Pseudophakia retards axial elongation in neonatal monkey eyes.

Pseudophakia Retards Axial Elongation in NeonatalMonkey Eyes

Scott R. Lambert,*-f AlcidesFernandes*-\ Carolyn Drews-Botsch,*%and Margarete Tigges*j;

Purpose. To evaluate the affect of removing the crystalline lens and implanting an intraocularlens on the axial elongation of a neonatal eye.

Methods. Monocular lensectomy coupled with the implantation of a monofocal or multifocalintraocular lens was performed on 21 neonatal rhesus monkeys. Fellow eyes were randomizedto part-time occlusion therapy or no treatment. Longitudinal axial elongation of the pseu-dophakic eyes was then compared to that of the fellow eyes, to the eyes of 19 monkeys mademonocularly aphakic as neonates, and to the eyes of 39 normal monkeys.

Results. At 5 weeks of age, aphakic and pseudophakic eyes were significandy shorter than theirfellow eyes (P < 0.01). After 1 year of follow-up, the mean axial lengths of the pseudophakicand aphakic eyes were 2.0 ± 0.2 mm and 2.3 ± 0.2 mm, respectively, shorter than their felloweyes. This axial length difference persisted through a second year of follow-up. The differencebetween the mean axial lengths of the aphakic and pseudophakic eyes was not significant (P> 0.10). Part-time occlusion of the fellow eyes did not affect axial elongation.

Conclusions. Removing the crystalline lens and implanting an intraocular lens in a neonatalmonkey eye retards its axial elongation. Invest Ophthalmol Vis Sci. 1996;37:451-458.

.Intraocular lenses (IOLs) are being used increasinglyto correct optically children with unilateral and bilat-eral aphakia.' ~8 However, uncertainty exists regardingthe most appropriate lens power to use in a youngchild.910 Although most authors recommend under-correcting young children in anticipation of a myopicshift later in childhood,3'611 there is little empiricaldata to support these recommendations. Ideally, a lenspower would be chosen that would optimize visualacuity during childhood but would not result in sig-nificant ametropia later in life. The growth of thenormal human eye during early childhood has beenstudied,12'13 but it is unknown how the removal of thecrystalline lens and the implantation of an IOL affectsocular growth.

We have developed a monkey model using neona-

From the * Department of Ophthalmology, the f Yerkes Regional Primate ResearchCenter, and the %Def>arlment of Epidemiology, Emory University, Atlanta, Georgia.Supported in part \yy National Institutes of Health grants EY08544, EYO9737,EY05975, and P30 EY06360 (NIH Departmental Core Grant); National Center forResearch Resources grant RR00I65 to the Yerkes Regional Primate. Research Center;and a Departmental Grant from Research to Prevent Blindness, Inc.Submitted for publication September 5, 1995; accepted October 13, 1995.Proprietary interest category: N.Reprint requests: Scott R. Lambert, Department of Ophthalmology, Emmy EyeCenter, 1327 Clifton Road, N.E., Atlanta, GA 30322.

tal rhesus monkeys to test various treatment paradigmsfor human infants with monocular cataracts. We choserhesus monkeys because their eyes are anatomicallysimilar to human eyes, they develop approximatelythe same level of visual acuity as humans, and theirvisual system develops three to four times faster thanthat of humans, allowing results to be obtained in ashorter period of time.14'15

We removed the lens from one eye of these mon-keys during the first two weeks of life and then cor-rected the aphakic eye to a near point with a contactlens. The fellow eye either was occluded with anopaque contact lens to mimic "patching" of the"good" eye or was left untreated. Although we foundthat different visual outcomes were obtained de-pending on the amount of time the fellow eye was"patched,"16 all the aphakic eyes had shorter axiallengths than their fellow eyes.1718 More recently, wehave extended these investigations to evaluate the ef-ficacy of optically correcting aphakic neonatal eyeswith monofocal or multifocal IOLs.1920 In this report,we describe the effects of a lensectomy coupled withthe implantation of a posterior chamber IOL on thepostnatal axial elongation of neonatal monkey eyes.

