We hope that you are enjoying a wonderful spring.

Advance Registration ends April 6, 2005 for the inaugural ISRS/AAO meeting, Emerging Trends in Refractive and Cataract Surgery, being held in Hong Kong from May 14 through 16.

We have assembled an outstanding program to provide a forum for exchange of the latest information in the field.

The venue is the spectacular Hong Kong Convention Center, overlooking one of the most magnificent harbors in the world.

As always, your questions and comments are most welcome.

Sincerely,
Marguerite McDonald, MD, FACS
Medical Editor, Refractive Outlook

IN THIS ISSUE
- Review of Phakic IOLs
- Journal Update: Transepithelial Phototherapeutic Keratectomy/Photorefrctive Keratectomy With Adjunctive Mitomycin-C for Complicated LASIK Flaps
- Journal Update: Alcohol and Mechanical Scraping for Epithelial Ingrowth Following Laser In Situ Keratomileusis
- Journal Update: Complications Ocular Higher-Order Aberrations in Eyes With Supernormal Vision
- Q&A

Review of Phakic IOLs

John A. Vukich, MD, Surgical Director, Davis Duehr Dean Center for Refractive Surgery, Davis Duehr Dean Department of Ophthalmology, Dean Medical Center, Madison, WI

Phakic intraocular lenses (PIOL) provide patients with an alternative to LASER corneal reshaping for the correction of refractive errors. The anterior chamber Verisyse™ manufactured by Ophtec (Gronegan, Netherlands) and marketed in the United States by Advanced Medical Optics (AMO) is currently available for use by surgeons in the United States. The Visian Implantable Collamer Lens (ICL™) manufactured by STAAR Surgical AG (Nidau, Switzerland) is a flexible, posterior chamber PIOL for the correction of myopia and is in the final phase of the U.S. approval process. Other styles of PIOLs including angle supported and foldable iris clip styles are under development. This article will focus primarily on the lenses that are either currently available or are anticipated to be available to American surgeons in the near future.

The safety and efficacy of PIOLs will ultimately determine whether or not they will be widely accepted by patients and physicians. The major attraction of PIOLs is to provide a noncorneal alternative for the correction of refractive errors. It is generally accepted that LASIK has limitations in the treatment of high levels of myopia.

Although most excimer refractive lasers are FDA approved for the treatment of up to -14 D of myopia, the majority of LASIK surgeons have limited the level of treatment to less than the approved indication. Often this is driven by insufficient residual corneal thickness, but it also reflects concerns regarding quality of vision. Other factors driving the interest in PIOLs relate to the need for a non-corneal alternative for those patients in whom there are atypical corneal topographical features. Much effort has been devoted to analyzing the corneal shape looking for subtle indications of keratoconnus or other conditions that may indicate an increased risk of corneal instability following laser correction. Phakic IOLs are an attractive alternative for patients seeking refractive correction and expands both the range of treatment as well as the choices for patients.

Visian Implantable Collamer Lens
The first implants of the ICL were performed in 1993. In May of 1997, the ICL was granted the European CE mark of approval and became available in European Union countries and others that recognize the CE mark. In February 1997 Investigational Device Exemption (IDE) was granted to begin clinical trials in the United States for premarket approval by the FDA. The myopic version of the ICL was recommended for approval by the FDA advisory panel in October of 2003 and is anticipated to be available in the United States in the near future. Current versions of the ICL are available between –3 D and –20 D and +1.50 D to +20 D. The US clinical trials of the spherical versions of the ICL were limited to patients with less than 2.5 D of preexisting astigmatism. A toric model is in clinical trials that will correct up to 6 D of astigmatism. 

A standard manifest and cycloplegic refraction is the basis for the calculation of the power of the selected implant. The ICL is manufactured in 11-, 11.5-, 12-, 12.5- and 13-millimeter lengths. White-to-white measurement (W-to-W) is used estimate the diameter of the ciliary sulcus and to determine the desired length of the ICL. For myopic patients, 0.5-mm is added to the W-to-W length and for hyperopic correction the ICL length is the same as the W-to-W. 

