age-dependent loss of accommodative amplitude in rhesus

Age-dependent loss of accommodativeamplitude in rhesus monkeys: an

animal model for presbyopiaL. Z. Bito, C. J. DeRousseau,* P. L. Kaufman,** and]. W. Bito

The refractive power and axial dimensions of the eye were measured under resting and fullyaccommodated conditions in 123 caged rhesus monkeys ranging in age from 0.5 to >30 years.The mean resting refraction measured under ketamine anesthesia was —5 diopters. Accom-modative amplitude, calculated as the difference between resting refraction arid the mostnegative refraction measured 0.5 to 1 hr after topical application of a maximally effective doseof a cholinomimetic, showed an age-dependent decline. The mean accommodative amplitude of1- to 5-year-old rhesus monkeys was a remarkable 34 D, while animals over 25 years of ageaveraged 5 D of accommodation. Some >25-year-old animals showed no measurable change inrefraction regardless of the dose or the type of cholinomimetic (carbachol, pilocarpine, orechothiophate) used. The resting axial thickness of the lens was found to increase with agethroughout adulthood, well past the end of the growth period. A strong correlation was foundbetween pharmacologically induced change in the refractive power of the eye and change inlenticular thickness. These similarities to the human condition suggest that the rhesus monkeyrepresents a highly suitable animal model for the study of accommodation and presbyopia.(INVEST OPHTHALMOL VIS SCI 23:23-31, 1982.)

Keywords: Macaca mulatta, presbyopia, accommodation, lens, aging, carbachol,pilocarpine, echothiophate iodide, ocular dimensions, anthropometry

A continuous decrease in accommodativeamplitude and the development of presby-

From the Department of Ophthalmology, Research Di-vision, College of Physicians and Surgeons, ColumbiaUniversity, and * Department of Anthropology, NewYork University, New York, N. Y.; **Department ofOphthalmology, University of Wisconsin MedicalSchool, Madison, Wise.

This study was supported by U.S.P.H.S. ResearchGrants EY 00333, EY 00402 (to Dr. Bito), EY 02698,EY 00137 (to Dr. Kaufman), and RR-00167 (to Wis-consin Regional Primate Research Center; publicationno. 21-019), and by the Knapp Fund of the Edward S.Harkness Eye Institute, Columbia University.

Submitted for publication July 16, 1981.Reprint requests: Dr. L. Z. Bito, Department of Oph-

thalmology, Research Division, College of P & S, Co-lumbia University, 630 West 168th St., New York,N. Y. 10032.

opia are generally considered to be inevitableconsequences of aging,1""3 presumably re-lated, at least in part, to the continuousgrowth of the lens.4*5 However, probably be-cause of the lack of an adequate animalmodel, no basic studies have been conductedto support these conclusions; previous stud-ies aimed at elucidating the mechanisms oflenticular growth were done on the rabbit,6*7

a species with little or no accommodativeability regardless of age.

Previous surveys of rhesus monkey popu-lations at the Caribbean Primate ResearchCenter in Puerto Rico8 have shown that theadult rhesus lens increases in axial thicknesswith age9' 10 well past the period when maxi-mal globe size is achieved.9 This pattern issimilar to the age-dependent changes ob-

0146-0404/82/070023+09$00.90/0 © 1982 Assoc. for Res. in Vis. and Ophthal., Inc. 23

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24 Bito et al.Invest. Ophthalmol. Vis. Sci.

July 1982

served in the human lens5' U ) 12 but is un-like lenticular growth in other mammals,which follows the growth curve of the wholeglobe.13"16 In addition to lenticular growth,these surveys8' 9 have also found that themean intraocular pressure (IOP) and its vari-ation with age in rhesus monkeys are similarto these parameters previously described forhuman populations.17* 18 These similaritiessuggested that the rhesus monkey mightprovide a highly suitable animal model forthe study of age-related ocular dysfunctions,including the development of presbyopia.

