and retinal ganglion cells.30 It is known that injury to the visual cortex and/or optic nerve, which then leads to damage to the retina, may be involved in the development of glaucoma.30,31 All of these factors inhibit oxygen supply and impair retinal function.30,31

High blood pressure is a risk factor for glaucoma, as are genetics, aging, and ethnicity (African Americans and Mexican Americans are at greater risk).32 Recently, researchers have proposed that glaucoma may be diabetes type 4 (the brain diabetes theory).33,34

According to this theory, glaucoma is a result of brain insulin resistance or central insulin signaling impairment, triggering the development of transsynaptic neurodegeneration. This theory indicates that therapeutic options for primary open angle glaucoma/normal pressure glaucoma should potentially target the brain as well as the eye.35

Oral and topical forskolin in the form of eye drops, alone or with other dietary supplements, has been shown to improve glaucoma symptoms.36 Coleus forskohlii is an aromatic herb found in India from the Himalayas to the southern part of the country. Forskolin is derived from the roots of this plant. In one study, patients with primary open angle glaucoma who were taking intraocular pressure-lowering drugs also consumed an oral supplement containing forskolin, homotaurine, carnosine, folic acid, vitamins B1, B2, and B6, and magnesium for a year.37 Patients in the forskolin supplement group experienced a further decrease in intraocular pressure and an improvement in Pattern Electroretinogram (PERG) amplitude – an electrical retinal response caused by stimuli in the visual field. Light sensitivity in the fovea, a small depression in the retina of the eye where visual acuity is the greatest, also improved. The improvements in PERG and foveal sensitivity suggested that the supplement produced a short-term neuroactive benefit.

In another study, an oral combination of forskolin and rutin reduced the rise in intraocular pressure that occurs after laser iridotomy, a procedure used in the treatment and prevention of closed angle glaucoma.38 Italian researchers also investigated the oral combination of forskolin and rutin in 52 patients with primary open angle glaucoma who were taking anti-glaucoma drugs and 45 controls.39 All patients in the forskolin-rutin intervention group, independent of the combination of medications they were treated with, experienced an additional 10% decline in intraocular pressure, beginning one week after supplementation began and continued for the 30-day study. The improvement was more pronounced in patients with higher intraocular pressure (≥21 mmHg) compared with subjects with low (<21) intraocular pressure. Intraocular pressure in the control group remained stable throughout the study.

The Connection Between Eye Diseases and Cognitive Function

Alzheimer’s disease and mild cognitive impairment are associated with a number of ocular problems.40 The manifestations of Alzheimer’s impact not only the brain, but also the retina, which is an extension of the brain. The retinas of Alzheimer’s patients exhibit a number of abnormalities such as retinal ganglion cell degeneration, reduction of blood flow, and vascular alterations.41

There are many commonalities between the brain and the retina. Like the brain, the retina contains neurons, astroglia, microglia, and a blood barrier.41 Axons of the optic nerve directly join the retina and the brain.42 Amyloid β-protein (Aβ) deposits are known to accumulate in the brains of patients with Alzheimer’s and are a hallmark of the disease. Evidence indicates that retinal ganglion cells (RGCs) synthesize amyloid precursor protein42 and in Alzheimer’s patients, Aβ deposits accumulate in the retina.40

The connection between cognitive and ocular health is further supported by the fact that higher levels of carotenoids such as lutein – known to reduce the risk of AMD and cataracts – also lower the risk of dementia and Alzheimer’s.43,44 Furthermore, lutein supplementation in older women enhanced cognitive function.44

Other Non-Ocular Diseases Connected to Eye Health

In addition to Alzheimer’s, other conditions are related to poor eye health. Because the retina and optic nerve are components of the central nervous system, their impairment may be indicative of not only eye diseases like glaucoma but also neurodegenerative disorders such as Parkinson’s.30 Furthermore, open-
angle glaucoma is associated with an increased risk of stroke in people who also have hypertension and/or diabetes.45 Additionally, depression and anxiety are common in older individuals with poor vision. One study found that the incidence of depression and anxiety in older people with ocular conditions is double that of older individuals in general.46 Even dry eye disease is associated with a high prevalence of depression.47 Therefore, in elderly patients with vision impairment, it is prudent to monitor for depression and anxiety in addition to directly treating ocular health.

Mitochondrial Involvement

Proper functioning of the mitochondria – the powerhouses of the cell responsible for manufacturing the energy molecule ATP – is crucial for eye health. This is not surprising given that within the brain, the visual system has some of the highest need for energy.48

Mitochondrial dysfunction plays a key role in many eye diseases. For example, mitochondria are thought to have a causal role in the development of glaucoma.49 Mitochondrial function is associated with oxidative metabolism and reactive oxygen species (ROS) production.49 Excessive ROS synthesis leads to the death of retinal ganglion cells and ultimately the loss of vision.49

In AMD, mitochondria in human retinal pigment epithelium cells are damaged, fragmented, and disrupted.50 As the age of the subjects from whom the retinal cells were derived increased, there was a significant decline in the number and area of mitochondria, as well as other mitochondrial abnormalities.50 Although these alterations were found in the mitochondria of retinal cells from both AMD and control subjects, these abnormalities were more pronounced in AMD compared with normal aging.50 Other researchers have observed that AMD severity correlates with a greater amount of mitochondrial DNA lesions and fragmentations in retinal pigment epithelium cells.51

Excessive reactive oxygen species (free radical) generation caused by mitochondrial dysfunction is also known to be involved in cataracts. Lipid peroxidation in the eye, the means by which lipids in the body undergo oxidation after exposure to reactive oxygen species, is one of the mechanisms involved in the development of cataracts.52 As one of the primary sources of reactive oxygen species, mitochondria therefore likely play a role in the lipid peroxidation of the eye lens.

