Abnormal curvature of the cornea, giving rise to an irregular astigmatism, is a difficult situation to manage. In eyes with keratoconus, spectacle correction is sufficient in early cases. Other modalities such as, use of contact lens or intracorneal rings are used in mild to moderate cases of keratoconus but have its own limitations. In moderate to severe cases, keratoplasty may be required.
Epikeratoplasty, an onlay lamellar keratoplasty, the least invasive form of all keratoplasty, has been advocated in the West with encouraging results.[1–8] We introduced the procedure in India as early as 1990 in a very simplified manner where neither sophisticated lathe machine for preparation of a lenticule is available nor the patient can afford to buy a freeze-dried lenticule for surgery.
Materials and Methods
59 eyes with keratoconus with best corrected visual acuity (BCVA) <20/200, astigmatism >12D without apical scarring but not tolerating contact lenses, underwent an epikeratoplasty between 1990 - 2000. Besides thorough systemic and ocular examinations, patients were subjected to slit- lamp biomicroscopy, keratometry, pachymetry, photokeratoscopy/Orbscan II (depending upon the availability), ultrasonography was performed to rule out any posterior segment pathology. Similarly, an electrophysiological examination (VER- visual evoked response) was carried out to rule out any associated retinitis pigmentosa, which could have been missed during fundus evaluation due to extensive cone. Schimer's testing was performed as a routine test prior to any keratoplasty to rule out any surface abnormality. Applanation tonometry was carried out in all to rule out any associated abnormal rise of intraocular pressure (IOP). For surgical intervention, either fresh or M.K.-preserved donor tissues were selected.
Patients were operated either with peribulbar or with general anesthesia depending upon the patient's cooperation. Our technique has been reported. In short, after the recipient eye was prepared and an annular mark was created over the cornea with the help of the double trephine, 8 mm and 9 mm in diameter. The outer cut of the annular mark was 0.3 mm deep while the inner cut was 0.1 mm deep. The 0.5 mm annular ring was removed with the help of a Lim's forceps and curved Vannas scissors. After removal of the ring, the corneal epithelium was removed mechanically from the 8 mm diameter central cornea. Extreme care was taken not to remove the epithelium beyond the annular ring. It was followed by a thorough wash to the recipient bed with balanced salt solution (BSS) to wash out any remnant of epithelial debris. To prepare the lenticule, the donor tissue was fixed with a Kings clamp. Using a 9.5 mm Storz trephine, a 0.3 mm deep cut was applied. And, a 0.3 mm thick plano refractive power lenticule was prepared by closed dissection technique . The prepared lenticule was sutured to the epithelial-free recipient bed by 16, interrupted 10-0 monofilament, sutures. Post-operative treatment included topical antibiotics 4 times daily, topical corticosteroids 2 hourly initially for week, later on in tapering frequency and maintain twice a day for 6 months and surface lubricant drops with a frequency of 6 to 8 times a day. Topical cycloplegic was instilled whenever indicated.
The post-operative examination included visual acuity and slit-lamp biomicroscopy, daily up to 1 week. Thereafter, BCVA, keratometry, and slit-lam biomicroscopy were performed at 4 weeks, 8 weeks, 12 weeks, and 6 months whenever the patients were available for follow-up up to 10 years.
Of the 59 patients, only 26 were available after 10 years. The mean age at surgery was 27.86 ± 5.6 years, range 21 - 46 years [Fig. 1]. The electrophysiological examination (VER) of patients included in the study has normal amplitude (average 10 micro volts) and latency (average 103 milli second). All the patients complained of photophobia and watering of varying degree for up to 48 - 72 hours in the operated eye. The visual acuity at the end of 1st, 4th, 8th, and 12th weeks varied in all eyes [Table 1]. At 3 months, 1 year, and 5 year, the best corrected visual acuity (BCVA) ≥20/60 was achieved in 84.7% (50/59 eyes), 84.4% (38/45 eyes) and 80.33 (25/30 eyes) of eyes, respectively. But, BCVA was reduced to 73% (19/26 eyes) at 10-year follow-up, which was usually explained by the presence of posterior subcapsular cataract (PSC) [Table 1]. The average amount of keratometric astigmatism at the end of 3 months was 2.66 ± 0.47 D, which remained stable at 1, 5, and 10 year follow-up [Tables 2 and 3]. All sutures were removed by 18 months. The observed reductions in astigmatism were stable after the suture removal. The average amount of myopia at 1 year –1.25 ± 0.24 D sphere and –2.39 ± 0.32 D cylinder which was –1.12 ± 0.62 D sphere, –1.18 ± 0.61 D sphere and –1.15 ± 0.54 D sphere at 1, 5, and 10 year follow-up, respectively, with no change in cylinder power [Table 3]. The average pachymetery was 529 ± 20 μ postoperatively, compared to 398 ± 20 μ preoperatively. Schirmer's was >15 mm in 5 minutes in all the patients’ pre and post operatively. Graft clarity was good in all but 1 eye [Figs. 2a–d]. Epithelial defect was the only frequent complication during an early post-operative period, which could be controlled in all except 1 subject where the graft sloughed off and a lamellar keratoplasty was called for the control of corneal melting. No rise in IOP was recorded in any of the patients. None of the eyes experienced recurrence of the keratoconus.