Investigative Ophthalmology & Visual Science, February 1996, Vol. 37, No. 2Copyright © Association for Research in Vision and Ophthalmology 451

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452 Investigative Ophthalmology 8c Visual Science, February 1996, Vol. 37, No. 2

MATERIALS AND METHODS

The 79 rhesus monkeys (Macaca mulatto) described inthis article were born at the field station of the YerkesRegional Primate Research Center. Thirty-nine nor-mal monkeys were used as controls, and their axiallengths were measured while they were anesthetizedfor other purposes.

Nineteen monkeys underwent lensectomy of theright eye at 3 to 10 days of age, as has been describedpreviously.16"18 Ten of these monkeys were includedin the study by Tigges and coworkers.18 Eight aphakicright eyes wore an extended wear contact lens toachieve a near-point correction, and 11 were left un-corrected. Contact lens wear was begun a mean of11 (range, 8 to 21) days after surgery. Contact lenscompliance for the right eyes ranged from 95% to99% (mean, 98%). Seventeen of the fellow left eyeswere left untreated, whereas two received 75% occlu-sion (9 hours of the 12-hour light-12-hour dark cycle)with an opaque contact lens. The actual percentage ofthe daily light cycle that these monkeys were occludedranged from 71% to 76% (mean, 73%). Contact lenswear was continued until the monkeys were a meanof 19.2 (range, 15.2 to 25.4) months of age for theright eye and a mean of 15.4 (range, 7.7 to 23.2)mondis of age for the left eye.

Twenty-one monkeys had a translucent contactlens placed on their right cornea widiin a few hoursof birth to mimic a congenital cataract. At 11 to 16days of age, they underwent lensectomy and anteriorvitrectomy of the right eye, which was coupled withthe implantation of an all polymethylmethacrylateIOL into the posterior chamber as has been de-scribed.1921 A monofocal IOL (Storz Intraocular Lens,St. Louis, MO) was implanted in 11 of these eyes, anda multifocal IOL (3M Vision Care, Minneapolis, MN)was implanted in the other 10 eyes. Secondary mem-branes developed in all the pseudophakic eyes and in55% of the aphakic eyes. As soon as they interferedwith the clarity of the visual axis, they were openedusing either a YAG laser (Microrupter III; H.S. Merid-ian, Berne, Switzerland) or intraocular surgery.21 Inaddition, reproliferating lens material was removedsurgically in 20.6% of the pseudophakic eyes and 5.6%of the aphakic eyes when it obstructed the visual axis.21

All the pseudophakic eyes with a monofocal IOLwore an extended wear contact lens to achieve a near-point correction. All but one (RDV3) of the pseu-dophakic eyes with a multifocal IOL wore an extendedwear contact lens, which provided distance correctionwhile the add on the IOL provided a near-point cor-rection. Contact lens wear was begun a mean of 20(range, 10 to 36) days after surgery. Contact lens com-pliance for the right eyes ranged from 87% to 99%(mean, 91%). Ten of the left eyes were randomized

to no treatment and 11 to 70% occlusion (6 hoursof the 8.5-hour light-15.5-hour dark cycle) with anopaque contact lens. The actual percentage of thedaily light cycle that these monkeys were occludedranged from 64% to 76% (mean, 71%). Monkeys weredivided into four treatment groups based on the typeof IOL implanted in the right eye and on whether theleft eye received part-time occlusion, as follows:

Group 1 (n = 5): OD = monofocal IOL, OS =untreated;

Group 2 (n = 6): OD = monofocal IOL, OS =70% occlusion;

Group 3 (n = 5): OD = multifocal IOL, OS =untreated;

Group 4 (n = 5): OD = multifocal IOL, OS =70% occlusion.

Contact lens wear was continued until the mon-keys were a mean of 13.3 (range, 6.1 to 16.7) monthsof age for the right eye and a mean of 11.9 (range,10.1 to 13.6) months of age for the left eye.

All contact lenses were manufactured in our labo-ratory.22 Contact lens compliance was assessed every 2hours while the monkeys were awake. Missing lenseswere replaced immediately.

