Laser refractive surgery

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Laser subepithelial keratomileusis (Lasek) is a refractive procedure that utilises aspects of both laser in situ keratomileusis (Lasik) and photorefractive keratectomy (PRK) which was first performed in 1996 by Dimitri Azar at the Massachusetts Eye and Ear Infirmary, Boston.1

Alternative terms for Lasek exist such as epithelial flap photorefractive keratectomy,2 subepithelial photorefractive keratectomy,3 laser-assisted subepithelial keratectomy,4 excimer laser subepithelial ablation5 and Epi-Lasek.6 A dilute alcohol solution is used to loosen the epithelial adhesions with the underlying stroma. This then allows the loosened epithelium to be brushed to the side for laser ablation to be applied to the stroma and the epithelial sheet is then returned.

Potential complications

Intraoperative
Alcohol leakage

The dilute alcohol solution is placed within a Lasek well during the procedure and hence there is the potential of leakage to the surrounding limbal and conjunctival regions. Toxicity to the limbal region may cause damage to epithelial stem cells which could delay wound healing and conjunctival epithelial cell damage will increase postoperative inflammation.7 The patient may notice immediate pain and increased postoperative pain. Lee et al report a 3.5 per cent incidence of alcohol leakage, significant problems secondary to leakage are extremely rare.8 Management is in the form of irrigation with balanced salt solution (BSS) followed by drying with a Merocel sponge. In order to prevent this from occurring, the Lasek well is held steady with slight pressure and the patient is advised to limit eye and head movement.

Incomplete flap

An incomplete flap may occur when there is a strongly adherent epithelium which has been reported to be more common in young men, postmenopausal women and long term contact lens wearers.9 In this case, a longer alcohol exposure time is necessary. If a complete flap creation is not possible the procedure may be converted to a photorefractive keratectomy (PRK) procedure. O'Brart et al report an incidence of adherent and incomplete flaps in 4 per cent of high myopes10 and 6 per cent in hyperopes.11 Other issues related to epithelial flaps include production of free epithelial flaps, dissolution, fragments, folds and flap slippage. These types of complications, however, have not been routinely demonstrated to result in any significant complication unlike similar issues occurring with the Lasik stromal flap.12

Early postoperative complications (within a week)

Ocular pain

One of the biggest disadvantages of Lasek is the unpredictability in postoperative pain. Typical pain management is in the form oral analgesics, dilute topical anaesthetic, artificial tears and non-steroidal anti-inflammatory drugs. Some practitioners prescribe concentrated topical anaesthetic with or without a dilute preparation for emergency/restricted use.

Increased pain is reported following Lasek compared to standard Lasik, however, with the advent of femtosecond instead of mechanical flap creation this scenario has been altered with early postoperative pain a common phenomena post femtosecond laser. Lasek has been reported to produce less pain than PRK,13 however Leccisotti reported no difference in postoperative pain between Lasek and PRK.14

Delayed epithelialisation

The normal epithelial closure time is usually within four days and the bandage contact lens is usually removed following epithelial closure. In the case of delayed epithelial closure, patients are at an increased risk of haze development, infection and melt. These patients may have predisposing factors such as dry eye syndrome, connective tissue disorders, recurrent corneal erosions, drug allergy and limbal stem cell deficiency.7 Hence careful preoperative evaluation is mandatory. In addition, careful attention to postoperative topical medication by avoidance of harmful preservatives in multidose drops and avoiding overuse of topical anaesthetics can minimise any problems by improving re-epithelialisation rates.

Epithelial closure may serve as an indirect sign to the end of pain perception and return of visual function after Lasek. Visual function may be variable due to epithelial cell death and proliferation during this period. However, epithelial closure times are variable - Kornilovsky reports four days,15 Camellin 4-5 days,16 Lee 3.68±0.69 days8 and Claringbold up to two weeks.9

Infection

The risk of infection following Lasek is very low and in the rare event of this, the process starts at the epithelial level, as opposed to the intrastromal level as seen in Lasik, and will therefore, theoretically be easier to manage.12,17 Prompt investigation and appropriate antimicrobial treatment is imperative as this is a sight-threatening complication. Sterile infiltrates can be treated with an increased frequency of topical steroid. However in the case of stromal infiltration and evidence of an overlying epithelial defect, the infiltrates need to be treated as infectious until otherwise proven.

