It’s the little things that are noticeable when you begin to lose eyesight, Dame Judi Dench has revealed. The 007 star known for her role as M, James Bond’s steely no-nonsense boss, says that she’s missed reading the newspaper and doing the crossword since she was diagnosed with macular degeneration in 2012.
She doesn’t read her scripts anymore, but has friends read the lines to her to memorize, and she finds it most frustrating to not be able to see the face of a person she’s dining with in the evening. But the most “appalling” moment dealing with her condition—what she calls the “most traumatic moment of her life”—came in 2017 when she was forced to give up her driver’s license.
“I just know I’ll kill somebody if I get behind the wheel of a car now,” the 87-year-old British star told Radio News.
The thought that she may lose her vision entirely is obviously daunting. “I don’t want to say. I can see enough . . . You adapt to it. So I ignore it altogether,” Dench said.
She is one of 600,000 people in the UK “adapting” to macular degeneration, the leading cause of blindness in the developed world, according to the US Centers for Disease Control and Prevention. Globally it affects 196 million people, and glaucoma, another leading cause of blindness, affects another 60 million. By 2040, those numbers are expected to grow to 288 million and 110 million people worldwide, respectively.1
Both macular degeneration and glaucoma are progressive neurodegenerative eye diseases that gradually erode vision, although they operate in very different ways and affect different regions of the eye. Doctors describe them both as age-related and say that, although the processes may be slowed, once the eye nerves are injured, the damage to the eyes and to the patient’s vision is irreversible.
While mainstream technologies and drugs are struggling to address the symptoms of eye disease, however, new light therapies in trials in Canada, Europe and the US in recent years are addressing eye diseases at their root cause of oxidative damage and inflammation, and the treatments are not just slowing an inevitable progression but halting the disease at the cellular level and improving eye function.
In macular degeneration, which is believed to have a hereditary component (Dench’s mother had the condition as well), there is no conventional cure. Doctors inject drugs directly into the eye (once a month for at least three years) to stop tiny blood vessels from growing beneath the eye. It’s a painful procedure, as one might imagine, and not without risks, including injury or infection to the eye.
Sometimes lasers are used to seal up leaks in the blood vessels beneath the macula (a part of the retina) in the wet form of macular degeneration or to burn away some blood vessels altogether if they are disrupting vision.
In laser therapy for dry macular degeneration, doctors direct a tiny laser beam to destroy drusen (small fatty deposits) sitting beneath the eye, but as a Cochrane review of this treatment found, while it can help to eliminate drusen, it won’t halt vision loss.2
In glaucoma, the optic nerve becomes damaged, and if left untreated, this can lead to vision loss. Often the damage happens silently without noticeable symptoms, which is one reason to have regular eye exams to detect high intraocular pressure (IOP) early for treatment.
For decades, glaucoma has been treated by lowering the IOP to prevent the condition from worsening—even though the condition is also known to occur in the absence of high IOP, and high IOP can exist without glaucoma as well.
Still, the mainstay of treatment has been prescription eyedrops, including prostaglandins and Rho kinase inhibitor, which increase aqueous fluid drainage from the eye; beta-blockers and carbonic anhydrase inhibitors, which slow the production of fluid in the eye to reduce eye pressure; or combinations of these drugs.
All these pharmaceuticals have side-effects, from red and itchy or burning eyes, changes in eye color and blurred vision to fatigue, loss of libido, depression and heart rhythm or blood pressure complications. With long-term use, they’re known to be toxic to the surface of the eye, too, leading to dry eye and other conditions.3
The concept of a “gut–brain axis,” which describes how microbes in the gut impact the function of neurons and the brain to affect mood and mental health, is now well established. You may also have heard of the “gut-skin axis,” which describes how microbes in the gut impact the health of skin and can be related to various dermatological diseases.
Now, researchers are also talking about the “gut–retina” or “gut–eye axis” and researching how the health of the eye can be strongly influenced by the microbes in the intestine.1 Abnormalities in the ecosystem of microbes living in the gut are now associated with several eye diseases, such as age-related macular degeneration, and are all attributable to an alteration of the immune system and to underlying inflammation.
For example, the bacterium Lactobacillus paracasei KW3110 has gained experimental interest for its protective effects on blue-light-induced damage to human retina cells.
