Download Extended-wear soft contact lenses for vision studies in

1636
INVESTIGATIVE OPHTHALMOLOGY b VISUAL SCIENCE / November 1985
sure in the suction chamber. Each point in the figure
represents the average of two measurements of hydration after equilibration at a given swelling pressure.
Discussion. A stable and predictable postoperative
refractive keratoplasty procedure with hydrogel implants requires precise dimensional measurements of
the implant. If the implant undergoes thinning within
its intralamellar bed, then its effect on the postoperative
corneal refractive power could be grossly misjudged.
Previous observations1 would indicate the hydrogel intracorneal implants did thin by 28%, as measured directly by an optical pachymeter. The Haag-Streit
pachymeter is scaled for the refractive index of stroma
(1.376) while we used it to measure the thickness of
hydrogels with refractive indices of 1.402 to 1.380 (respective hydrogel water contents of 58% to 70%). Upon
recalibrating the pachymeter for the slightly higher refractive index of the hydrogels, the apparent thickness
of the implants was at the most 4% thicker than the
actual thickness.
In order to confirm this apparent in vivo hydrogel
thinning, a series of in vivo measurements were made
with hydrogel implants in the rabbit cornea. The hydrogel implant hydration and diameter within the corneal stroma were determined and compared to the
preoperative values. The data indicated the hydrogel
was dimensionally stable within the cornea, contradictory to the in vivo pachymetry data.
The hydration of the hydrogels equilibrated to various pressures was measured to simulate the intracorneal environment of the stromal swelling pressure.
Hydrogels of up to 69.5% water content maintained
their hydration when exposed to normal (55 mmHg)
stromal swelling pressure. At 150-mmHg swelling
pressure, the 75% water content hydrogel lost only 7.5%
of its water content. It presumably lost free water from
the large gaps, ie, pores, in the polymer molecular network. The greater the distance the free water molecules
are from the hydrogen binding sites on the polymer,
the less firmly these water molecules are held in their
clathrate structure. Refojo4 reported that hydrogel
membranes containing more than 75% water at equilibrium permit a viscous flow of water in the membrane
Vol. 26
in contrast to the diffusional transport in the lower
water content materials. Suction forces of the magnitude used in our experiments to simulate the corneal
swelling pressures can draw water from the structure
until equilibrium is reached. The hydration stability of
hydrogels of less than 69.5% water content when exposed to in vivo swelling pressures would indicate that
either the water in the hydrogel is firmly bound to the
hydrophilic sites within the hydrogel network, or the
polymer's molecular network is resistant to the
compression forces exerted on it at the test pressures.
Also, the insignificant change in the in vivo hydrogel
implant diameters in the rabbit experiments is supportive of the stable implant hydration measurements.
A loss of hydration would result in a reduction in the
volume of the material and a concurrent reduction in
the dimensions of the lens, including diameter.
In conclusion, the physical dimensions of the hydrogel intracorneal lenses of water content of 69.5%
and less are stable in the in vivo cornea. This supports
the use of hydrogel materials in keratorefractive surgery
and adds credibility to the predictability of the procedure.
Key words: hydrogel, hydration, keratorefractive surgery,
cornea, swelling pressure, pachymetry
From the Department of Ophthalmology, Emory University. Supported by NIH Grant No. 5R01EY03696, a grant from the IOLAB
Corp., and in part by a Departmental Research Grant from Research
to Prevent Blindness, Inc. ""Currently a visiting Associate in Ophthalmology from the Eye Hospital, Erasmus University, Rotterdam,
The Netherlands. Submitted for publication: May 21, 1984. Reprint
requests to: Dr. B. E. McCarey, Emory University, P. O. Box 22274,
Atlanta, GA 30322.
References
1. McCarey BE and Andrews DM: Refractive keratoplasty with
intrastromal hydrogel lenticular implants. Invest Ophthalmol Vis
Sci 21:107, 1981.
2. Klyce SD, Dohlman CH, and Tolpin DW: In vivo determination
of corneal swelling pressure. Exp Eye Res 11:220, 1971.
3. Hara T and Maurice DM: Changes in the swelling pressure of
the corneal stroma with time, hydration and temperature determined by a new method. Exp Eye Res 14:40, 1972.
4. Refojo M: Permeation of water through some hydrogels. J Appl
Polymer Sci 9:3417, 1965.