To our knowledge there have only been two reports of bacterial keratitis following Lasek in the literature. Laplace et al published the first case with corneal scraping growing Staphylococcus haemolyticus ß-lactamase positive which was resistant to fluoroquinolones and sensitive to the topical drops prescribed before antibiogram.18

After one week of treatment, stromal infiltration and erosion improved and the best corrected visual acuity was 20/20. Rodriquez et al reported the second case of a patient presenting four weeks after Lasek with symptoms of foreign body sensation and redness in the left eye.19 Gram stain on the day of presentation showed branching filamentous gram-positive rods and cultures subsequently grew Mycobacterium chelonae.

The risk for infection is theoretically less after Lasek than after PRK due to the protective nature of the epithelial flap. Figures 1 and 2 show cases, following PRK of Staphylococcus aureus (non methicillin-resistant) bacterial keratitis and infectious crystalline keratopathy respectively.

A previous history of herpes simplex keratitis is a contraindication to keratorefractive surgery. Treatment for patients developing herpes simplex keratitis is acyclovir.

Contact lens intolerance

Intolerance to the bandage contact lens is an infrequent occurrence. Lee et al. reported contact lens intolerance following Lasek in five eyes from 84 eyes undergoing surgery (incidence 5.9 per cent). All cases had folds of Desçemet's membrane and all were switched to pressure patch. Four of these eyes were in patients over 40 years old, and one eye was in a 35-year-old patient. The reason for the intolerance was not certain and hence they concluded that they do not recommend the Lasek procedure in patients over 40 years of age.8 Few other groups would adhere to this age restriction.

Late postoperative complications (exceeding a week)

Corticosteroid-induced glaucoma

Corticosteroid eye drops are used in a variable fashion postoperatively to minimise the risk of haze formation. Despite randomised clinical studies indicating that steroids have no effect on corneal haze or visual performance after PRK,20 after Lasek, some groups use prolonged corticosteroid drops with the aim to regularise the healing process. Typically fluorometholone 0.1 per cent (FML) is tapered over a four-week period (four times per day for one week three times per day for one week twice per day for one week and once per day for one week) following Lasek. Corticosteroid-induced glaucoma and ocular hypertension occurred in 2.7 per cent of 1,590 eyes following PRK when FML was used for four to six months.21 This type of long-term usage has recently gone out of favour. If ocular hypertension occurs, the corticosteroid should be terminated and topical anti-glaucomatous medications prescribed until the intraocular pressure has normalised.7 It should also be remembered that following corneal refractive surgery, intraocular pressure will be underestimated due to the reduced corneal thickness.

Dry eye

Patients with pre-existing dry eye are not good candidates for keratorefractive surgery. Many patients present for refractive surgery due to contact lens intolerance caused by pre-existing dry eye. Non-severe dry eye may be treated appropriately and if acceptable resolution occurs with no systemic associations present, Lasek may be preformed. With Lasek, nerve dissection does not occur with a microkeratome, therefore reducing the risk of dry eye syndrome developing postoperatively. Ocular irritative symptoms may exist for up to six weeks postoperatively but thereafter usually subside.12 Irritation may indicate recurrent corneal erosions - patients typically report discomfort/pain upon waking. Lubricating ointment may help resolve this issue with instillation at bedtime. With continued persistence, surgical invention may be necessary in the form of peripheral anterior stromal punctures or epithelial debridement.7In patients with pre-existing recurrent corneal erosions, Lasek may not only correct the refractive error but is also often a cure recurrent erosions.1,9

Haze

The healing process, in particular epithelial healing, plays a significant role in haze production and visual recovery.22 Epithelial migration is the first stage in the wound healing process following Lasek (and PRK). This is followed by epithelial hyperplasia and stromal regeneration. Keratocyte apoptosis and myofibroblast transformation can be activated by cytokine induction which leads to keratocyte replenishment of the anterior stroma. Lee et al found that the amount of the tear film transforming factor-ß1 (TGF-ß1) released in the early postoperative days was significantly less following Lasek in comparison to PRK. They also found significantly less haze with Lasek and concluded that this may be due to the decreased release of TGF-ß1. No differences were noted at three and six months.23

Haze is associated with increasing depths of excimer laser ablation and small optical zone treatments.24 It is thought that the Lasek epithelium reduces haze in comparison to PRK however conflicting study results have been reported. Some studies have demonstrated no differences25 between Lasek and PRK while others have indicated reduced haze following Lasek.14

