Residency · Residency · Ophthalmology
Corticosteroids in Ophthalmology: Topical, Periocular, and Intravitreal
Introduction
Corticosteroids are among the most frequently used medications in ophthalmology, employed for their potent anti-inflammatory, immunosuppressive, and anti-angiogenic properties. Available in topical, periocular, intravitreal, and systemic formulations, they play central roles in managing uveitis, macular edema, ocular surface disease, and postoperative inflammation. Understanding their pharmacology, relative potencies, and adverse effects is essential.
Mechanism of Action
Genomic Effects
Corticosteroids bind intracellular glucocorticoid receptors (GR) in the cytoplasm. The steroid-receptor complex translocates to the nucleus and modulates gene transcription. Transactivation: upregulation of anti-inflammatory proteins (lipocortin-1/annexin A1, IL-10, IkB) Transrepression: downregulation of pro-inflammatory mediators (NF-kB, AP-1 pathways) Inhibits phospholipase A2 via lipocortin-1, blocking prostaglandin and leukotriene synthesis.
Non-Genomic Effects
Rapid membrane-stabilizing effects (minutes, not hours) Inhibition of leukocyte adhesion and migration. Reduction of vascular permeability. Anti-edema effects via tight junction stabilization.
Topical Corticosteroids
Classification by Potency
Potency is determined by anti-inflammatory effect relative to cortisol and by ocular penetration.
High Potency
Prednisolone acetate 1%: gold standard for anterior segment inflammation; excellent corneal penetration (acetate ester is lipophilic) Difluprednate 0.05% (Durezol): difluorinated prednisolone derivative; very high potency; dosed less frequently; higher IOP elevation risk. Dexamethasone 0.1%: potent; available as solution (less shake-dependent than suspensions)
Moderate Potency
Loteprednol etabonate 0.5% (Lotemax): retrometabolized ("soft") steroid; C-20 ester undergoes esterase-mediated deactivation. Lower risk of IOP elevation than prednisolone acetate. Effective for seasonal allergic conjunctivitis, postoperative inflammation, dry eye. Prednisolone sodium phosphate 1%: water-soluble; poorer corneal penetration than acetate form. Fluorometholone 0.1%: moderate potency; used for surface inflammation; low intraocular penetration.
Low Potency
Fluorometholone acetate 0.1%: slightly higher penetration than FML base. Medrysone 1%: very low potency; rarely used. Rimexolone 1% (Vexol): anterior chamber penetration with lower IOP risk.
Topical Ophthalmic Corticosteroids Comparison
| Agent | Potency | Formulation | IOP Risk | Key Use |
|---|---|---|---|---|
| Prednisolone acetate 1% | High | Suspension (shake well) | High | Gold standard anterior segment inflammation |
| Difluprednate 0.05% (Durezol) | Very high | Emulsion (no shaking) | Very high | Severe uveitis; post-surgical |
| Dexamethasone 0.1% | High | Solution | High | Anterior inflammation |
| Loteprednol 0.5% (Lotemax) | Moderate | Gel/suspension | Lower (soft steroid) | Allergic conjunctivitis; dry eye; post-op |
| Fluorometholone 0.1% | Low-moderate | Suspension | Low | Surface inflammation; chronic use |
| Rimexolone 1% (Vexol) | Low-moderate | Suspension | Low | Anterior chamber penetration with lower IOP risk |
| Prednisolone sodium phosphate 1% | Moderate | Solution | Moderate | Poor corneal penetration (hydrophilic) |
Prescribing Principles for Topical Steroids
Shake suspensions well before instillation (prednisolone acetate settles) Taper gradually; do not stop abruptly (risk of rebound inflammation) Monitor IOP at 2-4 weeks (earlier in known steroid responders) For chronic use, consider lower-potency agents or steroid-sparing alternatives.
Periocular Corticosteroids
Sub-Tenon Injection
Triamcinolone acetonide 40 mg/mL: most commonly used; posterior sub-Tenon injection. Depot effect provides sustained drug delivery over 2-3 months. Indications: intermediate and posterior uveitis, CME, non-infectious scleritis. Transscleral diffusion delivers drug to choroid and retina. Technique: topical anesthesia, conjunctival incision inferotemporal, blunt cannula into sub-Tenon space.
Subconjunctival Injection
Dexamethasone sodium phosphate (4 mg/mL) or triamcinolone acetonide. Primarily for anterior segment disease: severe anterior uveitis, post-surgical inflammation. Drug depot provides sustained anterior segment levels.
Orbital Floor Injection
Triamcinolone acetonide injected into the inferior orbital space. Used for orbital inflammation, thyroid eye disease (adjunctive) Risk of inadvertent globe perforation, central retinal artery occlusion (rare)
Complications of Periocular Steroids
IOP elevation (triamcinolone > dexamethasone) Cataract progression with repeated injections. Subconjunctival hemorrhage, ptosis, skin depigmentation. Globe perforation (rare but serious) Orbital fat atrophy with repeated injections.
