Thank you all for making Subspecialty Day 2004 in New Orleans the best one yet! Due to the interest expressed in epi-LASIK during that meeting, we have chosen to make it the cover story for this issue.

ISRS/AAO will hold its first international meeting May 14 through 16, 2005, in Hong Kong. The meeting, Emerging Trends in Refractive and Cataract Surgery, will assemble the international leaders in refractive and cataract surgery and provide a forum for exchange of the latest information in the field.

Sincerely,
Marguerite McDonald, MD, FACS
Medical Editor, Refractive Outlook

IN THIS ISSUE
- Epi-LASIK – A Step Forward in Refractive Surgery
- Journal Update: Wavefront Guided LASIK with Zyoptix 3.1 System for the Correction of Myopia and Compound Myoptic Astigmatism with 1 Year Follow Up: Clinical Outcome and Change in Higher Order Aberrations
- Journal Update: Predicting Time to Refractive Stability After Discontinuation of Rigid Contact Lens Wear Before Refractive Surgery
- Journal Update: Complications Associated with Anterior Basement Membrane Dystrophy After Laser in Situ Keratomileusis
- Q&A

FEATURE

Epi-LASIK – A Step Forward in Refractive Surgery

Professor Ioannis Pallikaris, MD, PhD, Vardinoyannion Eye Institute of Crete, President of the University of Crete, Inventor of the LASIK and Epi-LASIK Procedures

In 2003, we improved on the LASIK and PRK procedures with a new procedure called epi-LASIK, which eliminates the need to cut the cornea or use alcohol, respectively. Instead of a microkeratome, a unique instrument called an epikeratome is used to peel back the epithelium only, along a natural cleavage point (above Bowman’s layer and below the basement membrane) before the laser is used. After laser ablation, the thin epithelial sheet is laid back into place.

As the research which I summarize below has established, the short term viability of the cells of the epithelial sheet separated by epi-LASIK is far greater than when separation is done with alcohol. This is important because the epithelial sheet may act as a mechanical barrier between the ablated stroma and the tear film, aiding the corneal healing response. With epi-LASIK, the epithelium will still need to regenerate in three to four days, but the separated sheet provides protection to the healing surface for the first few days to enable better wound healing and better quality of vision.

Also, not cutting the cornea eliminates most of the complications previously associated with laser vision correction. There are no flap complications such as partial or buttonholed flaps, epithelial ingrowth, striae, interface infections, diffuse lamellar keratitis, etc. Not killing the epithelial cells immediately means less pain for the patient and a faster recovery time.

Our work on the epi-LASIK technology led to the development of a proprietary surgical system, the Centurion SES™ Epikeratome with EpiEdge™. The Centurion SES received clearance under 510(k) by the U.S. Food and Drug Administration in October 2003. The research that I and Vikentia J. Katsanevaki, MD, PhD, also of the Vardinoyannion Eye Institute of Crete, University of Crete, have conducted has contributed to a growing body of knowledge about epi-LASIK and Centurion SES.

In one histological study, we compared the effect of mechanical separation via epi-LASIK with alcohol-assisted excision on the histological ultrastructure of epithelial disks from corneas in 10 patients, and found that epi-LASIK did not affect the normal epithelial cell morphology and was less invasive to epithelial integrity. Transmission electron microscopy showed that when the epithelial sheets were separated via epi-LASIK, the lamina densa and lamina lucida were preserved and the hemidesmosomes had normal morphology along almost the entire length of the basement membrane. The basal epithelial cells of the separated epithelial disks showed minimal trauma and edema.

In contrast, specimens excised using 15% and 20% alcohol concentrations showed formation of cytoplasmic fragments of the basal epithelial cells, enlargement of the intercellular spaces, and extensive discontinuities in the basement membrane, which was excised at the level of the lamina lucida. The preservation of the basement membrane is important because it is believed to provide the stability and support that keeps the epithelium intact and preserves its physiological integrity (Azar DT, Ang RT, Lee J-B, et al. Laser subepithelial keratomileusis: electron microscopy and visual outcomes of flap photorefractive keratectomy. Curr Opin Ophthalmol 2001; 12:323-328).

In another study, to determine the viability of the separated epithelial sheet, we examined the epithelial sheets of three patients who underwent epi-LASIK for myopia. During the postoperative examination of these patients 24 hours after the procedure, the epithelial sheets were dislocated accidentally. The specimens were removed and the eyes healed, similar to conventional PRK.

The three sheets were stained and viewed using optical and transmission electron microscopy to determine viable versus degraded cells. In the first specimen, it was estimated that 87% of the cells were morphologically viable. The second and third specimens showed cell viabilities of 99% and 98%.

