refractive keratoplasty with intrastromal hydrogel lenticular implants

9
Refractive keratoplasty with intrastromal hydrogel lenticular implants Bernard E. McCarey and David M. Andrews The feasibility of using hydrogel lenticular implants of high water content to alter the anterior corneal curvature for purposes of refractive keratoplasty has been investigated in rabbits. Lenticules (6 mm in diameter) ofPermalens (Perfilcon-A) were trephined from contact lens and implanted ivithin an intralamellar pocket in the cornea. The in vitro glucose flux across the hydrogel (0.23 mm thick) was measured at 131 ± 7 ixglcm 2 lhr. For clinical comparison, non-water-permeable disks of Teflon were also implanted. The Teflon implant caused an aseptic ulcer to develop anterior and central to the implant by 9 ± 4 days. The hydrogel lenticular implant did not cause central ulceration during the 7 month postoperative follow-up. There was a thinning and eventual erosion of the stroma anterior to the edge of the hydrogel implant, 16 ± 7 weeks. The glycogen contents of the epithelium anterior to (1) the sham operation, i.e., lamellar pocket dissection, (2) the implanted hydrogel lenticule with or without the presence of an erosion, and (3) the control corneas were statistically from the same population. Yet there was a slight dehydration of the stroma anterior to the hydrogel implant when compared to control tissue. A thin-edged implant lenticule design should overcome the stromal thinning caused by the thick-edged implants. During the short-term follow-up, the hydrogel lenticular implant proved to be successful as a refractive keratoplasty implant material. Key words: refractive keratoplasty, hydrogel implant, rabbits, epithelium, glycogen, hydration, refraction TH« ie cornea is the most powerful refracting surface of the eye because of the large differ- ence in the index of refraction between air and cornea. Very small alterations in its cur- vature will create large changes in the eye's refraction. The field of refractive keratoplasty has been nurtured and refined by Barraquer 1 since 1949, yet only recently has it gained the full attention of the ophthalmic community. This might be linked to the layman's ac; ceptance of the idea of performing a surgical From the Department of Ophthalmology, Emory Uni- versity, Atlanta, Ga. Supported by grants from Georgia Lions Lighthouse, Georgia Lions Eye Bank, and Emory University McCandless Fund. Reprint requests: Dr. B. E. McCarey, P.O. Box 22274, Emory University, Atlanta, Ga. 30322. procedure such as intraocular lens implanta- tion, to correct major ocular refractive errors. Refractive keratoplasty procedures can be categorized into three groups: (1) purely surgical, such as wedge resection or radial keratotomy with induced scarring; (2) stromal lenticular additions, such as keratophakia, keratomileusis, and epikeratophakia; and (3) hydrogel lenticular implants (HLIs), which is the procedure investigated in this study. Intrastromal implants of plastic material have been used by researchers to investigate the mechanisms of corneal hydration control and nutrition and by the clinician as a therapy for endothelial dystrophies. Knowles 2 found that the cornea overlying a water-imperme- able membrane thinned and in many cases ulcerated. One of the causative factors was 0146-0404/81/070107+09$00.90/0 © 1981 Assoc. for Res. in Vis. and Ophthal., Inc. 107 Downloaded From: http://iovs.arvojournals.org/pdfaccess.ashx?url=/data/journals/iovs/933329/ on 04/10/2018

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Page 1: Refractive keratoplasty with intrastromal hydrogel lenticular implants

Refractive keratoplasty with intrastromalhydrogel lenticular implants

Bernard E. McCarey and David M. Andrews

The feasibility of using hydrogel lenticular implants of high water content to alter the anteriorcorneal curvature for purposes of refractive keratoplasty has been investigated in rabbits.Lenticules (6 mm in diameter) ofPermalens (Perfilcon-A) were trephined from contact lens andimplanted ivithin an intralamellar pocket in the cornea. The in vitro glucose flux across thehydrogel (0.23 mm thick) was measured at 131 ± 7 ixglcm2lhr. For clinical comparison,non-water-permeable disks of Teflon were also implanted. The Teflon implant caused anaseptic ulcer to develop anterior and central to the implant by 9 ± 4 days. The hydrogellenticular implant did not cause central ulceration during the 7 month postoperative follow-up.There was a thinning and eventual erosion of the stroma anterior to the edge of the hydrogelimplant, 16 ± 7 weeks. The glycogen contents of the epithelium anterior to (1) the shamoperation, i.e., lamellar pocket dissection, (2) the implanted hydrogel lenticule with or withoutthe presence of an erosion, and (3) the control corneas were statistically from the samepopulation. Yet there was a slight dehydration of the stroma anterior to the hydrogel implantwhen compared to control tissue. A thin-edged implant lenticule design should overcome thestromal thinning caused by the thick-edged implants. During the short-term follow-up, thehydrogel lenticular implant proved to be successful as a refractive keratoplasty implantmaterial.