Extended-Wear Soft Contact Lenses for Vision Studies in Monkeys
J. Allen Gammon, Ronald G. Boorhe, Charles V. Chandler, Morgarere Tigges, and James R. Wilson
The authors have designed and produced extended-wear contact lenses for rhesus monkeys. High-plus lenses to correct
neonatal aphakia as well as lenses dyed black for use as occludcrs to treat amblyopia have been evaluated. Four infant
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monkeys fitted with soft lenses have successfully worn these
extended-wear lenses almost continuously throughout their
first year of life. These experiments demonstrate that rhesus
monkeys tolerate extended-wear contact lenses well when
Reporrs
No. 11
1637
Table 1. Treatment history of four newborn rhesus monkeys fitted with extended-wear contact lenses
Date contact(s)
were first fitted
Animal
Dale of birth
Date of surgery
RSC
5/25/83
5/31/83
5/31/83
N827
5/27/83
5/31/83
5/31/83
N837
6/25/83
6/28/83
7/1/83
N846
7/25/83
8/8/83
8/8/83
these lenses are correctly designed, comfortably fitted, and
their wear carefully monitored. Furthermore, the results
demonstrate that usable levels of vision can be maintained in
monocularly aphakic infant monkeys. Since similar methods
are now used to treat children with monocular cataracts, our
animal model using extended-wear contact lenses on young
monkeys should facilitate new and clinically relevant amblyopia experiments. Invest Ophthalmol Vis Sci 26:1636-1639,
1985
Historically, various methods have been employed
to study the effects of abnormal visual experience on
the function and structure of the developing visual system. In the past, investigators have reared monkeys in
complete darkness, or have sutured eyelids closed to
eliminate form vision, or they have reared animals
wearing specially designed helmets or face masks to
restrict visual experience.1"6 Although these techniques
have provided useful information, each has drawbacks.
For example, dark rearing may cause hormonal and
behavioral changes. Lid sutures can be difficult to
maintain and do not permit interim monitoring of visual development during deprivation. Helmet rearing
is difficult because of growth of the skull. To reduce
these shortcomings, we have designed and produced
extended-wear soft contact lenses which fit the eyes of
newborn rhesus monkeys. Removal, replacement, and
alteration of these lenses is easy, making possible a variety of new experiments to study visual development.
This report describes the development and first use of
these custom-designed soft contact lenses. Preliminary
reports of some of these results have been presented
previously in abstract form. 78
Materials and Methods. In order to design a soft
contact lens specifically for petite, steep infant monkey
corneas, we first measured the ocular dimensions of
three newborn rhesus monkeys (horizontal corneal diameter: 9.3 mm; A-scan axial length: 14.3 mm). Using
these measurements, we initially obtained lenses manufactured to our specifications from American Medical
Optics (Division of American Hospital Supply Corporation; Irvine, CA). Later, we obtained contact lens
manufacturing equipment and began producing the
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Type of contacts
fitted on each eye
+35 to +45
Occluder Lens OS
+35 to +40 Lens OD
Occluder Lens OS
+35 to +40 OD
No Contact OS
+35 to +40 OD
No Contact OS
Date killed
6/26/84
8/10/84
1/3/85
1/11/85
79% water-content soft lenses in our own laboratory.
In addition to focusing lenses, black occluder contacts
were also made so that visual input to an eye could be
selectively blocked. An extensive inventory of such
lenses was produced and maintained so that lost or
damaged lenses could be quickly replaced.
Our experiments were conducted on four newborn
rhesus (Macaca mulatto) monkeys, hand-reared according to protocols of the Yerkes Primate Center
nursery. At 3 to 14 days of age, the natural lens was
surgically removed from the right eye to simulate the
treatment of a monocular cataract. This aphakic eye
was then fitted with a 7.0-mm base curve, high-plus
soft contact lens. The power of the contact lens was
selected to make the aphakic eye approximately 2
diopters myopic. The refractive state was confirmed
by retinoscopy with the soft contact lens in place. Two
of the infants also had a black occluder lens fitted to
their unoperated eyes (Table 1). During the first several
months of life, all monkeys were individually housed
in isolettes. Thereafter, they were reared in individual
cages. During infancy, animal care technicians inspected the eyes every 2 to 4 hr at each feeding. In
addition, the monkeys were examined several times
daily by one of the authors. All monkeys periodically
underwent more detailed examinations, which included a slit-lamp evaluation, retinoscopy, and fundoscopy. The eyes were also examined carefully whenever ocular problems were suspected. When necessary,
the contact lens was removed from an irritated eye,
and the infant was placed in a dark room until the lens
could be replaced.
