From Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, Ohio.
The author has no financial interest in the materials presented herein.
Correspondence: Ronald R. Krueger, MD, MSE, Cole Eye Institute, Cleveland Clinic Foundation, i32, 9500 Euclid Ave, Cleveland, OH 44195. Tel: 216.444.8158; Fax: 216.445.8475; E-mail: email@example.com
The first thing that the reader might question in viewing this editorial is “What does he mean by biomechanical manipulation?” It is true that corneal biomechanics has been a relatively new, hot topic in refractive surgery, but why manipulation? To answer this question, let me go back to the beginning of refractive surgery to outline a trend in the way our field has evolved.
The Long, Hard Road to Acceptance of Refractive Surgery
The early success of both keratomileusis and radial keratotomy, through the respective efforts of Barraquer in the 1960s1 and Fyodorov in the 1970s,2 brought one to the realization that refractive error could be surgically corrected. Despite their early successes, the conservative community in ophthalmology resisted widespread acceptance of these procedures because of the fear of surgical complications and the “unethical” point of view taken toward operating on a normal, healthy eye. As a result, the concept of refractive surgery was not embraced, and for a long time, ophthalmic surgeons stayed away. Gradually, with the development of new diagnostic and surgical tools and the performance of scientific clinical trials, the field of refractive surgery began to grow and evolve into what it is today. As refractive surgery evolved, we moved through the steps of 1) ignorance and recognition, to 2) fear and avoidance, to 3) compensation and correction, and eventually to 4) modification and manipulation of refractive errors. Monovision and multifocality are two examples of how we modify and manipulate refractive errors beyond just correcting them.3,4
Aberrations Are not to Be Feared, when They Can Be Manipulated
The quest for freedom from spectacles and contact lenses through the surgical correction of refractive errors was, of course, met by challenges and more reasons to fear—from both ophthalmic surgeons and patients. Not all patients were happy with their uncomplicated 20/20 outcome; they complained about a loss in the quality of their vision. With time, specialists in physiologic optics came to the rescue, and wavefront technology was introduced and able to define and measure aberrations that were the source of great patient unhappiness.5,6 By embracing wavefront technology, the field moved from ignorance regarding aberrations to fear and avoidance, but eventually, with the advent of customized laser vision correction, it moved beyond fear to compensation and even correction of aberrations.7 During this time, the ideal outcome was considered the complete absence of optical aberrations, and the quest was for super-vision. Although this quest is still desired for many patients, the advent of presbyopia correction has expanded our goals to not only fully correct aberrations, but manipulate them to their advantage. Multifocal corneas and intraocular lenses are now not only providing desirable distance visual acuity, but also the visual depth of focus that presbyopic patients demand. The sequence of ignoring and avoiding aberrations to correcting and now manipulating them is again defining the paradigm shift within refractive surgery, which was experienced with refractive error in the past. This present day paradigm shift of fearing and avoiding aberrations to embracing them has the potential to repeat itself again with biomechanics in the future.
Ectasia Should Be Feared, but What About Biomechanical Manipulation?
Now, what about biomechanics? The most feared complication of excimer laser vision correction is corneal ectasia. Although prior to 1998, it was completely unknown and ignored in association with laser vision correction, its first description by Theo Seiler8 introduced us to an unexpected postoperative source of progressive corneal steepening irregularity that ultimately led to its “most feared” status. Avoidance of corneal ectasia has become and still is the foremost concern of refractive surgeons.
However, the pattern of moving from ignorance and avoidance to compensation, correction, and manipulation is now beginning to develop within corneal biomechanics and ectasia. A new hope for the correction of keratectasia has been introduced, by Wollensak et al in 2003, in the technique of riboflavin/ultraviolet A (UVA) corneal cross-linking (CXL).9 This technique has introduced a method of stiffening the biomechanically weakened collagen of keratoconus and postoperative ectasia after LASIK to not only halt the progression of the irregularity, but in many cases stabilize and begin to regularize its corneal shape. Biomechanical compensation and correction of ectasia is now possible with CXL in many countries around the world, and current US Food and Drug Administration trials will eventually bring its benefits to the United States, as well.