Key words: refractive keratoplasty, hydrogel implant, rabbits, epithelium,glycogen, hydration, refraction

TH«ie cornea is the most powerful refractingsurface of the eye because of the large differ-ence in the index of refraction between airand cornea. Very small alterations in its cur-vature will create large changes in the eye'srefraction. The field of refractive keratoplastyhas been nurtured and refined by Barraquer1

since 1949, yet only recently has it gained thefull attention of the ophthalmic community.This might be linked to the layman's ac;ceptance of the idea of performing a surgical

From the Department of Ophthalmology, Emory Uni-versity, Atlanta, Ga.

Supported by grants from Georgia Lions Lighthouse,Georgia Lions Eye Bank, and Emory UniversityMcCandless Fund.

Reprint requests: Dr. B. E. McCarey, P.O. Box 22274,Emory University, Atlanta, Ga. 30322.

procedure such as intraocular lens implanta-tion, to correct major ocular refractive errors.

Refractive keratoplasty procedures can becategorized into three groups: (1) purelysurgical, such as wedge resection or radialkeratotomy with induced scarring; (2) stromallenticular additions, such as keratophakia,keratomileusis, and epikeratophakia; and (3)hydrogel lenticular implants (HLIs), which isthe procedure investigated in this study.

Intrastromal implants of plastic materialhave been used by researchers to investigatethe mechanisms of corneal hydration controland nutrition and by the clinician as a therapyfor endothelial dystrophies. Knowles2 foundthat the cornea overlying a water-imperme-able membrane thinned and in many casesulcerated. One of the causative factors was

0146-0404/81/070107+09$00.90/0 © 1981 Assoc. for Res. in Vis. and Ophthal., Inc. 107

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Page 2: Refractive keratoplasty with intrastromal hydrogel lenticular implants

108 McCarey and AndrewsInvest. Ophthalmol. Vis. Sci.

July 1981

investigated by Brown and Mishima3 who ob-served within the cornea an aqueous-to-tearmovement of water that was created by anincrease in the tear tonicity from evaporationduring the interval between blinks. A water-impermeable intrastromal implant will pre-vent the aqueous-to-stroma movement ofwater and will result in excessive concentra-tion of the tear film, stromal thinning anteriorto the implant, and eventually epithelial andstromal breakdown. The stromal resistance towater movement is so great that the watercannot flow around the implanted barrierrapidly enough to prevent this stroma dehy-dration. Truss et al.4 found that tissue nutri-ents such as glucose also had an aqueous-to-anterior cornea movement. Because ofthe thin shape of the cornea, minimal epithe-lial permeability, low tear concentrations ofglucose, and facilitated transfer of glucoseacross the endothelium, all of the cornealglucose (except for the peripheral 1 or 2 mm)is supplied by the aqueous.5 Thus, it is veryimportant that the intrastromal implant besufficiently permeable to water molecules,glucose, lactate ions, etc., to permit themaintenance of the normal corneal physiology.

A hydrogel is water permeable and thus isa more appropriate plastic material for in-trastromal implantation. Dohlman et al.6 im-planted discs of glyceryl methacrylate (GMA)hydrogel (88% water) within the stroma ofrabbit and cat corneas to investigate the tol-erance of the tissue to the GMA. They foundlittle or no inflammatory reaction in rabbitcorneas, but the membranes slowly extrudedwithin 3 months. The authors felt this wasrelated to the water permeability of the GMAand not to toxicity. In the cat cornea theGMA implant was well tolerated for the du-ration of the follow-up (11 months). Mesteret al.7 investigated intrastromal implantsmade of hydroxyethylmethacrylate (HEMA),which is 38% water. There were no extru-sions in rabbit corneas during the 18 monthfollow-up. The success of the HEMA im-plants as compared to the GMA implantsis difficult to explain. The GMA implantsranged in thickness from 0.19 to 0.57 mm,whereas the HEMA was 0.2 mm thick.

