Ординатура / Офтальмология / Английские материалы / Wavefront Customized Visual Correction The Quest for Super Vision II_Krueger, Applegate, MacRae_2003

Figure 34-1. Mean root mean square (RMS) wavefront values of the Zernike coefficient Z(4,0) of the wavefront aberration for a 4 mm pupil measured in 147 pseudophakic eyes implanted with different IOL models (27 Acrysof MA60MB, 48 PhakoFlex II SI40NB, and 72 CeeOn Edge 911A). The error bars indicate plus and minus one standard deviation. This data was collected in studies conducted by Prof. Dr. U Mester, PD; Dr. HJ Hettlich; and Dr. K Gerstmeyer (Minden Eye Clinic, Germany).

DESIGN OF A LENS FOR THE REDUCTION OF PSEUDOPHAKIC SPHERICAL ABERRATION

The Tecnis lens was designed to compensate for average corneal spherical aberration. Furthermore, because cataract surgery is predominantly performed in older eyes and uncertainty exists in the literature as to whether corneal spherical aberration changes with age (Oshika et al6 have shown no change while Guirao et al7 have shown that it increases slightly with age), the design of the Tecnis lens was based on the spherical aberration measured in a typical population of cataract patients.

The design population included 71 eyes of 71 subjects eligible for cataract surgery at St. Erik’s Eye Hospital in Stockholm, Sweden. Their ages ranged from 35 to 94 years, with a mean age of 74. Corneal topography was recorded for all subjects using the Orbscan I (Bausch & Lomb, Rochester, NY) on the day of surgery.

The measured elevation of the anterior corneal surface and its position in the pupil were used as inputs for determining the optical properties of all corneas. A calculation of wavefront aberration of the single-surface cornea model for each subject was performed using the computational method described previously by Guirao and Artal.20 Using a pupil centered on the subject’s line-of-sight, the surface was described by fitting the elevation height data with a series of Zernike polynomials (up to and including the fourth order) after applying a Gram-Schmidt orthogonalization procedure to the height data (for a 6 mm pupil size). Knowledge of the precise shape of the anterior corneal surface allowed the wavefront aberration created by this surface to be determined using a ray trace procedure.

Like the surface shape, wavefront aberration is represented as a sum of Zernike polynomials. Figure 34-2 presents the average and standard deviation of each of the higher-order Zernike aberration terms (third and fourth order) calculated for a 6 mm diameter aperture (the ordering of the Zernike coefficients listed follows the recently standardized double-index format for Zernike

Figure 34-2. Mean RMS wavefront error values of the thirdand fourth-order Zernike coefficients of the corneal wavefront aberration measured in 71 cataract patients for a 6 mm pupil. The error bars indicate plus and minus one standard deviation.

coefficients for reporting the optical aberrations of eyes).21 From this plot, it can be seen that two higher-order aberrations (trefoil Z[3,-3]) and spherical aberration (Z[4,0]) are, on average, significantly different from zero in this population. Because spherical aberration is the only rotationally symmetric higher-order aberration, it is the only aberration that can be corrected with a rotationally symmetric IOL.

A single-surface model cornea was constructed to have the same spherical aberration as the average calculated for the design population. The radius of curvature of this model cornea was the average radius determined from the Zernike fit to the elevation data, while the conic constant was adjusted until corneal spherical aberration was equal to the average for the 71 subjects. This one-surface model replaces the surfaces of the cornea and aqueous humour with one effective medium with the keratometric refractive index of 1.3375.

This new model cornea was incorporated into a pseudophakic eye model and used to design a new lens. The chosen initial starting point for lens design was an equi-biconvex lens made from high refractive index polysiloxane. This lens was placed 4.50 mm behind the anterior corneal surface (based upon measurements of IOL positioning in pseudophakic eyes).22-24 The refractive indices used in the eye model are consistent with accepted values for the refractive indices of the ocular media at 450, 546, and 650 nanometers (nm).25

The anterior surface of the lens was modified in such a way that the optical path lengths of all on-axis rays within the design aperture ( = 546) were the same. The resulting anterior surface shape can be described using the modified conicoid equation (equation 1), where R is the radius of curvature at the vertex, Q is the conic constant, and r is the radial distance from the vertex of the surface (this equation is not a simple conicoid—ad and ae are higher-order polynomial terms, and it is these terms that make the surface a modified conicoid instead of a pure conicoid). The resulting shape of the anterior surface of the Tecnis lens is a modified prolate ellipsoid (Q values between 0 and –1). Prolate surfaces are one type of aspheric surface in which the term aspheric is used to describe any surface that is not purely spherical (ie, having the same radius of curvature at every point on the surface).

Figure 34-3. Polychromatic MTF of two pseudophakic eye models (one including an IOL with spherical surfaces and the other including the new Tecnis Z-9000 lens) calculated for 5, 20, and 30 D lenses and a 4 mm pupil.

The optical quality (MTFs) of these newly designed Tecnis lenses were calculated in the pseudophakic eye model. To provide a reference, the new modified prolate lenses were compared with an equi-biconvex lens of the same power, made from the same material but having spherical surfaces. Thus, the only difference between these two lens models is the shape of the anterior surface. The MTFs calculated for l = 450, 546, and 650 nm were weighted using the photopic spectral luminous efficiency function V(l) of the human eye to determine the polychromatic MTF. The polychromatic MTF of these two eye models, best-focused to obtain the minimum Strehl ratio for l = 546 nm, was calculated and the comparison was made for 5, 20, and 30 D lenses in Figure 34-3 (4 mm pupil).

