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June 1, 2000
BELLFLOWER, Calif. — When used as an eye drop, cyclosporine A is safe
and effective in treating moderate to severe dry eye disease, according to
the results of two phase 3 multicenter, randomized studies that appeared
recently in Ophthalmology.
“This is a new application for cyclosporine,” lead author Kenneth N.
Sall, MD, a general ophthalmologist in private practice here, told
Ocular Surgery News. “The new drug application for
cyclosporine eye drops in patients with moderate to severe dry eye is
currently under review at the Food and Drug Administration.”
The two studies evaluated both 0.05% and 0.1% dosages of cyclosporine
twice daily. “There really wasn’t a big difference between the two doses,”
Dr. Sall said. “The lower dose is what Allergan intends to market.”
Previous studies have suggested that dry eye disease is the result of
an underlying cytokine and receptor-mediated inflammatory process
affecting both the lacrimal gland and the ocular surface. “There is this
feedback loop between the cornea and the lacrimal gland that tells the
gland to produce more tears,” Dr. Sall said. “This feedback loop is not
working properly in patients with moderate to severe dry eye.” Animal and
human studies also have demonstrated that topical treatment with the
immunomodulatory agent cyclosporine A “can have beneficial effects on the
underlying inflammatory pathologic condition of dry eye disease, as well
as improve the signs and symptoms of this condition,” he said.
“Cyclosporine helps restore the feedback loop so it functions better and
returns everything to a more normal state.”
![[bar]](OSN%20Cyclosporine%20_files/gradient.gif)
Study design
The two identical multicenter studies had a combined enrollment of 877
patients, mostly women (82%) and Caucasian (84%). Patients were divided in
approximately equal numbers into three treatment groups: cyclosporine
0.05%, cyclosporine 0.1% and placebo. During the 6-month treatment phase,
patients were instructed to instill one drop of study medication twice
daily in each eye (one on waking in the morning and the other at bedtime).
Individually packaged preservative-free artificial tears (Refresh
Lubricant Eye Drops; Allergan) also were provided as an adjunctive
treatment to be used as frequently as needed.
About 76% (671 out of 877) of enrolled patients completed the study.
The results of the two trials were combined for analysis. Among the
objective findings, “there was an improvement in corneal staining,” Dr.
Sall said. The improvement in corneal staining was significantly greater
in both cyclosporine groups than in the placebo group (P=.044) at 4
months and in the cyclosporine 0.05% group at 6 months (P=.008).
There also was a trend (P=.062) toward a significantly greater
improvement in the cyclosporine 0.1% group compared with the placebo group
at 6 months.
The Schirmer tear test also reflected a statistically significant
improvement with cyclosporine. “The cyclosporine patients had an increase
in tear production,” Dr. Sall said. At 3 months, there was a significant
worsening in the placebo group (P=.014) and a significant
difference among the treatment groups, with the cyclosporine group
significantly greater than the placebo group (P=.009). Furthermore,
at 6 months, there was a statistically significant improvement from
baseline for both cyclosporine groups.
Subjective symptoms improve
The most notable change in subjective ocular symptoms was blurred
vision. The decrease from baseline was statistically significant in both
cyclosporine groups at all follow-up visits (P=.012), but only at 6
months with the placebo group (P=.039). “The improvement in blurred
vision also was significantly greater in the cyclosporine 0.05% group
compared with the placebo group at all follow-up visits (P=.014),”
Dr. Sall said.
Moreover, “The patients on the drug compared with those on placebo
needed to use less additional supplemental eye drops for control of their
symptoms. This is a significant factor,” Dr. Sall said. “Here we have
patients all day long taking eye drops to keep their eyes moist, but the
patients on cyclosporine had to use less supplemental drops. It indicates
that their comfort improved.” In addition, the investigator’s evaluation
of global response to treatment “felt that patients on cyclosporine were
better,” he said.
“The drug is very safe and side effects are minimal,” Dr. Sall said.
“There were no serious adverse reactions.” The most commonly reported
treatment-related adverse event with cyclosporine was mild ocular burning
and stinging, followed by discharge in the eye and foreign body sensation.
“It also is important to note that only two patients experienced ocular
infection during treatment, and both of these patients were in the placebo
group,” Dr. Sall said.
Even greater benefit
Dr. Sall is optimistic that patients will enjoy an even greater benefit
from cyclosporine when used in combination with other drugs, such as “a
low-dose steroid eye drop to calm the eye.” He believes that many patients
will probably continue some artificial tear use but patient compliance
will be enhanced because “it will make them less dependent on artificial
tears.”
Prior to cyclosporine, “the whole therapy of dry eye has been ‘Okay,
your eyes are dry. We don’t have anything to make your eyes more moist
except a bottle of tears that you buy at the drugstore,’” Dr. Sall said.
“This therapy is new in that it helps your own lacrimal gland produce more
and better quality tears. So it’s therapeutic versus palliative.” In
essence, the treatment “represents a significant breakthrough in the
management of this common and frustrating condition. Physicians will be
very pleased when they start adding cyclosporine to their armamentarium
with other treatments for dry eye,” Dr. Sall said.
For Your Information:
- Kenneth N. Sall, MD, can be reached at 9604 Artesia Blvd., Ste.
203, Bellflower, CA 90706; (562) 804-1974; fax: (562) 804-4350;
e-mail: salleyectr@aol.com.
Dr. Sall has no direct financial interest in any of the products
mentioned in this article, nor is he a paid consultant for any
companies mentioned.
Reference:
- Sall K, Stevenson OD, Mundorf TK, et al. Two multicenter,
randomized studies of the efficacy and safety of cyclosporine
ophthalmic emulsion in moderate to severe dry eye disease.
Ophthalmology. 2000;107: 631-639.
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