Eye (1988) 2, 56-62

Epikeratophakia: Clinical Results and Experimental Development

CHAD K. ROSTRON Leicester

Summary The clinical course and visual, refractive, and keratometric results of a consecutive series of epikeratophakia procedures carried out by the author are presented. Indic�tions for the procedure included and adult and paediatric . Follow up time ranged from two to fourteen months. The first five patients operated on received commercially obtained cryolathed lenticules. The final three cases received lenticules which were lathed by the author at room temperature using a recently developed technique.

Epikeratophakia was devised by Werblin in sive' contammg sucrose. Maguen et al. 1979 and subsequently developed by Kauf­ published the results of a series of experi­ man and McDonald. In 1984 a multicentre mental keratophakia procedures in cats with trial was commenced using lenticules lathed good results, and suggested that the technique commercially by American Medical Optics could be applied to the production of len­ (now Allergan Medical Optics-AMO). The ticules for epikeratophakia.6 More recently procedure was initially devised for the refrac­ Rostron et al. have reported a modification of tive correction of adult and paediatric aphakia the technique of lathing at room temperature and subsequently modified to treat and used lenticules produced by this method and phakic hypermetropia. Epikeratophakia to carry out experimental epikeratophakia.7 with plano powered lenticules was developed Using this modified technique lenticules have to treat keratoconus, and such lathed tissue been produced for clinical use and this paper may also be used for lamellar keratoplasty. reports the results of human epikeratophakia Clinical experience with epikeratophakia in using tissue lathed at room temperature. the United States is now extensive and recent publications report favourable clinical Material and Methods 1.2.3.4 results. The series of patients reported represent the In 1982 Maguen et al. 5 reported a new tech­ author's first year of clinical experience with nique for lathing corneal tissue at room tem­ the procedure. The first five patients received perature. This was achieved by a preliminary lenticules obtained from AMO. These len­ lyophilisation (freeze drying) of the tissue to ticules were ordered on the basis of an aver· render it suitable for lathing. The corneal but­ aged keratometry reading and the refractive ton was held on the lathe by allowing it to error, which was corrected to the corneal become adherent to a polymethyl methacry­ plane and rounded to the nearest half dioptre. late (PMMA) base using a 'biological adhe- The lenticules were prepared by cryolathing.

Correspondence to: Mr. C. K. Rostron, FRCS, Department of Ophthaimology, Clinical Sciences Building, Leicester Royal Infirmary, PO Box 65, Leicester LE27LX. EPIKERATOPHAKIA 57

