This study will examine whether cyclosporin A eye drops alleviate dry eye syndrome, a
disorder of tear deficiency or excessive tear evaporation. The condition damages the
surface of the eye and causes discomfort.
Age-related dry eye syndrome may result from a problem with the immune system in which cells
called lymphocytes infiltrate the tear glands and cause a chronic, progressive inflammatory
process. Previous studies suggest that cyclosporin A may increase tear production or
decrease inflammation on the surface of the eye, or both, improving dry eye symptoms.
Patients in the study will undergo a complete eye examination, and a small tear sample will
be collected to study tear consistency and composition. A small amount of conjunctiva (the
clear, thin covering of the eye lining the eyelids and eyeball) will be removed to study
substances in it that might provide information on what causes dry eye. A blood sample also
will be taken to look for antibodies found in patients with Sjogren's syndrome, a disorder
characterized by dryness of the mouth, eyes and other mucous membranes. Patients will also
fill out forms providing information on the extent to which their dry eyes bother them.
Patients will be randomly divided into two treatment groups: one will take a cyclosporin
0.1% eye drop emulsion; the other will take the emulsion vehicle alone-that is, the same
drops but without the active ingredient cyclosporin. Both groups will take one drop in each
eye 4 times a day for 2 months. Neither the patients nor the doctors will know which
patients are receiving which medication until the study ends. All patients will also be
given artificial teardrops to use for comfort if needed.
Dry eye syndrome, also known as keratoconjunctivitis sicca or KCS, is a disorder of the tear
film leading to damage to the ocular surface and ocular discomfort. In aqueous tear
deficient dry eye, there is inadequate tear production. Patients with dry eye include those
who have KCS and those with a more severe form of KCS associated with Sjogren's Syndrome
(SS). In SS, lymphocytic infiltration of the lacrimal gland leads to destruction of acinar
structures and impaired glandular function. Although most cases of KCS are not due to
Sjogren's Syndrome, lymphocytic infiltration of the lacrimal glands of non-Sjogren's KCS
patients has been demonstrated and some authors suggest that age-related atrophic changes of
the lacrimal gland may be secondary to a chronic progressive inflammatory process. Several
clinical studies have indicated that systemic or topical CsA improves some objective or
subjective signs of KCS in patients with or without SS. In this protocol, patients with
aqueous tear deficient KCS will be randomized to treatment with topical CsA 0.1% or the
emulsion vehicle. To determine the safety and efficacy of CsA 0.1% treatment in patients
with KCS, comprehensive ophthalmologic examinations and standardized symptom assessments
will be performed. In addition, to determine the ability of topical CSA to alter ocular
surface inflammation, pre- and post-treatment conjunctival biopsy specimens will be analyzed
for infiltrating lymphocytes.
Diagnosis of CS with documented symptoms and signs (as required below) despite
conventional management which may include artificial tears, gels and ointments,
sympathomimetic agents and parasympathomimetic agents:
Schirmer (without anesthesia) less than or equal to 8 mm/5 min in at least one eye;
HOWEVER, if Schirmer (without anesthesia) is zero (0) mm, Schirmer with nasal stimulation
greater than or equal to 3 mm/ 5 min in the same eye, OR;
Schirmer (with anesthesia) less than or equal to 10 mm/ 5 min in at least one eye and sum
of interpalpebral staining greater than or equal to 3+ or corneal staining greater than or
equal to 1+ in the same eye.
Able and willing to provide informed consent.
Willingness and ability to meet followup requirements.
Female patients of childbearing potential must use reliable forms of contraception during
A negative pregnancy test result in women of childbearing potential.
Normal lid position and closure.
The following topical (creams, ointments or patches) or systemic medications are allowed
as long as the patient has been on a stable dose for at least 90 days before the baseline
visit: Estrogen-progesterone, or other estrogen derivatives.
If using concomitant medications, and the patient's condition is stable, the patient must
agree to remain on a stable dose of his or her concomitant medications throughout the
study period, or if the patient's condition is not stable, then they must agree not to use
Review of the instructions for use of concomitant medications during the study, prior to
the eye examination, and agreement from the patient that they will comply with the
instructions. A copy of the instructions must be given to the patient prior to
Patient must not have uncontrolled systemic disease (e.g., hypertension, diabetes) or the
presence of any significant illness (e.g., serious gastrointestinal, renal, hepatic,
endocrine, pulmonary, cardiac, neurologic disease, cancer, AIDS, or cerebral dysfunction)
that could, in the judgment of the investigator, interfere with interpretation of the
Patients must not have used ophthalmic topical or systemic cyclosporine in the past 90
Patients must not have Schirmer readings less than 3 mm/5 min, without anesthesia, in both
eyes after stimulation thereby indicating end stage lacrimal gland disease.
Patient must not have active ocular infection or non-KCS ocular inflammation.
Patient must not have a history of recurrent herpes keratitis or active disease within the
last six months.
Patient must not have corneal disorder or abnormality that effects corneal sensitivity or
normal spreading of the tear film (except SPK).
Patient must not have severe blepharitis or obvious inflammation of the lid margin which
in the judgment of the investigator may interfere with the interpretation of the study
No plug placement (laser, cautery, silicone, or collagen implant) within one month prior
to the screening visit.
No punctal occlusion performed during the study.
Patient must not have a history of anterior segment surgery or trauma which could affect
corneal sensitivity (e.g., cataract surgery or any surgery involving a limbal or corneal
incision within the last 12 months).
Patient must not have KCS secondary to the destruction of conjunctival goblet cells as
occurs with vitamin A deficiency or scarring such as that with cicatricial pemphigoid,
alkali burns, Stevens-Johnson syndrome, trachoma, or irradiation.
Patients must not use Saligan or antihistamines more than 3 times a week.