Autoimmune eye disease

The Ocular Manifestations of Autoimmune Disorder.

When people have an autoimmune disease, their cells can damage them, including those around their eyes, causing dry eye syndrome.

You have blurred vision, eye pain, light sensitivity, blepharitis, clogged oil glands, etc. Consult your ophthalmologist for a complete eye exam to improve vision.

Sometimes, your eyes can get damaged if eye surgeons detect your autoimmune disease. Perhaps the autoimmune disorder is affecting your eye problems.

Maybe your eyesight has deteriorated, and that may be the cause.

Understanding autoimmune conditions, as well as eye health, can assist in understanding how to care for your eye.

Many autoimmune disorders can make you go blind or otherwise affect your vision.

Certain autoimmune disorders specifically target the eyes, including ocular cicatricial pemphigoid, Mooren’s corneal ulcer, and some forms of uveitis.

Treatment will require systemic (e.g., oral as opposed to local, topical, ocular) therapy; the components of the immune system reside not in the eye but rather are systemic. Therefore, regulation of those components will require systemic treatment. Such therapy will suppress the overly aggressive immune system, allowing the body to eventually re-regulate itself, with the result often being that after the patient has been kept on systemic medications to suppress the inappropriate immune response for a finite length of time (for example, one year), medication can then be tapered and stopped.

Will collaborate with a chemotherapist who will monitor and manage the patient’s systemic therapy. At the same time, the ophthalmologist monitors the progress of the ocular manifestation of the autoimmune attack (inflammation). In most instances, this collaboration between ophthalmologists and chemotherapists works very well. Our experience in helping ophthalmologists establish such partnerships and effectively treat patients with autoimmune diseases have been successful.

How inflammation affects the eyes

An overactive immune system attacks various body parts, including organs and joints, and causes inflammation. The types of arthritis that can cause vision problems are usually associated with an autoimmune disease. They include rheumatoid arthritis (RA); psoriatic arthritis, which can accompany the skin condition psoriasis; and reactive arthritis, an uncommon and often temporary condition triggered by an infection.

In addition to Irritable Bowel Disease, lupus, and MS, other autoimmune diseases that may lead to uveitis are ankylosing spondylitis, sarcoidosis, and Behcet’s disease.

IBD, which includes ulcerative colitis and the more severe but less common Crohn’s disease, affects the gastrointestinal tract; lupus can affect multiple organs as well as joints; MS can damage the nerve fibers in the brain, spine, and eyes; ankylosing spondylitis attacks the spine; Behcet’s disease inflames the blood vessels, and sarcoidosis inflames the lungs and can affect other organs as well as joints.

In an older age group, shingles and sarcoidosis become important causes of uveitis,

While autoimmune diseases can run in families, not everyone whose parents had one will get one themselves. Triggers for these diseases can be a wide variety of environmental factors, including an infection you may have picked up at some point in your life, your socioeconomic status, and whether you smoke cigarettes or drink alcohol. These environmental factors can even stretch far back into your childhood, to your birth weight or whether you were breastfed as an infant.

Although there is no direct connection between uveitis and autoimmune diseases that attack the thyroid (such as Hashimoto’s thyroiditis and Graves’ disease), patients with any autoimmune disease are more prone to getting other autoimmune diseases. Some of which may affect the eyes.

What are autoimmune diseases?

Your immune system protects you from disease and infection by attacking germs into your body, such as viruses and bacteria. Your immune system can tell that the germs aren’t part of you, destroying them.

They are autoimmune because your immune system attacks your normal tissues by mistake instead of invading germs and viruses.

All these diseases have in common is inflammation, leading to pain, swelling, and other trouble. This inflammation can show up almost anywhere in your body. Sometimes that’s far away from a disease’s primary target.

If you have an autoimmune disease, your immune system attacks the normal cells of your organs and tissues by mistake – called an autoimmune attack.

There are more than 80 types of autoimmune disorders. They can affect almost any part of your body. For example, alopecia is an autoimmune disorder of the skin that causes hair loss. Autoimmune hepatitis affects the liver. In type 1 diabetes, the immune system attacks the pancreas. And in rheumatoid arthritis, the immune system can attack many parts of the body, including the joints, lungs, and eyes.

