Original Article

Anatomical and functional graft survival, 10 years after epikeratoplasty in

Anita Panda, Anoop K Gupta, Namrata Sharma1, Sasikala Nindrakrishna, Rasik Vajpayee1

Purpose: To report outcomes of epikeratoplasty in keratoconus (KC), utilizing manually-prepared plano Access this article online donor lenticules in terms of flattening of the cone, reduction in and improvement in the Website: . Materials and Methods: Patients with KC, having visual acuity <20/200, astigmatism >12 www.ijo.in diopters (D) but without corneal opacity underwent epikeratoplasty, using manually prepared plano DOI: donor lenticules from fresh or M.K preserved , between 1990 - 2000 and followed for 10 years, were 10.4103/0301-4738.105049 included in this report. Visual acuity slit-lamp-biomicroscopy, keratometry, and refraction were performed PMID: at 8 weeks, 12 weeks, and 6 months for all 59 patients. The same were carried out at 1 year, 5 years, and ***** 10 years depending upon the availability of the patient for that period. Results: Of the 59 patients, only 26 Quick Response Code: were available for follow-up after 10 years. At 3 months, 1 year and 5 years, best corrected visual acuity of (BCVA) ≥20/60 were achieved in 84.7%, 84.4% and 80.3% of , respectively. BCVA was 73% at 10-year follow- up, which was due to the presence of posterior subcapsular cataract (PSC). The average keratometric astigmatism and average flattening in diopters stabilized at the end of 3 months, which remained constant at 1, 5, and 10-year follow-up. The average diopter of was stabilized by 1 year, which was almost same at 10 year. Graft was clear in all but 1 at 10 year follow-up. Conclusion: Epikeratoplasty is a useful technique for keratoconic eyes without apical scarring who fail or unable to use contact lenses.