The tissue was subsequently lyophilised and were then replaced on the PMMA sent by airmail from the United States to this bas�s and desiccated for 48 hours at 4°C. country. No details are available of the lathing Under these circumstances the desiccated len­ parameters used or the technique of ticules did not become adherent to the base lyophilisation. because of the absence of biological adhesive. The final three cases received lenticules The lenticules were then placed in a vial on an prepared by the author, using a technique of Edwards' model 12K freeze dryer and lathing tissue at room temperature. Tissue for lyophilised at -50°C, 3 mbar for 24 hours. these patients was prepared in the following The vials were sealed whilst still under way: vacuum and the lenticules were maintained in Donor were enucleated and the cor­ this state at room temperature until used for neo-scleral rims preserved in McCarey-Kauf­ . man (MK) medium at 4°C. Donors were selected according to the same criteria applied Surgical Technique for penetrating keratoplasty, and all donors General anaesthesia was used in all cases. were screened for serum antibodies to HIV Topical antibiotics were used pre-operatively. Tissues were used for epikeratophakia only if At surgery, topical cocaine was applied to the it was deemed unsuitable for penetrating ker­ patient's corneal epithelium which was then atoplasty due to known or presumed poor stripped leaving a residual 1 mm rim at the endothelial cell count from prolonged death limbus. A partial thickness trephine cut was to enucleation time, or prolonged storage. made; 7 mm diameter for the aphakic patients After storage for up to four days the corneas and 9 mm for the keratoconus patients. A were removed from the MK medium. The wedge of tissue on the inner aspect of the corneal epithelium was stripped with a scalpel trephine cut was resected with Vannas' scis­ blade and the endothelium and Descemet's sors. A peripheral lamellar split was made at membrane were also removed. The corneo­ the base of the trephine cut to accommodate scleral button was then placed in cryopreser­ the lenticule wing zone. Lenticules were vative solution for thirty minutes. This solu­ rehydrated for 20 minutes in normal saline tion was prepared in our pharmacy under with gentamicin 100 microgm per ml. They sterile conditions from Dextran 70, dextrose were sutured in place with 16 to 24 interrupted and dimethyl sulphoxide (DMSO). Corneas 10/0 Dermalon sutures. Subconjunctival were frozen and preserved in this solution in methyl prednisolone acetate 20 mg and gen­ liquid nitrogen for periods ranging from one tamicin 20 mg were given and a high water t6 four months. When removed from liquid content bandage soft contact lens applied. nitrogen the corneas were allowed to thaw Post-operatively the bandage lens was worn and were cut to an appropriate diameter on a until the graft had re-epithelialised. Sutures corneal punch. The corneal button was then were removed at 1 to 2 months for the aphakic placed on a PMMA base which had a con­ patients and at 3 months for the keratoconus cavity of 8 mm radius cut into its surface. The patients. button was desiccated on the base at 4°C for twenty-four hours. This allowed sufficient Results drying of the to make it adherent to the Table I shows the background data for the underlying PMMA base and to allow it to be patients in this series. lathed at room temperature. Lathing was Figure 1 shows the unaided acuities before carried out on a cryolathe with the cryo circui­ and after surgery. Acuities are recorded for try switched off. The lathing parameters used only seven cases as in one case no measure­ were based on the theoretical model proposed ments were available due to the patient's by Werblin et al.8 Following lathing, the severe mental retardation (case 6). PMMA bases were removed from the Figure 2 shows best corrected acuity before cryolathe and the corneas soaked in Dextran and after surgery. Pre-operatively all patients 70 for five minutes to allow them to be were intolerant of the glasses or contact lenses removed atraumatically from the base. The used to measure this 'best corrected acuity', 58 CHAD K. ROSTRON

Table I

As s ociated Follow up Lenticule Cas e Indication conditions time (mths ) Age source

1 (I) Adult aphakia Uveitis optic atrophy 14 55 USA 1 (r) Adult aphakia Cataract uveitis 2 56 UK 2 Adult aphakia Previous uveitis 13 73 USA 3 Adult aphakia Penetrating injury 8 20 USA 4 Paediatric aphakia Previous uveitis 7 6 USA 5 'Unilateral' keratoconus Minimal axial scarring 5 29 USA 6 Bilateral keratoconus Down's Syndrome hydrops 2 10 UK 7 Limbal dermoid Amblyopia 2 26 UK

but this was not necessarily the case post­ the third post-operative day. This cleared with operatively. additional treatment of intensive topical steroids. Table II shows the details of pre- and post­ Following suture removal at one month post-oper­ operative visual acuities, refraction and atively an interface opacity appeared beneath the site of one of the suture tracks, apparently due to keratometry. proliferation of the corneal epithelium caught at Because of the heterogeneity of both the the graft/host interface. However, this regressed patients' conditions and the indications for spontaneously over the following 6 weeks. Best surgery further analysis will consider the corrected acuity was oilly 6/18 post-operatively due patients in sub-groups according to the indica­ to preretinal gliosis at the macula and a degree of tion for surgery. optic atrophy. This patient subsequently under­ went epikeratophakia in her second eye. As she Adult Aphakia had undergone previous refractive correction of her unilateral aphakia, refractive correction of her Patient 1 second eye was necessary when this eye sub­ This patient suffers from multiple sclerosis and sequently required cataract extraction. Because bilateral recurrent anterior uveitis. At the time of contact lens intolerance was anticipated, and intra­ initial surgery she was unilaterally aphakic and ocular lens implantation contraindicated due to could not tolerate her contact lens. She was chronic uveitis, epikeratophakia surgery was con­ unsuitable for intraocular lens implantation sidered the treatment of choice. To save her under­ becauSe of her uveitis, so epikeratophakia was going two separate operations, epikeratophakia carried out. Despite cover with pre-operative was carried out at the same time as the cataract systemic steroids, the surgery provoked a recur­ extraction. Post-operatively there was again a rence of her uveitis, with hyopopyon formation on rebound flare up of her uveitis with a small hypo-

