Uveitis, Non-Infectious  

What Is Non-Infectious Uveitis?

[dropcap]N[/dropcap]on-infectious uveitis, as opposed to that which is caused by an infection, is an inflammatory eye disorder characterized mainly by swelling of the uveal tract structures in the anterior (front) of the eye.  

Inflammation can also affect the lens, retina, optic nerve, and vitreous, producing reduced vision or blindness if left untreated. 

Q: What are structures of the uveal tract?

A: Structures of the uveal tract are composed of the iris, the ciliary body, and the choroid: 

• The iris is the colored circle at the front of the eye. It defines eye color, secretes nutrients to keep the lens healthy, and controls the amount of light that enters the eye by adjusting the size of the pupil (opening).
• The ciliary body is located between the iris and the choroid. It helps the eye focus by controlling the shape of the lens and it provides nutrients to keep the lens healthy.
• The choroid is a thin, spongy network of blood vessels, which primarily provides nutrients to the retina in the back of the eye.¹

Uveitis may be caused by problems or diseases occurring in the eye itself or it can be part of an inflammatory disease affecting other parts of the body. The uveal tract has a rich supply of blood vessels that contain immune cells to fight microbial invasion. These immune cells are lymphocytes, phagocytes, and plasma cells.

The uvea can be attacked by autoimmune antibodies produced in autoimmune diseases that affect similar tissues in other parts of the body such as psoriasis, Behcet’s syndrome, multiple sclerosis, sarcoidosis, Vogt Koyanagi Harada’s disease, and celiac disease.

Uveitis can last for a short (acute) or a long (chronic) time. The severest forms of uveitis reoccur many times.

What Is Non-Infectious Uveitis In Celiac Disease and/or Gluten Sensitivity?

• Relationship between non-infectious uveitis and celiac disease. Non-infectious uveitis affecting both eyes is a feature of riboflavin deficiency due to malabsorption in celiac disease and can present the patient with undiagnosed celiac disease.
• Relationship between non-infectious uveitis and riboflavin. Because riboflavin is required to maintain healthy eyes, riboflavin deficiency allows for degenerative changes to the uveal tract. Degenerative changes hinder the ability of these structures to protect against infection. Specifically, adequate riboflavin reduces cellular oxidative stress and appears to be able to regulate both innate (local inflammation) and immune responses and exhibits powerful anti-inflammatory properties.²
• Relationship between non-infectious uveitis and autoimmune activity. Uveitis can  be a response to autoimmune activity in uveal tissues due to celiac disease. The risk of uveitis remained significantly increased even 5 years after celiac disease diagnosis.³ 
• Relationship between non-infectious uveitis and infection. Any uveal tract infections that might develop because of inflammation are considered to be serious and would require immediate medical attention to prevent damage leading to blindness.
• Relationship between non-infectious uveitis and diet. Case reports of patients with undiagnosed celiac disease and uveitis show that uveitis, even when longstanding and unresposive to drug therapies, responds quickly to a gluten free diet.⁴,⁵,⁶

What Is the Prevalence Of Uveitis In Celiac Disease and/or Gluten Sensitivity?

A nationwide study found a moderately increased risk of uveitis in patients with biopsy-verified celiac disease. The risk of uveitis remained significantly increased even 5 years after celiac disease diagnosis.³

What Are The Symptoms Of Uveitis?

Non-infectious uveitis is marked by these symptoms in both eyes:

• Itching that feels dry and burning if rubbed.
• Painful burning of eyes.
• Light sensitivity.
• Increased floaters (seeing tiny spots that are sloughing cell debris in the anterior chamber of the eye).
• Redness.
• Blurred vision because of the uneven eye surface that develops from inflammation. 

How Does Uveitis Develop In Celiac Disease and/or Gluten Sensitivity?

• Non-infectious uveitis results from riboflavin deficiency due malabsorption caused by enteropathy in celiac disease.
• Uveitis also results from autoimmune activity in celiac disease.

Does Bilateral Uveitis Respond To Gluten-Free Diet?

Yes. Uveitis caused by riboflavin deficiency resolves quickly on gluten free diet containing adequate riboflavin.⁴,⁵,⁶

6 Steps To Improve Uveitis In Celiac Disease and/or Gluten Sensitivity:

• [dropcap]1[/dropcap]Remove the Trigger. Maintain a Strict, Nutritious Gluten Free Diet:

[box type=”shadow” ]Treatment. This condition responds to the complete elimination of gluten, which is the required treatment that improves both eye and gut health.

