Approach to Uveitis

Uveitis is inflammation of the uveal tract (iris, ciliary body, choroid) and often adjacent structures (retina, vitreous, optic nerve, sclera). It is a leading cause of blindness in working age adults.

• Anatomical classification: anterior (iritis, iridocyclitis), intermediate (vitreous and pars plana), posterior (choroiditis, retinitis, retinal vasculitis), and panuveitis (all compartments).
• Course: acute (sudden onset, limited under 3 months), recurrent (episodes separated by 3 months or more without treatment), chronic (persistent, relapse within 3 months of stopping treatment).
• Laterality and pattern: unilateral, bilateral, alternating.
• Aetiology groups: infectious (herpes viruses, tuberculosis, syphilis, toxoplasmosis, toxocariasis, Lyme, bartonella, HIV), non-infectious systemic (HLA-B27 spondyloarthropathy, sarcoidosis, Behçet disease, juvenile idiopathic arthritis, inflammatory bowel disease, multiple sclerosis, tubulointerstitial nephritis with uveitis, Vogt-Koyanagi-Harada disease), eye limited autoimmune (birdshot chorioretinopathy, pars planitis, multifocal choroiditis), masquerade syndromes (intraocular lymphoma, leukaemia, retinoblastoma, retinal detachment, endogenous tumours), and drug induced (rifabutin, bisphosphonates, checkpoint inhibitors, cidofovir).
• Granulomatous features (mutton fat keratic precipitates, iris nodules) suggest sarcoid, tuberculosis, syphilis, VKH, sympathetic ophthalmia, herpetic disease, and lens induced uveitis, but are not specific.

• Anterior: pain, photophobia, redness (ciliary flush), reduced vision, small pupil, keratic precipitates, anterior chamber cells and flare, hypopyon, posterior synechiae.
• Intermediate: floaters and blurred vision with little pain or redness; vitreous cells, snowballs and snowbanking, cystoid macular oedema.
• Posterior: floaters, reduced vision, field loss, with retinochoroidal lesions, vasculitis, vitritis, macular oedema.
• Panuveitis: all of these features together, often severe.
• Complications: cataract, glaucoma, band keratopathy, cystoid macular oedema, macular scarring, hypotony, retinal detachment, epiretinal membrane, neovascularisation, optic neuropathy.
• Red flags for infection or masquerade: unilateral, atypical course, over 60 years of age, poor response to steroids, vitritis without pain, immunosuppression.

• Detailed history (age, onset, trauma, travel, sexual history, animal and food exposure, systemic symptoms: back pain, joint pain, rash, oral and genital ulcers, cough, neurological and skin signs, drugs) and full ocular examination with gonioscopy, intraocular pressure and dilated fundus examination.
• Imaging: optical coherence tomography (macular oedema), fluorescein angiography (vasculitis, leakage), indocyanine green angiography (choroiditis), fundus autofluorescence, B-scan ultrasound when the view is poor.
• Targeted laboratory testing guided by the pattern, not a blanket screen: syphilis serology (treponemal and non-treponemal), interferon gamma release assay and chest imaging (tuberculosis and sarcoid), serum angiotensin converting enzyme and lysozyme, HLA-B27 (acute anterior recurrent or bilateral), full blood count, ESR, CRP, urinalysis and creatinine, HIV, Toxoplasma IgG and IgM, Lyme and bartonella serology where relevant, antinuclear antibody (juvenile arthritis).
• Aqueous or vitreous sampling for polymerase chain reaction (herpes simplex, varicella zoster, cytomegalovirus, Toxoplasma) and cytology or interleukin-10 to interleukin-6 ratio (lymphoma) when diagnosis is uncertain.

• Treat any infectious cause with the specific agent first, then add anti-inflammatory therapy.
• Anterior uveitis: prednisolone acetate 1 percent (hourly while awake for severe disease, then taper over 4 to 8 weeks), cycloplegic (cyclopentolate 1 percent three times daily or atropine 1 percent once or twice daily) to relieve pain and prevent synechiae, and pressure control.
• Posterior segment or severe disease: periocular steroid (sub-Tenon triamcinolone acetonide 40 mg), intravitreal triamcinolone 4 mg, dexamethasone implant 0.7 mg, fluocinolone implant, or oral prednisolone 1 mg/kg daily (maximum 60 to 80 mg) tapered over 4 to 8 weeks; intravenous methylprednisolone 500 to 1000 mg daily for 3 days for sight threatening disease.
• Steroid sparing immunosuppression for chronic, recurrent or steroid dependent disease (need over 7.5 mg prednisolone daily or more than 2 drops a day after 3 months): methotrexate 15 to 25 mg weekly with folic acid 5 mg weekly, mycophenolate mofetil 1 to 1.5 g twice daily, azathioprine 2 to 3 mg/kg daily, ciclosporin 2.5 to 5 mg/kg daily, tacrolimus 0.05 to 0.15 mg/kg daily.
• Biologics: adalimumab 80 mg loading then 40 mg every 2 weeks (first line biologic for non-infectious uveitis), infliximab 5 mg/kg at weeks 0, 2, 6 then every 4 to 8 weeks, tocilizumab, interferon alpha for Behçet disease. Screen for latent tuberculosis, hepatitis B and C and HIV before starting.
• Treat complications: macular oedema (sub-Tenon triamcinolone 40 mg, intravitreal dexamethasone implant 0.7 mg, or acetazolamide 250 mg twice daily), glaucoma, cataract surgery after at least 3 months of quiet inflammation, with perioperative steroid cover.
• Monitor drug toxicity (full blood count, liver and renal function every 4 to 12 weeks) and inflammation (anterior chamber cell grade, vitreous haze, OCT). Remission is defined as inactive disease off treatment for at least 3 months.