Ординатура / Офтальмология / Английские материалы / Glaucoma Medical Therapy Principles and Management_Netland_2008

28 Glaucoma Medical Therapy

29.Fraunfelder FT. Extraocular fluid dynamics: how best to apply topical ocular medication. Trans Am Ophthalmol Soc. 1977;74:457–487.

30.Olejnik O. Conventional systems in ophthalmic drug delivery. In: Mitra AK, ed.

Ophthalmic Drug Delivery Systems. New York: Dekker; 1993:177–198. Drugs and the Pharmaceutical Sciences; Vol 58.

31.Sieg JW, Robinson JR. Vehicle effects on ocular drug bioavailability, I: Evaluation of fluorometholone. J Pharm Sci. 1975;64:931–936.

32.Schoenwald RD, Stewart P. Effect of particle size on ophthalmic bioavailability of dexamethasone suspensions in rabbits. J Pharm Sci. 1980;69:391–394.

33.Sieg JW, Robinson JR. Vehicle effects on ocular drug bioavailability, II: Evaluation of pilocarpine. J Pharm Sci. 1977;66:1222–1228.

34.DeSantis LM, Patil PN. Pharmacokinetics. In: Mauger TF, Craig EL, eds. Havener’s Ocular Pharmacology. 6th ed. St Louis, MO: CV Mosby Co; 1994:22–52.

35.Mitra AK, Mickelson TJ. Mechanism of transcorneal permeation of pilocarpine. J Pharm Sci. 1988;77:771–775.

36.Norn MS. Tear fluid pH in normals, contact lens wearers, and pathological cases. Acta Ophthalmol. 1988;66:485–489.

37.Coles WH, Jaros PA. Dynamics of ocular surface pH. Br J Ophthalmol. 1984;68:549– 552.

38.Van Ooteghem MM. Factors influencing the retention of ophthalmic solutions on the eye surface. In: Saettone MF, Bucci M, Speiser P, eds. Ophthalmic Drug Delivery: Biopharmaceutical, Technological, and Clinical Aspects. New York: Springer-Verlag; 1987:7.

39.Bar-Ilan A, Neumann R. Basic considerations of ocular drug-delivery systems. In: Zimmerman TJ, ed. Textbook of Ocular Pharmacology. Philadelphia, PA: LippincottRaven; 1997:139–150.

40.Patton TF, Robinson TR. Ocular evaluation of polyvinyl alcohol vehicle in rabbits. J Pharm Sci. 1975;64:1312–1316.

41.Burstein NL. Preservative alteration of corneal permeability in humans and rabbits.

Invest Ophthalmol Vis Sci. 1984;25:1453–1457.

42.Hughes PM, Mitra AK. Overview of ocular drug delivery and iatrogenic ocular cytopathologies. In: Mitra AK, ed. Ophthalmic Drug Delivery Systems. New York: Dekker; 1993:1–27. Drugs and the Pharmaceutical Sciences; Vol 58.

43.Fraunfelder FT. Drug-Induced Ocular Side Effects and Drug Interactions. Philadelphia, PA: Lea & Febiger; 1976.

44.Bar-Ilan A, Aviv H, Friedman D, et al. Improved performance of ocular drugs formulated in submicron emulsions. Invest Ophthalmol Vis Sci. 1993(suppl);34:1488.

45.Roziere A, Mazuel C, Grove J, Plazonnet B. Gelrite: a novel, ion-activated, in-situ gelling polymer for ophthalmic vehicles: effect on bioavailability of timolol. Int J Pharm. 1989;57:163–168.

46.Ibrahim H, Gurny R, Buri P, et al. Ocular bioavailability of pilocarpine from phase transition latex system triggered by pH. Eur J Drug Metab Pharmacokinet. 1990; 15(suppl):206.

47.Harsh DC, Gehrke SH. Controlling the swelling characteristics of temperaturesensitive cellulose ether hydrogels. J Controlled Release. 1991;17:175–185.

48.Miller SC, Donovan MD. Effect of poloxamer 407 gel on the miotic activity of pilocarpine nitrate in rabbits. Int J Pharmacol. 1982;12:147–152.