Epikeratophakia was originally described as a surgical modality to correct aphakia. Subsequently, it has been used effectively in both myopia and in keratoconus. Kaufman pioneered epikeratoplasty by utilizing the cryolathe-prepared plano lenticule for the correction of keratoconus and was followed by others successfully.[5–17] As the technique is much simpler than any other lamellar procedures (as except peripheral annular ring removal, the recipient bed is not disturbed), lacks serious vision-threatening complications and is free of risk of rejection in comparison to penetrating keratoplasty, the gold standard for KC management, it was performed by various authors and became an effective alternative[14–17] to Javadi et al. were of the opinion that as it is an extra ocular procedure, it can be performed effectively both for keratoconus and keratoglobus. Krumeich et al. (1998) advocated the use of live epikeratophakia for grade I- II keratoconus with good success. As reported in literature, the donor lenticule is prepared by cryolathe machine either on the day of the surgery (fresh tissue), or it can be prepared several days or few weeks before surgery and maintained in frozen state (frozen tissue), or it can be cryolathed and freeze-dried, weeks to months preceding surgery (freeze dried tissue). The advantages of the lathed tissue are, it has a smooth stromal surface and the shortened surgical time as the lenticules are readily available and the tissue can be stored for more than 2 months for an easy availability. In Unites States, freeze-dried tissue is being used in a multicenter trial. In India, Gupta and Rao reported the efficacy of the technique by using the imported cryolathe cut lenticule, as we don’t have an access to the cryolathe machine in India, and our patients cannot afford to import the expensive frozen lenticule from the West. We prepared the lenticule manually in 1990, either from fresh or M.K-preserved donor tissue, and used in KC with an excellent outcome.
Our technique of obtaining the plano lenticule is very simple and exactly similar as that used for anterior lamellar keratoplasty. Further, it requires minimal intervention to the recipient cornea in comparison to either anterior lamellar or deep anterior lamellar keratoplasty. Thus, we were encouraged to carry on the technique for eyes with advanced keratoconus, but without any apical scar.
There are reports on donor lenticule fixation to the recipient bed by tissue adhesive. However, considering the fact that the mechanism of action of epikeratoplasty in KC for the improvement in the vision is primarily by flattening the cornea, we used sutures in all. In the present study, it was evident that though the pre-operative astigmatism was >12 D in all the 59 eyes, at the end of 12 weeks, 76.2 % (45/59 eyes) had astigmatism <4 D. Similarly, pre-operative visual acuity was <20/200 in all eyes, demonstrated minimal improvement at the end of 1st week, but improved gradually to ≥20/60 at the end of 12 weeks in 84.7% (50/59 eyes). Interestingly, both the astigmatism and BCVA were stable even at the end of 5-year follow-up, indicating the visual improvement following epikeratoplasty is a gradual process and stabilizes within 8 - 12 weeks and does not change significantly during long-term follow-up.
In the literature, epikeratoplasty has been compared with PK with comparable results.[24–26] One may wonder if the same can be compared with that of ATK/ DALK. However, considering the indication and surgical technique were quite different in epikeratoplasty than that of other form of keratoplasty, it is not an optimally ideal preposition to compare with that of others. Though the future comparative study with ALK/DALK will substantiate its validity.