For clinical studies, 62 healthy Japanese volunteers aged 35 to 45 years who had experienced eye fatigue were randomized into two groups and given a placebo or L. paracasei KW3110-containing supplements for eight weeks. The probiotic supplement suppressed cell death, and the people who received the treatment reported reduced eye fatigue.2
A follow-up study looked at the effect of L. paracasei KW3110 intake over six months on age-related inflammation and altered gut microbiota in physiologically aged mice. The results showed the lactobacilli had anti-inflammatory effects highlighted by a significant reduction of inflammatory molecules called cytokines and chemokines (IL-17, KV and IL-13) in treated mice compared to controls.3 Another experiment demonstrated the ability of L. paracasei to suppress inflammation in the photoreceptor cells of mice with light-induced retinopathy. The authors concluded that more research is needed, but L. paracasei may have a preventative effect against degenerative retinal diseases.4
An alternative that has recently edged its way into mainstream medical practice is laser therapy, which, in various forms, has been used to reduce eye pressure for 25 years. Nevertheless, many doctors have been more comfortable with a first-line drug approach.
Light therapy applies laser energy to a mesh of tissue in the eye called the trabecular meshwork, where aqueous fluid naturally drains. The laser ignites a chemical and biological change in the tissue that triggers drainage of fluid through the meshwork and out of the eye, lowering the IOP.
“I explain it to patients by saying we provide a light therapy to the eye,” says ophthalmologist Savak Teymoorian with the Harvard Eye Associates. “It is just like getting a tan in your eye; your body absorbs the light energy, and as a reaction, your body cleans the natural drainage system of the eye first. Your body does the work, but you just need a signal first.”
Argon laser trabeculoplasty (ALT) was the first laser procedure to be used in glaucoma. It employs a heat laser, which could cause scarring. ALT has mostly been replaced with a gentler procedure called selective laser trabeculoplasty (SLT), which is sometimes called “cold” laser therapy because it produces less heat.
The patient receives anesthetic drops in each eye, then rests their chin on a support so they are looking directly into the device, which the glaucoma specialist positions directly on the front surface of the eye.
This fires the laser into the eyes, blasting the trabecular meshwork of each eye, one at a time. The patient only hears a clicking sound and sees a yellow-green flash of light. The procedure is done in usually under five minutes per eye—less than a quarter of an hour in all.4
SLT is painless to undergo, causes less scarring than ALT and is successful in about 78 percent of cases at one-year follow-up, according to British researchers conducting the Laser in Glaucoma and Ocular Hypertension (LiGHT) trial, a comprehensive randomized control trial centered at Moorfields Eye Hospital in London.5
The researchers randomly assigned glaucoma patients to one of two groups—one that received initial treatment of high IOP with laser therapy (using eyedrops later, if needed) and one treated with standard prescription eyedrops to lower IOP—and compared the effect of the different therapies on patients’ quality of life.
The study, published in The Lancet in 2019, reported that for the first three years of therapy, quality of life in both groups was similar. However, three-quarters of patients initially treated with laser did not need any eyedrops to lower their eye pressure for three years.
Patients who were initially treated with laser were also less likely to require surgery for cataracts (blurring of the eye lens), and none needed to undergo surgery for glaucoma in the first three years. Among those patients treated with eyedrops, surgery was required for 11 eyes (out of 622 eyes). What’s more, the laser approach was safer, with fewer side-effects than the eyedrops or surgery, and it was cheaper, too.
Three years after laser treatment, no patients had had glaucoma surgery, compared to 11 of 622 eyes in the eyedrop-treatment group, and they were also significantly less likely to need eyedrops or cataract surgery
Researchers from the University of British Columbia in Canada have found that men who regularly take erectile dysfunction (ED) pills including Viagra may be at increased risk of sudden vision loss and other visual disturbances.1
The researchers looked at insurance claim records of 213,033 men using pills for ED including 123,347 men taking Pfizer’s Viagra, 78,609 on Cialis, 6,604 taking Levitra and 4,473 on Spedra to see which men went on to develop eye disorders.
The study, published in April in JAMA Ophthalmology, found that men using any of these medications were 158 percent more likely to have a serious retinal detachment, which occurs when fluid builds up behind the back of the eye and causes the sudden appearance of spots and flashes of light in the field of vision.
Retinal detachment is a medical emergency that could lead to blindness if left untreated.
The men using prescriptions for impotence were 102 percent more likely to suffer from ischemic optic neuropathy—restricted blood flow to the optic nerve, which can lead to loss of central vision. And they were 44 percent more likely to develop a retinal vascular occlusion—a blood clot in the retina, which can lead to dark spots or “floaters” in the field of vision and loss of vision.
The researchers speculated that ED drugs could be causing a loss of blood flow to the eyes while shunting it to the genitals.
The insurance claim records were from 2006 to 2020 to see which ones went on to develop eye conditions. None of the men had suffered eye problems in the year before they became regular users of the medication.