A peripheral iridectomy or iridotomy is required to prevent pupillary block. The timing of the iridectomy, either preoperatively or at the time of lens insertion is a matter of debate among ICL users. By far the most common technique and that which is recommended by the manufacturer, is to perform a YAG iridotomy seven to 14 days prior to surgery. The ICL insertion requires a minimum pupil size of 7-mm at the time of surgery. Topical bupivicaine 0.75 percent (Abbott Laboratories, Chicago) and lidocaine 2 percent drops (Abbott Laboratories) applied just prior to surgery is sufficient for most patients. Peribulbar anesthetic is an acceptable alternative and may be preferred in the early phase of a surgeon’s experience. 

The operative technique for the ICL contains many elements familiar to cataract surgeons. A sterile field is obtained using a standard prep and drape appropriate for intraocular surgery. A temporal clear cornea incision is made using the same architecture as for cataract surgery. A cord length of 3- to 3.2-mm with a 2-mm tunnel provides adequate room for the lens injector and a secure self-sealing closure. Occucoat (Storz Ophthalmics) or other low molecular, weight non-cohesive viscoelastic is preferred due to the minimal resistance it offers to unfolding of the implant in the anterior chamber. The lens is inserted using an injector mechanism. Once in the eye, the ICL must be repositioned posterior to the iris plane.

Efficacy of the ICL
Three-year experience from the U.S. Phase III clinical trial provides the best available analysis of the intermediate term safety and efficacy of the ICL. A total of 526 eyes were analyzed at three years. The mean preoperative spherical equivalent was -10.05 D, ranging from -3 D to -20 D. All patients had less than 2.5 D of preexisting astigmatism. Uncorrected visual acuity of  20/40 or better was achieved in 94.7 percent of eyes at 36 months. The proportion of eyes with UCVA 20/20 or better was 59.3 percent at 36 months postoperatively. Manifest refractive spherical equivalent within 1 D was achieved in 88.2 percent of eyes at 36 months.At three years, 92 percent of patients reported being very or extremely satisfied with their vision.

Safety Profile of the ICL
A gain of one or more lines of best corrected visual acuity was observed at three years in 49 percent of eyes compared with 8 percent that lost one or more lines of BSCVA. At three years, 19 of 526 eyes developed lens opacities for an incidence of 3.6 percent. The development of nonvisually significant lens opacities appears to be related at least in part to surgeon experience. Of the early onset lens opacities observed the U.S. clinical trials, all but one were among the first seven ICLs implanted by any surgeon. Early anterior subcapsular opacities tended to be focal, nonprogressive and were observed in 2 percent of patients. Clinically significant cataracts requiring surgical correction occurred in 0.9 percent of eyes at the three-year period. The time course of first appearance of observed anterior subcapsular opacities shows that the majority of changes occur in the first 12 months. Cumulative endothelial cell loss of 9.7 percent was observed at 36 months. Improvements in endothelial cell morphology provide encouraging but incomplete evidence of stabilization of cell loss by the three-year mark. 

Verisyse Anterior Chamber PIOL
Iris-fixated IOLs were first introduced in 1978 by Professor Jan G.F. Worst. Multiple design changes took place until 1991 when the current model was introduced as the Worst Myopic Claw lens. The lens is manufactured by Ophtec and is known internationally as the Artisan lens. The same lens is distributed in the United States and Japan by AMO where it is marketed as the Verisyse phakic IOL. The Verisyse myopic IOL was approved for use in the United States on September 10, 2004. The FDA clinical trial included patients with axial myopia between -5 D and -20 D and less than 2.5 D of preexisting cylinder. A minimum anterior chamber depth of 3.2-mm was required. The Verisyse is available in a 5- and 6-mm optic size.

Efficacy of the Verisyse PIOL
In the U.S. multicenter clinical trial, a total of 662 eyes were subject to analysis with a mean myopic spherical equivalent of -12.6 D. At three years, 92 percent of eyes had uncorrected visual acuity of 20/40 or better and 67.1 percent were 20/25 or better. Refractive spherical equivalent within 1 D of target was achieved in 94.8 percent of eyes at 36 months. Patient satisfaction ratings of good or excellent were reported at one year by 90 percent of patients.

