Ординатура / Офтальмология / Английские материалы / Ocular Periphery and Disorders_Dartt, Bex, Amore_2011

studies based on corneal topography showed that while defocus or astigmatism are generally successfully corrected, refractive surgery (RK, PRK, and LASIK) increased the amount of corneal aberrations. In addition, the distribution of aberrations changed from the third-order dominance found in normal subjects, to fourth-order dominance. This increase in corneal aberrations correlates well with the decrease found in contrast sensitivity. Seiler and colleagues, in standard myopic PRK (15 eyes, mean preoperative spherical error ¼ 4.8 D), and Moreno–Barriuso and colleagues, in standard myopic LASIK (22 eyes, mean preoperative spherical error ¼ 6.5 D), measured, for the first time, the changes in the total aberration pattern induced by either type of surgery. Both studies found a significant increase in thirdand higher-order aberrations (by a factor of 4.2 and 1.9 in the root mean square (RMS), respectively). The larger increase occurred for spherical and third-order aberrations. The changes of total spherical aberrations are not fully accounted by changes in the anterior corneal surface. In all eyes, total spherical aberration increased slightly less than corneal aberrations, likely due to significant changes in the posterior corneal shape (shifting toward more negative values of spherical aberration). The increase in the total spherical aberration is highly correlated to the amount of spherical error corrected, and it is associated with an increase in corneal asphericity.

Changes of corneal and total aberrations with LASIK surgery for hyperopia are even higher than those for LASIK surgery for myopia. While spherical aberration becomes more positive following myopic LASIK, it shifts toward negative values following hyperopic LASIK. For the same absolute amount of correction, the absolute increase of corneal spherical aberration is larger with hyperopic LASIK. Figure 3 shows wave preand postoperative high-order

aberration patterns in patients that had undergone myopic LASIK and hyperopic LASIK. Figure 4 compares the induced aberration (total and corneal) following myopic and hyperopic LASIK, respectively.

Modulation-transfer functions (MTFs) can be computed from the measured wave aberrations, and the optical changes can be compared to the visual changes (measured in terms of contrast-sensitivity function (CSF)). Marcos and colleagues found that the decrease in the MTF

Hyperopic LASIK Corneal aberration

Figure 4 Induced spherical aberration vs. spherical correction (positive for hyperopia and negative for myopia). Corneal spherical aberration increases at a rate of 0.17 mm D 1 in myopic LASIK and –0.23 mm D 1 in hyperopic LASIK. Total spherical aberration increases at a rate of 0.09 mm D 1 in myopic LASIK and –0.06 mm D 1 in hyperopic LASIK. The inset

depicts the fourth-order spherical-aberration Zernike term. From Llorente, L., Barbero, B., Merayo, J., and Marcos, S. (2004). Changes in corneal and total aberrations induced by LASIK surgery for hyperopia. Journal of Refractive Surgery 20: 203–216.

(between 3 and 18 cycles per degree (c/deg)) was 1.38 – similar to the decrease in the CSF, by a factor of 1.51 (in the same spatial frequency range) – on average in a group of 22 eyes that had undergone LASIK surgery for myopia. This indicates that the increase in optical aberrations plays a major role in the decrease of visual quality following LASIK. Figure 5 shows preand postoperative MTF and CSF, for 3-mm pupils, and the pre/post contrast ratio as a function of spatial frequency.

Causes for Spherical Aberration Increase Following Corneal Refractive Surgery

The causes for the increase of spherical aberration (and corneal asphericity) are still not well understood. Computer simulations of the postoperative corneal shape following subtraction of the standard ablation pattern (Munnerlyn equation) performed on real preoperative corneal elevation maps do not show the increased corneal asphericity found clinically. A parabolic approximation of this equation induces a slight increase of corneal asphericity, but much less than is found experimentally. It is likely that much of the discrepancy is due to the fact that

the energy is not properly transferred onto the cornea, due to changes in laser efficiency across the corneal surface. Several authors have derived theoretical expressions (based on the Beer–Lambert law and Fresnel equations) to account for the laser-energy losses from the center to the periphery of the cornea. Figure 6 depicts average results on 13 patients of postoperative corneal asphericities following computer simulation of the Munnerlyn ablation pattern (and its parabolic approximation), directly or considering laser-efficiency changes across the cornea (based on the equations proposed by Jime´nez and colleagues), in comparison with average preoperative asphericities and real postoperative asphericities in the same eyes.