• Gut health is the foundation to restore ALL health. Restored health will enable you to maintain a strict gluten free diet, just as other life tasks will be easier.
• A strict gluten free diet means removing 100% of wheat, barley, rye and oats from the diet.
• Cutting out bread and other obvious sources of gluten is not good enough for recovery. Even 1/8th teaspoon of flour or bread crumb is enough to sustain the inflammation that is damaging your small intestine, causing increased permeability (leaky gut) and allowing undigested gluten to enter your body where it can damage structures and function, and instigate immune inflammatory responses.

Correct Your Individual Nutritional Needs.

• Eat foods that can replenish missing nutrients. Find them under NUTRIENT DEFICIENCIES.
• Take nutritional supplements as needed. Find them under NUTRIENT DEFICIENCIES.

Recovery. You should begin to feel better within a week and notice more energy as inflammation subsides and the  absorbing cells that make up the surface lining of your small intestine are better able to function.

• Intestinal lining cells are replaced every 5 days. The healing process is like sunburn where the damaged surface layer of skin sloughs off and is replaced with new normal cells.
• Leaky gut normally resolves in two month after starting a gluten free diet and brings about a big improvement in health. Improvement in intestinal permeability precedes morphometric recovery (cell appearance and structure) of the small intestine in celiac disease.⁷
• The intestinal lining may take up to a year to heal.[/box]

• [dropcap]2[/dropcap] Reduce Inflammation. Foods to Eat and Foods Not to Eat:

Because gluten is inflammatory, eliminate OTHER inflammatory foods from your diet to reduce an additive effect to gluten. At the same time, try to eat foods that reduce inflammation (anti-inflammatory).

[box type=”shadow” ]Here Are Major Inflammatory Food Types That Reduce Healing:

• Damaging Foods. In susceptible persons, includes corn, dairy (cow), and soy. Lactose, the sugar in any animal milk disrupts intestinal permeability causing leaky gut.⁸
• Allergenic Foods. Includes foods that trigger the immune sytem to produce IgE antibodies. Allergy testing is the usual way to discover these offending foods.
• Shelf Stable Processed Foods. Includes any that contain additives and preservatives. Look for them on the nutrition label of the box or package. Additives and preservatives also disrupt intestinal permeability causing leaky gut.⁸
• Fats. Limit deep fried foods, trans-fats, saturated fats (animal fat/butter), and EXCESSIVE omega-6 fatty acid oils like corn oil. Rancid fats, sodium caprate (a medium chain fat), and sucrose monester fatty acid (a food grade surfactant) induce significant disruption of the intestinal barrier that causes leaky gut.⁸.
• Excessive Refined White Flours (bran layer removed). Includes products made from them such as cookies, bread, cakes, pies. Bran contains the vitamins and minerals that metabolize grains and slows the otherwise rapid entry of sugar from their digestion into the bloodstream. Also disrupt intestinal permeability causing leaky gut.⁸
• Refined Sugars.  Includes white sugar, corn fructose and high fructose corn syrup.
• Certain Spices. Includes paprika and cayenne pepper which disrupt intestinal permeability causing leaky gut.⁸
• Alcohol and Caffeine. Disrupt intestinal permeability causing leaky gut.⁸[/box]

[box type=”shadow” ]Here Are Important Anti-Inflammatory Food Types to Promote Health:

• Fruits. Contain ample amounts of vitamins, minerals and phytochemicals which are naturally occuring components in plants that detoxify toxins, carcinogens (reducing the risk by 50%) and mutagens.
• Non-Starchy Vegetables. Support intestinal integrity and provide ample amounts of vitamins, minerals and phytochemicals. Includes lettuce, kale, onion, broccoli, garlic, and others.
• High Quality Complex Carbohydrates. Provide vitamins, minerals, and fiber while boosting serotonin levels to help you relax and feel calm. Includes whole grains, legumes, and root vegetables such as carrots, parsnips, sweet potatoes, turnips, red beets, and others.
• Antioxidants. Protect the body from inflammatory oxidant molecules that continually occur and help us handle stress and reduce irritability. Includes vitamin C-containing foods such as lemon, grapefruit, apricot, Brussels sprouts and strawberries, and others. Also, includes vitamin E-containing foods such as nuts, seeds, avocado, olive oil, and others. Cocoa is good, too.
• Omega-3 Fatty Acids. Balance opposing omega-6 fatty acids and bad fats. Fish sources includes tuna, salmon, cod, and others. Plants sources include flax, chia seeds, canola oil, and others.
• Probiotics. Supply normal microbes needed for colon health and health of the body such as these fermented foods: yogurt, kefir, and unpasteurized apple cider vinegar.
• Prebiotics/ High Fiber Foods.  Food with fiber keeps our population of colonic microbes healthy.
• Protective Herbs and Spices.  See below #6 below for examples.[/box]

• [dropcap]3[/dropcap] Information Sheet You Can Take to Your Doctor or Other Health Professional:

Click here.

