Diagnosing, treating ocular manifestations of rheumatoid arthritis

August 23, 2013

Optometrists need to understand RA and how to manage its ophthalmic impact on patients.

Optometrists are often confronted with patients who suffer from a myriad of systemic diseases, many of which have ocular sequelae. One very common systemic disease that has many ocular manifestations is rheumatoid arthritis (RA). RA is a chronic autoimmune disease characterized by a symmetrical and destructive joint inflammation. In addition to causing joint problems, rheumatoid arthritis can often affect other organs of the body, such as the skin, eyes, lungs, and blood vessels.

Dr. BowlingThese patients will grace your door, and it is important that we be able to recognize the ocular effects of RA as well as understand its effects on the body. Because RA can produce wide-ranging ocular manifestations-including dry eye, episcleritis, keratitis, and keratoconjunctivitis sicca-optometrists need to understand not only the disease, but also how to manage its ophthalmic impact on patients.

RA is seen throughout the world and affects all races, about 0.8% of the general population,1 affecting women approximately 3 times more often than men. The disease is most often seen after age 40,1 but people of any age can be stricken with the disease. The onset of RA is most frequent during the fourth and fifth decades of life.2 The disease prevalence increases with age, and that threefold difference between the sexes diminishes in older age groups.2

Studies of affected family members show there is some genetic predisposition. Severe RA is found at approximately 4 times the expected rate in first-degree relatives of individuals with the disease associated with RFs present. About 10% of patients with RA will have an affected first-degree relative.1

The exact cause of RA remains unknown. It has been suggested that RA may be a response to an infectious agent in a genetically susceptible host,3,4 but convincing evidence that infectious agents may cause RA has not emerged. Environmental factors play a role in the etiology of the disease. Climate and urbanization have a major impact on incidence and severity. Smoking has also been identified as a risk factor for RA.1,3

Clinical, ophthalmic manifestations

Clinically, RA is a chronic inflammation of multiple joints. In approximately two thirds of patients it begins insidiously with fatigue, anorexia, generalized weakness, and musculoskeletal symptoms until the appearance of synovitis (inflammation in the lining of a joint) becomes apparent.2 Joints become swollen, tender, and warm; stiffness limits their movement. With time, multiple joints are affected, and the joints may become disfigured and immobile. The most commonly involved joints are in the hands, feet, and cervical spine, but larger joints like the knee and shoulder can be affected (see Figure 1).

Figure 1. Chronic joint inflammation in rheumatoid arthritis.Ocular manifestations occur in 25% of patients with RA.5 Keratoconjunctivitis sicca (KCS) is the most common ocular manifestation of RA; it occurs in 15-25% of patients.5 Episcleritis and scleritis occur less often-0.17% incidence of episcleritis and 0.67% incidence of scleritis have been reported.6 RA is the most common systemic condition associated with scleritis. Ocular involvement, severe dry eye in particular, may exist independently from severe RA presentations, and the eyes should be evaluated in all patents with RA, regardless of whether ocular manifestations are present.7

Dry eye and RA

Dry eye is the most common ophthalmic manifestation of RA, with a reported prevalence of 15-25%.8,9 Lacrimal and salivary gland secretion are significantly reduced in patients with RA. While it is well known that dry eye is frequently associated with RA, the correlation between dry eye severity and the activity of RA is unclear. One study has shown that there is no significant correlation between the disease activity and the severity of dry eye.7

The initial treatment of KCS in RA remains ocular surface lubrication with artificial tear substitutes and lubricating ointments. Non-preserved preparations are a more desirable choice. In eyes that are non-responsive to topical lubrication alone, consider additional medical interventions. A mild topical steroid 2 to 4 times per day can help treat the underlying inflammation often associated with dry eye (see Figure 2).

Sjögren’s syndrome commonly accompanies RA.10 The full triad of Sjögren’s syndrome consists of KCS (dry eyes), xerostomia (dry mouth), and a connective-tissue disorder, usually RA.11 RA may also cause dysfunction of other organs such as the kidneys (amyloidosis), gastrointestinal system (peptic ulcers), heart and blood vessels (cardiovascular disease, myocardial infarction), lungs (fibrosis), liver (anemia), pancreas (insulin resistance), and the central nervous system. Patients may also experience extreme fatigue and joint pain, and have a higher risk of developing lymphoma.12

Episcleritis and scleritis

Both episcleritis and scleritis are classically described in patients with RA. Episcleritis is sudden in onset, and the patient complains of discomfort rather than pain. Attacks last 1 to 2 weeks and are self-limiting but recur at intervals of 1 to 3 months. The prevalence of episcleritis in RA is reported to be about 0.17%, and in patients who present with episcleritis, about 5.6% have RA.2 There are two types of episcleritis, which are clinically different-simple and nodular; about one third of cases are bilateral. Between the two forms of episcleritis, simple episcleritis is more common in patients with RA. The presence of subconjunctival nodules that are mobile over the sclera differentiates nodular episcleritis from simple episcleritis.5,9 Both forms of episcleritis can be confused with severe conjunctivitis because of the bright red appearance of the eye. Therefore, diagnosis should be differentiated with the help of a thorough history and physical examination. Treatment of episcleritis is usually unnecessary, but in patients with significant discomfort, lubricant and topical NSAIDs may provide some relief. 

