What are the common autoimmune diseases that impact eye health. How do autoimmune conditions affect vision and ocular structures. What are the risk factors for developing autoimmune eye disorders. How can autoimmune-related eye problems be diagnosed and treated.

The Complex Relationship Between Autoimmune Diseases and Eye Health

Autoimmune diseases occur when the body’s natural defense system fails to distinguish between its own cells and foreign invaders. This malfunction leads to the immune system mistakenly attacking healthy cells, potentially affecting various parts of the body, including the eyes. The impact of autoimmune conditions on ocular health can be significant, causing a range of symptoms and potentially leading to vision loss if left untreated.

Understanding the intricate connection between autoimmune diseases and eye health is crucial for early detection, proper management, and preservation of vision. This comprehensive guide explores various autoimmune conditions that can affect the eyes, their symptoms, and potential risk factors.

Behcet Disease: A Rare Yet Serious Threat to Vision

Behcet Disease is a rare autoimmune condition characterized by ocular lesions, skin lesions, and genital ulcers. Its impact on vision health is particularly concerning, as it can affect both the anterior and posterior portions of the eye.

How does Behcet Disease impact eye health?

• Causes inflammation in various parts of the eye
• Can lead to vision loss if left untreated
• May cause recurrent episodes of eye inflammation

Early detection and proper management of Behcet Disease are crucial to prevent vision loss. Regular eye examinations and prompt treatment of ocular symptoms can help preserve sight in affected individuals.

Crohn’s Disease: Beyond the Digestive Tract

While primarily known as an inflammatory bowel disease, Crohn’s Disease can also affect eye health. The main ocular complication associated with Crohn’s Disease is episcleritis, a condition characterized by inflammation of the episclera, the thin layer of tissue covering the white part of the eye (sclera).

What are the ocular symptoms of Crohn’s Disease?

• Redness of the eye (episcleritis)
• Mild eye pain or discomfort
• Sensitivity to light

Although episcleritis is generally benign, it can cause discomfort and affect quality of life. Proper management of Crohn’s Disease, including its ocular manifestations, is essential for overall well-being.

Diabetes: A Silent Threat to Vision

Diabetes, while not traditionally classified as an autoimmune disease, has autoimmune components and can significantly impact eye health. The condition affects blood sugar levels, which in turn can lead to various ocular complications.

How does diabetes affect the eyes?

1. Swelling of the eye lens due to fluctuating blood sugar levels
2. Damage to blood vessels in the retina (diabetic retinopathy)
3. Increased risk of cataracts and glaucoma

Maintaining stable blood sugar levels through proper diabetes management is crucial for preserving eye health. Regular eye examinations are essential for early detection and treatment of diabetes-related eye complications.

Lupus: A Multi-System Autoimmune Disorder

Systemic lupus erythematosus (SLE), commonly known as lupus, is an autoimmune disease that can affect various parts of the body, including the eyes. The inflammation caused by lupus can lead to several ocular complications.

What are the ocular manifestations of lupus?

• Inflammation of the white outer layer of the eyeball (scleritis)
• Changes in the skin around the eyelids
• Damage to nerves controlling eye movement
• Dry eyes (keratoconjunctivitis sicca)

Proper management of lupus, including its ocular symptoms, is essential for maintaining overall health and preserving vision. Regular eye check-ups are crucial for individuals with lupus to monitor and address any eye-related complications.

Multiple Sclerosis: When Vision Becomes a Concern

Multiple sclerosis (MS) is a chronic condition affecting the brain and spinal cord. One of the common ocular symptoms associated with MS is optic neuritis, which involves inflammation of the optic nerve.

What are the visual symptoms of multiple sclerosis?

• Blurred vision
• Loss of color vision
• Pain with eye movement
• Visual field defects

Optic neuritis typically affects one eye and can be an early sign of MS. Prompt diagnosis and treatment of optic neuritis are crucial to prevent long-term vision loss. Individuals with MS should undergo regular eye examinations to monitor their ocular health.

Psoriasis: More Than Skin Deep

Psoriasis, primarily known as a skin condition, can also have implications for eye health. Some types of psoriasis are associated with an increased risk of developing inflammatory eye conditions.

What eye problems are linked to psoriasis?

• Conjunctivitis (pink eye)
• Blepharitis (inflammation of the eyelid)
• Uveitis (inflammation of the middle layer of the eye)

Individuals with psoriasis should be aware of potential eye-related complications and seek prompt medical attention if they experience any ocular symptoms. Regular eye check-ups can help in early detection and management of psoriasis-related eye problems.

Rheumatoid Arthritis: Beyond Joint Pain

Rheumatoid arthritis (RA) is an autoimmune and inflammatory disease that primarily affects the joints. However, it can also impact other parts of the body, including the eyes.

How does rheumatoid arthritis affect eye health?

• Dry eyes (keratoconjunctivitis sicca)
• Scleritis (inflammation of the white part of the eye)
• Episcleritis (inflammation of the tissue covering the sclera)
• Increased risk of cataracts

The most common ocular symptom in RA is dryness of the sclera, which, if left untreated, can lead to corneal damage. Regular eye examinations and proper management of RA are essential for maintaining ocular health and preventing vision complications.

Sjogren’s Syndrome: When Dryness Becomes a Problem

Sjogren’s syndrome is an autoimmune disorder characterized by its two primary symptoms: dry eyes and dry mouth. The condition affects the body’s moisture-producing glands, leading to various complications.

What are the ocular symptoms of Sjogren’s syndrome?

• Extreme dryness of the eyes
• Itching or burning sensation in the eyes
• Blurred vision
• Sensitivity to light

The decreased tear production in Sjogren’s syndrome can lead to corneal damage if left untreated. Management typically involves artificial tears, punctal plugs, and other treatments to maintain eye moisture and protect the ocular surface.

Thyroid Diseases: A Window to Eye Health

Thyroid diseases, including both hyper- and hypothyroidism, can have significant impacts on eye health. These conditions can increase the risk of developing glaucoma and other ocular complications.

