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May 1996, Vol 114, No. 5 >
ARTICLE | May 1996

Aging Effects on Accommodation and Outflow Facility Responses to Pilocarpine in Humans FREE

Mary Ann Croft, MS; Mary Jo Oyen, MD; Stephen J. Gange, PhD; Marian R. Fisher, PhD; Paul L. Kaufman, MD
Arch Ophthalmol. 1996;114(5):586-592. doi:10.1001/archopht.1996.01100130578015
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Objective:  To determine the relationships among age, outflow facility, and refractive and facility responses to pilocarpine in humans.

Methods:  Refraction, intraocular pressure, and outflow facility were determined in 30 normal volunteers aged 20 to 75 years, by coincidence refractometry, applanation tonometry, and Schiøtz tonography, respectively, before and 1 hour after a 30-μL drop of 2% or 6% pilocarpine. Simple regression of baseline facility, postpilocarpine facility, and facility change, on age and refractive change singly and jointly, was performed. Stepwise regression models and graphic conditioning plots were used to determine, for each facility variable, its relationship to age or refractive change specifically.

Results:  Baseline outflow facility and maximum pilocarpine-induced refractive change (ie, accommodation) declined with age, but the decrease in intraocular pressure and the facility response to pilocarpine did not. After adjusting for age, for baseline facility, there was no further relationship to 6% pilocarpine-induced accommodation, and a slight residual relationship to 2% pilocarpine-induced accommodation. After adjusting for both 2% or 6% pilocarpine-induced accommodation, the relationship to age was still significant. The facility increase after 2% or 6% pilocarpine did not depend on age and/or accommodative amplitude.

Conclusions:  In humans, as previously described in rhesus monkeys, an age-related loss of ciliary muscle mobility may compromise the basal function of the trabecular meshwork. However, unlike monkeys, humans exhibit no loss of the intraocular pressure or outflow facility response to pilocarpine with age.

