Uveitis: An Overview

Ling Paulina Gronczewska

Uveitis refers to inflammation of the uvea (the iris, ciliary body and choroid) but in clinical practice it encompasses intraocular inflammation affecting adjacent structures such as the retina, vitreous and optic nerve (1, 2). Although it represents a relatively small proportion of ophthalmic disease overall, it is responsible for a disproportionate amount of visual morbidity, accounting for around 10% of blindness worldwide (3). Uveitis can be acute or chronic, infectious or immune-mediated, and may occur in isolation or in association with a systemic condition (4). Because the eye is exquisitely sensitive to inflammation, even small degrees of intraocular disturbance can result in substantial symptoms or complications; for this reason, timely recognition and management are of great importance.

Uveitis has an estimated prevalence ranging from about 38 to 200 per 100,000 individuals, with variation reflecting demographic and geographical differences (5). It most commonly presents in young to middle-aged adults between the ages of 20 and 50 (6), a group in which visual impairment may have particularly significant social and economic consequences. Patterns of disease vary across the world: anterior uveitis is the most frequent form in Europe and North America, whereas posterior uveitis and panuveitis represent a larger proportion of cases in regions where infections such as tuberculosis and toxoplasmosis are endemic (6, 7). In many Western populations, up to half of acute, recurrent anterior uveitis cases are associated with HLA-B27, a genetic marker prevalent largely in Northern Europe (8). Taken together, these findings highlight how both host and environmental factors influence the burden of disease.

The causes of uveitis are diverse and classically divided into infectious and non-infectious categories. Non-infectious, immune-mediated uveitis predominates in high-income countries and may be idiopathic or associated with a range of systemic diseases. HLA-B27-related conditions such as ankylosing spondylitis, reactive arthritis, psoriatic arthritis and inflammatory bowel disease frequently manifest with recurrent acute anterior uveitis (9). Other systemic autoimmune disorders, including sarcoidosis, Behçet’s disease, juvenile idiopathic arthritis, Vogt–Koyanagi–Harada (VKH) disease and multiple sclerosis, are also well-recognised causes (10). For example, intermediate uveitis has a particular association with demyelinating disease (11). Infectious forms, however, must always be considered because misdiagnosis can lead to inappropriate immunosuppression. Viral pathogens such as herpes simplex virus, varicella-zoster virus and cytomegalovirus can cause anterior uveitis, often associated with raised intraocular pressure (12). Bacterial infections including syphilis, tuberculosis, Lyme disease and Bartonella can involve the eye in various ways (13). Toxoplasmosis remains a leading cause of posterior uveitis worldwide, producing characteristic retinochoroiditis (14). Fungal causes, such as Candida or Aspergillus, tend to occur in immunocompromised or iatrogenic contexts (15). Traumatic and iatrogenic uveitis, whether following blunt injury, intraocular surgery or as a reaction to certain medications, also forms part of the differential diagnosis.

The clinical manifestations of uveitis depend largely on the anatomical site of inflammation. Anterior uveitis, or iritis, typically presents with ocular pain, photophobia, redness and blurred vision. Patients often describe a deep, aching discomfort, and examination reveals ciliary flush, anterior chamber cells and flare, and sometimes keratic precipitates on the corneal endothelium. The pupil may be small and sluggish, and in severe cases a hypopyon can be present (16). Intermediate uveitis is characterised by vitreous inflammation, and patients complain mainly of floaters or blurred vision rather than pain. Fundus examination may reveal ‘snowballs’ (clumps of inflammatory cells in the vitreous) or ‘snowbanking’ along the pars plana (17). Posterior uveitis involves the retina or choroid and typically presents with painless visual disturbance, floaters or photopsia. Depending on the cause, clinicians may observe retinitis, choroiditis, retinal vasculitis or optic disc swelling. Macular oedema is a particularly common cause of reduced vision in many forms of uveitis (18). In panuveitis, all layers of the eye are affected, producing a mixture of anterior and posterior features and often significant visual impairment (19).

Diagnosis begins with a detailed history that explores systemic symptoms, prior infections, autoimmune conditions, medication use and any history of trauma or surgery. A careful slit-lamp examination assesses the degree and location of inflammation, while intraocular pressure measurement and dilated fundus evaluation help determine the full extent of disease (20). Modern imaging techniques support clinical assessment: optical coherence tomography is invaluable for detecting macular oedema, while fluorescein angiography demonstrates retinal vascular leakage and breakdown of the blood–retina barrier, indocyanine green angiography can reveal choroidal lesions not evident on clinical examination, and ultrasound B-scan is helpful when opacities obscure the fundus (20). Laboratory investigations should be guided by clinical suspicion rather than indiscriminately applied. Essential tests often include syphilis serology and tuberculosis screening, as these infections can mimic almost any form of uveitis. When an autoimmune cause is suspected, markers such as HLA-B27, serum ACE or lysozyme levels, antinuclear antibodies or rheumatoid factor may be appropriate, alongside chest imaging to assess for sarcoidosis, and in atypical or refractory cases, aqueous or vitreous sampling for polymerase chain reaction analysis or cytology may be required (21).

Management aims to control inflammation, prevent structural complications and address any underlying cause. The cornerstone of treatment for non-infectious anterior uveitis is topical corticosteroid therapy, usually with prednisolone acetate, titrated in frequency according to severity and tapered gradually to reduce the risk of relapse (22). Cycloplegic agents such as cyclopentolate or atropine are often added to relieve ciliary spasm and to prevent posterior synechiae (23). When inflammation is more severe, bilateral, or involves the posterior segment, systemic corticosteroids may be required (24). Because long-term steroid use carries significant ocular and systemic risks, steroid-sparing immunomodulatory therapy is frequently introduced in chronic or relapsing disease. Agents such as methotrexate, azathioprine and mycophenolate mofetil are commonly used first-line, while calcineurin inhibitors or biologic therapies, including anti-TNF agents like adalimumab, are reserved for more resistant cases (25). In contrast, infectious uveitis requires targeted antimicrobial therapy: antivirals for herpetic disease, antituberculous treatment for TB-associated uveitis, penicillin-based regimens for syphilis, or antiparasitic medication for toxoplasmosis. In these situations, corticosteroids may be used alongside antimicrobial therapy but should never be initiated without adequate pathogen coverage (26).

In summary, uveitis encompasses a broad spectrum of inflammatory eye diseases with diverse causes and manifestations. Its potential to cause significant and sometimes irreversible visual loss makes prompt diagnosis and appropriate management essential. Advances in imaging, immunomodulatory therapy and our understanding of immune-mediated ocular disease have greatly improved outcomes for many patients, yet the challenges of early detection and accurate identification of underlying causes remain central to effective care.

References

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