A number of post-operative complications such as, persistent epithelial defect (PED), severe anterior segment inflammation during early post-operative period, graft melting and interface haze during the intermediate post-operative period, and hypoesthesia, peripheral corneal ulcer and PSC cataract during the late post-operative period have been reported.[27–33] Presence of PED during the early post-operative period in our study suggests the surface irregularities are caused by tucking of the donor lenticule with the additional factor of tight suturing. In this series, we experienced 5 eyes (11.8%) with PED. of which 4 resolved but 1 lead to graft melting, requiring lenticule removal and anterior lamellar keratoplasy. An Interface haze is bothersome to the patient, which could be attributed to the persistence of the host epithelium and sometimes leads to abscess formation. This was seen in 1 of our cases during intermediate post-operative period. Reduced corneal sensitivity calls for urgent management to avoid sterile graft melting. Waller et al. (1995) and Kaminski et al. (2002) demonstrated reduced corneal sensitivity at 5-year and 10-year follow-up, respectively. This relative hypoesthesia is expected to create corneal problems. However, neither their study nor our study demonstrated any additional post-operative problems. No recurrence of KC in our series could be explained by large graft size (8.5 mm) wrapping the ectactic area with adjacent normal cornea.
Astigmatism was stable for up to 10-year follow-up. Posterior subcapsular cataract development was evident in 16.6% and 34.6% at 5-year and 10-year follow-up, respectively, and was the cause of reduction in vision in many of our patients during the long-term follow-up. The most important shortcoming in our report is the loss of follow-up. One may wonder if the rest 33 patients were simply lost to follow-up as they were comfortable and had no complaints, or were lost to follow-up due to need of an additional corneal intervention elsewhere. However, we presume that the latter may not be true as the patients had randomly come for the follow–up, and as per our protocol, only patients having constant follow up at 8 week, 12 week, 3 months, 6 months, 1 year, 5 years and 10 years were taken into account.
Other available treatment option like collagen cross linking is less invasive approach to stop the progression of keratoconus, which involves epithelial debridement, application of topical riboflavin drops and ultraviolet- An exposure at 370 nm for approximately 30 min; but it does not provide refractive correction. Further, this technique is relatively new, and long term success has to be evaluated yet. Similarly, intracorneal rings (PMMA segments) are effectively used for the treatment of keratoconus. But, treatment with intrastromal rings does not eliminate the progression of keratoconus; however, it may delay a corneal transplant procedure. Moreover this, both the above procedure cannot be carried out if the central corneal thickness is <400 μm while corneal thickness is not an issue for epikeratoplasty. The deep lamellar keratoplasty (DALK) technique aims to remove all or near total corneal stroma down to Descemet's membrane existing opacity, thus needing an expert who is quite well in lamellar technique whereas epikeratoplasty is minimally invasive form of keratoplasty, can be performed by any corneal surgeon. This was evident from a recent study from the UK on DALK by Jones et al., comparing the outcomes after PKP and DALK for keratoconus, showed suboptimal result following DALK was attributed to the less experience of the surgeon in DALK.
Till then, we conclude that the patients of keratoconus with contact lens intolerance but without apical scarring, irrespective of astigmatism and corneal thickness, can be benefited by epikeratoplasty both anatomically and functionally.
1. Werblin TP, Klyce SD. Epikeratophakia: The surgical correction of aphakia. I. Lathing of corneal tissue Curr Eye Res. 1981;1:123–9
2. Werblin TP, Kaufman HE. Epikeratophakia: The surgical correction of aphakia. II. Preliminary results in a non-human primate model Curr Eye Res. 1981;1:131–7
3. Werblin TP, Klyce SD. Epikeratophakia: The surgical correction of myopia. I. Lathing of cornealth tissue Curr Eye Res. 1981-1982;1:591–7
4. Kaufman HE, Werblin TP. Epikeratophakia for the treatment of keratoconus
Am J Ophthalmol. 1982;93:342–7