6/6 6/6

6/9 6/9

6/12 Best 6/12 Unaided corrected 6/16 6/18 o acuity acuity 612.

6/60 6/60

CF 'D 0 0 CF o

CF 6/60 6/36 6124 6/18 6/12 6/9 6/6 CF 6/60 6/36 6/24 6/18 6/\2 6/9 6/6

Unaided acuity after surgery Best corrected acuity after surgery

I<'ig.l Fig. 2 EPIKERATOPHAKIA 59

Table II

Pre-operative Pos t-operative

Vis ion Vision Vis ion with Vis ion with Cas e unaided glas ses Refraction Keratometry unaided glas ses Refraction Keratometry

1 (I) CF 6/18 +12 Sph. 7.70@ 90° 6/24 6/24 plano 6.10 @ 90° 7.67@ 180° +2.0x 10° 6.42@ 180° 1 (r) CF CF 7.68@ 90° CF CF -6.0 5.64 @ 90° 7.70 @ 180° N12 +0.5x 90° 5.78@ 180° 2 CF 6/12 +10.5 7.39@ 55° 6/24 6/9 +4.0 6.50@ 55° + 1.5x 145° 7.35@ 145° +1.5x 45° 6.58@ 145° 3 CF 6/6 +10.5 7.86@ 90° 6/9 6/6 -1.5 6.11 @ 90° +2.0x 90° 8.55@ 180° +2.0x 70° 6.63@ 180° 4 CF 1160 +15 7.88@ 90° 2/60 2/60 6.20 approx 7.88@ 180° N48 5 CF CF 6/12 6/12 7.40 @ 90° 7.20 @ 180° 7 6/36 6/36 6/24 +1.0 +5.0x125° pyon formation on the third post-operative day. eration from the branch of a tree. The wound was This was assumed to be sterile and responded well complicated by formation of a cataract which was to topical and systemic steroids. Although this case aspirated shortly after the injury. He had attempted has only a short follow up time, the latest post­ contact lens wear over a period of several years but operative refraction shows over correction in the had been intolerant. The epikeratophakia surgery second eye, and, as in the other eye, corrected and follow up were uncomplicated and achieved a is poor due to optic atrophy and pre­ satisfactory refractive result. He now has good retinal gliosis of the macula. vision (6/9) with binocular function for near and distance, and an unaided stereo acuity of 140 secs of Patient 2 arc at 16 inches. This patient had undergone intracapsular cataract extraction with broad in an eye which Paediatric Aphakia had showed signs of previous uveitis. The patient refused to consider wearing a contact lens, but was Patient 4 unhappy with the blurred vision from her uncor­ This child presented at the age of 4 years with visual rected unilateral aphakia. Following epi­ acuity 6/9 right and 6/6 left (Sheridan Gardner) and keratophakia, her post-operative course was with acute anterior uveitis in his right eye. complicated by a persistent epitheliopathy over the Investigation had shown no abnormality apart from apex of the graft. However, the epithelium stabil­ positive titre to toxacara. He was treated with ised after three months. At six months post-oper­ topical and systemic steroids and six months later, atively the residual uncorrected in in November 1984, visual acuity in the right eye had the operated eye was +5.75 D spherical equivalent deteriorated to counting fingers and there was con­ which still left her with a total of +8.5 D of siderable vitreous haze. He continued on topical anisometropia. Thus with a spectacle correction for steroids in low dosage and by April 1986 had devel­ her residual refractive error she experienced con­ oped a mature cataract in his right eye. Right extra­ stant aniseikonic diplopia. To overcome this she capsular cataract extraction was carried out in June subsequently underwent cataract extraction with 1986 and epikeratophakia in November 1986. intra-ocular lens implantation in her second eye, Sutures were removed under general anaesthesia at with intentional undercorrection to reduce her 2 weeks post-operatively and the graft was clear anisometropia to a tolerable degree. with good epithelial cover at that time. Two weeks later there was extensive secondary epithelial break Patient 3 down over the graft, producing much pain and This patient had suffered paracentral corneal lac- photophobia. Various bandage contact lenses and 60 CHAD K. ROSTRON patching were tried unsuccessfully. Due to the per­ left eye. One of these had been removed when she sistent epithelial defect tarsorraphy was carried out was 6 months old but the other had been left, as under general anaesthesia in January 1987. When although it encroached on her cornea to a greater the tarsorraphy was opened three weeks later the extent, it was partly hidden by the upper lid. The graft epithelium had stabilised but there was visual axis of the eye was clear, but the eye was residual graft surface