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Off-Label Use of Restasis™ in Eye Care
William D. Townsend, O.D.
UHCO Cornea & Contact Lenses and Contemporary Care
The 22nd Annual Symposium
December 3, 2005
1) Case I
a) 33 year old female presents with 3-day history of discomfort OD
b) OS reported to have reduced vision secondary to unknown corneal
condition
c) Systemic Hx significant for allergy, asthma, atopic dermatitis
d) Clinical findings
i) VA: OD 20/30 OS 20/200
ii) External
(1) OD: punctuate central staining, large oval ulcer superior cornea
with gr. 2+ injection, w/ eversion giant papillae,
(2) OS: central scar with neovascularization (deep) entering corneal
superiorly, Some giant papillae with eversion
(3) OU: skin of superior and inferior lids erythematous, dry and scaly in
appearance
iii) General findings
(1) Patchy dermatitis at the antecubital flexures
e) Assessment:
i) Atopic dermatitis
ii) Atopic keratoconjunctivitis
iii) Early keratitis secondary to atopic disease
f) Plan
i) Lotemax Q 4 hours
ii) Elestat Q 12 hours
iii) Non-preserved artificial tears PRN
g) Followup visit
i) VA: OD 20/50 OS 20/400
ii) Corneal changes appear to be stable, but not improved
iii) Patient complains of reduced vision and discomfort
iv) We elected to add Restasis BID OD
2) Restasis: approved by FDA December 26, 2002
a) Cyclosporine A 0.05% in ophthalmic emulsion
b) Approved for inflammatory dry eye
i) Cyclosporine
(1) Cyclic peptide produced by fungi Tolyopcladium Inflatum Gams
(2) Reversible immunomodulator of T-lymphocytes and B-lymphocytes
(3) Inhibits CD4+ T lymphocyte proliferation via inhibition of interleukin 2
receptor expression
(4) Inhibits
(a) Eosinophil and mast cell activation,
(b) Release of mediators
(c) Expression of genes involved in leukotriene synthesis
(d) Multiple cytokines required to activate cellular immunity.
(e) intracellular protein synthesis and gene activation in Tlymphocytes
(5) Original ocular application was in dogs
c) Potential off-label uses
i) Atopic keratoconjunctivitis
(1) Primary inflammatory players
(a) Epithelium: eosinophils and mast cells
(b) Substania propria
(i) CD25+ T lymphocytes(ii) Macrophages
(iii) Dendritic cells
(2) Predominant mechanism; type IV hypersensitivity
(3) Accompanying findings:
(a) Atopic dermatitis
(b) Giant papillae
(c) Keratitis w/ shield ulcer formation- 30% requires PK
(d) Neovascularization, pannus in 60% to 70% of patients
(4) Conventional therapy
(a) Topical steroids
(b) Topical “mast cell stabilizers”
(5) Akpek EK et al A randomized trial of cyclosporine 0.05% in topical
steroid-resistant atopic keratoconjuntivitis Ophthalmology March
2004
(a) Found that cyclosporine 0.05% was beneficial to patients with
steroid-resistant AKC when compared to placebo.
(b) Suggested cyclosporine may become a first line therapy for this
disease
ii) Vernal keratoconjunctivitis
(1) Primary inflammatory players
(a) Mast cells
(b) Eosinophils
(c) Lymphocytes
(d) Agent of initiation appears to be T-helper lymphocytes
(e) Not an IgE- mediated disease
(2) Estrogen and progesterone are also contributory to genesis
(3) Accompanying findings
(a) Bilateral inflammation
(b) Giant papillae
(c) Trantos dots
(d) Keratitis, shield ulcer
(4) Epidemiology
(a) Young males up until puberty
(b) 23% perennial, 16% seasonal, remainder a mixture
(c) Associated with atopy, asthma, rhinitis, eczema
(5) Bonini et al Vernal keratoconjunctivitis Eye ; April 2004
(a) Recommended cyclosporine 0.5% to 2% QID as an alternative
to corticosteroids
(6) Cetinkaya et al Topical cyclosporine in the management of shield
ulcers Cornea; March 2004
(a) In 4 case studies, found cyclosporine alone was effective in
treating shield ulcers associated with VKC
3) Conclusion
a) Cyclosporine is a potent immuno-modulator with potential as an agent for
managing ocular inflammatory disease
b) It lacks many of the undesirable side effects of corticosteroids, but is very
effective in reducing activation of eosinophils, T-lymphocytes, and the
release of inflammatory mediators
c) Further study is warranted to determine the possible benefits this agent
may offer in the long-term management of immune-based ocular disease