Dohlman et al. did not correlate the GMAthickness to the postoperative time of extru-sion. The water permeability, as determinedby Refojo,8 showed the 88% GMA to be 8.7times more permeable than the 38% HEMA.Since the thickness of the hydrogel has aninverse effect on the water permeability, theimplant thickness is very important; an ex-cessively thick implant could have resultedin the implant extrusions encountered byDohlman et al. Also, the GMA implants wereflat disks whereas the HEMA implants had abase curve matching the animal cornea whichwould indicate less stress and distortion tothe lamellar bundles with the HE MA implant.

In this investigation, one of the new gen-eration of hydrogels of high water contentwas used as an intracorneal lenticular implantfor the purpose of altering the corneal curva-ture, i.e., refractive keratoplasty. The Per-malens (Perfilcon-A) is an ideal HLI material.It is 71% water when equilibrated with anisotonic solution and thus compares well tothe 78% water content of the corneal stroma.The pore diameter of the Permalens hydrogelis 30 A,9 which is many times larger than aglucose molecule at 8.6 A. Thus, a bulk flowof glucose could exist across the Permalens inorder to maintain normal epithelial metabo-lism. The purpose of this investigation was toestablish the feasibility of using HLI for re-fractive keratoplasty.

Material and methodsImplant material. A clear Teflon membrane of

0.025 mm thickness was used as the intrastromalimplant material that would be impermeable towater, glucose, and small ions but permeable tooxygen. The membrane was stretched across a9/16 inch stainless steel ball, sterilized by heat,and cut with a trephine to a diameter of 6 mm. TheTeflon was implanted to determine the postopera-tive time delay until appearance of nutritional ne-crosis anterior to the implant.

The HLIs were made by trephining out thecentral 6 mm of a Permalens contact lens (CooperLaboratories, Inc.), which consists of 26% ter-polymer of 2-HEMA vinyl pyrrolidone and othermethacrylates. It has 71% water when equili-brated with isotonic saline. The optical zone of thelens is 6 mm. The HLIs had powers of 0.00,+ 11.00, and +14.00 with central thicknesses of

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Volume 21Number 1, Part 1 Refractive keratoplasty with hydrogel implants 109

0.2, 0.3, and 0.4 respectively, when equilibratedwith 308 mOsm NaCl-phosphate solution. TheHLI thickness was measured in air with a Haag-Streit Pachometer.

Glucose flux across hydrogel. Permalens con-tact lenses with a base curve of 6.8 mm, 0.00power, 0.234 mm thickness (measured submergedin isotonic saline with a specular microscope), and14.00 mm diameter were mounted between twoLucite block chambers (Fig. 1). An air-lift systemwas used to keep the solution in each half chamberwell stirred. The lenses were bathed at 24° C witha sodium chloride-phosphate buffer at pH 7.4 and308 mOsm on one side and the same buffer plus 5mM glucose on the other side. The chamber withthe glucose was maintained at pressure less than 1mm Hg greater than that in the contralateralchamber. The rate of appearance of the glucose onthe initially glucose-free side was used to calculatethe glucose flux. The glucose concentration wasmeasured by a hexokinase assay.

Surgical technique and folloiv-up. Thirty NewZealand albino rabbits, weighing approximately3.5 kg, were given 1% cyclopentolate hydrochlo-ride eye drops as a cycloplegic, and the preoperativemeasurements from retinoscopy and pachometrywere recorded. The animals were anesthetizedwith chlorpromazine (Thorazine), 9.0 mg/kg (in-tramuscularly), followed by pentobarbital, 30mg/kg (intravenously), and one or two drops of0.5% proparacaine hydrochloride to the cornea. Ablade breaker and razor were used to make a 4 mmincision tangential to and 3 mm from the limbusand approximating midstromal depth. A Martinezcorneal dissector with a sharp edge was used togently form a central lamellar pocket 8 mm diame-ter. An effort was made to remain in a single lamel-lar plane. The opening to the pocket was enlargedto 7 mm with corneal scissors. The HLI was slippedinto position with the aid of a spatula. The incisionwas closed with three to five sutures of 10-0 nylon.During the operation, the cornea was periodicallymoistened with 0.5% chloramphenicol. Neosporinointment was applied to the cornea once daily for 3postoperative days. On the seventh postoperativeday the sutures were removed. Periodically dur-ing the postoperative follow-up, the retinoscopyvalues and pachometry of the cornea and of the insitu HLI thickness were recorded.

