Uveitis: Steroids, Steroid-Sparing Agents and Biologics

What uveitis actually is

The uvea is the pigmented, vascular middle coat of the eye — and inflammation can strike any part of it. The uveal tract has three continuous parts: the iris at the front, the ciliary body just behind it, and the choroid lining the back of the eye. Uveitis is classified anatomically by where the inflammation is centred. Anterior uveitis (iritis / iridocyclitis) is the commonest — a red, painful, photophobic eye with cells in the anterior chamber. Intermediate uveitis inflames the vitreous and the region behind the ciliary body, typically causing floaters and haze rather than pain. Posterior uveitis attacks the choroid and retina, threatening central vision directly. Panuveitis involves all compartments at once. This anatomy is not academic: it dictates how you deliver the drug. Inflammation at the front can be reached by a drop; inflammation at the back cannot, and needs an injection, an implant, or systemic therapy to get the drug where it is needed.

The eye as a window on systemic disease

A large share of uveitis is the ocular signature of a disease elsewhere in the body, which is why the workup so often reaches beyond the eye. The classic association is HLA-B27 — the tissue type linked to the spondyloarthropathies (ankylosing spondylitis, reactive arthritis, psoriatic and inflammatory-bowel-associated arthritis) — which typically causes recurrent, unilateral, acute anterior uveitis. Sarcoidosis produces a granulomatous uveitis that can sit anywhere in the tract. Behçet's disease causes an explosive, sight-threatening occlusive retinal vasculitis. In children, juvenile idiopathic arthritis (JIA) causes a dangerously quiet chronic anterior uveitis — white and painless, yet quietly scarring — which is why these children are screened by slit lamp even when they feel completely well. And a critical group is infectious: herpes simplex and zoster, toxoplasmosis, tuberculosis, and syphilis can each masquerade as "autoimmune" uveitis. Sorting autoimmune from infectious is the hinge on which the entire treatment plan turns.

Rung 1: corticosteroids — and how you deliver them

Steroids are the workhorse of every uveitis regimen; the art is choosing the route that reaches the inflammation. Corticosteroids suppress the whole inflammatory cascade — the same broad anti-inflammatory action detailed in the Ocular steroids chapter — and they are first-line for non-infectious uveitis. Route follows anatomy. Anterior uveitis is treated topically, with intensive prednisolone acetate or dexamethasone drops tapered slowly as the cells settle. But drops barely reach the back of the eye, so posterior and intermediate disease needs the drug delivered locally by injection or implant: a periocular (sub-Tenon's) triamcinolone depot, an intravitreal triamcinolone injection, or a sustained-release intravitreal implant — a biodegradable dexamethasone implant (Ozurdex) lasting months, or a fluocinolone acetonide implant releasing drug for years. Severe, bilateral or sight-threatening disease is treated systemically with oral prednisolone (or intravenous methylprednisolone pulses to gain rapid control). The trade-off is unavoidable: the more effectively you flood the eye or the body with steroid, the more you invite the steroid's own ocular hazards.

The cycloplegic partner: relieving spasm and breaking synechiae

Alongside the steroid, anterior uveitis almost always earns a cycloplegic / mydriatic — an antimuscarinic drop such as cyclopentolate, homatropine or atropine, the same agents covered in the Mydriatics chapter. It does two jobs. First, it paralyses the ciliary muscle, relieving the deep, aching pain of ciliary spasm that makes uveitis so miserable. Second, and crucially, it dilates the pupil to keep the inflamed iris moving and away from the lens. Inflammation makes the iris sticky, and a small, still pupil can glue itself to the anterior lens capsule — posterior synechiae. Dilating the pupil pulls the iris off the lens, breaking fresh adhesions and preventing new ones. Left unchecked, a ring of synechiae can seal the pupil entirely (seclusio pupillae), block aqueous flow and drive a sudden rise in pressure. A cycloplegic is therefore not just for comfort — it is structural protection for the eye.

Rung 2: steroid-sparing immunosuppression

When the eye is chronically inflamed or the steroid dose won't come down, you need a second agent to carry the load. Long-term corticosteroids extract a heavy price in the eye — glaucoma and cataract — and in the body. So once uveitis becomes chronic, relapses whenever the steroid is tapered (steroid-dependent), or demands doses whose side effects are mounting, the strategy shifts to steroid-sparing immunosuppression: add a second drug to control inflammation while the steroid is weaned to a safe level. These are the very agents used across systemic autoimmune disease, and they are taught in full in the Inflammation & Joints section. The antimetabolites come first: methotrexate (the workhorse, and the standard choice in JIA-associated uveitis), mycophenolate mofetil, and azathioprine — all of which blunt lymphocyte proliferation. Alongside them the calcineurin inhibitors — ciclosporin and tacrolimus — which block T-cell activation by inhibiting the calcineurin–NFAT pathway. Choice depends on the underlying disease, the pattern of uveitis, and the patient (methotrexate and mycophenolate, for instance, are teratogenic and avoided in pregnancy).

The cost of these drugs is not in the eye but in the monitoring they demand — a burden carried over wholesale from the Inflammation section. Because they suppress the marrow, the liver and the immune defences, patients need regular blood counts and liver-function tests, screening for latent infection (hepatitis B and C, TB) before starting, and counselling on infection risk. Ciclosporin adds its own signature toxicities: hypertension and nephrotoxicity, so blood pressure and renal function are watched closely. None of this is optional; the whole point of steroid-sparing therapy is to trade one set of long-term risks for a more manageable one, and that bargain only holds if the monitoring is done.

Rung 3: biologics

When conventional immunosuppression fails, or when the disease is severe enough that waiting is dangerous, therapy climbs to the biologics — targeted antibodies against specific inflammatory mediators, again shared with the Inflammation & Joints toolkit. The anti-TNF agents lead: adalimumab and infliximab, monoclonal antibodies that neutralise tumour necrosis factor. Adalimumab is specifically licensed for non-infectious intermediate, posterior and panuveitis, and has become a mainstay for chronic, sight-threatening or steroid-refractory disease — including refractory JIA-associated uveitis, where it is often combined with methotrexate. Behçet's disease deserves special mention: its occlusive retinal vasculitis is so aggressive and blinding that guidelines push early, aggressive biologic therapy (infliximab or adalimumab) rather than waiting to climb the ladder rung by rung. Other biologics widen the arsenal — interferon-alfa in Behçet's, and agents targeting IL-6 or B cells in selected refractory cases. As with all biologics, the same rule holds louder than ever: screen for and exclude latent TB and hepatitis before starting, because TNF is central to the body's defence against exactly those infections.