Survey of Ophthalmology
Volume 47 , Pages S41-S52 , August 2002

Drug Delivery to the Posterior Segment from Drops

  • David M Maurice, PhD

      Affiliations

    • Corresponding Author InformationReprint address: David Maurice, PhD, Dept Ophthalmology, Columbia University, 630 West 168th Street, New York, NY 10032, USA

References 

  1. Ahmed I, Patton TF. Disposition of timolol and inulin in the rabbit eye following corneal versus non-corneal absorption. Int J Pharm. 1987;38:9–21
  2. Ahmed I, Francoeur ML, Thombre AG, Patton TF. The kinetics of timolol in the rabbit lens (implications for ocular drug delivery). Pharmaceut Res. 1989;6:772–778
  3. Alikacem N, Yoshizawa T, Nelson KD, Wilson CA. Quantitative MR imaging study of intravitreal sustained release of VEGF in rabbits. Invest Ophthalmol Vis Sci. 2000;41:1561–1569
  4. Anderson DR, Jin JC, Wright MM. The physiologic characteristics of relative pupillary block. Am J Ophthalmol. 1991;111:344–350
  5. Araie M, Takase M, Sakai Y, et al.  Beta-adrenergic blockers (ocular penetration and binding to the uveal pigment). Jpn J Ophthalmol. 1982;26:248–263
  6. Arend O, Harris A, Arend S, et al.  The acute effect of topical beta-adrenoreceptor blocking agents on retinal and optic nerve head circulation. Acta Ophthalmol Scand. 1998;76:43–49
  7. Auker CR, Parver LM, Doyle T, Carpenter DO. Choroidal blood flow. I. Ocular tissue temperature as a measure of flow. Arch Ophthalmol. 1982;100:1323–1326
  8. Bain WES, Maurice DM. Physiological variations in the intra-ocular pressure. Trans Ophthalmol Soc UK. 1959;79:249–260
  9. Bartels SP, Liu JH, Neufeld AH. Decreased beta-adrenergic responsiveness in cornea and iris-ciliary body following topical timolol or epinephrine in albino and pigmented rabbits. Invest Ophthalmol Vis Sci. 1983;24:718–724
  10. Berkowitz BA, Wilson CA, Tofts PS, Peshock RM. Effect of vitreous fluidity on the measurement of blood-retinal barrier permeability using contrast-enhanced MRI. Magn Res Med. 1994;31:61–66
  11. Bill A, Phillips CI. Uveoscleral drainage of aqueous humour in human eyes. Exp Eye Res. 1971;12:275–281
  12. Bill A, Maepea O. Mechanisms and routes of aqueous humor drainage. In:  Albert DM,  Jakobiec FA editor. Principles and Practice of Ophthalmology. Philadelphia: W. B. Saunders; 1994;p. 206
  13. Brazzell RK, Wooldridge CB, Hackett RB, McCue BA. Pharmacokinetics of the aldose reductase inhibitor imirestat following topical ocular administration. Pharmaceut Res. 1990;7:192–198
  14. Butler JM, Raviola G, Beers GJ, Carter AP. Computed tomography of aqueous humour outflow pathways. Exp Eye Res. 1984;39:709–719
  15. Cunha-Vaz JG, Maurice DM. The active transport of fluorescein by the retinal vessels and the retina. J Physiol. 1967;191:467–486
  16. Eguchi S, Araie M, Takase M. Movement of fluorescein and fluorescein glucuronide across the isolated rabbit iris-ciliary body. Jpn J Ophthalmol. 1987;31:440–454
  17. Ehlers N. On the size of the conjunctival sac. Acta Ophthalmologica (Copenh). 1965;43:205–210
  18. Feke GT, Zuckerman R, Green GJ, Weiter JJ. Response of human retinal blood flow to light and dark. Invest Ophthalmol Vis Sci. 1983;24:136–141
  19. Flower RW, Hochheimer BF. Quantification of indicator dye concentration in ocular blood vessels. Exp Eye Res. 1977;25:103–111
  20. Flower RW, Klein GJ. Pulsatile flow in the choroidal circulation (a preliminary investigation). Eye. 1990;4:310–318