Corneal epithelial glycogen content. The glyco-gen content in the corneal epithelium anterior tothe 6 mm implant or a central 6 mm zone of acornea subjected to sham operation, i.e., a lamel-lar pocket without an implant, was analyzed by the

Fig. 1. The schematic diagram illustrates the con-struction of the Lucite chamber for measuring therate of glucose flux across the hydrogel contactlens. The NaCl-PO4 buffer in the chamber ismixed by an air-lift system.

method of Thoft et al.10 After sacrificing the rabbitwith an overdose of pentobarbital, the epitheliumwas scraped off and immediately frozen with amixture of Dry Ice and acetone. The frozen epi-thelium was dried for at least 18 hr in a lyophilizerand then weighed. The epithelium was extractedin 1.0 ml of 20% sodium hydroxide for 15 min at100° C. The glycogen was precipitated twice inethanol, followed by a 30 min centrifugation at10,000 x g. The supernatant was discarded andthe precipitate hydrolyzed in 2N sulfuric acid for90 min at 100° C. After neutralization the glucosecontent was measured by the hexokinase/glu-cose-6-phosphate dehydrogenase reaction andthe glycogen level was expressed as glucose unitsper dry weight of epithelium

Stromal hydration. The corneal stroma watercontent was determined for the stroma anterior tothe HLI and anterior to the sham operated dissec-tion plane. These values were compared to normalfull-thickness cornea (control). In each case, thesample was harvested and weighed immediatelyafter scraping off the epithelium and reweighedafter 48 hr at 100° C in a vacuum oven.

ResultsTeflon membrane implant. The Teflon

implant within the corneal stroma did notstimulate vascularization or any generalizedtissue reaction during the first postoperativeweek. By 9 ± 4 days (n = 5), the epitheliumand stroma central and anterior to the im-plant became necrotic and soon afterwardsloughed off, revealing the Teflon implant(Fig. 2). During the next week or more, thenecrotic area increased in diameter while theeye remained clinically quiet, until one of the

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Page 4: Refractive keratoplasty with intrastromal hydrogel lenticular implants

110 McCarey and AndrewsInvest, Ophthalmol. Vis. Sci.

July 1981

Fig. 2. Rabbit corneas with Teflon membrane im-plants developed aseptic ulcers central and an-terior to the implant within 1 or 2 weeks postop-eratively. Typically, the eye remained quiet, i.e.,without vascular dilation or inflammation, evenwhen an ulcer 2 mm in diameter was present.

Fig. 3. The rabbit cornea tolerated the hydrogellenticular implant with little stromal edema orreaction at the stroma/implant interface.

common ocular microorganisms infected theexposed stroma.

Hydrogelmaterial. The glucose flux throughthe Permalens material (0.234 mm thick) was131 ± 7 /LAg/cm2/hr, n = 4. When comparingthe hydrogel implant thickness, as measuredby the slit-lamp Pachometer before implan-tation, to the in situ implant thickness withinthe stroma, a considerable thinning was ob-served in situ. The hydrogel thinned by28% ± 2, n = 13, in the stroma. This wouldcause a shrinking of the hydrogel pore diame-ter and an expected decrease in the in situglucose flux across the implant. Considering

Fig. 4. Thinning of corneal stroma often devel-oped anterior to the edge of the hydrogel lenticu-lar implant in the rabbit. The thinning was slow todevelop, taking on the average 4 months beforethe implant was exposed.

this factor, one might expect a 94 ^ig/cm2/hrglucose flux in situ for an implant of 0.234mm thickness.