REFERENCES

1 +
Lütjen-Drecoll E, Tamm E, Kaufman PL.  Age-related loss of morphologic responses to pilocarpine in rhesus monkey ciliary muscle . Arch Ophthalmol . 1988;;106:1591-1598.
2 +
Tamm E, Croft MA, Jungkunz W, Lütjen-Drecoll E, Kaufman PL.  Age-related loss of ciliary muscle mobility in the rhesus monkey: role of the choroid . Arch Ophthalmol . 1992;;110:871-876.
3 +
Neider MW, Crawford K, Kaufman PL, Bito LZ.  In vivo videography of the rhesus monkey accommodative apparatus: age-related loss of ciliary muscle response to central stimulation . Arch Ophthalmol . 1990;;108:69-74.
4 +
Gabelt BT, Crawford K, Kaufman PL.  Outflow facility and its response to pilocarpine decline in aging rhesus monkeys . Arch Ophthalmol . 1991;;109:879-882.
5 +
Kaufman PL, Wiedman T, Robinson JR.  Cholinergics . In: Sears ML, ed. Pharmacology of the Eye. Handbook of Experimental Pharmacology . New York, NY: Springer-Verlag NY Inc; 1984;;69:149-191.
6 +
Duane A.  Studies in monocular and binocular accommodation with their clinical applications . Am J Ophthalmol . 1922;;5:867-877.
7 +
Kaufman PL, Jefferson JW, Ackerman D, Baumgartner S.  Ocular side effects of oral lithium in humans . Acta Ophthalmol (Copenh) . 1985;;63:327-332.
8 +
Kaufman PL.  Aging and aqueous humor dynamics . In: Di Vencentiis M, ed. The Fundamental Aging Processes of the Eye . Florence, Italy: Baccini & Chiappi: 1987;:41-46.
9 +
Hoskins HD Jr, Kass MA.  Aqueous humor outflow . Becker-Shaffer's Diagnosis and Therapy of the Glaucomas . 6th ed. St Louis, Mo: CV Mosby Co; 1989;:420-434.
10 +
Kaufman PL, Gabelt BT.  Aging, accommodation and outflow facility . In: Lütjen-Drecoll E. ed. Basic Aspects of Glaucoma Research III . Stuttgart, Germany: Schattauer; 1993;:257-274.
11 +
Kolker AE, Hetherington JJ.  Tables for tonography and tonometry . Becker-Shaffer's Diagnosis and Therapy of the Glaucomas . 5th ed. St Louis, Mo: CV Mosby Co; 1983;:519-535.
12 +
Liang KY, Zeger S.  Longitudinal data analysis using generalized linear models . Biometrics . 1986;;73:13-22.
13 +
Bito LZ, DeRousseau CJ, Kaufman PL, Bito JW.  Age-dependent loss of accommodative amplitude in rhesus monkeys: an animal model for presbyopia . Invest Ophthalmol Vis Sci . 1982;;23:23-31.
14 +
Kaufman PL, Gabelt BT.  Cholinergic mechanisms and aqueous humor dynamics . In: Drance SM, Van Buskirk EM, Neufeld AH. eds. Pharmacology of Glaucoma . Baltimore, Md: Williams & Wilkins; 1992;:64-92.
15 +
Poyer JF, Gabelt BT, Kaufman PL.  The effect of topical PGF2α on uveoscleral outflow and outflow facility in the rabbit eye . Exp Eye Res . 1992;;54:277-283.
16 +
Rohen JW,  Lütjen-Drecoll E. Aging and non-aging processes in the anterior segment of the eye . In: Lütjen-Drecoll E, ed. Basic Aspects of Glaucoma Research III . Stuttgart, Germany: Schattauer; 1993;:191-224.
17 +
Lütjen-Drecoll E, Shimizu T, Rohrbach M, Rohen JW.  Quantitative analysis of 'plaque material' in the inner and outer wall of Schlemm's canal in normal and glaucomatous eyes . Exp Eye Res . 1986;;42:443-456.
18 +
Tamm S, Tamm E, Rohen JW.  Age-related changes of the human ciliary muscle: a quantitative morphometric study . Mech Ageing Dev . 1992;;62:209-221.