An interesting approach to the understanding of the induction of spherical aberration is the ablation of plastic spherical surfaces, which are subject to geometrical effects but not biomechanical response. Ablation of poly(methyl methacrylate) (PMMA)-model eyes produces an increase in spherical aberration, similar to the increase found in real corneas. In addition, a comparison of the ablation profile of flat and spherical surfaces allows direct estimation of the laser-efficiency losses on PMMA, which can be extrapolated to corneal tissue, without relying on the exact knowledge of the ablation profile programmed into the laser system, and

Postoperative corneal asphericity

−1

Spherical correction (D)

without the approximation of the theoretical approaches. Figure 6 shows estimated postoperative corneal asphericities following direct subtraction of the ablation profile obtained experimentally from profilometry of flat plastic surfaces and also considering the experimental efficiency factor.

Corneal Biomechanical Effects in

Refractive Surgery

Although not fully understood, it seems clear that the biomechanical properties of the cornea change following refractive surgery. RK relied fully on the mechanical relaxation of the cornea following incisions. During PRK, LASIK, or any other procedure involving central ablation, corneal lamellae are severed. In a simple elastic shell model, if considered alone, this would result in corneal steepening. However, it has been suggested that a lamellar tension relaxation in the peripheral stroma occurs which produces a compression of the anterior cornea and central flattening. The elastic modulus of the residual stromal bed and the corneal shear strength likely change following surgery, as the cohesive forces among lamellae, stromal swelling pressure, are affected by the procedure. These effects have a potential relevance in the pathogenesis of ectasia, characterized by a progressive thinning and a progressive central and inferior steepening of the cornea, affecting 0.3% of the LASIK patients, although a careful identification of patients with preexisting corneal pathology

(keratoconus) and reducing the risk of mechanical instability by leaving a minimal residual stromal thickness (of 300 mm or more) has proved to reduce the occurrence of corneal ectasia greatly. The change in the dynamical response of the cornea, inherent to its biomechanical properties, also affects the measurement of intraocular pressure with standard tonometers, which assume normalized values of corneal elasticity.

Other Side Effects and Complications of

PRK and LASIK

Apart from the indicated increased aberrations (resulting in halos and ghost images), haze and loss of best-corrected contrast sensitivity, other potential complications may occur during or following surgery. The most common side effect from refractive surgery is dry eye (occurring in 36% of patients), diffuse lamellar keratitis (2.3%), flap complications including slipped flap, debris or growth under flap and flap striae (0.244%), infection (0.4%), epithelial ingrowth (0.1%), glare, and light sensitivity.

Safety, Efficacy, and Satisfaction of

LASIK

An average of 700 000 patients in the US undergo LASIK annually. To date, more than 28.3 million LASIK

procedures have been performed worldwide. Collectively, 7830 patients (representing 16 502 eyes) participated in clinical trials from 1993 to 2005. In April 2008, the Food and Drug Administration (FDA) reaffirmed the safety and efficacy of the LASIK procedure. Although the number of patient complaints has increased in the last few years, the postoperative visual outcomes have improved in the most recent studies. In FDA studies recruiting patients that had undergone surgery prior to 2000, 1.4% of patients lost two lines or more of best spectacle-corrected visual acuity (BSCVA) versus 0.6% in studies after 2000. Prior to 2000, 1.68% of patients with a preoperative BSCVA 20/20 or higher had a postoperative BSCVA 20/25 or higher, compared with 0.16% after 2000. The surveys determining patient satisfaction with LASIK have found most patients satisfied, with satisfaction ranging between 92% and 98%. A metaanalysis – dated March 2008, performed by the American Society of Cataract and Refractive Surgery over 3000 peer-reviewed articles published over the past 10 years in clinical journals from around the world, including 19 studies comprising 2200 patients – that looked directly at satisfaction, revealed a 95.4% patient satisfaction rate among LASIK patients worldwide.

Toward an Optimization of the Corneal

Refractive Surgery Procedure

Recent technological advances in refractive surgery include high-frequency eye-tracking, improved laser-delivery systems, and flap creation by femtosecond lasers. The availability of clinical aberrometers, and flying spot technology, led to the development of wave-front-guided ablation profiles – aiming not only at correcting defocus and astigmatism, but also the eye’s high-order aberrations. However, major efforts must still focus on preventing the induction of high-order aberrations (particularly spherical aberration) by the procedure, particularly as these are not necessarily inherent to ablation algorithm (despite its simplicity, the standard Munnerlyn algorithm does not induce spherical aberration). Approaches range from theoretical correction of the ablation profile to empirical adjustment of the attempted corneal asphericity. Undoubtedly, a proper characterization of the ablation algorithm, and a calibration of the ablation pattern created by the laser is critical to achieve the desired postoperative corneal shape. Plastic models (in PMMA, and, more recently, a semi-rigid contact lens material – Filofocon A) have been proposed as calibration models for refractive surgery, and their ablation properties

