[Skip to Content]
[Skip to Content Landing]
Article
December 1994

Treatment of Keratoconjunctivitis Sicca in Rabbits With 3-Isobutyl-1-Methylxanthine

Author Affiliations

From the Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, Mass. Dr Gilbard and Darlene A. Dartt, PhD, the inventors, and the Schepens Eye Research Institute, Boston, Mass, the assignee, have a proprietary interest in the technology discussed in this report.

Arch Ophthalmol. 1994;112(12):1614-1616. doi:10.1001/archopht.1994.01090240120036
Abstract

Objective:  To examine the effects of topical 3-isobutyl-1-methylxanthine treatment on tear-film osmolarity, conjunctival goblet-cell densities, and corneal epithelial glycogen levels in a rabbit model for keratoconjunctivitis sicca.

Methods:  Keratoconjunctivitis sicca was surgically induced in the right eyes of 16 rabbits. In a masked protocol, eight of these operated-on eyes underwent treatment for 12 weeks with a 3.0-mmol solution of 3-isobutyl-1-methylxanthine. The remaining eight operated-on eyes were left untreated and served as controls.

Results:  The 3-isobutyl-1-methylxanthine treatment resulted in a rapid and significant decrease in tear osmolarity and sodium (P<.5) and potassium levels (P<.05) and a significant increase in conjunctival goblet-cell densities and corneal epithelial glycogen levels compared with untreated and operated-on controls (P<.001).

Conclusions:  3-Isobutyl-1-methylxanthine rapidly and significantly decreased tear-film osmolarity in this rabbit model for keratoconjunctivitis sicca and restored conjunctival goblet-cell densities and corneal glycogen levels, thus reversing the disease process.

References
1.
Gilbard JP, Dartt DA.  Changes in rabbit lacrimal gland fluid osmolarity with flow rate . Invest Ophthalmol Vis Sci . 1982;23:804-806.
2.
Gilbard JP, Gray KL, Rossi SR.  A proposed mechanism for increased tear-film osmolarity in contact lens wearers . Am J Ophthalmol . 1986;102:505-507.
3.
Gilbard JP, Rossi SR, Gray KL.  A new rabbit model for keratoconjunctivitis sicca . Invest Ophthalmol Vis Sci . 1987;28:225-228.
4.
Gilbard JP, Rossi SR, Gray KL, Hanninen LA, Kenyon KR.  Tear film osmolarity and ocular surface disease in two rabbit models for keratoconjunctivitis sicca . Invest Ophthalmol Vis Sci . 1988;29:374-378.
5.
Gilbard JP, Rossi SR, Gray KL, Hanninen LA.  Natural history of disease in a rabbit model for keratoconjunctivitis sicca . Acta Ophthalmol . 1989;67( (suppl 192) ):95-101.Article
6.
Gilbard JP, Rossi SR.  Tear film and ocular surface changes in a rabbit model of neurotrophic keratitis . Ophthalmology . 1990;97:308-312.Article
7.
Gilbard JP, Farris RL.  Ocular surface drying and tear film osmolarity in thyroid eye disease . Acta Ophthalmol . 1983;61:108-116.Article
8.
Gilbard JP, Rossi SR, Gray Heyda K.  Tear film and ocular surface changes after closure of the meibomian gland orifices in the rabbit . Ophthalmology . 1989;6:1180-1186.Article
9.
Gilbard JP, Rossi SR, Gray KL.  Mechanisms for increased tear film osmolarity . In: Cavanagh HD, ed. The Cornea: Transactions of the World Congress on the Cornea III . New York, NY: Raven Press; 1988:5-7.
10.
Ralph RA.  Conjunctival goblet cell density in normal subjects and in dry eye syndromes . Invest Ophthalmol . 1975;14:299-302.
11.
Nelson JD, Havener VR, Cameron JD.  Cellulose acetate impressions of the ocular surface . Arch Ophthalmol . 1983;101:1869-1872.Article
12.
Nelson JD, Wright JC.  Conjunctival goblet cell densities in ocular surface disease . Arch Ophthalmol . 1984;103:1049-1051.Article
13.
Abdel-Khalek LMR, Williamson J, Lee WR.  Morphological changes in the human conjunctival epithelium, II: in keratoconjunctivitis sicca . Br J Ophthalmol . 1978;62:800-806.Article
14.
Meyer E, Scharf Y, Schechner R, Zonis S, Scharf M, Nahir M.  Light and electron microscopic study of the conjunctiva in sicca syndrome . Ophthalmologica . 1985;190:45-51.Article
15.
Sjogren H.  Keratoconjunctivitis sicca . In: Ridley F, Sorsby A, eds. Modern Trends in Ophthalmology . London, England: Butterworth & Co Ltd; 1940:403-413.
16.
Gilbard JP, Rossi SR, Gray Heyda K, Dartt DA.  Stimulation of tear secretion by topical agents that increase cyclic nucleotide levels . Invest Ophthalmol Vis Sci . 1990;31:1381-1388.
17.
Gilbard, JP, Farris RL, Santamaria J.  Osmolarity of tear microvolumes in keratoconjunctivitis sicca . Arch Ophthalmol . 1978;96:677-681.Article
18.
Gilbard JP, Gray KL, Rossi SR.  Improved technique for storage of tear microvolumes . Invest Ophthalmol Vis Sci . 1987;28:401-403.
19.
Gilbard JP, Rossi SR, Gray Heyda K.  Ophthalmic solutions, the ocular surface, and a unique therapeutic artificial tear formulation . Am J Ophthalmol . 1989;107:348-355.
20.
Friend J, Kiorpes T, Kinoshita S.  Glycogen and DNA content of corneal epithelium: comparison of preparation methods . Invest Ophthalmol Vis Sci . 1983;24:203-207.
21.
Gilbard JP, Rossi SR.  An electrolyte-based solution that increases corneal glycogen and conjunctival goblet-cell density in a rabbit model for keratoconjunctivitis sicca . Ophthalmology . 1992;99:600-604.Article
22.
Gilbard JP, Rossi SR, Gray Heyda K, Dartt DA.  Stimulation of tear secretion and treatment of dry-eye disease with 3-isobutyl-1-methylxanthine . Arch Ophthalmol . 1991;109:672-676.Article
×