The refractive power and axial dimensionsof the eyes of 123 rhesus monkeys rangingfrom 0.5 to >30 years of age were thereforemeasured under resting conditions and aftermaximum pharmacologically induced cholin-ergic stimulation. Other ocular parameters(corneal curvature, IOP, occurrence of cata-racts) and age-related musculoskeletal changeswere also surveyed to evaluate the relation-ships between ocular and more generalsomatic aging processes.19' 20 Findings per-taining to resting refraction, accommodativeamplitude, and ocular dimensions in therhesus monkey eye are presented in this ar-ticle as functions of chronological age.

Methods

All rhesus monkeys examined for this study be-long to and were used at the Wisconsin RegionalPrimate Research Center and the Primate Labora-tory of the Psychology Department of the Univer-sity of Wisconsin, which collectively house one ofthe largest known populations of aging and agedrhesus monkeys. Most animals in the currentsample had previously been manipulated for a va-riety of studies, some strictly behavioral andothers involving invasive techniques such as ovari-ectomy and hormone administration. However,no single procedural history predominated in thesample. Animals were excluded from the studyonly if their background included eye surgeryand/or trauma.

Each animal examined was weighed in a trans-fer cage and then tranquilized with an averagedose of 14.9 ± 1.6 (S.D.) mg/kg i.m. ketamineHC1. A second dose of ketamine equalling half theoriginal dose combined with 0.3 mg of acepro-mazine maleate (Ayerst Laboratories, Inc., New

York, N. Y.) was administered approximately 1 hrafter initial anesthesia, and subsequent doses ofketamine were given as needed until completionof the examination. Neither the dose of initial an-esthesia nor the duration of anesthesia showed asignificant correlation with any of the parametersmeasured.

All eyes were routinely examined by slit lamp,and animals that showed any ocular abnormalities,including even slight lenticular opacity, were thor-oughly examined by an ophthalmologist (P. L. K.).IOP was measured with an Alcon floating-tippneumatonograph after the topical application of0.5% proparacaine HC1. Two animals that hadIOPs >8 mm Hg higher than the mean IOP of 15.7mm Hg previously reported for this species8' 9

were excluded from the accommodation study, andtogether with the occurrence of cataracts in animals>20 years of age, are described elsewhere.21

Cataractous eyes were not excluded, since they didnot seem to behave differently than other eyes withrespect to the development of presbyopia.

Baseline measurements of corneal curvature,resting refraction, and dimensions of the globewere taken, in that order. Corneal curvature wasmeasured with a keratometer (Bausch and LombCo., Rochester, N. Y.), with a +1.25 diopter (D)spherical lens to extend its range, and drum read-ings were converted to diopters of corneal poweraccording to conversion tables published by Bauschand Lomb Co. (1.1659 x the drum reading). AHartinger Coincidence Refractometer (Zeiss-Iena)was used to measure resting refraction and drug-induced accommodation of the globe; a —7.25 Dhard (polymethylmethacrylate) corneal contactlens was used on some eyes to extend the negativedioptric measuring range of the refractometer, andthe instrument readings were corrected appro-priately. Axial lengths of the anterior chamber,lens, vitreous cavity, and whole globe were mea-sured with an A-scan ultrasonic device (DigitalBiometric Ruler, Model 300; Sonometrics System,Inc., New York, N. Y.) as previously described.9

In preliminary experiments during the first dayof the survey, seven animals were treated topicallywith increasing doses of carbachol, pilocarpine,echothiophate, or acetylcholine to find the drugsand doses that caused maximum accommodation.In one set of animals, atropine applied to one eye15 to 45 min after the application of carbachol orpilocarpine to the contralateral eye did not cause aconsistent change in the refractive state of the eyeand was therefore not used in the standard pro-tocol. Topical application of two drops of 10%


Volume 23Number 1 Animal model for presbyopia 25

phenylephrine HC1 solution was found to maintainan adequate pupil diameter (1.5 to 2 mm) for mea-suring refraction without having a notable effecton resting refraction or on the extent of drug-induced accommodation. Since these preliminaryexperiments were not based on a standardizedprotocol, their results were excluded from theanalyses presented here.

