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Pluronic polyol: A potential alloplastic keratorefractive material
Pluronic polyol: A potential alloplastic keratorefractive material J.
P. Kim, B.S., R. L. Peiffer, D.V.M., Ph.D., R. E. Holman, M.D .
. B TR. Pluronic polyol p a neg the t mp ratu III i nl of 'Iation; it h Hpro imatel thr' diopt r. wa., n ted in the e p rimental group, whil no chang \\a., n in th onll'Ol gr >up. ) 'YoI'd
.. I\opl., ti<: mat ·rial. k·.-atm ·Iin 'li, '
\11"
·ry. pluroni<:
p() l~ol
Current research has focused on keratorefractive procedures-surgical alteration of the cornea to change refractive power and thus improve visual acuity. These techniques work by altering either the curvature of the anterior corneal surface or the corneal refractive index. Such techniques as epikeratophakia, keratomileusis, implantation of hydrogel or hard plastic lenses within the corneal stroma, and radial keratotomy offer promise but have the limitations of technical difficulty and/or limited or unpredictable correction. 1-8 The objective of this study was to evaluate pluronic polyol (polyoxypropylene-polyoxyethylene condensate) as a potential material for keratorefractive surgery. Pluronic polyol, a synthetic gel currently being tested as an artificial skin in the treatment of thermal burns, possesses a negative temperature coefficient of
gelation - it is liquid at low temperatures and gelatinous at high temperatures. Using a rabbit model, we injected pluronic polyol intrastromally to determine the tolerability of the cornea to the gel and the extent and reproducibility of refractive change. We hypothesized that if we injected the material as a liquid at cold temperature into a defined tissue space and allowed it to solidify, as pluronic will at body temperature, it should result in an alteration of the anterior surface curvature and the refractive error. MATERIALS AND METHODS Pluronic F10B (BASF Wyandotte Corporation, Performance Chemical, Parsippany, NJ) has a molecular weight of 14,600 and is a difunctional glycol base arranged in a "triblock" linear configuration. It is
From the Departments of Ophthalmology (Mr. Kim, Drs. Peiffer and Holman) and Pathology (Dr. Peiffer), School of Medicine, University of North Carolina, Chapel Hill, North Carolina. Sponsored in part by a grant from Research to Prevent Blindness, Inc., New York, New York. Originally presented as a poster exhibit at the 1986 ARVO meeting, Sarasota, Florida, April 1986. Reprint requests to R.L. Peiffer, Department of Ophthalmology, 617 Clinical Sciences Building (229H), University of North Carolina, Chapel Hill, North Carolina 27514. 312
J CATARACT REFRACT SURG-VOL
14, MAY 1988
formed by the condensation of propylene oxide onto a propylene glycol nucleus followed by the condensation of ethylene oxide onto both ends at the poly (oxypropylene) base. Osmolarity and refractive index have not been determined by the manufacturer. This study employed a 25 wt % aqueous solution of approximately 100% purity, which was prepared in a cold room (4°C) using 25 g of FI08 prill mixed into 75 g of water. Adequate agitation of the solution was obtained by a mixing bar and magnetic stirrer operating overnight. The resultant foamy mixture was then placed undisturbed in a refrigerator for one day. Sterilization was accomplished with an autoclave. Initial keratometry and pachymetry measurements were taken on 17 adult New Zealand albino rabbits to determine corneal curvature and thickness. Surgery was performed using intramuscular ketamine hydrochloride (35 mglkg) xylazine hydrochloride (5 mglkg) anesthesia and involved the dissection of a 7 mm diameter circular pocket within the axial corneal stroma of both eyes of the rabbits. An axial circular area was demarcated using a 7 mm trephine; a 5 mm wide incision was made in the nasal or temporal quadrant to a depth of 0.2 mm with a razor blade knife. The dissection of the stromal bed was carried out using a #66 Beaver blade. Autoclaved sterilized pluronic F108 in a liquid state, 0.03 ml, was injected into the prepared bed of one cornea; the fellow sham-operated eye was not injected and served as a control. The wound was closed with two simple interrupted deep stromal 9-0 nylon sutures that were removed after three to four weeks. Immediately after surgery, each animal was given a subconjunctival injection of tobramycin and an intramuscular injection of penicillin. Chloramphenicol ointment was applied to both eyes daily for the following month; in cases with significant corneal inflammation, rabbits were treated with topical 1.0% atropine sulfate ointment and antibiotics supplemented with corticosteroids (Maxitrol®). Postoperatively, rabbits were clinically evaluated by biomicroscopy, keratometry, and optical pachymetry. There were sacrifices at one week, one month, two months, and three months postoperatively to study the cornea by light and electron microscopy. Following euthanasia, the corneas to be studied by light microscopy were immediately fixed in 4.0% paraformaldehyde and processed routinely. Selected corneas were fixed in a 2.0% paraformaldehyde and 4.0% glutaraldehyde solution and were bisected and processed for transmission and scanning electron microscopy. Scanning electron microscopy corneal halves were mounted for study of both endothelial and epithelial surfaces . RESULTS The typical postoperative course of most animals included conjunctival hyperemia, extensive corneal
Fig. l.