have been thoroughly studied. Figure 7 shows an example of the ablation profile recorded on a plastic material and measured using noncontact profilometry. To date, empirical adjustments of the ablation normogram have – based on population average data – compensated for deviations from ametropia systematically found following surgery. However, customized corrections require a deeper knowledge of ablation, physical effects of the role of corneal hydration, and of the contribution of corneal biomechanical effects and their inter-individual variations on the refractive and highorder aberration outcomes. A fine control of the ablation profile and the biomechanical response will likely expand the range of applications of refractive surgery into presbyopic treatments. As an emerging technology, corneal collagen cross-linking is starting to be applied following refractive surgery as a way to control corneal ectasia by increasing corneal stiffness.

Other technologies further in the track include solidestate ultraviolet (UV) lasers and femtosecond lasers. Diode-pumbed UV laser, using a solide-state laser crystal as the laser medium and nonlinear crystals for frequency conversion instead of the high-voltage gas discharge of excimer lasers, are a safer, more stable, compact, and less expensive alternative to gas-operated excimer lasers. On the other hand, femtosecond lasers use ultrashort pulses (as opposed to pulse durations in the range of nanosecond or picosecond in excimer lasers) which allow laser–tissue interactions characterized by significantly smaller and more deterministic photodisruptive energy thresholds, as well as reduced shock waves and smaller cavitation bubbles, which result in smoother surface quality. Lamellar procedures (keratomileusis) as well as lenticule removal are envisaged with this procedure.

See also: Cornea Overview; Corneal Nerves: Anatomy; Hyperopia; Myopia; Refractive Surgery and Inlays.

Dorronsoro, C., Cano, D., Merayo, J., and Marcos, S. (2006). Experiments on PMMA models to predict the impact of corneal refractive surgery on corneal shape. Optics Express 14: 6142–6156.

Dorronsoro, C., Siegel, J., Remon, L., and Marcos, S. (2008). Suitability of Filofocon A and PMMA for experimental models in excimer laser ablation refractive surgery. Optics Express 16: 20955–20967.

Dupps, W. and Wilson, S. (2006). Biomechanics and wound healing in the cornea. Experimental Eye Research 83: 709–720.

Jime´nez, J., Anera, R., Jime´nez del Barco, L., and Hita, E. (2002). Effect on laser-ablation algorithms of reflection losses and nonnormal incidence on the anterior cornea. Applied Physics Letters 81(8): 1521–1523.

Krueger, R., Applegate, R. A., and MacRae, S. (eds.) (2004). Wavefront Customized Visual Correction: The Quest for Super Vision II.

Thorofare, NJ: Slack.

Llorente, L., Barbero, B., Merayo, J., and Marcos, S. (2004). Changes in corneal and total aberrations induced by LASIK surgery for hyperopia. Journal of Refractive Surgery 20: 203–216.

Marcos, S. (2001). Aberrations and visual performance following standard laser vision correction. Journal of Refractive Surgery 17: 596–601.

Marcos, S., Barbero, B., Llorente, L., and Merayo-Lloves, J. (2001). Optical response to LASIK for myopia from total and corneal aberrations. Investigative Ophthalmology and Visual Science 42: 3349–3356.

Marcos, S., Cano, D., and Barbero, S. (2003). The increase of corneal asphericity after standard myopic LASIK surgery is not inherent to the Munnerlyn algorithm. Journal of Refractive Surgery 19: 592–596.

Merayo-Lloves, J., Yan˜ez, B., Mayo, A., Martı´n, R., and Pastor, J. C. (2001). Experimental model of corneal haze. Journal of Refractive Surgery 17: 696–699.

Moreno-Barriuso, E., Merayo-Lloves, J., Marcos, S., et al. (2001). Ocular aberrations before and after myopic corneal refractive surgery: LASIK-induced changes measured with laser ray tracing.

Investigative Ophthalmology and Visual Science 42: 1396–1403. Mrochen, M., Krueger, R., Bueeler, M., and Seiler, T. (2002). Aberration-

sensing and wavefront-guided laser in situ keratomileusis: Management of decentered ablation. Journal of Refractive Surgery 18: 418–429.