How do thyroid diseases affect the eyes?

• Graves’ disease: Tissue buildup around the eye, increasing intraocular pressure
• Hypothyroidism: Impaired fluid circulation in the eye, leading to increased pressure
• Dry eyes and blurred vision
• Protruding eyes (exophthalmos) in some cases

Regular monitoring of thyroid function and eye health is crucial for individuals with thyroid diseases. Early detection and management of ocular complications can help prevent vision loss and maintain overall eye health.

Uveitis: When the Eye’s Middle Layer is Under Attack

Uveitis is an autoimmune disease that directly affects the uvea, the middle layer of tissue in the eye wall. This condition can cause significant vision problems if left untreated.

What are the symptoms of uveitis?

• Eye redness
• Eye pain
• Blurred vision
• Sensitivity to light
• Floaters in the visual field

Prompt diagnosis and treatment of uveitis are crucial to prevent vision loss. Treatment typically involves corticosteroids or other immunosuppressive medications to control inflammation and preserve vision.

Risk Factors for Autoimmune Eye Diseases

While the exact causes of autoimmune diseases remain unclear, several risk factors have been identified that may increase an individual’s likelihood of developing these conditions.

What factors increase the risk of autoimmune eye diseases?

• Genetics: Family history of autoimmune diseases
• Environmental triggers: Exposure to certain viruses or chemicals
• Obesity: Increased risk of rheumatoid arthritis and psoriatic arthritis
• Smoking: Linked to several autoimmune diseases, including lupus and multiple sclerosis
• Gender: Many autoimmune diseases are more common in women
• Age: Some autoimmune diseases are more likely to develop at certain ages

Understanding these risk factors can help individuals and healthcare providers take proactive measures to monitor eye health and detect potential autoimmune-related eye problems early.

Diagnosis and Management of Autoimmune Eye Diseases

Proper diagnosis and management of autoimmune eye diseases are crucial for preserving vision and maintaining overall eye health. The diagnostic process often involves a combination of eye examinations, blood tests, and imaging studies.

How are autoimmune eye diseases diagnosed and managed?

1. Comprehensive eye examination
2. Blood tests to detect specific antibodies or markers
3. Imaging studies (e.g., OCT, fluorescein angiography)
4. Collaboration between ophthalmologists and rheumatologists
5. Tailored treatment plans, which may include:
   • Corticosteroids
   • Immunosuppressive medications
   • Biologic therapies
   • Supportive treatments (e.g., artificial tears, lubricating eye drops)

Early detection and proper management of autoimmune eye diseases can significantly improve outcomes and help preserve vision. Regular eye check-ups and open communication with healthcare providers are essential for individuals with autoimmune conditions or those at risk.

The Importance of Regular Eye Examinations

For individuals with autoimmune diseases or those at risk of developing them, regular eye examinations are crucial. These check-ups can help detect early signs of ocular complications and allow for timely intervention.

Why are regular eye exams important for individuals with autoimmune diseases?

• Early detection of ocular complications
• Monitoring of disease progression
• Adjustment of treatment plans as needed
• Prevention of vision loss
• Improvement of overall quality of life

The frequency of eye examinations may vary depending on the specific autoimmune condition and individual risk factors. Consulting with an eye care professional can help determine the appropriate schedule for eye check-ups.

Lifestyle Modifications for Managing Autoimmune Eye Diseases

In addition to medical treatments, certain lifestyle modifications can help manage autoimmune eye diseases and improve overall eye health.

What lifestyle changes can help manage autoimmune eye diseases?

• Maintaining a healthy diet rich in anti-inflammatory foods
• Regular exercise to reduce inflammation and improve overall health
• Stress management techniques, such as meditation or yoga
• Avoiding smoking and limiting alcohol consumption
• Protecting eyes from UV radiation with sunglasses
• Maintaining good sleep hygiene
• Staying hydrated to support tear production

While these lifestyle modifications cannot cure autoimmune eye diseases, they can help manage symptoms, reduce inflammation, and support overall eye health. It’s important to discuss any lifestyle changes with a healthcare provider to ensure they are appropriate for individual circumstances.

The Future of Autoimmune Eye Disease Treatment

Research into autoimmune eye diseases continues to advance, offering hope for improved treatments and potentially even cures in the future.

What are some promising areas of research in autoimmune eye diseases?

• Targeted biologic therapies
• Gene therapy approaches
• Stem cell treatments
• Personalized medicine based on genetic profiles
• Novel drug delivery systems for ocular medications

As our understanding of autoimmune diseases and their impact on eye health continues to grow, new treatment options are likely to emerge. Staying informed about these developments and discussing them with healthcare providers can help individuals make informed decisions about their eye care.

Autoimmune Diseases That Affect the Eyes

An autoimmune disease occurs when the natural defense system of a body is not able to differentiate its own cells from foreign cells. As a result, the immune system mistakenly attacks normal cells. Nearly every part of the body – including the eyes – can take the brunt of autoimmune diseases.

In this article, a reputable eye clinic takes a closer look at some of the autoimmune diseases that can heavily affect the eyes, the common symptoms of these conditions and their risk factors.

Autoimmune Diseases That Are Linked to Vision Health

There are more than 80 types of autoimmune diseases that affect a wide range of body parts, from nerves and joints to eyes. Some autoimmune diseases that typically affect the eyes are:

Behcet Disease
This rare autoimmune disease characterized by ocular lesions, skin lesions and genital ulcers is a leading case of blindness in some parts of the world. It can affect the anterior and posterior portions of the eye.

Crohn’s Disease
This type of inflammatory bowel disease causes swelling of the tissues in the digestive tract. The main eye-related problem that can occur with Crohn’s disease is episcleritis, a common and benign cause of red eye.

Diabetes
A potential effect of diabetes is swelling of the eye lens. If blood sugar levels change from low to normal too quickly, the shape of the eye lens can be affected, leading to blurred vision. High blood sugar can also damage the blood vessels in the retina, the light-sensitive part of the eye.