This now brings us to the question of biomechanical manipulation and with it, the concept of “controlled ectasia.” We all remember the incisional refractive surgery procedures of a previous era that promised stable correction of refractive error, but with time demonstrated they could be unstable. Hexagonal keratotomy and single pass (deep) automated lamellar keratoplasty were two methods of intentionally steepening the cornea for the correction of hyperopia, and the latter was actually referred to as “controlled ectasia.”10 Unfortunately, nothing is controlled about ectasia, and these procedures failed to deliver what they promised. Even radial keratotomy, which effectively flattened the central cornea by steepening the paracentral zone with deep radial incisions, eventually led to progressive hyperopia in a significant proportion of eyes over time.11 In hindsight, our current understanding of corneal biomechanics clearly explains this phenomenon. After all, not only the strongest corneal lamellae in the anterior one-third of the cornea, but also the deeper corneal lamellae, are violated with this procedure.
Intrastromal Femtosecond Lasers for Presbyopia Is a Form of Biomechanical Manipulation
With the advent of intrastromal incisions using femtosecond lasers, the precision and selectivity in cutting corneal lamellae has been given nearly limitless potential. The IntraLase femtosecond laser (Abbott Medical Optics, Santa Ana, Calif), being first used in making uniformly thin corneal flaps, not only demonstrated an increase in the safety of LASIK, but also enhanced the biomechanics of flap making with less induction of higher order aberrations.12,13 The IntraLase and other ultrashort pulse lasers can selectively deliver any intrastromal cutting pattern, giving it the potential to control the biomechanical response of the cornea. Yet, it’s not only the predictability of the pattern of laser pulse placement that makes femtosecond lasers so magical, but the intrastromal delivery. Imagine performing intrastromal radial keratotomy without ever violating Bowman’s layer or the strongest anterior corneal lamellae. Although the refractive effect would be much smaller compared to incisional radial keratotomy, the likelihood of progressive hyperopia probably would be greatly reduced due to the preservation of these anterior corneal structures. Without violating these lamellae, the biomechanical response could be kept in check to maintain long-term stability.
This very concept was recently adopted into clinical practice by Colombian refractive surgeon, Luis Ruiz, who developed a procedure for increasing the central multifocality of the cornea without compromising distance vision for the correction of presbyopia (INTRACOR). In this issue of the Journal of Refractive Surgery, Ruiz et al14 report >6-month follow-up on their first 83 eyes using the TECHNOLAS femtosecond laser platform (Technolas Perfect Vision GmbH, Munich, Germany) to deliver a series of concentric circular cuts intrastromally, while preserving the most anterior corneal fibers and Bowman’s layer. In addition to the pattern of concentric cylinders that creates the hyperprolate corneal shape for enhancing near vision, Ruiz has also added intrastromal radial incisions (intrastromal radial keratotomy) for those eyes with pre-existing myopia, so that the distance vision in these eyes can also be corrected intrastromally. Because no tissue is being removed by the intrastromal femtosecond laser cuts, the effect is entirely biomechanical and specifically patterned to achieve the optimal aberration pattern for both distance and near vision.
To validate this new procedure, other surgeon investigators, Michael Holzer and colleagues in Germany, have also published their experience with the INTRACOR presbyopic technique, reporting 3-month follow-up that showed a similar efficacy of restoring near vision in 25 presbyopic eyes.15 This improvement of uncorrected near visual acuity is achieved by a specific aberration pattern (negative shift in spherical aberration with a positive shift in secondary spherical aberration), creating a hyperprolate corneal shape. Although, as a safety concern with the German data, there was a loss of two or more lines of corrected distance visual acuity (CDVA) in 8% of eyes at 3 months; the same two-line loss with the Columbian data was found in only 4.8% of eyes at 6 months and 0% at both 9 and 12 months, suggesting an improvement of CDVA over time. As a single side effect, symptomatic halos were reported, especially at night by the majority of patients in both studies. Although noted immediately (the next day) after surgery, these symptoms also improved and resolved with time.