The LiGHT trial triggered a paradigm shift in glaucoma treatment. For some doctors, old habits die hard, and many were still inclined to choose drugs over laser as the first treatment option, trying the light only if the drops didn’t work.
The UK National Institute for Health and Care Excellence (NICE) decided to push the lasers this year. Citing the LiGHT study results, NICE announced changes to its guidelines in January 2022, making SLT therapy the primary intervention for open-angle glaucoma (the most common type of glaucoma) over eye drops.6
“It’s unusual for a trial such as the LiGHT study to have such a profound impact, and fantastic that NICE have considered our results to be so robust that they have relied on them for a major shift in guidelines,” Ophthalmology Consultant and Chief Investigator Gus Gazzard from Moorfields Eye Hospital said.
Other practice guidelines, including those from the American Academy of Ophthalmology’s Preferred Practice Pattern and the European Glaucoma Society, also recently changed their guidelines as a result of the LiGHT study and now recommend SLT as a first-line therapy instead of drugs.
SLT lowers internal eye pressure by an average of 30 percent, according to the Glaucoma Research Foundation, and its effects can last from one to five years and in some cases even longer. A common side-effect is transient inflammation, although in 5 percent of cases, IOP can rise rather than drop.
“Rarely, the pressure in the eye rises to a very high pressure and does not come down,” according to the Moorfields Eye Hospital patient information resources. This is a “very unusual occurrence,” and glaucoma surgery is required in that case.4
Other complications can also occur, and some can be serious, including burns and iritis (swelling around the iris, the colored part of the eye around the pupil), but risks are generally less than from glaucoma drugs or surgery to drain the eye of aqueous fluid.7
Although SLT can be repeated, it’s not certain how often or effective this is. According to the Glaucoma Research Foundation, some doctors opt to treat only half of the eye’s mesh network on the first go, then treat the second half later if the effectiveness of the first intervention wanes (this is not considered a repeat treatment) to prolong the benefits of the therapy.
Just as SLT is becoming the frontline therapy for glaucoma, more refined laser therapies are being investigated. Direct selective laser therapy (DSLT) is an adaption of SLT, but without the lens that sits on the eye. It’s even simpler and quicker compared to standard SLT, and trials are underway in seven countries, including the US and in the UK at Moorfields Eye Hospital in London.8
Micropulse laser trabeculoplasty (MLT) or micropulse diode laser trabeculoplasty (MDLT) and intense pulsed light (IPL) are beginning to attract attention as even safer laser eye therapies with the same effectiveness as SLT or ALT.
MLT and IPL reduce the amount of potentially damaging heat energy delivered to eye tissues by pulsing the energy in small bursts, allowing cooling in between. Studies show the treatment has similar potential benefits to other laser therapies with fewer side-effects, and the hope is that it will further improve on SLT.9
A promising tool to treat eye disorders, as well as many more medical conditions, is low-level light therapy. Low-level light in the far-red to near-infrared range of the spectrum (~600-1000 nm), used therapeutically, is called photobiomodulation. As a therapy, it has gained worldwide attention in recent years for its promise to treat a wide range of diseases, including neurodegenerative eye diseases, by restoring function at the cellular level.
Red to near-infrared light is cold light without any potential for harm from heat. It’s believed that it works by hitting photoreceptive cells in the body that convert light energy to chemical energy, which is a catalyst for cell function, repair and healing. Unlike conventional high-energy laser light, near-infrared light does not have the destructive effects that can come from heating tissue, such as coagulating or vaporizing.
Low-level light therapy restores functions of damaged mitochondria by upregulating factors like cytochrome c oxidase. “Eyes and neurons rely on cytochrome c oxidase to generate energy for metabolic process,” according to a recent review paper on the subject.
“NIR [near-infrared] light can penetrate these tissues and assist recoveries of neurons in methanol intoxication, optic nerve trauma and neuropathy, retinal injuries and pigmentosa, and macular degeneration.”10
It turns out that photobiomodulation—which increases mitochondrial function, reduces oxidative damage and dampens inflammation—directly counters the processes that underlie age-related macular degeneration and other eye diseases, including glaucoma and dry eye disease.