(Kim) Rabbit pluronic eye one week postoperatively. Conjunctival hyperemia and extensive corneal vascularization were noted , in addition to small epithelial defects around the sutures.
vascularization, and small epithelial defects at the onset (Figure 1). The vascularization tended to extend from the limbus toward the surgical incision within the anterior corneal stroma. Subsequent corneal scarring was evident at the incision site to a variable degree . By the end of three months postoperatively, inflammation had resolved leaving minimal scarring (Figure 2). Slitlamp examination also revealed this scarring and neovascularization, in addition to the presence of numerous punctate stromal opacities within the implant bed (Figure 3).
Fig. 2.
J CATARACT REFRACT SURG-VOL
(Kim) Pluronic eye three months postoperatively. Mild scarring was evident. 14, MAY 1988
313
Fig. 3.
(Kim) Two months postoperatively, the well-defined implant bed revealed numerous punctate stromal opacities.
Histologically, at one week postsurgery, the thickness of the epithelium and stroma varied, and stromal invasion by infiltrating inflammatory cells, new vessels, and epithelial cells (epithelial ingrowth) was observed along the dissection plane (Figure 4). Minimal collagen disarray was also evident in the dissection bed (Figure 5). Scanning electron microscopy of epithelium and endothelium failed to demonstrate significant differences between pluronic and sham-operated eyes. There was, however, a suggestion of decreased numbers of dark young epithelial cells in the pluronic eyes
Fig. 5.
(Kim) Three months postoperatively, the pluronic eye showed minimal collagen disarray at the dissection bed (toluidine blue; original magnification X 31).
(Figure 6). The only significant alteration noted by transmission electron microscopy was the presence of membrane-bound cytoplasmic vacuoles, with a contained granular material, within the keratocyte cytoplasm (Figure 7). These electron microscopic changes were observed in specimens obtained at each study interval. In Table 1, one can see that the initial increase in corneal thickness peaked at one week postoperatively and returned to near normal levels by the end of the third week. Approximately three diopters of refractive flattening was noted in the experimental group, while no change was seen in the control group.
Fig. 4.
314
(Kim) The pluronic eye one week postoperatively. Variation in the thickness of both the epithelium and stroma was noted. The stroma was characterized by infiltrating inflammatory cells, vascularization, and epithelial ingrowth at the dissection plane (hematoxylin and eosin; original magnification X 16).
DISCUSSION Although the immediate postoperative condition of the eyes revealed hyperemia, vascularization, epithelial defects, and scarring, the corneas appeared to tolerate the pluronic polyol well by the end of three months. Light microscopy demonstrated irregular thickness of the epithelium, vascularization of the stroma, minimal scarring at the level of the stromal
J CATARACT REFRACT SURG-VOL
14, MAY 1988
Fig.. 7.
Fig. 6.
(Kim) Ther'e was a decreas€ in dark young epithelial cells in the plurG.nic eyes, indicating ~hat there may have been decreased ejpithelial cell humover (original magnification X 100).
bed, variable pre~,ence of inflLlllllllJIlHitory cells, and occasional epithelinl ingrowth_ 'llhese .observations were made in both sham-operated te;yes and plurooic corneas without significant differelilQe . Scallning eloctron microscopy reve,aled the presence ofr.embranebound vacuoles withim the keratocyt:et; of the pluronic corneas at all periods studied. The pluronie .appeared to be rapidly phagocyh:zed by the stromal ~lls. We
(Kim) Transmission electron microscopy showed membrane-bound cytoplasmic vacuoles containing granular material within the keratocyte.
failed to find a well-defined intrastromal disc of material upon gross or microscopic examination. Given the gelation characteristics of the material, it is unlikely that it leaked out of the implant bed. However, according to the manufacturer, at least a 30 wt % aqueous solution of pluronic F108 would theoretically be required to create an optimal gel at temperatures between lOoe and 50oe . It is possible that our trials did not achieve adequate gelation of the material. It should also be noted that the constituents of F108 react discretely and are not chemically cross-linked like conventional hydrogels. As a consequence, it might be
Table 1. Changes in the rabbit eyes. Both pluronic and control animals showed an initial increase in corneal thickness, peaking one week postoperatively, and a return to near-normal levels by the end of the third week. Refractive flattening of approximately three diopters was noted in bhe pluronic eyes, with no change seen in the sham-operated eyes.