  21. Fraunfelder FT. Extraocular fluid dynamics (how best to apply topical ocular medication). Trans Am Ophthalmol Soc. 1977;74:457–487
  22. Friedrich S, Cheng YL, Saville B. Drug distribution in the vitreous humor of the human eye (the effects of intravitreal injection position and volume). Curr Eye Res. 1997;16:663–669
  23. Fujio N, Kitazawa T. Intraocular penetration of 14C-Carteolol hydrochloride (beta-blocker) in the albino rabbits. Acta Soc Ophthalmol Jpn. 1984;88:236–241
  24. Fujio N, Kusumoto N, Odomi M. Ocular distribution of carteolol after single and repeated ocular instillation in pigmented rabbits. Acta Ophthalmol. 1994;72:688–693
  25. Grimes PA. Carboxyfluorescein transfer across the blood-retinal barrier evaluated by quantitative fluorescence microscopy (comparison with fluorescein). Exp Eye Res. 1988;46:769–783
  26. Grunwald JE. Effect of topical timolol on the human retinal circulation. Invest Ophthalmol Vis Sci. 1986;27:1713–1719
  27. Grunwald JE. Effect of timolol maleate on the retinal circulation of human eyes with ocular hypertension. Invest Ophthalmol Vis Sci. 1990;31:521–526
  28. Grunwald JE. Effect of two weeks of timolol maleate treatment on the normal retinal circulation. Invest Ophthalmol Vis Sci. 1991;32:39–45
  29. Grunwald JE, Mathur S, DuPont J. Effects of dorzolamide hydrochloride 2% on the retinal circulation. Acta Ophthalmol Scand. 1997;75:236–238
  30. Guss R, Johnson F, Maurice D. Rhodamine B as a test molecule in intraocular dynamics. Invest Ophthalmol Vis Sci. 1984;25:758–762
  31. Haefliger IO, Lietz A, Griesser SM, et al.  Modulation of Heidelberg Retinal Flowmeter parameter flow at the papilla of healthy subjects (effect of carbogen, oxygen, high intraocular pressure, and beta-blockers). Surv Ophthalmol. 1999;43:S59–S65
  32. Hamard H, Schmitt C, Plazonnet B, Le Douarec JS: Etude de la penetration oculaire de la dexamethasone, in DeMailly P, Hamard H, Luton JP, (eds). Oeil et cortisone. Paris: Masson and Cie, 1975, pp 3–81
  33. Harris A, Spaeth GL, Sergott RC, et al.  Retrobulbar arterial hemodynamic effects of betaxolol and timolol in normal-tension glaucoma. Am J Ophthalmol. 1995;120:168–175
  34. Harris A, Arend O, Arend S, Martin B. Effects of topical dorzolamide on retinal and retrobulbar hemodynamics. Acta Ophthalmol Scand. 1996;74:569–572
  35. Harris A, Kagemann L, Cioffi GA. Assessment of human ocular hemodynamics. Surv Ophthalmol. 1998;42:509–533
  36. Harris A, Arend O, Kagemann L, et al.  Dorzolamide, visual function and ocular hemodynamics in normal-tension glaucoma. J Ocular Pharmacol Therap. 1999;15:189–197
  37. Harris A, Arend O, Chung HS, et al.  A comparative study of betaxolol and dorzolamide effect on ocular circulation in normal-tension glaucoma patients. Ophthalmology. 2000;107:430–434
  38. Hayreh SS. The 1994 Von Sallman Lecture. The optic nerve head circulation in health and disease. Exp Eye Res. 1995;61:259–272
  39. Hayreh SS. Factors influencing blood flow in the optic nerve head. J Glaucoma. 1997;6:412–425
  40. Hayreh SS. Evaluation of optic nerve head circulation (review of the methods used). J Glaucoma. 1997;6:319–330
  41. Hogan MJ, Alvarado JA, Weddell JE. Histology of the human eye. Philadelphia: W. B. Saunders; 1971; p 386
  42. Holm O. A photogrammetric method for estimation of the pupillary aqueous flow in the living human eye, I. Acta Ophthalmol. 1968;46:254–277