49.Kumar S, Haglund BO, Himmelstein KJ. In situ–forming gels of ophthalmic drug delivery. J Ocul Pharmacol. 1994;10:47–56.

50.Heller J. Controlled drug release from monolithic systems. In: Saettone MF, Bucci M, Speiser P, eds. Ophthalmic Drug Delivery: Biopharmaceutical, Technological, and Clinical Aspects. New York: Springer-Verlag; 1987:179.

51.Bartlett JD, Cullen AP. Clinical administration of ocular drugs. In: Bartlett JD, Jaanus SD, eds. Clinical Ocular Pharmacology. 2nd ed. Boston, MA: Butterworths; 1989:46–48.

52.Lamberts DW. Solid delivery devices. Int Ophthalmol Clin. 1980;20:63–77.

53.Bawa R. Ocular inserts. In: Mitra AK, ed. Ophthalmic Drug Delivery Systems. New York: Dekker; 1993:232–234. Drugs and the Pharmaceutical Sciences; Vol 58.

54.Zimmerman TJ, Leader B, Kaufman HE. Advances in ocular pharmacology. Annu Rev Pharmacol Toxicol. 1980;20:415–428.

55.Quigley HA, Pollack IP, Harbin TS. Pilocarpine Ocuserts: long-term clinical trials and selected pharmacodynamics. Arch Ophthalmol. 1975;93:771–775.

56.Shell JW, Baker RW. Diffusional systems for controlled release of drugs to the eye. Ann Ophthalmol. 1974;6:1037–1043,1045.

57.Urquhart J. Development of the Ocusert pilocarpine ocular therapeutic systems: a case history in ophthalmic product development. In: Robinson JR, ed. Ophthalmic Drug Delivery Systems. Washington, DC: American Pharmaceutical Association; 1980:105.

58.Hitchings RA, Smith RJ. Experience with pilocarpine Ocuserts. Trans Ophthalmol Soc UK. 1977;97:202–205.

59.Drance SM, Mitchell DW, Schulzer M. The effects of Ocusert pilocarpine on anterior chamber depth, visual acuity and intraocular pressure in man. Can J Ophthalmol. 1977;12:24–28.

60.Francois J, Goes F, Zagorski Z. Comparative ultrasonographic study of the effect of pilocarpine 2% and Ocusert P 20 on the eye components. Am J Ophthalmol. 1978; 86:233–238.

61.Novak S, Stewart RH. The Ocusert system in the management of glaucoma. Tex Med. 1975;71:63–65.

62.Armaly MF, Rao KR. The effect of pilocarpine Ocusert with different release rates on ocular pressure. Invest Ophthalmol. 1973;12:491–496.

63.Weiner N, Martin F, Riaz M. Liposomes as a drug delivery system. Drug Dev Indust Pharm. 1989;15:1523–1554.

64.Schulman JA, Peyman GA. Intracameral, intravitreal and retinal drug delivery. In: Mitra AK, ed. Ophthalmic Drug Delivery Systems. New York: Dekker; 1993:395– 397. Drugs and the Pharmaceutical Sciences; Vol 58.

65.Davis NM, Kellaway IW, Greaves JL, Wilson CG. Advanced corneal delivery systems: liposomes. In: Mitra AK, ed. Ophthalmic Drug Delivery Systems. New York: Dekker; 1993:289–303. Drugs and the Pharmaceutical Sciences; Vol 58.

66.New RRC, Black CDV, Parker RJ, et al. Liposomes in biological systems. In: New RRC, ed. Liposome. Oxford: IRL Press at Oxford University; 1990:221.

67.Lee VH, Urrea PT, Smith RE, Schanzlin DJ. Ocular drug bioavailability from topically applied liposomes. Surv Ophthalmol. 1985;29:335–348.

68.Schaeffer HE, Krohn DL. Liposomes in topical drug delivery. Invest Ophthalmol Vis Sci. 1982;22:220–227.

69.Juliano RL, Stamp D. Lectin-mediated attachment of glycoprotein-bearing liposomes to cells. Nature. 1976;261:235–238.

