Ординатура / Офтальмология / Английские материалы / Wavefront Analysis Aberrometers and Corneal Topography_Boyd_2003

Different aberrations can be dissociated so that estimates can be made of the effect of particular aberrations on visual function. For example, all lower or all higher order aberrations can be removed as a group and depicted on separate aberration maps. Thus, it is possible to express the percentage of total aberrations represented by sphere and cylinder (lower, second order). This could be important for screening patients for classical excimer laser ablation based on spherocylindrical refractions. This approach might helpful for identifying patients who are likely to do just as well with conventional excimer laser surgery as customized ablation.

Wavefront data can be represented graphically as 2-dimensional or 3-dimensional maps. Each term can also be represented numerically so that statistical analyses can be performed. The root mean square of wavefront error (RMS) is the most common analysis used in describing the level of aberrations in a particular eye. RMS provides a rather gross index for describing the variation of the wavefront from the ideal. Attempts have been made to establish standards for describing wavefront patterns in the eye.20 Aberrations vary with pupil size. Importantly, these standards determined that wavefront data from

human eyes should be calculated over a 6 mm pupil size. This is reasonable since the distribution of pupil sizes in a population of refractive candidates is a "Sinus" or Bell-shaped curve with 5.86 mm as mean (+/- 0.9).21

The most common ways of depicting wavefront errors utilize color maps with units in either microns or diopters. Both units have advantages and disadvantages. There is, however, continuing controversy about whether diopters or microns are the best units for depicting information that is understandable to the clinician.

Since wavefront measurements vary with pupil size, it is important to have accurate measurements in individual patients to allow detailed studies to be performed. In addition, it may prove useful to take into account the patient’s occupation and lifestyle depending on their pupil size under different lighting conditions when planning corneal surgical procedures. There are several methods used for measuring pupil size. The most commonly used methods at present are comparison cards and the infrared pupillometer (Figure 7). In the authors’ experience, however, these methods are highly variable depending on the observer. More accurate and

objective pupillometry systems are being introduced (Figure 8). For example, the Procyon System (Keeler) allows pupil size to be rapidly determined under a variety of lighting conditions and provides a permanent record.

Wavefront data can be used to calculate point spread functions. In turn, point spread functions can be used to generate simulated images that simulate what a patient might see with a particular wavefront and point spread function in their eye. These simulations can be used to provide clinicians and scientists with a better appreciation of the effect of individual aberrations on vision. They are also helpful for educating patients.

THE ROLE OF CORNEAL

TOPOGRAPHY

Wavefront systems have provided a new understanding of factors affecting the quality of vision. Some have suggested that measurements from these systems are sufficient to plan procedures to correct vision quality problems in eyes that have poor outcomes from prior corneal surgery. However, the authors believe that corneal topographic data will need to be integrated with wavefront data in order to correct complex surface abnormalities such as peninsulas, central islands, and other irregular shapes on the corneal surface.15,22 How can the corneal surface be changed through custom ablation with the preci-

sion required to reduce aberrations to an acceptable level unless the beginning shape of a complex peninsula is taken into account in planning surgery? Corneal topography is also critical in determining candidacy for corneal refractive surgery. For example, until wavefront patterns are better appreciated, topography is needed to exclude patients with pellucid marginal degeneration

Fig. 8. Images of the pupil provided with the Procyon pupillometer. This computerized device automatically analyzes the size of the pupil under a variety of standardized lighting conditions and provides an objective measure of the pupil size. Interobserver variation is reduced with such a system.

and keratoconus.23-25 Corneal topography allows the surgeon to better evaluate proper centration, central

islands and other anomalies after corneal surgery.26 It also provides a clearer understanding of corneal changes that occur over time with processes such as wound healing or keractasia.

Preoperative corneal shape is an important factor in determining outcomes, especially for cases with higher corrections. Excessive flattening or steepening of the corneal surface can be associated with disabling aberrations. The surgeon needs to be aware of the beginning corneal curvature to plan the procedure and exclude patients in whom unacceptable changes would occur.

It is possible to use wavefront and topographic information together to divide total aberrations into corneal and non-corneal (lens, vitreous, retina, etc.) aberrations. For example, the CT View applications allow clinicians and scientists to analyze raw data from different wavefront and corneal topography systems. We believe this type of information will facilitate planning for surgery and studying the effects of corneal ablation.

Nidek (Gamagori,Japan), Bausch & Lomb (Rochester, NY), and Zeiss-Meditec (Dublin,CA) are developing hybrid systems that integrate compatible wavefront and topography information. It seems likely that systems such as these will provide a more complete understanding of the optical system of the eye in planning for surgery.

SURFACE ABLATION vs.