  43. Joshi A, Maurice D, Paugh JR. A new method for determining corneal epithelial barrier to fluorescein in humans. Invest Ophthalmol Vis Sci. 1996;37:1008–1016
  44. Kaiser RJ, Maurice DM. The diffusion of fluorescein in the lens. Exp Eye Res. 1964;3:156–165
  45. Kessler C, Bleckmann H, Kleintges G. Influence of the concentration of metipranolol eye drops on the drug concentration in human aqueous humour. Graefes Arch Clin Exp Ophthalmol. 1991;229:487–491
  46. Koyano S, Araie M, Eguchi S. Movement of fluorescein and its glucuronide across retinal pigment epithelium-choroid. Invest Ophthalmol Vis Sci. 1993;34:531–538
  47. Langham ME, Farrell RA, O'Brien V, et al.  Blood flow in the human eye. Acta Ophthalmol. 1989;191(Suppl):9–13
  48. Lee TW-Y, Robinson JR. Drug delivery to the posterior segment of the eye (some insights on the penetration pathways after subconjunctival injection). J Ocular Pharmacol Therap. 2001;17:565–572
  49. Lee YH, Lee VH. Formulation influence on ocular and systemic absorption of topically applied atenolol in the pigmented rabbit. J Ocular Pharmacol. 1993;9:47–58
  50. Longo A, Geiser M, Riva CE. Subfoveal choroidal blood flow in response to light-dark exposure. Invest Ophthalmol Vis Sci. 2000;41:2678–2683
  51. Macdonald EA, Maurice DM. Loss of fluorescein across the conjunctiva. Exp Eye Res. 1991;53:427–430
  52. Martinez A, Gonzalez F, Capeans C, et al.  Dorzolamide effect on ocular blood flow. Invest Ophthalmol Vis Sci. 1999;40:1270–1275
  53. Maumenee AE. Causes of optic nerve damage in glaucoma. Robert N. Shaffer lecture. Ophthalmology. 1983;90:741–752
  54. Maurice D, Velilla S, Chuang L-S. The penetration of drugs from tears to the retina. Invest Ophthalmol Vis Sci. 1999;40(Suppl):S83
  55. Maurice DM. A recording tonometer. Br J Ophthalmol. 1958;42:321–335
  56. Maurice DM, Mishima S. Ocular pharmacokinetics. In:  Sears ML editors. Handbook of Experimental Pharmacology. Vol. 69. Berlin: Springer-Verlag; 1984;p. 19–116
  57. Maurice DM, Srinivas SP. Use of fluorometry in assessing the efficacy of a cation-sensitive gel as an ophthalmic vehicle (comparison with scintigraphy). J Pharmaceut Sci. 1992;81:615–619
  58. Maurice DM. Mixing of the tear film under the eyelids. Adv Exp Med Biol. 1994;350:263–266
  59. Maurice DM. The Von Sallmann Lecture 1996 (an ophthalmological explanation of REM sleep). Exp Eye Res. 1998;66:139–145
  60. Miyake K, Ohtsuki K. Fluorescence fundusphotography by retrobulbar administration of the dye, photochemical trans- illumination. Jpn J Ophthalmol. 1981;25:280–298
  61. Mizuno K, Koide T, Yoshimura M, Araie M. Neuroprotective effect and intraocular penetration of nipradilol, a beta-blocker with nitric oxide donative action. Invest Ophthalmol Vis Sci. 2001;42:688–694
  62. Nagataki S, Mishima S. Pharmacokinetics of instilled drugs in the human eye. Int Ophthalmol Clin. 1980;20:33–49
  63. Netland PA, Feke GT, Konno S, et al.  Optic nerve head circulation after topical calcium channel blocker. J Glaucoma. 1996;5:200–206
  64. Neufeld AH. Experimental studies on the mechanism of action of timolol. Surv Ophthalmol. 1979;23:363–370
  65. Nicolela MT, Hnik P, Schulzer M, Drance SM. Reproducibility of retinal and optic nerve head blood flow measurements with scanning laser Doppler flowmetry. J Glaucoma. 1997;6:157–164
  66. Nilsson SF, Linder J, Bill A. Characteristics of uveal vasodilation produced by facial nerve stimulation in monkeys, cats and rabbits. Exp Eye Res. 1985;40:841–852
