The eye is a small but very intricate structure. Its evolution is complex with a postulated time span of some 540 million years. 

Eyes are generally adapted to the environment and life requirements of the organism which bears them. From a human perspective the eye not only has a function for photoreception but can often be a barometer of illness. The statement of “the eyes being a window to the soul” can also be based on the fact that virtually all of the systemic inflammatory diseases that require a rheumatology input tend to affect the eye or its surrounding structures. 

This link between the symbol of the eye and health can be seen to stretch back to ancient Egypt. The Eye of Horus is an ancient Egyptian symbol of protection, royal power and good health. What might the rheumatologist see when looking through the “windows to the soul”?

Uveitis

The most common systemic illness associated with uveitis is ankylosing spondylitis (AS). Anterior uveitis is more common than posterior or intermediate uveitis. About 50% of individuals who develop an anterior uveitis are HLA-B27-positive. 

The uveitis associated with HLA-B27 is almost always unilateral, recurrent, is of relatively short duration, eg. less than three months, resolves completely between attacks, and is associated with reduced intraocular pressure. 

This is in direct contrast to anterior uveitis caused by herpes simplex, which is recurrent and has a raised intraocular pressure. Hypopyon, namely pus in the eye, of the anterior chamber is occasionally present in HLA-B27-associated uveitis. Recurrent episodes can affect the other eye, but it is extremely rare for both eyes to be involved.

Uveitis associated with reactive arthritis is indistinguishable from uveitis associated with AS. Although conjunctivitis is part of the traditional triad of reactive arthritis it is uncommon. Of note the triad for reactive arthritis is uveitis, urethritis and arthritis, which is often remembered by medical students by “cant see, can pee, cant climb a tree”. 

Approximately 5% of patients with inflammatory bowel disease and 7% of patients with psoriatic arthritis also develop uveitis. Although some of these patients have disease that is unilateral, anterior and recurrent, many have disease that is bilateral, chronic and posterior to the lens. It is also important to note that it has been reported that half of all patients with Crohn’s disease or psoriatic arthritis (PsA) and uveitis are HLA-B27-positive.

Sarcoidosis

Sarcoidosis is also associated with uveitis. In the US it is the second most common systemic disease associated with uveitis. Sarcoidosis is associated with affecting a wide range of structures within the eye. These include the orbit, anterior uvea, lacrimal gland, vitreous humour, retina and optic nerve. Sarcoidosis frequently manifests initially as an eye problem, almost as frequently as lung symptoms. The sensitivity and specificity of a serum angiotensin-converting enzyme level for sarcoid that is primarily ocular is unknown. 

Behçet’s syndrome

Juvenile idiopathic arthritis, Behçet’s syndrome, relapsing polychondritis and vasculitis such as Kawasaki disease are also associated with uveitis. In Behçet’s syndrome, uveitis is often the symptom that directs the therapy. That being so it is often the symptom that most requires systemic immunotherapy. Eye inflammation is usually bilateral and recurrent. With recurrences in the setting of Behçet’s syndrome there tends not to be complete resolution between attacks. Ultimately the hallmark of Behçet’s syndrome-associated uveitis is a retinal vasculitis and retinal arteries are especially prone to be affected. The visual prognosis with Behçet’s syndrome is poor and blindness is frequent in untreated eye disease. 

Treatment of uveitis

The therapy of uveitis depends on multiple factors, such as severity, location, patient preference and the specific diagnosis. Systemic immunosuppressive therapy is generally reserved for patients with active, non-infectious causes of inflammation. For systemic immunosuppression to be indicated, usually the inflammation is bilateral and severe enough to interfere with activities of daily living. A variety of immunomodulatory medications have been tried and these include azathioprine, cyclophosphamide, methotrexate and infliximab. 

Scleritis

Scleritis often is divided into five categories: diffuse anterior, nodular, necrotising, scleromalacia perforans and posterior. The first three each result in a red, painful eye. 

Pain is more variable in scleromalacia perforans, in which a nodule pathologically similar to a rheumatoid nodule forms in the sclera. Pain is also variable with posterior scleritis and, as it can occur in a localised fashion at the back of the eye, the eye may not be red. 

It is estimated that 50% of patients with scleritis have an associated systemic illness, the most common illness being rheumatoid arthritis (RA). It is unusual for scleritis to be an initial manifestation of RA, however in those who do develop scleritis it has been reported that they have a shorter life expectancy compared to other patients with RA.

Wegener’s granulomatosis is probably the second most common disease associated with scleritis. It can often be the initial manifestation. Therefore it would be advised that it should be routine to obtain anti-neutrophilic cytoplasmic antibody serology on any patient who presents with scleritis without obvious systemic disease. 

Orbital disease

Graves’ disease is the most common orbital inflammatory disease, while from a rheumatology perspective Wegener’s granulomatosis is the disease that most commonly affects the orbit. The inflammation can be extremely painful and may result in blindness. 

Inflammation is sometimes more recalcitrant to therapy than other aspects of Wegener’s granulomatosis. 

There is evidence now being published in the rheumatology literature that rituximab may be the treatment of choice for these patients.

Optic neuritis

Disease of the optic nerve can result for many reasons. These include vascular insufficiency as occurs in giant cell arteritis, immunologic attack, and toxic substances which can include medications in certain situations. Regarding immune-mediated disease, that most commonly associated is multiple sclerosis. 

From a rheumatology viewpoint, temporal arteritis is the most important condition that affects the optic nerve, with sudden blindness the most feared consequence. In temporal arteritis there is granulomatous inflammation of multiple arteries, which frequently includes the temporal artery and the posterior ciliary arteries. 

Inflammation in these latter vessels leads to anterior ischaemic optic neuropathy (AION), which is ischaemia of the optic nerve that manifests as sudden visual loss. Temporal arteritis can also affect the central retinal artery, which may also result in blindness. It is important to recognise that temporal arteritis can cause diplopia by affecting circulation to extraocular muscles. 

Anterior ischaemic optic neuropathy

The loss of vision associated with temporal arteritis is frequently labelled arteritic AION to distinguish it from the more common non-arteritic AION that is usually attributable to small vessel artherosclerosis. Patients with arteritic AION are typically older than 50 years and have an erythrocyte sedimentation rate (ESR) of > 50mm/hr. 

Many patients with arteritic AION have associated symptoms of polymyalgia rheumatica, jaw claudication, scalp tenderness or temporal artery tenderness. The biopsy of the temporal artery shows vasculitis in about 80% of patients if an adequate length of vessel is sampled. 

A negative biopsy result in a symptomatic patient should be taken as a false negative based on sampling of an unaffected area of the vessel. The reason for such is that non-treatment of a patient with temporal arteritis can result in irreversible blindness.