EpistemisCiclosporin A, Lifitegrast
Topical immunomodulators selectively interrupt the inflammatory cycle mediated by T lymphocytes in the lacrimal and conjunctival glands, restoring natural tear production in moderate to severe dry eye.
Mechanism
💊 Commercial NamesIkervis, Restasis, Xiidra, Cequa, Ciclosporin Ophthalmic Formulas.
🔬 Pharmacological GroupCiclosporin (calcineurin inhibitor), Lifitegrast (selective leukocyte function-associated antigen type 1 [LFA-1] antagonist). Immunomodulators.
Mechanism of Action
Severe dry eye is characterized by chronic dural inflammation mediated by T lymphocytes that secrete cytokines that destroy goblet cells and acinar glands:
- Inhibition of Calcineurin by Cyclosporin A: Cyclosporin diffuses intracellularly into T lymphocytes on the ocular surface and binds to the cytoplasmic immunophilin **cyclophilin**. This complex binds and selectively inhibits the phosphatase enzyme **calcineurin**, blocking the dephosphorylation and translocation to the nucleus of the transcription factor NFAT (Nuclear Factor of Activated T Lymphocytes). Since NFAT cannot bind to gene promoters, the transcription of Interleukin-2 (IL-2), a cytokine responsible for the expansion and proliferation of autoreactive T lymphocytes, is blocked. This stops conjunctival epithelial cell apoptosis, restores the density of mucin-producing goblet cells, and restores normal dural tear film production.
- LFA-1 antagonism by Lifitegrast: Lifitegrast is a small molecule that competitively binds to the surface receptor LFA-1 expressed on leukocytes and prevents its binding to intercellular adhesion molecule 1 (ICAM-1) expressed on the endothelial cells of conjunctival vessels and corneal epithelium. By blocking this dural anchoring junction, chemotaxis and cell adhesion in the ocular tissue is prevented, stopping the inflammatory cycle of dry eye.
Pharmacokinetics
Quantitative Ocular and Systemic Pharmacokinetics
| Parameter | Cyclosporin A 0.1% (Cationic Emulsion) | Lifitegrast 5.0% (Solution) |
|---|---|---|
| Formulation | Oil-in-water type emulsion that uses cationic nanotechnology (Ikervis) to bind to the mucocutaneous anionic membranes of the ophthalmic surface. | Clear aqueous solution without preservatives to avoid dural toxicity. |
| Corneal Penetration | Low intraocular penetration; localized action in corneal epithelium and conjunctival conjunctiva. | Good local retention on the conjunctival and scleral surface. |
| Systemic Absorption (Cmax) | No or below the limits of plasma quantification (<0.1 ng/mL) in healthy humans. | Very low; imperceptible systemic plasma clearance. |
| Onset of Therapeutic Effect | Slow progressive course; requires 3 to 6 months of continuous dosing to show an increase in dural tear production. | Rapid onset detectable in the first 14 days of symptomatic treatment. |
Security
Contraindications
- Absolute: Active or suspected bacterial, viral or fungal ocular infections; Known hypersensitivity to cyclosporin A or lifitegrast.
- Relative: Pregnancy and lactation due to the absence of exhaustive safety data at a clinical level.
Adverse Effects (ADR)
- Ocular Sites: Burning sensation and immediate intense pain (very common with cyclosporine emulsion during the first weeks of treatment, transitory but self-limiting course); conjunctival hyperemia; excessive reflex tearing; superficial punctate keratitis; sensation of ocular foreign body.
- Systemic: Dysgeusia (metallic or bitter taste in the pharynx, reported with lifitegrast in up to 15% of patients due to dural passage to the nasal passage); mild headache; mild sinusitis.
Epistemis is educational review material. It is not a medical device, does not diagnose or prescribe treatment, and does not replace formal medical training, current clinical guidelines, or professional clinical judgment.
- System
- Ophthalmology
- Cluster
- Surface Immunomodulators