Netto, M. V., Mohan, R. R., Ambro´sio, R., Jr., et al. (2005). Wound healing in the cornea: A review of refractive surgery complications and new prospects for therapy. Cornea 24: 509–522.

Pallikaris, I. G., Agarwal, S., and Agarwal, A. (2003). Refractive Surgery. Thorofare, NJ: Slack.

Seiler, T., Kaemmerer, M., Mierdel, P., and Krinke, H.-E. (2000). Ocular optical aberrations after photorefractive keratectomy for myopia and myopic astigmatism. Archive of Ophthalmology 118: 17–21.

Further Reading

Applegate, R. A., Hilmantel, G., and Howland, H. C. (1996). Corneal aberrations increase with the magnitude of radial keratotomy refractive correction. Optometry and Vision Science 73(9): 585–589.

Applegate, R. A. and Howland, H. C. (1997). Refractive surgery, optical aberrations, and visual perfomance. Journal of Refractive Surgery 13: 295–299.

Buratto, L. and Brint, S. F. (eds.) (2003). Custom LASIK: Surgical Techniques and Commplications. Thorofare, NJ: Slack.

Cano, D., Barbero, B., and Marcos, S. (2004). Comparison of real and computer-simulated outcomes of LASIK refractive surgery. Journal of the Optical Society of America A 21: 926–936.

Relevant Websites

http://www.geteyesmart.org – American Academy of Ophthalmology and Its Partners.

http://www.ascrs.org – American Society of Cataract and Refractive Surgery (ASCRS).

http://www.escrs.org – European Society of Cataract and Refractive Surgery.

http://www.aao.org/isrs – International Society of Refractive Surgery. http://www.fda.gov – US Food and Drug Administration. http://www.vision.csic.es – Visual Optics and Biophotonics Lab,

Instituto de Optica, CSIC.

Glossary

Astigmatism – A refractive defect in which vision is blurred due to the inability of the optics of the eye to focus a point object into a sharp, focused image on the retina due to an irregular or toric curvature of the cornea or lens.

Cycloplegic refraction – A measurement of the refractive state of the eye without the effects of accommodation. A cycloplegic drop is used to temporarily paralyze the accommodation muscle. Corneal ectasia – A serious complication involving a cone-like bulging of the cornea following its weakening during laser-assisted in situ keratomileusis (LASIK).

Diffuse lamellar keratitis – Noninfectious inflammatory complication of LASIK.

Form fruste keratoconus – An abortive form of bulging of the cornea.

Hyperopia – Refractive defect caused by an eye that is too short or a cornea that is too flat, so that images focus at a point behind the retina. It is also called farsightedness.

Intracorneal ring (ICR) – Small ring inserted into the periphery of the cornea to change its shape and correct nearsightedness.

Laser-assisted subepithelial keratectomy (LASEK) – A refractive surgery where only the corneal epithelia is cut to reshape the cornea.

Laser-assisted in situ keratomileusis (LASIK) –

A refractive surgery where the corneal epithelia and stroma is cut to reshape the cornea.

Manifest – Easily seen.

Myopia – Refractive defect of the eye where the light focuses in front of the retina rather than on the retina. It is also called nearsightedness.

Photorefractive keratectomy (PRK) – A refractive surgery where the corneal epithelia is removed to reshape the cornea.

Presbyopia – Reduced ability to see near objects caused by loss if the elasticity of the lens.

Radial keratotomy (RK) – Surgical procedure to correct myopia where radial incisions are made into the cornea at precise depths allowing the sides of the cornea to bulge out and flatten the central cornea.

Introduction

Corneal refractive surgery offers the patient the possibility of becoming independent of spectacles and/or contact lenses. The attainment of this treatment goal is of particular importance to individuals who are restricted in their professional and social life by their contact lens or spectacle intolerance. The developments and outcomes of various refractive surgery techniques have received increasing attention in the medical literature and public media. This phenomenon is mainly related to the numerous success stories and the dramatic changes achieved by correction of the refractive error and the resultant independence of spectacles and contact lenses.

Numerous corneal refractive surgery techniques are available for the correction of refractive errors, with the majority of treatments consisting of myopic and myopic– astigmatic corrections. The field of refractive surgery has greatly evolved since the commencement of excimer laser treatments and surgical implantations of corneal inlays. The techniques have been refined and are continually evolving to be more specifically directed toward the individual optical design. The optical system can differ greatly between individuals and depends on various factors, such as the amount of the refractive error and the degree of optical aberrations. Therefore, laser-ablation techniques have changed from the standard correction of the refractive error to personalized and optimized laser treatments and from broad-beam to scanning-spot or flying-spot devices.