A mean of 20 examinations under anesthesia(range, 12 to 26) were performed on each monkey inthe pseudophakic group at regular intervals (every1 to 2 months). A mean of 11 examinations underanesthesia (range, 7 to 16) were performed on eachmonkey in the aphakic group at regular intervals. Amean of four longitudinal examinations under anes-thesia (range, 2 to 13) were performed on 19 of thenormal monkeys. A single examination under anesthe-sia was performed on the other 20 normal monkeys.Intraocular pressure was measured using applanationtonometry (Perkins [Clement Clarke, UK] tonome-ter) for both eyes during each examination underanesthesia. One pseudophakic monkey (RZF3) devel-oped glaucoma (intraocular pressure [IOP] > 21 mmHg during two or more examinations) during the ex-periment and was excluded from the analysis. Theinterocular (OD-OS) IOP difference for the othermonkeys with monocular pseudophakia ranged from-2.7 to +2.9 (mean, +0.9) mm Hg. The interocularIOP difference for the monkeys with monocular apha-kia ranged from +0.8 to +6.4 (mean, +2.4) mm Hg.The interocular IOP difference for the normal mon-keys ranged from —1.0 to +1.0 (mean, 0). Seven pseu-dophakic monkeys experienced breakage of one orboth IOL haptics a mean of 21 months (range, 6 to31 months) after their implantation.21'23 Axial lengthmeasurements obtained after the breakage of one orboth IOL haptics were not included in this analysis.

A-scan ultrasonography was performed using a So-


Pseudophakia Retards Axial Elongation 453

nomed (Lake Success, NY) A-1000 unit while the mon-keys were sedated with intramuscular acepromazineand ketamine. The instrument was fitted with a shortfocal length crystal and used modified software formeasurements of the small, steep eyes of these mon-keys. Tissue velocity settings were adjusted for the dif-ferent groups (Phakic, 1550 m/second; aphakic, 1532m/second; pseudophakic with multifocal IOL [0.7mm thickness], 1552 m/second; pseudophakic eyeswith monofocal IOL [0.8 mm thickness], 1554 m/second). Ten axial length measurements were madeon each monkey from the normal and aphakic groupsduring each examination. Because of difficulty ob-taining 10 axial length measurements for some mon-keys from the pseudophakic group, a mean of only9.4 (range, 2 to 10) axial length measurements wereobtained for each eye during individual examinations.We analyzed the axial length measurements for eightage bins: 1 (0 to 2) week, 5 (3 to 7) weeks, 10 (8 to12) weeks, 26 (18 to 34) weeks, 52 (47 to 57) weeks,78 (68 to 88) weeks, 104 (94 to 114) weeks, and 130(120 to 140) weeks. When multiple examinations wereperformed during one age bin, the axial length mea-surements obtained during the examination closestto the median age in the age bin was used for dataanalysis.

All procedures were performed in strict compli-ance with the ARVO Statement for the Use of Animalsin Ophthalmic and Vision Research, and the protocolswere approved by the Institutional Animal Care andUse Committee at Emory University.

Parametric and nonparametric analysis of vari-ance (ANOVA) was used to evaluate the effect of apha-kia, pseudophakia, and occlusion of the fellow eye onmean axial lengths and on mean interocular differ-ences in axial lengths using the Biomedical ProgramStatistical Software. Repeated measure ANOVAs werelimited to monkeys measured at 1, 26, and 52 weeks.All other analyses used data from all monkeys forwhich data from specific time points were available.

RESULTS

Normal Monkeys

The mean axial lengths of both eyes of the monkeysfrom the normal, aphakic, and pseudophakic groupsare shown in Table 1. Both the right and left eyes ofthe normal monkeys elongated a mean of 4.9 mmduring this 2-year interval. Approximately 80% of thisaxial elongation occurred during the first year. Thedifference in axial length of the right and left eyeswas not statistically significant for any age bin (P >0.10). Because data on only one normal monkey wasavailable in the 130-week age bin, no comparisoncould be made for this age bin.

