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Stimulation of Tear Secretion and Treatment of Dry-Eye Disease With 3-Isobutyl-1-methylxanthine

Stimulation of Tear Secretion and Treatment of Dry-Eye Disease With 3-Isobutyl-1-methylxanthine Abstract • We examined the effect of topically applied 3 - isobutyl - 1 - methylxanthine (IBMX), a known secretagogue, on tear secretion and dry-eye disease in a clinical study. We found that IBMX produced a dose-dependent decrease in tear film osmolarity that was significant at 3.0 mmol/L (P<.0005) in patients with dry-eye disease. This effect was not blocked by prior administration of proparacaine hydrochloride (P<.05). Throughout a 4-week, open-label, vehicle-controlled study, IBMX decreased tear film osmolarity significantly, whereas vehicle alone did not. After 4 weeks, mean (±SEM) osmolarity in IBMX-treated eyes decreased from 325±3.2 mOsm/L to 312±1.8 mOsm/L but remained unchanged in vehicle-treated eyes (323±4.4 mOsm/L vs 320±4.2 mOsm/L). In our study, IBMX was significantly more effective than vehicle alone in decreasing rose bengal staining (P<.02). Hence, topical IBMX stimulated tear secretion and decreased ocular surface disease in patients with dry-eye disease. References 1. Gilbard JP. Topical therapy for dry eyes . Trans Ophthalmol Soc U K . 1985;104:484-488. 2. Frost-Larsen K, Isager H, Manthorpe R. Sjogren's syndrome treated with bromhexine: a randomised clinical study . BMJ . 1978;1:1579-1581.Crossref 3. Mackie I, Seal DV. Sjogren's syndrome, bromhexine, and tear secretion . BMJ . 1978;2:638.Crossref 4. Tapper-Jones LM, Aldred MJ, Cadogan SJ, et al. Sjogren's syndrome treated with bromhexine: a reassessment . BMJ . 1980;280:1356.Crossref 5. Avisar R, Savir H, Machtey I, et al. Clinical trial of bromhexine in Sjogren's syndrome . Ann Ophthalmol . 1981;13:971-973. 6. Scharf JM, Obedeanu N, Meshulam T, et al. Influence of bromhexine on tear lysozyme level in keratoconjunctivitis sicca . Am J Ophthalmol . 1981;92:21-23. 7. Prause JU, Frost-Larsen K, Høj L, Isager H, Manthorpe R. Lacrimal and salivary secretion in Sjogren's syndrome: the effect of systemic treatment with bromhexine . Acta Ophthalmol . 1984;62:489-497.Crossref 8. Dartt DA, Shulman M, Gray KL, Rossi SR, Matkin C, Gilbard JP. Stimulation of rabbit lacrimal gland secretion with biologically active peptides . Am J Physiol . 1988;254(Gastrointestinal Liver Physiology 17):G300-G306. 9. Gilbard JP, Dartt DA, Rood RP, Rossi SR, Gray KL, Donowitz M. Increased tear secretion in pancreatic cholera: a newly recognized symptom in an experiment of nature . Am J Med . 1988;85:552-554.Crossref 10. 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. 11. Gilbard JP, Farris RL. Tear osmolarity and ocular surface disease in keratoconjunctivitis sicca . Arch Ophthalmol . 1979;97:1642-1646.Crossref 12. van Bijsterveld OP. Diagnostic tests in the sicca syndrome . Arch Ophthalmol . 1969;82:10-14.Crossref 13. Gilbard JP, Rossi SR, Gray KL. A new rabbit model for keratoconjunctivitis sicca . Invest Ophthalmol Vis Sci . 1987;28:225-228. 14. 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. 15. Gilbard JP, Farris RL, Santamaria J. Osmolarity of tear microvolumes in keratoconjunctivitis sicca . Arch Ophthalmol . 1978;96:677-681.Crossref 16. Gilbard JP, Farris RL. Ocular surface drying and tear film osmolarity in thyroid eye disease . Acta Ophthalmol . 1983;61:108-116.Crossref 17. Gilbard JP, Gray KL, Rossi SR. Improved technique for storage of tear microvolumes . Invest Ophthalmol Vis Sci . 1987;28:401-403. 18. Rall TW. Central nervous system stimulants: the methylxanthines . In: Gilman AG, Goodman LS, Rall TW, Murad F, eds. Goodman and Gilman's The Pharmacological Basis of Therapeutics . 7th ed. New York, NY: Macmillan Publishing Co Inc; 1985:591-593. 19. Geggel HS, Friend J, Thoft RA. Conjunctival epithelial wound healing . Invest Ophthalmol Vis Sci . 1984;25:860-863. 20. Jordan A, Baum J. Basic tear flow: does it exist? Ophthalmology . 1980;87:920-930.Crossref 21. 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Ophthalmology American Medical Association

Stimulation of Tear Secretion and Treatment of Dry-Eye Disease With 3-Isobutyl-1-methylxanthine

