Review of Uveitis Underscores Urgency of Early Action

Medscape

5 hours ago

A major new review on the diagnosis and treatment of uveitis, led by researchers at the University of Bristol, UK, has been published in the Journal of the American Medical Association (JAMA). The review provides comprehensive guidance to help clinicians address this leading cause of vision loss – a condition which the authors said is often detected too late to prevent irreversible damage.
Medscape News UK spoke with first author Panayiotis Maghsoudlou, PhD, National Institute for Health and Care Research academic clinical lecturer in ophthalmology at Bristol Medical School.
How does your review differ from information already in the literature?
Panayiotis Maghsoudlou
In this JAMA review, we set out to create a rigorous, evidence-based, and clinically useful summary that speaks directly to a broad range of healthcare professionals. Unlike standard narrative reviews, JAMA articles are developed through close editorial collaboration with authors to ensure maximum clinical utility across specialties — in this case, from GPs identifying red flags, to emergency physicians triaging acute cases, to rheumatologists managing systemic disease.
JAMA applies a strict evidence hierarchy, so we relied exclusively on high-level data such as randomised controlled trials, meta-analyses, and cohort studies, avoiding anecdote or personal opinion. We also developed diagnostic algorithms, referral pathways, and summary tables to help clinicians rapidly extract actionable information at the point of care. Our aim was to produce a clear, practical, and highly cited resource that supports informed decision-making in busy clinical settings.
Despite being a leading cause of preventable blindness, uveitis remains under-diagnosed and undertreated. Why has this situation developed?
We believe this gap stems from several factors. Uveitis can present subtly, with non-specific symptoms like eye redness, photophobia, or floaters that are easily missed or attributed to more common conditions. It also has multiple subtypes, each with different causes, presentations, and management strategies – making early recognition challenging, especially in general practice.
Crucially, the hallmark clinical sign — cells floating in the anterior chamber of the eye — can only be detected on slit-lamp examination, which requires specialist assessment. Furthermore, public and professional awareness remains low, and there is no unified diagnostic or referral pathway in many healthcare systems. As a result, patients often present late. Our review aims to close this gap by offering clear, evidence-based guidance to support earlier diagnosis and tailored treatment.
How prevalent is the condition in the UK?
Population-based data indicate that anterior uveitis constitutes roughly 50%-70% of all cases in the UK, with an overall prevalence estimated between 25 and 50 per 100,000 adults. Most affected individuals fall into the 20-50-year age bracket.
The UK is a high-prevalence region for birdshot uveitis, a rare autoimmune type of uveitis linked to the HLA-A*29 antigen. UK incidence is estimated at 0.035 cases per 100,000 person-years.
Your review says up to half of cases of uveitis are idiopathic and a high proportion of the rest associated with systemic disease. What other causes might present?
Referral patterns have shifted over the last decade. We have seen decreases in Fuchs' uveitis, Behçet's uveitis, and ocular toxoplasmosis. There have been significant increases reported for syphilis and tuberculosis – reflecting increased population-level infections. Also increasing are rates of herpetic retinitis, vitreoretinal lymphoma, and sarcoidosis.
How much do you expect advances in treatment such as biologic agents to make a difference in the coming years?
We expect biologics to have a transformative impact, particularly for patients with non-infectious, sight-threatening, or refractory uveitis. Agents like adalimumab already have strong evidence for reducing treatment failure and preserving vision, while avoiding the long-term complications of systemic steroids.
However, the key challenge is securing funding to run dedicated uveitis trials, which are essential for regulators to approve these therapies with a formal indication. At present, we too often rely on rheumatology-led access to biologics, which limits availability for ophthalmic use. This patchwork approach also means ophthalmologists may be less familiar with these drugs, and patients face more hoops to jump through for approval. Generating robust, indication-specific data is the next step to improving access and outcomes.
What are your key 'take home' points for ophthalmologists?
Tailor treatment to anatomical location: Recognise that anterior uveitis may respond to topical drops, but posterior or pan-uveitis demands prompt systemic immunosuppression to preserve vision. If conventional disease-modifying antirheumatic drugs (DMARDs, eg. methotrexate, mycophenolate mofetil) fail, escalate without delay to biologics (eg. adalimumab) to prevent irreversible damage.
Engage specialist support early: For recurrent, chronic, or refractory cases, collaborate promptly with tertiary uveitis centres or rheumatology teams. Rheumatology colleagues or uveitis centres usually have dedicated nursing staff experienced in counselling patients and monitoring blood tests – crucial for safe initiation and ongoing management of immunosuppressive therapy. Early multi-disciplinary involvement can prevent delays that might jeopardise vision.
Emphasise pattern recognition and second opinions: Uveitis comprises a multitude of phenotypes; if a patient's inflammation fails to respond as expected, seek a second or even third expert opinion. Persistent or atypical presentations may reflect a 'masquerade' syndrome — most notably primary vitreoretinal lymphoma — rather than straightforward immune-mediated uveitis. A high index of suspicion and timely investigation (for instance, vitreous biopsy or advanced imaging) are vital when the clinical course is unusual.