Lupus
Inflammation caused by lupus can affect many systems of the body, including the skin, brain, heart and lungs. The effects of lupus in and around the eyes include inflammation of the white outer layer of the eyeball, changes in the skin around the eyelids and damage to nerves controlling eye movement.

Multiple Sclerosis
This is a lifelong condition that can affect the brain and spinal cord. Optic neuritis or inflammation of the optic nerve is a common symptom of this disease. It usually occurs in one eye and can cause blurred vision, loss of color vision and pain with eye movement.

Psoriasis
A common chronic skin disease, psoriasis causes rashes with itchy, scaly patches all over the body, most typically on the scalp, knees and elbows. Some types of psoriasis are linked to a heightened risk of developing inflammatory eye conditions, such as conjunctivitis or inflammation of the eyelid.

Reactive Arthritis
Formerly known as Reiter’s syndrome, reactive arthritis is a condition that causes redness and swelling in various joints of the body. Many people with this condition also develop conjunctivitis.

Rheumatoid Arthritis
This is an autoimmune and inflammatory disease that causes painful swelling in affected parts of the body. Its most common eye-related symptom is dryness of the sclera, which, if left untreated, can cause damage to the cornea, the clear surface that helps the eye focus.

Sjogren’s Syndrome
A disorder of the immune system, Sjogren’s syndrome is identified by its two most common symptoms: dry eyes and a dry mouth. Because of the decrease in tear production, the eyes may feel extremely dry, itchy or burning.

Thyroid Diseases
This is a group of autoimmune diseases that result in high or low thyroid function. It increases the risk of developing glaucoma, a condition that causes high pressure inside the eye. With Graves’ disease, for instance, tissues build up around the eye and increase pressure. With low-thyroid disorders, on the other hand, pressure builds up because the eye is not able to effectively circulate its fluids.

Uveitis
This is an autoimmune disease that directly affects the middle layer of tissue in the eye wall called uvea. Its common symptoms include eye redness, pain and blurred vision. It can affect one or both eyes and can cause vision loss if left untreated by an eye specialist.

Risk Factors of Autoimmune Diseases

While the exact cause of autoimmune diseases is unknown, some people are more likely to develop an autoimmune disease than others. Risk factors that increase the chances of developing autoimmune diseases include:

Genetics: Certain autoimmune diseases like lupus and multiple sclerosis do tend to run in families, meaning that certain genes make some people more likely to develop them. Viruses, chemicals and other things in the environment can trigger an autoimmune disease if the body already possesses the genes for it.

Weight: Obesity increases the risk of developing rheumatoid arthritis or psoriatic arthritis. This could be due to heavier weight putting significant strain on the joints or fat tissues producing substances that encourage inflammation.

Smoking: Research has also linked smoking to the development of several immune and autoimmune diseases, such as lupus, rheumatoid arthritis, hyperthyroidism and multiple sclerosis. Smoking has wide-reaching effects on the immune system, including increasing inflammation levels and allergic conditions.

Medications: Some blood pressure medications or antibiotics can trigger drug-induced lupus, a generally milder version of the idiopathic disorder. Specific medications used to lower cholesterol can also trigger statin-induced myopathy, a rare autoimmune disease causing muscle weakness.

Medicines That Can Help Treat Eye Symptoms of Autoimmune Diseases

Fortunately, there are over-the-counter medicines that can help alleviate the eye-related symptoms of autoimmune diseases. These include artificial tears, lubricating gels and ointments, all of which can help with dry eyes. These medicines bring moisture back to the surface of the eye. Other inflammatory conditions are sometimes treated with oral non-steroidal anti-inflammatory drugs that are available over the counter. Patients who do not respond to oral medications should be referred to an ophthalmologist for possible treatment with immunosuppressive medications.

The Importance of Getting Regular Eye Examinations

Aside from eating a balanced diet and leading a healthy lifestyle, one of the most critical steps to preserve eyesight is to regularly attend appointments with an ophthalmologist. According to the American Academy of Ophthalmology, all adults should undergo eye screening at age 40 to maintain healthy vision, especially if they have not seen an eye specialist previously. Generally, however, adults aged 18 to 60 should get a comprehensive eye exam at least every two years.

If you happen to be affected by an autoimmune disease:

• You should not wait until you are 40 years old to get a vision health screening. If you have not been to an ophthalmologist in the past year, it will be for your own benefit to see one now.

• Make sure you talk to your doctor about how often you need a vision screening. If you are experiencing symptoms related to vision health issues, then you will definitely need to get screened more frequently. Some patients get screened as often as every six months, but this is for severe cases.

• It is also important to get regular eye examinations if you are taking medications for autoimmune disease treatment, such as hydroxychloroquine, which can cause ocular toxicity to various parts of the eye. Other medications for autoimmune diseases that can have negative effects on vision health include corticosteroids, which can increase the risk of cataracts and glaucoma when used long-term.

Most autoimmune diseases can be managed with medication, although serious eye damage and, in some cases, blindness can happen if they are not treated. An eye doctor and an autoimmune specialist should work closely together to effectively treat eye symptoms that occur with autoimmune diseases.

Uveitis – Causes – NHS

Uveitis happens when the eye becomes red and swollen (inflamed).

Inflammation is the body’s response to illness or infection.

Most cases of uveitis are linked to a problem with the immune system (the body’s defence against infection and illness).

Rarely, uveitis may happen without the eye becoming red or swollen.

Immune system problems

Uveitis often happens in people who have an autoimmune condition. This is where the immune system mistakenly attacks healthy tissue.