The theoretical visual benefit (Figure 34-4) as defined by Williams et al26 is, in this case, defined as the ratio of the polychromatic MTF calculated in the model eye with the Tecnis lens to the MTF calculated with the spherical reference lens. This value is representative of the increase in contrast present in an image on the retina for objects of different spatial frequencies (for 5, 20, and 30 D lenses). An improvement in the measured MTF translates to an improvement in image contrast. The resultant enhancement in contrast is expected to provide patients with implanted eyes with an increase in contrast sensitivity. These outcomes support the need for a clinical evaluation of a modified prolate IOL to improve the quality of vision following cataract surgery.

CLINICAL RESULTS WITH THE TECNIS LENS

In a randomized, open-label, single-center study,27 37 bilateral cataract patients were implanted with two different IOLs. Each patient received one Tecnis lens (modified prolate anterior sur-

Figure 34-4. Theoretical visual benefit provided by a 5, 20, and 30 D Tecnis lens for a 4 mm pupil.

face) and one conventional IOL (spherical anterior and posterior surfaces and positive spherical aberration) both made from high refractive index silicone. These two lenses were compared intraindividually to determine if decreasing ocular spherical aberration leads to a measurable improvement in the quality of vision. All cataract surgery procedures were performed at the Department of Ophthalmology, Bundesknappschaft’s Hospital, Sulzbach, Germany and every effort was made to minimize differences in the treatment in each of the patient’s two eyes. To this end, all patients had both of their surgeries performed by the same doctor. The patients included in the study were cataract patients with otherwise healthy eyes. Patients with any ocular pathology (other than cataracts) or optical irregularity were excluded from the study, and the choice of which eye was to receive which lens was randomized. The surgical procedure used for implantation of both lenses has been described in detail by Mester et al.27 Quality of vision was assessed by measuring contrast sensitivity and optical quality by wavefront aberration. The improvement in visual quality and difference in wavefront aberration were assessed using a two-sided paired t-test. A significant difference is reported for p values less than 0.01. All results reported here are from a visit conducted 3 months postoperatively.

Wavefront aberration of the whole eye was measured using a Shack-Hartmann wavefront sensor with a fully pharmacologically dilated pupil. The principles associated with this technique for measuring the ocular wavefront aberration of the eye are described in detail elsewhere.8,28

Wavefront aberration measurements were obtained in 30 eyes implanted with Tecnis lenses (study eyes) and 29 eyes implanted with the spherically surfaced control lens (control eyes). Figure 34- 5 shows the average Zernike coefficients of the measured ocular wavefront aberration of the study eyes and of the control eyes for a 4 mm pupil. These measurements reveal that there is no statistically significant difference in any of the wavefront aberration terms except for Z(4,0), which is representative of spherical aberration. (A t-test was used to compare the sample means, p < 0.01.) In particular, the study eyes have, on average, no significant spherical aberration (Z[4,0] = 0.0069 ± 0.0309 mm RMS error), while the control eyes suffer from significant amounts of positive spherical aberration (Z[4,0] = 0.0813 ± 0.0258 mm RMS error).

Figure 34-5. Mean RMS wavefront error values of the thirdand fourth-order Zernike coefficients of the wavefront aberration measured in eyes implanted with the Tecnis lens and eyes implanted with a conventional IOL with spherical surfaces (4 mm pupil). The error bars indicate plus and minus one standard deviation.

Figure 34-6B. Mean best-corrected log contrast sensitivity values measured in eyes implanted with the Tecnis lens and eyes implanted with a conventional IOL with spherical surfaces. The error bars indicate plus and minus 1 standard deviation. Measured under photopic lighting conditions (85 cd/m2).

The Tecnis lens on average had no significant spherical aberration, while the conventional control eye had significant residual amounts of spherical aberrations.

Best-corrected contrast sensitivity function (CSF) was measured in both eyes using the VSRC CST-1500 view-in tester with the FACT sine-wave grating (Vision Sciences Research, San Ramon, Calif) (1.5, 3, 6, 12, and 18 cycles per degree [c/deg]) contrast sensitivity chart viewed under photopic normal (85 [candles/meter2] cd/m2) and mesopic low light (6 cd/m2) lighting conditions. The average photopic and mesopic log CSF values for the two groups

Figure 34-6A. Mean best-corrected log contrast sensitivity values measured in eyes implanted with the Tecnis lens and eyes implanted with a conventional IOL with spherical surfaces. The error bars indicate plus and minus one standard deviation. Measured under mesopic lighting conditions (6 candles/meters2 [cd/m2]).

of eyes are shown in Figures 34-6A and 34-6B. The eyes implanted with the Tecnis IOL performed significantly better for all spatial frequencies and both lighting conditions (p <0.01). There was more improvement measured under mesopic conditions, due to the fact that when the pupil is wider the negative effects of aberrations are more pronounced. The measured increase in CSF indicates that the patients could detect objects of lower contrast with their Tecnis eye than with the eye implanted with the conventional control lens. For example, at 6 c/deg, the eyes implanted with the Tecnis lens had an average CSF of 67.2, while the control eyes had an average CSF of 48.3. This means that the average contrast threshold of control eyes is ~39% higher than that of the Tecnis eyes. The average measured visual benefit (Figure 34-7) is the ratio of the CSF in the study eyes to the CSF in the control eyes. A “visual benefit” of 1 means there would be no visual benefit, while a visual benefit of 2 indicates a doubling of the MTF, which means a shaper image. This factor varies from 1.1 for 3 c/deg to 1.9 for 18 c/deg for photopic conditions and from 1.2 for 3 c/deg to 2.2 for 18 c/deg for mesopic contrast sensitivity and is consistently greater than 1 (equivalent CSF).

The Tecnis lens had a significant improvement in all spatial frequencies tested for photopic and mesopic conditions compared to the conventionally designed control lens.