Key words: Astigmatism, epikeratoplasty, keratoconus

Abnormal curvature of the , giving rise to an irregular Similarly, an electrophysiological examination (VER- visual astigmatism, is a difficult situation to manage. In eyes with evoked response) was carried out to rule out any associated keratoconus, spectacle correction is sufficient in early cases. retinitis pigmentosa, which could have been missed during Other modalities such as, use of contact lens or intracorneal fundus evaluation due to extensive cone. Schimer’s testing rings are used in mild to moderate cases of keratoconus was performed as a routine test prior to any keratoplasty to but have its own limitations. In moderate to severe cases, rule out any surface abnormality. Applanation tonometry was keratoplasty may be required. carried out in all to rule out any associated abnormal rise of intraocular pressure (IOP). For surgical intervention, either Epikeratoplasty, an onlay lamellar keratoplasty, the least fresh or M.K.-preserved donor tissues were selected. invasive form of all keratoplasty, has been advocated in the West with encouraging results.[1-8] We introduced the procedure Surgical technique in India as early as 1990 in a very simplified manner where Patients were operated either with peribulbar or with general neither sophisticated lathe machine for preparation of a anesthesia depending upon the patient’s cooperation. Our lenticule is available nor the patient can afford to buy a freeze- technique has been reported.[9] In short, after the recipient dried lenticule for . eye was prepared and an annular mark was created over Materials and Methods the cornea with the help of the double trephine, 8 mm and 9 mm in diameter. The outer cut of the annular mark was 59 eyes with keratoconus with best corrected visual acuity 0.3 mm deep while the inner cut was 0.1 mm deep. The 0.5 mm (BCVA) <20/200, astigmatism >12D without apical scarring but annular ring was removed with the help of a Lim’s forceps not tolerating contact lenses, underwent an epikeratoplasty and curved Vannas scissors. After removal of the ring, the between 1990 - 2000. Besides thorough systemic and corneal epithelium was removed mechanically from the 8 ocular examinations, patients were subjected to slit- lamp mm diameter central cornea. Extreme care was taken not to biomicroscopy, keratometry, pachymetry, photokeratoscopy/ remove the epithelium beyond the annular ring. It was followed Orbscan II (depending upon the availability), ultrasonography by a thorough wash to the recipient bed with balanced salt was performed to rule out any posterior segment pathology. 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 Cornea and OSD Services, 1Cornea and Refractive Services, applied. And, a 0.3 mm thick plano refractive power lenticule Dr. R. P. Centre, A.I.I.M.S, New Delhi, India was prepared by closed dissection technique. The prepared Correspondence to: Prof. Anita Panda, Head of the Department, lenticule was sutured to the epithelial-free recipient bed by Cornea and OSD Services, Dr. Rajendra Prasad Centre for Ophthalmic 16, interrupted 10-0 monofilament, sutures. Post-operative Sciences, All India Institute of medical Sciences, Ansari Nagar, treatment included topical antibiotics 4 times daily, topical New Delhi - 110029, India. E-mail: [email protected] corticosteroids 2 hourly initially for week, later on in tapering Manuscript received: 25.12.10; Revision accepted: 16.04.12 frequency and maintain twice a day for 6 months and surface January 2013 Panda, et al.: Epikeratoplasty in keratoconus 19 lubricant drops with a frequency of 6 to 8 times a day. Topical But, BCVA was reduced to 73% (19/26 eyes) at 10-year follow- cycloplegic was instilled whenever indicated. up, which was usually explained by the presence of posterior subcapsular cataract (PSC) [Table 1]. The average amount of The post-operative examination included visual acuity and keratometric astigmatism at the end of 3 months was 2.66 ± slit-lamp biomicroscopy, daily up to 1 week. Thereafter, BCVA, 0.47 D, which remained stable at 1, 5, and 10 year follow-up keratometry, and slit-lam biomicroscopy were performed at 4 [Tables 2 and 3]. All sutures were removed by 18 months. weeks, 8 weeks, 12 weeks, and 6 months whenever the patients The observed reductions in astigmatism were stable after the were available for follow-up up to 10 years. suture removal. The average amount of myopia at 1 year −1.25 Results ± 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 Of the 59 patients, only 26 were available after 10 years. at 1, 5, and 10 year follow-up, respectively, with no change The mean age at surgery was 27.86 ± 5.6 years, range 21 - 46 in cylinder power [Table 3]. The average pachymetery was years [Fig. 1]. The electrophysiological examination (VER) of 529 ± 20 µ postoperatively, compared to 398 ± 20 µ preoperatively. patients included in the study has normal amplitude (average Schirmer’s was >15 mm in 5 minutes in all the patients’ pre 10 micro volts) and latency (average 103 milli second). All the and post operatively. Graft clarity was good in all but 1 eye patients complained of photophobia and watering of varying [Figs. 2a-d]. Epithelial defect was the only frequent complication degree for up to 48 - 72 hours in the operated eye. The visual during an early post-operative period, which could be acuity at the end of 1st, 4th, 8th, and 12th weeks varied in all eyes controlled in all except 1 subject where the graft sloughed off [Table 1]. At 3 months, 1 year, and 5 year, the best corrected and a lamellar keratoplasty was called for the control of corneal visual acuity (BCVA) ≥20/60 was achieved in 84.7% (50/59 eyes), melting. No rise in IOP was recorded in any of the patients. 84.4% (38/45 eyes) and 80.33 (25/30 eyes) of eyes, respectively. None of the eyes experienced recurrence of the keratoconus. Discussion Epikeratophakia was originally described as a surgical modality to correct .[1,2] Subsequently, it has been used effectively in both myopia[3] and in keratoconus.[4] Kaufman pioneered epikeratoplasty by utilizing the cryolathe-prepared plano lenticule for the correction of keratoconus[4] 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.[18] Krumeich et al. (1998) advocated the use of live epikeratophakia for grade I- II keratoconus with good Figure 1: Bar-diagram showing age of the patients enrolled into the success.[11] As reported in literature, the donor lenticule is study prepared by cryolathe machine either on the day of the surgery