Autoimmune conditions known to cause uveitis include:

• ankylosing spondylitis – a condition 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 disease and ulcerative colitis
• psoriasis – a skin condition
• 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 idiopathic arthritis– a type of arthritis that affects children

Infection

Uveitis can also be caused by an infection, such as:

• toxoplasmosis – an infection caused by a parasite
• herpes simplex virus – the virus responsible for cold sores
• varicella-zoster virus – the virus that causes chickenpox and shingles
• cytomegalovirus – a common infection that does not usually cause any noticeable symptoms, but can cause sight-threatening uveitis in people with a lowered immune system
• tuberculosis
• HIV and syphilis are rare causes

Other causes

Uveitis can also be caused by:

• trauma or injury to the eyes, or eye surgery
• some types of cancers, such as Non-Hodgkin lymphoma, although this is a very rare cause of uveitis

Sometimes, a specific cause of uveitis cannot be identified.

Gene HLA-B27

Although uveitis is not passed down through families, a gene 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 ankylosing spondylitis and ulcerative colitis.

Page last reviewed: 03 January 2020
Next review due: 03 January 2023

Features of ophthalmic pathology in autoimmune diseases | Lukashenko

1. Basantsova N.Yu., Zinchenko Yu.S., Starshinova A.A., Yablonsky P.K. Features of the diagnosis of neuropathy of small fibers in various diseases (literature review) // Pediatrician, 2018. V. 9, No. 6. P. 101-110.

2. Vizel A.A. Sarcoidosis: monograph. M.: Atmosfera, 2010. 416 p.

3. Godzenko A.A. Prospects for the treatment of uveitis in rheumatic diseases // Modern Rheumatology, 2011. V. 2, No. 37. C. 42.

4. Zaitseva N.S., Katsnelson L.A. Uveitis. Moscow: Medicine, 1984. 318 p.

5. Kansky D. Clinical ophthalmology: a systematic approach. Per. from English. M.: Logosfera, 2006. P. 744.

6. Plekhanov A.N., Fomina A.S., Sverkunova O.P., Ivanova Yu.V. Autoimmune uveitis. Review // Ophthalmology, 2019. V. 16, No. 1. P. 5-11.

7. Polunin G.S., Safonova T.N., Polunina E.G. Features of the clinical course of various forms of dry eye syndrome – the basis for the development of adequate methods of treatment // Bulletin of the ophthalmologist, 2006. V. 102, No. 5. P. 17-20.

8. Roit A, Brostoff J, Meil ​​D. Immunology. Per. from English. M.: Mir, 2000. 208 p.

9. Ustinova E.I. Endogenous uveitis (selected lectures for ophthalmologists). St. Petersburg: Eco-Vector, 2017. 204 p.

10. Shishkin A.N. Diffuse diseases of connective tissue / Systemic pathology of connective tissue. Ruk. For doctors / Ed. Yu.I. Stroeva, L.P. Churilova. St. Petersburg: Elbi-SPb, 2014. S. 282-313.

11. Akiki R.K., Statler B., Greenberg P.B., Janigian R.H. Unilateral birdshot chorioretinopathy in an elderly patient. R.I. Med. J., 2019Vol. 102, no. 1, pp. 60-61.

12. Alhatem A., Cavalcanti B., Hamrah P. In vivo confocal microscopy in dry eye disease and related conditions. Semin. Ophthalmol., 2012, Vol. 27, no. 5-6, pp. 138-148.

13. Avichezer D., Chan C.C., Silver P.B., Wiggert B., Caspi R.R. Residues 1-20 of IRBP and whole IRBP elicit different uveitogenic and immunological responses in interferon gamma deficient mice. Exp. Eye Res, 2000, Vol. 71, no. 2, pp. 111-118.

14. Becker M.D., Adamus G., Davey M.D., Rosenbaum J.T. The role of T-cells in autoimmune uveitis. Ocul. Immunol. Inflam., 2000, Vol. 8, no. 2, pp. 93-100.

15. BENITEZ-DEL-CASTILLO J.M., Acosta M.C., Wassfi M.A., Díaz-Valle D., Gegóndez J.A., Fernandez C., Garcíasánchez J. Relation Between Corneal Innervation with Con Focal Microscopy and Corneal Sensitivity with NonContact Esthesiometry in Pathents with Dry eye. Invest. Ophthalmol. Vis. Sc., 2007, Vol. 48, no. 1, rr. 173-181.

16. Bose T., Diedrichs-Möhring M., Wildner G. Dry eye disease and uveitis: A closer look at immune mechanisms in animal models of two ocular autoimmune diseases. J. Autoimmun. Rev., 2016, no. 15 (12), pp. 1181-1192.

17. Boulton A.J., Malik R.A., Arezzo J.C., Sosenko J.M. Diabetic somatic neuropathies. Diabetes Care, 2004, Vol. 27, no. 6, rr. 1458-1486.

18. Coulon C., Kodjikian L., Rochepeau C., Perard L., Jardel S., Burillon C., Broussolle C., Jamilloux Y., Seve P. Ethnicity and association with ocular, systemic manifestations and prognosis in 194 patients with sarcoid uveitis. Graefes. Arch. Clin. Exp. Ophthalmol., 2019, Vol. 257, no. 11, pp. 2495-2503.

19. Cruzat A., Qazi Y., Hamrah P. In vivo confocal microscopy of corneal nerves in health and disease. Ocul. Surf., 2017, Vol. 15, no. 1, pp. 15-47.

20. Davatchi F. Behcet’s disease. J. Int. Rheum. Dis., 2014, Vol. 17, no. 4, pp. 355-357.

21. Davatchi F., Shahram F., Chams-Davatchi C., Shams H., Nadji A., Akhlaghi M., Faezi T., Ghodsi Z., Faridar A., ​​Ashofteh F., Abdollahi B.S. Behcet’s disease: from east to west. Clin. Rheumatol., 2010, Vol. 29, no. 8, pp. 823-833.

22. Direskeneli H. Behçet’s disease: infectious aetiology, new autoantigens, and HLA-B51. Ann. Rheum. Dis., 2001, Vol. 60, no. 11, pp. 996-1002.

