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    Corneal nerve regeneration: how can we accelerate the process?

    Cyclosporine A speeds restoration of post LASIK corneal sensitivity

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    The effect of LASIK on corneal nerves is well known; the loss of corneal sensation can lead to a decrease in tear flow, can slow epithelial wound healing and can cause dry eye and neurotrophic keratitis. So how can refractive surgeons speed up the healing process after surgery and help prevent these unwanted side effects? Professor Gholam Peyman from the University of Arizona, Tucson, USA may have found the answer. In a recent study, which examined the effects of the immunosuppressive agent cyclosporine 0.05% (Restasis; Allergan) on corneal sensitivity, he found that this drug might actually have a beneficial effect on corneal nerve regeneration, in addition to its use as a treatment for dry eye.

    The road to discovery

    "When I invented LASIK in 1985,1 I knew that corneal incisions would cut the corneal nerves but felt that the benefits, would outweigh the possible disadvantages," explained Professor Peyman. "However I did not foresee that it would cause dry eye in up to 70% of patients." A recent study2 to assess the subjective symptoms and objective clinical signs of dry eye, in addition to corneal sensitivity after high myopic LASIK, found that the majority of the 20 patients reported ongoing dry eye symptoms. The researchers noted, however, that the objective clinical signs of tear insufficiency and hypoesthesia were not demonstrable and proposed that the symptoms, therefore, represented a form of corneal neuropathy rather than dry eye syndrome.

    A number of investigations3,4 have already evaluated the effects of cyclosporine A, and other similar compounds, in tissue cultures and concluded that the potency of the agents, their bioavailability and the dissociation of neurotrophic from immunosuppressant actions give them a possible therapeutic relevance in the treatment of neurodegenerative diseases. However, the results were a little ambiguous. "I thought that, since cyclosporine A is already available as a treatment for dry eye, it would be worth while finding out whether it could enhance corneal nerve regeneration after LASIK", said Professor Peyman.

    Under the microscope

    Professor Peyman conducted the first human prospective, randomized, single-centre, masked study to determine whether cyclosporine 0.05% could help regenerate nerve tissue following LASIK surgery. Thirty-eight eyes of 19 patients were included in the study, each of whom had no prior history of dry eye or diabetes mellitus and had not previously undergone refractive surgery.

    The subjects received cyclosporine 0.05% twice daily, starting on the day of surgery, in one eye, in addition to using their standard postoperative regimen of eyedrops in both eyes. They were evaluated one day, one week and three months postoperatively. "Though one can not generalize, I believe that a period of between four and six months will prove to be the ideal period for restoring corneal sensitivity," added Professor Peyman.


    Figure 1: Diagram depicting the nine points of corneal sensitivity evaluated during the study.
    Corneal sensitivity was measured with a Cochet-Bonnet aesthesiometer at nine points on the cornea — four outside the flap margins and five within the flap diameter (Figure 1). Statistical analysis was conducted using the Wilcoxon Sum Rank Test and p=0.05 was considered to be statistically significant.

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    Amelia Tope
    Amelia Tope is the former Associate Editor of Ophthalmology Times Europe. She may be reached by Tel: +44 (0)1244 393 153 or E-mail:

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