Mitochondrial dysfunction occurs in diabetic retinopathy as well. In rats, dysfunction in mitochondrial energy production in the retina occurs as early as two months before development of diabetic hyperglycemia and retinopathy.53 Additionally, metabolic abnormalities caused by high glucose lead to retinal cell loss associated with diabetic retinopathy.54

Due to the important role of the mitochondria in eye health and the ocular damage that occurs after excessive reactive oxygen species production, supporting mitochondria with effective antioxidant nutrients is advised. A number of studies have demonstrated that antioxidants such as vitamins C and E, coenzyme Q10 (CoQ10), omega-3 fatty acids and other substances such as green tea and gingko biloba may support normal intraocular pressure and protect retinal neurons against oxidative stress in primary open-angle glaucoma.55

Coenzyme Q10 also has been found to protect the mitochondria in AMD.56 It is a particularly important nutrient for eye health in the elderly since CoQ10 concentrations in the retina decline by approximately 40% during aging.57

Melatonin, by virtue of its ability to act as an antioxidant and mitochondrial protector as well as other mechanisms, can support the health of individuals with a number of eye diseases including cataracts, glaucoma, AMD, and diabetic retinopathy.58.59

Modern Threats to Vision Health

The large amount of time individuals spend in front of their computer results in a new type of eye strain unique to modern man. Computer use results in eye fatigue, which can impair visual function. After the benefits of bilberry were publicized in a 2015 study, Dr. Meletis began recommending this botanical to his patients who spend a lot of time staring at a computer screen. In the study, a prospective, randomized, double-blind, placebo-controlled trial, 88 office workers aged 20 to 40 years who were frequent computer users were randomized to receive either 480 mg/day of bilberry or a placebo for eight weeks.60 Eye dryness and various symptoms of eye fatigue were determined using a questionnaire. The researchers observed improved measures of eye fatigue in the group receiving bilberry extract compared with controls. Compared with controls, Bilberry extract reduced subjective symptoms of eye fatigue, including ocular fatigue sensation caused by computer viewing, ocular pain, eye heaviness, uncomfortable sensation, and the sense that there was a foreign body in the eye.

Dry Eyes and Floaters

Dry eyes and floaters are two other common ocular problems. Dry eyes occur more often in people over 67 years, although the prevalence of this condition becomes less common after the age of 80.61 Dry eye leads to oxidative stress since tears soothe the eyes with molecules that protect against oxidative damage to the cornea.62 Consequently, supplementation with antioxidants may protect the ocular surface against oxidative damage. In one study, a combination of essential polyunsaturated omega-3 fatty acids combined with vitamins A, C, and E, tyrosine, cysteine, glutathione, zinc, copper, and manganese given to patients with dry eyes, lowered markers of inflammation and dry eye symptoms.63

In his clinical practice, Dr. Meletis has used oral hyaluronic acid (HA) in patients with dry eye and observed good results. HA protects the ocular surface epithelium due to its moisturizing effect.65 A number of studies in humans and animals have shown that eye drops containing HA reduce symptoms and signs of dry eye.64,65-67 In one study, eye drops containing crosslinked HA and CoQ10 given to 40 patients with mild to moderate dry eye disorder improved symptoms of dry eye more effectively than HA alone.68

HA can be effective for floaters as well. Floaters – those wiggly lines or dots that appear to float in front of your eyes – occur due to alterations in the vitreous body, the gel that fills much of the hollow sphere of the eye. Most of the vitreous gel is water, but 1% is comprised of solid elements including HA and collagen. HA plays an important role in regulating the gel consistency of vitreous through HA’s affinity for water molecules. However, with aging, HA levels decline.69

This age-related breakdown in HA molecules causes them to release their water supply and form liquefied gaps in the vitreous gel. At the same time, collagen filaments clump together to form larger fibrils, which leads to further destruction of the vitreous gel. The collagen fibrils are suspended in the liquid vitreous pockets, appearing to float. The breakdown of the vitreous gel can lead to posterior vitreous detachment, where the vitreous completely separates from the retina. Most cases of posterior vitreous detachment occur in people over the age of 70. While there are no studies that we are aware of demonstrating a beneficial effect of HA supplementation on floaters, Dr. Meletis has used HA in patients experiencing this condition and believes the important role that HA plays in maintaining the integrity of the vitreous gel warrants its use in people with floaters.

Another Beneficial Nutrient for Ocular Health

Curcumin is emerging as a nutrient with potential benefits for eye health. A number of rodent studies have indicated it has a variety of beneficial effects on ocular health including inhibiting the development and progression of retinitis pigmentosa,70 a group of inherited neurodegenerative diseases characterized by the reduction of photoreceptor cells, ultimately leading to blindness. Rodent studies also demonstrate a beneficial effect of curcumin in the management of diabetic retinopathy.71,72 In humans, a lecithinized curcumin delivery system assisted with the management of diabetic microangiopathy and retinopathy.73

Conclusion

Many threats to eye health exist, especially as we grow older. However, a number of dietary supplements including lutein, forskolin, melatonin, hyaluronic acid, bilberry, CoQ10, and N-acetylcarnosine eye drops can protect vision. Furthermore, lifestyle changes such as eating a low-glycemic diet can also strengthen the eyes.

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