23. Kernel A., Dedorsson I., Johansson B., Wickstrom C.P., Ludvigsson J., Tuvemo T., Neidemd J., Sjostrom K., Malmgreen K., Kanulf P., Mellvig Gjotterberg M., Sule J ., Persson L.A., Larsson L.I., Aman J., Dahlquist. Prevalence of diabetic retinopathy in children and adolescens with IDDM. A population-based multicentre study. Diabetologia, 1997, Vol. 40, no. 3, pp. 307-310.

24. Malik R.A, Kallinikos P., Abbott C.A., van Schie C.H.M., Morgan P., Efron N., Boulton A.J.M. Corneal confocal microscopy: a noninvasive surrogate of nerve fiber damage and repair in diabetic patients. Diabetology, 2003, Vol. 46, pp. 683-688.

25. Malik R.A., Veves A., Walker D., Siddique I., Lye R.H., Schady W., Boulton A.J. Sural nerve fiber pathology in diabetic patients with mild neuropathy: relationship to pain, quantitative sensory testing and peripheral nerve electrophysiology. Acta Neuropathol., 2001, Vol. 101, pp. 367-374.

26. Messmer E.M., Schmid-Tannwald C., Zapp D., Kampik A. In vivo confocal microscopy of corneal small fiber damage in diabetes mellitus. Graefs Arch. Clin. Exp. Ophthalmol., 2010, Vol. 248, no. 9, rr. 1307-1312.

27. Messmer E.M. The pathophysiology, diagnosis, and treatment of dry eye disease. Dtsch Arztebl. Int., 2015, Vol. 112, no. 5, pp. 71-81.

28. Morgan J.P., Robins R.A., Dua H.S., Tighe P.J. S antigen specific effector T cell activation detected by cytokine flow cytometry. Br. J. Ophthalmol., 2002, Vol. 86, no. 5, pp. 517-520.

29. No authors listed. The definition and classification of dry eye disease: report of the Definition and Classification Subcommittee of the International Dry Eye WorkShop. Ocul. Surf., 2007, Vol. 5, no. 2, pp. 75-92.

30. Pasadhika S., Rosenbaum J.T. Ocular Sarcoidosis. Clin. Chest. Med., 2015, Vol. 36, no. 4, pp. 669-683.

31. Pascolini D., Mariotti S.P.M. Global estimates of visual impairment: 2010. Br. J. Ophthalmol., 2012, Vol. 96, no. 5, pp. 614-618.

32. Raizman M. Corticosteroid therapy of eye diseases. Arch. Ophthalmol., 1996, Vol. 114, no. 8, rr. 1000-1001.

33. Rosenberg M.E., Tervo T.M., Immonen I.J., Müller L.J., Grönhagen-Riska C., Vesaluoma M.H. Corneal structure and sensitivity in type 1 diabetes mellitus. Invest. Ophthalmol. Vis. Sc., 2000, Vol. 41, no. 2, pp. 2915-2921.

34. Sakane T., Takeno M., Suzuki N., Inaba G. Behçet’s disease. N. Engl. J. Med., 1999, Vol. 341, no. 17, pp. 1284-1291.

35. Sherman M.A., Ardashev I.V. A case of recurrent Devic’s optiomyelitis. J. Nevrol. Psychiatr. Im. S.S. Korsakova, 2015, Vol. 115, no. 2, Pt. 2, pp. 38-44.

36. Tuisku I.S., Konttinen Y.T., Konttinen L. M., Tervo T.M. Alterations in corneal sensitivity and nerve morphology in patients with primary Sjogren’s syndrome. Exp. Eye Res., 2008, Vol. 86, no. 6, rr. 879-885.

37. Tuisku I.S., Lindbohm N., Wilson S.E., Tervo T.M. Dry eye and corneal sensitivity after high myopic LASIK. J. Refract. Surg., 2007, Vol. 23, no. 4, pp. 338-342.

38. Tuominen I.S., Konttinen Y.T., Vesaluoma M.H., Moilanen J.A., Helintö M., Tervo T.M. Corneal innervation and morphology in primary Sjögren’s syndrome. Invest. Ophthalmol. Vis. Sc., 2003, Vol. 44, no. 6, rr. 2545-2549.

39. Villani E., Baudouin C., Efron N., Hamrah P., Kojima T., Patel S.V., Pflugfelder S.C., Zhivov A., Dogru M. In vivo confocal microscopy of the ocular surface: from bench to bedside . Curr. Eye, 2014, Vol. 39, no. 3, pp. 213-231.

40. Yazici H. The place of Behçet’s syndrome among the autoimmune diseases. Int. Rev. Immunol., 1997, Vol. 14, no. 1, rr. 1-10.

41. Zierhut M., Schlote T., Tomida J., Stiemer R. Immunology of uveitis and ocular allergy. Acta Ophthalmol., 2000, Vol. 78, pp. 22-25.

Management of patients with dry eye syndrome in systemic autoimmune and infectious diseases | Chernakova G.M., Klescheva E.A.

The article discusses the features of the clinical course of the “dry eye” syndrome against the background of systemic autoimmune and chronic infectious diseases. Key aspects of the pathogenesis and modern therapy of dry eye syndrome in patients with rheumatoid arthritis, systemic lupus erythematosus, autoimmune thyroiditis, HIV infection, viral hepatitis B and C, Epstein-Barr virus are highlighted.

The constancy of the composition of tissue fluids is a necessary condition for resistance to environmental factors and is maintained through various physiological mechanisms. Indicators such as osmotic pressure, the total concentration of electrolytes and the concentration of individual ions, as well as the values ​​of the acid-base state, even with significant changes in environmental conditions, are kept at a certain level in biological fluids (including lacrimal fluid),
deviations from which are insignificant [1]. The above mechanisms that ensure the constancy of the composition of a particular biological fluid are called “homeostasis”.
Based on the latest DEWS-II definition of dry eye syndrome (DEWS), it is the loss of tear film homeostasis that is the basis for the development of pathological processes leading to the formation of the disease. Instability and hyperosmolarity of the tear film, inflammation and damage to the ocular surface, as well as neurosensory disorders play a leading role in the pathogenesis of DES (synonyms: corneal-conjunctival xerosis, lacrimal dysfunction syndrome, dry eye disease, English: dry eye syndrome) [2] . In addition, the definition emphasizes the multifactorial nature of this pathology, which, along with poorly understood pathophysiology and the potential progressive nature of the course of the disease, a limited range of diagnostic tests (associated with the high cost of research) creates difficulties in the diagnosis and treatment of DES [3] .