• [dropcap]4[/dropcap] Manage Your Medications Safely:

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Certain medications deplete riboflavin (vitamin B2) that can cause bilateral uveitis.  Ask your doctor or pharmacist about this possible adverse effect if you are taking these drugs.

FEMALE HORMONES disrupt intestinal permeability which complicate celiac disease.

• Oral Contraceptives (Norinyl®, Ortho-Novum®, Triphasil®, and others) deplete Vitamin B2.
• Oral Estrogen/Hormone Replacement (Evista®, Prempro®, Premarin®, Estratab® and others) deplete Vitamin B2.

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• [dropcap]5[/dropcap]Nutritional Supplements To Help Correct Deficiencies:

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The type and quantity of nutritional supplements that may be needed depend on which nutrients are deficient.

• Multivitamin/mineral combination once a day is useful to improve overall nutrient levels. This is a safe dose, but always check with your doctor to avoid interactions with medications. Riboflavin is part of this supplement.
• Riboflavin as prescribed or B-Vitamin Complex that delivers 100% to 300% of RDA. Note: Formulation in the thousands deplete minerals as their excess is eliminated from the body in urine.

Storage Note: Store container tightly sealed, away from heat, moisture and direct light to avoid loss of potency. That is, in a safe kitchen cabinet – not in the bathroom or on the kitchen table.[/box]

• [dropcap]6[/dropcap]Manage Natural Remedies: 

[box type=”shadow” ]Hydration:

• Eight glasses of water are recommended per day unless there is a contraindication such as kidney or heart disease. The Institute of Medicine recommends approximately 2.7 liters (91 ounces) of total water, from all beverages and foods, each day for women and 3.7 liters (125 ounces) daily of total water for men.
• If you are thirsty, drink water. Add fresh, squeezed lemon to water. Lemon is anti-inflammatory, alkalizing and provides vitamin C.
• Hydration Test: Urine should be pale yellow. Fingertips should be plump, without pruning but this may not be reliable when fingers are swollen with edema. Lips should be plump, without puckering. The feeling of thirst can be unreliable.
• What is wrong with soda, coffee, tea, and alcohol? These drinks are dehydrating, increase acid, and deplete nutrients.[/box]

[box type=”shadow” ]Carminatives. The following  anti-inflammatory plant sources called carminitives help heal the digestive tract. They also tone the digestive muscles which improves peristalsis, thus aiding in the expulsion of gas from the stomach and intestine to relieve digestive colic and gastric discomfort.

Carminative Food Remedies:

• Raspberry.
• Carrot is also a cleansing digestive tonic.
• Grape is also bile stimulating and a cleansing remedy for sluggish digestion and laxative.
• Redbeets also stimulate and improve digestion and are easily digested.
• Cabbage also stimulates and improves digestion and is also a liver decongestant.
• Lettuce also stimulates and improves digestion and is also an alterative, meaning it improves the function of organs involved with the digestion and excretion of waste products to bring about a gradual change.
• Potatoes are antispasmodic (due to atropine like properties) and a liver remedy.

Carminative Herb Remedies:

• Sage is also a digestive, astringent, bile stimulant and energy tonic that heals the mucosa.  Drink as tea or use in cooking.
• Chamomile, lemon balm, and fennel, (as a tea) also help relieve nervous tension.
• Parsley also relieves indigestion.
• Rosemary as a tea and in cooking also is a nervous system tonic for stress and fatigue, bile stimulant, and can relieve headaches and indigestion.
• Thyme is also soothing remedy useful for stimulating digestion of rich, fatty foods.

Carminative Spice Remedies:

• Cloves are also antispasmodic.
• Nutmeg is also useful for indigestion.
• Ginger.[/box]

[box type=”shadow” ]Exercise Helps:

Exercise improves circulation and rids the body of toxins.

• Walking is aerobic exercise that reconditions the whole body to improve stamina. Read more about Exercise and Fitness.
• Weight training builds muscle. Read more about Exercise and Fitness.
• Stretching improves flexibilty. Read more about Exercise and Fitness.

Note: Exercise is important, but the amount and type of exercise undertaken depends on your health. Your first priority is to heal. [/box]

What Do Medical Research Studies Tell About Uveitis In Celiac Disease and/or Gluten Sensitivity?

