Periocular and Intraocular Steroids

1. Topical Corticosteroids

Agents Available

Indications

• Anterior uveitis (AAU and CAU)
• Postoperative inflammation (cataract, refractive, corneal surgery)
• Allergic conjunctivitis, dry eye syndrome, external ocular inflammation
• Episcleritis, scleritis (adjunctive)
• After glaucoma filtering surgery (to reduce fibroblast scarring of the bleb)

Dosing Regimen (for moderate-severe anterior uveitis)

• 1 drop hourly for 3 days
• Every 2 hours for 3 days
• 4x/day for 1 week
• 3x/day for 1 week
• 2x/day for 1 week
• Once daily for 1 week, then stop
• Treatment is typically completed by 5-6 weeks and carefully tapered

2. Periocular Steroids

Posterior sub-Tenon steroid injection (Kanski's Clinical Ophthalmology, Fig. 12.9)

Drugs Used

• Triamcinolone acetonide 40 mg/mL - most common depot agent
• Methylprednisolone acetate 40 mg/mL
• Betamethasone (sodium phosphate + acetate suspension, 6 mg/mL) - for subconjunctival use

Dose

• Subtenon / orbital floor: 1 mL (40 mg triamcinolone) via 25-gauge needle
• Subconjunctival: 0.5-1.0 mL triamcinolone 40 mg/mL
• Peak action: ~4 weeks; duration: up to 3 months

Indications

• Posterior segment inflammation (intermediate/posterior/panuveitis)
• Cystoid macular edema (CMO) from uveitis or post-surgical
• Unilateral severe anterior uveitis not responding to topical therapy
• Patients non-compliant with topical drops
• Perioperative inflammation control (at time of surgery)
• When systemic steroids are contraindicated (supplement or replacement)

Technique - Inferior Transseptal (Orbital Floor) Approach

1. Instill topical anesthetic (e.g., tetracaine)
2. Clean lower eyelid skin with antiseptic (povidone-iodine 5%)
3. Shake steroid vial; draw up 1 mL into 2 mL syringe with 25-gauge 5/8 inch needle
4. Patient maintains straight-ahead gaze
5. Needle inserted through skin near bony orbital margin, advanced tangentially to the globe
6. Confirm no blood on aspiration, then inject full 1 mL slowly

Technique - Posterior Sub-Tenon Approach

1. Topical anesthetic + cotton pledget in superior fornix for 2 minutes
2. Patient looks in direction opposite to superotemporal injection site
3. Bevel toward globe, pierce bulbar conjunctiva in superior fornix
4. Advance posteriorly following globe contour - make side-to-side motions to confirm globe not engaged (limbal movement = sclera engaged - stop)
5. Advance to needle hub, aspirate to confirm no blood, inject full 1 mL slowly

There is no clear evidence of superiority of one route over the other, but the orbital floor approach may have lower risk of globe perforation, IOP rise, and ptosis. - Kanski's, p. 454

Complications of Periocular Injection

• Subconjunctival hemorrhage
• Globe penetration (rare but serious)
• Refractory IOP elevation (up to 25%)
• Cataract
• Ptosis
• Eyelid hemorrhage / ischemic necrosis
• Retrobulbar hemorrhage
• Subdermal fat atrophy
• Extraocular muscle paresis
• Optic nerve injury
• Retinal/choroidal vascular occlusion
• Cutaneous hypopigmentation
• Systemic absorption (rare)

Important: Periocular depot steroids should be used with extreme caution in scleritis due to risk of scleral melting. Always rule out infectious uveitis before injecting. - Wills Eye Manual, p. 935

Periocular triamcinolone is off-label and must be discussed with patients. A trial of full-strength topical steroids helps identify steroid responders before committing to depot injection. - Wills Eye Manual, p. 935

3. Intraocular (Intravitreal) Steroids

A. Intravitreal Triamcinolone Acetonide (IVTA)

• Dose: 4 mg in 0.1 mL (i.e., one-tenth of the orbital periocular dose)
• FDA-approved for ocular inflammatory conditions unresponsive to topical corticosteroids and for visualization during vitrectomy
• IOP elevation typically lasts 2-4 months post-injection

• CMO unresponsive to periocular steroids or other therapy
• Diabetic macular edema (DME)
• Macular edema from retinal vein occlusion
• Posterior/panuveitis
• Rarely, high-risk anterior uveitis patients at the time of intraocular surgery

• Elevation of IOP
• Posterior subcapsular cataract
• Endophthalmitis (sterile or infectious)
• Intraocular hemorrhage
• Retinal detachment
• Pseudohypopyon (settling of triamcinolone crystals in anterior chamber)

B. Sustained-Release Intravitreal Implants

Intravitreal preservative-free triamcinolone and the dexamethasone/fluocinolone implants are more effective for uveitic macular edema than periocular triamcinolone. - Wills Eye Manual, p. 943

4. Steroid-Induced Complications (Relevant to All Routes)

Steroid-Induced Glaucoma

• ~1 in 3 individuals show some IOP rise to potent topical steroids ("steroid responders")
• Secondary open-angle glaucoma with normal-appearing angle
• Mechanism: increased resistance to aqueous outflow via altered trabecular meshwork extracellular matrix / endothelial cell function
• IOP rise is dose-, potency-, and duration-dependent; usually begins 2-4 weeks after starting
• After IVTA: IOP elevation lasts 2-4 months
• After dexamethasone implant (Ozurdex): up to 6 months
• Risk factors: existing glaucoma/OHT, family history of glaucoma, high myopia, young age, connective tissue disease (especially RA)
• Management: discontinue steroid (IOP normalizes within days-weeks); switch to less potent drop (fluorometholone, loteprednol); persistent elevation - medical or surgical management
• 3% of patients have persistent IOP elevation despite stopping steroids

Posterior Subcapsular Cataract (PSC)

• Less common with topical than systemic steroids
• Risk increases with dose and duration
• A major reason intravitreal implants require careful long-term follow-up

Other Toxicities

• Secondary infections (bacterial, fungal; reactivation of HSV keratitis)
• Corneal melting (especially with periocular steroids in scleritis)
• Systemic absorption effects (rare with topical; more relevant in children)

5. Step-Up Treatment Algorithm for Uveitis

1st line:  Topical prednisolone acetate 1% q1-2h ± cycloplegia
              ↓ (severe, unilateral, unresponsive)
2nd line:  Periocular repository steroid (subtenon triamcinolone 40 mg/mL, 0.5-1.0 mL)
           Repeat every 6-8 weeks x 3 if needed
              ↓ (bilateral, or no response after 3 injections)
3rd line:  Systemic steroids (prednisone 40-60 mg/day, taper over weeks)
           OR intravitreal sustained-release implant (Ozurdex 0.7 mg; fluocinolone 0.19 mg)
              ↓ (refractory / steroid-sparing needed)
4th line:  Immunomodulatory therapy (methotrexate, mycophenolate, anti-TNF agents)
           + Rheumatology referral

In children and adolescents, systemic steroids may be preferred over bilateral periocular injections to avoid growth suppression, but long-term systemic use carries its own significant risk. Bilateral disease generally favors systemic therapy. - Wills Eye Manual, p. 943

6. Key Drug Comparisons

• Kanski's Clinical Ophthalmology: A Systematic Approach, 10th ed., pp. 453-455
• The Wills Eye Manual, 8th ed., pp. 826, 935, 942-943
• Goodman & Gilman's The Pharmacological Basis of Therapeutics, p. 976