DES in autoimmune diseases

It should be noted that DES is often a manifestation of systemic diseases of both infectious and non-infectious nature [4]. The most frequent reports of the development of DES against the background of systemic autoimmune diseases (rheumatoid arthritis (RA), autoimmune thyroiditis (Hashimoto’s thyroiditis), systemic lupus erythematosus (SLE), polymyositis, mixed cryoglobulinemia, polyarteritis nodosa, scleroderma) [5–7].
Among extra-articular manifestations secondary to the immunopathological process, disruption of the exocrine glands (especially lacrimal and salivary glands) is well known in patients with RA [8, 9]. This contingent of patients is at risk of developing Sjögren’s syndrome, a chronic inflammatory autoimmune disease characterized by lymphocytic infiltration primarily of the lacrimal and salivary glands, which leads to a decrease in glandular functions and the subsequent development of xerophthalmia and xerostomia. In such cases, the pathology of the exocrine glands is secondary to the underlying pathological process [10].
The prevalence of DES in patients with RA varies from 4% to 31% and depends on genetic and geographical factors, as well as the duration and activity of the disease [11]. In addition, RA is a disease with a severe course, a pronounced pain syndrome, and, as a result, the symptoms of xerophthalmia often go unnoticed by rheumatologists, which is associated with a milder severity of DES compared to the main pathological process.
For example, Hajiabbasi et al. in 2016, 83 patients with RA were examined to identify symptoms of xerophthalmia. The authors diagnosed DES in 80% of cases [12]. Uhlig et al., using the Schirmer test as an objective research method and a questionnaire as a subjective assessment of the condition of the ocular surface (complaints of “dry” eyes, a feeling of “sand” and the need to use tear replacement drugs 3 or more times during the day), revealed DES in 383 patients with RA out of 631 examined (60.7%). In addition, the authors note a different severity of DES symptoms in patients with RA, from mild (with complaints of intermittent “dryness” of the eyes and a feeling of “sand” that do not require tear replacement therapy) to severe (with a significant decrease in tear production, corneal damage and the need to use tear substitutes
more than 4 rubles/day) [13].

D.Yu. Maychuk et al. (2014) conducted a reverse study: they detected RA in more than 21% of patients with filamentous keratitis out of 30 examined. The authors suggested the presence of common links in the pathogenesis of these diseases, which require further detailed study [14].
In addition, DES is the most common ophthalmic manifestation of SLE [15, 16]. Jensen et al. report the presence of at least one of the symptoms of DES (feeling of “sand” and “foreign body”, blurred vision, the need for instillation of tear replacement drugs) in 85% (n=17) of patients with SLE, and in 20% of cases (n=4 ), researchers diagnosed Sjögren’s syndrome. The mean value of the results of the Schirmer test conducted by all subjects was 7.5 mm. This indicator in the group of healthy volunteers was 16 mm [15].
It should be noted that the involvement of eye structures in the pathological process is not a criterion for diagnosing SLE, despite this, DES is a noticeable feature of this disease [17]. The prevalence of DES in patients with SLE varies
from 9 to 19% according to different authors [16, 17]. Symptoms of reduced tear production, on the one hand, may be minor and remain unnoticed by a patient with SLE and/or a rheumatologist, on the other hand, cause noticeable discomfort, decreased visual acuity, and lead to the development of cicatricial pemphigoid in more severe cases.
The development of DES symptoms in patients with SLE is associated not only with a decrease in tear production, but also with an increase in the osmolarity of the tear film. For example, Duru et al. (2016) found a statistically significant increase in tear film osmolarity in patients with SLE compared to healthy volunteers. The authors note the presence of a negative correlation between the osmolarity values ​​and the results of the Schirmer test, as well as the absence of a relationship between the changed parameters and the age of patients and the duration of the disease [18].
In cases of discoid SLE (a limited skin form of the disease), in addition to erythematous lesions of the facial skin (classic “butterfly”), the eyelids (a scaly, pigmented skin lesion) are often involved in the pathological process with the development of blepharitis in the future, which contributes to a more severe course of DES [19].
In a mouse model of SLE induced by immunization with human monoclonal antinuclear antibodies, Chan et al. (1995) revealed the deposition of pathological immune complexes in the skin of the eyelids, which led to bilateral hypertrophy of the meibomian glands and chronic inflammation of the eyelids [20].
It should be noted that the involvement of ocular surface structures in the pathological process and the development of DES may be a marker of a more severe course of the underlying disease, which should be taken into account when examining patients with SLE [17].
DES against the background of autoimmune thyroiditis is also an urgent problem today. It is interesting that the development and functional features of the exocrine glands (lacrimal, salivary) and the thyroid gland are similar. Braley-Mullen and Yu (2015) induced the development of autoimmune thyroiditis in NOD.H-2h5 mice by introducing drinking water with sodium iodide (NaI) into the animals’ diet. Along with symptoms of autoimmune inflammation of the thyroid gland in mice, the researchers observed the development of Sjögren’s syndrome with the formation of lymphoid structures in the lacrimal and salivary glands, similar to those in the thyroid gland. The composition of lymphoid formations included T- and B-lymphocytes, dendritic cells, which indicated the inflammatory nature of the pathological process [21].
Quite interesting is the information on the diagnosis of autoimmune thyroiditis in patients with Sjögren’s syndrome in 30–50% of cases. Studies of the levels of antithyroid antibodies and basal thyroid-stimulating hormone in patients with Sjögren’s syndrome show several times the normal values, which indicates the involvement of the thyroid gland in autoimmune inflammation [22].
A decrease in tear production in patients with systemic autoimmune diseases and subsequent development of DES, as well as the progression of the disease against the background of the main (systemic) process, seems to be associated with the general mechanisms of development of these conditions [14]. Studies over the past 20 years have shown that the leading role in the development of DES in systemic autoimmune
pathologies are played by lymphocytic and plasmacytic infiltration of the periepithelial space of the lacrimal gland with the development of the so-called autoimmune epithelitis [23, 24]. It is assumed that epithelial cells, on the one hand, are the targets of an autoimmune response, on the other hand, they themselves are capable of initiating local inflammatory reactions. However, the reason for this kind of “internal activation” of epitheliocytes is not entirely clear. One of the hypotheses of the “wrong” response of the immune system is a latent viral infection [25].