DISCUSSION

The aberration compensation provided by the Tecnis lens significantly reduces the total ocular spherical aberration in pseudophakic eyes. This reduction in ocular spherical aberration leads to an increase in the contrast of the retinal image and an increase in the CSF of patients implanted with this lens. This study reveals that wavefront aberration measurement is a valuable tool for IOL design.

Figure 34-7. Measured visual benefit provided by the Tecnis lens for mesopic and photopic lighting conditions.

The notion of varying the surface shapes of an IOL in order to improve pseudophakic quality of vision is not new. An elegant analysis of the effects of different lens shapes on both onand offaxis image quality of IOLs was performed by Atchison.29,30 It was determined that the best retinal image quality is provided by a lens that is close to plano-convex, with the more curved surface facing the cornea (in this study, only plano and spherical surfaces were used). Furthermore, Lu, Smith, and Atchison have investigated the possibility of improving ocular optical quality with aspheric IOLs and it was generally agreed that a theoretical improvement is possible for well-centered implants.31,32

In the 1980s, ORC marketed an IOL with an aspheric anterior surface. This lens (the ORC model UV400) was designed using different principles and did not succeed in improving pseudophakic visual quality. It was premature to put such a lens on the market at a time when the surgical technique used often resulted in large amounts of tilt and decentration.33 Manufacturing technology was also not refined enough to make the high precision surfaces that current single-point diamond turning achieves today. The only other aspheric lens on the market today that the authors are aware of is a refractive/diffractive bifocal lens sold by Acri.Tec (Berlin, Germany)—models 737D and 733D. Modifying current lens models to include aspheric surface profiles would be a natural way for other IOL producers to improve the pseudophakic visual quality provided by their lenses. Therefore, it is likely that other ophthalmic companies are developing aspheric IOLs.

As suggested above, the pseudophakic optical quality of a nonspherical lens is more sensitive to misalignments. Van der Mooren et al34 showed, using the MTF calculated in the pseudophakic eye model (discussed in the design section of this chapter), that if the Tecnis lens is decentered less than 0.50 mm and tilted less than 9 degrees, it will exceed the optical performance of a spherical IOL. Recent studies of tilt and decentration of foldable IOLs have found average decentration values of 0.15 mm, 0.28 mm, and 0.30 mm and average tilts of 1.13 degrees, 2.83 degrees, and 2.41 degrees.35-37 Thus, these studies confirm that modern IOL implantation is well within the decentration and tilt tolerances needed to achieve improved optical performance with the Tecnis lens.

Aberration-Correcting Intraocular Lenses 289

The two lenses used in the clinical study outlined in Clinical Results With the Tecnis Lens (see p. 287) were not exactly the same—the lenses were made by different manufacturers and have different haptic designs and overall diameters. However, the major factors contributing to optical quality (ie, the refractive index of the optic material and the diameter of the optic) are very similar. In fact, the single major difference between the two lenses that contributes to intraocular optical quality is that the control lens has two spherical surfaces (resulting in a lens with positive spherical aberration) while the Tecnis lens has one spherical surface and one modified prolate surface (and thus contributes negative spherical aberration to the system). Thus, the small differences in optical quality contributed by the other differences in the two lenses are overshadowed by the larger differences contributed by the spherical aberration.

The Tecnis lens was designed to compensate for the average corneal spherical aberration of the cataract population and therefore does not provide precise compensation for each individual’s corneal spherical aberration. Thus, all patients do not obtain the same benefit from the lens, and some patients may even have slightly better contrast sensitivity with a conventional spherical lens. In the clinical study described above, approximately 10% of the patients had lower mesopic contrast sensitivity in their Tecnis eye than in their control eye. In order for every patient to appreciate minimized ocular spherical aberration and thus improved contrast sensitivity, lenses customized to correct for each individual’s unique corneal spherical aberration would be required. A design that compensates for all monochromatic aberrations (spherical aberration, coma, astigmatism, etc) of an individual’s cornea should yield the best possible visual performance for that individual. For example, Williams et al have reported a measured average visual benefit of between 150% and 300% for a customized correction of all monochromatic aberrations in the spatial frequencies considered in our clinical study (1.5 to 18 c/deg).26 With these possible gains, customizing IOLs to com-

In order for every patient to appreciate minimized ocular spherical aberration and thus improved contrast sensitivity, lenses customized to correct for each individual’s unique corneal spherical aberration would be required. A design that compensates for all monochromatic aberrations (spherical aberration, coma, astigmatism, etc) of an individual’s cornea should yield the best possible visual performance for that individual. This may be a design in future IOLs.

Editor’s note:

The field of wavefront-corrected IOL is moving rapidly to minimize higher-order aberration with the first and most important step being aspheric IOLs, which are designed based on a normalized correction in spherical aberration in a normal population. It is not truly “customized” based on the individual’s higher-order aberration pattern. In the future, it would be optimal to be able to adjust the IOL after insertion into the eye to compensation for subtle decentration and other higher-order aberrations measured after cataract surgery. Such wondrous systems are still under development and will take years to implement, but this first step of reducing spherical aberration in pseudophakes is an important one.

S. MacRae, MD

pensate for individual corneal monochromatic aberrations is a natural next step in improving pseudophakic visual quality.

DEFINITIONS

contrast sensitivity: The ability to detect objects with varying contrast levels. Measured with specially designed charts. haptic: Loop attached to an IOL that is used to support the lens

in the capsular bag or sulcus.

pseudophakia: The condition of having an IOL implant taking the place of a cataractous lens.

REFERENCES

1.Norrby NES, Grossman LW, Geraghty EP, et al. Determining the imaging quality of intraocular lenses. J Cataract Refract Surg. 1998; 24:703-714.

2.Norrby NES. Standardized methods for assessing the imaging quality of intraocular lenses. Appl Opt. 1995;34:7327-7333.