Tissue response to hydrogel lenticular im-plant: clinical observation. After inser-tion of the HLI into the rabbit cornea, mostof the eyes were clinically quiet with little orno conjunctival vessel dilation and edema,except at the site of the incision. The eyesthat did exhibit some reaction quieted downafter suture removal (Fig. 3). The HLI didnot stimulate vessel formation or stromalscarring as determined by slit-lamp examina-tion. Even after 1XA months the stroma didnot attach to the HLI and thus the HLI couldbe removed after making an incision throughthe stroma.

Of the 30 corneas with HLIs, eight eyeshad slowly progressive thinning of the stromaanterior to the edge of the implant (Fig. 4).At a mean time of 16 ± 7 weeks a small zoneof stroma, usually about 0.5 mm by 1 or 2mm, had eroded away anterior to the HLIedge. It is impossible to know whether all theeyes with HLI implants would have devel-oped erosions, since animals were sacrificedperiodically for tissue analysis, prior to anysigns of erosion. The eyes did not have areactive response to the stromal thinning/erosion and the implants remained in place.Since the lamellar pocket was opened by the

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Page 5: Refractive keratoplasty with intrastromal hydrogel lenticular implants

Volume 21Number 1, Part 1 Refractive keratoplasty with hydrogel implants 111

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Fig. 5. The glycogen content of the cornea! epithelium was determined in control corneas, aswell as anterior to the lamellar dissection plane (i.e., sham operation) and the hydrogel lenticu-lar implant with and without stromal erosion. The mean value and standard deviation for thegiven number of experiments (indicated by the number at the base of each column) has beengraphed. The cornea with the stromal erosion had the same glycogen content as the controlcornea, thus indicating the erosion to be nonnutritional in nature.

stromal erosions, the cornea was prone to in-fection, yet for up to 9 additional weeks theeyes remained nonreactive. During this pe-riod the stroma continued to recede at a veryslow rate or remained stable with stromaledema at the margin of the opening. Thestromal thinning was unlike that with theTeflon implant since it was always restrictedto the stroma anterior to the edge of the im-plant. The HLI within the stroma was 0.15 to0,34 mm thick, whereas the contralateralcontrol cornea was 0.35 to 0.45 mm thick.Thus the stromal thinning could be caused bythe stress created from an implant that wasfrom 50% to 100% the thickness of the corneareceiving it. Also, the HLI was trephinedfrom a contact lens which resulted in an im-plant lenticule with an abrupt edge of 0.23mm thickness, the carrier lens thickness.These factors would indicate the erosion wasmechanical in nature and not a nutritionaldisturbance.

Epithelial glycogen content. The cornealepithelial glycogen content had statistically

the same (p = 0.8) mean value in the con-tralateral control eye as it had in the eyeswith HLIs in place, Fig. 5. There were foureyes with the HLI in place for 3 months andthree eyes with it in place for 5 months. Thesham-operated eyes, i.e., a lamellar pocketwithout an implant, had statistically the same(p = 0.6) epithelial glycogen content as theeye with an HLI. Significantly, the epithe-lium of the eyes with an ongoing extrusionhad the same (p = 0.8) glycogen content astheir contralateral control eyes. This is evi-dence that the stromal thinning was notcaused by lack of glucose supply to the cor-neal layers anterior to the HLI.

There is no correlation (r = 0.0001) be-tween the HLI thickness, as, measured insitu, and the glycogen content of the epithe-lium above the implant (Fig. 6). The range ofimplant thickness was 0.15 to 0.34 mm. Thiswould indicate that for this range of implantthickness, there was a bulk flow of glucosemoving across the implant.

Stromal water. The water content of the

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Page 6: Refractive keratoplasty with intrastromal hydrogel lenticular implants

112 McCarey and AndrewsInvest. Ophthalmol. Vis. Sci.

July 1981

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Fig. 6. The epithelial glycogen content of the corneas with implants in place for 3 to 5 monthsdid not correlate with the thickness of the hydrogel lenticular implant when in the range of0.15 to 0.34 mm.

stroma anterior to the HLI was slightly de-hydrated to 65% ± 3, n = 7, as compared toits contralateral control, 77% ± 2 , n = 7(Fig. 7). It was highly significant (p < 0.001)that the mean values were from differentpopulations. It appears that upon initial im-plantation of the HLI, the water evaporatingfrom the anterior surface of the cornea wasgreater than the amount flowing through theHLI. This reached an equilibrated statewhen the imbibition pressure within the an-terior stroma increased and in turn increasedthe posterior-to-anterior gradient for wateracross the HLI, which also would havecaused a decrease in the water gradient fromthe stroma to the tears. The water content ofthe anterior stroma in the sham operatedcornea (73% ± 2 , n = 6) was significantlymore hydrated than the corneas with HLIs(65% ± 3, n = 7) and less hydrated than thecontrol corneas (77% ± 2, n = 11).