DES due to systemic viral infection

Viruses are capable of initiating autoimmune reactions through a variety of mechanisms that affect tissues and organs, as evidenced by animal experiments and human studies. A viral infection can induce the expression of the so-called neoantigen on the surface of epithelial cells of the lacrimal gland and conjunctiva (due to the similarity of viral antigens and antigens of host cells), which leads to the formation of nonspecific autoantibodies, activation of cytotoxic T-lymphocytes attacking cells of one’s own body. Thus, epithelial cells of the eye surface acquire the properties of antigen-presenting cells, which are responsible not only for the “discovery” of the antigen to the immune system, but also for the production of chemokines, which provide additional attraction of T- and B-lymphocytes, macrophages,
plasma cells in the focus of inflammation. Ultimately, damage and dysfunction of cells and tissues occur due to apoptosis and inflammation [25, 26].
To date, a large number of studies have been devoted to the development of DES in patients with HIV-
infection, viral hepatitis B and C, infected with the Epstein-Barr virus (EBV). Taking into account the fact that the above infectious diseases are a global problem of modern medicine
(due to the steady increase in the incidence and the lack of effective methods of therapy), the problem of diagnosing and treating eye pathology (including DES) against the background of a systemic viral infection seems to be quite relevant [27].
More than 50% of HIV positive patients have ocular surface disease, and DES is the most common. These figures significantly exceed those in the general population [9, 28].
According to studies by Burtin et al., 70% of patients with HIV infection had DES symptoms, and 85% of cases revealed at least one clinical sign of ocular surface dysfunction, using the Schirmer test, tear film break time study, number count as diagnostic methods. dendritic cells [29]. Geier et al. showed that a decrease in tear production occurs in about 20-25% of 144 HIV-infected patients, with no correlation with the number of CD4+ lymphocytes or with the severity of HIV infection [30].
One of the pathogenetic mechanisms for the development of HIV-associated DES, according to many authors, is inflammation, the cause of which, perhaps, is the direct effect of the virus on the cells and tissues of the ocular surface. This theory is based on the results of studies in which virus DNA was found in all structures of the eye (conjunctiva, cornea, vitreous body, and retina) [31–35].
Apparently, generalized HIV infection triggers a cascade of inflammatory reactions with the generation of pro-inflammatory cytokines by cells of various tissues and organs, including the lacrimal gland and conjunctiva, which is confirmed by the detection of elevated levels of epidermal growth factor (EGF) in the lacrimal fluid of HIV-infected patients and interferon-γ inducible protein 10 (IFNγ-inducible protein 10, IP-10) in comparison with a group of uninfected subjects with DES [36]. IP-10 is one of the key cytokines that directs immunocompetent cells to the focus of inflammation, while being both a stimulator and a supporting factor in inflammatory reactions.
EGF is a “goodie” involved in maintaining homeostasis and regenerating damaged tissues. However, an excessive level of this cytokine can lead to hypertrophy of the ocular surface tissues (including the lacrimal gland), lymphocytic infiltration and, as a result, a decrease in tear production [37]. High levels of EGF and IP-10 in the tear fluid of HIV-infected patients with DES correlated with reduced Schirmer test scores and tear film break time in studies by Balne et al. in 2016 [36].
Viral hepatitis B and C (HBV and HCV) are chronic systemic diseases characterized by the development of a specific inflammatory process in liver cells with a wide range of extrahepatic manifestations. DES is the most common form of eye damage in viral hepatitis [38, 39]. Pathogenetic mechanisms for the development of DES in patients with viral hepatitis are, firstly, the ability of viruses to penetrate into the cells of the lacrimal glands, conjunctiva and cornea, while having a direct damaging effect. Secondly, the chronic persistence of viruses promotes the synthesis of
cryoglobulins (pathological immune complexes) that can be deposited in the tissue of the lacrimal gland, causing its damage [40]. In addition, the development of DES (as well as its more severe form, Sjögren’s syndrome) in patients with HBV and HCV is one of the side effects of antiviral therapy (AVT) with recombinant interferon (interferon-α) and ribavirin for long periods [41]. So, G. E. Akberova et al. diagnosed DES of varying severity in 100% of patients with HCV, both receiving AVT and without it. In addition, the authors determined the presence of hepatitis C virus RNA in the lacrimal fluid in 2 patients with severe DES. This fact allowed the researchers to suggest that the persistence of the hepatitis C virus in conjunctival cells is an aggravating factor in the development of DES [42]. Siagris et al. (2002) determined the symptoms of DES in 36.6% of subjects with HCV, while paying attention to the more frequent detection of the disease in patients of the older age group (the average age of patients with DES was 61. 4±14.7 years) [43].
VEB is another viral pathogen that has established itself as the initiator of the development of DES. EBV is a type 4 herpes virus that infects epithelial cells located in the oropharyngeal tissues, salivary glands, and B-lymphocytes. The virus is found worldwide, and most people become infected with EBV during the first two decades of life. Primary VEB-
the infection is usually asymptomatic and resolves spontaneously. In some cases, EBV can cause infectious mononucleosis characterized by fever, pharyngitis, and generalized lymphadenopathy [44]. After primary infection, asymptomatic latency of the virus develops with periodic reactivation of the infection in the salivary glands [45].
Recently, there have been reports of the ability of EBV to initiate the proliferation of lymphocytes in the lacrimal gland, which leads to a decrease in tear production and the development of severe DES [46, 47]. The EBV genome was found in cells of lacrimal gland biopsies from patients with Sjögren’s syndrome, which allowed some authors to consider EBV as a risk factor for the development of this condition [48].
Thus, the development of DES in patients with systemic autoimmune diseases and chronic generalized infections has common links of pathogenesis, namely: the development of local chronic inflammation due to lymphoid and plasma infiltration, the deposition of pathological immune complexes (cryoglobulins) in the structures of the ocular surface (cells of the lacrimal gland and conjunctiva). ) followed by damage. Chronic inflammation at the local level induces oxidative stress as a result of redox imbalance towards hyperproduction of free radicals. The antioxidant system is not able to inactivate lipid peroxidation products, which are formed in large quantities, which leads to the formation of a vicious circle: inflammation – oxidative stress – inflammation [49]. The role of oxidative stress in the development of DES is confirmed by the detection of hydroperoxides both in the systemic circulation and in the epithelium of the bulbar conjunctiva and lacrimal fluid, as well as an increase in the level of myeloperoxidase in patients with DES [49, 50].