In our clinical study of 96 patients undergoing epi-LASIK, we examined self-reported post-operative pain scores, using a 5-point scale. Immediately post-op, patients reported a mean pain score of nearly 2.0, corresponding to “a burning feeling.” At two hours, the mean reported score was approximately 1.0 (“discomfort”). At eight hours, the mean score was less than 0.5, and at 24 hours, it was close to 0.0.

Another of our studies examined the incidence of haze from one to six months after epi-LASIK.  At one month, 10% reported mild haze, 38% had a trace of haze and 52% were clear. By six months, 92% were clear and 8% reported a trace of haze.

Burkhard Dick, M.D., Ph.D., director of refractive surgery at Johannes Gutenberg University, Mainz, Germany, reported 6-month results on 22 cases performed with the Centurion SES as part of a multi-center European trial. At six months, the average refraction went from -3.25 D preoperative, to -0.1 D, similar to results we have obtained. There was no loss of lines of best-corrected acuity, and 19 percent of the patients gained a line or more of best-corrected vision. The histopathological examination conducted by Dr. Dick also established that the epithelium was fully intact after separation.

In May 2004, Norwood Abbey acquired the world-wide rights to the medical devices and intellectual property associated with the epi-LASIK laser vision correction surgery, and markets the Centurion through its subsidiary Norwood EyeCare. I believe Norwood can really enhance the progress of epi-LASIK. They have already introduced a new 9.0mm suction ring size, allowing surgeons will be able to select either the 9.0mm or 10.0mm ring to suit the size of the eye, reducing the chance of involvement of epithelial stem cells at the limbus.

And, Norwood EyeCare has begun a 3-month U.S. Prospective study of post-operative comfort, visual recovery and wave-front guided custom ablation with Centurion SES. It will be especially exciting to see how the coupling of epi-LASIK and wave-front may impact visual outcomes. Marguerite McDonald is the principal investigator and medical monitor for the study. Daniel Durrie and Lee Shahinian are clinical investigators.

The refractive community has already enthusiastically accepted epi-LASIK. Data from the U.S. Prospective study, and eventually, comparative trials of epi-LASIK with other vision correction approaches, will allow us to further evaluate epi-LASIK as a strong alternative for photorefractive correction.

Dr. Pallikaris is a consultant to Norwood EyeCare and a foundation member of its Medical and Scientific Advisory Board.

Devices to perform epi-LASIK are also available from VisiJet/Gebauer, Moria, and AMO.

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Sandy T. Feldman, MD

Wavefront Guided LASIK with Zyoptix 3.1 System for the Correction of Myopia and Compound Myoptic Astigmatism with 1 Year Follow Up: Clinical Outcome and Change in Higher Order Aberrations

Kohnen T, Buhren J, Kuhne C, Mirshahi A, Ophthalmology 2004; 111: 2175-2185.

Purpose:
To report the one year effectiveness and change in aberrations after wavefront guided LASIK for myopia and myopic astigmatism using the Zyoptix system.

Methods:
A prospective, nonrandomized center trial was used to evaluate the safety and efficacy of Zyoptix wavefront guided laser. Subjects had mean myopic of -5.22D [range -0.25 to -9.00D] and astigmatism range 0 to -3.25 D. A total of 97 eyes of 51 patients were included in this study.

Results:
One year postoperatively, the mean % of eyes achieving 20/20, 20/40 uncorrected acuity was 83%, 98%. The % of eyes achieving refractions within 05 D, 1.0 D of emmetropia was 77%, 95% respectively. 40 eyes experienced a gain of best corrected spectacle acuity of one line, five eyes experienced a gain of two lines. Primary spherical aberration increased as did the total higher order aberrations, root mean square. A reduction of HOA was observed in 45.5% of eyes, 3mm zone.

Conclusion:
Wavefront guided LASIK using the Zyoptix 3.1 is safe and effective treatment of myopia and myopic astigmatism. A reduction of HOA occurred in only half of the eyes.

Comments:
This paper illustrates the safety and efficacy of wavefront guided LASIK for myopia and astigmatism with the Zyoptix system. While wavefront guided LASIK has not yet achieved the perfection, a reduction of HOA in about half of the eyes is still an advance that wavefront guided LASIK achieves.

Predicting Time to Refractive Stability After Discontinuation of Rigid Contact Lens Wear Before Refractive Surgery

Tsai PS, Dowidar A, Naseri A, McLeod SD. J Cataract Refract Surg 2004: 30: 2290-5.

Purpose:
To determine whether 3 weeks of rigid lenses discontinuation is enough time to achieve refractive stability.

Methods:
The authors performed a retrospective chart review of patients interested in refractive surgery from 1999-2001. Patients were examined after discontinuation of rigid lenses for 3 weeks and in 3 week intervals until a stable refraction was achieved. Stability was defined as within 0.25 D of sphere and cylinder with less than 25 degrees of axis change.