Collagen Cross-Linking Is Overcoming the Fear of Uncontrolled Biomechanical Manipulation
Now that we have the technology for selectively weakening the corneal biomechanics with intrastromal femtosecond lasers, it would be best to counterbalance this effect with the potential to strengthen the corneal biomechanics using surface and/or intrastromally delivered CXL methods.16 Although the combination of both intrastromal weakening and strengthening has not yet been applied together clinically, one can at least acknowledge that the surgical tools for inducing and/or correcting these biomechanical changes now exist.
The missing piece, at present, is a diagnostic device for determining the regional biomechanical strength of the cornea. Although the Ocular Response Analyzer (ORA; Reichert Instruments, Depew, NY) was utilized by Ruiz et al as a global metric of biomechanical response, both the corneal hysteresis and corneal resistance factor showed a minimal change with INTRACOR, whereas a significant reduction of these indices has been previously observed in eyes with LASIK.17 Perhaps the preservation of the anterior corneal stromal fibers explains the favorable biomechanical difference in stability when using INTRACOR; however, the biomechanical nature of this procedure suggests that a more localized measure of corneal elasticity is required. Several technologies of localized stress/strain testing are currently being investigated for prototype development and commercialization. These include optical coherence elastography of dynamic speckle (strain) in response to a localized perturbation (stress)18 as well as a form of radial shearing using electronic speckle interferometry.19 Whether one or more of these “elastography mapping technologies” is successfully adopted in clinical practice will depend on the perceived need and financial incentive for their commercialization. At present, both riboflavin/UVA CXL and INTRACOR are two strong and apposing surgical interventions for biomechanical compensation and manipulation of the cornea. Their growing success will both fuel and depend upon the development of a localized, diagnostic “elastography” device.
Biomechanical Manipulation Is the Future of Refractive Surgery
The concept of refractive, aberration, and biomechanical manipulation has primarily been proposed in an effort to enhance the depth of focus of patients with presbyopia. Solutions offering monovision (refractive), multifocal shaped (aberration), and multifocal relaxation (biomechanical) mechanisms of enhancing depth of focus are now being realized. Even within the crystalline lens, biomechanical manipulation with femtosecond laser intralenticular photodisruption has also been proposed in an effort to restore the loss of accommodation.20,21 With the fear of ectasia still foremost in the minds of practitioners, apprehension may exist for embracing the idea of biomechanical corneal weakening. But, with the combination of intrastromal femtosecond laser cutting and strengthening with CXL, my future prediction for the next frontier of refractive surgery is in the development of biomechanical compensation and manipulation. Time will tell if the INTRACOR procedure of Ruiz et al, first published in this issue of the Journal, will demonstrate long-term safety and efficacy, but even if it doesn’t, other techniques or modifications of this technique will likely pave the way for the future of biomechanical manipulation in refractive surgery.
- Barraquer JI. Keratomileusis. Int Surg. 1967;48:103–117.
- Fyodorov SN, Durnev VV. Operation of dosaged dissection of corneal circular ligament in cases of myopia of mild degree. Ann Ophthalmol. 1979;11:1885–1890.
- Miranda D, Krueger RR. Monovision laser in situ keratomileusis for pre-presbyopic and presbyopic patients. J Refract Surg. 2004;20:325–328.
- Alió JL, Chaubard JJ, Caliz A, Sala E, Patel S. Correction of presbyopia by Technovision central multifocal LASIK (presby-LASIK). J Refract Surg. 2006;22:453–460.
