Eye (1990) 4, 594–602; doi: 10.1038/eye.1990.83

Precorneal residence times of sodium hyaluronate solutions studied by quantitative gamma scintigraphy

G R Snibson1, J L Greaves2, N D W Soper3, J I Prydal4, C G Wilson2 and A J Bron1

  1. 1University of Oxford, Department of Ophthalmology
  2. 2University of Nottingham, Department of Physiology and Pharmacology
  3. 3Department of Nuclear Medicine, John Radcliffe Hospital, Oxford
  4. 4University of Cambridge, Department of Physiology

Correspondence: Professor A. J. Bron, Nuffield Laboratory of Ophthalmology, Walton Street, Oxford OX2 6AW



Sodium hyaluronate solutions have been advocated in the management of a variety of dry-eye states. By virtue of their non-Newtonian rheological properties, formulations exhibiting high zero-shear viscosities may be used as an artificial tear with the expectation of prolonged precorneal residence times and improved tolerance. Quantitative gamma scintigraphy was used to evaluate the residence times of 0.2% and 0.3% sodium hyaluronate solutions and a polymer-free solution of buffered saline in 12 patients with keratoconjunctivitis sicca and a group of six normal volunteers. Using several indices of residence time, mean values for the sodium hyalur onate solutions were significantly longer than those for buffered saline. Parallel changes in tear film thickness were also demonstrated using a technique based on laser interferometry.