Results:
The authors show that refractive stability was achieved within six weeks in 33/55 eyes and more than that in 24/55 eyes. What differed significantly was the number of years of contact lens wear between these two groups.

Conclusion:
This study shows that rigid contact lens wearers differ in the time needed to achieve stability and that long term RGP wearers will likely require more than three weeks to achieve stability.

Comment:
This study confirms that RGP lens wearers differ in the time needed to achieve stability following discontinuation of lens use and that the significant difference was observed between 21.59 years versus 26.06 years of use.

Complications Associated with Anterior Basement Membrane Dystrophy After Laser in Situ Keratomileusis

Rezende R, Uchoa U, Cohen EJ, Laibson PR, Rapuano CJ. J Cataract Refract Surg 2004; 30: 2328-2331.

Purpose:
To evaluate the effect of anterior basement membrane dystrophy [ABMD] on complications of LASIK.

Methods:
This retrospective study evaluated records of 35 eyes of 18 patients who presented with ABMD after LASIK. Excluded were the records from patients with a history of trauma.

Results:
Epithelial ingrowth requiring treatment occurred in 13 eyes [37.1%]. 77.9% percent of patients were evaluated because of a visual complaint while 22.1% of eyes had no visual complaint but recurrent corneal erosions. Irregular astigmatism was detected in 45.7% of eyes.

Conclusions:
This study documents that patients with ABMD had visual complaints and/or recurrent erosions after LASIK.

Comments:
This study details the side effects that one encounters following LASIK in eyes with ABMD. ABMD should be one of the factors that surgeons assess prior to performing LASIK. These patients may do better with surface procedures, which treat the disease as well refractive error.

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Vikentia Katsanevaki, MD, PhD

Is latent herpetic infection a contraindication for excimer laser correction of ametropias?

An area of concern for ophthalmologists and patients having an excimer laser photoablative procedure is whether latent herpetic infection will reactivate and cause keratitis in the operative eyes after the treatment. Although surgical procedures involving the excimer laser have not been conclusively proven to act as a stimulus for the reactivation of latent herpes simplex virus (HSV-1) in humans, it is a reasonable concern since ultraviolet exposure may initiate dendritic eruption. The excimer laser, which uses ultraviolet radiation, may provide such a trigger.

This concern is confirmed by sporadic case reports in the literature: Several investigators report herpetic keratitis after PRK and PTK, as well as after LASIK. In some cases, the treatment had detrimental effect on vision: in a reported case of phototherapeutic keratectomy for treatment of a herpetic scar, the operative eye was complicated with stromal infiltration, which progressed to desmetocele and corneal perforation.

Herpetic reactivation; however, is not confirmed by all the studies: in a reported series the recurrence after photoablation did not occur more frequently than prior to ablation. Additionally, the reactivation is often reported several months after the treatment. Most probably, these late recurrences may be related to the topical corticosteroid therapy rather than to laser exposure itself.

Another concern about treatment of eyes with prior herpetic ocular infection is the shedding of virus with the photoablation resulting from either laser exposure or by mechanical irritation. Moreover, some evidence suggests that HSV may be spread in the laser plume. Although these studies do not demonstrate evidence of spreading in the clinical setting, it does raise concerns for the surgeon, the staff and other patients.

Antiviral prophylaxis with oral acyclovir has proved successful in the management of recurrent genital, orolabial, and ocular herpetic disease. The success of antiviral prophylaxis with acyclovir requires adequate oral doses to achieve the necessary therapeutic serum levels.

Recently, valacyclovir, the prodrug of acyclovir, has been introduced for patient use offering the advantage of greater serum concentrations of acyclovir with a smaller oral dose.

A recent study has demonstrated that in the rabbit model the systemic administration of valacyclovir reduces the number of HSV-1 positive eyes and the extent of HSV-1 ocular shedding after LASIK. The clinical implications of this study suggest that patients with a history of recurrent ocular herpes may be able to safely have LASIK with less risk of a recurrent herpetic episode, while on valacyclovir antiviral prophylaxis.

In summary, chemioprophylaxis seems a reasonable precaution for excimer laser treatment in patients with known history of herpetic keratitis. This prophylaxis seems to minimize the risks of treatment in this patient population. However the dosage, route of administration and duration of therapy is not yet clear; anecdotally, different surgeons advocate therapy starting one day to two weeks before the laser treatment and up to a couple of weeks after LASIK. Controlled clinical trials are to establish the true value of antiviral prophylactic medical treatment in humans, the appropriate treatment protocols and finally elucidate the treatment risk/benefit ratio of LASIK in those patients. For the time being, the suitability of those patients as LASIK candidates is not well established and they should be counseled appropriately.

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Our readers are advised to check the labeling regarding their particular laser platform. For instance, the VISX S4 laser lists a history of herpes simplex keratitis under "warnings" (but not under "contraindications").