Safety Analysis of the Verisyse
Of the 309 eyes observed at the three-year period, 19 lens opacities were noted for an incidence of 5.2 percent. Nuclear sclerotic changes accounted for 11 of the lens opacities with the rest being divided among anterior subcapsular and cortical changes. Four eyes (1.3 percent) underwent cataract surgery for visually significant lens changes. Removal of the Verisyse was required in 11.7 percent of eyes due to trauma, chronic inflammation or cataract formation. Reattachment of the Verisyse was necessary in 1 percent of eyes. Endothelial cell loss of 1.1 percent at one year and 3.8 percent at two years was observed. 

Quality of Vision with PIOL
The quality of visual acuity with the PIOL is subjectively rated very highly by patients. Objective comparison of visual quality by measuring postoperative wavefront aberrations, allows us to compare the image quality due to higher-order aberrations. In one published study, a comparison of the measured coma and spherical aberration in post-operative LASIK and PIOL eyes demonstrated significantly less of these higher-order aberrations following PIOL treatment.⁸  

Conclusion
The recovery of visual acuity is rapid with PIOLs and commonly the quality of vision is excellent just minutes after surgery. Many reports documenting the efficacy of both the Visian ICL and Verisyse anterior chamber lens have been published. Initial results with both anterior and posterior chamber PIOLs have been encouraging, and both styles of lens have demonstrated similar rates of complications. Bioptics, which combine LASIK and PIOLs for extreme cases of myopia, has also shown promise.^3,1 Crystalline lens opacities have been reported with both styles of PIOLs and must be viewed as an accepted risk of phakic implants. The potential for accelerated corneal endothelial cell loss remains a concern with both anterior and posterior chamber PIOLs and will require continued surveillance. Established long-term safety will ultimately influence the range of correction for which PIOLS are offered. Provided the overall incidence of complications remains low, it seems likely that PIOLs will gain increased acceptance as an alternative to corneal refractive procedures.

References:

1.  Arne JL, Lesueur LC. Phakic posterior chamber lenses for high myopia: functional and anatomical outcomes. J. Cataract Refract Surg. 2000; 26:369-374.
2.  Fink AM, Gore C, Rosen E. Cataract development after implantation of the Staar Collamer posterior chamber phakic lens. J Cataract Refract Surg. 1999; 25(2):278-282.
3.  Garcia M, Gonzalez C, Pascual I et al. Magnification and visual acuity in highly myopic phakic eyes corrected with an anterior chamber intraocular lens versus by other methods. J. Cataract & Refract Surg. 1996;22:1416-1422.
4.  Lovisolo CF and Pessando PM. The implantable contact lens (ICL^TM) and other phakic IOLs. Fabiano Ed S Stefano Belbo (CW) Italy 1999.
5.  Pesando PM, Ghiringhello MP, Tagliavacche P. Posterior chamber collamer phakic intraocular lens for myopia and hyperopia. J Refract Surg. 1999; 15(4):415-423.
6.  Sanders DR, BrownDC, Martin RG et al. Implantable contact lens for moderate to high myopia:  phase I FDA clinical study with 6 month follow-up. J Cataract Refract Surg 1998; 24(5):607-61.
7.  Sarver EJ, Sanders DR, Vukich JA. Comparison of image quality for high myopes corrected with laser in situ keratomileusis and phakic intraocular lens. J Refract Surg.
8.  The Implantable Contact Lens in Treatment of Myopia (ITM) Study Group. Incidence of lens opacities and clinically significant cataracts with the implantable contact lens (ICL); comparison of 2 lens designs. J Refract Surg 2002;18:673-682.
9.  The Implantable Contact Lens in Treatment of Myopia (ITM) Study Group. U.S. Food and Drug Administration clinical trial of the implantable contact lens for moderate to high myopia. Ophthalmology 2003;110:255-266.
10.  Zaldivar R, Davidorf JM, Oscherow S et al. Combined posterior chamber phakic intraocular lens and laser in situ keratomileusis: bioptics for extreme myopia. J Refract Surg 2000;15:299-308.