irregularity and subepithelial amblyopic from a high degree of oblique astigma­ scarring at the site of the previous epithelial defect. tism. The patient sought removal of the dermoid He is currently undergoing occlusion therapy, but for cosmetic reasons and lyophilised tissue which with limited compliance. Accurate post-operative had been lathed to a uniform thickness of 0.45 mm keratometry and refraction measurements have not was used as a lamellar graft to replace the corneal been possible due to the child's poor co-operation. defect following excision of the dermoid. Re-epi­ thelialisation over the inner edge of the graft was Keratoconus slow due to unevenness of the graft-host interface. However, the epithelium eventually healed at 6 Patient 5 weeks post-operatively. Removal of a loose suture This patient had a 6-year history of 'unilateral' ker­ at one week post-operatively was complicated by atoconus and at presentation was felt to have too haemorrhage into the graft/host interface, but this steep a cone to be successfully fitted with a contact cleared over the ensuing weeks. lens. Pre-operative acuity in this eye was counting fingers unaided and with glasses, but improved to Discussion 6/24 with pinhole. The post-operative course was Whilst the small size of this series precludes complicated by a transient secondary epithelial statistical analysis of the results, consideration breakdown over the centre of the graft associated of individual cases demonstrates several with suture loosening. However, this resolved by important aspects of this procedure. The large wearing a bandage contact lens. Final visual acuity was 6/12 unaided and the patient continues with series of cases reported from the multicentre spectacle correction for his other eye, which cor­ epikeratophakia trial in the United States give rects to 6/6. a good indication of the level of success that can be expected with this operation. The Patient 6 results of treatment of adult and paediatric This child with Down's Syndrome and severe men­ aphakia are certainly encouraging, U and the tal retardation also suffered from bilateral procedure can offer a realistic alternative to keratoconus and congenital cataracts. Both catar­ those for whom secondary intraocular lens acts had been needled on several occasions during implantation would be the only other option.9 infancy. She was considered unsuitable for pen­ etrating keratoplasty due to her poor co-operation Adult Aphakia Correction and tendency to rub her eyes. This appeared to be associated with progression of her keratoconus, Two of the cases in this series were corrected and unfortunately while awaiting surgery she devel­ to within 1.0 D of emmetropia, and the result oped acute corneal hydrops in the eye upon which it 3 was planned to operate. At the time of surgery the in case with restoration of bihocular function cornea was found to be considerably ectatic, is an example of epikeratophakia at its best. oedematous, and had widespread corneal However, case number 2 showed a marked opacification. To simplify post-operative manage­ degree of under correction, changing from .ment, bandage contact lens wear was not attempted + 11 D pre-operatively to +5.75 D post-oper­ but tarsorraphy was carried out at the time of sur­ atively; less than 50 per cent of the desired gery. When the tarsorraphy was opened at 3 weeks change. A degree of inaccuracy in aphakic the graft was found to have epithelialised satisfac­ correction can sometimes be tolerated, as the torily. The epitheli has um remained stable and patient may already wear spectacles, so the sutures were removed at three months. Due to the residual ametropia can be corrected with child's severe retardation, measurement of visual acuity and keratometry were not possible. glasses. However, in this case, the under cor­ rection was so marked that the;: procedure Patch Graftillg completely failed to reduce the anisometropia to a tolerable degree. Because there is no way Patient 7 of checking a lenticule's power prior to its This patient had two corneo-scleral dermoids in her application, and because the lathing para- EPIKERATOPHAKIA 61 meters used for this commercially obtained results which deviated significantly from the lenticule were unknown, it is only possible to theoretical prediction, but that by changing conjecture as to the cause of this under correc­ the surgical technique and lenticule design tion. Whilst the lenticule may have been inac­ results could be obtained that approximated curately cut in the first place, it seems more more cl()sely to the theoretical model. 