Several autoimmune disorders exist where the eye or various eye parts are attacked by the white blood cells. Often the autoimmune disorder is systemic, i.e., a variety of organs throughout the body system are being attacked.

Examples of such autoimmune disorders include:

• rheumatoid arthritis,
• systemic lupus erythematosus,
• polyarteritis nodosa, relapsing polychondritis,
• Granulomatosis with Polyangiitis (formerly called Wegener’s), scleroderma,
• Behcet’s disease, Reactive Arthritis (formerly called Reiter’s syndrome),
• Inflammatory bowel disease (ulcerative colitis and Crohn’s disease)
• Ankylosing spondylitis.

What causes autoimmune diseases?

No one is sure why autoimmune diseases happen. But you can’t catch them from other people.

Autoimmune disorders tend to run in families, which means that specific genes may make some people more likely to develop a problem.

Viruses, certain chemicals, and other things in the environment may trigger an autoimmune disease if you already have its genes.

A rheumatologist can have a vital role if a systemic disease is suspected associated with eye inflammation.

Who is at risk for autoimmune diseases?

Millions of Americans of all ages have autoimmune disorders.

Women develop many types of autoimmune diseases much more often than men. And if you have one autoimmune disease, you are more likely to get another.

What are the symptoms of autoimmune diseases?

The symptoms of an autoimmune disease depend on the part of your body that’s affected.

Many autoimmune diseases cause redness, swelling, heat, and pain, which are the signs and symptoms of inflammation. But other illnesses can cause the same symptoms.

The signs of autoimmune diseases can come and go.

During an autoimmune attack, your condition may get severe for a while. Later on, you may have a remission, which means that your condition get better or disappear for a while.

Blurred vision often accompanies autoimmune eye disorder.

How are autoimmune diseases diagnosed?

Your eye doctor often have a hard time diagnosing autoimmune disorders. There’s usually no specific test to show whether you have a particular autoimmune disease.

And the symptoms can be confusing. That’s because many autoimmune diseases have similar symptoms. And some symptoms, such as muscle aches, are common in many other illnesses. So it can take a long time and some visits to different types of doctors to get a diagnosis.

To help your eye doctor find out if an autoimmune disease is causing your symptoms:

• Learn about the health conditions in your family history. What health problems did your grandparents, aunts, uncles, and cousins have? Write down what you learn and share it with your doctor.
• Keep track of your symptoms, including how long they last and what makes them better or worse. Share your notes with your doctor.
• See a specialist who deals with the symptoms that bother you most. For example, see a dermatologist (skin doctor) if you have a rash.

What are the treatments for autoimmune diseases?

The treatment depends on the disease.

In most cases, the goal of treatment is to suppress (slow down) your immune system and ease swelling, redness, and pain from inflammation. Your doctor may give you corticosteroids or other medicines to help you feel better.

Helping ophthalmologists establish such collaborations and effectively treat patients with autoimmune diseases affecting the eye has been gratifyingly successful in almost every country around the globe. This represents a significant change from years ago when many patients still lost all use of one or both eyes from the ravages of improperly treated autoimmune disease affecting the eye. The hope for the future is for more selective treatment strategies for specific autoimmune diseases.

For some diseases, you may need treatment for the rest of your life.

Anti-inflammatories

Your doctor will likely prescribe anti-inflammatory medication to help restore blood flow. If your optometrist diagnoses you with retinal vasculitis and doesn’t have any known autoimmune disorder, talk to your eye doctor about that possibility.

Retinal vasculitis is associated with many autoimmune disorders and rarely presents on its own.

The goal is to allow your body to eventually re-regulate itself, with the result often being that after the patient has been kept on systemic medications to suppress the inappropriate immune response for a finite length of time (for example, one year), medication can then be tapered and stopped without recurrence of the autoimmune attack. Sometimes resumption of the episode does occur, in which case the patient must be re-treated.

Ophthalmologists, in general, are not accustomed to treating patients systemically and, in particular, are not trained to use immunosuppressive drugs to control autoimmune phenomena.

Antimalarials. Plaquenil can occasionally cause decreased vision. If you have an autoimmune disease, you are probably alert to changes throughout your body — but don’t forget to take care of your eyes with regular screenings and attention to vision changes by your eye doctor.

Immuno-suppressants.