E yes
1
Preoperative
Control X Thickness (mm)
2
3
4
5
Weeks Postope rative 6 7 8
9
10
11
12
0.440
0.60214 0.505 14 0.464 13 0.455 14 0.44310 0.439 10 0.4605 0.456 5 0.456 5 0.458 5 0.458 5 0.456 5
Vertical:
46.58
Horizontal:
46 .37
46.823 46.04 4 46.855 46.26' 46.635 46.506 46.743 46.124 45.52 6 45.67 7 46.04 5 45.426
0.448
0.603 15 0.509 15 0.475 12 0.472 13 0.4479 0.443 10 0.4525 0.4525 0.4525 0.4525 0.4515 0.4525
Vertical:
46.72
45.475 45.41' 45.476
Horizontal:
46 .29
45.905 44.817 45.63 6
X Keratometry (D)
46.863 46.74 3 46.78 3 46.704 46.78 4 46.72 4 46.193 45.303 45 .803 46.04 4 45.424 45.804
Pluronic
X Thickness (mm) X Keratometry ( D)
41.40 11 44.257 44 .23' 4l.2411 44 .277 44 .63 7
43.604 43.494 43 .624 43.604 43.495 43.405 43.74 4 43 .55 4 43.63 4 43 .65 4 43.605 43 .525
*Superscript indicates number of animals
J CATARACT REFRACT SURG-VOL
14, MAY 1988
315
expected that even with optimal gelation some pluronic would slowly diffuse away from the injection site with tissue fluid dilution and with some tissue/cellular uptake. Thus, the material might serve as a transient agent to alter corneal shape. In spite of possible phagocytosis by keratocytes or resorption throughout the stroma, Table 1 shows a consistent refractive change. In the three rabbits with minimal refractive change, significant complications such as abscess formation , granulation, infection , moderate-to-severe vascularization, and extensive scarring were encountered. These findings were in large part due to surgical complications in which the superficial anterior cornea was torn during dissection . The res ultant procedure was prolonged, and the animal experienced a greater degree of postoperative trauma. It must be emphasized that this animal model differs significantly from the primate eye since there is no Bowman's layer in the rabbit cornea. Although the results show refractive change and adequate tolerance to the material, the mechanism for this effect is not understood. Perhaps th e use of a higher weight percentage of aqueous solution or the use of another type of pluronic, with greater rigidity and resistance to phagocytosis, could clarify this question. If the gel
316
J CATARACT
cannot be maintained within the implant bed for extended periods, it would be interesting to note if this transient mode of corneal deformation could have a long-term effect on refraction. Nevertheless, the results do suggest a potential for this type of material in keratorefractive surgery. REFERENCES 1. Fasanella RM : Refractive surgery. TrailS Ophthalmol Soc UK
102:282-290, 1982 2. Taylor DM, Stern AL, Romanchuk KG: Keratophakia: Clinical evaluation. Trans Am Ophthalmol Soc 79:47-63 , 1981 3. Jensen AD, Maumenee AE: Refractive errors following keratoplasty. Trans Am Ophthalmol Soc 72:123-131, 1974 4. Binde r PS: Hydrogel implants for the correction of myopia . Curr Eye Res 2:435-441, 1983 5. Werblin TP, Blaydes JE, Fryczkowski A, Peiffer RL: Alloplastic implants in non-human primates: I. Surgical technique. Cornea 1:331-336, 1982 6. Ohrloff C, Duffin RM, Apple DJ, Olson RJ : Opacification, vascularization , and chronic inflammation produced by hydrogel corneal lame llar implants. Am ] Ophtha/mol 98:422-425, 1984 7. McCarey BE, Andrews DM, Hatchell DL, Pederson H: Hydrogel implants for refractive keratoplasty: Corneal morphology. Curr Eye Res 2:29-38, 1982 8. Samples JR , Binder PS, Zavala EY, Baumgartner SD, et al: Morphology of hydrogel implants used for refractive keratoplasty. Invest Ophthalmol Vis Sci 25:843-850 , 1984