Refractive alteration. Retinoscopy valuesshow a flattening of the normal rabbit corneawith increasing age. Thus it was necessary toexpress the data as a net change, i.e., refrac-tive change with the HLI minus refraction ofcontralateral control eye. The results show astabilization of the refraction by about thesixth postoperative week. The net spherical

equivalent alteration by the HLI was approx-imately equal to the power of the contact lensfrom which the HLI was trephined (Table I),in spite of the fact that the HLI has an edgethickness in excess of 0.2 mm.

Discussion

The corneal response to the water-imper-meable Teflon membrane was similar to theresponses to other water-impermeable mem-branes reported in the literature.2' 3 Knowlesused various plastics, such as polyethylene,polyvinylidine, and polypropylene, which re-sulted in the aseptic ulceration of the centralcornea anterior to the implant within 9 to 34days. He also noted the absence of inflam-mation and the sharp localization of the de-fect anterior to the implant without alterationto the posterior tissue. Because of the pro-longed and variable delay in the appearanceof the degenerative process, Knowles believedthat something more than simple interfer-ence with nutrition was at work. He felt theprocess might be the result of one or more ofthe following: (1) lack of vital nutrients fromthe aqueous, (2) accumulation of a toxic sub-stance, and (3) selective drying of the corneaanterior to the implant.

A permeable implant material that is non-

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Page 7: Refractive keratoplasty with intrastromal hydrogel lenticular implants

Volume 21Number 1, Part 1

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Refractive keratoplasty with hydrogel implants 113

CONTROLS LAMELLAR PAIREO LAMELLAR PAIRED LAfcCLLAR

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Fig. 7. The percentage of water in the stroma (grams of water per gram of dry stroma) anteriorto the lamellarly directed plane or implant was determined. The presence of the hydrogelimplant resulted in stromal dehydration relative to the contralateral control eye.

Table I. Refractive change with

Base curve (mm)

6.86.88.0

Power (diopters)

0.0010.56 ± 0.27

14.00

hydrogel lenticular implants

Thickness (mm)

0.20.30.4

Net spherical equivalent change minus paired control

-1.5 ±0.9* (4)+6.9 ± 2.8 (6)

+ 16.6 ± 1.2 (2)

*Mean ± S.D.; numbers of samples in parentheses.

toxic to the corneal tissue should overcomethe difficulty which the Teflon membranefailed to overcome. Refojo8 stated that in hy-drogel material of high water content (94% to74%), the net water flux can be considered tofollow primarily viscous flow mechanisms;that is, the molecules move in groups orbulk. In the hydrogel of lower water content(39% to 63%) the molecules are restricted todiffusion coefficient calculations. Since it isdesirable to have the least water resistance^the Permalens hydrogel material with 71%water was selected as a hydrogel lenticularimplant for refractive keratoplasty. The datashowing no correlation between the HLIthickness and epithelial glycogen content{Fig. 6) can be explained either by a bulk flowof glucose across it, as suggested by Refojo'sstatement,8 or by the flux of glucose being

greater than the anterior stromal and epithe-lial utilization of glucose. Rabbit corneal glu-cose utilization has been reported to rangefrom 104 (Riley11) to 39 /ug/cm2/hr (Thoft andFriend12). The epithelial glucose consump-tion was estimated at less than 20 /Ag/cm2/hrunder normal conditions.12 From these data,a conservative approximation of 50 /xg/cm2/hr for the anterior corneal layers might beexpected. The data in this investigation indi-cated a glucose flux of 94 /ig/cm2/hr for Per-malens material, taking into account the insitu dehydration of the hydrogel. Also, therewas no correlation between epithelial glyco-gen content and HLI thicknesses between0.15 and 0.34 mm (Fig. 6). Thus, it can beassumed that for this range of HLI thickness,the rate of glucose movement across theHLI exceeded the glucose consumption of