A rheumatologist can prescribe these types of medications, also known as immunosuppressants, including methotrexate, prednisone, or adalimumab (Humira).

These medications suppress an overly aggressive immune system, effectively telling it to back off and stop attacking your body’s healthy tissue, including the tissue in your eyes.

Since the immune system exists in glands and other areas throughout the body, if you have an autoimmune disease affecting your eyes, you’ll need a systemic treatment such as a pill rather than eye drops, which would treat only the eyes.

Suppose the underlying disease is well controlled with immunosuppressant medications, according to Sen. In that case, this makes the odds better for preserving your vision as well.

Neuromyelitis Optica

Neuromyelitis optica (NMO) is a central nervous system disorder that primarily affects the eye nerves (optic neuritis) and the spinal cord (myelitis). NMO is also known as neuromyelitis optica spectrum disorder or Devic’s disease.

Spinal cord damage can include disturbances in sensations, loss of bladder and bowel control, uncontrollable hiccupping, and nausea.

In addition, muscle weakness may make breathing difficult and can cause life-threatening respiratory failure in people with neuromyelitis optica.

There are two forms of neuromyelitis optica, the relapsing form and the monophasic form. The relapsing form is most common. This form is characterized by recurrent episodes of optic neuritis and transverse myelitis. These episodes can be months or years apart, and there is usually partial recovery between episodes.

Uveitis

People with various atypical arthritis, autoimmune bowel diseases (IDB), lung diseases, and autoimmune diseases may occasionally suffer; it leads to an unusual but severe eye disorder called uveitis, leading to significant vision loss.

Uveitis often happens in people who have an autoimmune condition – where the immune system mistakenly attacks normal tissue. Autoimmune disorders known to cause uveitis include: ankylosing spondylitis – a disease where the spine and other areas of the body become inflamed reactive arthritis – a condition that causes inflammation in various areas of the body conditions that cause bowel inflammation – such as Crohn’s

National Institutes of Health Page last updated on 18 August 2020 Page last reviewed.

Sjogren’s Syndrome

Sjögren’s syndrome primarily demonstrates keratoconjunctivitis sicca. Symptoms have a similar symptomatic profile as keratoconjunctivitis, causing RAS.

Rheumatoid arthritis

About 25% of patients with rheumatoid arthritis will experience ocular inflammatory signs in their rheumatoid arthritis. The conditions include keratoconjunctivitis a.c, scleritis s. scleritis, episcleritis keratoconjunctivitis peripheral corneal ulcers, and a lesser-known condition such as a cornea

Keratoconjunctivitis sicca is the most common ocular manifestation of RA and is estimated to be 15 -25 percent common.

Symptoms tend to appear at the end of the day due to evaporation of tear-films.

Rheumatoid arthritis and lupus may cause eye inflammation and dry eye. In addition, hydroxychloroquine (Plaquenil), a medication commonly used to treat rheumatoid arthritis and lupus, can damage the eye and lead to retinal atrophy.

Systemic Lupus Erythematosus (SLE)

Eye inflammation is one of the many possible effects of lupus. Symptoms include blurred vision, headaches, sore eyes, dry eyes, and sensitivity to light.

Ocular disease is common in 20% of SLE sufferers. In particular, ocular diseases indicate a recent reactivation of a previously undiagnosed SLE remission.

External ocular manifestation is keratoconjunctivitis sicca conjunctivitis uveitis sclerites. SLE causes neuro-ophthalmic complications primarily from microinfarctions, hemorrhage, or vasculitis originating from multiple locations within and around the eyesight.

Lupus can harm the eyes in various ways, including inflaming the eye tissues themselves, damaging the nerves that control movement and vision and damaging the skin of the eyelids.

However, the most common eye issues experienced by people with lupus are changes to the blood vessels in the retina. When the immune system attacks the circulatory system, not enough blood reaches the retinal blood vessels. The eye tries to fix the problem but creates more blood vessels, which don’t have access to blood and only restrict your vision further.

However, the most common eye issues experienced by people with lupus are changes to the blood vessels in the retina – retinal vasculitis. When the immune system attacks the circulatory system, not enough blood reaches the retinal blood vessels. The eye tries to fix the problem but creates more blood vessels, which don’t have access to blood and only restrict your vision further. The primary method for dealing with retinal vasculitis is to treat lupus itself.