Figure 2. Lissamine green staining of cornea and conjunctiva in a patient with RA.Scleritis in RA is associated with a more ominous prognosis than episcleritis. Scleritis and episcleritis are distinguished on the basis of anatomy and appearance. Symptoms may be similar, but the pain in scleritis is more severe and more evident. One way to differentiate the two is to palpate the globe. After asking the patient to look down with eyelids closed, gently press on the globe. Patients with scleritis have tenderness on palpation, while those with episcleritis do not.13 The prevalence of scleritis on RA is reported to be 0.67% to 6.3%, although as many as 33% of all patients presenting with scleritis may have RA.2 In fact, RA is the most common systemic condition associated with scleritis. Patients complain of insidious onset of a deep, boring pain that may radiate to the forehead or jaw. Active scleritis involves inflammation of the deep episcleral layer associated with scleral edema. It tends to be bilateral in patients with RA.14,15


Corneal involvement often occurs along with anterior scleritis, but rarely with episcleritis. Sclerosing keratitis occurs adjacent to the inflamed sclera and is characterized by corneal opacification and vascularization.15 The scarring does not disappear with treatment, and may progress with recurrences of the scleritis.

Peripheral ulcerative keratitis (PUK) occurs in many systemic diseases, including RA. Signs of active PUK include guttering within the corneal limbus and corneal thinning. There is usually congestion and elevation of adjacent conjunctiva.2

Central ulcerative keratitis (CUK) occurs due to shedding of the corneal epithelium followed by keratolysis, rapid corneal stromal melting. It occurs in a relatively non-inflamed eye without prominent infiltration. The pathophysiology is not well understood, although a T-cell-mediated auto immune process has been described.2

Other ophthalmic involvement in RA

Cranial nerve palsies and geniculocortical blindness have been reported in RA. Orbital apex syndrome (characterized by retro-orbital paralysis of extraocular muscles, impairment of the branches of the 1st division of the trigeminal nerve, and, frequently, extension to involve the optic nerve) resulting from orbital rheumatoid nodules has also been described.16 Venous stasis retinopathy, as a rare complication, has been described in RA as part of a hyperviscosity syndrome secondary to polyclonal gammopathy.17 RA can cause Brown’s syndrome, a type of restrictive strabismus due to superior oblique tendon nodules with inflammation where there is limitation of elevation in adduction.18

Complications of systemic treatment

Long-term use of oral steroids in treating RA can produce posterior subcapsular cataracts. Although the opacities may remain stationary or progress, they rarely regress when the drug is discontinued.19 Chronic topical or systemic steroids can also result in glaucoma.20 Ocular side effects of methotrexate, an antimetabolite and antifolate drug used in treating RA, include periorbital edema, blepharitis, conjunctival hyperemia, increased tearing, and photophobia. The drug has been found in the tears and may cause ocular irritation requiring lubricant therapy.2 The use of antimalarial drugs chloroquine (CQ) and hydroxychloroquine (HCQ) are associated with ocular toxic effects. The ocular toxic effects of CQ and HCQ include corneal deposits and pigmentary retinopathy. Whorl-like corneal epithelial deposits, called vortex keratopathy (also known as cornea verticillata), may occur in patients on CQ. Up to 95% of patients on treatment with CQ exhibit corneal deposits,21 compared with approximately 10% of patients taking HCQ.

The occurrence of corneal deposits was found as a statistically significant predictor of mild retinopathy.22 Retinopathy associated with CQ or HCQ is reportedly related to duration of treatment, total dose, and patient age. The retinopathy can range from fine pigmentary mottling with loss of foveal reflex to a “bull’s-eye” maculopathy consisting of a central hyperpigmented zone surrounded by a relatively depigmented ring, which, in turn, is surrounded by a hyperpigmented ring. In advanced cases, retinal arteriole attenuation and optic disc pallor may be observed and the retinopathy may be irreversible.23

Your patients with RA need your expertise in caring for the possible ocular manifestations of this disease and may need you to coordinate their systemic care. This is a great opportunity to contact the patient’s general physician to make him or her aware of your findings and to show your patient you are capable of managing all of his ocular problems.ODT


1.   Lipsky PE. Rheumatoid Arthritis. In Fauci AS, Kasper DL, Longo DL, eds, Harrison’s Principles of Internal Medicine, 17th ed. New York, 2008, McGraw-Hill.