19 +
Tielsch JM. Sommer A, Katz J, Royal RM, Quigley HA, Javitt J.  Racial variations in the prevalence of primary open-angle glaucoma: the Baltimore Eye Survey . JAMA . 1991;;266:369-374.
20 +
Poyer JF, Kaufman PL, Flugen C.  Age does not affect contractile responses of the isolated rhesus monkey ciliary muscle to muscarinic agonists . Curr Eye Res . 1993;;12:413-422.
21 +
WoldeMussie E, Feldmann BJ, Chen J.  Characterization of muscarinic receptors in cultured human iris sphincter and ciliary smooth muscle cells . Exp Eye Res . 1993;;56:385-392.
22 +
Poyer JF, Gabelt BT, Kaufman PL.  The effect of muscarinic agonists and selective receptor subtype antagonists on the contractile response of the isolated rhesus monkey ciliary muscle . Exp Eye Res . 1994;;59:729-736.
23 +
Zhang X, Hernandez MR, Yang H, Erickson K.  Expression of muscarinic receptor subtype mRNA in human ciliary muscle . Invest Ophthalmol Vis Sci . 1995;;36:1645-1657.
24 +
Gupta N, Drance SM, McAllister R, et al.  Localization of M3 muscarinic receptor subtype and mRNA in the human eye . Ophthalmic Res . 1994;;26:207-304.
25 +
Gabelt BT, Kaufman PL.  Inhibition of outflow facility, accommodative, and miotic responses to pilocarpine in rhesus monkeys by muscarinic receptor subtype antagonists . J Pharmacol Exp Ther . 1992;;263:1133-1139.
26 +
Gabelt BT, Kaufman PL.  Inhibition of aceclidine-stimulated outflow facility, accommodation and miosis in rhesus monkeys by muscarinic receptor subtype antagonists . Exp Eye Res . 1994;;58:623-630.
27 +
Gabelt BT, Kaufman PL, Polansky JR.  Ciliary muscle muscarinic binding sites, choline acetyltransferase and acetylcholinesterase in aging rhesus monkeys . Invest Ophthalmol Vis Sci . 1990;;31:2431-2436.
28 +
Rohen JW, Futa R, Lütjen-Drecoll E.  The fine structure of the cribriform meshwork in normal and glaucomatous eyes as seen in tangenitial sections . Invest Ophthalmol Vis Sci . 1981;;21:574-585.
29 +
Rohen JW, Lütjen-Drecoll E, Bárány E.  The relationship between the ciliary muscle and the trabecular meshwork and Its importance for the effect of miotics on aqueous outflow resistance . Graefes Arch Clin Exp Ophthalmol . 1967;;172:23-47.
30 +
Kaufman PL.  Accommodation and presbyopia: neuromuscular and biophysical aspects . In: Hart WM Jr. ed. Adler's Physiology of the Eye: Clinical Application . St Louis, Mo: CV Mosby Co; 1992;:391-411.
31 +
Flügel C, Bárány E, Lütjen-Drecoll E.  Histochemical differences within the ciliary muscle and its function in accommodation . Exp Eye Res . 1990;;50:219-226.
32 +
Kaufman PL, Gabelt BT.  Cholinergic mechanisms and aqueous humor dynamics . In: Drance SM, Neufeld AH, Van Buskirk EM, eds. Pharmacology of Glaucoma . Baltimore, Md: Williams & Wilkins; 1992;:64-92.
33 +
Crawford K, Terasawa E, Kaufman PL.  Reproducible stimulation of ciliary muscle contraction in the cynomolgus monkey via a permanent indwelling midbrain electrode . Brain Res . 1989;;503:265-272.
34 +
Crawford KS, Kaufman PL, Bito LZ.  The role of the iris in accommodation of rhesus monkeys . Invest Ophthalmol Vis Sci . 1990;;31:2185-2190.
35 +
Gibbens MV.  The consensual ophthalmic reaction . Br J Ophthalmol . 1988;;72:746-749.