3.Ophthalmic Implants—Intraocular lenses. Part 2: Optical properties and test methods. ISO 11979-2. ISO, Geneva, Switzerland; 1999.

4.Or H, Soylu T. The enhancement of the contrast sensitivity in cataract surgery patients with a preoperative visual acuity of 0.4-0.7 and its comparison with the normals. Paper presented at: the XXIX International Congress of Ophthalmology; April 21-25, 2002; Sydney, Australia.

5.Guirao A, Redondo M, Geraghty E, Piers PA, Norrby S, Artal P. Corneal optical aberrations and retinal image quality in patients implanted with monofocal IOLs. Arch Ophthalmol. 2002;120:1143.

6.Oshika, T, Klyce SD, Applegate RA, Howland HC. Changes in corneal wavefront aberrations with aging. Invest Ophthalmol Vis Sci. 1999;40:1351-1355.

7.Guirao A, Redondo M, Artal P. Optical aberrations of the human cornea as a function of age. J Opt Soc Am A. 2000;17:1697-1702.

8.Liang J, Grimm B, Goelz S, Bille JF. Objective measurement of wave aberrations of the human eye with the use of a Hartmann-Shack wave-front sensor. J Opt Soc Am A. 1994;11:1949-1957.

9.Porter J, Guirao A, Cox I, Williams DR. Monochromatic aberrations of the human eye in a large population. J Opt Soc Am A. 2001;18:1793-1803.

10.Artal P, Berrio E, Guirao A, Piers P. Contribution of the cornea and internal surfaces to the change of ocular aberration with age. J Opt Soc Am A. 2002;19:137-143.

11.El Hage SG, Berny F. Contribution of the crystalline lens to the spherical aberration of the eye. J Opt Soc Am A. 1973;63:205-211.

12.Artal P, Guirao A, Berrio E, Williams D. Compensation of corneal aberrations by the internal optics in the human eye. Journal of Vision. 2001;1:1-8.

13.Smith G, Cox MJ, Calver R, Garner LF. The spherical aberration of the crystalline lens of the human eye. Vision Res. 2001;41:235-243.

14.Glasser A, Campbell MC. Biometric, optical and physical changes in the isolated human crystalline lens with age in relation to presbyopia. Vision Res. 1999;39:1991-2015.

15.Smith G, Atchison DA, Pierscionek BK. Modeling the power of the aging eye. J Opt Soc Am A. 1992;9:2111-2117.

16.Dubbelman M, Van der Heijde GL. The shape of the aging human lens: curvature, equivalent refractive index and the lens paradox. Vision Res. 2001;41:1867-1877.

17.Guirao A, Gonzalez C, Redondo M, Geraghty E, Norrby S, Artal P. Average optical performance of the human eye as a function of age in a normal population. Invest Ophthalmol Vis Sci. 1999;40:203-213.

18.Nio YK, Jansonius NM, Fidler V, Fidler V, Geraghty E, Norrby S, Kooijman AC. Age-related changes of defocus-specific contrast sensitivity in healthy subjects. Ophthalmic Physiol Opt. 2000;20:323-334.

19.Barbero S, Marcos S, Llorente L, Optical changes in corneal and internal optics with cataract surgery. Abstract. Invest Ophthalmol Vis Sci. 2002;388.

20.Guirao A, Artal P. Corneal wave aberration from videokeratography: accuracy and limitations of the procedure. J Opt Soc Am A. 2000;17:955-965.

21.Thibos LN, Applegate RA, Schwiegerling JT, Webb R, VSIA Standards Taskforce Members. Standards for reporting the optical aberrations of eyes. Vision Science and its Applications, OSA Trends in Optics and Photonics. 2000;35:110-130.

22.Findl O, Drexler W, Menapace R, et al. Changes in intraocular lens position after neodymium:YAG capsulotomy. J Cataract Refract Surg. 1999;25:659-662.

23.Landau IM, Laurell CG. Ultrasound biomicroscopy examination of intraocular lens haptic position after phacoemulsification with continuous curvilinear capsulorrhexis and extracapsular cataract extraction with linear capsulotomy. Acta Ophthalmol Scand. 1999;77:394-396.

24.Olsen T, Corydon L, Gimbel H. Intraocular lens power calculation with an improved anterior chamber depth prediction algorithm.

J Cataract Refract Surg. 1995;21:313-319.

25.Navarro R, Santamaria J, Bescos J. Accommodation-dependent model of the human eye with aspherics. J Opt Soc Am A. 1985;2:12731281.

26.Williams DR, Yoon GY, Guirao A, Hofer H, Porter J. How far can we extend the limits of human vision. In: MacRae SM, Kreuger RR, Applegate RA, eds. Customized Corneal Ablation: The Quest for SuperVision. Thorofare, NJ: SLACK Incorporated; 2001:11-32.

27.Mester U, Dillinger P, Anterist N. The impact of a modified optic design on visual function. A clinical comparative study. J Cataract Refract Surg. 2003;4:627.

28.Prieto PM, Vargas-Martin F, Goelz S, Artal P. Analysis of the performance of the Hartmann-Shack sensor in the human eye. J Opt Soc Am A. 2000;17:1388-1398.

29.Atchison DA. Optical design of intraocular lenses. I. on-axis performance. Optom Vision Sci. 1989;66(8):492-506.

30.Atchison DA. Optical design of intraocular lenses. II. off-axis performance. Optom Vision Sci. 1989;66(9):579-590.

31.Lu C, Smith G. The aspherizing of intraocular lenses. Ophthalmic Physiol Opt. 2000;20:323-334.

32.Atchison DA. Design of aspheric intraocular lenses. Ophthalmic Physiol Opt. 1991;11:137-146.