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JOURNAL UPDATE

Sandy T. Feldman, MD

Transepithelial Phototherapeutic Keratectomy/Photorefrctive Keratectomy With Adjunctive Mitomycin-C for Complicated LASIK Flaps

Muller LT, Candal EM, Epstein RJ, Dennis RF, Majmumadar PA. J Cataract Refract Surg. 2005: 31:291-7.

Method:
A case series of 10 eyes of 10 patients that had LASIK flap complications and underwent PTK/PRK with mitomycin-C application [two minutes] for correction of refractive errors. Patients were examined postoperatively and uncorrected visual acuity, best corrected visual acuity, manifest refraction and slit lamp examination were measured.

Result:
Postoperatively, the mean uncorrectected acuity was 20/28, best spectacle corrected acuity was 20/21, and the spherical equivalent ranged from +0.37 to -1 D with a follow up ranging from eight to 28 months.

Conclusion:
PTK/PRK with adjunctive MMC therapy resulted in improved uncorrected and best spectacle corrected visual acuity in 10 eyes following complicated LASIK surgery.

Comments:
This paper illustrates the safety and efficacy of using a single application of 0.02 percent mitomycin combined with PTK/PRK for the treatment of flap complications following LASIK.

Alcohol and Mechanical Scraping for Epithelial Ingrowth Following Laser In Situ Keratomileusis

Lahners WJ, Hardten DR, Lindstrom RL. J Refract Surg 2005: 21:148-51.

Purpose:
To determine whether the recurrence rates of 70 percent isopropyl alcohol in addition to mechanical removal of epithelial ingrowth following LASIK.

Methods:
The authors performed a retrospective chart review of patients undergoing the removal of epithelial ingrowth with or without the use of adjunctive alcohol.

Results:
The recurrence of clinically significant epithelial ingrowth in the group without alcohol was 43.8 percent, and in the group with adjunctive alcohol removal was 34.2 percent. The difference between the groups was not clinically significant.

Conclusion:
This study shows that the adjunctive use of 70 percent isopropyl alcohol did not reduce clinically significant epithelial ingrowth recurrence rates as compared with mechanical removal alone.

Comment:
This study shows that the use of 70 percent isopropyl alcohol was not helpful in reducing epithelial ingrowth recurrence following removal. This study points to further evidence that incomplete removal is the not the reason that ingrowth occurs. Further clinical studies are needed to determine whether addressing the wound edge by suturing and/or fibrin adhesive may reduce the recurrence rates.

Ocular Higher-Order Aberrations in Eyes With Supernormal Vision

Levy Y, Siegal O, Avni I, Zadok D. Am J Ophthalmol; 139: 225-8.

Purpose:
To evaluate higher order aberrations in eyes with supernormal vision.

Methods:
This observational case series measured ocular higher order aberrations across a naturally dilated pupil using the Nidek OPD scan wavefront aberrometer. Specifically root mean square values, total spherical aberration, total coma and total trefoil were measured.

Results:
Mean RMS values were 0.334 microns +/- 0.192, 0.110 microns +/-0.077 for total spherical aberrations, 0.136 microns +/-0.081 total coma, and 0.268 microns +/- 0.220.

Conclusions:
This study documents that patients with supernormal vision had levels of HOA’s similar to reported in myopic eyes.

Comments:
This study shows that eyes with supernormal vision did contain higher order aberrations. Due to high variability between subjects and the possibility that other metrics such as Strehl ration are more important in visual quality, refractive surgeons should realize the complexity of the wavefront measurement and its impact on quality of vision as well uncorrected visual acuity.

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Q&A

Vikentia Katsanevaki, MD, PhD and Stephen D. Klyce, PhD

How do aberrations correlate to vision and visual complaints?

Retinal image quality is degraded by scatter, diffraction and optical aberrations. The optical quality of a healthy emmetropic eye is maximized for a pupil size of approximately 3-mm, balancing diffraction effects of smaller pupils and high order  aberrations that are maximized with larger pupil sizes.