This article presents an overview of the available corneal refractive procedures and their outcomes.

Radial Keratotomy

Prior to the popularity of excimer photoablative refractive surgery, the technique of radial keratotomy (RK) was among the most widely used surgical techniques for the correction of myopia. RK involves making deep radial incisions in the paracentral and peripheral anterior cornea using a diamond blade knife. The technique results in the flattening of the central corneal curvature and steepening of the peripheral area, which reduces the degree of myopia.

The number of RK incisions, diameter of the optic zone, and patient age determine the refractive outcome after RK. Incision direction was shown to be another predictor, with

the centripetal (vs. the centrifugal) incision decreasing myopia to a higher degree.

Although the treatment by RK initially resulted in satisfactory refractive results, it appeared not to be as predictable as current refractive surgery techniques. The Prospective Evaluation of Radial Keratotomy (PERK) study was a nine-center clinical trial which analyzed the long-term (10-year) effects and stability of myopic RK (with a range of 2.00 to 8.75 diopters (D)). They showed that 53% of eyes achieved an uncorrected visual acuity (UCVA) 20/20, and 85% of eyes achieved UCVA of 20/40. They also showed that 38% of eyes had a refractive error within 0.50 D and 60% 1.0 D of the intended correction.

A common and challenging side effect of RK was the development of secondary and progressive hyperopia. This hyperopic shift occurred in 43% of reported cases, with an additional incidence of 1–2% annually. A less common side effect following RK is the development of irregular astigmatism, which can be induced by the intersection of the incisions with the visual axis or by the eccentricity of the optical zone. Some other side effects are fluctuating vision and glare.

Apart from treating myopia, RK has also been used for the correction of astigmatism (also known as arcuate keratotomy), although the predictability of this technique is known to be slightly less than that for the correction of myopia. The procedure has been shown to be an effective and safe method for correcting moderate to severe naturally occurring astigmatism.

The popularity of RK has declined since the approval of the excimer laser in 1995, due to the superior outcomes of photorefractive keratectomy (PRK) and LASIK. However, keratotomy techniques (arcuate keratotomy and limbal relaxing incisions) are still used for the treatment of astigmatism in cataract surgery and in postsurgical patients.

Photorefractive Keratectomy

In the early 1990s, PRK was the main treatment for low-to-moderate myopia. This technique went through various developments, varying from laser systems, to treatment algorithms, to the choice of transition and ablation zones. The treatment involves the use of a far-ultraviolet (193-nm) argon fluoride excimer laser, which permanently removes the most anterior portion of the corneal stromal tissue in a very precise manner. The ablation occurs with minimal damage to the adjacent corneal tissue. Prior to the performance of the laser-ablation procedure, the corneal epithelium is removed – either manually with a blade or a rotating brush or after alcohol administration. Afterward, a bandage contact lens is applied on the treated corneal surface.

Short-term problems following PRK include discomfort in the first 24 h; a delay in visual recovery lasting 3–5 days during epithelial healing; and a loss of corneal transparency – also called haze – lasting weeks to months following the procedure. PRK ablations often show an immediate postoperative hyperopic shift, due to a thinner epithelium. The hyperopic shift is often compensated by a period of regression that stabilizes between 1 and 6 months. Refractive stability after PRK is generally achieved after 6 months to 1 year and is maintained for up to a period of 5 years.

Long-term studies on the outcome of PRK found no evidence of progressive time-dependent hyperopic shift or late regression, with trace haze in 4% after 12 years with no loss of best-corrected visual acuity (BCVA). In general, corneal haze was transient and decreases rapidly 1 year after treatment.

Laser-assisted in situ Keratomileusis

The technique of LASIK was first described in 1991. The surgical technique includes the creation of an epithelialstromal flap using a microkeratome. The flap is attached to the periphery of the cornea by a hinge of uncut tissue and has a diameter of 8–10 mm. When using the mechanical microkeratome, the thickness of the flap ranges between 130 mm (with the newest microkeratomes) and 180 mm (with the older microkeratomes). Subsequently the flap is peeled back and ablation of the corneal stroma is performed using an excimer laser. Following the photoablation, the flap is repositioned on the treated corneal stroma (Figure 1). The introduction of this technique meant a major change in the field of refractive surgery. The side effects associated with PRK made LASIK treatment the leading procedure in refractive surgery. The popularity of LASIK is related to the relatively fast visual recovery time, minimal discomfort immediately following treatment, and the minimal incidence of haze.