A 2021 review looked at several recent studies that found low-level light therapy improved outcomes in patients with macular degeneration, including one study in which 348 eyes at various stages of macular degeneration were treated with blasts of 670-nm red light, resulting in measurably improved visual acuity and color vision.11
In the Toronto and Oak Ridge Photobiomodulation Study for Dry Age-Related Macular Degeneration (TORPA trial), visual acuity and contrast sensitivity improved immediately and up to 12 months after treatment in patients older than 50 with macular degeneration, with all 18 eyes tested showing improvement.12
A larger follow-up study expanded to 42 eyes and using multiple wavelengths of low-level light also found a significant improvement in visual acuity and contrast sensitivity immediately and three months after completion of the three-week treatment. Additionally, drusen volume decreased, and central drusen thickness was significantly reduced, with no pain or side-effects.13
Similarly, the 2019 pilot LIGHTSITE I study by Canadian, Swiss and American researchers evaluated light therapy in 46 eyes of people in the early stages of dry age-related macular degeneration, who received 670-nm red light in nine treatment installments. Visual acuity increased by up to four letters, then declined to baseline six months after treatment, suggesting some level of consistent therapy would be required to maintain the benefits.14
Further studies (LIGHTSITE II and LIGHTSITE III) were launched after these groundbreaking results. The LIGHTSITE II trial was carried out in the UK, Germany, France, Spain and Italy. As Ben Burton, an honorary professor at the University of East Anglia who led the study in the UK, reported to the EURETINA 2021 Virtual Congress, a total of 44 patients (53 eyes; 17 men, 27 women; mean age, 74.1 years) with dry age-related macular degeneration were enrolled.
The treated patients were given three rounds of photobiomodulation therapy from LumiThera Inc. weekly over three to four weeks. Each painless treatment lasted for four to five minutes per eye.
Nine months out, the treated patients had sustained improvements in visual acuity, gaining an average of 4 letters versus 0.5 letters in the sham group. “The patients had sustained BCVA improvement at 9 months . . . More than 33 percent of the light-treated eyes gained 5 letters at 9 months . . . PMD treatment also was associated with no significant drusen growth at 9 months in contrast to the sham group.” The researchers noted no safety concerns.15
LIGHTSITE III is an ongoing trial being conducted at multiple centers in the United States. “Early results from the LIGHTSITE III trial are indeed very encouraging,” said Diana Do, a professor of ophthalmology and member of the Retina Division at the Byers Eye Institute at Stanford University, which is one of the clinical sites for LIGHTSITE III.16
Up to a third of people are affected at some point by dry eye syndrome, which, just as the name says, leaves the eyes low on tear fluid, causing a gritty feeling and blurred or distorted vision and can lead to inflammation and damage to the eye surface.
Researchers in Korea decided to experiment with low-level light therapy (LLLT), which has been used successfully for wound healing, skin rejuvenation, pain and to treat inflammatory disorders including eye disorders, as a treatment for dry eye syndrome.
They split 38 people diagnosed with the condition into two groups, 20 assigned to receive low-level light therapy (LLLT) using 590-nm and then 830-nm wavelengths of light directed at their eyes, and 18 who received a placebo treatment. Neither the patients nor the investigators knew who was receiving the therapy or the sham.
Those who received the LLLT at a dose of about 60 J/cm2 per treatment session saw improvements in signs and symptoms of dry eye, the researchers from the Department of Ophthalmology, Dankook University Hospital concluded. Their study, published in March in Nature Scientific Reports, reported that LLLT can stimulate tear gland function.
“Such efficacy, in addition to the well-tolerated profile of LLLT,” the researchers concluded, “makes it a potentially useful treatment option for dry eye in clinical practice.”1
While low-level light therapies are making big but slow steps in the clinical trial world, there are still practical ways to employ the new technology at the grassroots level immediately, with preventative potential against eye disease.
A recent study found that looking at a deep red light for a few minutes every morning can help improve eyesight, especially if it’s starting to fail.
Researchers at the Institute of Ophthalmology at University College London tested light therapy on 20 volunteers, aged between 34 and 70, who used a 670-nm red light LED flashlight for three minutes every morning between 8 and 9 a.m.
They found that, on average, there was a major improvement in the participants’ color vision—improving color contrast by as much as 20 percent—hours after the light exposure, and for some, the effect lasted an entire week.
It helps support the retina, which ages faster than any other organ in the body and starts to lose its photoreceptor abilities by the time we reach 40.
But looking into a long wavelength (670 nanometer) red light for three minutes every day when we first wake up can slow down the aging process.
It’s an inexpensive way to improve our vision, the researchers say, and it can be achieved by using a simple 8mW/cm2 flashlight that transmits a long wavelength light. Flashlights and LED bulbs at that wavelength are available from online retailers like Amazon and eBay.
