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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 Downloaded From: http://iovs.arvojournals.org/ on 05/12/2017 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 Downloaded From: http://iovs.arvojournals.org/ on 05/12/2017 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 1608 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 Downloaded From: http://iovs.arvojournals.org/ on 05/12/2017 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- Downloaded From: http://iovs.arvojournals.org/ on 05/12/2017 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