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Page 8: Refractive keratoplasty with intrastromal hydrogel lenticular implants

114 McCarey and Andrews

the corneal tissue anterior to the implant.The stroma anterior to the HLI was

slightly dehydrated in comparison to controlcorneal tissue (Fig. 7), presumably because ofinsufficient hydrogel water permeability rel-ative to the rate of evaporation. This wasconsistent with slit-lamp observation of thestroma, i.e., grayish light scatter posterior toHLI and golden light anterior to HLI. Ac-cording to the findings of Hedbys and Mi-shima13 the normally hydrated stroma (77%to 79% H2O) has a water flow conductivityvalue of 150 X 10~14 cm4/sec/dyne. ThePermalens has a flow conductivity of 21 X10~14 cm4/sec/dyne at a hydration of 71%. Aswas pointed out, there is a 28% thinning ofthe hydrogel within the stroma; thus the wa-ter flow conductivity of the hydrogel wouldreduce to 15 X 10~14 cm4/sec/dyne. Presum-ably this in situ thinning of the HLI would betrue of any hydrogel. Thus, the Permalens istenfold and the HEMA is 250-fold less per-meable to water than the corneal stroma. Thestromal water flow conductivity values mea-sured by Hedbys and Mishima represent themaximum attainable values. They do not re-flect the amount of water that is osmoticallymoved across the cornea (posterior to an-terior surface) because of the increased osmo-larity of the tear film between blinks. Thisvalue is difficult to measure because thewater that evaporates from the anterior cor-neal surface is supplied from both the stromaand the tear film. The disparity between thePermalens water flow conductivity and thatof the stroma could be avoided by increasingthe water content of the hydrogel to possibly80% or 90%. Refojo8 found that a GMA hy-drogel with 89% water had the same waterflow conductivity as the stroma.

A difficulty encountered with the HLI inrabbit corneas was a thinning of the stromaanterior to the edge of the implant, witheventual exposure of the implant. This thin-ning was not restricted to a particular quad-rant, regardless of the location of the lamellarpocket opening. This problem could becaused by (1) the lamellar dissection not re-maining in one plane, (2) the thick-edgedimplant creating mechanical stress within thestroma, or (3) inadequate nutritional supply.

The data rule out the possibility of the prob-lem being nutritional, and since it is an al-most universal problem (if enough postop-erative time passes) it would seem unlikely tobe a surgical problem. It is most likely re-lated to poor implant design, which could becorrected by thin-edged implant lenticules.This would result in an implant of thinnercentral thickness for a given power, lessstress or stretching of the stromal collagenfibrils, and less edge visibility within thestroma.

The preliminary finding that the HLI diop-tric power, as determined by the manufac-turer, was approximately equal to the post-operative refraction of the animal eye is en-couraging, but not surprising. Barraquer14

has developed the keratophakia and kerato-mileusis procedure on the basis that he coulddetermine the appropriate stromal lenticularpower needed for the patient's refractive cor-rection. The procedure with the hydrogelimplants differs only in the implant's refrac-tive index. Churms15 has studied the opticaltheory of the hydrogel lenticular implant. Heconcluded that the hydrogel lenticule caninduce approximately an additional 15%change in the ocular power over that of astromal lenticular implant. There are manyfactors which must be clarified before accu-rate predictability can be realized. The im-portance of the depth of the implant bed, therigidity of the hydrogel material, the altera-tion of the hydrogel hydration in situ, anddiameter of the implant are not well defined.

The findings of this investigation encour-age the idea that hydrogel lenticular implantscan have an important role in refractivekeratoplasty procedures, but the data are re-stricted to short-term follow-up. A 1 to 3 yearpostoperative follow-up, in not only rabbitsbut also cats and primates, is essential beforehuman application can be considered. Thepossibility of slow stromal alterations byeither a remolding or an encapsulation of thenonbiologic hydrogel material must be in-vestigated carefully by in vitro measurementsand histologic ultrastructure studies.

We thank Cooper Laboratories, Inc., for supplyingthe Permalens contact lenses and Sarah J. Scholl for hertechnical assistance.

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