The following protocol was established for theremainder of the survey. After all baseline read-ings were taken, both eyes were treated with twodrops of 10% phenylephrine HCl, and in mostcases the animal received 0.01 mg/kg i.m. at-ropine sulfate, a dose found here and previously(P. L. Kaufman, unpublished observation) to besufficient to minimize the systemic, but not theaccommodative, effects of the topically appliedcholinomimetics. One eye then received five con-secutive corneal applications (5 /A each) of a 40%solution of pilocarpine HCl about 0.5 min apart,for a total dose of 10 mg. An identical regimen ofcarbachol was applied to the contralateral eye.One eye of 12 animals received four applications of5 fx\ of 2.5% echothiophate iodide (total dose of500 /xg/eye) instead of pilocarpine. In all cases,blinking was prevented for 0.5 min after each drugapplication. These doses of pilocarpine and car-bachol were at least 10 times greater, while thedose of echothiophate was at least 5 times greater,than their respective minimum doses required tocause maximal accommodation in these macaques.

Refraction and all ultrasonic measurementswere repeated 0.5 to 1 hr after drug application.To verify the refractoriness of old animals tocholinomimetic-induced changes in refraction, theentire protocol of drug applications and mea-surements was repeated on several old monkeys 1hr after the application of the first dose. In somecases, to minimize the systemic side effects causedby these cholinomimetics (e.g., lowered bloodpressure), a second larger dose (0.02 mg/kg) ofatropine was administered intramuscularly 1 hrafter pilocarpine or carbachol application, and re-fraction was measured 15 to 30 min later.

Statistical analyses were done with the SCSSConversational System22 on the DEC-20 com-puter at the Columbia University Center forComputing Activities. Resting refractions andmost ultrasonic measurements obtained on theright and left eyes were not statistically different;all baseline parameters were therefore averagedand analyses were performed on these averages.Means ± S.D. are presented, and correlations aredefined as significant if p < 0.05.

<

COLJ

0 10 20AGE (years)

Fig. 1. Relationship of resting refraction under an-esthesia to age in rhesus monkeys. Resting refrac-tion does not vary significantly with age, althougholder age groups do show a greater proportion ofindividuals with a refraction more negative than 1S.D. from the population mean. Animals with un-usually myopic resting refractions (indicated by ar-rows) also show some of the longest globes in thesample (see Fig. 2).

Results

The mean resting refraction of these rhesusmonkeys was — 5 D, with a mode of —4 D,and the regression of resting refraction on agewas not significant (Fig. 1). However, thepercentage of animals showing a resting re-fraction 1 S.D. below the mean increasedfrom 0% in <5-year-olds to 36% in >27-year-old animals. Three animals (noted by ar-rows in Figs. 1 and 2) who showed restingrefractions 2 S.D. below the mean alsoshowed unusually long globes, and in onecase (the shortest globe of the three) cornealcurvature was 5 D steeper than the averageof 53.2 ± 1.9 D. Resting refraction was ingeneral highly correlated with axial lengthof the globe (r = -0.50, p < 0.001), longerglobes showing more myopic refractions, butno consistent relationship was observedbetween resting refraction and corneal cur-vature.

Axial length of the globe (anterior surface


26 Bito et al.Invest. Ophthalmol. Vis. Sci.

July 1982

10 20AGE (years)

30

Fig. 2. Axial length of the globe as a function of agein rhesus monkeys. Globe growth, represented bythe regression of axial length on age in years (Y =0.33X + 17.23; r = 0.70, p < 0.001), appears toslow around 6 years of age. Adults show no signifi-cant change in globe size with age (Y = 0.01X +19.16; r = 0.12, p = 0.174). Some adult variabil-ity can be explained by sex differences in globesize, with males generally possessing a largerglobe than females. Individuals with resting re-fractions more myopic than 2 S.D. from the meanare indicated by arrows.

of the cornea to anterior surface of the retina)increased with age up to 6 years but was notsignificantly correlated with age in adults(Fig. 2). The mean axial length of the adultglobe was 19.5 ± 1.0 mm (males, 20.03 ±0.73; females, 19.18 ± 1.01). In contrast, thethickness (axial length) of the lens decreasedwith age in the 0.5- to 5-year-old group andthen showed a continuous and highly signifi-cant increase with age in adulthood (Fig. 3).This increase in lens thickness in adults is, inpart, at the expense of anterior chamberdepth, which although more variable thansome of the other measured ocular dimen-sions, showed a negative correlation with agein adults (r = - 0.28, p < 0.05).