Table 1: Post-operative visual acuity VA 1st wk 4th wk 8th wk 12th wk 6 M 1 yr 5 yrs ≥ 10 yrs N = 59 N = 59 N = 59 N = 59 N = 59 N = 45 N = 30 N = 26 < 20/200 3 1 1 1 1 20/200 -20/60 43 40 13 8 8 7 5 7* (4PSC) > 20/60 13 18 45 50 50 38 25 19* (2PSC) VA: Visual acuity, wk: week, M: Month, yr: year, yrs: years, N: Number of patients, PSC: Posterior subcapsular cataract

Table 2: Post-operative keratometric astigmatism Astigmatism 1st wk 4th wk 8th wk 12th wk 6 m 1 yr 5 yrs ≥ 10 yrs (diopter) N = 59 N = 59 N = 59 N = 59 N = 59 N = 45 N = 30 N = 26 > 5 2 1 1 1 1 1 1 3 – 5 18 19 19 13 13 9 6 7 < 3 39 39 39 45 45 36 23 18 wk: week, m: month, yr: year, yrs: years, N: Number of patients 20 Indian Journal of Ophthalmology Vol. 61 No. 1

Table 3: Post-operative composite data 8th wk 12th wk 6 m 1 yr 5 yrs ≥ 10 yrs N = 26 N = 26 N = 26 N = 26 N = 26 N = 26 Average keratometric astigmatism in D Minimum 2 2 2 2 2 2 Maximum 3.50 3.50 3.50 3.50 3.50 3.50 Mean 2.6827 2.6635 2.6635 2.6635 2.6635 2.6635 SD 0.4927 0.4793 0.4793 0.4793 0.4793 0.4793 Visual acuity Minimum 0.25 0.33 0.33 0.33 0.33 0.28 Maximum 0.67 0.67 0.67 0.67 0.67 0.67 Mean 0.4218 0.4867 0.4867 0.4867 0.4867 0.4516 SD 0.1259 0.1166 0.1166 0.1166 0.1166 0.1219 Average myopia in D Minimum −1.75 −1.75 −1.75 −1.75 −1.75 −1.75 Maximum 1 −1 −1 1.25 1.75 1.75 Mean −1.1827 −1.2596 −1.2496 −1.1154 −1.1827 −1.1538 SD 0.5077 0.2498 0.2498 0.6254 0.6124 0.5481 Average cylinder in D Minimum −2 −2 −2 −2 −2 2 Maximum −3.5 −3.5 −3.5 −3.5 −3.5 −3.5 Mean −2.3942 −2.3942 −2.3942 −2.3942 −2.3942 −2.3942 SD 0.3254 0.3254 0.3256 0.3258 0.3254 0.3254 wk: week, m: month, yr: year, yrs: years, n: Number of patients, D: Diopter, SD: Standard deviation

a multicenter trial. In India, Gupta and Rao reported the efficacy of the technique by using the imported cryolathe cut lenticule,[7] 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.[9] a b 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. c d There are reports on donor lenticule fixation to the recipient Figure 2: (a) Clinical photograph with slit-illumination showing bed by tissue adhesive.[20,21] However, considering the fact keratoconic cornea without any apical Scarring. (b) Clinical photograph that the mechanism of action of epikeratoplasty in KC for with slit-illumination showing cornea at 3-month post-operative follow- up. (c) Clinical photograph with diffuse-illumination showing cornea the improvement in the vision is primarily by flattening the [22] at 1-yr post-operative follow-up. (d) Clinical photograph with slit- cornea, we used sutures in all. In the present study, it was illumination showing cornea at 10-yrs post-operative follow-up 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 (fresh tissue), or it can be prepared several days or few weeks was <20/200 in all eyes, demonstrated minimal improvement before surgery and maintained in frozen state (frozen tissue),[7] at the end of 1st week, but improved gradually to ≥20/60 at the or it can be cryolathed and freeze-dried, weeks to months end of 12 weeks in 84.7% (50/59 eyes). Interestingly, both the preceding surgery (freeze dried tissue).[19] The advantages of astigmatism and BCVA were stable even at the end of 5-year the lathed tissue are, it has a smooth stromal surface and the follow-up, indicating the visual improvement following shortened surgical time as the lenticules are readily available epikeratoplasty is a gradual process and stabilizes within 8 - 12 and the tissue can be stored for more than 2 months for an easy weeks[9] and does not change significantly during long-term availability. In Unites States, freeze-dried tissue is being used in follow-up.[23] January 2013 Panda, et al.: Epikeratoplasty in keratoconus 21