Lupus currently doesn’t have a cure but can manage its symptoms. Visit your ophthalmologist often.

Juvenile rheumatoid arthritis

Juvenile Rheumatoid Arthritis causes around 80 % of all children with uveitis. Although uveitis may arise at any age of juvenile RA, most are found in pauciarticular. The majority are symptomless or suffer from blurry vision. On inspection, patients can have decreased visual acuity, band keratopathy, synechia, cataracts, or increased optic pressure. Symptoms of RA in young adults can be diagnosed at any age by referrals to pediatricians. Visit your ophthalmologist often.

Graves’ Disease

In most people, exophthalmos occurs 50 percent. It has a strong association with smoking in patients who are either Hypothyroid / Hypothyroid. Computed tomography or imaging is recommended when signs of optic nerve compression are present, such as decreased visual ability, lower visual field relative efferent pupillary defects, and reduced color vision. Your ophthalmologist can help you manage your disease.

Graves’ Ophthalmopathy

Graves’ disease can cause thyroid eye disease (TED), which mainly affects the muscles and tissue directly outside of the eyeball and can lead to bulging and dry eyes,

And other autoimmune disorders can cause eye conditions with various symptoms, including corneal ulcers and scarring in one or both eyes. Visit your ophthalmologist often to preserve your vision.

Hashimotos Thyroiditis

Hashimoto’s thyroiditis, also known as chronic lymphocytic thyroiditis, is the most common cause of hypothyroidism in the United States. It is an autoimmune disorder involving chronic inflammation of the thyroid. This condition tends to run in families.

Hashimoto’s disease is an autoimmune disorder affecting the thyroid gland. The thyroid is a butterfly-shaped gland located at the base of the neck just below Adam’s apple. The thyroid produces hormones that help regulate many functions in the body.

Spondyloarthropathies

In seronegative spondylospondyloarthropathies, a common ocular rash occurs in ankylosing. The pain is a ciliary spasm resulting from anterior choroidal inflammation. The disorder appears in 25 percent of patients with ankylosing spondylitis, in up to 38 percent of patients suffering Reiter syndrome, in about 20 percent of psoriasis patients. Nine percent of patients have a form of unilateral ocular symptoms. As stated above, uveitis patients should consult with an ophthalmologist if possible.

Giant Cell Arteritis

Up to 60 % of those with giant cell arteritis present ocular symptoms, including severe pain and nausea, and pain in the face and neck.

Ocular involvement is joint when there is no systematic symptom or symptomatic signs. Patients may experience temporal vein tendering or a decrease in temporal vein pulse. The diagnosis was made by biopsy, erythroblast permeability, and elevated C-reactive protein. Biopsy results can last at least ten days following treatment with corticosteroid injection.

Multiple sclerosis (MS)

This autoimmune disorder targets the brain and nervous system. The immune system attacks the nerves, which try to repair themselves with scar tissue. However, the scar tissue interrupts the signals traveling through the central nervous system, causing numbness, muscle weakness, lack of body control, pain, and reduced cognitive function.

Ocular manifestations for MS have two types: afferent and erector disorder. Optic neuritis can be detected in 80 percent of MS patients. Symptomatic symptoms are present between 10 & 20 of these. Symptomatic visual field defect in MS sufferers is due to demyelinations in visual pathways. Bilateral internuclear ophthalmoplegia usually occurs from demyelinating disorders. Lesions often cause dysmetria, nystagmus, and cerebral nerve palsies to the brain stem and cerebellum lesions.

Multiple sclerosis (MS). The connection between vision problems and this autoimmune disorder is so strong that eye doctors may be the first ones to suspect an autoimmune disorder,

In multiple sclerosis or myasthenia gravis, double vision or drooping eyelids can occur. A typical initial indicator of MS is an inflammation of the optic nerve, known as optic neuritis, which restricts your vision by either blurring it or limiting it.

Other eye issues associated with MS include uncontrolled eye movements and double vision due to weak muscles preventing your eyes from coordinating with each other. In every case, the symptoms usually resolve themselves during general MS treatment. Still, your eye doctor might recommend corticosteroids as well.

In addition to all those symptoms, you may also suffer from eye problems. Vision problems may be one of the first signs that you have MS, which is one reason why regular eye exams are so important. A typical initial indicator of MS is an inflammation of the optic nerve, known asoptic neuritis, which restricts your vision by either blurring it or limiting it completely.

