How is cyclosporin (cyclosporine) used for optic conditions?

Cyclosporine Ophthalmic Use in Ocular Conditions

Cyclosporine 0.05% ophthalmic emulsion (Restasis) is FDA-approved and recommended as a second-line anti-inflammatory therapy for moderate to severe dry eye disease when artificial tears are insufficient, working by inhibiting T-cell activation and inflammatory cytokine production. 1, 2

Primary Indication: Dry Eye Disease

Mechanism of Action

• Cyclosporine prevents activation and nuclear translocation of cytoplasmic transcription factors required for T-cell activation and inflammatory cytokine production 1
• It inhibits mitochondrial pathways of apoptosis in ocular surface cells 1
• The drug acts as a partial immunomodulator in patients whose tear production is suppressed due to ocular inflammation associated with keratoconjunctivitis sicca 2

Clinical Efficacy in Dry Eye

• In patients with mild, moderate, and severe dry eye, cyclosporine 0.05% demonstrated success rates of 74%, 72%, and 67% respectively 1, 3
• A statistically significant 10-mm increase in Schirmer test results occurred in 15% of cyclosporine-treated patients compared with 5% of vehicle-treated patients at 6 months 1
• The drug may increase conjunctival goblet cell numbers, though evidence that this translates to improved mucus production is lacking 1

Dosing and Administration

• Standard dosing is twice daily (approximately 12 hours apart) using single-use vials 2
• After 1 full year of twice-daily therapy, dosage can be decreased to once daily in some patients without loss of beneficial effects 1
• For severe refractory dry eye, higher frequency dosing (3-4 times daily) may be necessary when twice-daily regimen is inadequate 4
• Each 0.4 mL single-use vial should be inverted before use, used immediately after opening, and then discarded 2

Treatment Algorithm for Dry Eye

• First-line (mild disease): Preservative-free artificial tears (methylcellulose or hyaluronate-based) at least twice daily, increased as needed 3
• Second-line (moderate disease): Add cyclosporine 0.05% twice daily when artificial tears are insufficient 1, 3
• Alternative second-line: Lifitegrast 5% can be used instead of cyclosporine for patients with inadequate response to artificial tears 5
• Short-term adjunct: Topical corticosteroids (loteprednol etabonate 0.25%) for 2-4 weeks maximum to suppress acute inflammation 1
• Severe/refractory disease: Consider increasing cyclosporine frequency to 3-4 times daily, autologous serum drops, or punctal occlusion 3, 4

Evidence Quality Considerations

Cochrane Review Findings (2019)

The most comprehensive systematic review found inconsistent evidence regarding cyclosporine's effects 6:

• Evidence is inconsistent about effects on ocular discomfort, fluorescein staining, Schirmer test, and tear break-up time 6
• May increase conjunctival goblet cell density (MD 22.5 cells per unit, 95% CI 16.3 to 28.8), but clinical significance unclear 6
• The 2024 AAO guideline acknowledges this inconsistency but still recommends cyclosporine based on clinical experience and disease-modifying potential 1

Additional Ophthalmic Indications (Off-Label)

Dupilumab-Related Ocular Surface Disorders

• Cyclosporine eyedrops showed 63% response rate in managing dupilumab-related ocular surface disorders 1
• Should usually be initiated by ophthalmologists, though may be suitable for dermatologists under agreed local pathways 1
• Licensed for severe keratitis in dry eye disease that has not responded to tear substitutes 1

Sjögren's Syndrome

• Cyclosporine 0.05% is approved for keratoconjunctivitis sicca and can be used in Sjögren's-related dry eye 1
• Should be reserved for refractory or severe ocular dryness managed by experienced ophthalmologists 1
• Used as short-term therapy (maximum 2-4 weeks) for severe cases 1

Other Inflammatory Ocular Conditions (Research Evidence)

Cyclosporine has shown efficacy in several other conditions, though these remain off-label 7, 8:

• High-risk corneal transplant rejection prevention (61% of 2% formulation prescriptions) 8
• Vernal keratoconjunctivitis (5-10% of prescriptions) 8
• Atopic keratoconjunctivitis (5-8% of prescriptions) 8
• Ocular graft-versus-host disease 4
• Posterior blepharitis and ocular rosacea 7

Adverse Effects and Tolerability

Common Side Effects

• Ocular burning was reported in 17% of patients, typically mild and transient 1
• Other effects include redness, itching, and irritation (37% of patients experience some adverse effect) 8
• New-onset burning or irritation may occur in 13.6% when increasing to high-frequency dosing 4
• Treatment-related adverse events are more likely with cyclosporine than vehicle (RR 1.33,95% CI 1.00 to 1.78) 6

Safety Profile

• No detectable drug accumulation in blood during 12 months of treatment; blood concentrations remain below 0.1 ng/mL 2
• No increase in bacterial or fungal ocular infections reported 2
• Generally well-tolerated with no serious systemic adverse effects from topical use 7

Critical Pitfalls to Avoid

• Do not use cyclosporine as first-line therapy—artificial tears must be tried first for mild dry eye 1, 3
• Do not expect immediate results—therapeutic effects typically require 3-6 months of consistent use 1
• Do not use in patients currently taking topical anti-inflammatory drugs or using punctal plugs without ophthalmology consultation—increased tear production was not seen in these patients 2
• Do not combine with long-term topical corticosteroids—limit steroid use to 2-4 weeks maximum to avoid complications (infections, increased intraocular pressure, cataracts) 1
• Do not discontinue prematurely due to burning sensation—this is common (17%) and usually resolves with continued use 1
• Monitor patients who fail twice-daily dosing—they may benefit from increased frequency (3-4 times daily) rather than discontinuation 4