- Thibos LN, Hong X. Clinical applications of the Shack Hartmann aberrometer. Optom Vis Sci. 1999;76:817–825. doi:10.1097/00006324-199912000-00016 [CrossRef]
- Chalita MR, Chavala S, Xu M, Krueger RR. Wavefront analysis in post-LASIK eyes and its correlation with visual symptoms, refraction and topography. Ophthalmology. 2004;111:447–453. doi:10.1016/j.ophtha.2003.06.022 [CrossRef]
- Chalita MR, Xu M, Krueger RR. Alcon CustomCornea wavefront-guided retreatments after laser in situ keratomileusis. J Refract Surg. 2004;20:S624–S630.
- Seiler T, Quurke AW. Iatrogenic keratoectasia after LASIK in a case of forme fruste keratoconus. J Cataract Refract Surg. 1998;24:1007–1009.
- Wollensak G, Spoerl E, Seiler T. Riboflavin/ultraviolet-A-induced collagen crosslinking for the treatment of keratoconus. Am J Ophthalmol. 2003;135:620–627. doi:10.1016/S0002-9394(02)02220-1 [CrossRef]
- Lyle WA, Jin GJ. Hyperopic automated lamellar keratoplasty: complications and visual results. Arch Ophthalmol. 1998;116:425–428.
- Deitz MR, Sanders DR. Progressive hyperopia with long-term follow-up of radial keratotomy. Arch Ophthalmol. 1985;103:782–784.
- Krueger RR, Dupps WJ Jr, . Biomechanical effects of femtosecond and microkeratome-based flap creation: prospective contralateral examination of two patients. J Refract Surg. 2007;23:800–807.
- Medeiros FW, Stapleton WM, Hammel J, Krueger RR, Netto MV, Wilson SE. Wavefront analysis comparison of LASIK outcomes with the femtosecond laser and mechanical microkeratomes. J Refract Surg. 2007;23:880–887.
- Ruiz LA, Cepeda L, Fuentes V. Intrastromal correction of presbyopia with a femtosecond laser system. J Refract Surg. 2009;25:847–854.
- Holzer M, Mannsfeld A, Ehmer A, Auffarth GU. Early outcomes of INTRACOR femtosecond laser treatment for presbyopia. J Refract Surg. 2009;25:855–861.
- Krueger RR, Ramos-Esteban JC, Kanellopoulos AJ. Staged intrastromal delivery of riboflavin with UVA cross-linking in advanced bullous keratopathy: laboratory investigation and first clinical case. J Refract Surg. 2008;24:S730–S736.
- Pepose JS, Feigenbaum SK, Qazi MA, Sanderson JP, Roberts CJ. Changes in corneal biomechanics and intraocular pressure following LASIK using static, dynamic and noncontact tonometry. Am J Ophthalmol. 2007;143:39–47. doi:10.1016/j.ajo.2006.09.036 [CrossRef]
- Ford M, Dupps WJ, Huprikar N, Lin R, Rollins AM. OCT elastography by pressure-induced optical feature flow. Progress in biomedical optics and imaging. Proceedings of SPIE. 2006;6138OP (E-pub March 7, 2006).
- Jaycock PD, Lobo L, Ibrahim J, Tyrer J, Marshall J. Interferometric technique to measure biomechanical changes in the cornea induced by refractive surgery. J Cataract Refract Surg. 2005;31:175–184. doi:10.1016/j.jcrs.2004.10.038 [CrossRef]
- Myers R, Krueger R. Novel approaches to correction of presbyopia with laser modification of the crystalline lens. J Refract Surg. 1998;14:136–139.
- Krueger RR, Kuszak J, Lubatschowski H, Myers RI, Ripken T, Heisterkamp A. First safety study of femtosecond laser photo-disruption in animal lenses: tissue morphology and cataractogenesis. J Cataract Refract Surg. 2005;31:2386–2394. doi:10.1016/j.jcrs.2005.05.034 [CrossRef]