Ocular topical steroid therapy is a treatment that achieves high local ocular concentrations while avoiding systemic administration for ocular inflammation, postoperative inflammation, allergic conjunctivitis, etc. There are five routes: eye drops, subconjunctival injection, sub-Tenon’s injection, intracameral injection, and intravitreal injection.
Indications are broad, including uveitis (iridocyclitis, posterior uveitis, panuveitis), control of postoperative inflammation after cataract, glaucoma, and vitreous surgery, prevention of rejection after corneal transplantation, and allergic conjunctivitis.
Topical steroid therapy
Steroid eye drops: Basic treatment for anterior segment inflammation. Options include fluorometholone, loteprednol, prednisolone, and difluprednate.
Posterior sub-Tenon injection: First-line for chronic posterior segment inflammation and macular edema. Kenacort-A 40 mg/mL 0.5 mL (off-label in some countries).
Intravitreal implant: For refractory uveitic macular edema (UME), Ozurdex 0.7 mg (duration approximately 4–6 months).
Medications for complications
Intraocular pressure-lowering drugs: For steroid-induced glaucoma. Beta-blockers, carbonic anhydrase inhibitors, and alpha-2 agonists are preferred. In uveitis, prostaglandin analogs and pilocarpine are generally avoided.
Mydriatics: To prevent posterior synechiae during anterior chamber inflammation. Mydrin M/P is standard.
Nonsteroidal anti-inflammatory eye drops: Alternative after inflammation has stabilized.
An international survey of non-infectious uveitis (53 countries, 221 participants) found that all patients underwent screening before starting systemic immunomodulatory therapy 1). Topical steroids can complement systemic treatment depending on the site and severity of inflammation.
The main clinical findings for determining the indication of topical steroid therapy are shown below.
| Finding | Details |
|---|---|
| Keratic precipitates (KP) | Fine to mutton-fat (sarcoidosis, tuberculosis) |
| Anterior chamber flare and cells | Graded 1+ to 4+ according to SUN criteria |
| Posterior synechiae | Prevent or break with mydriatics |
| Vitreous haze | Indicator of intermediate and posterior uveitis |
| Cystoid macular edema (CME) | Assessed by OCT. Good indication for posterior sub-Tenon injection |
| Secondary glaucoma | Elevated intraocular pressure → topical antihypertensives (choose carefully) |
Uveitis is classified by location into anterior, intermediate, posterior, and panuveitis. The choice of topical treatment depends on this classification and the degree of inflammation. Cystoid macular edema (CME) is a major cause of vision loss in uveitis, characterized by fluid accumulation in the macula and cyst formation in the inner nuclear layer6).
When severe inflammation occurs in the anterior chamber, the iris may adhere to the anterior lens capsule, causing posterior synechiae. Mydriatics relax the ciliary muscle and pupillary sphincter, preventing or breaking these adhesions. For Behçet’s disease, tropicamide (Mydrin M) 1–3 times daily is prescribed; for Vogt-Koyanagi-Harada disease, Mydrin P once daily at night is an example.
Indications for topical steroid therapy are broadly divided into infectious and non-infectious uveitis.
Main causes of non-infectious uveitis:
Main causes of infectious uveitis:
In infectious uveitis, administering steroids alone without adequately controlling the infection can worsen the infection. Therefore, the principle is to prioritize treatment of the underlying cause.
Before starting topical steroid therapy, it is essential to rule out infectious uveitis. When proceeding to systemic immunomodulatory therapy, screening was performed in all cases in an international survey 1). Inflammation severity is assessed based on the classification of the SUN (Standardization of Uveitis Nomenclature) Working Group.
Examples of screening when considering systemic immunomodulatory therapy:
Assessment of inflammation intensity is primarily done by slit-lamp examination, with semi-quantitative evaluation of anterior chamber flare and cell count according to SUN criteria. For posterior segment macular edema, OCT is essential, and central retinal thickness (CST) is measured quantitatively to determine the indication for sub-Tenon injection or intravitreal administration and to evaluate treatment response 5).
After excluding infectious causes, the route of administration is selected based on the site of inflammation (anterior, intermediate, or posterior) and severity.
Steroid monotherapy before controlling infection in infectious uveitis carries a risk of rapid exacerbation and is generally contraindicated. In particular, posterior sub-Tenon injection can cause rapid worsening if performed in infectious uveitis. It is important to delay injection until after infection control, or to administer antibiotics simultaneously.