Monocularly Aphakic Monkeys

An ANOVA was performed to determine the effect ofocclusion and contact lens correction on the axialelongation of the eyes in the monocularly aphakicmonkeys. Neither significandy affected the axiallengths of the right or left eyes from the differentmonocular aphakia treatment groups; as a result, thedata from all monocularly aphakic monkeys were ana-lyzed as a single group. In the 1-week age bin, thedifference in axial length between the left and righteyes (mean ± SEM, 0.1 ± 0.05 mm; range, +0.6 to—0.3 mm) was not significant (P > 0.10). However,by 5 weeks, the right eyes were significandy shorterthan the left eyes (mean ± SEM, —1.1 ± 0.1 mm;range, +0.1 to —1.8 mm; P < 0.01) and remained sofor all subsequent age bins (P < 0.01). The interocularaxial length difference remained relatively constantonce the monkeys were 52 weeks of age (mean ±SEM, -2.3 ± 0.2 mm; range, -1.3 to -4.0 mm) al-though the difference was reduced slighdy in the 78-week age bin (mean ± SEM, —2.0 ± 0.2 mm; range,-1.0 to -2.6) (Fig. 1).

Monocularly Pseudophakic Monkeys

An ANOVA also was performed to determine the ef-fect of occlusion and different IOL types on the axialelongation of the eyes in the four monocular pseu-dophakia treatment groups. Part-time occlusion(70%) did not affect the axial lengths of either theleft or right eyes in any of these treatment groups.The interocular axial length difference was signifi-cantly greater for monkeys receiving multifocal IOLthan monofocal IOL at 26 weeks (P = 0.03), 52 weeks(P = 0.05), 78 weeks (P < 0.01), and 104 weeks (P =0.03), but not at 130 weeks (P = 0.25) (Table 2). Tosimplify the comparison between monocularly apha-kic and pseudophakic monkeys, the data from all pseu-dophakic treatment groups were then pooled. Thedifference in the axial lengths of the left and righteyes from the pooled monocularly pseudophakiagroup was not statistically different in the 1-week agebin (P > 0.10). However by the 5-week age bin, theright eyes were significandy shorter than the left eyes(mean ± SEM, -0.7 ± 0.2 mm; range, +0.3 to -1.8mm) (P < 0.01). This difference was statistically sig-nificant for all subsequent age bins (P < 0.01). Whenthe monkeys were 52 weeks of age, all (except one)right eyes were shorter than the left eyes (mean ±SEM, -2.0 ± 0.2 mm; range, +0.1 to -3.7 mm). Thisdifference remained relatively unchanged during thesecond year of follow-up (Fig. 1). Interocular axiallength differences for all 20 monocularly pseudopha-kic monkeys are plotted in Figure 2. Filled, invertedtriangles in these figures show data from the pseu-dophakic right eyes and the open circles from the


454 Investigative Ophthalmology & Visual Science, February 1996, Vol. 37, No. 2

TABLE l. Longitudinal Axial Lengths (mm) of Right and Left Eyes

NormalsODOS

Monocular aphakiaODOS

Monocular pseudophakiaODOS

Values are mean ± SEM.OD = right eye; OS = left eye.

1

n=l13.6 ± 0.213.6 ± 0.2

n = 1713.2 ± 0.113.1 ± 0.1

n = 2013.2 ± 0.113.1 ± 0.1

5

rc= 1114.7 ± 0.214.8 ± 0.2

n = 1413.3 ± 0.214.5 ± 0.2

n = 1213.5 ± 0.314.2 ± 0.2

10

n= 1115.6 ± 0.215.6 ± 0.2

n = 814.0 ± 0.215.4 ± 0.2

n = 1914.0 ± 0.215.3 ± 0.1

Age Bin (weeks)

26

n= 1316.6 ± 0.116.7 ± 0.1

n = 1714.7 ± 0.216.5 ± 0.2

n = 2015.0 ± 0.216.8 ± 0.1

52

n = 917.4 ± 0.117.6 ± 0.1

n = 1615.2 ± 0.317.5 ± 0.1

n = 1915.7 ± 0.317.7 ± 0.2

78

n = 417.3 ± 0.717.4 ± 0.7

n = 715.8 ± 0.417.8 ± 0.4

n = 1816.1 ± 0.418.1 ± 0.2

104

n = 518.5 ± 0.318.5 ± 0.4

n = 615.9 ± 0.118.2 ± 0.2

n = 1716.3 ± 0.418.3 ± 0.2

phakic left eyes. Except for RTR3, the left eye waslonger than the right eye at the end of the experimentfor each monkey. In the 16 monkeys followed for 104weeks or longer, the pseudophakic eyes were shorterthan their fellow eyes by 1 mm or more in 13 monkeys(81%), 2 mm or more in 10 monkeys (63%), and 3mm or more in 4 monkeys (25%).