REFRACT SURG- VOL 14, MAY 1988
P. Kim, B.S., R. L. Peiffer, D.V.M., Ph.D., R. E. Holman, M.D .
. B TR. Pluronic polyol p a neg the t mp ratu III i nl of 'Iation; it h H
.. I\opl., ti<: mat ·rial. k·.-atm ·Iin 'li, '
\11"
·ry. pluroni<:
p() l~ol
Current research has focused on keratorefractive procedures-surgical alteration of the cornea to change refractive power and thus improve visual acuity. These techniques work by altering either the curvature of the anterior corneal surface or the corneal refractive index. Such techniques as epikeratophakia, keratomileusis, implantation of hydrogel or hard plastic lenses within the corneal stroma, and radial keratotomy offer promise but have the limitations of technical difficulty and/or limited or unpredictable correction. 1-8 The objective of this study was to evaluate pluronic polyol (polyoxypropylene-polyoxyethylene condensate) as a potential material for keratorefractive surgery. Pluronic polyol, a synthetic gel currently being tested as an artificial skin in the treatment of thermal burns, possesses a negative temperature coefficient of
gelation - it is liquid at low temperatures and gelatinous at high temperatures. Using a rabbit model, we injected pluronic polyol intrastromally to determine the tolerability of the cornea to the gel and the extent and reproducibility of refractive change. We hypothesized that if we injected the material as a liquid at cold temperature into a defined tissue space and allowed it to solidify, as pluronic will at body temperature, it should result in an alteration of the anterior surface curvature and the refractive error. MATERIALS AND METHODS Pluronic F10B (BASF Wyandotte Corporation, Performance Chemical, Parsippany, NJ) has a molecular weight of 14,600 and is a difunctional glycol base arranged in a "triblock" linear configuration. It is
From the Departments of Ophthalmology (Mr. Kim, Drs. Peiffer and Holman) and Pathology (Dr. Peiffer), School of Medicine, University of North Carolina, Chapel Hill, North Carolina. Sponsored in part by a grant from Research to Prevent Blindness, Inc., New York, New York. Originally presented as a poster exhibit at the 1986 ARVO meeting, Sarasota, Florida, April 1986. Reprint requests to R.L. Peiffer, Department of Ophthalmology, 617 Clinical Sciences Building (229H), University of North Carolina, Chapel Hill, North Carolina 27514. 312
J CATARACT REFRACT SURG-VOL
14, MAY 1988
formed by the condensation of propylene oxide onto a propylene glycol nucleus followed by the condensation of ethylene oxide onto both ends at the poly (oxypropylene) base. Osmolarity and refractive index have not been determined by the manufacturer. This study employed a 25 wt % aqueous solution of approximately 100% purity, which was prepared in a cold room (4°C) using 25 g of FI08 prill mixed into 75 g of water. Adequate agitation of the solution was obtained by a mixing bar and magnetic stirrer operating overnight. The resultant foamy mixture was then placed undisturbed in a refrigerator for one day. Sterilization was accomplished with an autoclave. Initial keratometry and pachymetry measurements were taken on 17 adult New Zealand albino rabbits to determine corneal curvature and thickness. Surgery was performed using intramuscular ketamine hydrochloride (35 mglkg) xylazine hydrochloride (5 mglkg) anesthesia and involved the dissection of a 7 mm diameter circular pocket within the axial corneal stroma of both eyes of the rabbits. An axial circular area was demarcated using a 7 mm trephine; a 5 mm wide incision was made in the nasal or temporal quadrant to a depth of 0.2 mm with a razor blade knife. The dissection of the stromal bed was carried out using a #66 Beaver blade. Autoclaved sterilized pluronic F108 in a liquid state, 0.03 ml, was injected into the prepared bed of one cornea; the fellow sham-operated eye was not injected and served as a control. The wound was closed with two simple interrupted deep stromal 9-0 nylon sutures that were removed after three to four weeks. Immediately after surgery, each animal was given a subconjunctival injection of tobramycin and an intramuscular injection of penicillin. Chloramphenicol ointment was applied to both eyes daily for the following month; in cases with significant corneal inflammation, rabbits were treated with topical 1.0% atropine sulfate ointment and antibiotics supplemented with corticosteroids (Maxitrol®). Postoperatively, rabbits were clinically evaluated by biomicroscopy, keratometry, and optical pachymetry. There were sacrifices at one week, one month, two months, and three months postoperatively to study the cornea by light and electron microscopy. Following euthanasia, the corneas to be studied by light microscopy were immediately fixed in 4.0% paraformaldehyde and processed routinely. Selected corneas were fixed in a 2.0% paraformaldehyde and 4.0% glutaraldehyde solution and were bisected and processed for transmission and scanning electron microscopy. Scanning electron microscopy corneal halves were mounted for study of both endothelial and epithelial surfaces . RESULTS The typical postoperative course of most animals included conjunctival hyperemia, extensive corneal
Fig. l.