70.Barza M, Baum J, Szoka F Jr. Pharmacokinetics of subconjunctival liposomeencapsulated gentamicin in normal rabbit eyes. Invest Ophthalmol Vis Sci. 1984;25: 486–490.

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71.Alghadyan AA, Peyman GA, Khoobehi B, et al. Liposome-bound cyclosporine: aqueous and vitreous level after subconjunctival injection. Int Ophthalmol. 1988;12:101–104.

72.Fishman PH, Peyman GA, Lesar T. Intravitreal liposome-encapsulated gentamicin in a rabbit model: prolonged therapeutic levels. Invest Ophthalmol Vis Sci. 1986;27:1103– 1106.

73.Tremblay C, Barza M, Szoka F, et al. Reduced toxicity of liposome-associated amphotericin B injected intravitreally in rabbits. Invest Ophthalmol Vis Sci. 1985;26: 711–718.

74.Alghadyan AA, Peyman GA, Khoobehi B, et al. Liposome-bound cyclosporine: clearance after intravitreal injection. Int Ophthalmol. 1988;12:109–112.

75.Norley SG, Huang L, Rouse BT. Targeting of drug loaded immunoliposomes to herpes simplex virus infected corneal cells: an effective means of inhibiting virus replication in vitro. J Immunol. 1986;136:681–685.

76.Norley SG, Sendele D, Huang L, Rouse BT. Inhibition of herpes simplex virus replication in the mouse cornea by drug containing immunoliposomes. Invest Ophthalmol Vis Sci. 1987;28:591–595.

77.Alvarez-Lorenzo C, Hiratani H, Gomez-Amoza JL, et al. Soft contact lenses capable of sustained delivery of timolol. J Pharm Sci. 2002;91:2182–2192.

78.Alvarez-Lorenzo C, Concheiro A. Molecularly imprinted polymers for drug delivery. J Chromatogr B. 2004;804:231–245.

79.Ashton P, Blandford DL, Pearson PA, et al. Review: implants. J Ocul Pharmacol. 1994;10:691–701.

80.Smith TJ, Pearson PA, Blandford DL, et al. Intravitreal sustained-release ganciclovir. Arch Ophthalmol. 1992;110:255–258.

81.Martin DF, Ferris FL, Parks DJ, et al. Ganciclovir implant exchange: timing, surgical procedure, and complications. Arch Ophthalmol. 1997;115:1389–1394.

82.Jaffe GJ, Yang CS, Wang XC, et al. Intravitreal sustained-release cyclosporine in the treatment of experimental uveitis. Ophthalmology. 1998;105:46–56.

83.Enyedi LB, Pearson PA, Ashton P, Jaffe GJ. An intravitreal device providing sustained release of cyclosporine and dexamethasone. Curr Eye Res. 1996;15:549–557.

84.Smith TJ, Ashton P. Sustained-release subconjunctival 5-fluorouracil. Ophthalmic Surg Lasers. 1996;27:763–767.

85.Yang CS, Khawly JA, Hainsworth DP, et al. An intravitreal sustained-release triamcinolone and 5-fluorouracil codrug in the treatment of experimental proliferative vitreoretinopathy. Arch Ophthalmol. 1998;116:69–77.

86.Berger AS, Cheng CK, Pearson PA, et al. Intravitreal sustained release corticosteroid– 5-fluorouracil conjugate in the treatment of experimental proliferative vitreoretinopathy. Invest Ophthalmol Vis Sci. 1996;37:2318–2325.

87.Lim LL, Smith JR, Rosenbaum JT. Retisert (Bausch & Lomb/control delivery system).

Cur Opin Invest Drugs. 2005;6:1159–1167.

88.Fluocinolone acetonide ophthalmic-Bausch & Lomb: fluocinolone acetonide Envision TD implant. Drugs R D. 2005;6:116–119.

89.Chrousos GP. Adrenocorticosteroids and adrenocortical antagonists. In: Katzung B ed. Basic and Clinical Pharmacology. 9th ed. New York: Large Medical Books/McGrawHill; 2004:641–660.

90.Francois J. Corticosteroid glaucoma. Ann Ophthalmol. 1977;9:1075–1080.