For low-to-moderate myopia (less than 6 D), LASIK has proven to be very effective, predictable, and safe – achieving an UCVA of 20/40 or more in 86–100% of eyes and an UCVA of 20/20 in 45–94% of eyes. The technique has shown to achieve a very accurate correction, with 71–96% of eyes achieving a refractive error within 0.50 D of the intended correction and 88–100% of eyes within 1.00 D of the intended correction. For moderate-to-high myopia (> 6.0 D), the results show more variation.

Since PRK and LASIK candidates typically have healthy eyes, achieving and maintaining high levels of (subjective) satisfaction after surgery are very important. In 2005, a clinical study showed that the overall patient satisfaction

following LASIK treatment was 4.10 0.71 (a score of 5 meaning that the patient was totally satisfied). Patients are generally very satisfied with their uncorrected vision, visual recovery, and quality of life following LASIK treatment, with the majority of patients reporting that they would have the surgery again (92.3%), if required.

Myopic regression is a condition that can occur after LASIK. The risk of myopic regression increases with the degree of preoperative myopia and patient age. Long-term studies on LASIK for treatment of moderate and extreme myopia showed a trend toward myopic regression, changing from 52–96% of eyes within 1.0 D of the attempted correction after 1 year to 46–91% after 5–6-years followup. In contrast, LASIK studies with lower degrees of preoperative myopia (< 6.0 D) show stable visual results during long-term follow-up.

Although the risks associated with LASIK are considered to be low, intraoperative and postoperative flap-related complications are sight threatening and have resulted in a permanent loss of BCVA. The overall incidence of intraoperative LASIK-flap complications – such as incomplete flaps, buttonholes, free caps, and torn flaps – is approximately 4%. Postoperative flap-related complications include diffuse lamellar keratitis, infection, spontaneously or trauma-related flap displacement, and epithelial ingrowth.

Furthermore, LASIK may cause (transient) dry eyes, which may be related to the neurotrophic effects of cutting the nerves during the creation of the flap. It tends to resolve 6–9 months following LASIK treatment, as the nerves grow back into the flap.

Despite the aim of many surgeons to keep the residual corneal thickness of the stromal bed at least 250 mm, postoperative corneal ectasia (dilation) may occur following LASIK treatment. This rare, but important, complication seems to be related to biomechanical changes in the cornea after treatment and occurs at rates much lower than 1%. Risk factors that might contribute to the development of ectasia following LASIK have been suggested to be: high intraocular pressure, irregular topography, thin corneas, thin remaining corneal beds, forme fruste keratoconus, thick corneal flaps, large optical zones, and, possibly, high myopia.

Laser-Assisted Subepithelial

Keratectomy

LASEK aims to preserve the original anatomy of the cornea and to avoid potential risks posed by the creation of a LASIK flap. The treatment is, in fact, a blend of PRK and LASIK, aiming to decrease the potential complications of the two treatments. In LASEK treatment, diluted ethanol solution is applied to loosen the corneal epithelium, following which the epithelium is partially removed from Bowman’s layer, leaving it connected only at a hinge. Laser treatment is applied directly to Bowman’s layer, and afterwards the epithelial sheet is placed back over the treated stroma. The eye is covered by a bandage contact lens to prevent movement of the epithelial flap due to blinking and eye movements.

LASEK does not have the risk of flap-related complications such as with LASIK, because LASEK can easily be converted to the PRK procedure if the epithelial flap tears or breaks. Furthermore, a larger residual bed is created – which retains the cornea’s biomechanical strength and reduces the risk of corneal ectasia associated with LASIK. One of the main therapeutic advantages of LASEK is that it can be performed in cases in which LASIK may be contraindicated. These include eyes with thin, steep, and flat corneas; epithelial basement-membrane dystrophy; large pupils (requiring wider and, therefore, deeper ablations); higher myopia; and deep-set eyes or tight orbits.

Reports have shown that LASEK is a safe, effective, and predictable treatment, which can be seen as a good alternative to LASIK and PRK for the surgical correction of myopia. A major review of the literature showed that 95% of eyes achieved an UCVA 20/40 and 74% 20/20. Seventy-four percent of eyes achieved a refraction within0.5 D of the desired refraction and 90% of eyes were within 1.0 D of the desired refraction. Loss of two or more lines of BCVA was demonstrated in 2% of eyes.