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1 +
Lütjen-Drecoll E, Tamm E, Kaufman PL.  Age-related loss of morphologic responses to pilocarpine in rhesus monkey ciliary muscle . Arch Ophthalmol . 1988;;106:1591-1598.
2 +
Tamm E, Croft MA, Jungkunz W, Lütjen-Drecoll E, Kaufman PL.  Age-related loss of ciliary muscle mobility in the rhesus monkey: role of the choroid . Arch Ophthalmol . 1992;;110:871-876.
3 +
Neider MW, Crawford K, Kaufman PL, Bito LZ.  In vivo videography of the rhesus monkey accommodative apparatus: age-related loss of ciliary muscle response to central stimulation . Arch Ophthalmol . 1990;;108:69-74.
4 +
Gabelt BT, Crawford K, Kaufman PL.  Outflow facility and its response to pilocarpine decline in aging rhesus monkeys . Arch Ophthalmol . 1991;;109:879-882.
5 +
Kaufman PL, Wiedman T, Robinson JR.  Cholinergics . In: Sears ML, ed. Pharmacology of the Eye. Handbook of Experimental Pharmacology . New York, NY: Springer-Verlag NY Inc; 1984;;69:149-191.
6 +
Duane A.  Studies in monocular and binocular accommodation with their clinical applications . Am J Ophthalmol . 1922;;5:867-877.
7 +
Kaufman PL, Jefferson JW, Ackerman D, Baumgartner S.  Ocular side effects of oral lithium in humans . Acta Ophthalmol (Copenh) . 1985;;63:327-332.
8 +
Kaufman PL.  Aging and aqueous humor dynamics . In: Di Vencentiis M, ed. The Fundamental Aging Processes of the Eye . Florence, Italy: Baccini & Chiappi: 1987;:41-46.
9 +
Hoskins HD Jr, Kass MA.  Aqueous humor outflow . Becker-Shaffer's Diagnosis and Therapy of the Glaucomas . 6th ed. St Louis, Mo: CV Mosby Co; 1989;:420-434.
10 +
Kaufman PL, Gabelt BT.  Aging, accommodation and outflow facility . In: Lütjen-Drecoll E. ed. Basic Aspects of Glaucoma Research III . Stuttgart, Germany: Schattauer; 1993;:257-274.
11 +
Kolker AE, Hetherington JJ.  Tables for tonography and tonometry . Becker-Shaffer's Diagnosis and Therapy of the Glaucomas . 5th ed. St Louis, Mo: CV Mosby Co; 1983;:519-535.
12 +
Liang KY, Zeger S.  Longitudinal data analysis using generalized linear models . Biometrics . 1986;;73:13-22.
13 +
Bito LZ, DeRousseau CJ, Kaufman PL, Bito JW.  Age-dependent loss of accommodative amplitude in rhesus monkeys: an animal model for presbyopia . Invest Ophthalmol Vis Sci . 1982;;23:23-31.
14 +
Kaufman PL, Gabelt BT.  Cholinergic mechanisms and aqueous humor dynamics . In: Drance SM, Van Buskirk EM, Neufeld AH. eds. Pharmacology of Glaucoma . Baltimore, Md: Williams & Wilkins; 1992;:64-92.
15 +
Poyer JF, Gabelt BT, Kaufman PL.  The effect of topical PGF2α on uveoscleral outflow and outflow facility in the rabbit eye . Exp Eye Res . 1992;;54:277-283.
16 +
Rohen JW,  Lütjen-Drecoll E. Aging and non-aging processes in the anterior segment of the eye . In: Lütjen-Drecoll E, ed. Basic Aspects of Glaucoma Research III . Stuttgart, Germany: Schattauer; 1993;:191-224.
17 +
Lütjen-Drecoll E, Shimizu T, Rohrbach M, Rohen JW.  Quantitative analysis of 'plaque material' in the inner and outer wall of Schlemm's canal in normal and glaucomatous eyes . Exp Eye Res . 1986;;42:443-456.
18 +
Tamm S, Tamm E, Rohen JW.  Age-related changes of the human ciliary muscle: a quantitative morphometric study . Mech Ageing Dev . 1992;;62:209-221.
19 +
Tielsch JM. Sommer A, Katz J, Royal RM, Quigley HA, Javitt J.  Racial variations in the prevalence of primary open-angle glaucoma: the Baltimore Eye Survey . JAMA . 1991;;266:369-374.
20 +
Poyer JF, Kaufman PL, Flugen C.  Age does not affect contractile responses of the isolated rhesus monkey ciliary muscle to muscarinic agonists . Curr Eye Res . 1993;;12:413-422.
21 +
WoldeMussie E, Feldmann BJ, Chen J.  Characterization of muscarinic receptors in cultured human iris sphincter and ciliary smooth muscle cells . Exp Eye Res . 1993;;56:385-392.
22 +
Poyer JF, Gabelt BT, Kaufman PL.  The effect of muscarinic agonists and selective receptor subtype antagonists on the contractile response of the isolated rhesus monkey ciliary muscle . Exp Eye Res . 1994;;59:729-736.
23 +
Zhang X, Hernandez MR, Yang H, Erickson K.  Expression of muscarinic receptor subtype mRNA in human ciliary muscle . Invest Ophthalmol Vis Sci . 1995;;36:1645-1657.
24 +
Gupta N, Drance SM, McAllister R, et al.  Localization of M3 muscarinic receptor subtype and mRNA in the human eye . Ophthalmic Res . 1994;;26:207-304.
25 +
Gabelt BT, Kaufman PL.  Inhibition of outflow facility, accommodative, and miotic responses to pilocarpine in rhesus monkeys by muscarinic receptor subtype antagonists . J Pharmacol Exp Ther . 1992;;263:1133-1139.
26 +
Gabelt BT, Kaufman PL.  Inhibition of aceclidine-stimulated outflow facility, accommodation and miosis in rhesus monkeys by muscarinic receptor subtype antagonists . Exp Eye Res . 1994;;58:623-630.
27 +
Gabelt BT, Kaufman PL, Polansky JR.  Ciliary muscle muscarinic binding sites, choline acetyltransferase and acetylcholinesterase in aging rhesus monkeys . Invest Ophthalmol Vis Sci . 1990;;31:2431-2436.
28 +
Rohen JW, Futa R, Lütjen-Drecoll E.  The fine structure of the cribriform meshwork in normal and glaucomatous eyes as seen in tangenitial sections . Invest Ophthalmol Vis Sci . 1981;;21:574-585.
29 +
Rohen JW, Lütjen-Drecoll E, Bárány E.  The relationship between the ciliary muscle and the trabecular meshwork and Its importance for the effect of miotics on aqueous outflow resistance . Graefes Arch Clin Exp Ophthalmol . 1967;;172:23-47.
30 +
Kaufman PL.  Accommodation and presbyopia: neuromuscular and biophysical aspects . In: Hart WM Jr. ed. Adler's Physiology of the Eye: Clinical Application . St Louis, Mo: CV Mosby Co; 1992;:391-411.
31 +
Flügel C, Bárány E, Lütjen-Drecoll E.  Histochemical differences within the ciliary muscle and its function in accommodation . Exp Eye Res . 1990;;50:219-226.
32 +
Kaufman PL, Gabelt BT.  Cholinergic mechanisms and aqueous humor dynamics . In: Drance SM, Neufeld AH, Van Buskirk EM, eds. Pharmacology of Glaucoma . Baltimore, Md: Williams & Wilkins; 1992;:64-92.
33 +
Crawford K, Terasawa E, Kaufman PL.  Reproducible stimulation of ciliary muscle contraction in the cynomolgus monkey via a permanent indwelling midbrain electrode . Brain Res . 1989;;503:265-272.
34 +
Crawford KS, Kaufman PL, Bito LZ.  The role of the iris in accommodation of rhesus monkeys . Invest Ophthalmol Vis Sci . 1990;;31:2185-2190.
35 +
Gibbens MV.  The consensual ophthalmic reaction . Br J Ophthalmol . 1988;;72:746-749.

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