5. Werblin TP. Epikeratophakia: Techniques, complications, and clinical results Int Ophthalmol Clin. 1983;23:45–58
6. McDonald MB, Kaufman HE, Durrie DS, Keates RH, Sanders DR. Epikeratophakia for keratoconus
. The nationwide study Arch Ophthalmol. 1986;104:1294–300
7. Gupta S, Rao GN. Results of epikeratoplasty Indian J Ophthalmol. 1987;35:181–2
8. Lehtosalo J, Uusitalo RJ, Mianowizc J. Epikeratophakia for treatment of keratoconus
Arch Ophthalmol. 1989;107:3–18
9. Panda A. A cost effective lenticule preparation for keratoconus
Ocular Surg International. 1994;5:3
10. Fronterrè A, Portesani GP. Epikeratoplasty for pellucid marginal corneal degeneration Cornea. 1991;10:450–3
11. Krumeich JH, Daniel J, Knülle A. Live-epikeratophakia for keratoconus
J Cataract Refract Surg. 1998;24:456–63
12. Kim WJ, Lee JH. Epikeratoplasty for keratoconus
Korean J Ophthalmol. 1991;5:30–3
13. Fouraker BD, Schanzlin DJ. Update on epikeratoplasty Refract Corneal Surg. 1991;7:57–9
14. Goosey JD, Prager TC, Goosey CB, Bird EF, Sanderson JC. A comparison of penetrating keratoplasty to epikeratoplasty in the surgical management of keratoconus
Am J Ophthalmol. 1991;112:103–5
15. Fronterre A, Portesani GP. Comparison of epikeratoplasty and penetrating keratoplasty for keratoconus
Refract Corneal Surg. 1991;7:167–73
16. Lembach RG, Lass J, Foulks GN. A comparison of penetrating keratoplasty to epikeratoplasty in the surgical management of keratoconus
Am J Ophthalmol. 1991;112:103–5
17. Wagoner MD, Smith SD, Rademaker WJ, Mahmood MA. Penetrating keratoplasty vs.epikeratoplasty for the surgical treatment of keratoconus
J Refract Surg. 2001;17:138–46
18. Javadi MA, Kanavi MR, Ahmadi M, Yazdani S. Outcomes of epikeratoplasty for advanced keratoglobus Cornea. 2007;26:154–7
19. Binder PS, Zavala EY, Baumgartner SD, Nayak SK. Combined morphologic effects of cryolathing and lyophilization on epikeratoplasty lenticules Arch Ophthalmol. 1986;104:671–9
20. Brittain GP, Rostron CK, Morton DB, Rees JE. The use of a biological adhesive to achieve sutureless epikeratophakia Eye. 1989;3:56–63
21. Colin J. Experimental sutureless synthetic epikeratophakia Arch Ophthalmol. 1989;107:318
22. Spitznas M, Eckert J, Frising M, Eter N. Long-term functional and topographic results seven years after epikeratophakia for keratoconus
Graefes Arch Clin Exp Ophthalmol. 2002;240:639–43
23. Waller SG, Steinert RF, Wagoner MD. Long-term results of epikeratoplasty for keratoconus
24. Vajpayee RB, Sharma N. Epikeratoplasty for keratoconus
using manually dissected fresh lenticules: 4-year follow-up J Refract Surg. 1997;13:659–62
25. Høvding G, Haugen OH, Bertelsen T. Epikeratophakia for keratoconus
in mentally retarded patients. The use of fresh, free-hand made lamellar grafts Acta Ophthalmol (Copenh). 1992;70:730–5
26. Høvding G, Bertelsen T. Epikeratophakia for keratoconus
. Long-term results using fresh, free-hand made lamellar grafts Acta Ophthalmol (Copenh). 1992;70:461–9
27. Kaminski SL, Biowski R, Lukas JR, Koyuncu D, Grabner G. Corneal sensitivity 10 years after epikeratoplasty J Refract Surg. 2002;18:731–6
28. Teichmann KD, Wagoner MD. Mooren ulcer following epikeratoplasty for keratoconus
Arch Ophthalmol. 1998;116:1381–2
29. Bechara SJ, Grossniklaus HE, Waring GO. Sterile stromal melt of epikeratoplasty lenticule Arch Ophthalmol. 1992;110:1528–9
30. Shands PR, Lass JH. Severe anterior segment inflammation following corneal surgery for keratoconus
Ophthalmic Surg. 1990;21:645–6
31. Morgan KS, Beuerman RW. Interface opacities in epikeratophakia Arch Ophthalmol. 1986;104:1505–8
32. Price FW Jr, Binder PS. Scarring of a recipient cornea following epikeratoplasty Arch Ophthalmol. 1987;105:1556–60
33. Hemady RK, Bajart AM, Wagoner MD. Interface abscess after epikeratoplasty Am J Ophthalmol. 1990;109:735–6
34. Wollensak G, Spörl E, Seiler T. Treatment of keratoconus
by collagen cross linking Ophthalmologe. 2003;100:44–9
35. Burris TE, Ayer CT, Evensen DA, Davenport JM. Effects of instrastromal corneal ring size and thickness on corneal flattening in human eyes Refract Corneal Surg. 1991;7:46–50
36. Jones MN, Armitage WJ, Ayliffe W, Larkin DF, Kaye SBNHSBT Ocular Tissue Advisory Group and Contributing Ophthalmologists (OTAG Audit Study 5). . Penetrating and deep anterior lamellar keratoplasty for keratoconus
: A comparison of graft outcomes in the United Kingdom Invest Ophthalmol Vis Sci. 2009;50:562–9
Source of Support: Nil.
Conflict of Interest: No.