First-line treatment for anterior segment inflammation. In order of increasing potency: fluorometholone → loteprednol → rimexolone → prednisolone → difluprednate.
| Drug Name | Concentration | Characteristics/Uses | Main Side Effects |
|---|---|---|---|
| Fluorometholone (FML) | 0.1, 0.02% | For mild inflammation | Increased intraocular pressure (low) |
| Loteprednol (Lotemax) | 0.2, 0.5, 1% | Low intraocular pressure risk | Increased intraocular pressure (low) |
| Prednisolone (Pred Forte) | 0.12, 1% | Standard treatment for intraocular inflammation | Cataract, increased intraocular pressure |
| Difluprednate (Durezol) | 0.05% | Potent; for severe cases | Cataract, increased intraocular pressure |
Example of topical treatment for Behçet’s disease: Rinderon eye drops (0.1%) 4-6 times daily, Mydrin M 1-3 times daily. Example for Harada disease: Rinderon eye drops (0.1%) 3 times daily, Mydrin P once at night.
Tapering of topical steroids (eye drops) is not mandatory. If the treatment duration is less than 3-4 weeks, tapering is unnecessary regardless of dose. If used for more than 3-4 weeks, gradual dose reduction is recommended.
Used as pulse therapy for acute inflammation.
This is the first procedure performed to control chronic inflammation in the posterior segment, and is well indicated for vitreous opacity associated with macular edema and retinal vasculitis. It is particularly effective for cystoid macular edema and diffuse vitreous opacity.
Medications and prescription examples:
Characteristics of effect:
Key points of the procedure:
Alternative technique using a sharp needle: A slightly thicker sharp needle of about 25 G can be used from the inferotemporal fornix. Advantages include less bleeding and pain, shorter injection time, and almost no drug reflux.
Side effects and precautions:
Stepwise escalation guidelines (based on uveitis treatment guidelines) 5):
For posterior sub-Tenon injection of triamcinolone acetonide (Kenacort-A), the peak effect occurs about 1 month after injection, and efficacy can be expected for about 3 months. The drug remains in the sub-Tenon space for 3 months, but the risks of side effects such as cataracts and increased intraocular pressure also persist. When performing multiple injections, it is recommended to space them at least 2 months apart.
Intravitreal steroid administration is selected for refractory uveitic macular edema (UME).
| Drug | Dose / Duration | Key Evidence |
|---|---|---|
| Triamcinolone (MacuAid) | 4 mg, about 3 months | Visual improvement about 50%, cataract almost certain after 4-5 injections, increased IOP 20-45% |
| Dexamethasone implant (Ozurdex) | 0.7 mg, about 4-6 months | Fan 2023 meta-analysis: BCVA at 6 months -0.24 logMAR, CMT at 6 months -140.25 μm, IOP increase 13.6%, cataract formation 5.4%3) |
| Fluocinolone (Iluvien) | 0.19 mg, about 36 months | Cataract surgery 73.8%, glaucoma surgery 11.9% (high long-term risk) |
| Fluocinolone (Retisert) | 0.59 mg, approximately 30 months | Cataract surgery >90%, glaucoma surgery 40% (very high long-term risk) |
The MUST (Multicenter Uveitis Steroid Treatment) trial directly compared intravitreal fluocinolone implant with systemic immunomodulatory therapy and found no difference in long-term visual outcomes between the two groups, but the implant group had significantly higher rates of cataract and glaucoma surgery 7).
The POINT trial directly compared periocular triamcinolone (PTA), intravitreal triamcinolone (ITA), and intravitreal DEX implant (IDI), with central foveal thickness reductions of 23%, 39%, and 46%, respectively 8). The HURON trial confirmed significant reduction in central foveal thickness and improvement in vitreous haze at 8 weeks with Ozurdex 4).
Ozurdex (dexamethasone intravitreal implant) is covered by insurance for diabetic macular edema and macular edema due to retinal vein occlusion. However, as of April 2026, it is not covered for uveitic macular edema. Please check with your doctor.
The suprachoroidal space (SCS; the potential space between the choroid and sclera) is a new route for direct drug administration. Animal studies have shown that drug exposure to the posterior segment is 12 times higher compared to intravitreal administration, while exposure to the anterior segment is reduced by 96% 2).