33.Auran, JD, Koester CJ, Donn A. In vivo measurement of posterior chamber intraocular lens decentration and tilt. Arch Ophthalmol. 1990;108:75-79.

34.Van der Mooren M, Piers P, Norrby S, Schievink H. Optical performance of the Pharmacia Tecnis Z9000 IOL designed to match the human cornea. Paper presented at: the American Society of Cataract and Refractive Surgery Annual Meeting; 2002.

35.Akkin C, Ozler SA, Mentes J. Tilt and decentration of bag-fixated lenses: a comparative study between capsulorrhexis and envelope techniques. Doc Ophthalmol. 1994;87:199-209.

36.Mutlu FM, Bilge AH, Altinsoy HI, Yamusak E. The role of capsulotomy and intraocular lens type on tilt and decentration of polymethylmethacrylate and foldable acrylic lenses. Ophthalmologica. 1998;212:359-363.

37.Hayashi K, Harada M, Hayashi H, Nakao F, Hayashi F. Decentration and tilt of polymethyl methacrylate, silicone, and acrylic soft intraocular lenses. Ophthalmology. 1997;104:793-798.

INTRODUCTION

Cataract surgery with intraocular lens (IOL) implantation is the most commonly performed surgical procedure in patients over 60 years of age in the United States. Approximately 2.7 million cataract surgeries will be performed in the United States this year.1 While this procedure has undergone numerous refinements over the past 25 years, certain problems remain. In particular, calculations of IOL power are sometimes imprecise because of improper preoperative measurements, postoperative astigmatism from irregular wound healing, or variability in placement of the IOL.2-5 Of 298 emmetropic patients undergoing phacoemulsification or extracapsular cataract surgery with posterior chamber lens placement, only 45% had an emmetropic refraction postoperatively.1 The remaining patients required spectacle correction for optimal distance vision. Ninety-four percent of patients in this group had a postoperative refractive error within 2 diopters (D) of emmetropia. In a series of patients undergoing cataract surgery with either a rigid or foldable IOL, only 35% of patients had uncorrected visual acuity of 20/25 or better. Other studies of uncorrected visual acuity after cataract surgery show that about 50% of patients require spectacles postoperatively to achieve best possible distance vision.6

Of 298 emmetropic patients undergoing phacoemulsification or extracapsular cataract surgery with posterior chamber lens placement, only 45% had an emmetropic refraction postoperatively.1

In addition to imprecise IOL power determinations postoperatively, uncorrected visual acuity is often limited by pre-existing corneal astigmatism. Recently, STAAR Surgical (Monrovia, Calif) introduced a toric IOL that corrects pre-existing astigmatic errors. The IOL comes in only two toric powers—2 and 3.5 D— and the axis must be precisely aligned at surgery. Other than surgical repositioning, there is no way to adjust the IOL’s axis, which may shift postoperatively.7 Furthermore, individualized correction of astigmatism is limited by unavailability of multiple toric powers. An additional problem with using pre-existing astigmatic errors to gauge axis and power of a toric IOL is the unpredictable effect of the cataract wound on final refractive error. After the refractive effect of the cataract wound stabilizes, there can be a shift in both magnitude and axis of astigmatism,

minimizing the corrective effect of a toric IOL. A means to postoperatively correct astigmatic refractive errors after cataract surgery would be very desirable.

Recent commercialization of multifocal IOLs in which patients can potentially be spectacle-free for both near and distance has further increased the need for precise IOL power deter- minations.8-10 The Advanced Medical Optics, Inc (Santa Ana, Calif) Array multifocal IOL has concentric zones of progressive aspheric lenses, permitting simultaneous focusing at distance, near, and intermediate range. If the power calculation is correct for a multifocal IOL, the patient can be freed from using spectacles postoperatively. While some patients with multifocal lenses note glare at night and mild limitation of near visual acuity, overall patient satisfaction in early studies has been very high.9,10 The critical feature related to patient satisfaction with the multifocal IOL is spectacle independence. In fact, a survey of patients with both monofocal and multifocal lenses indicated a willingness to pay approximately $2.00 per day to be free of spectacles after cataract surgery. Assuming a 5-year life expectancy after cataract surgery and a discount rate of 5%, this daily cost would be worth over $3000.9 However, the ability to achieve spectaclefree vision with multifocal IOLs is limited by similar imprecision in IOL calculation noted above for monofocal IOLs.

Growing interest in phakic IOLs for refractive correction of high myopia has accentuated the need for greater precision in IOL power determination. Because of the need to ablate excessive corneal tissue to correct large refractive errors, posterior chamber, iris-fixated, or anterior chamber phakic IOLs provide better optical quality than excimer laser surgery (laser in-situ keratomileusis [LASIK] or photoreactive keratectomy [PRK]). While phakic IOLs are not associated with disabling optical aberrations, optimization of this refractive therapy remains limited by imprecision in IOL power selection.11-13

An additional unexpected need for improved precision in IOL power determination has recently emerged. Eyes undergoing corneal refractive procedures (approximately 1 million/year in the United States) that subsequently develop cataracts are problematic when estimating pseudophakic IOL power. Corneal topographic alterations induced by refractive surgery create imprecision in keratometric measurements.14-16 Several series of patients who had refractive surgery (PRK, LASIK, radial keratotomy) and later required cataract surgery demonstrate surprisingly large hyperopic errors in IOL power determination.14 As the number of myopic patients who have undergone refractive

292 Chapter 35

Figure 35-1. Schematic of positive power adjustment mechanism. (A) Selective irradiation of the central zone of IOL polymerizes macromer, creating a chemical potential between the irradiated and nonirradiated regions. (B) To re-establish equilibrium, excess macromer diffuses into the irradiated region, causing swelling. (C) Irradiation of the entire IOL “locks” the lens power and the shape change.

surgery increases and these patients age, difficulty in accurately predicting IOL power will become an increasingly significant clinical problem. The ability to address this problem with noninvasive postoperative IOL adjustability would be especially valuable in refractive surgery patients, many of whom are accustomed to spectacle-free vision.