In the literature, epikeratoplasty has been compared with PK for epikeratoplasty. The deep lamellar keratoplasty (DALK) with comparable results.[24-26] One may wonder if the same can technique aims to remove all or near total corneal stroma be compared with that of ATK/ DALK. However, considering down to Descemet’s membrane existing opacity, thus needing the indication and surgical technique were quite different in an expert who is quite well in lamellar technique whereas epikeratoplasty than that of other form of keratoplasty, it is not epikeratoplasty is minimally invasive form of keratoplasty, can an optimally ideal preposition to compare with that of others. be performed by any corneal surgeon. This was evident from a Though the future comparative study with ALK/DALK will recent study from the UK on DALK by Jones et al., comparing substantiate its validity. the outcomes after PKP and DALK for keratoconus, showed suboptimal result following DALK was attributed to the less A number of post-operative complications such as, persistent experience of the surgeon in DALK.[36] epithelial defect (PED), severe anterior segment inflammation during early post-operative period, graft melting and interface Till then, we conclude that the patients of keratoconus with haze during the intermediate post-operative period, and contact lens intolerance but without apical scarring, irrespective hypoesthesia, peripheral and PSC cataract during of astigmatism and corneal thickness, can be benefited by the late post-operative period have been reported.[27-33] Presence epikeratoplasty both anatomically and functionally. of PED during the early post-operative period in our study suggests the surface irregularities are caused by tucking of the References donor lenticule with the additional factor of tight suturing. In 1. Werblin TP, Klyce SD. Epikeratophakia: The surgical correction of this series, we experienced 5 eyes (11.8%) with PED. of which aphakia. I. Lathing of corneal tissue. Curr Eye Res 1981;1:123-9. 4 resolved but 1 lead to graft melting, requiring lenticule 2. Werblin TP, Kaufman HE. Epikeratophakia: The surgical correction removal and anterior lamellar keratoplasy. An Interface haze of aphakia. II. Preliminary results in a non-human primate model. is bothersome to the patient, which could be attributed to the Curr Eye Res 1981;1:131-7. [31,32] persistence of the host epithelium and sometimes leads 3. Werblin TP, Klyce SD. Epikeratophakia: The surgical correction of to abscess formation. This was seen in 1 of our cases during myopia. I. Lathing of corneal tissue. Curr Eye Res 1981-1982;1:591-7. intermediate post-operative period. Reduced corneal sensitivity 4. Kaufman HE, Werblin TP. Epikeratophakia for the treatment of calls for urgent management to avoid sterile graft melting. keratoconus. Am J Ophthalmol 1982;93:342-7. Waller et al. (1995) and Kaminski et al. (2002) demonstrated 5. Werblin TP. Epikeratophakia: Techniques, complications, and reduced corneal sensitivity at 5-year and 10-year follow-up, clinical results. Int Ophthalmol Clin 1983;23:45-58. [28,29] respectively. This relative hypoesthesia is expected to 6. McDonald MB, Kaufman HE, Durrie DS, Keates RH, Sanders DR. create corneal problems. However, neither their study nor our Epikeratophakia for keratoconus. The nationwide study. Arch study demonstrated any additional post-operative problems. Ophthalmol 1986;104:1294-300. No recurrence of KC in our series could be explained by large 7. Gupta S, Rao GN. Results of epikeratoplasty. Indian J Ophthalmol graft size (8.5 mm) wrapping the ectactic area with adjacent 1987;35:181-2. normal cornea. 8. Lehtosalo J, Uusitalo RJ, Mianowizc J. 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