  1. Bron AJ: Duke-Elder Lecture: Prospects for the dry eye. Trans Ophthalmol Soc UK 1985, 104: 801–26. | PubMed |
  2. Lemp MA: General measures in management of the dry eye. Int Ophthalmol Clin 1987, 27: 36–43. | Article | PubMed | ISI |
  3. Blaug SM and Canada AT: Relationship of viscosity, contact time, and prolongation of action of methylcellulose—containing ophthalmic solutions. Am J Hosp Pharm 1965, 22: 662–6. | PubMed |
  4. Wilson CG, Olejnik O, Hardy JG: Precorneal drainage of polyvinyl alcohol solutions in the rabbit assessed by gamma scintigraphy. J Pharm Pharmacol 1986, 35: 451. | Article |
  5. Werblin TP, Rheinstrom SD, Kaufman HE: The use of slow-release artificial tears int he long-term management of keratitis sicca. Ophthalmology 1981, 88(1): 78–81.
  6. Dohlman CH: Punctal occlusion in keratoconjunctivitis sicca. Trans ophthalmol Soc UK 1978, 98: 1277–81.
  7. Chrai SS and Robinson JR: Ocular evaluation of methylcellulose vehicle in albino rabbits. J Pharm Sci 1974, 63: 1218. | Article | PubMed | ISI |
  8. Bach FC, Adam JB, McWhirter HC, Johnson JE: Ocular retention of artificial tear solutions. Ann Ophthalmol 1972, 4: 116–19. | PubMed |
  9. Bothner H and Wik O: Rheology of intraocular fluids. In Rosen ES ed. Viscoelastic Materials: Basic science and clinical applications. Pergamon Press, 1989: 3–22.
  10. Adler CA, Maurice DM, Paterson ME: The effect of viscosity of the vehicle on the penetration of fluorescein into the human eye. Exp Eye Res 1971, 11: 34–42. | Article | PubMed | ISI |
  11. Dudinski O, Finnin BC, Reed BL: Acceptability of thickened eye drops to human subjects. Curr Ther Res 1983, 33(2): 322–37.
  12. Polack FM and McNiece MT: The treatment of dry eyes with Na hyaluronate (Healon): a preliminary report. Cornea 1982, 1: 133–36.
  13. DeLuise VP and Peterson WS: The use of topical Healon tears in the management of refractory dry-eye syndrome. Ann Ophthalmol 1984, 16: 823–4. | PubMed | ISI |
  14. Stuart JC and Linn JG: Dilute sodium hyaluronate (Healon) in the treatment of ocular surface disorders. Ann Ophthalmol 1985, 17: 190–92. | PubMed | ISI |
  15. Gee S and Tabbara KF: The effects of hyaluronic acid on patients with keratoconjunctivitis sicca. Saudi Bull Ophthalmol 1987, 2(3): 24–6.
  16. Limberg MB, McCaa C, Kissling GE, Kaufman HE: Topical application of hyaluronic acid and chondroitin sulfate in the treatment of dry eyes. Am J Ophthalmol 1987, 103: 194–7. | PubMed | ISI |
  17. Laflamme MY and Swieca R: A comparative study of two preservative-free tear substitutes in the management of severe dry eye. Can J Ophthalmol 1988, 23: 174–6. | PubMed | ISI |
  18. Nelson JD and Farris RL: Sodium hyaluronate and polyvinyl alcohol artificial tear preparations: a comparison in patients with keratoconjunctivitis sicca. Arch Ophthalmol 1988, 106: 484–7. | PubMed | ISI |
  19. Mengher LS, Pandher KS, Bron AJ: Value of sodium hyaluronate (0.1% Healon) in the treatment of dry eyes (Abstract). Ophthal Res 1986, 18: 140. | ISI |
  20. Waltman SR and Patrowicz TC: The effects of hydroxypropyl methylcellulose and polyvinyl alcohol on intraocular penetration of topical fluorescein in man. Invest Ophthalmol 1970, 9: 966–70. | PubMed | ISI |
  21. Haas JS and Merril DL: The effect of methylcellulose on responses to solutions of pilocarpine. Am J Ophthalmol 1962, 54: 2.
  22. Saettone MF, Giannacinni B, Savigni P, Wirth A: The effect of different ophthalmic vehicles on the activity of tropicamide in man. J Pharm Pharmac 1980, 32:519–21. | Article | ISI |
  23. Mueller WH and Deardorff DL: Ophthalmic vehicles: the effect of methylcellulose on the penetration of homatropine hydrobromide through the cornea. J Am Pharm Assoc 1956, 45: 334–41. | ISI |
  24. Rossomondo RM, Carlton WH, Trueblood JH, Thomas RP: A new method of evaluating lacrimal drainage. Arch Ophthalmol 1972, 88: 532–5. | PubMed |
  25. Fitzgerald P, Hadgraft J, Kreuter J, Wilson CG: A gamma scintigraphic evaluation of microparticulate ophthalmic delivery systems: liposomes and nanoparticles. Int J Pharm 1987, 40: 81–4. | Article | ISI |
  26. Zaki I, Fitzgerald P, Hardy JG, Wilson CG: A comparison of the effect of viscosity on the precorneal residence of solutions in rabbit and man. J Pharm Pharmacol 1986, 38: 463–66. | Article | PubMed | ISI |
  27. Chrai SS, Patton AM, Mehta A, Robinson JR: Lacrimal and instilled fluid dynamics in rabbit eyes. J Pharm Sci 1973, 62: 1112–21. | Article | PubMed | ISI |
  28. Trueblood JH, Rossomondo RM, Carlton WH, Wilson LA: Corneal contact times of ophthalmic vehicles: evaluation by microscintigraphy. Arch Ophthalmol 1975, 93: 127–30. | PubMed | ISI |
  29. Mengher LS, Bron AJ, Tonge SR, Gilbert DJ: Noninvasive assessment of tear film stability. In Holly FJ ed. The preocular tear film in health, disease, and contact lens wear. Lubbock, Texas. 1986: 663–69.
  30. Prydal JI: Dynamic time resolution of human tear film thickness. Paper presented at the 1989 Oxford Ophthalmological Congress. (Unpublished.)
  31. Kaura R and Tiffany J: The role of mucous glycoproteins in the tear film. In Holly FJ ed. The preocular tear film in health, disease, and contact lens wear. Lubbock, Texas. 1986: 728–32.
  32. Wilson CG: Scintigraphic evaluation of polymeric formulations for ophthalmic use. In Saettone MS, Bucci G, Speiser P eds. Ophthalmic drug delivery. Biopharmaceutical, technological and clinical aspects. Fidia Research Series, Liviana Press, Padova, 1987, 11: 141–50.
  33. Wilson CG, Olejnik O, Greaves JL, Kennedy D: Animal models for studying the precorneal residence of ophthalmic solutions (abstract). ARVO Supplement Invest Ophthalmol Vis Sci 1989, 30: 247.
  34. Nelson JD: Impression Cytology. Cornea 1988, 7: 71–81. | Article | PubMed | ISI | ChemPort |
  35. Weber P, Lubkin V, Kramer P, Liebeskind A, McKelvey W: Dacryoscintigraphy to determine lacrimal outflow rates in normal versus dry eye patients. ARVO Abstracts 1987, 158.
  36. Gurny R, Ibrahim H, Aebi A, Buri P, Wilson CG, Washington N, Edman P, Camber O: Design and evaluation of controlled release systems for the eye. Journal of Controlled Release 1987, 6: 367–73. | Article |
  37. Saettone MF, Chetoni P, Torracca MT, Burgalassi S, Giannaccini B: Evaluation of muco-adhesive properties and in vivo activity of ophthalmic vehicles based on hyaluronic acid. Int J Pharm 1989, 51: 203–12. | Article | ISI |
  38. Madsen K, Stenevi U, Apple DJ, Härfstrand A: Histochemical and receptor binding studies of hyaluronic acid and hyaluronic acid binding sites on corneal endothelium. Ophthalmic Practice 1989, 7:2–8.
  39. Hazlett LD and Barrett R: Sodium hyaluronate eye drop. A scanning and transmissioin electron microscopy study of the corneal surface. Ophthal Res 1987, 19: 277–84. | Article | ISI |
  40. Benedetto DA, Shah DO, Kaufman HE: The instilled fluid dynamics and surface chemistry of polymers in the preocular tear film. Invest Ophthalmol 1975, 14: 887–902. | PubMed | ISI |
  41. Sand BB, Marner K, Norn MS: Sodium hyaluronate in the treatment of keratoconjunctivitis sicca. Acta Ophthalmol 1989, 67: 181–3. | ISI |