RESEARCH STUDY SUMMARIES

“Increased risk of uveitis in coeliac disease: a nationwide cohort study.” This nationwide study investigating the risk of uveitis in patients with biopsy-verified celiac disease found a moderately increased risk of uveitis in patients with biopsy-verified celiac disease. Celiac disease might be considered in patients with uveitis of unknown etiology.

Small intestinal biopsy reports performed between July 1969 and February 2008 were collected from all 28 pathology departments in Sweden. From these reports, 29,044 patients with celiac disease  (equals villous atrophy, Marsh 3) were identified. Uveitis was defined according to relevant International Classification of Disease codes in the Swedish National Patient Register. Cox regression was used to estimate hazard ratio (HR) for uveitis in individuals with celiac disease compared with those in reference individuals matched for age, sex, county and calendar year.

During follow-up, 148 patients with celiac disease developed uveitis (expected count 112), corresponding to a HR of 1.32. The absolute risk of uveitis was 50/100,000 person-years in celiac disease. The risk estimate did not change more than marginally when adjusted for type 1 diabetes, rheumatoid arthritis and autoimmune thyroid disease (HR 1.30).The risk of uveitis remained significantly increased even 5 years after celiac disease diagnosis (HR 1.31).⁹

CASE REPORT SUMMARIES

“Uveitis in celiac disease with an excellent response to gluten-free diet: third case described.” This report describes the case of a patient with celiac disease who achieved a complete response to a gluten-free diet. A 28-year-old woman presented with diarrhea, oral ulcers, and refractory uveitis (unresponsive to therapy) of 2.5-years duration. She was treated with prednisone, mydriatic drops, and infliximab with no response. She was referred to our hospital at which point her previous diagnosis of uveitis was confirmed; she was also diagnosed with right-sided sacro-ileitis. The patient did not have arthritis or any skin conditions. Three tests for fecal parasites and a fecal leukocyte were negative. Endoscopy revealed atrophic appearance of the duodenal mucosa. Biopsy showed atrophy of the duodenal villi with intra-epithelial lymphocytes, hyperplasia of the crypts, and chronic inflammatory infiltrate. The search for antiendomysial antibody was greater than 1/1,280.

The patient was started on a gluten-free diet and after 3 months demonstrated significant improvement of gastrointestinal symptoms and uveitis, as well as a reduction of antiendomysial antibodies (1/80). After 6 months, there was complete remission of gastrointestinal symptoms and total control of uveitis. The antiendomysial antibody was negative at that time. Clinical uveitis as a manifestation of celiac disease has been described in only two cases in the literature. This case study is the third to demonstrate that uveitis is a clinical symptom that can be addressed in patients with celiac disease.¹⁰

“Uveitis: a rare presentation finding of celiac disease in childhood.” This case report describes diagnosis of celiac disease with subsequent resolution of uveitis in an 11-year-old girl who was referred to outpatient clinic because of short stature.  She had been diagnosed as uveitis of the right eye a month before. She did not have any gastrointestinal symptoms and no history of oral or genital ulcers. Her weight was 32 kg (<3rd percentile) and her height was 126 cm (<3rd percentile); her systemic examination was normal. Biomicroscopic examination of the right eye revealed posterior synechiae.

Laboratory examinations demonstrated normal complete blood count. Erythrocyte sedimentation rate was 24 mm/h and C- reactive protein was 0.2 mg/dl (0-0.8). Liver and renal function tests and electrolytes were as follows: alanine aminotransferase 54 U/L, aspartate aminotransferase 26 U/L, blood urea nitrogen 14.5 mg/dl, serum creatinine 0.3 mg/dl, sodium 141 mEq/L, potassium 4.46 mEq/L, glucose 91 mg/dl, calcium 9.9 mg/dl, phosphorus 4.5 mg/dl, alkaline phosphatase 173 U/L, total protein 7.6 g/dl, and albumin 4.8 g/dl. Thyroid function tests, urine analysis and complement levels were normal, and antinuclear antibody, anti-dsDNA, and thyroid- specifıc autoantibodies were negative. Bone age was consistent with 11 years. Because of her short stature and growth failure, celiac antibodies were studied. As antigliadin IgG and antiendomysium IgA antibodies were strongly positive, endoscopic small bowel biopsy was performed, and diagnosis of type 3b celiac disease was established.

