Transcript Dry Eye Continuum of Care

1
Conjunctival Goblet cell Density
Following Sequential Therapy
With Artificial Tear and
Cyclosporine 0.05%
Frank A. Bucci, Jr, MD1; Stephen C. Pflugfelder, MD2;
Solherny Pangelinan, MD2
1Bucci
Laser Vision Institute, Wilkes-Barre, PA; 2Ocular Surface Center,
Baylor College of Medicine, Houston, TX
2
INTRODUCTION
•
Inflammation plays a major role in the development of dry eye disease1,
which is characterized by abnormal tear film composition.2-4
•
Goblet cell are important for normal composition of tear film and may serve
as an indicator of ocular surface health.
–
Goblet cells secrete the soluble mucin MUC5AC, which increases the viscosity
and resistance of the tear film against thinning and breakup during the blink
cycle.5
–
The number of conjunctival goblet cells is decreased in dry eye patients.6
– Soluble mucin concentration is also reduced by 60% in the tear film.
•
Cyclosporine 0.05% was demonstrated to significantly improve tear
production and alleviate disease symptoms in dry eye patients.7
•
The aim of this study was to evaluate conjunctival goblet cell density and
the levels of tear growth factor and cytokines following sequential therapy
with artificial tears and cyclosporine 0.05% in patients with dry eye disease.
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METHODS
• Multicenter, randomized, prospective trial
• Enrolled dry eye patients with
– Ocular Surface Disease Index (OSDI) score ≥ 25
– Tear fluorescein break-up time ≤ 8 seconds.
• Study treatments:
Systane® or
REFRESH Liquigel®b
Washouta
-2
0
Cyclosporine 0.05% BID
3
6
Weeks
Evaluation of goblet cell density in inferior bulbar conjunctiva
Determination of growth factors and cytokine levels in tear
aPatients
received non-preserved artificial tear REFRESH PLUS®.
bPatients were randomized to receive either of the artificial tears QID.
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4
METHODS
• Impression cytology
– Cytology samples were taken from the inferior bulbar
conjunctiva using a nitrocellulose membrane.
– Membranes were stained with a modified periodic acid–Schiff
(PAS) Papanicolaou stain.8
– Goblet cells were counted in 5 (400 x 400 mm) representative
microscopic fields in each membrane.
• Tear Immunoassays
– Epidermal growth factor (EGF) and a panel of 8 inflammatory
cytokines/chemokines (IL-1 , IL-1 , IL-2, IL-6, IL-8, IL-12, IL13, and RANTES) were measured on a Luminex multiplex
system using Upstate Biotechnology Beadlyte reagents.
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RESULTS
Patient Disposition
• A total of 19 patients were enrolled
• 16 patients completed the study
– 9 patients had inadequate samples
– 7 patients were included in the analyses
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Conjunctival Goblet Cell Density
Mean Number of Goblet
Cells Per Field
80
53.8*
60
*P < .001
compared
to weeks 0
and 3
40
20
0
20.8
18.3
1
Week 0
(Baseline)
2
3
Week 3
Week 9
(Artificial tear) (Cyclosporine 0.05%)
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Tear EGF and Cytokine Levels
• An increase in the level of tear IL-13 was noted after
the treatment with cyclosporine 0.05% at week 9.
This difference, however, did not reach statistical
significance.
• The levels of tear EGF and other cytokines were not
changed after the treatment with artificial tears or
cyclosporine 0.05%.
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CONCLUSIONS
• Cyclosporine 0.05%, but not artificial tears, increased
goblet cell density in conjunctiva of dry eye patients.
• These findings suggest that chronic dry eye patients
may benefit more from cyclosporine 0.05% therapy
than artificial tears.
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REFERENCES
1. Wilson SE. Inflammation: a unifying theory for the origin of dry eye syndrome. Manag
Care 2003;12:14-19.
2. Ogasawara K, Mitsubayashi K, Tsuru T, Karube I. Electrical conductivity of tear fluid in
healthy persons and keratoconjunctivitis sicca patients measured by a flexible
conductimetric sensor. Graefes Arch Clin Exp Ophthalmol 1996;234:542-546.
3.
Solomon A, Dursun D, Liu Z, Xie Y, Macri A, Pflugfelder SC. Pro- and antiinflammatory forms of interleukin-1 in the tear fluid and conjunctiva of patients with
dry-eye disease. Invest Ophthalmol Vis Sci 2001;42:2283-2292.
4. Zhao H, Jumblatt JE, Wood TO, Jumblatt MM. Quantification of MUC5AC protein in
human tears. Cornea 2001;20:873-877.
5. Pflugfelder SC, Tseng SC, Yoshino K, et al. Correlation of goblet cell density and
mucosal epithelial membrane mucin expression with rose bengal staining in patients
with ocular irritation. Ophthalmology. 1997;104:223–235.
6. Argueso P, Balaram M, Spurr-Michaud S, et al. Decreased levels of the goblet cell
mucin MUC5AC in tears of patients with Sjogren syndrome. Invest Ophthalmol Vis Sci.
2002;43:1004–1011.
7. Sall K, Stevenson OD, Mundorf TK, Reis BL, and the CsA Phase 3 Study Group. Two
multicenter, randomized studies of the efficacy and safety of cyclosporine ophthalmic
emulsion in moderate to severe dry eye disease [published correction appears in
Ophthalmology. 2000;107:1220]. Ophthalmology. 2000;107:631-639.
8. Tseng SC. Staging of conjunctival squamous metaplasia by impression cytology.
Ophthalmology. 1985;92:728–733.