  67. Parver LM, Auker C, Carpenter DO. Choroidal blood flow as a heat dissipating mechanism in the macula. Am J Ophthalmol. 1980;89:641–646
  68. Parver LM, Auker CR, Carpenter DO, Doyle T. Choroidal blood flow II. Reflexive control in the monkey. Arch Ophthalmol. 1982;100:1327–1330
  69. Parver LM, Auker CR, Carpenter DO. Choroidal blood flow. III. Reflexive control in human eyes. Arch Ophthalmol. 1983;101:1604–1606
  70. Parver LM, Mitchard R, Ham WT. Sensitivity to retinal light damage and surgical blood oxygen levels. Ann Ophthalmol. 1989;21:386–388 391,
  71. Petrig BL, Riva CE, Hayreh SS. Laser Doppler flowmetry and optic nerve head blood flow. Am J Ophthalmol. 1999;127:413–425
  72. Pillunat LE, Bohm AG, Koller AU, et al.  Effect of topical dorzolamide on optic nerve head blood flow. Graefes Arch Clin Exp Ophthalmol. 1999;237:495–500
  73. Piltz J, Gross R, Shin DH, et al.  Contralateral effect of topical beta-adrenergic antagonists in initial one-eyed trials in the ocular hypertension treatment study. Am J Ophthalmol. 2000;130:441–453
  74. Piltz-Seymour JR. Laser Doppler flowmetry of the optic nerve head in glaucoma. Surv Ophthalmol. 1999;43:S191–S198
  75. Pleyer U, Lutz S, Jusko WJ, et al.  Ocular absorption of topically applied FK506 from liposomal and oil formulations in the rabbit eye. Invest Ophthalmol Vis Sci. 1993;34:2737–2742
  76. Rankin SJ. Color Doppler imaging of the retrobulbar circulation in glaucoma. Surv Ophthalmol. 1999;43:S176–S182
  77. Richard G, Weber J. Effect of the beta-blockers timolol and pindolol on retinal hemodynamics—a videoangiography study. Klin Monatsbl Augenheilkd. 1987;190:34–39
  78. Riva CE, Feke GT, Eberli B, Benary V. Bidirectional LDV system for absolute measurement of blood speed in retinal vessels. Applied Optics. 1979;18:2301–2306
  79. Riva CE, Grunwald JE, Sinclair SH, O'Keefe K. Fundus camera based retinal LDV. Applied Optics. 1981;20:117–120
  80. Riva CE, Grunwald JE, Petrig BL. Reactivity of the human retinal circulation to darkness (a laser Doppler velocimetry study). Invest Ophthalmol Vis Sci. 1983;24:737–740
  81. Riva CE, Petrig BL. Retinal blood flow (Laser Doppler velocimetry and blue field simulation technique). In:  Masters BR editors. Non-Invasive Diagnostic Techniques in Ophthalmology. New York: Springer Verlag; 1990;p. 390–409
  82. Riva CE, Logean E, Petrig BL, Falsini B. Effect of dark adaptation on retinal blood flow. Klin Monatsbl Augenheilkd. 2000;216:309–310
  83. Salazar-Bookaman MM, Wainer I, Patil PN. Relevance of drug-melanin interactions to ocular pharmacology and toxicology. J Ocular Pharmacol. 1994;10:217–239
  84. Salminen L, Urtti A. Disposition of ophthalmic timolol in treated and untreated rabbit eyes. A multiple and single dose study. Exp Eye Res. 1984;38:203–206
  85. Schmetterer L, Wolzt M, Lexer F, et al.  The effect of hyperoxia and hypercapnia on fundus pulsations in the macular and optic disc region in healthy young men. Exp Eye Res. 1995;61:685–690
  86. Schmetterer L, Strenn K, Findl O, et al.  Effects of antiglaucoma drugs on ocular hemodynamics in healthy volunteers. Clin Pharmacol Therap. 1997;61:583–595
  87. Schoenwald RD, Deshpande GS, Rethwisch DG, Barfknecht CF. Penetration into the anterior chamber via the conjunctival/scleral pathway. J Ocular Pharmacol Therap. 1997;13:41–59
  88. Seong GJ, Lee HK, Hong YJ. Effects of 0.005% latanoprost on optic nerve head and peripapillary retinal blood flow. Ophthalmologica. 1999;213:355–359