The use of mitomycin C (MMC) to modify the wound healing process is controversial. MMC is an alkylating antibiotic derived from Streptomyces caespitosus, with antifibroblastic properties. It inhibits protein synthesis by blocking DNA and RNA replication.26 MMC is also used as an antimetabolite in ophthalmology. It is sometimes used during topical chemotherapy for corneal and conjunctival tumours, pterygium surgery to prevent recurrence, glaucoma surgery to inhibit fibrosis and excimer laser surface ablation to prevent haze and regression. When used in surface treatment, it causes keratocyte apoptosis and inhibits proliferation, hence preventing haze.27-34 The American Academy of Ophthalmology recommends its use with ablations deeper than 50-75µm or prescriptions greater than -4.00 to -6.00 dioptres35 however, this will depend on climatic conditions. MMC is more commonly used to avoid haze in cases of surface retreatment, surface treatment following radial keratotomy, keratoplasty or button-holed Lasik flaps. The use of MMC requires an adjustment in the planned treatment and if this is not performed, overcorrection will result. Corneal toxicity has been observed with MMC concentration and exposure times much greater than those currently used after surface ablation. Other reported side effects are stromal melting and endothelial damage.36-40 Several studies have demonstrated epithelial, stromal and endothelial safety when the dilution is 0.02 per cent (0.2 mg/ml) or less, with an exposure time of one minute or less.34,41-44 However, little is known about the long-term safety of MMC. Patients who develop haze within the first few months following Lasek often respond well to topical corticosteroid but it is suggested that this may simply delay the onset of haze.20 Figure 3 illustrates the development of corneal haze in rabbit eyes three weeks after keratorefractive surgery.45

Over-correction/under-correction

An over-correction or under-correction of the refractive error usually manifests itself within the first few weeks or months after surgery. Rouweyha et al report over-correction as their most frequent Lasek complication with 5.2 per cent requiring retreatment with a mean over-correction of -1.00D. Myopic regression of approximately 2D occurred for unknown reasons in 8 per cent of high myopic eyes within six months. This was associated with haze formation causing decreased vision and required retreatment.17

Ectasia

Lasek may avoid several of the inherent complications including corneal ectasia in comparison to Lasik. This is partly due to the fact that with Lasik, there is a deep lamellar incision made which will always carry the risk of future iatrogenic ectasia, more so than a surface procedure such as Lasek. Despite this, keratoconus in all its forms should be regarded as a relative, if not an absolute contraindication when considering Lasek. Although a rare occurrence, there have been reports of iatrogenic ectasia following PRK and hence patients should be appropriately examined prior to surgery.46-48 There are a number of possible treatment options for patients that develop ectasia after Lasek such as contact lenses, intracorneal ring segments, corneal cross-linking, lamellar grafting and penetrating keratoplasty.49

Conclusion

Lasek has the purported advantages of less pain, quicker visual recovery and a lower incidence of haze formation in comparison to PRK. It has the advantages over Lasik of reduced complication rates as it avoids a lamellar cut flap creation. Despite this, as with any surgical procedure it is not complication free itself.

Many refractive surgery investigators believe that Lasek may become the preferred procedure for wavefront-guided treatments. The advantage of these complex ablations may not be negated by variable induced aberrations due to a microkeratome-created flap. However, with Lasek there is a greater wound healing response which may also hinder the correction of individual aberrations.

Further research in this area, in particular into the histopathology and biochemistry of corneal wound healing, epithelial and stromal interaction following ablation and improved flap creation may aid customisation. ?

References

1. Azar DT, Ang RT, Lee JB, et al. Laser subepithelial keratomileusis: electron microscopy and visual outcomes of flap photorefractive keratectomy. Curr Opin Ophthalmol, 2001 12(4): 323-328.
2. Shah S, Sebai Sarhan AR, Doyle SJ, et al. The epithelial flap for photorefractive keratectomy. Br J Ophthalmol, 2001 85(4):393-396.
3. Kornilovsky IM. Clinical results after subepithelial photorefractive keratectomy (Lasek). J Refract Surg, 2001 17:S222-3.
4. Shahinian L. Laser-assisted subepithelial keratectomy for low to high myopia and astigmatism. J Cataract Refract Surg, 2002 28:1334-1342.
5. Lohmann CP, Winkler Von Mohrenfels C, Gabler B, et al. [Excimer laser subepithelial ablation (ELSA) or laser epithelial keratomileusis (Lasek) - a new kerato-refractive procedure for myopia. Surgical technique and first clinical results on 24 eyes and 3 months follow-up]. Klin Monatsbl Augenheilkd, 2002 219:26-32.
6. Anderson NJ, Beran RF, Schneider TL. Epi-Lasek for the correction of myopia and myopic astigmatism. J Cataract Refract Surg, 2002 28:1343-1347.
7. O'Brart DPS. Lasek complications. In: Ali