Treatment of patients with DES

The commonality of pathogenetic processes in the development of DES in patients with systemic infectious and non-infectious diseases allows us to consider the relief of oxidative stress and breaking the bonds of the mentioned vicious circle as the main direction of drug therapy. It should be noted that systemic therapy of the underlying disease is necessary and mandatory and remains within the competence of rheumatologists and/or infectious disease specialists. However, identifying symptoms of reduced tear production against the background of systemic autoimmune diseases and chronic infections, determining the severity of DES and prescribing therapy that improves the quality of life of patients are the duties of an ophthalmologist. In this regard, the Artelac line of preparations is of interest: Artelac Splash and Artelac Balance by Bausch & Lomb.
The tactics of treatment should be determined based on the severity of DES against the background of systemic pathology and guided by the recommendations of the expert council on the “red eye”, according to which low-viscosity drugs are most effective in mild and extremely severe DES, medium viscosity and gels – in moderate and severe degrees [ 51].
In this context, Artelac Splash should be considered as the drug of choice in patients with mild symptoms (complaints of a slight feeling of “dryness”, a foreign body) and the results of objective studies approaching normal values, and with extremely severe forms of DES. The advantage of this drug is the high content of hyaluronic acid (HA) – 0.24%. In addition, the absence of preservatives in the presented preparation reduces the risk of developing toxic and toxic-allergic reactions during its use, which is relevant for patients with DES against the background of systemic autoimmune and infectious diseases, as well as against the background of long-term use of drugs that cause dry eyes ( antiglaucoma, beta-blockers, antihistamines, antispasmodics, antidepressants, oral contraceptives, diuretics).
Taking into account the role of oxidative stress in the development of DES against the background of systemic diseases, the appointment of local instillations of drugs with antioxidant properties seems to be pathogenetically justified. Perhaps the only drug with similar properties is Artelak Balance, which contains, in addition to 0.15% HA, the antioxidant cyanocobalamin (vitamin B ₁₂ ). Versura et al. report the results of using Artelac Balance in patients with moderate DES symptoms for 2 months. The authors note an objective decrease in the parameters of eye inflammation (guided by the results of the Schirmer test, determination of tear film rupture time and osmolarity) and a subjective decrease in the severity of symptoms of discomfort [52].
In the literature, there are data on the effective use of Artelac Balance in patients with DES of moderate severity against the background of viral hepatitis C [42]. The authors note a decrease in the severity of DES symptoms, explaining the positive effect of the use of this drug by protecting the ocular surface epithelium from damage by free radicals and improving metabolic processes in eye tissues [42]. Attention should be paid to the fact that Artelac Balance contains a gentle preservative (Oxyd™), which decomposes into water, oxygen and salt upon contact with the ocular surface, which eliminates the pathological effect of the preservative on the structures of the eye [52].
Summing up, it should be noted that patients with systemic autoimmune pathology, chronic generalized infections need constant monitoring not only by doctors of specialized specialties, but also by ophthalmologists. Taking into account the severity of the course of systemic diseases, both infectious and non-infectious, the symptoms of damage to the ocular surface often go unnoticed, and, as a result, there is no medical support for DES. Thus, there is a risk of progression of xerophthalmia with the development of severe and extremely severe forms of DES, which are more difficult to treat. In addition, the presence of undiagnosed DES worsens the quality of life of patients with severe systemic pathology.
Taking into account the fact that oxidative stress, which develops as a result of inflammation at the local level, plays a key role in the pathogenesis of DES in patients with systemic infectious and non-infectious diseases, it is necessary to use not only tear replacement drugs to relieve the symptoms of xerophthalmia, but also antioxidant drugs. Thus, for the treatment of DES in patients with systemic autoimmune diseases and chronic generalized infections, the use of Artelac Splash and Artelac Balance seems to be pathogenetically significant.

Information about the authors: Chernakova Galina Melsovna – Candidate of Medical Sciences, Associate Professor. FGAU NMIC “IRTC “Eye Microsurgery” named after A.I. acad. S. N. Fedorova” of the Ministry of Health of Russia. 127486, Russian Federation, Moscow, Beskudnikovsky Boulevard, 59a. Kleshcheva Elena Alexandrovna – PhD, ophthalmologist. FGBOU DPO RMANPO of the Ministry of Health of Russia. 123995, Russian Federation, Moscow, st. Barrikadnaya, 2/1. Contact information: Kleshcheva Elena Alexandrovna, e-mail: [email protected] . Financial transparency: none of the authors has a financial interest in the presented materials or methods. No conflict of interest . Article received 04/30/2018.