Comparing LASEK with PRK and LASIK, it has been indicated that the recovery period following LASEK is shorter than that following PRK, but might be somewhat slower than that following LASIK. Discomfort following LASEK seems to be less than after PRK, which is probably

related to the fact that the epithelial flap acts as a biological therapeutic lens that protects the ablated stroma. However, other studies have demonstrated that the epithelial flap is probably not viable, is replaced by regenerated epithelial cells, and, as such, does not provide advantages in comparison to PRK.

The biological properties of the epithelium might inhibit haze formation following the LASEK treatment. Furthermore, the procedure can be combined with the use of mitomycin-C (MMC) – a cytostatic drug known to inhibit proliferating cells and can be used to prevent postablation corneal haze in high-risk cases, such as in patients requiring retreatment.

Epithelial Laser in situ Keratomileusis (epi-LASIK)

Epi-LASIK uses a modified microkeratome (epikeratome) to create a thin corneal epithelial flap before surface ablation is performed. The blade and the angle of cutting of the epikeratome are optimized for a subepithelial dissection, which does not disrupt the corneal stroma such as the LASIK microkeratome. The difference between epiLASIK and LASEK is that the separation of the epithelium is obtained mechanically without the use of alcohol. Epi-LASIK has been proposed as a safe alternative to LASIK and is especially suitable for patients with low-to- moderate myopia and myopic astigmatism, thin corneas, and in individuals with steeper or flatter corneas, where the cutting of a LASIK flap could potentially impose flaprelated complications. The healing period and visual recovery tends to be slower than traditional LASIK. Postoperative discomfort usually occurs within the first 48 h after surgery.

A recent study presented the 1-year results of epiLASIK and stated that this technique is a safe and efficient method for the correction of low and moderate myopia, demonstrating that all of the eyes treated reached an UCVA of 20/40 or better and 86% an UCVA of 20/20 or better. More than 80% of eyes were within 0.5 D of the attempted correction and 97% were within 1 D of the attempted correction.

In comparison with LASEK, it has been suggested that the incidence of haze following ablation of the cornea is lower with epi-LASIK. Longer-term clinical studies are needed to confirm the reported results on epi-LASIK.

Femtosecond Laser in situ Keratomileusis (FS-LASIK)

At the beginning of this century the femtosecond laser, which creates a corneal flap by vaporizing small volumes of tissue using micro-photodisruption at a predetermined

depth, was introduced. Furthermore, when using the femtosecond laser, the flap thickness is much more accurate and thinner (between 90 and 110 mm) than with the excimer laser. The corneal flaps can also be customized with a variable flap thickness and diameter based on the requirements of the patient.

The greatest benefit of these thinner femtosecondcreated flaps is that they result in a greater stability of the cornea when compared to mechanically created flaps. It has been described that the greatest strength of the cornea lies within the first 150 mm of the cornea. Thus, thinner flaps will help to protect the integrity of the cornea and will lead to thicker residual stromal beds, which results in a decreased risk of corneal ectasia. Studies have shown that flaps created with a femtosecond laser provide better visual results than flaps created with a microkeratome. Furthermore, FS-LASIK demonstrates better visual outcomes than PRK in the first 6 months of follow-up. Following this period, both treatments show similar visual results. As for epi-LASIK, long-term followup studies are required to demonstrate the efficacy and safety of FS-LASIK.

Potential limitations of the femtosecond laser include increased costs of the procedure, increased surgical time, and a higher incidence of diffuse lamellar keratitis. The use of topical corticosteroids keeps the last complication at manageable levels. Furthermore, the newer highfrequency femtosecond lasers will probably diminish the incidence of diffuse lamellar keratitis.

Treatment of Hyperopia

Photorefractive keratectomy, LASIK, and LASEK can also be applied for the treatment of low hyperopia (<2 D). In hyperopic treatments, most of the laser ablation is located at the periphery of the treatment zone. Mechanical weakening of the peripheral cornea might lead to a forward-bowing of the central cornea, which increases the intended laser effect. These biomechanical changes and a different wound healing cause increased levels of regression following the hyperopic treatment. Therefore, only low levels of hyperopia can be treated using laser refractive surgery.

The Food and Drug Administration (FDA)-approved studies investigating the treatment of low hyperopia using LASIK showed that 90% of eyes achieved a UCVA 20/40 and only 63% a UCVA 20/20. Sixty-seven percent of eyes achieved a refraction within 0.5 D of the desired refraction and 90% of eyes were within 1.0 D of the desired refraction. Loss of two or more lines of BCVA was demonstrated in almost 2% of eyes after more than 3 months of follow-up. Hyperopic PRK and LASEK treatments show similar clinical results when compared to hyperopic LASIK treatments.