PEACHTREE trial (Phase III): In the SCS-TA 4 mg group, 46.9% of patients achieved ≥15-letter BCVA improvement at 24 weeks (sham group 15.6%, p<0.001), and mean central foveal thickness reduction was 152.6 μm vs. 17.9 μm (p<0.001) 2).
MAGNOLIA extension trial: 50% of the SCS-TA group did not require rescue therapy for up to 9 months after the second injection 2).
It was approved in the US in 2021, but as of April 2026, it is not yet approved in Japan.
Steroid glaucoma: For elevated intraocular pressure, use topical antihypertensive eye drops (prostaglandin analogs, beta-blockers, carbonic anhydrase inhibitors, alpha-2 agonists) → oral carbonic anhydrase inhibitors → intravenous D-mannitol infusion in that order 5).
Steroid cataract: Long-term steroid use (especially systemic) increases the risk of posterior subcapsular cataract. Children are more susceptible than adults. Repeating intraocular steroids 4-5 times almost certainly leads to cataract progression.
Inadvertent administration for infectious uveitis: Sub-Tenon injection before infection control is strictly prohibited as it may cause rapid exacerbation.
Glucocorticoids bind to receptors (GR) and suppress intraocular inflammation by inhibiting inflammatory cytokine production. They suppress the NF-κB signaling pathway and broadly inhibit the production of inflammatory cytokines such as TNF-α, IL-1β, and IL-6.
Mechanism of intraocular pressure elevation: Steroid-induced mucopolysaccharide deposition in the trabecular meshwork and increased water-binding capacity → increased aqueous outflow resistance → elevated intraocular pressure. This is the main mechanism of steroid-induced glaucoma. In steroid responders, intraocular pressure elevation is observed 2–4 weeks after starting eye drops. Intraocular pressure elevation after depot injection may persist for 3–6 months.
Pathophysiology of cystoid macular edema: CME associated with uveitis develops when inflammatory cytokines (mainly VEGF and TNF-α) damage retinal vascular endothelial cell junction proteins (occludin, claudin, etc.) and disrupt the blood-retinal barrier (BRB)6). Steroids are effective through both mechanisms: restoration of the BRB and suppression of inflammatory cytokine production.
Mechanism of depot formulation: Triamcinolone acetonide is a depot formulation that provides long-term effects (approximately 3 months) by sustained release from the injection site. Slow dissolution in tissue maintains stable drug concentration.
Mechanism of intravitreal implant: The DEX implant (Ozurdex) contains 0.7 mg of dexamethasone incorporated in a biodegradable polymer (poly(lactic-co-glycolic acid)) and releases continuously for approximately 4–6 months. It shows a pattern of high-concentration release in the first 1–2 months, followed by gradual decline3).
Local treatment flow for anterior uveitis
Step 1: Steroid eye drops (select potency according to inflammation severity)
Step 2: Mydriatic agents (e.g., Mydrin P) to prevent posterior synechiae
Step 3: If intraocular pressure rises, use beta-blockers and carbonic anhydrase inhibitors (prostaglandin analogs and pilocarpine are contraindicated)
Step 4: If control is insufficient → systemic steroids or sub-Tenon injection
Local treatment flow for posterior segment
Posterior sub-Tenon injection: Kenacort-A 40 mg/mL 0.5 mL (administered from the inferotemporal side)
Indications: Cystoid macular edema, diffuse vitreous opacity, posterior pole inflammation
Intravitreal implant (refractory cases): Ozurdex 0.7 mg / Triamcinolone 4 mg
Suprachoroidal injection (research stage): Xipere 4 mg (not approved in Japan)
SCS-TA (Xipere) was approved in the United States in 2021, but as of April 2026, it is not yet approved in Japan. Based on the favorable results of the PEACHTREE trial 2), attention is focused on the progress toward domestic approval.
Development of biosimilars for dexamethasone implants and long-acting implants is progressing, with expectations for reduced treatment costs and improved treatment access. Research is also advancing on personalized drug selection through early identification of steroid responders (patients prone to intraocular pressure elevation). Elucidation of the detailed mechanisms of blood-retinal barrier disruption in retinal inflammation is also expected to lead to the development of more selective targeted therapies 6).
The optimal combination, administration sequence, and discontinuation criteria for local steroids and systemic immunomodulatory therapy continue to be investigated. From the long-term follow-up of the MUST trial 7), it is recommended that the choice between intravitreal implants and systemic treatment should consider individual patient risks of cataract and glaucoma.