  89. Sherman SH, Green K, Laties AM. The fate of anterior chamber fluorescein in the monkey eye. 1. The anterior chamber outflow pathways. Exp Eye Res. 1978;27:159–173
  90. Sponsel WE, Terry S, Khuu HD, et al.  Periocular accumulation of timolol and betaxolol in glaucoma patients under long-term therapy. Surv Ophthalmol. 1999;43:S210–S213
  91. Stjernschantz J, Selen G, Astin M, et al.  Effect of latanoprost on regional blood flow and capillary permeability in the monkey eye. Arch Ophthalmol. 1999;117:1363–1367
  92. Sugiyama K, Bacon DR, Cioffi GA, et al.  The effects of phenylephrine on the ciliary body and optic nerve head microvasculature in rabbits. J Glaucoma. 1992;1:156–164
  93. Sugiyama T, Utsumi T, Azuma I, Fujii H. Measurement of optic nerve head circulation (comparison of laser speckle and hydrogen clearance methods). Jpn J Ophthalmol. 1996;40:339–343
  94. Tamaki Y, Araie M, Kawamoto E, et al.  Non-contact, two-dimensional measurement of tissue circulation in choroid and optic nerve head using laser speckle phenomenon. Exp Eye Res. 1995;60:373–383
  95. Tamaki Y, Araie M, Tomita K, et al.  Effect of topical beta-blockers on tissue blood flow in the human optic nerve head. Curr Eye Res. 1997;16:1102–1110
  96. Tamaki Y, Araie M, Hasegawa T, Nagahara M. Optic nerve head circulation after intraocular pressure reduction achieved by trabeculectomy. Ophthalmology. 2001;108:627–632
  97. Tomic L, Maepea O, Sperber GO, Alm A. Comparison of retinal transit times and retinal blood flow (a study in monkeys). Invest Ophthalmol Vis Sci. 2001;42:752–755
  98. Tomidokoro A, Araie M, Tamaki Y, Tomita K. In vivo measurement of iridial circulation using laser speckle phenomenon. Invest Ophthalmol Vis Sci. 1998;39:364–371
  99. Toris CB, Gregerson DS, Pederson JE. Uveoscleral outflow using different-sized fluorescent tracers in normal and inflamed eyes. Exp Eye Res. 1987;45:525–532
  100. Tsuchiya M, Hayasaka S, Mizuno K. Affinity of ocular acid-insoluble melanin for drugs in vitro. Invest Ophthalmol Vis Sci. 1987;28:822–825
  101. Tsukahara Y, Maurice DM. Local pressure effects on vitreous kinetics. Exp Eye Res. 1995;60:563–573
  102. Urtti A. Delivery of antiglaucoma drugs (ocular vs systemic absorption). J Ocular Pharmacol. 1994;10:349–357
  103. Valeri P, Palmery M, Martinelli B, Catanese B. Absorption of bendazac lysine after topical application to the rabbit eye. Pharmacol Res Commun. 1987;19:517–525
  104. Whitson JT, Love R, Brown RH, et al.  The effect of reduced eyedrop size and eyelid closure on the therapeutic index of phenylephrine. Am J Ophthalmol. 1993;115:357–359
  105. Wine NA, Gornall AG, Basu PK. The ocular uptake of subconjunctivally injected C14 hydrocortisone. 1. Time and major route of penetration. Am J Ophthalmol. 1964;58:362–366
  106. Wolf S, Werner E, Schulte K, Reim M. Acute effect of metipranolol on the retinal circulation. Br J Ophthalmol. 1998;82:892–896
  107. Yaoeda K, Shirakashi M, Funaki S, et al.  Measurement of microcirculation in the optic nerve head by laser speckle flowgraphy and scanning laser Doppler flowmetry. Am J Ophthalmol. 2000;129:734–739
  108. Yoshida A, Feke GT, Ogasawara H, et al.  Effect of timolol on human retinal, choroidal and optic nerve head circulation. Ophthalmic Res. 1991;23:162–170

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Survey of Ophthalmology
Volume 47 , Pages S41-S52 , August 2002