91.Cantrill HL, Palmberg, Zink HA, et al. Comparison of in vitro potency of corticosteroids with ability to raise intraocular pressure. Am J Ophthalmol. 1975;79:1012– 1017.

92.Armaly MF. Effect of corticosteroids on intraocular pressure and fluid dynamics: I. The effect of desamethasone in the normal eye. Arch Ophthalmol. 1963;70:482–491.

93.Armaly MF. Effect of corticosteroids on intraocular pressure and fluid dynamics: II. The effect of desamethasone on the glaucomatous eye. Arch Ophthalmol. 1963;70: 492–499.

94.Weinreb RN, Polansky JR, Kramer SG, et al. Acute effects of dexamethasone on introcular pressure in glaucoma. Invest Ophthalmol Vis Sci. 1985;26:170–175.

95.Smithen LM, Ober MD, Maranan L, et al. Intravitreal triamcinolone acetonide and intraocular pressure. Am J Ophthalmol. 2004;138:740–743.

96.Herschler J. Increased intraocular pressure induced by repository corticosteroids. Am J Ophthalmol. 1976;82:90–93.

97.Espildora J, Vicuna P, Diaz E. Cortisone-induced glaucoma: a report on 44 affected eyes. J Fr Ophthalmol. 1981;4:503–508.

98.Kersey JP, Broadway DC. Corticosteroid-induced glaucoma: a review of the literature. Eye. 2006;20:407–416.

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34 Glaucoma Medical Therapy

Figure 2.1. Chemical structures of the prostaglandin analogs.

of PGs consistently showed that very high doses of topical or intracameral PGs raised IOP. Studies over the next two decades led to the development of a PG analog that was effective and well tolerated, and the development of other PG analogs followed.

Because their mechanism of action is different from most other glaucoma medications, PGs can produce a substantial additional reduction in IOP when added to treatment regimens consisting of other topical and/or systemic ocular hypotensive agents.

2.1 MECHANISM OF ACTION

The primary mechanism by which most PGs reduce IOP is by increasing outflow, especially through the uveoscleral outflow pathway (figure 2.2). Numerous animal and human studies have confirmed this mechanism of action.11,12 In several studies, PGs have been demonstrated to increase outflow facility.12–17 PGs do not reduce aqueous production.

The mechanism by which PGs increase uveoscleral outflow is continuing to be elucidated. One mechanism may be the relaxation of the ciliary muscle. This is

supported by studies in monkeys that have shown pilocarpine pretreatment blocks the effect of PGs on uveoscleral outflow or IOP.11,12,15 An increase in ciliary body

Figure 2.2. Two major routes aqueous outflow. Prostaglandin analogs act by increasing outflow, primarily through the uveoscleral pathway (blue arrows), with some contribution through the conventional trabecular outflow pathway (green arrows).

thickness has been measured by ultrasound biomicroscopy in human eyes treated with latanoprost.18 Additionally, PGs may cause dilated spaces between ciliary muscle bundles. This is thought to result from PG-induced stimulation of collagenases and other matrix metalloproteinases.11,19 However, other studies, using both light and electron microscopy, have found no evidence of dilated spaces between ciliary muscle bundles or other alterations in the ciliary muscle or other ocular tissues in monkeys treated with PGF2a.20

2.2 INDICATIONS

Originally approved for second-line therapy when introduced in 1996, latanoprost has been FDA approved as a first-line treatment of open-angle glaucoma or ocular hypertension since 2002. Travoprost and bimatoprost were initially approved by the FDA for second-line therapy, and subsequently both drugs have been approved for first-line treatment.