10 In likely that the under correction obtained in early trials of epikeratophakia in humans no this case was due both to over tight suture attempt was made to achieve specific refrac­ technique and to the effect of leaving sutures tive corrections and lenticules were only des­ in place for too long. In this patient it was ignated as 'low plus' and 'high plus'.l1 More noted in the early post-operative phase that recent reportsl.2 have documented the clinical there was significant folding in Descemet's outcome of over 800 cases but the lathing membrane largely confined to the area parameters used were not specified. Nor has beneath the lenticule. This may have been due the relationship between the theoretically to relative corneal decompensation, but it described lathing parameters and those actu­ might alternatively indicate that the suture ally used in these studies been stated. tension was too great, which could have In this series the refractive results obtained caused flattening of the central cornea with in case 1 (I) and case 3 were quite reasonable, reduction of the refractive effect achieved by but cases 1 (r) and 2 showed quite wide devia­ the lenticule. The possibility of modifying the tion from the predicted result. It appears that result by trephining down through the wing factors such as the surgical technique used, zone of the lenticule to release the wound and in particular the suture tightness, can tension was considered. However, in this case have a profound effect on the refractive result it was felt inappropriate to subject the patient obtained. For this reason further research is to another operative procedure with an needed to findways to cut down the possibility unpredictable result. Instead it was decided of inducing such errors. Development of a that a better way to eliminate the suture less technique could both improve the anisometropia would be to proceed with cat­ accuracy and diminish the operating time for aract extraction in her other eye, which was this procedure. considered suitable for intra-ocular lens implantation since it showed no signs of pre­ vious uveitis. She now has binocularity Paediatric Aphakia Correction restored with a low hypermetropic spectacle The use of epikeratophakia in paediatric correction for both eyes. aphakia with contact lens intolerance has Conversely, in the second eye of case 1, achieved some very successful results.2 Inevit­ there was an over correction of 5.75 D. In this ably a proportion of patients fail to achieve instance there was no clinical evidence of the good acuities due to poor compliance with sutures being too tight, and the sutures were occlusion therapy, but it is not always possible removed early, so this probably represents a to predict the degree of compliance before situation where surgically induced under cor­ embarking on treatment. The child in this rection was minimised. As this case under­ series suffered from a secondary epithelial went combined cataract extraction and breakdown on the graft, and whilst this did epikeratophakia, the lenticule power was pre­ not necessitate graft removal, it left a degree dicted by ocular biometry and the use of the of scarring when it healed. It is difficult to SRK formula corrected to the corneal plane, apportion how much the final visual outcome and this might accouht for some error in the will be affected by the scarring, but the final refractive result. It is also possible that amblyopia would appear to be the major the over correction was due to the lathing detrimental factor at this point of follow up. In parameters being incorrect. Lathing of this reported series of paediatric cases around 10 lenticule was carried out according to the the­ per cent of grafts need removal, most com­ oretical model described by Werblin et al. 8 monly from problems with epithelial defects. Werblin found that experimental epi­ However, a proportion of these cases can be keratophakia in monkeys produced refractive successfully re-grafted. 2 62 CHAD K. ROSTRON