At about 6 months of age, each infant was trained
on an operant task and then tested for acuity. Behavioral training and testing methods are described in detail elsewhere.9 Briefly, the infants were trained in a
face mask cage to discriminate a grating stimulus from
a homogeneous field. Correct responses were rewarded
with apple juice. Incorrect responses resulted in a short
time out period. After the animal learned this task, the
bars in the grating were made progressively finer until
the animal's acuity limit was found. Gross visual function of each animal was also evaluated regularly by
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INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE / November 1985
Vol. 26
behavior using only one eye. The experiments described above conform to the ARVO Resolution of the
Use of Animals in Research.
Results. All of our monkeys fitted with custom-designed lenses tolerated these devices well. Behaviorally,
the animals accepted the lenses without frequent eye
rubbing or apparent awareness that a device was on
their eye (Fig. 1). The most frequent problem encountered was spontaneous loss of the lenses. For the first
few days after initial fitting, lens loss was a significant
problem. However, lens losses decreased to nominal
levels after a few days of wear. Occasional problems
were encountered, such as corneal epithelial lesions
and minor vascularization of the corneal periphery.
More serious ocular complications were not observed.
Visual behavior appeared very similar to untreated
nursery reared animals of the same ages. Videotape
recordings of the animals' monocular visual function
showed behavior that indicated usable vision in the
corrected aphakic eyes. However, the monkeys appeared blind when forced to use the eye which had
been occluded from birth. Quantitative measurements
of monocular visual acuity are shown in Table 2. Electrophysiological recordings from the cortex and anatomical studies of the eyes and brains are in progress.
Fig. 1. Monkey shown wearing an extended-wear aphakic lens on
her right eye and a soft occluder contact lens on her left eye (Animal
N-827).
offering small food morsels while observing ocular fixation and visually guided motor responses. At about 1
yr of age, the monkeys were placed in an open room
which was novel to them. In order to observe their
overall monocular visual function, we placed an occluder contact lens first on one eye and then on the
opposite eye while video recording their spontaneous
Discussion. Our results document that soft contact
lenses can be fitted and successfully worn by infant
monkeys for extended periods. We have confirmed that
usable vision can be maintained in neonatal aphakia
by contact lens rearing. Minor problems such as lens
loss and minor corneal complications can be overcome
by prompt identification and appropriate treatment.
Our initial use of these lenses has been to correct
monocular aphakia in newborn monkeys. In two of
our animals the contralateral eye was also occluded
with a black, soft contact lens (Fig. 1). This treatment
is similar but not necessarily equivalent to patching of
the better seeing eye commonly employed clinically
for the treatment of amblyopia in children.10 Use of
Table 2. Results of treatment of four newborn monkeys fitted with extended-wear contact lenses
Animal & treatment
Total number of
contact lenses used
Visual acuity
Number of
problems*
right eye
left eye
RSC (OD corrected)
(OS occluded)
14
4
20/150
brightness
only
N827 (OD corrected)
(OS occluded)
LI
n
20/150
brightness
only
N837 (OD corrected)
f
i
20/400
20/40 (normal
for age)
N846 (OD corrected)
5
2
20/200
20/40 (normal
for age)
* Problems encountered can be grouped into three general categories as follows: (1) Ocular inflammation/irritation evidenced by redness, discharge or
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ptosis; (2) corneal lesions such as abrasions, ulcers or peripheral vascularization:
(3) contact lens problems such as torn edges or deposits on the lens.
No. 11
1639
Reports
the black occluder contact lens forced the animal to
use its aphakic eye fitted with a high plus soft lens to
sharpen the images on this retina. The behavior of these
animals is normal, and usable vision can be maintained
in their aphakic eyes if the contralateral eyes are occluded. Our results demonstrate that aphakia can be
corrected in monkeys with soft contact lenses.
Since similar contact lenses and methods are now
used to treat children with congenital cataracts, our
monkey model is especially appropriate for investigating treatment variables to prevent amblyopia, such as
specific patching regimens and different contact lens
parameters. Additional studies are needed to clarify
the best therapy for optimal visual development after
induced or natural aberrations such as congenital
monocular cataracts.
Key words: monkey, infant, aphakia, extended-wear contact
lens, amblyopia
Acknowledgments: We appreciate the help of Dr. Joe
Dixon, Dr. David Ewell, Dr. Alcides Fernandes, Kaye Ford,
Annie Gammon, Tom Gay, John Logan, Dr. Bernie McCarey, and Dr. Johannes Tigges. Special thanks are due to the
veterinarians at Yerkes, Dr. J. Orkin, Dr. E. Strobert, Dr.