Comparison of All Groups

In the 1-week age bin, axial lengths of the right eyesdid not differ between the monocular aphakia, mon-

Axial Length Differences (OD - OS)

4!a

0.5

0.0

-0.5

-1.0

-1.3

-2.0

-2.5

O Normal Groupa Monocular Aphakia<& Monocular Pseudophakia

10

Age in weeks

100

FIGURE l. Axial length difference between the right and lefteyes of the normal (n = 39), monocular aphakia (n = 18),and monocular pseudophakia (n = 20) groups plotted as afunction of age.

ocular pseudophakia, and normal groups (P> 0.10),but in the 5-week and all subsequent age bins, the righteyes from the monocular aphakia and pseudophakiagroups were significantly shorter than the right eyesfrom the normal group (P < 0.01). Although the in-terocular axial length difference was slightly greaterfor the monkeys in the monocular aphakia than inthe monocular pseudophakia group for the 5-, 10-,52-, and 104-week age bins, this difference was notstatistically significant (P> 0.10). There was no differ-ence between the axial lengths of the left eyes of themonkeys from the normal group and the left eyes ofthe monkeys from the monocular aphakia and monoc-ular pseudophakia groups (P > 0.10).

DISCUSSION

We found that removing the crystalline lens in oneeye of a neonatal monkey and implanting an IOLresulted in retardation of axial elongation of this eyecompared to the fellow eye in 19 of 20 monkeys. Inmost cases, the interocular axial length difference in-creased until the monkeys were 1 year of age andthen remained stable thereafter. A similar effect wasobserved in monocularly aphakic monkeys. Retarda-tion of axial elongation has been reported as well innewborn rabbit eyes after lens extraction.24

Several mechanisms could account for this effect.First, intraocular surgery by itself could have retardedthe axial elongation of these eyes. This seems unlikelybecause sham intraocular surgery has been reportednot to affect the growth of a neonatal monkey eye.18

Second, the removal of the crystalline lens and theanterior vitreous may have altered the axial elongationof these eyes. Wilson and colleagues17 hypothesizedthat the crystalline lens may produce a trophic factorwhose absence during the neonatal period may retardocular growth or, alternatively, that disrupting the lenszonules may interfere with ocular growth. Using an



TABLE 2. Longitudinal Axial Lengths (mm) of Pseudophakic and Fellow Eyes

Group 1OD (monofocal IOL)OS (untreated)

Group 2OD (monofocal IOL)OS (70% occlusion)

Group 3OD (multifocal IOL)OS (untreated)

Group 4OD (multifocal IOL)OS (70% occlusion)

1

n = 413.1 ± 0.113.1 ± 0.2

n = 613.7 ± 0.313.4 ± 0.1

n = 513.1 ± 0.313.1 ± 0.2

n = 512.7 ± 0.212.7 ± 0.2

5

n = 313.4 ± 0.714.5 ± 0.03

n = 314.0 ± 0.514.5 ± 0.2

n = 513.5 ± 0.414.0 ± 0.3

n = 512.8 ± 0.914.1 ± 0.5

10

n = 414.1 ± 0.315.6 ± 0.2

n = 614.3 ± 0.215.5 ± 0.1

n = 513.8 ± 0.515.2 ± 0.3

n = 413.7 ± 0.715.1 ± 0.3

Age Bin

26

n = 415.7 ± 0.616.9 ± 0.2

n = 615.3 ± 0.216.9 ± 0.1

n = 514.9 ± 0.816.8 ± 0.3

n = 514.1 ± 0.516.6 ± 0.5

(weeks)

52

n = 516.3 ± 0.417.6 ± 0.2

n = 516.5 ± 0.518.3 ± 0.2

n = 415.6 ± 1.017.3 ± 0.3

n = 514.3 ± 0.417.3 ± 0.6

78

n = 416.8 ± 0.418.0 ± 0.2

n = 517.0 ± 0.518.4 ± 0.2

n = 416.1 ± 1.017.9 ± 0.4

n = 514.5 ± 0.417.9 ± 0.5

104

n = 316.9 ± 0.718.0 ± 0.02

n = 517.1 ± 0.618.7 ± 0.2

n = 416.5 ± 1.018.1 ± 0.3

n = 515.0 ± 0.5f18.2 ± 0.4

130

n = 317.0 ± 0.518.2 ± 0.1

n = 417.1 ± 0.519.0 ± 0.3

n = 317.0 ± 1.618.4 ± 0.6

n = 515.4 ± 0.518.3 ± 0.6

Values are mean ± SEM.OD = right eye; OS = left eye; IOL = intraocular lens.