Under our testing conditions, the accom-modative amplitude of young (0.5 to 5 years)rhesus monkeys was found to average a re-

0 10 20AGE (years)

Fig. 3. Lens thickness as a function of age inrhesus monkeys. The slope of the regression oflens thickness on age in years was negative in 1- to5-year-old rhesus monkeys (Y = — 0.07X + 3.89;r = -0.48, p < 0.05) and positive in adults (Y =0.03X + 3.05; r = 0.66, p < 0.001).

markable 34.4 D; after this age the amplitudegradually decreased (Fig. 4). Some of the>25-year-old animals showed little or nomeasurable change in refraction from base-line values even when treated with echothio-phate iodide or with two doses of pilocarpineor carbachol about 1 hr apart, each treatmentusing doses that were 10-fold greater than theminimum dose required to cause up to 40 Dof accommodation in younger animals. Like-wise, a small supplemental dose of systemicatropine given to reverse possible cardiovas-cular effects of the cholinergic drugs inducedno changes in the refraction of these olderindividuals.

Although the decrease in accommodativeamplitude as a function of age showed a veryhigh statistical significance (r = — 0.85, p <0.001), variability in accommodative ampli-tude within each age group was notable. Forexample, a few old monkeys (>20 year)showed over 10 D of accommodation, and one24-year-old female with a resting refraction of-16 D and an unusually long globe, accommo-



10 20AGE (years)

30

Fig. 4. Accommodative amplitude as a function ofage in rhesus monkeys. Amplitude of drug-in-duced accommodation decreases linearly with agein 1- to 25-year-old animals (Y = -1.31X +39.54; r = -0 .85, p < 0.001), tapering, off to aresidual accommodative capacity of <5 D in mostold individuals. Note, however, that many old in-dividuals showed some accommodative amplitudeand one 24-year-old female, indicated by the ar-row, accommodated over 30 D. Accommodativeamplitude is defined as the maximal drug-inducedaccommodative response of an individual minusthe resting refraction averaged from both eyes ofthat individual.

dated over 30 D (Fig. 4, arrows). In youngeranimals, some variability could be explainedby differences in the type of cholinomimeticdrug applied to the eye, carbachol inducingsomewhat more accommodation (36.0 ± 5 . 2D in 1- to 5-year-olds) than did pilocarpine(31.1 ± 5.6 D in 1- to 5-year-olds). In olderanimals, however, differences between theeffects of the various drugs were not sig-nificant.

There was a high degree of correlation be-tween accommodative amplitude and the cor-responding changes in lens thickness (r =0.78, p < 0.001; Fig. 5), anterior chamberdepth (r = -0.55, p < 0.001), and vitreousdepth (r = -0.20, p < 0.05). Axial length of

0 0.5 1.0 1.5

CHANGE IN LENS THICKNESS (mm)

Fig. 5. Relationship between accommodative am-plitude and accommodative change in lens thick-ness in rhesus monkeys. Change in refractive statein response to application of cholinergic drugs issignificantly correlated with a correspondingchange in lens thickness (r = 0.78, p < 0.001).

the globe, i.e., the distance between the an-terior surfaces of the cornea and the retina,however, did not change significantly withaccommodation.

Discussion

Our results clearly show that rhesus mon-keys undergo an age-related decrease in phar-macologically induced accommodative ampli-tude highly comparable to the age-dependentdecrease in physiologically induced accom-modative amplitude in humans.3 Taking intoconsideration differences in life span and max-imum accommodative capacity, the patternsof decrease in accommodative amplitude as afunction of chronological age are strikinglysimilar in these two species (Fig. 6). In bothhumans and rhesus monkeys the greatest am-plitude of accommodation is found in juve-niles, well before either species attainsskeletal maturity at 5 to 6 years of age inrhesus23 and around 18 years in human popu-lations.24 Both species show the greatest rate


28 Bito et al. Invest. Ophthalmol. Vis. Set.July 1982

HUMAN AGE (years)

12 24 36 48 60 72

RHESUS AGE (years)