Think systemically, treat holistically: Always consider underlying systemic associations — ankylosing spondylitis, sarcoidosis, Behçet's disease, and inflammatory bowel disease, among others — and liaise with the appropriate specialists (rheumatologists, gastroenterologists, or infectious disease experts) for comprehensive care. Systemic evaluation is as important as ocular management.
Communicate clearly with patients: Explain that uveitis may be chronic or relapsing and that long-term follow-up is often necessary. Discuss the balance between treatment benefits and potential side-effects, emphasising adherence to both medication and monitoring schedules.
What are your key 'take home' points for GPs and what key clues as to the type (anterior, posterior etc) or cause (idiopathic, infectious, rheumatologic associated) should they have on their radar?
Differentiate by presentation:
Anterior uveitis typically presents with acute pain (worsens when trying to read), photophobia, and a red eye with a ciliary flush (a deep red ring around the iris)
Intermediate uveitis often manifests insidiously: painless floaters, mild blurring.
Posterior uveitis presents with visual loss, scotomata, or photopsia.
Be alert to systemic clues: Enquire about joint pains, back stiffness, or skin rashes (hinting at HLA-B27–associated disease or psoriasis/ankylosing spondylitis), mouth/genital ulcers (Behçet's), respiratory symptoms (sarcoidosis, tuberculosis), travel or sexual history (syphilis, tuberculosis, toxoplasmosis), and neurological symptoms (intermediate uveitis often precedes a diagnosis of MS). A history of lymphoma or malignancy raises suspicion of a masquerade syndrome.
Timely referral matters: All suspected uveitis cases should be referred to ophthalmology within 24-48 hours – faster if vision is threatened. Delays allow complications such as macular oedema or glaucomatous optic neuropathy to become irreversible.
What might be a GP's referral threshold, and how urgent is this in the absence of vision loss/signs of sepsis?
Uveitis without vision loss is still a same/next-day ophthalmology referral. The absence of vision loss doesn't reduce urgency – it may just mean you're catching it early enough to prevent permanent damage. When in doubt, refer urgently. A 24-hour delay can mean the difference between full recovery and lifelong vision problems.
Patients with visual symptoms and systemic illness (eg, fever, hypotension) should be referred to the emergency department for evaluation and treatment due to the risk of vision-threatening endophthalmitis and potentially life-threatening sepsis.
How common is resulting vision loss/sepsis and what is the prognosis overall?
In larger cohort studies, vision loss occurs in 10%-20% of uveitis patients, with markedly higher rates in intermediate, posterior, and panuveitis compared with anterior disease. Early adoption of DMARDs [disease-modifying antirheumatic drugs] and biologic therapies is likely reducing these vision loss rates, but definitive long-term data demonstrating improved visual outcomes are not yet available.
Delayed diagnosis remains a critical modifiable risk factor. Patients with chronic inflammation face compounded risk through complications (e.g. glaucoma, cystoid macular oedema) that can progressively compromise visual function. As cohorts treated with contemporary immunosuppressive protocols from disease onset mature, clearer evidence of visual preservation should emerge over the coming decade.
Are patients vulnerable to repeat episodes in the absence of underlying disease?
Yes, even in the absence of an identified underlying systemic or infectious cause, patients with idiopathic uveitis (which accounts for up to 50% of cases) can still experience recurrent episodes. A large cohort study reported a 38.1% recurrence rate in the ipsilateral eye and a 15.2% recurrence rate in the contralateral eye over 10 years, with an overall recurrence risk of about 49.5% in either eye during the study period.
This underscores the need for patient education on recognising key symptoms — such as eye pain, redness, photophobia, new floaters, or blurred vision — and the importance of ongoing follow-up, even when symptoms resolve between episodes.
How long should monitoring go on for, and how often?
There is no internationally agreed consensus on monitoring intervals for adults with uveitis, and follow-up is typically ophthalmology-led, based on disease type, severity, and underlying cause.
Anterior uveitis often requires less frequent monitoring once stable.
Posterior uveitis, particularly when sight-threatening or associated with syndromic conditions like Behçet disease or Vogt–Koyanagi–Harada (VKH) syndrome, needs more frequent and sustained follow-up, often monthly or even more regularly during active phases.
Uveitis has many underlying causes — from autoimmune conditions (e.g. sarcoidosis, HLA-B27-related disease) to infections (e.g. tuberculosis, toxoplasmosis) — and this heterogeneity makes standardising monitoring difficult. Long-term review is essential to detect recurrences, complications, or treatment-related adverse effects.
What is your most important message for healthcare professionals?
Early systemic immunosuppression has been shown to preserve vision in many cases of non-infectious uveitis. Even so, approximately 1 in 5 patients will still experience significant vision loss despite modern DMARD- and biologic-based regimens.
Initiating systemic therapy before irreversible damage (such as macular scarring or glaucomatous optic neuropathy) occurs is paramount.
Panayiotis Maghsoudlou, PhD, declared receiving honoraria from Bayer.