movement occurs during the treatment procedure. Advanced eye trackers must be able to detect both types of cyclotorsion movements.

Static cyclotorsion detection is performed by comparing pre-operative topography or limbal features when the patient is upright with the topography, iris or limbal features when the patient is supine. Dynamic cyclotorsion tracking is performed by tracking the iris or limbal features during the treatment process. Advanced eye trackers, for example in the Amaris laser platform (Schwind Eye-tech), are able to perform both static and dynamic cyclotorsion tracking.

5.3.1.6 Newer Ablation Profiles

Standard excimer laser ablations of the cornea are known to result in a more oblate cornea after myopic correction and a more prolate cornea after hyperopic correction. Hence, myopic laser refractive surgery induces a positive spherical aberration while hyperopic corrections induce a negative spherical aberration [33, 65, 69]. LASIK is also reported to induce more higherorder aberrations after surgery. Most excimer laser delivery systems today come with ablation profiles designed to reduce the induction of such aberrations. For example, aspheric ablation profiles in the Bausch and Lomb 217 Zyoptix 100 and the Zeiss MEL 80 are designed to maintain the prolate shape of the cornea after myopic laser treatment and reduce the induction of spherical aberrations. Customised or wavefrontguided ablation profiles are also available and the aim of these profiles is to correct pre-existing individual optical aberrations while correcting the refractive error during excimer laser refractive surgery.

Customised or wavefront-guided LASIK have been shown to be as safe and efficacious as conventional LASIK [1, 8, 17, 49]. Wavefront-guided LASIK has also been shown to reduce the amount of induced higher-order aberrations compared to conventional LASIK [24]. But other studies have shown that wave- front-guided LASIK only reduced higher-order aberrations in less than 50% of eyes [32]. Furthermore, the clinical benefits of performing wavefront-guided LASIK compared to conventional LASIK in a normal eye may not be apparent [53]. Some of the factors which may affect the results of customised or wave- front-guided LASIK include variables in the LASIK procedure, which includes accurate centration of the laser spot, creation and replacement of the corneal flap

and wound healing. Cyclotorsion in the supine position may also influence the spot position as related to the aberrometer data. The size of the laser spot diameter is also an important factor for the success of advanced ablation profile. The smaller the spot size the more precise is the ablation.

The design of the excimer laser platform is crucial to enable accurate corneal ablation based on the preoperative topography or aberrometry investigations. Advanced eye-tracker systems, for example in the Schwind Amaris, will allow accurate placement of the laser post, despite movements of the patient’s eye. A smaller laser spot size will also allow precise etching of the cornea stromal bed. Most conventional excimer lasers have a spot size of 0.8 mm or more. The new Schwind Amaris has a spot size of only 0.54 mm, allowing more precise ablations. Thus, we can observe that for successful results of newer laser ablations profiles, they must be accompanied by improvements in the design of the excimer laser platform.

5.3.2PRK and Advanced Surface Ablations (ASA)

There is a recent resurgence in the prevalence of photorefractive keratectomy (PRK) and other ASA techniques like Epi-LASIK which are performed due to increasing awareness of complications, in particular, corneal ectasia after LASIK and flap-related complications. However, haze formation in these techniques remains a concern and various methods of reducing the risk of haze can be observed in recent years. The following trends can be observed in PRK and ASA techniques:

1.Decrease thermal load on the cornea

2.Use of wound-healing modulators

3.Trend towards Epi-LASIK

5.3.2.1 Decrease Thermal Load on the Cornea

Haze is an important complication related to PRK and to a lesser extent, ASA techniques. Haze results in a reduction in transparency of the cornea and its exact aetiology is unknown. There is a higher incidence of haze after PRK in eyes with higher degrees of myopia [4, 5]. Studies have also shown that there is a greater