Clinical studies have also demonstrated that PGs lower IOP in patients with

normal tension glaucoma,21–24 exfoliation syndrome,25–31 pigment dispersion syndrome,17,27,31 and chronic angle-closure glaucoma.32–35 There are limited reports of

clinical experience with the use of latanoprost in other types of glaucoma.28 Caution is recommended in uveitic glaucoma, although some studies demonstrate safety and

36 Glaucoma Medical Therapy

efficacy of PGs in uveitic glaucoma.36 PGs, like other glaucoma medications, may be less effective in pediatric patients.37

PG analogs have several advantages over other ocular hypotensive medications. Their main advantage over the beta blockers is the apparent lack of systemic side effects. Compared with beta blockers, PG analogs are more potent and effective ocular hypotensive agents with once-a-day dosing, and they are equally well toler-

ated by patients. Whereas beta blockers do not reduce aqueous flow during sleep, PGs are as effective at night as during the day.38,39 Reducing IOP at night may have

the added advantage of reducing glaucomatous damage during sleep when ocular perfusion pressure may be reduced secondary to decreased systemic blood pressure.40 Because of their mechanism of action, PG analogs potentially can reduce IOP below episcleral venous pressure, unlike medications that increase outflow facility. This, along with their more favorable effect on ocular perfusion pressure, presents a

potential advantage in normal tension glaucoma, which may require very low IOPs for adequate control.22–24

2.3 CONTRAINDICATIONS

PG analogs are contraindicated in any patient who is allergic or sensitive to these drugs. Patients who are pregnant or nursing should use caution. There are limited studies in pediatric patients, and although side effects are infrequent and mild, some children have had an inadequate response to PGs.37 Although limited studies are available, it remains unclear what effect PGs have on ocular inflammation in postoperative patients and what role PGs may have in treating patients with elevated IOP following cataract surgery or other intraocular surgery.41 There have been some reports of an association of latanoprost with cystoid macular edema (CME), which is discussed in section 2.5.5.36 Although the controlled clinical trials have not shown a causal relationship between PGs and these problems, PGs should be used with caution in patients with multiple risk factors for CME, with iritis or herpes simplex keratitis, or in the immediate postoperative period following intraocular surgery.36 Until further clinical studies have clarified the relationship between the PGs and CME, it should not be the drug of first choice in complicated aphakic or

pseudophakic eyes with torn posterior capsules and other known risk factors for

CME.36,42,43

2.4 TREATMENT REGIMEN

The recommended treatment regimen for latanoprost, travoprost, and bimatoprost is one drop applied topically once daily in the evening. Evening, rather than morning, administration appears to be more efficacious and may block the early morning diurnal spike in IOP that may be observed in many patients.29 With the exception of unoprostone, which has a recommended dosage of twice daily, none of the other

PGs should be used more than once daily since more frequent dosage decreases the IOP-lowering effect.2,4,44

2.5 SIDE EFFECTS

The side effect profiles of the various PG analogs are compared in table 2.1. Eye irritation, conjunctival hyperemia, and eyelash changes are the most frequently reported side effects. Eye irritation, burning, and pain are reported with variable frequency in the various studies, and the rates of these symptoms with the various PG analogs are not substantially different from each other or from timolol. A wide range of other signs or symptoms such as superficial punctate keratitis, blurred vision, cataract, and headache have been reported at low rates in various clinical studies. The side effects of iris color changes, eyelash changes, and periocular skin color changes are specifically associated with the PG analogs.

Bimatoprost and travoprost have been reported to give a higher incidence of hyperemia and eyelash changes compared to latanoprost,2,3,45,46 and package insert

labeling reflects this difference. There is no clear evidence that the incidence or severity of other side effects vary substantially among these medications. At the time this chapter was prepared, peer-reviewed reports were not available regarding benzalkonium chloride-free travoprost ophthalmic solution 0.004% (Travatan Z). More experience is required with the newer PG analogs to determine whether the incidence of rare side effects is different among the PGs.

2.5.1 Conjunctival Hyperemia. Conjunctival hyperemia is reported significantly

more frequently with bimatoprost and travoprost than with latanoprost (table 2.1).2,3,45,46 In general, the level of hyperemia is very mild for most patients and

usually is not noticed by the patient and not severe enough to require discontinuation of the medication.2,3,29,45–49 Based on the phase III clinical trials and as stated in

the package inserts, 3% of patients required discontinuation of therapy with travoprost or bimatoprost because of intolerance to conjunctival hyperemia, whereas

Table 2.1 Percentage of Patients in Comparative Trials Exhibiting Specific Ocular Signs and Symptoms

NR, Not reported

aSignificant differences compared to latanoprost in at least one study.