R. B. Swenson, and their staff for the expert care of our newborn monkeys.
From the Departments of Ophthalmology, Anatomy and Psychology, and the Yerkes Regional Primate Research Center, Emory
University, Atlanta, Georgia. This research was supported by NEI
grants 1 R03 EY05361-0I, EY-00638, NIH grant RR-00165, the
National Children's Eyecare Foundation, The National Society for
the Prevention of Blindness, American Medical Optics, an Emory
University Biomedical Research Support Grant, and an unrestricted
grant to the Department of Ophthalmology from Research to Prevent
Blindness. Submitted for publication: February 25, 1985. Reprint
requests: J. Allen Gammon, M.D., 1365 Clifton Road, Atlanta,
Georgia, 30322.
References
1. Chow KL, Riesen AH, and Newell FW: Degeneration of retinal
ganglion cells in infant chimpanzees reared in darkness. J Comp
Neurol 107:27, 1957.
2. von Noorden GK and Crawford MLJ: The effect of total unilateral occlusion vs. lid suture on the visual system of infant
monkeys. Invest Ophthalmol Vis Sci 21:142, 1981.
3. von Noorden GK: Experimental amblyopia in monkeys: Further
behavioral observations and clinical correlations. Invest
Ophthalmol 12:721, 1973.
4. Wiesel TN: Postnatal development of the visual cortex and the
influence of environment. Nature 299:583, 1982.
5. Mitchell DE and Timmey B: Postnatal development of function
in the mammalian visual system. In Handbook of Physiology
(Section 1)3, 1984, pp. 507-55.
6. Boothe RG, Dobson V, and Teller DY: Postnatal development
of vision in human and nonhuman primates. Ann Rev Neurosci
8:495, 1985.
7. Boothe RG, Gammon JA, Tigges M, and Wilson JR: Behavioral
measurements of acuity obtained from aphakic monkeys raised
with extended wear soft contact lenses. ARVO Abstracts. Invest
Ophthalmol Vis Sci 25(Suppl):216, 1984.
8. Gammon JA, Wilson J, and Tigges M: Production of anisometropia in infant monkeys as a model to study visual development after cataract removal. ARVO Abstracts. Invest
Ophthalmol Vis Sci 25(Suppl):215, 1984.
9. Williams R, Boothe R, Kiorpes L, and Teller D: Oblique effects
in normally reared monkeys (Macaca nemestrina); meridional
variations in contrast sensitivity measured with operant techniques. Vision Res 21:1253, 1981.
10. Jampolsky A: Unequal visual inputs and strabismus management: a comparison of human and animal strabismus. In Symposium on Strabismus, (Transactions New Orleans Academy of
Ophthalmology) St. Louis, TheC. V. Mosby Co., 1978, pp. 358492.
Codmium Reduces Extrooculor Muscle Controctility in Vitro ond in Vivo
Goodwin M. Breinin, Nicholas Sadovnikoff, Robert Pfeffer, Jacob Dovidowirz, and Danre J. Chiarandini
Cadmium, a blocker of calcium channels in various excitable
cells, reduces the contractility of extraocular muscles. When
applied to rat extraocular muscles in vitro, it reduces the
sustained or tonic tension generated by the tonic multiply
innervated fibers of the global layer of the muscles. When
injected in vivo into rabbit extraocular muscles, it produces
a temporary paralysis of the muscles and a deviation of the
eye position. These effects are presumed to involve a blockade
of the calcium channels of the muscle fibers and of the neuromuscular junctions. It is proposed that, on the basis of these
effects, a non-surgical treatment of strabismus could be developed. Invest Ophthalmol Vis Sci 26:1639-1642, 1985
Previous work has shown that rat extraocular muscles have the unique property of generating a sustained
or tonic tension when depolarized in vitro.1 This sus-
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tained tension can last for several hours and thus differs
markedly from the transient contraction observed with
the same stimulation in limb muscles.
It has been shown that the tonic tension in extraocular muscles is critically dependent on extracellular
calcium.1-8 The present experiments were performed
to investigate the possible effects on the contractility
of extraocular muscles of cadmium, a blocker of calcium channels in various excitable cells.2 It was found
that cadmium, when applied to rat extraocular muscles
in vitro, reduced the tonic tension, and that when injected in vivo into rabbit extraocular muscles, it produced a temporary paralysis of the muscles.
Materials and Methods. In vitro experiments: Albino
rats weighing 175-200 g were used. The dissection and