intensity of keratocyte proliferation and myofibroblast generation after PRK for high corrections, in contrast to PRK for low corrections [40, 66]. Another study showed that corneas undergoing PRK for higher corrections were subject to greater rises in temperature for longer periods of time [38]. Thus, the thermal load on the cornea during PRK may be a risk factor for haze formation. The magnitude of corneal wound repair and the development and duration of corneal haze also increased proportionally with increasing stromal photoablation depth (i.e. the volume of stromal tissue removal) [41]. It is possible that lasers which remove less stromal tissue will induce less haze for the same amount of refractive correction. Hence, newer excimer laser platforms like the SCHWIND Amaris which has a smaller spot size, dual fluence levels and a special thermal effect control may help to reduce the thermal load on the cornea during PRK and also during ASA techniques. This may help to reduce the incidence of haze in these procedures.

5.3.2.2 Use of Wound-Healing Modulators

Corneal wound healing is a complex cascading sequence of events. Multiple cytokines and growth factors, such as interleukin (IL)-1, tumour necrosis factor (TNF) α, bone morphogenic proteins 2 and 4 (BMB), epidermal growth factor (EGF) and plateletderived growth factor (PDGF), are released from the corneal epithelium and epithelial basement membrane after epithelial injury [47, 67]. In the event of impaired epithelial mechanical barrier function associated with this injury, for example in PRK, these mediators of cellular responses are able to reach the stroma and bind to their respective receptors to the keratocyte cells, where they trigger a variety of biological responses. One of the biological responses includes the generation of myofibroblasts, presumably derived from keratocytes, under the influence of transforming growth factor (TGF)-β [70]. An important characteristic of myofibroblasts is reduced corneal transparency relative to keratocytes. Studies have showed greater intensity of myofibroblast generation after PRK corrections, in contrast to PRK for low myopia. However, the exact role of myofibroblast generation in haze formation remains unclear. But modulating the wound response may help to reduce the risk of haze formation.

Mitomycin C (MMC) has been showed to reduce scar formation in rabbits after PRK [58, 68]. Mitomycin

C induces apoptosis of keratocytes and myofibroblasts, but the predominant effect in inhibiting or treating haze appears to be at the level of blocked replication of keratocytes or other progenitor cells of myofibroblasts [48]. In a study by Bedei et al., the application of MMC 0.02% solution immediately after PRK produced lower haze rates and had better predictability and improved efficacy 1 year after treatment [10]. Other studies also showed reduced incidence and severity of haze after PRK with the application of MMC intraoperatively [36, 46]. In our centre, we routinely use MMC 0.02% for PRK with ablations of greater than 50 mm.

Other wound modulators are also hypothesised to reduce haze formation. Several wound modulators have been studied and have shown promise in reducing haze formation. Anti-TGF-β was shown to reduce keratocyte activation and transformation and inhibited stromal fibrosis, leading to a reduction in early light reflectivity as well as to a more rapid decline in rabbits after PRK. Anti-TGF-β treatment may be useful in reducing post-PRK corneal haze development in patients by inhibiting the recruitment of highly reflective, activated keratocytes, inhibiting myofibroblast transformation and reducing stromal fibrosis [42]. Urokinase-type plasminogen activator has been shown to prevent haze after photorefractive keratectomy in rabbits in one study [19]. Another study showed that cytochrome c peroxidase significantly accelerates epithelial healing after PRK [56]. However, further studies are needed to confirm if cytochrome c peroxidase is able to prevent corneal haze.

While many of these new wound modulators have been shown to be effective in reducing haze after PRK in animals. More studies will be needed to confirm if they will be effective in humans.

5.3.2.3 Trend Towards EPI-LASIK

The theoretical advantage of advanced surface ablation procedures such as laser epithelial keratomileusis (LASEK) and Epi-LASIK is that these procedures preserve the epithelial button which is repositioned over the laser-ablated corneal surface. This epithelial sheet is thought to act as a natural contact lens that decreases post-operative pain and haze formation. The intact corneal epithelium may play an important part curbing sub-epithelial haze and differentiation of myofibroblasts in corneal wound healing [45]. Epi-LASIK uses specific microkeratome with a blunt oscillating blade