As the number of myopic patients who have undergone refractive surgery increases and these patients age, difficulty in accurately predicting IOL power will become an increasingly significant clinical problem.

Therefore, despite advances in cataract and refractive surgery, imprecise IOL power determination remains an important clinical problem to address. Material and optical scientists working at Calhoun Vision, Inc (Pasadena, Calif) and the California Institute of Technology (Pasadena, Calif) have developed a light adjustable IOL that once implanted in the eye may be adjusted with safe levels of near visible radiation to effect refractive changes in the lens. This light adjustable lens (LAL) will give the cataract and refractive surgeon, for the first time, the ability to noninvasively and reproducibly correct both the lower-order (defocus and astigmatism) and some of the higher-order (spherical, coma, tetrafoil, etc) aberrations that adversely affect human vision.

TECHNOLOGY DESCRIPTION:

MECHANISM OF LENS POWER ADJUSTMENT

The Calhoun LAL contains essentially three distinct chemical entities. The first is the matrix polymer that gives the lens its basic shape, refractive index, and material properties. The second component is known as the macromer and is, by design, chemically similar to the matrix polymer. The most important difference between the two is the presence of photopolymerizable end groups on the macromer such that the application of the appropriate frequency of light will cause the macromer molecules to form chemical bonds between each other. The third major component of the Calhoun LAL is a ultraviolet (UV)-absorbing molecule that protects that retina from ambient UV irradiation.

Editor’s note:

Irradiated macromer, which differs from the surrounding matrix polymer by end groups that can be chemically bound together by the light, is incorporated into the meshwork of matrix polymer, setting up a chemical concentration gradient that allows inirradiated macromer to diffuse into the irradiated area, resulting in a change in lens curvature. Wavefront customized irradiation with the appropriate frequency of light results in a wavefront customized change in lens curvature.

R. Krueger, MD, MSE

The mechanism upon which the Calhoun LAL technology is based is akin to holography and is depicted graphically in Figure 35-1. Application of light to the LAL will cause the photopolymerized macromers in the irradiated region to form an interpenetrating network within the target area of the lens. This action produces a change in the chemical potential between the irradiated and unirradiated regions of the lens. To re-establish thermodynamic equilibrium, macromers in the unirradiated portion of the lens will diffuse into the irradiated region, producing a swelling in the irradiated region that effects a change in the lens curvature. As an example, if the central portion of the lens is irradiated and the outside portion is left nonirradiated, unreacted macromer diffuses into the center portion causing an increase in the lens power and a hyperopic shift. Likewise, by irradiating the outer periphery of the lens, macromer migrates outward, causing a decrease in the lens power and a myopic correction.

By controlling the irradiation dosage (ie, beam intensity and duration), spatial intensity profile, and target area, physical changes in the radius of curvature of the lens surface are achieved, thus modifying the refractive power of an implanted Calhoun LAL to either add or subtract spherical power, adjust along toric axes, or correct higher-order aberrations. Once the appropriate power adjustment is achieved, the entire lens is irradiated to polymerize the remaining unreacted macromer to prevent any additional change in lens power. By irradiating the entire lens, macromer diffusion is prevented, thus no change in lens power results. This second irradiation procedure is referred to as lock-in.

A B

Figure 35-2. In-vitro illustration of LAL power change. (A) Fizeau interference fringes of a Calhoun LAL immersed in water at 35ºC before irradiation at best focus (double pass). The fringes present on the periphery of the LAL are due to spherical aberration. (B) Fizeau interference fringes of the same lens 24 hours postirradiation.

Figure 35-4. Optical quality of the irradiated lens via MTF. MTF of the Calhoun LAL measured from preirradiation through the photolocking procedure. The measurements were performed using the ISO model eye and in accordance with ISO document 11979-2. For comparison, the MTF of a PhakoFlex II SI40NB silicone IOL was measured in an identical manner and plotted on the same graph.

Once the appropriate power adjustment is achieved, the entire lens is irradiated to polymerize the remaining unreacted macromer to prevent any additional change in lens power.

SPHERICAL CORRECTIONS

To illustrate an in-vitro example of this process, a Calhoun LAL was fixed in a water cell maintained at 35ºC. The Calhoun LAL was placed one focal length away from the focus of a 4 inch transmission sphere (f/3.3) fitted to a Fizeau interferometer (WYKO 400) (VeeCo, Tuscon, Ariz). Figure 35-2A displays the interference fringes of the Calhoun LAL at its best focus or null position prior to irradiation. The periphery of the Calhoun LAL was irradiated, causing the diffusion of macromer from the central portion of the lens out to the edges. Figure 35-2B displays the interference fringes 24 hours postirradiation at the original best focus position. The most striking feature of this figure is the addition of ~14 (in double pass) fringes of defocus (or wavefront curvature) added to the lens, which corresponds to -2 D of myopic correction.

A B C

Figure 35-3. Calhoun LAL optical quality before and after power change USAF target imaged in air through (A) Calhoun LAL preirradiation and (B) the same Calhoun LAL 24 hours postirradiation after -2 D have been subtracted from the lens. (C) Commercial silicone IOL (PhakoFlex II SI40NB) (+20 D) for comparison.