Fig. 6. Human and rhesus patterns of age-dependent loss in accommodative amplitude. Themean (±S.D.) rhesus monkey accommodative am-plitude for each age group (3 year intervals), su-perimposed on the time curve of decrease in ac-commodative amplitude in humans, reveals a re-markable similarity in the patterns of age changein the two species. The curves representinghuman accommodative capacity (shaded area)were taken from figures constructed by Duane(1912)3 to include most "normal" cases.

of decline in amplitude in the second trimes-ter of their respective life spans. Postmeno-pausal age groups, >25 years old in rhesusmonkeys25 and >45 years old in humans,26

show a relatively stable residual accommoda-tive capacity. It should be noted that thetechnique used by Duane3 to generate thecurve for development of human presbyopia(reproduced in Fig. 6) may have overesti-mated accommodative amplitudes by approx-imately 1.5 D.27 However, this error appearsto be a constant and should not appreciablyaffect the shape of the curve presented byDuane.

The age-dependent decline in accommoda-tive amplitude in humans has been consid-ered to be the result of declining ciliary mus-cle function, continuing increase in the sizeand a concomitant flattening of the lens,changes in elasticity of the lens substance andcapsule, and/or changes in the distribution ofzonular insertions with respect to the lens

equator.5'28> 29 Some evidence has been pre-sented indicating that the first factor, declin-ing ciliary muscle activity, cannot account forthe loss of accommodative capacity in hu-mans.30' 31 Although the relative contributionsof the remaining lenticular factors remain tobe elucidated, it should be noted that mostand possibly all of these factors can be directlyor indirectly related to the continuous growthof the lens. In this and in a previous study9

on free-ranging rhesus monkeys, lenticularthickness was found to increase with agewell past the period of rapid general andocular growth, mimicking human lenticulargrowth.11 Thus there is no reason to believethat in rhesus monkeys the etiology of theage-dependent decrease in accommodativeamplitude is basically different from that ofhumans.

The maximal accommodation of over 40 Dobserved in some rhesus juveniles in thisstudy is more than the accommodative ampli-tude previously reported for any terrestrialmammal.32"35 Anecdotal reports suggest thathuman infants may similarly possess the larg-est accommodative amplitudes for their spe-cies, as much as 20 D,32 although reportedsurveys of human populations3' 36 do not in-clude young children or infants. The lack ofadequate population data on human juvenilescannot, however, explain the discrepancy inmaximal accommodative amplitude noted be-tween the two species, since not only juve-niles but also older age groups of rhesusmonkeys show about twice as much accom-modative capacity as those reported for hu-mans of comparable ages (see Fig. 6).

We may conclude, therefore, that rhesusmonkeys possess a greater capacity for ac-commodation and have a much closer nearpoint than do humans. This may be, in part,an allometric phenomenon related to speciesdifferences in body size and specifically in in-terpupillary distance, since the smaller rhesusmonkey infant requires a much greater ac-commodation per given angle of convergencethan does the larger human infant. It shouldbe noted, however, that an emmetropic eyecapable of 20 D of accommodation has a nearpoint of 5 cm, whereas 40 D brings the near



point only 2.5 cm closer to the eyes. Hence,the measured discrepancy between rhesusand human accommodative range may notimply an important difference in function.

Although we cannot rule out the possibilitythat cholinergic drug-induced accommoda-tion is greater than physiologic accommoda-tion, maximum accommodation under eser-ine was found to be only 1 to 3 D greater thanvoluntary accommodation in humans.37 Inaddition, accommodation induced by electri-cal stimulation of the midbrain was found tobe up to 27 to 29 D in cynomolgus (Macacafascicularis) and owl monkeys (Aotus trivir-gatus) of unspecified ages.38 Other authors,using electrical stimulation or local adminis-tration of cholinergic drugs, have also re-ported over 20 D of accommodation in non-human primates.39' 40 Although considerablylower amplitudes (4 to 12 D) have often beennoted in response to voluntary accommoda-tion or to electrical or unspecified stimulationin monkeys,34' 41~43 these reports do not gen-erally take into account the ages of the ani-mals examined. Only one study39 appears tohave considered the effect of age on accom-modative amplitude in primates, finding thattwo cynomolgus monkeys, apparently old onthe basis of general appearance and toothwear, showed amplitudes of 9 to 10 D aftertopical application of carbachol as comparedwith values near 20 D in apparently youngeranimals. These considerations indicate thatour results do not necessarily overestimatethe physiologic capacity of the rhesus eye toaccommodate.