(Kim) Rabbit pluronic eye one week postoperatively. Conjunctival hyperemia and extensive corneal vascularization were noted , in addition to small epithelial defects around the sutures.
vascularization, and small epithelial defects at the onset (Figure 1). The vascularization tended to extend from the limbus toward the surgical incision within the anterior corneal stroma. Subsequent corneal scarring was evident at the incision site to a variable degree . By the end of three months postoperatively, inflammation had resolved leaving minimal scarring (Figure 2). Slitlamp examination also revealed this scarring and neovascularization, in addition to the presence of numerous punctate stromal opacities within the implant bed (Figure 3).
Fig. 2.
J CATARACT REFRACT SURG-VOL
(Kim) Pluronic eye three months postoperatively. Mild scarring was evident. 14, MAY 1988
313
Fig. 3.
(Kim) Two months postoperatively, the well-defined implant bed revealed numerous punctate stromal opacities.
Histologically, at one week postsurgery, the thickness of the epithelium and stroma varied, and stromal invasion by infiltrating inflammatory cells, new vessels, and epithelial cells (epithelial ingrowth) was observed along the dissection plane (Figure 4). Minimal collagen disarray was also evident in the dissection bed (Figure 5). Scanning electron microscopy of epithelium and endothelium failed to demonstrate significant differences between pluronic and sham-operated eyes. There was, however, a suggestion of decreased numbers of dark young epithelial cells in the pluronic eyes
Fig. 5.
(Kim) Three months postoperatively, the pluronic eye showed minimal collagen disarray at the dissection bed (toluidine blue; original magnification X 31).
(Figure 6). The only significant alteration noted by transmission electron microscopy was the presence of membrane-bound cytoplasmic vacuoles, with a contained granular material, within the keratocyte cytoplasm (Figure 7). These electron microscopic changes were observed in specimens obtained at each study interval. In Table 1, one can see that the initial increase in corneal thickness peaked at one week postoperatively and returned to near normal levels by the end of the third week. Approximately three diopters of refractive flattening was noted in the experimental group, while no change was seen in the control group.
Fig. 4.
314
(Kim) The pluronic eye one week postoperatively. Variation in the thickness of both the epithelium and stroma was noted. The stroma was characterized by infiltrating inflammatory cells, vascularization, and epithelial ingrowth at the dissection plane (hematoxylin and eosin; original magnification X 16).
DISCUSSION Although the immediate postoperative condition of the eyes revealed hyperemia, vascularization, epithelial defects, and scarring, the corneas appeared to tolerate the pluronic polyol well by the end of three months. Light microscopy demonstrated irregular thickness of the epithelium, vascularization of the stroma, minimal scarring at the level of the stromal
J CATARACT REFRACT SURG-VOL
14, MAY 1988
Fig.. 7.
Fig. 6.
(Kim) Ther'e was a decreas€ in dark young epithelial cells in the plurG.nic eyes, indicating ~hat there may have been decreased ejpithelial cell humover (original magnification X 100).
bed, variable pre~,ence of inflLlllllllJIlHitory cells, and occasional epithelinl ingrowth_ 'llhese .observations were made in both sham-operated te;yes and plurooic corneas without significant differelilQe . Scallning eloctron microscopy reve,aled the presence ofr.embranebound vacuoles withim the keratocyt:et; of the pluronic corneas at all periods studied. The pluronie .appeared to be rapidly phagocyh:zed by the stromal ~lls. We
(Kim) Transmission electron microscopy showed membrane-bound cytoplasmic vacuoles containing granular material within the keratocyte.
failed to find a well-defined intrastromal disc of material upon gross or microscopic examination. Given the gelation characteristics of the material, it is unlikely that it leaked out of the implant bed. However, according to the manufacturer, at least a 30 wt % aqueous solution of pluronic F108 would theoretically be required to create an optimal gel at temperatures between lOoe and 50oe . It is possible that our trials did not achieve adequate gelation of the material. It should also be noted that the constituents of F108 react discretely and are not chemically cross-linked like conventional hydrogels. As a consequence, it might be
Table 1. Changes in the rabbit eyes. Both pluronic and control animals showed an initial increase in corneal thickness, peaking one week postoperatively, and a return to near-normal levels by the end of the third week. Refractive flattening of approximately three diopters was noted in bhe pluronic eyes, with no change seen in the sham-operated eyes.