avian model, it has been shown that removing thelens during embryogenesis profoundly retards axialelongation and arrests the further formation of vitre-ous humor.25'26 This effect appears to be independentof the lens extraction itself because ocular growth canbe normalized by reimplanting the lens in the aphakiceye. Congenital absence of the lens in a mutant strainof mice also has been shown to be associated withmicrophthalmus.27 A final possibility is that axial elon-gation may have been retarded in these eyes secondaryto visual deprivation during a critical stage of theirdevelopment.

Although severe visual deprivation produced bylid suturing,28 corneal opacification,29 or an opaquecontact lens usually results in axial elongation,18 lesserdegrees of visual deprivation have been shown to re-tard axial elongation.30"33 Bradley and colleagues31 re-ported that monkeys (Macaca mulatto) reared frombirth with monocular visual deprivation produced bya translucent contact lens developed a mean differ-ence of 0.74 mm between the treated and fellow eyesduring a 25-week follow-up. Kiorpes and Wallman32

also reported that the treated eyes of 10 of 19 monkeys(Macaca nemestrind) made strabismic or monocularlydefocused with a —10 D contact lens were shorter.This effect only occurred in monkeys that developedamblyopia and that were treated during the firstmonth of life. On average, the amblyopic eyes were2.1 mm shorter than the untreated fellow eyes. Smithand colleagues33 have reported that the treated eyesof 5 of 8 neonatal monkeys (Macaca mulatto) defo-cused in one eye with a —9 D contact lens for 2 to 4months were shorter; however, this interocular axiallength difference was lost in 3 of 5 monkeys after thedefocusing lens was removed.

Excessive axial elongation secondary to visual dep-rivation is age and light dependent and is probablyregulated locally within the eye. It is most pronounced

if visual deprivation occurs early in life, and it fails todevelop if visual deprivation occurs after the comple-tion of ocular growth.28'34 It does not develop in mon-keys reared in the dark.35 Monocular lid suturing doesnot affect axial elongation in dark-reared monkeys.31''37

It has been postulated that excessive axial elongationafter visual deprivation occurs independent of visionand accommodation because it will develop even ifthe visual cortex is ablated, the optic nerve is severed,or accommodation is blocked by the chronic instilla-tion of atropine.28 Eyes developing excessive axialelongation secondary to visual deprivation have de-creased levels of retinal dopamine,38 and excessiveaxial elongation can be prevented if a dopamine ago-nist is applied topically to the eye.39

Although Manzitti and coworkers40 have reporteda retardation of axial elongation in a large group ofchildren who underwent early bilateral cataract sur-gery similar to the effect we observed in infantile mon-keys, others have noted the opposite effect after theremoval of congenital cataracts.41"45 However, thesestudies were confounded by a delay in treatment. Forexample, Yamamoto44 reported excessive axial elonga-tion in the aphakic eyes of two children treated formonocular cataracts, but both children were nearly 1year of age before the cataracts were removed, anda sizable axial length difference was present in bothchildren before cataract extraction. Although theaxial length difference increased in one of these chil-dren after the removal of the cataract, the axial lengthdifference in the other child remained roughly thesame after 1 year of follow-up. Huber45 also notedgreater axial elongation in pseudophakic eyes com-pared to fellow eyes of seven children who underwentmonocular cataract extraction. All but one of thesechildren was 6 years of age or older at the time ofsurgery. Finally, Rasooly and BenEzra43 noted a meanaxial elongation of 1.5 mm in aphakic eyes compared