Behavioral observations provide furtherevidence that a large amplitude of accommo-dation is normal for young macaques. Rhesusmonkeys perform visual tasks ranging fromsocial grooming and inspection of insects,dirt, etc. held very close to their eyes, torecognition of friend and foe at distancesgreat enough to ensure safety (DeRousseau,unpublished observations). It tends to be theyounger animals on the periphery of thegroup who most frequently act as "look outs"and also perform the greater proportion ofnear-vision tasks such as grooming; older in-dividuals are more centrally located in the

group and are more often the recipientsrather than the givers of grooming.44 Thus,not only the range of visual behavior but alsothe age-dependent differences in behavioralpatterns are consistent with our findings onaccommodative amplitude in this species. Infact, although changes in social grooming be-havior with age have been related to changesin dominance rank,44 our findings suggest thatthe decline in accommodative capacity mustbe considered in the interpretation of suchage-dependent shifts in behavioral patterns.

The average resting refraction under ket-amine of — 5 D cannot be taken as an indica-tion that rhesus monkeys tend to be normallymyopic, since our "resting refraction" doesnot necessarily represent the far point ofthese animals. Monkeys have been shown toexhibit about 1.5 D of accommodation in dark-ness, corresponding to the well-describedhuman syndrome of night myopia,45 and toaccommodate still further, about 3 D, whenanesthetized or asleep.46

Young47' 48 measured the resting refractionof the eyes of caged and "wild-captured" OldWorld monkeys after topical application of acycloplegic and suggested that caged mon-keys tend to show a higher frequency ofmyopia. In addition, Young49 reports that re-fractions were made more negative by plac-ing animals in restricted visual spaces. Al-though Young's work is certainly suggestive,his reports did not or could not always takeinto account the age of the animals, while hisexperimental work was generally done onsamples of insufficient size to control for allpossible confounding factors. Furthermore,it is not clear whether under the conditions ofhis refractions a true far point was measured,and he did not attempt to measure accom-modative amplitude.

The observed variability in accommodativeamplitude in older monkeys in our sample,for example, the existence of a 24-year-oldfemale that showed an accommodative ampli-tude of >30 D, suggests that presbyopia isnot a totally predictable and inevitable con-sequence of aging in rhesus monkeys. Thismay appear to be in conflict with generallyaccepted textbook concepts about the predic-


30 Bito et at.Invest. Ophthalmol. Vis. Sci.

July 1982

tability of the development of presbyopia inhumans. However, in Duane's classic studyof human accommodation,3 which is quotedin all current textbooks, almost a third of thesubjects examined were excluded from hisanalyses. Thus, Duane's population may haveincluded greater variability than his pub-lished figures indicate; a more random sam-ple of a human population may well showvariability in the accommodative amplitudeof older individuals similar to that observedin the present study on rhesus monkeys. Fur-ther longitudinal and more detailed cross-sectional studies may, in fact, isolate condi-tions that modify the time-course of accom-modative loss and the onset of presbyopia.The results of this preliminary survey clearlyindicate that the rhesus monkey can serve asan animal model for such studies and for basicstudies aimed at elucidating the age-depen-dent decrease in accommodative amplitudeand the etiology of presbyopia.

We are grateful to Dr. R. W. Goy, Dr. W. D.Houser, Mr. D. J. Mohr, and their staff at theWisconsin Regional Primate Research Center, andto Dr. S. J. Suomi, Dr. J. W. Davenport, Dr. R.Bowman, Mr. C. Ripp, Jr., and their staff at thePrimate Laboratory of the Psychology Depart-ment, University of Wisconsin, Madison, for pro-viding access to and aid in working with their ani-mals. Ms. K. A. Erickson, Ms. E. M. Klein, andMr. R. Nichols expertly performed many of themeasurements.

REFERENCES1. Moses RA: Accommodation. In Adler's Physiology of

the eye, Clinical Application, Moses RA, editor. St.Louis, 1981, The C. V. Mosby Co., ch. 11.