E yes
1
Preoperative
Control X Thickness (mm)
2
3
4
5
Weeks Postope rative 6 7 8
9
10
11
12
0.440
0.60214 0.505 14 0.464 13 0.455 14 0.44310 0.439 10 0.4605 0.456 5 0.456 5 0.458 5 0.458 5 0.456 5
Vertical:
46.58
Horizontal:
46 .37
46.823 46.04 4 46.855 46.26' 46.635 46.506 46.743 46.124 45.52 6 45.67 7 46.04 5 45.426
0.448
0.603 15 0.509 15 0.475 12 0.472 13 0.4479 0.443 10 0.4525 0.4525 0.4525 0.4525 0.4515 0.4525
Vertical:
46.72
45.475 45.41' 45.476
Horizontal:
46 .29
45.905 44.817 45.63 6
X Keratometry (D)
46.863 46.74 3 46.78 3 46.704 46.78 4 46.72 4 46.193 45.303 45 .803 46.04 4 45.424 45.804
Pluronic
X Thickness (mm) X Keratometry ( D)
41.40 11 44.257 44 .23' 4l.2411 44 .277 44 .63 7
43.604 43.494 43 .624 43.604 43.495 43.405 43.74 4 43 .55 4 43.63 4 43 .65 4 43.605 43 .525
*Superscript indicates number of animals
J CATARACT REFRACT SURG-VOL
14, MAY 1988
315
expected that even with optimal gelation some pluronic would slowly diffuse away from the injection site with tissue fluid dilution and with some tissue/cellular uptake. Thus, the material might serve as a transient agent to alter corneal shape. In spite of possible phagocytosis by keratocytes or resorption throughout the stroma, Table 1 shows a consistent refractive change. In the three rabbits with minimal refractive change, significant complications such as abscess formation , granulation, infection , moderate-to-severe vascularization, and extensive scarring were encountered. These findings were in large part due to surgical complications in which the superficial anterior cornea was torn during dissection . The res ultant procedure was prolonged, and the animal experienced a greater degree of postoperative trauma. It must be emphasized that this animal model differs significantly from the primate eye since there is no Bowman's layer in the rabbit cornea. Although the results show refractive change and adequate tolerance to the material, the mechanism for this effect is not understood. Perhaps th e use of a higher weight percentage of aqueous solution or the use of another type of pluronic, with greater rigidity and resistance to phagocytosis, could clarify this question. If the gel
316
J CATARACT
cannot be maintained within the implant bed for extended periods, it would be interesting to note if this transient mode of corneal deformation could have a long-term effect on refraction. Nevertheless, the results do suggest a potential for this type of material in keratorefractive surgery. REFERENCES 1. Fasanella RM : Refractive surgery. TrailS Ophthalmol Soc UK
102:282-290, 1982 2. Taylor DM, Stern AL, Romanchuk KG: Keratophakia: Clinical evaluation. Trans Am Ophthalmol Soc 79:47-63 , 1981 3. Jensen AD, Maumenee AE: Refractive errors following keratoplasty. Trans Am Ophthalmol Soc 72:123-131, 1974 4. Binde r PS: Hydrogel implants for the correction of myopia . Curr Eye Res 2:435-441, 1983 5. Werblin TP, Blaydes JE, Fryczkowski A, Peiffer RL: Alloplastic implants in non-human primates: I. Surgical technique. Cornea 1:331-336, 1982 6. Ohrloff C, Duffin RM, Apple DJ, Olson RJ : Opacification, vascularization , and chronic inflammation produced by hydrogel corneal lame llar implants. Am ] Ophtha/mol 98:422-425, 1984 7. McCarey BE, Andrews DM, Hatchell DL, Pederson H: Hydrogel implants for refractive keratoplasty: Corneal morphology. Curr Eye Res 2:29-38, 1982 8. Samples JR , Binder PS, Zavala EY, Baumgartner SD, et al: Morphology of hydrogel implants used for refractive keratoplasty. Invest Ophthalmol Vis Sci 25:843-850 , 1984
REFRACT SURG- VOL 14, MAY 1988