Intravitreal Corticosteroids
Triamcinolone Acetonide (IVTA)
Off-label intravitreal injection: 1-4 mg in 0.05-0.1 mL. Triesence (preservative-free, 40 mg/mL): FDA-approved for visualization during vitrectomy and for uveitis. Indications: DME (DRCR.net Protocol B and I), uveitic CME, RVO-associated macular edema. Duration of action: approximately 3-6 months. Significant IOP elevation in 30-50% of patients; cataract progression in nearly all phakic eyes within 2 years.
Dexamethasone Intravitreal Implant (Ozurdex)
Biodegradable poly(lactic-co-glycolic acid) implant releasing dexamethasone over 4-6 months. FDA-approved for: RVO macular edema, non-infectious posterior uveitis, DME (in pseudophakic eyes or scheduled for cataract surgery) Injected via 22-gauge applicator through the pars plana. Peak effect at 2-3 months; duration approximately 4-6 months. IOP elevation: 15-30%; usually manageable with topical therapy. Cataract progression in phakic eyes (50-60% over 2 years)
Advantages: controlled release, fewer injections than IVTA.
Fluocinolone Acetonide Implants
Retisert (0.59 mg)
Non-biodegradable surgically implanted device sutured to the pars plana. Duration: approximately 30 months. MUST Study: effective for chronic non-infectious posterior uveitis. Very high rates of IOP elevation (77%) and cataract surgery (100% of phakic eyes) Reserved for severe, recalcitrant uveitis.
Yutiq (0.18 mg)
Non-biodegradable micro-insert delivered via 25-gauge injector (office procedure) Duration: approximately 36 months. Lower steroid load than Retisert; reduced (but still significant) IOP and cataract risk. FDA-approved for chronic non-infectious posterior uveitis.
Iluvien (0.19 mg)
Non-biodegradable micro-insert; 25-gauge injector. FDA-approved for DME in patients previously treated with corticosteroids without clinically significant IOP rise. Duration: up to 36 months.
Systemic Corticosteroids in Ophthalmology
Common Indications
Optic neuritis (IV methylprednisolone per ONTT protocol) Severe bilateral posterior uveitis or panuveitis (VKH, sympathetic ophthalmia) Giant cell arteritis (prevent fellow eye vision loss) Orbital inflammatory disease. Acute exacerbations while awaiting IMT onset.
Dosing
Prednisone: 1 mg/kg/day (typically 60-80 mg/day) with taper over 6-12 weeks. IV methylprednisolone: 1 g/day for 3 days (pulse therapy for optic neuritis, GCA) Goal: taper to 7.5 mg/day or less within 3 months; transition to steroid-sparing IMT if unable.
Systemic Side Effects
Hyperglycemia, weight gain, cushingoid features. Osteoporosis (prescribe calcium, vitamin D; consider bisphosphonate if prolonged use) Adrenal suppression (do not withdraw abruptly after > 2 weeks of use) Peptic ulcer disease, psychosis, insomnia, immunosuppression. Avascular necrosis of the femoral head.
Steroid Response and Glaucoma
Epidemiology
Steroid responders: approximately 30-40% of the general population develop IOP elevation with topical steroids. 5-6% are high responders (IOP rise > 15 mmHg) Risk factors: primary open-angle glaucoma, family history, high myopia, diabetes, young age.
Mechanism
Increased outflow resistance via: Increased extracellular matrix deposition in trabecular meshwork. Decreased phagocytic activity of trabecular meshwork cells. Cross-linking of trabecular meshwork glycosaminoglycans. Myocilin gene expression changes.
Management
Monitor IOP in all patients on corticosteroids (topical, periocular, or intravitreal) Discontinue or switch to a lower-potency agent if IOP elevation occurs. Topical IOP-lowering medications (timolol, brimonidine, dorzolamide) Surgical intervention (trabeculectomy, tube shunt) for refractory cases. Intravitreal implant removal may be considered for non-biodegradable devices.
Key Clinical Pearls
Prednisolone acetate 1% is the gold standard topical steroid for anterior uveitis; always shake the bottle well before use as the suspension settles. Loteprednol etabonate is a retrometabolized "soft steroid" with a lower risk of IOP elevation, making it suitable for surface inflammation and maintenance therapy. Intravitreal triamcinolone causes clinically significant IOP elevation in 30-50% and cataract in nearly all phakic patients; patient selection is critical. All patients on ocular corticosteroids require IOP monitoring; the first check should be at 2-4 weeks after initiation.
References
- McGhee CN, Dean S, Danesh-Meyer H. Locally administered ocular corticosteroids: benefits and risks. Drug Saf. 2002;25(1):33-55.
- Haller JA, Bandello F, Belfort R Jr, et al. Dexamethasone intravitreal implant in patients with macular edema related to branch or central retinal vein occlusion (GENEVA study). Ophthalmology. 2011;118(12):2453-2460.
- Multicenter Uveitis Steroid Treatment (MUST) Trial Research Group. Benefits of systemic anti-inflammatory therapy versus fluocinolone acetonide intraocular implant for intermediate, posterior, and panuveitis. Ophthalmology. 2011;118(10):1916-1926.
- Jones R III, Rhee DJ. Corticosteroid-induced ocular hypertension and glaucoma: a brief review and update of the literature. Curr Opin Ophthalmol. 2006;17(2):163-167.