2.   Anitha B. Ocular manifestations of rheumatoid arthritis: Correlation with disease activity and management protocols. Masters Thesis. Rajiv Gandhi University of Health Sciences, Karnataka, Bangalore, 2011.

3.   Gregersen PK, Silver J, Winchester RJ. The shared epitope hypothesis: An approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis, Arthritis Rheum. 1987;30(11)1205-1213.

4.   Zvaifler NJ. Rheumatoid Arthritis. In Stein JH, ed. Internal Medicine, 5th ed. St. Louis, 1998, Mosby.

5.   Fuerst DJ, Tanzer DJ, Smith RE. Rheumatoid diseases. Int Ophthalmol Clin 1998; 38(4):47–80.

6.   Dana R, Chong E, Foster CS. Adult Rheumatoid Arthritis. In Albert DM, Miller JW, eds. Albert Jakobiec’s Principles and Practice of Ophthalmology, 3rd ed. Philadelphia, 2008, Saunders.

7.   Fujita M, Igarashi T, Kurai T, et al. Correlation between dry eye and rheumatoid arthritis activity. Am J Ophthalmol 2005; 140(5);808-813.

8.   McGavin DD, Williamson J, Forrester JV et al. Episcleritis and scleritis: a study of their clinical manifestations and association with rheumatoid arthritis, Br J Ophthalmol 1976; 60(3):192-226.

9.   Harper SL, Foster CS. The ocular manifestations of rheumatoid disease. Int Ophthalmol Clin 1998; 38(1):1–19.

10. Hughes GRV, Whaley K. Sjögren’s syndrome. Br Med Journal 1972; 4(5839):533-536.

11. Bloch KJ, Buchanan WW, Wohl MJ, et al. Sjögren’s syndrome: A clinical, pathological, and serological study of sixty-two cases. Medicine (Baltimore) 1965; 44(5):187-231.

12. Sjögren’s Syndrome Foundation. About Sjogren’s. http://www.sjogrens.org/home/about-sjogrens-syndrome. Accessed 6-1-2013.

13. Patel SJ, Lundy DC. Ocular manifestations of autoimmune disease. Am Fam Physician 2002; 66(6):991-998.

14. Dana R, Chong E, Foster CS. Adult rheumatoid arthritis. In Albert DM, Miller JW, eds. Albert & Jakobiec’s Principles and Practice of Ophthalmology, 3rd ed. Philadelphia 2008: Saunders.

15. Sainz de la Maza M, Foster CS, Jabbur NS. Scleritis associated with rheumatoid arthritis and with other systemic immune-mediated diseases. Ophthalmology 1994; 101(7):1287-1288.

16. Konishi T, Saida T, Nishitani H. Orbital apex syndrome caused by rheumatoid nodules. J Neurol Neurosurg Psychiatry 1986; 49(4):460-462.

17. Sarnat RL, Jampol LM. Hyperviscosity retinopathy secondary to polyclonal gammopathy in a patient with rheumatoid arthritis, Ophthalmology 1986; 93(1):124-127.

18. Beck M, Hickling P. Treatment of bilateral superior oblique tendon sheath syndrome complicating rheumatoid arthritis, Br J Ophthalmol 1980; 64(5):358-361.

19. Jumping L, Tripathi RC, Tripathi BJ. Drug-Induced ocular disorders. Drug Safety 2008; 31(2):127-141.

20. Lowe TA. Rheumatoid Arthritis. In Thomann KH, Marks ES, Adamczyk DT, eds. Primary Eye Care in Systemic Diseases, 2nd ed. New York, 2001, McGraw-Hill.

21. Easterbrook M. Detection and prevention of maculopathy associated with antimalarial agents. Int Ophthalmol Clin 1999; 39(2):49-57.

22. Neubauer AS, Samari-Kermani K, Schaller U, et al. Detecting chloroquine retinopathy: electro-oculogram versus colour vision, Br J Ophthalmol 2003; 87(7):902-908.

23. Weiner A, Sandberg MA, Gaudio AR, et al. Hydroxychloroquine Retinopathy. Am J Ophthalmol 1991; 112(5):528-534.


Take-Home Message

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that produces ocular manifestations in 25% of patients with RA. The ocular manifestations include dry eye, episcleritis, keratitis, and keratoconjunctivitis sicca.