2. Alpern M: Accommodation and the pupil. Part II. InThe Eye. Muscular Mechanisms, vol. 3, Davson H,editor. New York, 1969, Academic Press, Inc.

3. Duane A: Normal values of the accommodation at allages. Transactions of the American Medical Associ-ation, Section on Ophthalmology, 1912, p. 383.

4. Fisher RF: Presbyopia and the changes with age inthe human crystalline lens. J Physiol 228:765, 1973.

5. Weale RA: Presbyopia. Br J Ophthalmol 46:660,1962.

6. Bito LZ and Harding CV: Patterns of cellular organi-zation and cell division in the epithelium of the cul-tured lens. Exp Eye Res 4:146, 1965.

7. Bito LZ, Davson H, and Snider N: The effect ofautonomic drugs on mitosis and DNA synthesis in

the lens epithelium and on the composition of theaqueous humor. Exp Eye Res 4:54, 1965.

8. Bito LZ, Merritt SQ, and DeRousseau CJ: In-traocular pressure of rhesus monkeys (Macacamulatta). I. An initial survey of two free-breedingcolonies. INVEST OPHTHALMOL VIS SCI 18:785, 1979.

9. DeRousseau CJ and Bito LZ: Intraocular pressure ofrhesus monkeys (Macaca mulatta). II. Juvenile ocu-lar hypertension and its apparent relationship toocular growth. Exp Eye Res 32:407, 1981.

10. Denlinger JL, Eisner G, and Balazs EA: Age-relatedchanges in the vitreous and lens of rhesus monkeys(Macaca mulatta). I. Initial biomicroscopic and bio-chemical survey of free-ranging animals. Exp EyeRes 31:67, 1980.

11. Smith P: Diseases of crystalline lens and cap-sule. 1. On the growth of the crystalline lens. TransOphthalmol Soc UK 3:79, 1883.

12. Weale RA: Sex, age and the birefringence of thehuman crystalline lens. Exp Eye Res 29:449, 1979.

13. Eli LO: Metabolism of the crystalline lens. I. Watercontent and growth rate. Am J Opthalmol 32:215,1949.

14. Norrby A: On the growth of the crystalline lens, theeyeball and the cornea in the rat. Acta Ophthalmol[Suppl]49:5, 1958.

15. Krause AC: Chemistry of the lens. VII. Growth andsenescence. Arch Ophthalmol 13:71, 1935.

16. Brown EVL and Evans El: Studies of the crystallinelens. V. The nature of the reducing substances inthe lens. Trans Am Ophthalmol Soc 33:220, 1935.

17. Bankes JLK, Perkins ES, Tsolakis S, and Wright JE:Bedford glaucoma survey. Br Med J 1:791, 1968.

18. Kornblueth W, Aladjemoff L, Magora F, and BenDor D: Intraocular pressure in children measuredunder general anesthesia. Arch Ophthalmol 72:489,1964.

19. Bito LZ, Kaufman PL, DeRousseau CJ, and BitoJW: Development and aging of the eye. I. Accom-modative range, lenticular growth, development ofpresbyopia, and occurrence of senile cataracts andocular hypertension in rhesus monkeys. Proc IntSoc Eye Res 1:71, 1980.

20. DeRousseau CJ, Kaufman PL, and Bito JW: Devel-opment of presbyopia, degenerative disk diseaseand other predictable age-dependent afflictions inrhesus monkeys. Am J Phys Anthropol 54:214,1981.

21. Kaufman PL and Bito LZ: The occurrence of senilecataracts, ocular hypertension and glaucoma inrhesus monkeys. Exp Eye Res 34:287, 1982.

22. Nie NH, Hull CH, Franklin MN, Jenkins JG, SoursKJ, Norusis MJ, and Beadle V: A User's Guide tothe SCSS Conversational System. New York, 1980,McGraw-Hill Book Co., Inc.

23. Gavan JA and Hutchinson TC: The problem of ageestimation: a study using rhesus monkeys (Macacamulatta). Am J Phys Anthropol 38:69, 1973.