LAMELLAR ABLATION

Laser energy can be delivered on the stromal surface in the form of either surface ablation (PRK or LASEK29,30) or lamellar surgery (LASIK). LASIK offers advantages related to patient comfort and speed of visual recovery that has made this technique the dominant refractive procedure.27,28 However, surface ablation remains an excellent option and could be superior for custom ablations in which features designed to correct aberrations are often measure just a few microns. Creation of the flap alone alters aberrations in an unpredictable way and will, therefore, be a confounding factor in custom ablations. Other variables that are characteristic of LASIK, such as fine striae, slight displacement of the flap, and epithelial ingrowth, will also complicate custom corneal ablations. A two-step approach has been advocated for custom LASIK surgery.31 This

strategy has the potential to overcome some of these problems with LASIK. Further study will be needed to determine whether the theoretical differences between surface and lamellar ablation are of practical significance in custom corneal ablation.

LIMITATIONS OF WAVEFRONT MEASUREMENTS AND CUSTOM ABLATIONS: CORNEAL WOUND HEALING, AGE, AND OTHER FACTORS

Important biomechanical and corneal wound healing issues contribute to the results after both traditional excimer laser ablation procedures and custom corneal ablations. These factors contribute to the unpredictability of keratorefractive surgery in some patients. They can also be important factors in the safety of PRK, LASEK, or LASIK. For example, complications of these procedures like haze and diffuse lamellar keratitis are related to abnormal patterns of wound healing. Undercorrection or overcorrection of the intended correction is most commonly related to lower or higher wound healing, respectively. Other complications, such as iatrogenic keratectasia in LASIK patients, can occur secondary to altered biomechanical properties of the cornea.32-35

In parallel with advances in corneal refractive surgery there has been more complete characterization of the corneal wound healing response.36-50 Full characterization of the wound healing cascade is fundamental to pharmacological and technical approaches for controlling or normalizing this response, thereby reducing biological diversity in variables such as epithelial hyperplasia that will tend to mask attempts at custom ablation.

All refractive procedures performed on the cornea have injury to the epithelium in common. It is this injury and release of cytokines such as inter- leukin-1 that initiates a sequence of events that likely evolved as part of the protective system for preserving vision. For example, keratocyte apoptosis is the first detectable event after epithelial injury associated with mechanical trauma,39 corneal surgical

procedures36,40,41 or herpetic (HSV) keratitis.42 We have hypothesized that this system of cellular suicide evolved as a protective mechanism to serve as an early firewall to retard spread of viruses such as herpes simplex and smallpox virus into the eye and central nervous system.42

Within a few hours of epithelial injuryinduced apoptosis, the remaining keratocytes surrounding the stromal zone of depletion begin to proliferate.43 Inflammatory cells like monocytes are also attracted into the stroma by chemotactic factors released from keratocytes and epithelial cells.44 Myofibroblasts can also be generated depending on the type and level of injury.50 Myofibroblasts are wound healing-type of keratocyte-derived cells that are characterized by the expression of alpha smooth muscle actin (SMA).45,46,50 These cells, along with activated keratocytes, produce disorganized collagen, glycosaminoglycans, and the growth factors that stimulate healing of the overlying epithelium.45,46 Myofibroblasts also have altered transparency relative to keratocytes related to diminished corneal crystallin expression and they are a major factor in the development of stromal haze.47,48

There is a gradual return to a normal physiologic state in the corneal stroma following normal PRK, LASEK, or LASIK procedures. This normalization is associated with disappearance of the myofibroblasts through programmed cell death or phenotype reversal to quiescent keratocytes.49,50 Also, there is remodeling of disordered collagen produced by myofibroblasts and activated keratocytes during this phase of corneal wound healing.50 The corneal epithelium may undergo hyperplasia following corneal injury as a result of growth factors produced by activated keratocytes and myofibroblasts. The level of epithelial hyperplasia varies from patient to patient and with factors such as the level of correction in PRK. Stromal remodeling and epithelial hyperplasia are thought to be the most important mechanisms leading to regression of the refractive effect of PRK, LASEK, or LASIK surgery.37,52 –54

These same factors will introduce variability following custom corneal ablation procedures.

There are fundamental differences in the location and intensity of wound healing following different types of keratorefractive surgery. For example, after PRK, keratocyte apoptosis and the subsequent events of the healing cascade occur immediately beneath the epithelium contrasting with LASIK, in which keratocyte apoptosis happens at the level of the flap interface and at the site where the blade penetrated the epithelium (Figure 9).

In addition, in the rabbit model significant quantitative differences are noted between low (-4.5 D) PRK, high (-9.0 D) PRK and high (-9.0) LASIK corrections.50 These differences parallel those seen clinically in humans.