RNH3

RWF3

Group 3

RRS3 .RTT3

0 IS 90 73 100 1t9

Group 4

Age in weeks

FIGURE 2. Axial length measurements of the right (T) and left (O) eyes plotted as a functionof age. Monkeys in the first row (group 1) had a monofocal intraocular lens (IOL) implantedin the right eye and no treatment of the left eye. Monkeys in the second row (group 2) hada monofocal IOL implanted in the right eye and 70% occlusion of the left eye. Monkeys inthe third row (group 3) had a multifocal IOL implanted in the right eye and no treatmentof the left eye. Monkeys in the fourth row (group 4) had a multifocal IOL implanted in theright eye and 70% occlusion therapy of the left eye.

to fellow eyes of 17 children with congenital monocu-lar cataracts, but the mean age of these children was7 months when the cataracts were removed. A delay intreatment may result in an extended period of severevisual deprivation that may produce excessive axialelongation, which may then mitigate the effect of lensremoval. Furthermore, because most of the axial elon-gation of human eyes occurs in the first 2 years of life,removing the lens at a later age may have a differenteffect.13'40 In addition, many eyes with congenital cata-racts have other ocular abnormalities, such as mi-crophthalmia or glaucoma, and may grow abnormallyeven without treatment.'16"49

All die eyes in our study experienced visual depri-vation to varying degrees. Visual deprivation began inthe right eyes of the monkeys in the aphakic group

when they underwent a lensectomy at 3 to 10 days ofage. All diese eyes continued to be deprived visuallyto some extent for the remainder of die experimentregardless of whether they were left uncorrected orcorrected to a near point witii a contact lens. Visualdeprivation began in the right eyes of die monkeys indie monocular pseudophakia group within a fewhours of birdi, when a translucent contact lens wasplaced on these eyes, and it was exacerbated when alensectomy was performed on diese eyes 11 to 16 dayslater. The quality of the retinal image in many of dieaphakic and pseudophakic eyes was compromised fur-ther by secondary membranes that formed after sur-gery.21 What is surprising is diat the degree of visualdeprivation, which correlated highly widi the visualoutcome,16'20 did not correlate widi die effect we ob-



served on axial elongation. Thus, the axial elongationof the 11 aphakic eyes left untreated—which experi-enced the most severe of visual deprivation—was re-tarded to a degree similar to the pseudophakic eyesthat experienced the least degree of visual depriva-tion.

A final factor that may explain the interocularaxial length difference of the monkeys in the monocu-lar aphakia and pseudophakia treatment groups is adifference in the IOP between the aphakic-pseu-dophakic and fellow eyes. It is well known that elevatedIOP results in excessive ocular enlargement in infan-tile eyes. For this reason, we excluded from the analysisone monkey that developed glaucoma during the ex-periment. Interestingly, the only monkey (RTR3) thathad a longer pseudophakic eye than fellow eye wasalso the monkey with the greatest interocular IOP dif-ference (+2.9 mm Hg) among all the monkeys withmonocular pseudophakia. However, even though theinterocular IOP difference was slightly greater for themonkeys with monocular aphakia, no correlation wasnoted between the interocular IOP difference and theinterocular axial length difference for these monkeys.Though hypotony can result in retardation of axialelongation, the mean IOP was higher in all the apha-kic eyes and in all but two of the pseudophakic eyescompared to the fellow eyes. Therefore, it seems un-likely that the IOP was a significant factor in produc-ing a retardation of axial elongation in the aphakicpseudophakic eyes.

Given the similarities between the visual systemsof monkeys and humans, the retardation of axial elon-gation we observed in pseudophakic infantile monkeyeyes may occur in infantile human eyes. If this provesto be the case, it may be advisable to implant higherpowered IOLs in infants than predicted if emmetropiais to be achieved later in childhood. However, it isimportant to realize that a number of other variables,such as a delay in treatment, coexisting glaucoma, andmicrophthalmos, may further confound the axialgrowth of these eyes.

Key Words

cataract models, cataract surgery, development, emmetropi-zation, lens opacity

Acknowledgments

The authors thank the veterinary and animal care staff ofthe Yerkes Regional Primate Research Center for providingexcellent care for these monkeys. They also thank FrankKiernan for help in preparing the figures and Eric Ladinskyfor extracting data from our data base. The Yerkes RegionalPrimate Research Center is fully accredited by the AmericanAssociation for Accreditation of Laboratory Animal Care.

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Pseudophakia retards axial elongation in neonatal monkey eyes.

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