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Subspecialties Cornea / Ocular Surface, Practice Management, Education and Training

Uveitis 101

Up to 10 percent of blindness in the US is caused by uveitis (1); annual incidence ranges from 17 to 52 per 100,000 persons and increases with age (1, 2). Though it can be the result of viral, bacterial, fungal, or parasitic infection, uveitis in North America is most often associated with autoimmune disease. Here, three uveitis specialists present five clinical pearls that cover off presentation, diagnosis, investigation, and management. 

1. Ocular signs and symptoms may point towards the anatomical location of the eye inflammation
Acute eye pain, photophobia, and secondary headache are most often seen in an ophthalmology practice as symptoms of dry eye disease. But such symptoms can herald the onset of an acute attack of anterior uveitis – though few anterior chamber cells may be seen initially. Conjunctival injection, ciliary flush, and a poorly reactive pupil from posterior synechiae (see Figure 1A) are also signs of anterior segment inflammation. In severe cases, aggregates of inflammatory cells can be seen on the posterior cornea (see Figure 1B) and settle in the anterior chamber forming a hypopyon. A hypopyon is most often associated with HLA-B27 disease, Behçet disease, and corneal infections or endophthalmitis. Laterality is a helpful feature. Identifying unilateral versus bilateral inflammation will narrow down the list of differential diagnoses. For example, viral anterior uveitis is often unilateral and recurrent. Herpes viruses (VZV, HSV, CMV) are the second most common cause of anterior uveitis, occurring in 5–19 percent of cases, and may present with iris transillumination defects (see Figure 1C) (3). Floaters or visual disturbances in the absence of pain and redness typically indicates intermediate (vitreous) or posterior (retina or choroid) uveitis. In an epidemiological study of over 200,000 patients in the US, the prevalence of anterior, intermediate, and posterior/panuveitis were 72 percent, 6 percent, and 21 percent respectively (4). Given that anterior uveitis is most prevalent, our review will discuss the presentation and work-up of anterior uveitis.
 

2. A review of current ocular treatment should be completed for all new patients

40 percent of patients with ankylosing spondylitis experience acute anterior uveitis at some point in their disease course.

For new uveitis patients, it is important to review current ophthalmic treatments including dose, concentration, duration of therapy and route of delivery. Recurrence of inflammation while tapering topical treatment may indicate that a shift to another local therapy is needed, such as periocular or sub-Tenon steroid injection, or that long-term immunosuppressive therapy is needed if recurrences are as frequent as every 2-3 months. As many as 40 percent of patients with ankylosing spondylitis experience acute anterior uveitis at some point in their disease course (5). An evidence-based algorithm, called the Dublin Uveitis Evaluation Tool (DUET), guides ophthalmologists and primary care physicians to refer patients to rheumatologists. The DUET algorithm was noted to have excellent sensitivity (96 percent) and specificity (97 percent) (5).

3. Uveitis work-up should be guided by the anatomical location of inflammation
HLA-B27 is recommended as the only test for a first episode of acute unilateral anterior uveitis. Additional investigations should be considered for recurrent uveitis, bilateral uveitis or granulomatous inflammation. HLA-B27, CBC, ACE, liver function tests, syphilis screen, tuberculin skin test and/or Interferon-gamma release assay and chest radiograph are all helpful in evaluating spondyloarthropathy, sarcoidosis, syphilis and tuberculosis as initial investigations (6). Around 30–45 percent of anterior uveitis is associated with systemic disease, commonly the seronegative spondyloarthropathies, sarcoidosis, and syphilis (1, 2). ANA and rheumatoid factor are therefore unnecessary investigations for adult anterior uveitis.

4. Patients with uveitis should be closely monitored

The best care for patients with uveitis and glaucoma is a co-managed approach.

The approach to therapy will vary depending on the etiology (infectious or non-infectious) and patients should be followed weekly or more frequently in the acute phase to ensure response to treatment. Topical steroids should start to be tapered only when anterior chamber cells have completely resolved. Chronic uveitis, requiring topical, periocular or intravitreal steroid therapy, results in the often-seen complications of cataract and glaucoma. A low threshold for advancing therapy in glaucoma, and treating elevated intraocular pressures with surgery over laser, mean that the best care for patients with uveitis and glaucoma is a co-managed approach and in consultation with a glaucoma specialist. If prednisone at high doses is used to treat ocular inflammation, patients should be informed about side effects on bone density and the rare but serious side effect of osteonecrosis. Use of prednisone at high doses for any duration should be managed with family physicians, rheumatologists or other specialists for monitoring of bone density and supplemental calcium and vitamin D prescribed to prevent osteoporosis and reduce fracture risk. 

5. Consider Masquerade syndromes
The first step in diagnosing anterior uveitis is ruling out posterior segment disease. A thorough and attentive dilated fundus examination is important to identify posterior segment pathology as a cause of anterior chamber inflammation. For example, focal chorioretinitis from Toxoplasma gondii could present as an acute anterior uveitis with a painful red eye and anterior chamber inflammation. Neoplastic cells mimic intraocular inflammation as well. Primary intraocular or CNS lymphoma should be suspected in patients over the age of 50 with vitritis. The inflammation may be initially responsive to periocular steroid injections or intravitreal steroid implants, but then poorly responsive to repeat treatments or oral corticosteroid therapy (7). Other uveitis masquerades are chronic retinal detachment, multiple intraocular surgeries, such as tube shunts and cyclodestructive therapy, retinitis pigmentosa, and intraocular foreign bodies. 

Uveitis can be challenging to treat, both for comprehensive ophthalmologists and uveitis specialists. The keys to uveitis management include: a thorough slit lamp examination, appropriate work-up and investigations, close monitoring of patients on treatment, and knowing when to consider other diagnoses. Following these five simple, but essential, clinical pearls can provide an approach to the diagnosis and management of uveitis and other ocular inflammatory conditions. 

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  1. D Gritz and I Wong, “Incidence and prevalence of uveitis in Northern California; the Northern California Epidemiology of Uveitis Study”, Ophthalmology, 111, 491 (2004). PMID: 15019324.
  2. L Harman et al., “Uveitis: the Collaborative Diagnostic Evaluation”, Am Fam Physician, 90, 711 (2014). PMID: 25403035.
  3. A Jap and S Chee, “Viral anterior uveitis”, Curr Opin Ophthalmol, 22, 483 (2011). PMID: 21918442.
  4. N Acharya et al., “Incidence and Prevalence of Uveitis: Results From the Pacific Ocular Inflammation Study”, JAMA Ophthalmol, 131, 1405 (2013). PMID: 24008391.
  5. M Khan et al., “Acute Anterior Uveitis and Spondyloarthritis: More Than Meets the Eye”, Curr Rheumatol Rep, 17, 59 (2015). PMID: 26233598.
  6. A Parisot et al., “Randomized controlled trial evaluating a standardized strategy for uveitis etiologic diagnosis (ULISSE)”, Am J Ophthalmol, 178, 176 (2017). PMID: 28366648.
  7. R Read et al., “Neoplastic masquerade syndromes”, Surv Ophthalmol, 47, 81 (2002). PMID: 11918892.

About the Authors

Jingyi Ma

Research Fellow at Prism Eye Institute, Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, Ontario, Canada.


Irfan Nizarali Kherani

Clinical Fellow in the Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, Ontario, Canada.


Chloe Gottlieb

Assistant Professor of Ophthalmology at the University of Ottawa Eye Institute, The Ottawa Hospital, Ottawa, Ontario, Canada.

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