A gluten-free diet was started and steroid therapy for uveitis was continued. Juvenile idiopathic arthritis. Increase in height and weight gain were established with gluten-free diet at the end of six months, and uveitis was completely treated. She has been followed for two years with negative antiendomysium IgA antibodies, and ophthalmologic examination showed no signs of uveitis.¹¹

“Uveitis responding on gluten free diet in a girl with celiac disease and diabetes mellitus type 1.” This report describes the case of a 9-year old girl with a history of diabetes mellitus type 1, who presented with visual loss of the left eye. The right eye examination was unremarkable. Slit-lamp examination revealed few small and fine keratic precipitates. 2+ flare was noted in the vitreous. There was no choroiditis, papillitis or retinal vasculitis. No etiology was found. The patient was treated by topical and systemic corticosteroids without any improvement. Celiac disease was discovered by the presence of celiac antibodies in the work-up of joint pain and diabetes mellitus type 1. Antiendomysium antibodies and anti-transglutaminase antibodies were both positive. A small bowel biopsy confirmed celiac disease.

A gluten free diet was set up and corticosteroids were tapered off. Recovery of the uveitis was obvious during gluten free diet and normalized within two months.¹²

“Uveitis complicating celiac disease and cured by gluten-free diet.” This case report describes a patient with uveitis and celiac disease who was cured by a gluten free diet.⁴

Sources:

1. http://www.nei.nih.gov/health/uveitis/uveitis.asp [↩]
2. Ghosal A, Said HM. Mechanism and regulation of vitamin B2 (riboflavin) uptake by mouse and human pancreatic β-cells/islets: physiological and molecular aspects. Am J Physiol Gastrointest Liver Physiol. 2012 November Vol. 303no. G1052-G1058DOI: 10.1152/ajpgi.00314.2012 [↩]
3. Mollazadegan K, Kugelberg M, Tallstedt L, Ludvigsson JF. Increased risk of uveitis in coeliac disease: a nationwide cohort study. Br J Ophthalmol. 2012 Jun;96(6):857-61. doi: 10.1136/bjophthalmol-2011-301051. [↩] [↩]
4. Hyrailles V; Desprez D; Beaurere L; et.al. Uveitis complicating celiac disease and cured by gluten-free diet. Gastroenterologie clinique et biologique. May 1995;19(5):543-4. [↩] [↩] [↩]
5. Krifa F, Knani L, Sakly W, Ghedira I, Essoussi AS, Boukadida J, Ben Hadj Hamida F. Uveitis responding on gluten free diet in a girl with celiac disease and diabetes mellitus type 1. Gastroenterol Clin Biol. 2010 Apr-May;34(4-5):319-20. doi: 10.1016/j.gcb.2010.03.006. [↩] [↩]
6. Klack K, Pereira RM, de Carvalho JF. Uveitis in celiac disease with an excellent response to gluten-free diet: third case described. Rheumatol Int. 2011 Mar;31(3):399-402. doi: 10.1007/s00296-009-1177-z. [↩] [↩]
7. Cummins AG, Thompson FM, Butler RN, et al. Improvement in intestinal permeability precedes morphometric recovery of the small intestine in coeliac disease. Clinical Science. Apr 2001;100(4):379-86. [↩]
8. Farhadi A, Banan A, Fields J, Keshavarzian A. Intestinal barrier: an interface between health and disease. Journal of Gastroenterology and Hepatology. 2003;18:479-91. [↩] [↩] [↩] [↩] [↩] [↩]
9. Mollazadegan K, Kugelberg M, Tallstedt L, Ludvigsson JF. Increased risk of uveitis in coeliac disease: a nationwide cohort study. Br J Ophthalmol. 2012 Jun;96(6):857-61. doi: 10.1136/bjophthalmol-2011-301051. [↩]
10. Klack K, Pereira RM, de Carvalho JF. Uveitis in celiac disease with an excellent response to gluten-free diet: third case described. Rheumatol Int. 2011 Mar;31(3):399-402. doi: 10.1007/s00296-009-1177-z. [↩]
11. Arikan-Ayyildiz Z, Uslu N, Balamtekin N, Saltik-Temizel IN. Uveitis: a rare presentation finding of celiac disease in childhood. Turk J Pediatr. 2011 Mar-Apr;53(2):235-6. [↩]
12. Krifa F, Knani L, Sakly W, Ghedira I, Essoussi AS, Boukadida J, Ben Hadj Hamida F. Uveitis responding on gluten free diet in a girl with celiac disease and diabetes mellitus type 1. Gastroenterol Clin Biol. 2010 Apr-May;34(4-5):319-20. doi: 10.1016/j.gcb.2010.03.006. [↩]