After the Calhoun LAL is irradiated, it is imperative that the lens maintain a resolution efficiency that is acceptable to the patient. To monitor the resolution efficiency of the Calhoun LAL before and after irradiation, the Calhoun LAL shown in Figure 35-2 was placed on a collimation bench fitted with a standard 1951 United States Air Force (USAF) “6th root of two” resolution target. The image of the resolution target (measured in air) before irradiation is shown in Figure 35-3A. Inspection of this image shows that the Calhoun LAL, in air, can easily resolve the group 4 element 1 (G4 E1) of the target. Figure 35-3B shows the imaged target 24 hours postirradiation after inducing -2 D of change. Inspection of the images shows that the Calhoun LAL can resolve G4 E1 on the chart, indicating that resolution efficiency is not compromised after irradiation. For comparison, a standard, commercial +20 D IOL (PhakoFlex II SI40NB, Advanced Medical Optics Inc, Santa Ana, Calif) is shown in Figure 35-3C.

The image resolution before irradiation is not compromised after irradiation.

Another metric that can be used to assess the optical performance of the Calhoun LAL is measurement of the modulation transfer function (MTF). Figure 35-4 displays the MTF of a representative Calhoun LAL through the adjustment and photolocking procedures. For comparison, the MTF of a standard +20 D PhakoFlex II SI40NB IOL is also plotted. Inspection of the data indicates that after the photolocking procedure, the Calhoun LAL still maintains an MTF above the minimum value of 0.43 at 100 line-pairs per millimeter (lp/mm) established by the International Organization for Standards (ISO) and compares quite favorably to commercially available IOLs.

MULTIFOCALITY AND THE

CALHOUN LIGHT ADJUSTABLE LENS

Accommodation, as it relates to the human visual system, refers to the ability of a person to use his or her unassisted ocular structure to view objects at both near (eg, reading) and far (eg, driving) distances. The mechanism whereby humans accommodate involves contraction and relaxation of the ciliary body, which inserts into the capsular bag surrounding the natural lens. Under the application of ciliary stress, the human lens will undergo a shape change, effectively altering the radius of curva-

294 Chapter 35

Figure 35-5. Illustration of the Calhoun LAL multifocality and multiple irradiations. The base power of the Calhoun LAL is +22.5 D. Each of these interferograms was taken at the preirradiation best focus position along the axis of the interferometer.

ture of the lens. This action produces a concomitant change in the power of the lens. However, as people grow older, the ability to accommodate is reduced dramatically. This condition is known as presbyopia and currently affects more than 100 million people in the United States.

To effectively treat both presbyopia and cataracts, the patient can be implanted with a multifocal IOL. The general concepts and designs of multifocal IOLs have been described in the literature. The simplest design for a multifocal IOL is commonly referred to as the “bull’s-eye” configuration and consists of a small, central add zone (1.5 millimeters [mm] to 2.5 mm in diameter) that provides near vision.17,18 The power of the central add zone is typically between 3 to 4 D greater than the base power of the IOL, which translates to an effective add of 2.5 to 3.5 D for the entire ocular system. The portion of the lens outside the central add zone is referred to as the base power and is used for distance viewing. In theory, as the pupil constricts for near viewing, only that central add zone of the lens will have light from the image passing through it. However, under bright viewing condition, the pupil will also constrict, leaving the patient 2 to 3 D myopic. This can be potentially problematic for a person who is driving in a direction with the sun shining straight at them (eg, driving west around the time of sunset). To counteract this problem, a multifocal IOL could have an annular design with the central and peripheral portion of the lens designed for distance viewing and a paracentral ring (2.1 to 3.5 mm) for near vision. This design will maintain distance viewing even if the pupil constricts.17,18 The most widely adopted multifocal IOL currently sold in the United States is the Array lens, which consists of five concentric, aspheric annular zones. Each zone is a multifocal element and thus pupil size should play little or no role in determining final image quality.

However, as with standard IOLs, the power and focal zones of multifocal lenses must be estimated prior to implantation. Errors in estimating the needed power, as well as shifting of the lens postoperatively due to wound healing, often result in less than optimal vision. The latter effect is particularly problematic for the case of the bull’s-eye lens if a transverse (ie, perpendicular to the visual axis) shift of the IOL occurred during healing. This would effectively move the add part off the visual axis of the eye, resulting in the loss of desired multifocality. The Array and paracentral

IOL designs can partly overcome the dislocation problem during wound healing, although any IOL movement longitudinally (the direction along the visual axis), pre-existing astigmatism, or astigmatism induced by the surgical procedure cannot be compensated for using these multifocal IOL designs. This results in the patient having to choose between additional surgery to replace or reposition the lens or to use additional corrective lenses.

Therefore, a need exists for an IOL that can be adjusted postoperatively after implantation and wound healing to form a multifocal IOL. This type of lens can be designed in vivo to correct an initial emmetropic state and then the multifocality may be added during a second treatment. Such a lens would remove any guesswork involved in presurgical power selection, overcome the wound healing response inherent in IOL implantation, allow the size of the add or subtract zone(s) to be customized to correspond to the patient’s magnitude and characteristics of dilation under different illumination conditions, and allow the corrected zones to be placed along the patient’s visual axis.

This type of multifocal IOL can be designed in vivo to correct an initial emmetropic state and then the multifocality may be added during a second treatment. Such a lens would allow the size of the add or subtract zone(s) to be customized to correspond to the patient’s magnitude and characteristics of dilation under different illumination conditions, and allow the corrected zones to be placed along the patient’s visual axis.