24. Harrison GA, Weiner JS, Tanner JM, and BarnicotNA: Human Biology. An Introduction to Human



Evolution, Variation, Growth and Ecology. Oxford,1977, Oxford University Press.

25. Catchpole HR and van Wagener G: Reproduction inthe rhesus monkey, Macaca mulatta. In The RhesusMonkey, vol. II, Bourne, GH, editor. New York,1975, Academic Press, Inc.

26. Sherman BM, West JH, and Korenman SG: Themenopausal transition: analysis of LH, FSH, es-tradiol and progestrone concentrations during men-strual cycles of older women. J Clin Endocrinol 42:629, 1976.

27. Hamasaki D, Ong J, and Marg E: The amplitude ofaccommodation in presbyopia. Am J Optom 33:3,1956.

28. Fisher RF: The force of contraction of the humanciliary muscle during accommodation. J Physiol 270:51, 1977.

29. Farnsworth PN and Shyne SE: Anterior zonularshifts with age. Exp Eye Res 28:291, 1979.

30. Saladin JJ and Stark L: Presbyopia: new evidencefrom impedance cyclography supporting the Hess-Gullstrand theory. Vision Res 15:537, 1975.

31. Swegmark G: Studies with impedance cyclographyon human ocular accommodation at different ages.Acta Ophthalmol 46:1186, 1969.

32. Duke-Elder S: System of Ophthalmology. Vol. I.The Eye in Evolution. St. Louis, 1958, The C. V.Mosby Co.

33. Collins ET: The Bowman Lecture, 1921. Changesin the visual organs correlated with the adoption ofarboreal life and with the assumption of the erectposture. Trans Ophthalmol Soc UK 41:10, 1921.

34. Weale RA: Natural history of optics. In The Eye.Comparative Physiology, vol. 6., Davson H andGraham LT Jr., editor. New York, 1974, AcademicPress, Inc., ch. 1.

35. Walls GL: The Vertebrate Eye and its AdaptiveRadiation. New York, 1963, Hafner Publishing Co.,ch. 10.

36. Bruckner R: Uber Methoden longitudinaler Altern-

forschung am Auge. Ophthalmologica 133:59, 1959.37. Fincham EF: The proportion of ciliary muscle force

required for accommodation. J Physiol 128:99, 1955.38. Chin NB, Ishikawa S, Lappin H, Davidowitz J, and

Breinin GM: Accommodation in monkeys inducedby midbrain stimulation. INVEST OPHTHALMOL 7:

386, 1968.39. Tornqvist G: Effect of topical carbachol on the pupil

and refraction in young and presbyopic monkeys.INVEST OPHTHALMOL 5:186, 1966.

40. Kaufman PL, Rohen JW, and Barany EH: Hy-peropia and loss of accommodation following ciliarymuscle disinsertion in the cynomolgus monkey:physiologic and scanning electron microscopic stud-ies. INVEST OPHTHALMOL VIS SCI 18: 665, 1979.

41. Barrett JW: Do mammals accommodate? Ophthal-mic Rev 17:255, 1898.

42. Duke-Elder S: System of Ophthalmology. Vol. III.Normal and Abnormal Development. Part. 1. Em-bryology. St. Louis, 1963, The C. V. Mosby Co.

43. Jampel RS and Mindel J: The nucleus for accommo-dation in the midbrain of the macaque. INVESTOPHTHALMOL 6:40, 1967.

44. Sade DS: Sociometrics of Macaca mulatta. I. Link-ages and cliques in grooming matrices. Folia Prima-tol 18:196, 1972.

45. Owens DA and Liebowitz HW: The intermediateresting point of accommodation: recent evidenceand applications. Proc Int Soc Eye Res 1:71, 1980.

46. Westheimer G and Blair SM: Accommodation of theeye during sleep and anesthesia. Vision Res 13:1035, 1973.

47. Young FA: The distribution of refractive errors inmonkeys. Exp Eye Res 3:230, 1964.

48. Young FA: Visual-optical characteristics of cagedand semifree-ranging monkeys. Am J Phys An-thropol 38:377, 1973.

49. Young FA: The development and retention ofmyopia by monkeys. Am J Optom 38:545, 1961.


age-dependent loss of accommodative amplitude in rhesus

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