Keratoconus and Patch Grafting their patients, Mr. D. Shaw for assistance with com" The treatment of keratoconus by onlay lamel­ puting, and my wife for preparing the manuscript. lar epikeratoplasty now offers an alternative References in a situation where previously the only surgi­ 1 McDonald MB, Kaufman HE, Aquavella JV et al.: cal option available was penetrating ker­ The Nationwide study of epikeratophakia for atoplasty. Early reports of the technique have aphakia in adults. Am] Ophthalmol1987, 103: been favourable and the results in this study 358-65 . 2 Mogan KS, McDonald MC, Hiles DA et al.: The also support these findings.3 One of the main nationwide study of epikeratophakia for aphakia benefits of epikeratoplasty is its lack of prob­ in children. Am] Ophthalmol1987,103: 366-74 . lems with rejection and the results of epi­ 3 McDonald MB, Kaufman HE, Durrie DS et al.: keratophakia can only be fairly compared Epikeratophakia for keratoconus. The nation­ wide study. Arch Ophthalmol 1986, 104: 12 94- with those of penetrating keratoplasty when 1300 . longer follow up times are available. 4 Busin M, Halliday BL, Arffa RC et al.: Precarved Plano powered lenticules can readily be Iyophilised tissue for lamellar keratoplasty in prepared using the room temperature tech­ recurrent pterygium. Am ] Ophthalmol 1986, 102: 22 2- 7. nique, and when lyophilised this tissue is con­ 5 Maguen E and Nesburn AB: A new technique for venient for use both for the treatment of lathing Iyophilised cornea for refractive ker­ keratoconus and, as in case 7, for patch graft­ atoplasty. Arch Ophthalmol1982,100: 11 9-21. ing. The storage of tissue in a lyophilised state 6 Maguen E, Pinhas S, Verity SM, Nesburn AB: Kera­ is one of the factors that has done much to tophakia with Iyophilised cornea lathed at room temperature: new techniques and experimental popularise epikeratophakia as a procedure. surgical results. Ophthalmol Surg198 3, 14: 75 9- Techniques such as BKS 100012 and excimer 62. laser13 can be used to cut lenticules for epi­ 7 Rostron CK, Sandford-Smith JH, Morton DB: keratophakia without causing keratocyte or Experimental epikeratophakia using tissue ( epithelial cell death, and thus provide a 'liv­ lathed at room temperature. Br] Ophthalmol In press). ing' lenticule. However, this means that the 8 Werblin TP and Klyce SD: Epikeratophakia: the lenticule must be prepared by the surgeon, or surgical correction of aphakia. I. Lathing of cor­ rapidly transported in culture medium to the neal tissue. Curr Eye Res 1981,1: 123-9 . centre where it is to be used. The preparation 9 Durrie DS, Habrich DL, Dietze TR: Secondary intraocular lens implantation vs epikeratophakia of 'living' tissue is not necessarily an advan­ for the treatment of aphakia. Am] Ophthalmol tage that outweighs the convenience of having 1987,103: 384-91. I tissue in a lyophilised state. Whether any of O Werblin TP and Kaufman HE: Epikeratophakia: these new techniques will prove able to the surgical correction of aphakia. II. Prelimin­ achieve greater accuracy in refractive correc­ ary results in a nonhuman primate model. Curr Eye Res 1981,1: 131-7. tion will only be established by further experi­ 11 Morgan KS, Arffa RC, Marvelli TL et al.: Five year mental evaluation and clinical trials. follow-up of epikeratophakia in children. Oph­ thalmology 1986, 93: 423- 32 . 12 Swinger CA, Krumeich J, Cassidy D: Planar lamel­ lar refractive keratoplasty. ] Ref Surg 1986, 2: 17 -24 . I should like to thank Professor A. R. Rosenthal, Mr. 13 Lieurance RC, Patel AC, Lee Wan W et al.: Excimer J. H. Sandford-Smith, Mr. A. R. Fielder, Mr. J. Cap­ laser cut lenticules for epikeratophakia. Am ] pin and Mr. D. J. Austin for allowing me to report on Ophthalmo/1987,103: 475-6.