An example of this capability for the Calhoun LAL is depicted in Figure 35-5. Figure 35-5A displays the interference fringes of a +22.5 D LAL at its preirradiation best focus position along the optical axis of the interferometer. Now let us assume that a cataract surgeon implanted this lens in a patient, but due to wound healing and inaccurate biometric preoperative measurements the postoperative refraction indicates that in order to bring the patient to emmetropia 2 D of power would have to be removed from the Calhoun LAL. Furthermore, let us assume that the physician initially would like the patient to be left slightly myopic post-treatment, a common practice among cataract surgeons. Figure 35-5B shows the Calhoun LAL postirradiation at the same position along the optical axis of the interferometer as in Figure 35-5A. The most striking feature of this interferogram is the appearance of 10 fringes (five waves in double pass) of spherical power change, which corresponds to a removal -1.5 D from the Calhoun LAL. Before final photolocking, the physician can then instruct the patient to try this correction and determine if he or she is satisfied or if he or she would require further adjustment. For this scenario, we shall assume that the patient would like to be brought to full emmetropia. The surgeon can retreat the Calhoun LAL to remove another -0.5 D of power from the lens. The ability of the Calhoun LAL to be treated multiple times is illustrated in Figure 35-5C, which shows the interference fringes of the Calhoun LAL after a second adjustment and the appearance of an additional four fringes (two waves) of power change corresponding to subtraction of another -0.5 D. At this point, the physician is free to impart a degree of bifocality to the Calhoun LAL by either adding or subtracting a desired amount of power in the central portion of the Calhoun LAL with a diameter that meets the patient’s dilation characteristics. This is illustrated in Figure 35-5D, which shows the appearance of a 2 mm, +2 D add zone in the central portion of the Calhoun LAL as indicated by the nulled central fringe area.

A B

Figure 35-6. Correction of astigmatism with the Calhoun LAL.

(A) Raw interference fringes of the LAL after application of astigmatic correction to the LAL. The interference fringes were recorded at the best focus position between the tangential and sagittal foci. (B) Threedimensional (3-D) wavefront rendering of the fringes shown in A.

ASTIGMATIC CORRECTIONS

In addition to simple defocus errors, another lower-order optical aberration that dramatically reduces vision quality is astigmatism. These toric errors are either pre-existing or induced during the cataract surgical procedure. The Calhoun LAL technology can be extended to treat these errors as well. This is accomplished by irradiating along the predetermined astigmatic meridian with a toric spatial intensity profile (Figure 35-6).

CORRECTION OF HIGHER-ORDER ABERRATIONS

WITH A DIGITAL MIRROR DEVICE

As described above, the Calhoun LAL has been shown in the laboratory to be quite adequate in the correction of myopic, hyperopic, and toric errors. However, with the recent push by researchers and physicians toward more accurate determinations of the refractive state of the eye as well as the desire to measure and potentially correct higher-order ocular aberrations, it is a logical extension of the Calhoun LAL technology to address these types of corrections as well. As previously mentioned, the refractive change induced in the Calhoun LAL is dependent not only upon the intensity, wavelength, and duration of the exposure but also the spatial intensity profile of the applied light. One method that can be used to spatially profile the light across the full aperture of the Calhoun LAL is the use of apodizing filters. This approach has been used quite successfully in the correction of both spherical and toric changes in the Calhoun LAL and can be universally applied to patients to correct these lower-order aberrations. However, the main drawback to this type of approach for higher-order aberrations is that it would require a customized apodizing filter for each patient, which would not be cost or time effective. A pre-existing technology that can be applied to the LAL to address this problem is the use of a digital mirror device (DMD).

Editor’s note:

The DMD allows for customization of light delivery that cannot be achieved by preset apodizing filters used in correcting lower-order aberrations. The DMD has a micromirror array that either reflects each pixel of light into or away from the projection lens, thereby customizing the light profile according a higher-order wavefront pattern.

R. Krueger, MD, MSE

A picture of a digital light delivery breadboard system is shown in Figure 35-7. At the heart of this instrument is the DMD, which is a pixilated, micromechanical spatial light modulator formed monolithically on a silicon substrate. Typical DMD chips have dimensions of 0.594 x 0.501 inches and the micromirrors are 13 to 17 microns (µm) on an edge and are covered with a reflective aluminum coating. The micromirrors are arranged in an xy array, and the chips contain row drivers, column drivers, and timing circuitry. The addressing circuitry under each mirror pixel is a memory cell that drives two electrodes under the mirror with complimentary voltages. Depending on the state of the memory cell (a “1” or “0”), each mirror is electrostatically attracted by a combination of the bias and address voltages to one of the other address electrodes. Physically, the mirror can rotate ±10 degrees. A “1” in the memory causes the mirror to rotate +10 degrees, while a “0” in the memory causes the mirror to rotate -10 degrees. A mirror rotated to +10 degrees reflects incoming light into the projection lens and onto the IOL through the eye. When the mirror is rotated -10 degrees, the reflected light misses the projection lens.

Thus, the great utility and advantage of the DMD device in its relation to the Calhoun LAL is the ability of the researcher/ physician to define any spatial intensity profile that is applied to the Calhoun LAL. To assess the ability of the Calhoun LAL to correct higher-order aberrations using the DMD, the Zernike aberration known as tetrafoil and described by the equation:

S44 = (4 2 - 3) 2cos2

was programmed into the DMD and the Calhoun LAL was irradiated with this spatial intensity profile. Figure 35-8 shows the grayscale representation of the tetrafoil Zernike term that was applied to the Calhoun LAL.

Figure 35-9A depicts the raw interference fringes of the Calhoun LAL after irradiation with the tetrafoil spatial intensity profile. This figure dramatically shows that the projected spatial intensity profile was reproduced on the wavefront of the Calhoun LAL. To further illustrate this point, the 3-D wavefront calculated from the interference fringes shown in A is displayed in Figure 35-9B. This 3-D rendering shows the four-fold symmetry of the wavefront. In practice, once the Calhoun LAL has been implanted and refractive stabilization has occurred, a wavefront measurement of the eye’s aberrations is made. The phase conjugate to these aberrations can then be put into the DMD device; the spatial intensity profile is created and then projected onto the Calhoun LAL to correct the aberration.