The Effect of Cyclosporine on LASIK Outcomes
The Effect of Cyclosporine on LASIK Outcomes
A study has found that 30 days of topical cyclosporine following LASIK for myopia may improve visual outcomes and reduce the enhancement rate.
By David J. Schanzlin, MD
The primary advantages of LASIK over other refractive procedures include a relative absence of pain and rapid visual recovery. However, a sizeable fraction of LASIK patients shows symptoms of a neurotrophic dry eye following the procedure, and dry eye symptoms are a significant problem even in patients with no indication of ocular dryness prior to surgery.
As multiple studies have recently shown, tear film abnormalities can affect vision. It is therefore reasonable to suppose that an agent such as cyclosporine 0.05% (Restasis®; Allergan), which is used to restore healthy tear production in dry eye patients, might improve visual outcomes in LASIK patients, even those without symptoms prior to their procedure.
LASIK and Cyclosporine
Topical cyclosporine is routinely used to treat LASIK patients with a prior history of dry eye disease. Studies have demonstrated that treatment with cyclosporine in these patients provides better refractive predictability at 3 and 6 months following surgery than treatment with artificial tears.1Cyclosporine 0.05% was later shown to provide greater corneal sensitivity at 3 months after surgery in patients without a history of dry eye disease, leading to the suggestion that it enhances corneal nerve regeneration.2
Continuing with the supposition that cyclosporine is beneficial for LASIK patients without dry eye disease, we studied the effects of using topical cyclosporine for 12 weeks after surgery and found a relationship between cyclosporine use and better and faster recovery of uncorrected visual acuity.3Based partly on these results, we decided to make postoperative cyclosporine part of the pharmaceutical regimen for all LASIK patients.
At the time, we did not know whether 3 months of cyclosporine treatment was necessary, or whether a similar result might be obtained with a shorter period of dosing. To investigate this question, as well as to look at the effect of cyclosporine on visual acuity, refraction, and enhancement rates, we performed a retrospective comparison of consecutive cases performed immediately before and immediately after cyclosporine was added to the postoperative pharmaceutical regimen.
LASIK was performed on 221 myopic eyes (126 patients) by a single surgeon using either a VISX™ S4 CustomVue™ laser (AMO) or a WaveLight Allegretto laser (Alcon). Flaps were created with a femtosecond laser (AMO). Preoperative refractive errors ranged from plano to -6.50 D, with cylinders up to 2.50 D. The patient demographics were similar in the treatment and control groups, and statistical testing showed that data could be pooled. (Table 1).
After surgery, all patients were instructed to take prednisolone acetate 1% (Pred Forte®; Allergan), gatifloxacin 0.3% (Zymar®; Allergan), and Refresh® Tears (Allergan) four times a day. The steroid and the antibiotic were stopped after 1 week, while the artificial tear was continued for a month. 109 consecutive eyes had topical cyclosporine 0.05%, twice daily, added to this regimen starting one day after surgery and continuing for 1 month; and 112 consecutive eyes received no cyclosporine treatment.
At the 3-month visit, the spherical refractive error in the control group was closer to plano than in the treated group (Figure 1). Refractive cylinder was similar in both groups, but the mean spherical equivalent was closer to plano in the treated group. The mean visual acuity was significantly better in the cyclosporine-treated eyes compared to the control eyes (LogMAR -0.002 ± 0.07 vs 0.031 ± 0.112; P= .033) (Figure 2).
Perhaps the most impressive (and certainly the most clinically relevant) result was that at 3 months following surgery, the enhancement rate in eyes treated with cyclosporine was significantly lower than in the control eyes (2.8% vs 9.8%; P = .031).
The Role of Cyclosporine in LASIK
In our first study, patients had been given cyclosporine 0.05% for 3 months following surgery, but we could see improvement as early as 1 week. In this study, we reduced the treatment time to 1 month and found that was sufficient to produce a beneficial effect that was still demonstrable at the 3-month visit. One month of topical cyclosporine twice a day following LASIK is now a standard part of our postoperative pharmaceutical regimen.
The enhancement rate is a key indicator of patients’ perceived quality of vision. In this series, there was a three-fold lower enhancement rate in the treatment vs the control group. So not only did the cyclosporine-treated patients have better acuity scores, but they were happier with their vision—at least to the degree that they were much less inclined to enhance their vision with additional surgery.
That said, the acuity scores in the control group were by no means bad. While statistically significant, the absolute acuity difference between the control and treatment groups was very small—the difference in enhancement rates is disproportionately greater than the acuity differences. Perhaps, when refractive differences are small, differences in satisfaction may be more influenced by the quality of the tear film than by differences in refractive error.
Patients with a 0.5 D refractive error and an unstable tear film may be less happy with their vision than other patients with same refractive error but a healthy, stable tear film. In recognition of this, we now we put patients on topical cyclosporine and perform punctal occlusion to plump up their tear film before offering to do an enhancement. We find that with refractive errors less than 0.75 D, a thicker tear film will provide better visual acuity, often making an enhancement unnecessary.
At this point, lasers have reached a state of impressive accuracy and sophistication. Significant improvement in outcomes may now be a matter of controlling wound healing and maintaining the tear film and ocular surface after surgery.
THE BOTTOM LINE
We found that topical cyclosporine twice a day after surgery, starting the day after surgery and continued for 1 month, improved visual outcomes and reduced the rate of enhancement. A thick, stable tear improves vision and may explain the significantly lower enhancement and better uncorrected visual acuity in the cyclosporine treated eyes.
David J. Schanzlin, MD, is professor of clinical ophthalmology at the University of California, San Diego, and the director of keratorefractive surgery at the Shiley Eye Center. He is the immediate Past President of the International Society of Refractive Surgery. This study was supported by an unrestricted educational grant from Allergan, Inc., Irvine, CA. This paper was prepared with the assistance of medical writer Adrianne Resek.
- Salib GM, McDonald MB, Smolek M. Safety and efficacy of cyclosporine 0.05% drops versus unpreserved artificial tears in dry-eye patients having laser in situ keratomileusis. J Cataract Refract Surg.2006 May;32(5):772-8.
- Peyman GA, Sanders DR, Batlle JF, et al. Cyclosporine 0.05% ophthalmic preparation to aid recovery from loss of corneal sensitivity after LASIK. J Refract Surg.2008 Apr;24(4):337-43.
- Ursea R, Purcell TL, Tan BU, et al. The effect of cyclosporine A (Restasis) on recovery of visual acuity following LASIK. J Refract Surg.2008 May;24(5):473-6.