Inflammatory bowel disease

Examples of such diseases include:

• rheumatoid arthritis,
• systemic lupus erythematosus,
• polyarteritis nodosa,
• relapsing polychondritis,
• Granulomatosis with Polyangiitis (formerly called Wegener’s),
• scleroderma,
• Behcet’s disease,
• Reactive arthritis (formerly called Reiter’s syndrome),
• Inflammatory bowel disease (ulcerative colitis and Crohn’s disease) and ankylosing spondylitis.

The eye may be affected as a target of immune-inflammatory attacks in these diseases. The eye may, however, in certain instances be the specific and only target affected by certain autoimmune disorders.

Ulcerative colitis

They are known as HLA-B27 has been linked to an increased risk of developing uveitis at the front of the eye (anterior uveitis). About half of all people with anterior uveitis have the HLA-B27 gene. The gene has been found in people with certain autoimmune conditions, including ulcerative colitis.

Psoriatic arthritis

Psoriasis causes an extreme buildup of skin cells on the skin’s surface. While skin cells generally have a month-long life cycle, those with psoriasis experience new cell growth every few days – leading to patches of red, dry skin.

Psoriasis is a skin condition of psoriatic arthritis – a type of arthritis that develops in some people with psoriasis multiple sclerosis – a condition mainly affecting the nerves Behçet’s disease – a rare condition that causes mouth ulcers and genital ulcers sarcoidosis – a rare inflammatory condition that affects the lungs, skin, and eyes juvenile.

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Stephen Foster, M.D. Ocular Autoimmune Disease: An Introduction. 2018. The Ocular Immunology and Uveitis Foundation. 26 December 2018 . Health Categories First Aid & Emergencies Topics A-Z Slideshows Images Quizzes Medications eMedicineHealth About Us.

Alan H. Friedman, MD, clinical professor of ophthalmology and pathology at the Mount Sinai School of Medicine in New York City.

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References

1. Delves PJ ed. Autoimmunity. In: Encyclopedia of Immunology, 2nd ed. London: Elsevier Ltd. p. 292–6.

2. Ruby AJ, Jampol LM. Crohn’s Disease and Retinal Vascular Disease. Am J Ophthalmol (1990) 110(4):349–53. doi: 10.1016/S0002-9394(14)77013-8

3. Patil SA, Cross RK. Update in the Management of Extraintestinal Manifestations of Inflammatory Bowel Disease. Curr Gastroenterol Rep (2013) 15(3):1–5. doi: 10.1007/s11894-013-0314-8

4. Jacobson DL, Gange SJ, Rose NR, Graham NMH. Epidemiology and Estimated Population Burden of Selected Autoimmune Diseases in the United States. Clin Immunol Immunopathol (1997) 84(3):223–43. doi: 10.1006/clin.1997.4412

5. Lerner A. 11th Annual Congress on Immunology: The World Incidence and Prevalence of Autoimmune Diseases is Increasing. J Timely Top Clin Immunol (2018) 2:42. doi: 10.1038/1931030a0

6. Markets M and. Autoimmune Disease Diagnosis Market by Product (Consumables, Assay Kits, Instruments), Test Type (Inflammatory Markers, Routine Laboratory Tests), Disease (RA, SLE, Thyroiditis, Scleroderma), End User (Hospitals, Clinical Labs) – Global Forecast to 2025. (2020).

7. Somers EC, Thomas SL, Smeeth L, Hall AJ. Are Individuals With an Autoimmune Disease at Higher Risk of a Second Autoimmune Disorder? Am J Epidemiol (2009) 169(6):749–55. doi: 10.1093/aje/kwn408

8. Eslami F, Borzouei S, Khanlarzadeh E, Seif S. Prevalence of Increased Intraocular Pressure in Patients With Graves’ Ophthalmopathy and Association With Ophthalmic Signs and Symptoms in the North-West of Iran. Clin Ophthalmol (2019) 13:1353–9. doi: 10.2147/OPTH.S205112

