Topical Cyclosporine

Topical Cyclosporine Dear Editor: A successfully performed keratoplasty with a clear corneal graft may fail due to repeated episodes of endothelial rejection, a major cause of graft failure worldwide.1 Topical cyclosporine-A 2% has been considered a potential therapy for treating2 and preventing corneal graft rejection.3 Efficacy has been reported for oral cyclosporine4 and tacrolimus5 in high-risk keratoplasty, but potential systemic toxicity may limit their use.4 We performed a prospective, randomized, controlled, clinical trial to evaluate the efficacy of topical cyclosporine-A 2% in prevention of recurrence of corneal graft rejection in patients who had suffered a single episode of corneal graft rejection and were treated successfully with the standard therapy. After complete resolution of the rejection episode, the patients were enrolled and assigned into 2 groups: (1) the study group, in which topical cyclosporine-A 2% was instilled 4 times daily (QID); and (2) a control group, in which preservativefree artificial tears QID were prescribed and the treatment continued for 1 year. All patients in both groups were using topical dexamethasone sodium phosphate 0.1% QID at the time of enrollment, which was tapered over 1 year. The most common indication for keratoplasty was corneal scar (Table 1, available at http://aaojournal.org). At initial presentation and at each follow-up visit (1 month, 3 months, 6 months, 1 year, and 2 years), the parameters evaluated were uncorrected visual acuity (UCVA), best spectacle corrected visual acuity (BSCVA), and slit lamp biomicroscopy for corneal and anterior segment structures, suture status, and any evidence of graft rejection. If rejection occurred in any of the eyes, it was treated with standard treatment regimen. The number of eyes that suffered 1 rejection episode after enrollment was 9 (n⫽23) in study group and 11 (n⫽23) in control group (P⫽0.35). The number of eyes that suffered 2 rejection episodes after enrollment was 5 in study group and 9 in control group (P⫽0.33). One eye in the study group and 2 eyes in the control group suffered 3 rejection episodes. The mean number of rejection episodes after enrollment was 1.66⫾0.70 in study group and 2.00⫾0.63 in control group (P⫽0.28). The mean time interval for the occurrence of first rejection episode after enrollment was 133.33⫾15.82 days in study group (n⫽9) and 114.18⫾ 12.09 days in control group (n⫽11; P⫽0.35). All the 9 eyes in the study group, that suffered rejection episode after enrollment reversed completely after treatment. In the control group, 10 eyes (n⫽11) reversed completely and one eye went into graft failure (P⫽0.86). The mean duration of reversal was 19.6⫾1.35 days and 20.33⫾ 1.34 days in the 2 groups and were statistically similar. At the end of 2 years, the number of clear grafts in the study group was 18, and the number of clear grafts in the control group was 17. The mean BCVA during enrollment was 0.71⫾0.22 in the study group and 0.62⫾0.21 in control group. The mean BCVA at the end of 2 years with clear grafts in the study group was 0.75⫾0.16, and in the control group it was 0.70⫾0.20 (P⫽0.49).

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Topical cyclosporine is considered a potential agent to prevent corneal graft rejection as it inhibits activation of T-cell lymphocytes. A comparative evaluation of combination treatment of topical cyclosporine 2% and topical corticosteroids, and treatment with topical corticosteroids alone was performed following pediatric keratoplasty in 22 eyes. The rejection-free graft survival rate was significantly better in cyclosporine group.6 The results of our study showed that the use of topical cyclosporine did not significantly reduce the recurrence of graft rejection episodes. Another study noted that topical cyclosporine 0.05% is not as effective as topical prednisolone 1% for prevention of graft rejection.7 The rejection free interval was slightly greater in the eyes that were put on cyclosporine drops (Figure 1, available at http://aaojounral.org); however, the difference was not large enough to support a statement that topical cyclosporine delays the recurrence of corneal graft rejection. Another study has shown no advantage of topical cyclosporine in increasing the rejection free period in corneal grafts.7 The duration of reversal of rejection episode was also similar in the 2 groups. This highlights that the topical cyclosporine does not apparently have any role in enhancing the reversal of rejection episode. The study results suggest that the addition of topical cyclosporine to the routine treatment with topical steroids does not appear to provide any significant advantage in terms of graft survival, recurrence of rejection episodes, duration of recurrence free period, and the duration of reversal of corneal graft rejection episode. RAJESH SINHA, MD, FRCS SREENIVAS VISHNU, PHD NAMRATA SHARMA, MD New Delhi, India RASIK B. VAJPAYEE, MS, FRCSEd Melbourne, Australia References 1. Price FW Jr, Whitson WE, Johns S, Gonzales JS. Risk factors for corneal graft failure. J Refract Surg 1996;12:134 – 43; discussion 143–7. 2. Poon A, Constantinou M, Lamoureux E, Taylor HR. Topical cyclosporin A in the treatment of acute graft rejection: a randomized controlled trial. Clin Experiment Ophthalmol 2008;36:415–21. 3. Inoue K, Amano S, Kimura C, et al. Long-term effects of topical cyclosporine A treatment after penetrating keratoplasty. Jpn J Ophthalmol 2000;44:302–5. 4. Poon AC, Forbes JE, Dart JK, et al. Systemic cyclosporin A in high risk penetrating keratoplasties: a case-control study. Br J Ophthalmol 2001;85:1464 –9. 5. Sloper CM, Powell RJ, Dua HS. Tacrolimus (FK506) in the management of high-risk corneal and limbal grafts. Ophthalmology 2001;108:1838 – 44. 6. Cosar CB, Laibson PR, Cohen EJ, Rapuano CJ. Topical cyclosporine in pediatric keratoplasty. Eye Contact Lens 2003; 29:103–7. 7. Price MO, Price FW Jr. Efficacy of topical cyclosporine 0.05% for prevention of corneal transplant rejection episodes. Ophthalmology 2006;113:1785–90.

Table 1. Indications of Keratoplasty Indications

Study Group (n ⴝ 23)

Control Group (n ⴝ 23)

Bullous keratopathy Keratoconus Corneal scars Failed graft Macular corneal dystrophy

6 2 11 3 1

7 2 9 3 2

Figure 1. Kaplan-Meier diagram comparing rejection free interval in the 2 groups (group 0 ⫽ control; group 1 ⫽ study group).

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