Pharmalogical modulation of corneal would healing has long been a goal of refractive surgeons and scientists. It is possible that agents that decrease keratocyte apoptosis, keratocyte proliferation, or generation of myofibroblasts could improve the predictability and safety of PRK, LASEK, and LASIK. Importantly, the alterations produced by these drugs could still be significant even if the cellular effect is modest. For example, in rabbit studies of high (-9D) and low (-4.5) PRK there was still considerable apoptosis in the low correction group, even though the level was significantly lower than that in the higher correction group.50 The same was true of keratocyte proliferation. However, only the high correction group had myofibroblast generation associated with haze in the central cornea.50 This suggests that a drug that decreases keratocyte apoptosis or proliferation could have the potential to prevent generation of myofibroblasts. Since these myofibroblasts are also likely to be associated with epithelial hyperplasia, this type of treatment could also result in more predictable custom corneal ablation. It is also possible that the new technologies used to create the flap, such as the fentosecond laser, will offer advantages in terms of the uniformity of the flap thickness and the wound healing response that will facilitate the reproducibility and effectiveness of custom corneal

ablation. Further study will be needed to determine whether these pharmacological or technical approaches will be efficacious.

ARE ALL ABERRATIONS

CREATED EQUAL?

The goal of customized ablations is to improve the quality of vision. There are several aspects of ocular aberrations and visual function that are poorly understood. For example, Shallhorn (American Society of Cataract and Refractive Surgery, Boston, MA, 2001) studied pilots with visual acuity better than 20/16 and found that these subjects had more vertical coma, as well as spherical aberrations. Thus, some types of aberration could turn out to be beneficial or at least of no significance for specific visual tasks or in the visual function of particular individuals.

If we compare vision to photography we can consider important factors that are relevant for understanding visual function. The camera, similar to

the eye, has an aspheric lens system that focuses light rays on the film (retina). The light rays enter the camera and the eye through a controlled diaphragm (the pupil). After the picture is taken with a camera it still must be developed properly to generate a high quality image. After development of the photo the image can be scanned and processed to further enhance the quality of the image. The developing and processing of a photographic image is analogous to processing of visual information in the brain. Thus, the brain may compensate for some aberrations depending on the type, the level, or the age of the patient. Some patient’s brains may compensate for a particular aberration while others may not. There are also likely to be central aberrations related to the development or function of the central nervous system. We must remember that wavefront analyzers only provide information about the visual system from the tear film to the retinal surface.

Some computer programs such as the CTView (Server and Associates, inc, Celibration, FL) can generate, through convolution calculations, optically-aberrated charts and/or images. Thus, it is

possible to exclude some types of aberrations, in order to determine the impact of each specific aberration on the image formation. Applegate used such system to address the impact of different aberrations on visual function, with a constant root mean square (RMS) value. The RMS is statistically averaged error of the total aberrations in the eye. Its calculation is similar to that for standard deviation in statistics. RMS tells us something about many points in the imaging system and, therefore, it is a much more meaningful global measure of aberrations than peak to valley measurements. In that study, Applegate found that some individual aberrations degrade vision quality more than others. In general, the central, lower frequency terms, have a more adverse impact on image formation. These terms tend to be located near the center of the Zernike aberration pyramid (Figure 2).55

Thus, simple correction of all aberrations (creating a flat wavefront) only makes sense in mathematical models. It is likely that a more complete appreciation of individual aberrations will lead to technology to rapidly access the positive or negative impact of each term for an individual patient, so that an optimal target wavefront can be determined. This will likely lead to truly customized spectacles, contact lenses, intraocular lenses, and laser ablations.

CONCLUSIONS

Customized spectacles, contact lenses, intraocular lenses, and refractive surgical procedures will have an important role in the future of ophthalmology. True customization to the individual visual demands of the patient is predictable. These efforts will take into account the effects of specific optical aberrations on vision quality and include analysis of central nervous system processing to give a complete picture of visual function. Control of corneal wound healing and a better understanding of corneal biomechanics will be critical for full realization of the potential of custom corneal ablations.

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_____________________________

Renato Ambrósio Jr, MD Department of Ophthalmology,

University of Washington, Seattle, WA Department of Ophthalmology, University of São Paulo, São Paulo, Brazil Instituto de Olhos Renato Ambrósio,

Rio de Janeiro, Brazil

Marcelo V. Netto, MD

Department of Ophthalmology,

University of Washington, Seattle, WA

Steven E. Wilson, MD

Professor and Chair

Department of Ophthalmology,

Grace E. Hill Chair in Vision Research

University of Washington,

Seattle, WA

Corresponding author: Steven E. Wilson, M.D., Department of Ophthalmology, Box 356385, Seattle, WA 98195-6485,

Tel: 206-543-5575, Fax: 206-543-4414

Acknowledgements: Supported in part by an unrestricted grant from Research to Prevent Blindness, New York, NY, and US Public Health Service grant EY10056 from the National Eye Institute, National Institutes of Health, Bethesda, MD.

Proprietary interest statement: The authors have no proprietary or financial interest in relation to this manuscript.