General Side Effects of Laser Refractive

Surgery

Although many developments in keratorefractive surgical techniques have improved the clinical outcome and have shown great success rates, several quality-of-vision problems have been reported. Qualitative visual disturbances can affect patients’ daily activities and include subjective complaints such as glare, halos, and difficulty with night driving. These complaints are more likely to occur with laser corrections of more than 7–8 D of myopia or more than 2–3 D of hyperopia and often diminish after the first six postoperative months. Glare, halos, and night-vision complaints may be attributed to a loss of contrast sensitivity or low-contrast visual acuity. These complaints have been described after all refractive surgery techniques, varying in degrees of incidence.

Reports on patient satisfaction following LASIK treatment showed that predictors for night-vision complaints can include:

. preoperative high levels of myopia (more than 5 D),

. advanced age,

. a flatter preoperative corneal curvature,

. surgical enhancements,

. optical zones <6 mm,

. postoperative residual refractive error >0.5 D from emmetropia (normal refraction), and

. postoperative residual cylinder – a type of higher-order aberration (HOA) of the cornea.

Remarkably, pupil size was not shown to be a significant predictor of night-vision complaints in any of these studies. There is variable evidence in the literature on excluding patients based on large pupil size. It has been suggested in the past that a large pupil, in combination with a small optical zone, is a dominant factor leading to increased night-vision complaints. However, other recent studies demonstrate that the correlation between pupil size and night-vision complaints or between night-vision complaints and the pupil– optical zone disparity is much less critical than previously thought. Pupil size seems to indeed be a significant predictor of glare and halos following LASIK, especially in the first postoperative month, yet it was demonstrated that pupil size is not a significant variable 6 or 12 months following treatment. Postoperative remodeling of the corneal shape by the epithelium may be responsible for these findings.

Other common complications of laser refractive surgery include underand overcorrection (30%), irregular astigmatism (30%), and dry eyes (4–30%, depending on the type of refractive treatment).

Wave front and Laser Refractive Surgery

When applying conventional laser refractive surgery, the ablations are calculated using the data obtained during

manifest and cycloplegic refractions. However, HOAs can cause glare and halos and lead to decreased quality of vision. Wave front technology was developed to categorize and limit the amount of HOA induced by refractive surgery. The wave front sensor measures defocus, astigmatism, and total and individual HOA. Customized wave front-guided corneal ablation combines wave front sensing and wave front correction and, therefore, corrects refractive errors beyond spherical and cylindrical errors.

Over the last decade, several clinical reports have studied HOAs in refractive surgery patients. Some of these studies have shown an increase in patient satisfaction, reduced night-vision complaints, and a lower increase of HOA following wave front-guided treatments, compared to conventional ablation; however, more and larger randomized studies are needed to further analyze and validate the results of these treatments. At the present time, it is not clear whether the excellent results are due to an improved postoperative asphericity profile or the consequence of treating the preexistent HOAs.

Corneal Inlays

The use of corneal inlays as a refractive procedure involves the insertion of a synthetic or biological material into the cornea, which changes the refractive power of the eye by either altering the anterior corneal curvature, or the refractive index of the inlay material, or a combination of these two mechanisms. These inlays can be placed in the stroma or beneath the epithelium of the cornea. The main advantage of this technique over the above-mentioned laser refractive treatments is the reversibility of the procedure.

The inlay material has to meet various physical and biological characteristics in order to minimize complications. Biological materials have shown to be biodegradable and insufficiently permeable to maintain a healthy cornea. Furthermore, hydrogel inlays have been demonstrated to be biocompatible but have insufficient porosity to maintain optimal nutrient flow. Many complications, including corneal haze, epithelial thinning, inlay encapsulation, epithelial opacification, corneal vascularisation, inlay decentration, and fibrosis, have been reported following the implantation of corneal inlays.

At present, a phase 1 trial is being conducted using a synthetic corneal inlay made of a polymer of perfluoropolyether, which is placed into the stroma following the creation of a corneal flap with a microkeratome. The study involves implantation of the inlays in unsighted eyes. Despite the experimental phase of these synthetic inlays, it is believed that they might meet all the required physical and biological characteristics which will help minimize the above-mentioned complications.

Corneal inlays have been developed not only to correct myopia and hyperopia, but also to correct presbyopia.