However, it’s important to do the exercise first thing in the morning; there was no sight improvement in those who did the sessions in the afternoon.17
While research into the role of microbiota in modulating eye health is rapidly growing, it’s likely to eventually overlap with light therapy, too. Photobiomics is an emerging field of research where light therapy has been applied directly to the abdomens of mice and humans to alter the intestinal microbiome in a way that is beneficial to health. The therapy is used along with nutrition to impact the gut microbiota.18
Nutrition plays an essential role in eye health, of course. In a study published in 2016, Harvard researchers analyzed the diets of more than 100,000 men and women in two long-term studies and found that those who ate the most leafy greens cut their risk of developing glaucoma by 20 to 30 percent.19
The National Eye Institute sponsored two large-scale studies—Age-Related Eye Disease Study (AREDS) and AREDS2—to investigate the effects of nutritional supplements on macular degeneration. Subjects were given the following supplements:
Researchers reported that the vitamins and minerals cut the five-year risk of macular degeneration progressing from intermediate-level disease to advanced stages by 25 percent and decreased the risk of vision loss by 19 percent. In the AREDS2 study, subjects were given 10 mg of lutein and 2 mg of zeaxanthin as antioxidants instead of 15 mg of beta carotene, but the results were the same.20
It’s also recently been shown that niacin (also known as vitamin B3) can affect eye health. In a study published in the journal Nutrients in 2018, researchers looked at the diets of 6,000 men and women over age 40 and calculated their niacin intake. Those with the highest niacin intake—24 mg a day—were 64 percent less at risk of developing glaucoma compared to those who had a lower average daily niacin intake of 21 mg.21
Diet can directly influence nutritional status, but one way it does this is by profoundly influencing the microbiota in the intestines.22 Shining a light on abdomens to vitalize bacteria that heal the gut and influence health, including eye health, is on the horizon.23
Main Article
|
References |
|
|
1 |
Ophthalmology, 2014; 121(11): 2081–90 |
|
2 |
Cochrane Database Syst Rev, 2009; (3): CD006537 |
|
3 |
Graefes Arch Clin Exp Ophthalmol, 2021; 259(5): 1243–51 |
|
4 |
Manchester Royal Eye Hospital, “Information for Patients: Selective Laser Trabeculoplasty.” Sep, 2021 |
|
5 |
Br J Ophthalmol, 2018; 102(5): 593–8 |
|
6 |
UK National Institute for Health and Care Excellence, “Glaucoma: Diagnosis and Management.” Jan 2022 |
|
7 |
Clin Ophthalmol, 2016; 10: 137–43 |
|
8 |
Br J Ophthalmol, 2021; bjophthalmol-2021-319379 |
|
9 |
Vision (Basel), 2022; 6(1): 8 |
|
10 |
Int J Med Sci, 2021; 18(1): 109–19 |
|
11 |
Clin Ophthalmol, 2021; 15: 3709–20 |
|
12 |
Investig Ophthalmol Vis Sci, 2012; 53(14): 2049 |
|
13 |
Acta Ophthalmol, 2017; 95(4): e270–7 |
|
14 |
Retina, 2020; 40(8): 1471–82 |
|
15 |
Modern Retina, “LIGHTSITE II: Photobiomodulation a novel therapy for dry AMD.” Sep 12, 2021 |
|
16 |
LumiThera, “LumiThera Announces US LIGHTSITE III Clinical Trial Meets Primary Efficacy Endpoint in Improving Vision in Dry Age-Related Macular Degeneration Subjects.” Mar 23, 2022 |
|
17 |
Sci Rep, 2021; 11: 22872 |
|
18 |
Photobiomodul Photomed Laser Surg, 2019; 37(11): 681–93 |
|
19 |
JAMA Ophthalmol, 2016; 134(3): 294–303 |
|
20 |
US National Eye Institute, “AREDS/AREDS2 Clinical Trials.” Nov 19, 2020 |
|
21 |
Nutrients, 2018; 10(4): 387 |
|
22 |
BMJ, 2018; 361: k2179 |
|
23 |
Chiropractic Economics, “Photobiomics: A look to the future of combined laser and nutrition therapy.” Oct 5, 2021 |
Microbes and eye health
|
References |
|
|
1 |
Front Microbiol, 2021; 12: 726792 |
|
2 |
Nutrients, 2018; 10(8): 1058 |
|
3 |
Aging, 2018; 10: 2723–40 |
|
4 |
Nutrients, 2018; 10(12): 1991 |
Viagra may lead to blindness
|
References |
|
|
1 |
JAMA Ophthalmol, 2022 Apr 7; e220663 |
Low-level light therapy for dry eyes
|
References |
|
|
1 |
Sci Rep, 2022; 12(1): 3575 |
What do you think? Start a conversation over on the... WDDTY Community