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References (23)

Publisher
American Medical Association
Copyright
Copyright © 1991 American Medical Association. All Rights Reserved.
ISSN
0003-9950
eISSN
1538-3687
DOI
10.1001/archopht.1991.01080050086035
Publisher site
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Abstract

Abstract • We examined the effect of topically applied 3 - isobutyl - 1 - methylxanthine (IBMX), a known secretagogue, on tear secretion and dry-eye disease in a clinical study. We found that IBMX produced a dose-dependent decrease in tear film osmolarity that was significant at 3.0 mmol/L (P<.0005) in patients with dry-eye disease. This effect was not blocked by prior administration of proparacaine hydrochloride (P<.05). Throughout a 4-week, open-label, vehicle-controlled study, IBMX decreased tear film osmolarity significantly, whereas vehicle alone did not. After 4 weeks, mean (±SEM) osmolarity in IBMX-treated eyes decreased from 325±3.2 mOsm/L to 312±1.8 mOsm/L but remained unchanged in vehicle-treated eyes (323±4.4 mOsm/L vs 320±4.2 mOsm/L). In our study, IBMX was significantly more effective than vehicle alone in decreasing rose bengal staining (P<.02). Hence, topical IBMX stimulated tear secretion and decreased ocular surface disease in patients with dry-eye disease. References 1. Gilbard JP. Topical therapy for dry eyes . Trans Ophthalmol Soc U K . 1985;104:484-488. 2. Frost-Larsen K, Isager H, Manthorpe R. Sjogren's syndrome treated with bromhexine: a randomised clinical study . BMJ . 1978;1:1579-1581.Crossref 3. Mackie I, Seal DV. Sjogren's syndrome, bromhexine, and tear secretion . BMJ . 1978;2:638.Crossref 4. Tapper-Jones LM, Aldred MJ, Cadogan SJ, et al. Sjogren's syndrome treated with bromhexine: a reassessment . BMJ . 1980;280:1356.Crossref 5. Avisar R, Savir H, Machtey I, et al. Clinical trial of bromhexine in Sjogren's syndrome . Ann Ophthalmol . 1981;13:971-973. 6. Scharf JM, Obedeanu N, Meshulam T, et al. Influence of bromhexine on tear lysozyme level in keratoconjunctivitis sicca . Am J Ophthalmol . 1981;92:21-23. 7. Prause JU, Frost-Larsen K, Høj L, Isager H, Manthorpe R. Lacrimal and salivary secretion in Sjogren's syndrome: the effect of systemic treatment with bromhexine . Acta Ophthalmol . 1984;62:489-497.Crossref 8. Dartt DA, Shulman M, Gray KL, Rossi SR, Matkin C, Gilbard JP. Stimulation of rabbit lacrimal gland secretion with biologically active peptides . Am J Physiol . 1988;254(Gastrointestinal Liver Physiology 17):G300-G306. 9. Gilbard JP, Dartt DA, Rood RP, Rossi SR, Gray KL, Donowitz M. Increased tear secretion in pancreatic cholera: a newly recognized symptom in an experiment of nature . Am J Med . 1988;85:552-554.Crossref 10. 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. 11. Gilbard JP, Farris RL. Tear osmolarity and ocular surface disease in keratoconjunctivitis sicca . Arch Ophthalmol . 1979;97:1642-1646.Crossref 12. van Bijsterveld OP. Diagnostic tests in the sicca syndrome . Arch Ophthalmol . 1969;82:10-14.Crossref 13. Gilbard JP, Rossi SR, Gray KL. A new rabbit model for keratoconjunctivitis sicca . Invest Ophthalmol Vis Sci . 1987;28:225-228. 14. 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. 15. Gilbard JP, Farris RL, Santamaria J. Osmolarity of tear microvolumes in keratoconjunctivitis sicca . Arch Ophthalmol . 1978;96:677-681.Crossref 16. Gilbard JP, Farris RL. Ocular surface drying and tear film osmolarity in thyroid eye disease . Acta Ophthalmol . 1983;61:108-116.Crossref 17. Gilbard JP, Gray KL, Rossi SR. Improved technique for storage of tear microvolumes . Invest Ophthalmol Vis Sci . 1987;28:401-403. 18. Rall TW. Central nervous system stimulants: the methylxanthines . In: Gilman AG, Goodman LS, Rall TW, Murad F, eds. Goodman and Gilman's The Pharmacological Basis of Therapeutics . 7th ed. New York, NY: Macmillan Publishing Co Inc; 1985:591-593. 19. Geggel HS, Friend J, Thoft RA. Conjunctival epithelial wound healing . Invest Ophthalmol Vis Sci . 1984;25:860-863. 20. Jordan A, Baum J. Basic tear flow: does it exist? Ophthalmology . 1980;87:920-930.Crossref 21. 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.

Journal

Archives of Ophthalmology – American Medical Association

Published: May 1, 1991

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