Evaluation of clinical performance in clinical practice has been traditionally examined with measurement of Snellen high contrast visual acuity. The evolution of refractive surgery with the concomitant visual complaints such as glare, halos, and monocular diplopia necessitated the development of new objective methods to record, quantify and understand the effects of corneal surgery on visual performance.

In the early developmental period of excimer laser refractive surgery, corneal topography was the single examination that could provide an objective evaluation of corneal optical quality. Specially designed software programs such as the Surface Regularity Index (SRI)¹ on the Tomey TMS, the Holladay Diagnostic Summary² on the EyeSys topographer, and the ray tracing program of Technomed C-Scan³ were the first industry attempts to provide clinicians advanced diagnostic tools for the evaluation of complicated refractive patients. These programs use the raw data of the corneal anterior surface videokeratography and provide an objective evaluation of corneal optics as well as an estimation of Snellen high contrast visual performance of the examined eye. After laser refractive surgery, degradation of the retinal image is principally due to sub-optimal anterior corneal surface changes. Due to the complexity of the optics of the human eye with the compensatory interactions between the normal cornea and the natural lens, measurement of corneal topography alone is often not adequate for a complete post-surgical optical evaluation.

Wavefront sensing together with corneal topography provide the clinician with a complete description of the optics of each patient’s eye. Commercialization of rapid, automated wavefront sensing now provides a much better understanding of human eye optics as well as the effects of refractive corrections on visual performance. According to the American National Standards Institute⁴, the standard method for reporting optical aberrations in the eye (wavefront error) is with the normalized Zernike expansion. Zernike decomposition provides insight into the relative importance to visual performance of specific aberrations such as the so-called lower order terms: tip, tilt, defocus, and cylinder. More complex forms of aberration can be lumped together to collectively assess what are called the higher order aberrations or HOAs. Some of these terms, particularly the simpler terms, including spherical aberration and coma, can be used to correlate with specific visual complaints. For example, a refractive surgery patient who presents postoperatively with increased spherical aberrations and complains of haloes at night very likely suffers from a treatment zone diameter smaller than the mesopic pupil size.

Although wavefront aberrometry provides an objective method to evaluate the optics of the human eye, there remain obstacles to a direct correlation of a wavefront measurement to subjective vision complaints and to describe this relationship using a single number.  The individual Zernike components, both low order and high order, are called modes. These are not equally important for optimal visual performance. Convolution of point-spread functions with images (for example, an eye chart or scenery) has shown that the modes with simple shapes (like coma and trefoil) blur images more than those with more complex shapes like pentafoil. Furthermore, interaction of pairs of aberrations can either improve or degrade acuity differently than would be expected from the blur caused by individual components themselves. Due to these complex interactions, the commonly presented Zernike mode values and wave RMS error are generally not adequate to describe subjective visual performance.

The number of metrics that can be explored to serve in the clinical setting may at first seem a daunting task. To this end, a large number of metrics have been proposed and tested, with the “visual Strehl ratio” seeming to have the highest correlation to visual function.⁵ The visual Strehl is a measure of optical performance at the retinal plane, and, therefore, includes the combined aberrations of the optics of the whole eye. One of the important challenges for the future is to determine whether any metric or any combination of metrics can successfully correlate to and predict the type of specific visual complaints experienced by some of our refractive surgical patients.

Vikentia Katsanevaki, MD, PhD 
vikatsan@med.uoc.gr

Stephen D. Klyce, PhD
sklyce@klyce.com

References:
1. Wilson SE, Klyce SD: Quantitative descriptors of corneal topography: A clinical study, Arch Ophthalmol 109:349-53, 1991.
2. Holladay JT: Corneal topography using the Holladay Diagnostic Summary. J Cataract Refract Surg 1997;23:209-21.
3. Ucakhan OO: Predicted corneal visual acuity in keratoconus as determined by ray tracing. Acta Ophthalmol Scand 2003;81:264-70.
4. American National Standard Ophthalmics-Methods for Reporting Optical Aberrations of the Eye. ANSI Z80.28-2004. Optical Laboratories Association, American National Standards Institute, Inc, 2004.
5. Cheng X, Thibos LN, Bradley A: Estimating visual quality from wavefront aberration measurements. J Refract Surg 200;19:S579-84.

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