9. Patel SJ, Lundy DC. Ocular Manifestations of Autoimmune Disease. Am Family Phys (2002) 66(6):991–8.

10. Zlatanović G, Veselinović D, Cekić S, Živković M, Đorđević-Jocić J, Zlatanović M. Ocular Manifestation of Rheumatoid Arthritis-Different Forms and Frequency. Bosn J Basic Med Sci (2010) 10(4):323. doi: 10.17305/bjbms.2010.2680

11. Mintz R, Feller ER, Bahr RL, Shah SA. Ocular Manifestations of Inflammatory Bowel Disease. Inflamm Bowel Dis (2004) 10(2):135–9. doi: 10.1097/00054725-200403000-00012

12. Almaliotis D, Zakalka M, Gerofotis A, Chatzicharalampous K, Efstathiou M, Daniilidis M, et al. Ocular Manifestations in Rheumatoid Arthritis. Open J Ophthalmol (2016) 6:170–5. doi: 10.4236/ojoph.2016.63024

13. World Health Organisation. Chronic Rheumatic Conditions. (2020).

14. Abouda SA, Elkhaleka MOA, Alyb NH, Elaleemc EAA. Ocular Involvement and its Manifestations in Rheumatoid Arthritis Patients. Delta J Ophthamol (2017) 18:57–62. doi: 10.4103/DJO.DJO_17_17

15. Abd-allah NM, Hassan AA, Omar G, Hamdy M, Abdelaziz TA, Mahmoud W, et al. Dry Eye in Rheumatoid Arthritis : Relation to Disease Activity. Immunol Med (2020) 43(2):92–7. doi: 10.1080/25785826.2020.1729597

16. Gurlevik U, Karakoyun A, Yasar E. When Rheumatoid Arthritis is Mentioned, Should Only Dryness Come to Mind ? Clin Rheumatol (2020) 39(11):3317–21. doi: 10.1007/s10067-020-05124-1

17. Kal A, Duman E, Sezenoz AS, Ulusoy MO, Kal O. Evaluation of Retrobulbar Blood Flow and Choroidal Thickness in Patients With Rheumatoid Arthritis. Int Ophthamol (2018) 6(1):1825–31. doi: 10.1007/s10792-017-0656-6

18. Silva BL, Cardozo JB, Marback P, Carrhá F, Galvão V, Santiago MB. Peripheral Ulcerative Keratitis : A Serious Complication of Rheumatoid Arthritis. Rheumatol Int (2010) 30:1267–8. doi: 10.1007/s00296-009-1161-7

19. Giordano N, D’Ettorre M, Biasi G, Fioravanti A, Moretti L, Marcolongo R. Retinal Vasculitis in Rheumatoid Arthritis: An Angiographic Study. Clin Exp Rheumatol (1990) 8(2):121–5. doi: 10.1097/00006982-199010000-00019

20. Carsons SE, Patel BC. Sjogren Syndrome. (2020).

21. Akpek EK, Mathews P, Hahn S, Hessen M, Kim J, Grader-Beck T, et al. Ocular and Systemic Morbidity in a Longitudinal Cohort of Sjögren’s Syndrome. Ophthalmology (2015) 122(1):56–61. doi: 10.1016/j.ophtha.2014.07.026

22. Akpek EK, Klimava A, Thorne JE, Martin D, Lekhanont K, Ostrovsky A. Evaluation of Patients With Dry Eye for Presence of Underlying Sjögren Syndrome. Cornea (2009) 28(5):493–7. doi: 10.1097/ICO.0b013e31818d3846

23. Mathews P, Hahn S, Hessen M, Kim J, Grader-Beck T, Birnbaum J, et al. Ocular Complications of Primary Sjogren’s Syndrome in Men. Am J Ophthalmol (2017) 160(3):447–52.e1. doi: 10.1016/j.ajo.2015.06.004.

24. Saldanha IJ, Bunya VY, McCoy SS, Makara M, Baer AN, Akpek EK. Ocular Manifestations and Burden Related To Sjögren’s Syndrome: Results of a Patient Survey. Am J Ophthalmol (2020) 219:40–8. doi: 10.1016/j.ajo.2020.05.043.

25. Auluck I, Taylor S, Karimi A. Lessons of the Month 2: A Case of Behçet’s Disease: 70% Have Ophthalmic Involvement. Clin Med J R Coll Phys London (2019) 19(6):519–22. doi: 10.7861/clinmed.2019.0149